Estradiol Stimulates Vasodilatory and Metabolic Pathways in Cultured Human Endothelial Cells

Vascular effects of estradiol are being investigated because there are controversies among clinical and experimental studies. DNA microarrays were used to investigate global gene expression patterns in cultured human umbilical vein endothelial cells (HUVEC) exposed to 1 nmol/L estradiol for 24 hours. When compared to control, 187 genes were identified as differentially expressed with 1.9-fold change threshold. Supervised principal component analysis and hierarchical cluster analysis revealed the differences between control and estradiol-treated samples. Physiological concentrations of estradiol are sufficient to elicit significant changes in HUVEC gene expression. Notch signaling, actin cytoskeleton signaling, pentose phosphate pathway, axonal guidance signaling and integrin signaling were the top-five canonical pathways significantly regulated by estrogen. A total of 26 regulatory networks were identified as estrogen responsive. Microarray data were confirmed by quantitative RT-PCR in cardiovascular meaning genes; cyclooxigenase (COX)1, dimethylarginine dimethylaminohydrolase (DDAH)2, phospholipase A2 group IV (PLA2G4) B, and 7-dehydrocholesterol reductase were up-regulated by estradiol in a dose-dependent and estrogen receptor-dependent way, whereas COX2, DDAH1 and PLA2G4A remained unaltered. Moreover, estradiol-induced COX1 gene expression resulted in increased COX1 protein content and enhanced prostacyclin production. DDAH2 protein content was also increased, which in turn decreased asymmetric dimethylarginine concentration and increased NO release. All stimulated effects of estradiol on gene and protein expression were estrogen receptor-dependent, since were abolished in the presence of the estrogen receptor antagonist ICI 182780. This study identifies new vascular mechanisms of action by which estradiol may contribute to a wide range of biological processes

Magnetic properties of ZnO nanoparticles

We experimentally show that it is possible to induce room-temperature ferromagnetic-like behavior in ZnO nanoparticles without doping with magnetic impurities but simply inducing an alteration of their electronic configuration. Capping ZnO nanoparticles (similar to 10 nm size) with different organic molecules produces an alteration of their electronic configuration that depends on the particular molecule, as evidenced by photoluminescence and X-ray absorption spectroscopies and altering their magnetic properties that varies from diamagnetic to ferromagnetic-like behavior

Analysis of the rumen microbiome and metabolome to study the effect of an antimethanogenic treatment applied in early life of kid goats

This work aimed to gain insight into the transition from milk to solid feeding at weaning combining genomics and metabolomics on rumen contents from goat kids treated with a methanogenic inhibitor (bromochloromethane, BCM). Sixteen goats giving birth to two kids were used. Eight does were treated (D+) with BCM after giving birth and over 2 months. One kid per doe in both groups was treated with BCM (k+) for 3 months while the other was untreated (k–). Rumen samples were collected from kids at weaning (W) and 1 (W + 1) and 4 (W + 4) months after and from does at weaning and subjected to 16S pyrosequencing and metabolomics analyses combining GC/LC-MS. Results from pyrosequencing showed a clear effect of age of kids, with more diverse bacterial community as solid feed becomes more important after weaning. A number of specific OTUs were significantly different as a result of BCM treatment of the kid at W while at W + 1 and W + 4 less OTUs were significantly changed. At W + 1, Prevotella was increased and Butyrivibrio decreased in BCM treated kids. At W + 4 only the effect of treating mothers resulted in significant changes in the abundance of some OTUs: Ruminococcus, Butyrivibrio and Prevotella. The analysis of the OTUs shared by different treatments revealed that kids at weaning had the largest number of unique OTUs compared with kids at W + 1 (137), W + 4 (238), and does (D) (23). D + k+ kids consistently shared more OTUs with mothers than the other three groups at the three sampling times. The metalobomic study identified 473 different metabolites. In does, lipid super pathway included the highest number of metabolites that were modified by BCM, while in kids all super-pathways were evenly affected. The metabolomic profile of samples from kids at W was different in composition as compared to W + 1 and W + 4, which may be directly ascribed to the process of rumen maturation and changes in the solid diet. This study shows the complexity of the bacterial community and metabolome in the rumen before weaning, which clearly differ from that after weaning and highlight the importance of the dam in transmitting the primary bacterial community after birth.</p

From the North-Iberian Margin to the Alboran Basin: A lithosphere geo-transect across the Iberian Plate

