Regulation of Epicardial Cell Fate during Cardiac Development and Disease: An Overview

This work was partially supported by grants BFU2015-67131 (Spanish Ministry of Economy and Competitiveness) and PID2019-107492GB-100 (Spanish Ministry of Science and Innovation).The epicardium is the outermost cell layer in the vertebrate heart that originates during development from mesothelial precursors located in the proepicardium and septum transversum. The epicardial layer plays a key role during cardiogenesis since a subset of epicardial-derived cells (EPDCs) undergo an epithelial–mesenchymal transition (EMT); migrate into the myocardium; and differentiate into distinct cell types, such as coronary vascular smooth muscle cells, cardiac fibroblasts, endothelial cells, and presumably a subpopulation of cardiomyocytes, thus contributing to complete heart formation. Furthermore, the epicardium is a source of paracrine factors that support cardiac growth at the last stages of cardiogenesis. Although several lineage trace studies have provided some evidence about epicardial cell fate determination, the molecular mechanisms underlying epicardial cell heterogeneity remain not fully understood. Interestingly, seminal works during the last decade have pointed out that the adult epicardium is reactivated after heart damage, re-expressing some embryonic genes and contributing to cardiac remodeling. Therefore, the epicardium has been proposed as a potential target in the treatment of cardiovascular disease. In this review, we summarize the previous knowledge regarding the regulation of epicardial cell contribution during development and the control of epicardial reactivation in cardiac repair after damage.Spanish Government BFU2015-67131 PID2019-107492GB-10

Toxicity and biodegradation of zinc ferrite nanoparticles in Xenopus laevis

Zn-doped Fe3O4 magnetic nanoparticles have been proposed as the ideal ferrite for some biomedical applications like magnetic hyperthermia or photothermal therapy because of the possibility to adjust their size and chemical composition in order to design tailored treatments. However, reliable approaches are needed to risk assess Zn ferrite nanoparticles before clinical development. In this work, the in vitro toxicity of the nanoparticles was evaluated in five cellular models (Caco-2, HepG2, MDCK, Calu-3 and Raw 264.7) representing different target organs/systems (gastrointestinal system, liver, kidney, respiratory system and immune system). For the first time, these nanoparticles were evaluated in an in vivo Xenopus laevis model to study whole organism toxicity and their impact on iron and zinc metabolic pathways. Short and long-term in vivo exposure studies provided insights into the contrasting adverse effects between acute and chronic exposure. Quantitative PCR combined with elemental analysis and AC magnetic susceptibility measurements revealed that at short-term exposure (72 h) the nanoparticles’ absorption process is predominant, with the consequent over-expression of metal transporters and metal response proteins. At long-term exposure (120 h), there is an up-regulation of metal accumulation involved genes and the return to basal levels of both iron and zinc transporters, involved in the uptake of metals. This suggests that at this stage the nanoparticles’ absorption process is residual compared with the following steps in metabolism, distribution and/or excretion processes, indicated by the increase of iron accumulation proteins at both transcriptional and translational level. This testing approach based on a battery of cellular systems and the use of the Xenopus laevis model could be a viable strategy for studying the toxicity, degradability and ultimately the long-term fate of zinc ferrites in the organism

Predictive factors and early biomarkers of response in multiple sclerosis patients treated with natalizumab

There are an increasing number of treatments available for multiple sclerosis (MS). The early identification of optimal responders to individual treatments is important to achieve individualized therapy. With this aim, we performed a multicenter retrospective longitudinal study including 186 MS patients treated with natalizumab who were followed for 2 years. We analyzed the following variables at recruitment: sex, current age, age at disease onset, disease duration, EDSS, number of T2 and Gd + lesions, IgG and IgM oligoclonal bands, HLA class II (DR, DRB, DQA, DQB, and DRB1*15:01), IgG and IgM antibody titers against human herpesvirus 6 (HHV-6) and the antibody response to Epstein–Barr virus (EBV) through the measurement of the anti-EBNA-1 and anti-VCA IgG titers, in relation to clinical response (no relapses or disability progression), and to NEDA-3 (no evidence of disease activity in terms of clinical response and no changes in MRI scans either) after 2-years follow-up. Baseline EDSS score, baseline EBNA-1 IgG titers and percentage change of HHV6 IgG titers between baseline and 6 month visits were significantly different in clinical responders and in NEDA-3 status (all of them remained significant in the multivariate analysis). We identified three variables for the early identification of natalizumab optimal responders in a rapid and cost-effective approach

