200 research outputs found

    Caracterización microambiental de la Cueva de Pozalagua (Vizcaya): aplicación a la gestión y protección de cavidades turísticas

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    There are summarized the data obtained after monitoring some microenvironmental parameters in the Pozalagua cave from 1st April 2001 to 1st july 2002. The singularity of this show cave is because the high amount of helictites type speleothems. Host rock, speleothems and infiltration waters have been analysed as well as the effect of the visits into the cave have been evaluated. It is stated that visits influence the temperature and CO2 levels inside the cave and the natural system need some time in recover from this changes. During massive visits increase in cave temperature is over the natural annual thermal oscillation. Management guidelines focused in visits schedule have been proposed in order to minimize the effects of the visits and to keep the cave microenvironment near the natural conditions.Se presentan los datos obtenidos tras el registro en continuo de diversos parámetros microambientales en la Cueva de Pozalagua (Vizcaya) durante el período del 1 de abril de 2001 al 1 de julio de 2002. La singularidad de esta cueva turística se debe a la alta presencia de espeleotemas tipo excéntricas o helictitas. Tras la caracterización de la roca encajante y diversos espeleotemas, así como de la hidroquímica de las aguas de infiltración que circulan por la misma, se ha evaluado el efecto que tienen las visitas turísticas en esta cavidad. Se constata que las visitas influyen claramente en la temperatura de la cavidad y en los niveles de CO2 de la misma, de lo que el sistema natural tarda tiempo en recuperarse. En períodos de visitas masivas se ha comprobado que el incremento de temperatura que se produce en la cavidad es superior a la oscilación térmica natural de la misma durante un ciclo anual. Se proponen medidas de gestión de la cavidad, principalmente enfocadas a optimizar el régimen de visitas, que minimicen el impacto de las mismas y que permitan mantener las condiciones microambientales de la cavidad cercanas a las condiciones originales naturales

    In vivo inhibition of the mitochondrial H+-ATP synthase in neurons promotes metabolic preconditioning

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    A key transducer in energy conservation and signaling cell death is the mitochondrial H+-ATP synthase. The expression of the ATPase inhibitory factor 1 (IF1) is a strategy used by cancer cells to inhibit the activity of the H+-ATP synthase to generate a ROS signal that switches on cellular programs of survival. We have generated a mouse model expressing a mutant of human IF1 in brain neurons to assess the role of the H+-ATP synthase in cell death in vivo. The expression of hIF1 inhibits the activity of oxidative phosphorylation and mediates the shift of neurons to an enhanced aerobic glycolysis. Metabolic reprogramming induces brain preconditioning affording protection against quinolinic acid-induced excitotoxicity. Mechanistically, preconditioning involves the activation of the Akt/p70S6K and PARP repair pathways and Bcl-xL protection from cell death. Overall, our findings provide the first in vivo evidence highlighting the H +-ATP synthase as a target to prevent neuronal cell deathThis work was supported by grants from the MEC (BFU2010-18903), CIBERER and by Comunidad de Madrid (S2011/BMD-2402) to JMC; MINECO (PLE2009-0101 and SAF2010-17167), TerCel (RD12/0019/0013), and Neurostem-CM (S2010-BMD-2336) to AMS and ISCIII Grant PI 10/02628 to CN, Spai

    The bioenergetic signature of isogenic colon cancer cells predicts the cell death response to treatment with 3-bromopyruvate, iodoacetate or 5-fluorouracil

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    <p>Abstract</p> <p>Background</p> <p>Metabolic reprogramming resulting in enhanced glycolysis is a phenotypic trait of cancer cells, which is imposed by the tumor microenvironment and is linked to the down-regulation of the catalytic subunit of the mitochondrial H<sup>+</sup>-ATPase (β-F1-ATPase). The <it>bioenergetic signature </it>is a protein ratio (β-F1-ATPase/GAPDH), which provides an estimate of glucose metabolism in tumors and serves as a prognostic indicator for cancer patients. Targeting energetic metabolism could be a viable alternative to conventional anticancer chemotherapies. Herein, we document that the <it>bioenergetic signature </it>of isogenic colon cancer cells provides a gauge to predict the cell-death response to the metabolic inhibitors, 3-bromopyruvate (3BrP) and iodoacetate (IA), and the anti-metabolite, 5-fluorouracil (5-FU).</p> <p>Methods</p> <p>The <it>bioenergetic signature </it>of the cells was determined by western blotting. Aerobic glycolysis was determined from lactate production rates. The cell death was analyzed by fluorescence microscopy and flow cytometry. Cellular ATP concentrations were determined using bioluminiscence. Pearson's correlation coefficient was applied to assess the relationship between the <it>bioenergetic signature </it>and the cell death response. <it>In vivo </it>tumor regression activities of the compounds were assessed using a xenograft mouse model injected with the highly glycolytic HCT116 colocarcinoma cells.</p> <p>Results</p> <p>We demonstrate that the <it>bioenergetic signature </it>of isogenic HCT116 cancer cells inversely correlates with the potential to execute necrosis in response to 3BrP or IA treatment. Conversely, the <it>bioenergetic signature </it>directly correlates with the potential to execute apoptosis in response to 5-FU treatment in the same cells. However, despite the large differences observed in the <it>in vitro </it>cell-death responses associated with 3BrP, IA and 5-FU, the <it>in vivo </it>tumor regression activities of these agents were comparable.</p> <p>Conclusions</p> <p>Overall, we suggest that the determination of the <it>bioenergetic signature </it>of colon carcinomas could provide a tool for predicting the therapeutic response to various chemotherapeutic strategies aimed at combating tumor progression.</p