A ~ 1000-km-long lithospheric transect running from the North-Iberian Margin to the Alboran Basin (W-Mediterranean) is investigated. The main goal is to image the changes in the crustal and upper mantle structure occurring in: i) the North-Iberian margin, whose deformation in Alpine times gave rise to the uplift of the Cantabrian Mountains related to Iberia-Eurasia incipient subduction; ii) the Spanish Meseta, characterized by the presence of Cenozoic basins on top of a Variscan basement with weak Alpine deformation in the Central System, and localized Neogene-Quaternary deep volcanism; and iii) the Betic-Alboran system related to Africa-Iberia collision and the roll-back of the Ligurian-Tethyan domain. The modeling approach, combines potential fields, elevation, thermal, seismic, and petrological data under a self-consistent scheme. The crustal structure is mainly constrained by seismic data whereas the upper mantle is constrained by tomographic models. The results highlight the lateral variations in the topography of the lithosphere-asthenosphere boundary (LAB), suggesting a strong lithospheric mantle strain below the Cantabrian and Betic mountain belts. The LAB depth ranges from 180 km beneath the Cantabrian Mountains to 135-110. km beneath Iberia Meseta deepening again to values of 160. km beneath the Betic Cordillera. The Central System, with a mean elevation of 1300. m, has a negligible signature on the LAB depth. We have considered four lithospheric mantle compositions: a predominantly average Phanerozoic in the continental mainland, two more fertile compositions in the Alboran Sea and in the Calatrava Volcanic Province, and a hydrated uppermost mantle in the North-Iberian Margin. These compositional differences allowed us to reproduce the main trends of the geophysical observables as well as the inferred P- and S-wave seismic velocities from tomography models and seismic experiments available in the study transect. The high mean topography of Iberia can be partly consistent with a low-velocity/high-temperature/low-density layer in the sublithospheric mantle.The presented work has been supported by Topo-Iberia Consolider-IngenioCSD2006-0004, GASAM/TopoMed (CGL2008-03474-E/BTE/07-TOPO-EUROPE-FP-006), TECLA (CGL2011-26670) funded by the Spanish Government, and PYRTEC-IP2 (SV-PA-10-03, funded by the Government of Asturias/ESF TOPO-EUROPE Programme) projects. AC benefitted from a JAE-PreCP grant from CSIC. JCA acknowledges the support from ARC GrantDP120102372.Peer Reviewe

CSA06 Computing, Software and Analysis challenge at the Spanish Tier-1 and Tier-2 sites

This note describes the participation of the Spanish centres PIC, CIEMAT and IFCA as Tier-1 and Tier-2 sites in the CMS CSA06 Computing, Software and Analysis challenge. A number of the facilities, services and workflows have been demonstrated at the 2008 25% scale. Very valuable experience has been gained running the complex computing system under realistic conditions at a significant scale. The focus of this note is on presenting achieved results, operational experience and lessons learnt during the challenge

Ulmus laevis in the Iberian Peninsula: a review of its ecology and conservation

European white elm (Ulmus laevis Pallas) populations are scarce, small and fragmented in the Iberian Peninsula. Due to these characteristics the indigenous status of the species in the region has been questioned, whilst the species? role in Iberian riparian forest ecology has been neglected. Herein we review past studies regarding this species? distribution and ecology in the Iberian Peninsula, with special emphasis on the establishment of conservation priorities. We first present a collection of palaeogeographic, historic and genetic data suggesting that the Iberian Peninsula was a glacial refuge for U. laevis. Secondly, we analyse U. laevis distribution in relation to soil physico- chemical properties and water availability in Spain. Following this, we focus on the reproductive biology of the species, and investigate the effect of masting and empty seed production on predation and regeneration establishment. Finally, based on this knowledge, we propose conservation policies for U. laevis in the Iberian Peninsula

Risk of gastric cancer in the environs of industrial facilities in the MCC-Spain study

