Growth hormone remodels the 3D-structure of the mitochondria of inflammatory macrophages and promotes metabolic reprogramming

IntroductionMacrophages are a heterogeneous population of innate immune cells that support tissue homeostasis through their involvement in tissue development and repair, and pathogen defense. Emerging data reveal that metabolism may control macrophage polarization and function and, conversely, phenotypic polarization may drive metabolic reprogramming.MethodsHere we use biochemical analysis, correlative cryogenic fluorescence microscopy and cryo-focused ion-beam scanning electron microscopy.ResultsWe demonstrate that growth hormone (GH) reprograms inflammatory GM-CSF-primed monocyte-derived macrophages (GM-MØ) by functioning as a metabolic modulator. We found that exogenous treatment of GM-MØ with recombinant human GH reduced glycolysis and lactate production to levels similar to those found in anti-inflammatory M-MØ. Moreover, GH treatment of GM-MØ augmented mitochondrial volume and altered mitochondrial dynamics, including the remodeling of the inner membrane to increase the density of cristae.ConclusionsOur data demonstrate that GH likely serves a modulatory role in the metabolism of inflammatory macrophages and suggest that metabolic reprogramming of macrophages should be considered as a new target to intervene in inflammatory diseases

Cost-effectiveness analysis of pemetrexed versus docetaxel in the second-line treatment of non-small cell lung cancer in Spain: results for the non-squamous histology population

BackgroundThe objective of this study was to conduct a cost-effectiveness evaluation of pemetrexed compared to docetaxel in the treatment of advanced or metastatic non-small cell lung cancer (NSCLC) for patients with predominantly non-squamous histology in the Spanish healthcare setting.MethodsA Markov model was designed consisting of stable, responsive, progressive disease and death states. Patients could also experience adverse events as long as they received chemotherapy. Clinical inputs were based on an analysis of a phase III clinical trial that identified a statistically significant improvement in overall survival for non-squamous patients treated with pemetrexed compared with docetaxel. Costs were collected from the Spanish healthcare perspective.ResultsOutcomes of the model included total costs, total quality-adjusted life years (QALYs), total life years gained (LYG) and total progression-free survival (PFS). Mean survival was 1.03 years for the pemetrexed arm and 0.89 years in the docetaxel arm; QALYs were 0.52 compared to 0.42. Per-patient lifetime costs were € 34677 and € 32343, respectively. Incremental cost-effectiveness ratios were € 23967 per QALY gained and € 17225 per LYG.ConclusionsPemetrexed as a second-line treatment option for patients with a predominantly non-squamous histology in NSCLC is a cost-effective alternative to docetaxel according to the € 30000/QALY threshold commonly accepted in Spain

La Real Armada y el mundo hispánico en el siglo XVIII

La coordinación de este libro estuvo a cargo de Agustín Guimerá Ravina y Olivier ChalinePeer reviewe

The Tree Biodiversity Network (BIOTREE-NET): prospects for biodiversity research and conservation in the Neotropics

Biodiversity research and conservation efforts in the tropics are hindered by the lack of knowledge of the assemblages found there, with many species undescribed or poorly known. Our initiative, the Tree Biodiversity Network (BIOTREE-NET), aims to address this problem by assembling georeferenced data from a wide range of sources, making these data easily accessible and easily queried, and promoting data sharing. The database (GIVD ID NA-00-002) currently comprises ca. 50,000 tree records of ca. 5,000 species (230 in the IUCN Red List) from \u3e2,000 forest plots in 11 countries. The focus is on trees because of their pivotal role in tropical forest ecosystems (which contain most of the world\u27s biodiversity) in terms of ecosystem function, carbon storage and effects on other species. BIOTREE-NET currently focuses on southern Mexico and Central America, but we aim to expand coverage to other parts of tropical America. The database is relational, comprising 12 linked data tables. We summarise its structure and contents. Key tables contain data on forest plots (including size, location and date(s) sampled), individual trees (including diameter, when available, and both recorded and standardised species name), species (including biological traits of each species) and the researchers who collected the data. Many types of queries are facilitated and species distribution modelling is enabled. Examining the data in BIOTREE-NET to date, we found an uneven distribution of data in space and across biomes, reflecting the general state of knowledge of the tropics. More than 90% of the data were collected since 1990 and plot size varies widely, but with most less than one hectare in size. A wide range of minimum sizes is used to define a \u27tree\u27. The database helps to identify gaps that need filling by further data collection and collation. The data can be publicly accessed through a web application at http://portal.biotreenet.com. Researchers are invited and encouraged to contribute data to BIOTREE-NET

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

La Red Internacional de Inventarios Forestales (BIOTREE-NET) en Mesoamérica: avances, retos y perspectivas futuras

