Resveratrol Improves Survival, Hemodynamics and Energetics in a Rat Model of Hypertension Leading to Heart Failure

Heart failure (HF) is characterized by contractile dysfunction associated with altered energy metabolism. This study was aimed at determining whether resveratrol, a polyphenol known to activate energy metabolism, could be beneficial as a metabolic therapy of HF. Survival, ventricular and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive model of HF, the Dahl salt-sensitive rat fed with a high-salt diet (HS-NT). Resveratrol (18 mg/kg/day; HS-RSV) was given for 8 weeks after hypertension and cardiac hypertrophy were established (which occurred 3 weeks after salt addition). Resveratrol treatment improved survival (64% in HS-RSV versus 15% in HS-NT, p<0.001), and prevented the 25% reduction in body weight in HS-NT (P<0.001). Moreover, RSV counteracted the development of cardiac dysfunction (fractional shortening −34% in HS-NT) as evaluated by echocardiography, which occurred without regression of hypertension or hypertrophy. Moreover, aortic endothelial dysfunction present in HS-NT was prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARα (peroxisome proliferator-activated receptor α) expression. We conclude that resveratrol treatment exerts beneficial protective effects on survival, endothelium–dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activators could be a relevant therapy in hypertension-induced HF

Captación y selección de materias primas en la primera metalurgia del Sureste de la península ibérica

The authors are grateful for the technical and human support provided by SGIker of UPV/EHU and European funding (ERDF and ESF). We are also in debt with Eduardo Galán, Ruth Maicas and Carmen Cacho, curators of the Museo Arqueológico Nacional (Madrid) for facilitating the sampling and study of metal objects as well as with Ignacio Soriano Llopis for his help on the selection and sampling of the Palmela points, with Massimo Chiaradia who performed the analyses of the Palmela points at the Department of Earth Sciences (University of Geneva, Switzerland) and with Óscar García Vuelta for his pictures of some assemblages. We also appreciate and the careful work of editing and style of the TP editorial team.The role of metallurgy in the Copper Age communities of the Iberian Southeast is a recurrent question of archaeological research in western Europe. Based on lead isotope and trace element analyses of archaeometallurgical remains, this paper addresses the territorial organisation of metallurgical production during the Copper Age (3100-2200 cal BC) in the Vera Basin (Almería, Spain), the region with the earliest metallurgical evidence in western Europe. This paper comprises the study of materials from the three main settlements with metallurgical activity in the area (Las Pilas, Santa Bárbara and Almizaraque), as well as some metal objects from these and other sites (La Encantada I, Loma de Belmonte and Las Churuletas 1). The results support a model of small-scale regional production whereby settlements exploited the resources of their nearby surroundings (up to 30 km as the crow flies). However, metallurgical exploitation prioritised mineralisations rich in arsenic and other elements, even when other sources were more readily accessible: for the case of Las Pilas, the exploitation of Pinar de Bédar sources instead of Sierra Cabrera, closer to the site; for the cases of Santa Bárbara and Almizaraque, the sources of Cerro Minado. The possibility that Almizaraque and Las Pilas also exploited the minerals of Herrerías, although to a lesser extent, remains open. Broader exchange networks are indicated by the data from finished objects, from which greater mobility can be inferred.El papel de la metalurgia en las comunidades de la Edad del Cobre del Sureste de la península ibérica es una cuestión recurrente en la investigación arqueológica en Europa occidental. A partir del análisis de isótopos de plomo y elementos traza de restos arqueometalúrgicos, este artículo aborda la organización territorial de la producción metalúrgica durante la Edad del Cobre (3100-2200 cal aC) en la cuenca de Vera (Almería, España); la región con las primeras evidencias metalúrgicas en Europa Occidental. Este artículo incluye el estudio de materiales de los tres principales asentamientos con actividad metalúrgica en la zona (Las Pilas, Santa Bárbara y Almizaraque), así como algunos objetos metálicos de estos y otros sitios (La Encantada I, Loma de Belmonte y Las Churuletas 1). Los resultados sustentan un modelo de producción regional a pequeña escala mediante el cual los asentamientos explotaron varios de los recursos de su entorno cercanos (hasta 30 km en línea recta). Se priorizaron las mineralizaciones ricas en arsénico y otros elementos, incluso cuando otras fuentes eran más accesibles: para el caso de Las Pilas, la explotación de las fuentes de Pinar de Bédar en lugar de las de Sierra Cabrera, más cercanas al yacimiento; y para los casos de Santa Bárbara y Almizaraque, las fuentes de Cerro Minado. La posibilidad de que tanto Almizaraque como Las Pilas también explotaran los minerales de Herrerías, aunque en menor medida, permanece abierta. La existencia de redes de intercambio más amplias queda reflejada por los datos de los objetos, a partir de los cuales se puede inferir una mayor movilidad.European funding (ERDF)European funding (ESF)This study was suported by the following sources of funding: a Marie Curie Intra European Fellowship (PN623183) funded within the 7th European Community Framework Programme; two Research and Development (R&D) projects funded by the Spanish Ministry of Science, Innovation and Universities: “Metal and amber: Models of raw materials circulation in Iberian Recent Prehistory” (HAR2017-82685-R) and “Tecnología y Sociedad. Las primeras artesanías de las comunidades neolíticas en Andalucía oriental entre el VI y el III milenio a.n.e” (HAR 2016-78197-P); and a Research Excellence Chair 2011-2016 “Activités minières et métallurgiques: anthropisation des milieux et productions matérielles”, funded by the Centre National de la Recherche Scientifique (CNRS)