Background: Gastric cancer is the fifth most frequent tumor worldwide. In Spain, it presents a large geographic variability in incidence, suggesting a possible role of environmental factors in its etiology. Therefore, epidemiologic research focused on environmental exposures is necessary. Objectives: To assess the association between risk of gastric cancer (by histological type and tumor site) and residential proximity to industrial installations, according to categories of industrial groups and specific pollutants released, in the context of a population-based multicase-control study of incident cancer conducted in Spain (MCC-Spain). Methods: In this study, 2664 controls and 137 gastric cancer cases from 9 provinces, frequency matched by province of residence, age, and sex were included. Distances from the individuals' residences to the 106 industries located in the study areas were computed. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance (from 1 km to 3 km) to industries, adjusting for matching variables and potential confounders. Results: Overall, no excess risk of gastric cancer was observed in people living close to the industrial installations, with ORs ranging from 0.73 (at ≤2.5 km) to 0.93 (at ≤1.5 km). However, by industrial sector, excess risks (OR; 95%CI) were found near organic chemical industry (3.51; 1.42-8.69 at ≤2 km), inorganic chemical industry (3.33; 1.12-9.85 at ≤2 km), food/beverage sector (2.48; 1.12-5.50 at ≤2 km), and surface treatment using organic solvents (3.59; 1.40-9.22 at ≤3 km). By specific pollutant, a statistically significant excess risk (OR; 95%CI) was found near (≤3 km) industries releasing nonylphenol (6.43; 2.30-17.97) and antimony (4.82; 1.94-12.01). Conclusions: The results suggest no association between risk of gastric cancer and living in the proximity to the industrial facilities as a whole. However, a few associations were detected near some industrial sectors and installations releasing specific pollutants.The authors thank all those who took part in this study by providing questionnaire data. This study was funded by: Scientific Foundation of the Spanish Association Against Cancer (Fundación Científica de la Asociación Española Contra el Cáncer (AECC) e grants EVP-1178/14 and GCTRA18022MORE); “Acción Transversal del Cáncer”, approved on the Spanish Ministry Council on October 11, 2007; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP); Spain’s Health Research Fund (Fondo de Investigación Sanitaria - FIS 12/01416); Carlos III Institute of Health (ISCIII) grants, co-funded by ERDF fundsea way to build Europee (grants PI08/0533, PI08/1359, PI08/1770, PS09/00773, PS09/01286, PS09/01662, PS09/01903, PS09/02078, PI11/00226, PI11/01403, PI11/01810, PI11/01889, PI11/02213, PI12/00150, PI12/00265, PI12/00488, PI12/00715, PI12/01270, PI14/00613, PI14/01219, PI15/00069, PI15/00914, PI15/01032, PI17-00092, PI17CIII/00034); the Fundación Marqués de Valdecilla (API 10/09); the Junta de Castilla y León (LE22A10-2); the Consejería de Salud of the Junta de Andalucía (PI-0571-2009, PI-0306-2011, salud201200057018tra); the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10); the Recercaixa (2010ACUP 00310); the European Commission grants FOOD-CT-2006-036224-HIWATE; the Catalan Government-Agency for Management of University and Research Grants (AGAUR) grants 2017SGR723 and 2014SGR850; the Catalan Government DURSI grant 2014SGR647; the Fundación Caja de Ahorros de Asturias; and the University of Oviedo. ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program.N

Control compounds for preclinical drug-induced liver injury assessment: Consensus-driven systematic review by the ProEuroDILI network

Background & Aims Idiosyncratic drug-induced liver injury (DILI) is a complex and unpredictable event caused by drugs, and herbal or dietary supplements. Early identification of human hepatotoxicity at preclinical stages remains a major challenge, in which the selection of validated in vitro systems and test drugs has a significant impact. In this systematic review, we analyzed the compounds used in hepatotoxicity assays and established a list of DILI-positive and -negative control drugs for validation of in vitro models of DILI, supported by literature and clinical evidence and endorsed by an expert committee from the COST Action ProEuroDILI Network (CA17112). Methods Following 2020 PRISMA guidelines, original research articles focusing on DILI which used in vitro human models and performed at least one hepatotoxicity assay with positive and negative control compounds, were included. Bias of the studies was assessed by a modified ‘Toxicological Data Reliability Assessment Tool’. Results A total of 51 studies (out of 2,936) met the inclusion criteria, with 30 categorized as reliable without restrictions. Although there was a broad consensus on positive compounds, the selection of negative compounds lacked clarity. 2D monoculture, short exposure times and cytotoxicity endpoints were the most tested, although there was no consensus on drug concentrations. Conclusions Extensive analysis highlighted the lack of agreement on control compounds for in vitro DILI assessment. Following comprehensive in vitro and clinical data analysis together with input from the expert committee, an evidence-based consensus-driven list of 10 positive and negative control drugs for validation of in vitro models of DILI is proposed.Funding for open access charge: Universidad de Málaga / CBUA