Conservation efforts in Neotropical regions are often hindered by lack of data, since for many species there is a vacuum of information, and many species have not even been described yet. The International Network of Forest Inventory Plots (BIOTREE-NET) gathers and facilitates access to tree data from forest inventory plots in Mesoamerica, while encouraging data exchange between researchers, managers and conservationists. The information is organised and standardised into a single database that includes spatially explicit data. This article describes the scope and objectives of the network, its progress, and the challenges and future perspectives. The database includes above 50000 tree records of over 5000 species from more than 2000 plots distributed from southern Mexico through to Panama. Information is heterogeneous, both in nature and shape, as well as in the geographical coverage of inventory plots. The database has a relational structure, with 12 inter-connected tables that include information about plots, species names, dbh, and functional attributes of trees. A new system that corrects typographical errors and achieves taxonomic and nomenclatural standardization was developed using The Plant List (http://theplantlist.org/) as reference. Species distribution models have been computed for around 1700 species using different methods, and they will be publicly accessible through the web site in the future (http://portal.biotreenet.com). Although BIOTREE-NET has contributed to the development of improved species distribution models, its main potential lies, in our opinion, in studies at the community level. Finally, we emphasise the need to expand the network and encourage researchers willing to share data and to join the network and contribute to the generation of further knowledge about forest biodiversity in Neotropical regions

Trafalgar y la desconexión hispana del Atlántico

Actas de la VIII Reunión Científica de la Fundación Española de Historia Moderna. Madrid Junio de 2004La batalla de Trafalgar entre Inglaterra, España y Francia fue el momento histórico sobre el mar más importante del siglo XIX. Tras la batalla, Gran Bretaña no pudo ser invadida por el ejército de Napoleón. El Imperio francés concentró sus fuerzas de expansión sobre el Continente Europeo, con una estrategia de grandes victorias terrestres. Pero la Corona de España perdió desde entonces la iniciativa en el Océano Atlántico, con graves consecuencias para mantener su Imperio en América. Trafalgar fue el final de una época y el principio de otra.Peer reviewe

Géneros híbridos y libros mixtos en el Siglo de Oro

Este dossier pretende reflexionar sobre algunas obras que hoy percibimos a medio camino entre dos formas de expresión artística, como la prosa y el verso ; o entre dos disciplinas, como la historia y la literatura, o entre ésta, la filosofía y la política. Es posible que en el Siglo de Oro los diversos asedios a los géneros clásicos —épica, lírica, dramática— obedezcan a la creatividad de los grandes autores y al espíritu polémico con que recibían determinadas innovaciones. Pero también lo es que el mundo de la imprenta, denominada hoy industria editorial, intuyera la rentabilidad de mezclar poesía e imagen, o escritura y grabado, para ofrecer un producto híbrido, más atractivo a los lectores ; o de lanzar folletos de circunstancias, como los libelos políticos, que no estaban entre los géneros canónicos. Los siete artículos de la monografía analizan algunos de dichos fenómenos a partir de obras mixtas, y como contrapunto se formula una nueva hipótesis sobre el género (o géneros) y los propósitos del Criticón de Baltasar Gracián. Ce dossier propose une réflexion autour de certaines œuvres, perçues actuellement à mi-chemin entre deux genres artistiques, comme la prose et le vers, ou bien entre deux disciplines : histoire et littérature, littérature et philosophie, ou encore littérature et politique. Il est probable qu’au Siècle d’or, les divers assauts faits aux genres classiques — épique, lyrique, dramatique — soient dus à la créativité des grands auteurs de l’époque et à l’esprit de polémique dans lequel certaines nouveautés étaient reçues. Mais il est vraisemblable aussi que le monde de l’imprimerie, que nous appelerions aujourd’hui édition, a pu entrevoir l’intérêt de mélanger la poésie et l’image, ou l’écriture et la gravure, pour proposer un produit hybride, plus attirant pour les lecteurs ; ou bien de lancer des brochures de circonstance, tels que les libelles politiques, qui ne faisaient pas partie des genres canoniques. Les sept articles de notre monographie analysent certains desdits phénomènes, à partir de certaines œuvres mêlées, tandis que le contrepoint propose une nouvelle hypothèse sur le genre (les genres) et les intentions du Criticón de Baltasar Gracián. This dossier looks at some works that today are viewed as falling somewhere between two forms of artistic expression such as prose and verse, or between two disciplines such as history and literature, or again between literature, philosophy and politics. In the Golden Age the various assaults on the classic genres—epic, lyric, dramatic— may have been a product of the creativity of great writers and the argumentative spirit in which they received certain innovations. But it is also possible that the generality of printers—which today we call the publishing industry—anticipated the profits to be derived from mixing poetry and image, or writing and engraving, to offer a hybrid product, more attractive o readers; or of putting out gossip sheets,such as political libels, which were not among the standard genres. The seven articles in this monograph analyse these phenomena in the light of some mixed works; in counterpoint it offers a new hypothesis regarding the genre (or genres) and the intent behind Baltasar Criticón