Acceptability in the Older Population: The Importance of an Appropriate Tablet Size

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).Presenting many advantages, solid oral dosage forms (SODFs) are widely manufactured and frequently prescribed in older populations regardless of the specific characteristics of patients. Commonly, patients with dysphagia (swallowing disorders) experience difficulties taking SODFs, which may lead to non-adherence or misuse. SODF characteristics (e.g., size, shape, thickness) are likely to influence swallowability. Herein, we used the acceptability reference framework (the ClinSearch acceptability score test (CAST))—a 3D-map juxtaposing two acceptability profiles—to investigate the impact of tablet size on acceptability. We collected 938 observer reports on the tablet intake by patients ≥ 65 y in hospitals or care homes. As we might expect, tablets could be classified as accepted in older patients without dysphagia (n = 790), while not in those with swallowing disorders (n = 146). However, reducing the tablet size had a significant impact on acceptability in this subpopulation: tablets < 6.5 mm appeared to be accepted by patients with swallowing disorders. Among the 309 distinct tablets assessed in this study, ranging in size from 4.7 to 21.5 mm, 83% are ≥ 6.5 mm and consequently may be poorly accepted by institutionalized older people and older inpatients suffering from dysphagia. This underlines the need to develop and prescribe medicines with the best adapted characteristics to reach an optimal acceptability in targeted users.Peer reviewedFinal Published versio

Global Environmental Change : Local perceptions, understandings and explanations

Global environmental change (GEC) is an increasingly discussed phenomenon in the scientific literature as evidence of its presence and impacts continues to grow. Yet, while the documentation of GEC is becoming more readily available, local perceptions of GEC— particularly in small-scale societies—and preferences about how to deal with it, are still largely overlooked. Local knowledge and perceptions of GEC are important in that agents make decisions (including on natural resource management) based on individual perceptions. We carried out a systematic literature review that aims to provide an exhaustive state-of-the-art of the degree to and manner in which the study of local perceptions of change are being addressed in GEC research. We reviewed 126 articles found in peer-reviewed journals (between 1998 and 2014) that address local perceptions of GEC. We used three particular lenses of analysis that are known to influence local perceptions, namely (i) cognition, (ii) culture and knowledge, and (iii) possibilities for adaptation.We present our findings on the geographical distribution of the current research, the most common changes reported, perceived drivers and impacts of change, and local explanations and evaluations of change and impacts. Overall, we found the studies to be geographically biased, lacking methodological reporting, mostly theory based with little primary data, and lacking of indepth analysis of the psychological and ontological influences in perception and implications for adaptation. We provide recommendations for future GEC research and propose the development of a “meta-language” around adaptation, perception, and mediation to encourage a greater appreciation and understanding of the diversity around these phenomena across multiple scales, and improved codesign and facilitation of locally relevant adaptation and mitigation strategies.Peer reviewe