Resonance capture cross section of 207Pb

The radiative neutron capture cross section of 207Pb has been measured at the CERN neutron time of flight installation n_TOF using the pulse height weighting technique in the resolved energy region. The measurement has been performed with an optimized setup of two C6D6 scintillation detectors, which allowed us to reduce scattered neutron backgrounds down to a negligible level. Resonance parameters and radiative kernels have been determined for 16 resonances by means of an R-matrix analysis in the neutron energy range from 3 keV to 320 keV. Good agreement with previous measurements was found at low neutron energies, whereas substantial discrepancies appear beyond 45 keV. With the present results, we obtain an s-process contribution of 77(8)% to the solar abundance of 207Pb. This corresponds to an r-process component of 23(8)%, which is important for deriving the U/Th ages of metal poor halo stars.Comment: 7 pages, 3 figures, to be published in Phys. Rev.

Dinosaur bonebed amber from an original swamp forest soil

Dinosaur bonebeds with amber content, yet scarce, offer a superior wealth and quality of data on ancient terrestrial ecosystems. However, the preserved palaeodiversity and/or taphonomic characteristics of these exceptional localities had hitherto limited their palaeobiological potential. Here, we describe the amber from the Lower Cretaceous dinosaur bonebed of Ariño (Teruel, Spain) using a multidisciplinary approach. Amber is found in both a root layer with amber strictly in situ and a litter layer mainly composed of aerial pieces unusually rich in bioinclusions, encompassing 11 insect orders, arachnids, and a few plant and vertebrate remains, including a feather. Additional palaeontological data¿charophytes, palynomorphs, ostracods¿ are provided. Ariño arguably represents the most prolific and palaeobiologically diverse locality in which fossiliferous amber and a dinosaur bonebed have been found in association, and the only one known where the vast majority of the palaeontological assemblage suffered no or low-grade pre-burial transport. This has unlocked unprecedentedly complete and reliable palaeoecological data out of two complementary windows of preservation¿the bonebed and the amber¿from the same site

The Pierre Auger Observatory III: Other Astrophysical Observations

Astrophysical observations of ultra-high-energy cosmic rays with the Pierre Auger ObservatoryComment: Contributions to the 32nd International Cosmic Ray Conference, Beijing, China, August 201

A search for point sources of EeV photons

Measurements of air showers made using the hybrid technique developed with the fluorescence and surface detectors of the Pierre Auger Observatory allow a sensitive search for point sources of EeV photons anywhere in the exposed sky. A multivariate analysis reduces the background of hadronic cosmic rays. The search is sensitive to a declination band from -85{\deg} to +20{\deg}, in an energy range from 10^17.3 eV to 10^18.5 eV. No photon point source has been detected. An upper limit on the photon flux has been derived for every direction. The mean value of the energy flux limit that results from this, assuming a photon spectral index of -2, is 0.06 eV cm^-2 s^-1, and no celestial direction exceeds 0.25 eV cm^-2 s^-1. These upper limits constrain scenarios in which EeV cosmic ray protons are emitted by non-transient sources in the Galaxy.Comment: 28 pages, 10 figures, accepted for publication in The Astrophysical Journa

Towards a target label-free suboptimum oligonucleotide displacement-based detection system

A novel method for the future development of label-free DNA sensors is proposed here. The approach is based on the displacement of a labelled suboptimum mutated oligonucleotide hybridised with the immobilised biotin-capture probe. The target fully complementary to the biotin-capture probe can displace the labelled oligonucleotide causing a subsequent decrease of the signal that verifies the presence of the target. The decrease of signal was demonstrated to be proportional to the target concentration. A study of the hybridisation of mutated and complementary labelled oligonucleotides with an immobilised biotin-capture probe was carried out. Different kinetic and thermodynamic behaviour was observed for heterogeneous hybridisation of biotin-capture probe with complementary or suboptimum oligonucleotides. The displacement method evaluated colourimetrically achieved the objective of decreasing the response time from 1 h for direct hybridisation of 19-mer oligonucleotides in the direct enzyme-linked oligonucleotide assay (ELONA) to 5 min in the case of displacement detection in the micromolar concentration range