Gene-metabolite annotation with shortest reactional distance enhances metabolite genome-wide association studies results

Metabolite genome-wide association studies (mGWAS) have advanced our understanding of the genetic control of metabolite levels. However, interpreting these associations remains challenging due to a lack of tools to annotate gene-metabolite pairs beyond the use of conservative statistical significance threshold. Here, we introduce the shortest reactional distance (SRD) metric, drawing from the comprehensive KEGG database, to enhance the biological interpretation of mGWAS results. We applied this approach to three independent mGWAS, including a case study on sickle cell disease patients. Our analysis reveals an enrichment of small SRD values in reported mGWAS pairs, with SRD values significantly correlating with mGWAS p values, even beyond the standard conservative thresholds. We demonstrate the utility of SRD annotation in identifying potential false negatives and inaccuracies within current metabolic pathway databases. Our findings highlight the SRD metric as an objective, quantitative and easy-to-compute annotation for gene-metabolite pairs, suitable to integrate statistical evidence to biological networks

Response to "Practice what you preach : Ensuring scientific spheres integrate Indigenous Peoples' and Local Communities' rights and agency too" by Lopez-Maldonado

Non peer reviewe

Hybridization of a RoR HPP with a BESS—The XFLEX HYDRO Vogelgrun Demonstrator

In the XFLEX HYDRO Vogelgrun demonstrator, a run-of-river hydropower plant, the hybridization of one turbine-generator unit with a battery energy storage system is being investigated. This paper describes the integration methodology of the hybrid control algorithm without replacing the existing speed governor of the unit. Furthermore, the comparison of the performances of a non-hybrid and hybrid unit is discussed, and first experiences gained during the operation and monitoring of the hybrid operating mode are presented.This work has been realized with the participation of INES.2S. David Valentín and Alexandre Presas acknowledge the Serra Húnter program. The corresponding author would like to express his gratitude to Nicolas Ruchonnet for his contributions during the revision.Postprint (published version

High-resolution imaging of the Pyrenees and Massif Central from the data of the PYROPE and IBERARRAY portable array deployments

International audienceThe lithospheric structures beneath the Pyrenees, which holds the key to settle long-standing controversies regarding the opening of the Bay of Biscay and the formation of the Pyrenees, are still poorly known. The temporary PYROPE and IBERARRAY experiments have recently filled a strong deficit of seismological stations in this part of western Europe, offering a new and unique opportunity to image crustal and mantle structures with unprecedented resolution. Here we report the results of the first tomographic study of the Pyrenees relying on this rich data set. The important aspects of our tomographic study are the precision of both absolute and relative traveltime measurements obtained by a nonlinear simulated annealing waveform fit and the detailed crustal model that has been constructed to compute accurate crustal corrections. Beneath the Massif Central, the most prominent feature is a widespread slow anomaly that reflects a strong thermal anomaly resulting from the thinning of the lithosphere and upwelling of the asthenosphere. Our tomographic images clearly exclude scenarios involving subduction of oceanic lithosphere beneath the Pyrenees. In contrast, they reveal the segmentation of lithospheric structures, mainly by two major lithospheric faults, the Toulouse fault in the central Pyrenees and the Pamplona fault in the western Pyrenees. These inherited Hercynian faults were reactivated during the Cretaceous rifting of the Aquitaine and Iberian margins and during the Cenozoic Alpine convergence. Therefore, the Pyrenees can be seen as resulting from the tectonic inversion of a segmented continental rift that was buried by subduction beneath the European plate

The Generation Challenge Programme comparative plant stress-responsive gene catalogue

The Generation Challenge Programme (GCP; www.generationcp.org) has developed an online resource documenting stress-responsive genes comparatively across plant species. This public resource is a compendium of protein families, phylogenetic trees, multiple sequence alignments (MSA) and associated experimental evidence. The central objective of this resource is to elucidate orthologous and paralogous relationships between plant genes that may be involved in response to environmental stress, mainly abiotic stresses such as water deficit (‘drought’). The web-based graphical user interface (GUI) of the resource includes query and visualization tools that allow diverse searches and browsing of the underlying project database. The web interface can be accessed at http://dayhoff.generationcp.org