    Impaired mitochondrial oxidative phosphorylation in the peroxisomal disease X-linked adrenoleukodystrophy

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    This is a pre-copyedited, author-produced PDF of an article accepted for publication in Human Molecular Genetics following peer review. The version of record Human Molecular Genetics 22.16 (2013): 3296-3305 is available online at http://hmg.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=23604518X-linked adrenoleukodystrophy (X-ALD) is an inherited metabolic disorder of the nervous system characterized by axonopathy in spinal cords and/or cerebral demyelination, adrenal insufficiency and accumulation of very long-chain fatty acids (VLCFAs) in plasma and tissues. The disease is caused by malfunction of the ABCD1 gene, which encodes a peroxisomal transporter of VLCFAs or VLCFA-CoA. In the mouse, Abcd1 loss causes late onset axonal degeneration in the spinal cord, associated with locomotor disability resembling the most common phenotype in patients, adrenomyeloneuropathy. We have formerly shown that an excess of the VLCFA C26:0 induces oxidative damage, which underlies the axonal degeneration exhibited by the Abcd1(-) mice. In the present study, we sought to investigate the noxious effects of C26:0 on mitochondria function. Our data indicate that in X-ALD patients' fibroblasts, excess of C26:0 generates mtDNA oxidation and specifically impairs oxidative phosphorylation (OXPHOS) triggering mitochondrial ROS production from electron transport chain complexes. This correlates with impaired complex V phosphorylative activity, as visualized by high-resolution respirometry on spinal cord slices of Abcd1(-) mice. Further, we identified a marked oxidation of key OXPHOS system subunits in Abcd1(-) mouse spinal cords at presymptomatic stages. Altogether, our results illustrate some of the mechanistic intricacies by which the excess of a fatty acid targeted to peroxisomes activates a deleterious process of oxidative damage to mitochondria, leading to a multifaceted dysfunction of this organelle. These findings may be of relevance for patient management while unveiling novel therapeutic targets for X-ALDThis study was supported by grants from the European Commission (FP7-241622), the European Leukodystrophy Association (ELA2009-036C5; ELA2008-040C4), the Spanish Institute for Health Carlos III (FIS PI080991 and FIS PI11/01043), the Autonomous Government of Catalonia (2009SGR85) to A.P. and the Spanish Institute for Health Carlos III (Miguel Servet program CP11/00080) to S.F. The CIBER on Rare Diseases (CIBERER) is an initiative of the ISCIII. The study was developed under the COST action BM0604 (to A.P.). J.L.-E. was a fellow of the Department of Education, Universities and Research of the Basque Country Government (BFI07.126). S.F. was a fellow of the European Leukodystrophy Association (ELA 2010-020F1). The studies conducted at the Department of Experimental Medicine were supported in part by R&D grants from the Spanish Ministry of Science and Innovation (BFU2009-11879/BFI), the Spanish Ministry of Health (PI11/1532), the Autonomous Government of Catalonia (2009SGR735), the ‘La Caixa’ Foundation and COST B35 Action of the European Union. D.C. is a fellow from the Spanish Ministry of Health (FI08-00707). The studies conducted at the Department of Biochemistry and Molecular Biology, University of Barcelona, were supported by grants SAF2008-01896 and SAF2011-23636 from the Spanish Ministry of Science and Innovatio

    Die Wettbewerbsfähigkeit der arabischen Mittelmeerländer im internationalen Vergleich

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    6 p.- Papers presented at the International Workshop "The Conservation of Subterranean Cultural Heritage", held 25-27 March 2014, in Seville, Spain.Paranhos constitutes one of the main water galleries excavated in the granite substratum of Porto City (Portugal) to gather the groundwater for public use during the past five centuries. This gallery is a Subterranean Cultural Heritage site with a potential use for underground geotourism under safe conditions. An environmental monitoring programme has been conducte in the site comprising rapid multi-parameters. This programme has allowed the identification of urban-induced causes of contamination of the aquifer and internal tunnel atmosphere (waste-water and gas leakage). This study has also comprised the determination of effective radioactive dose in different sectors of the tunnel for potential visitors based on 222Rn studies.Financiado con el Proyecto (HAR-2010-11432-E) Red de Ciencia y Tecnología para la Conservación del Patrimonio CulturalPeer reviewe

    La cueva de el Sidron (Borines, Piloña, Asturias) : primeros resultados

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    Se exponen los resultados preliminares de las excavaciones arqueológicas llevadas a cabo en la Cueva de El Sidrón entre 2000 y 2002, de acuerdo con los tres objetivos principales que conciernen al registro fósil humano: las características antropológicas, cómo y cuándo llegaron allí y la relación entre fósiles y cultura. Las primeras conclusiones obtenidas son que los restos humanos pertenecen al Neandertal, que el registro arqueológico corresponde a un tecno-complejo del Paleolítico Medio y que están en posición secundaria.We expose the preliminary results ofthe archaeological excavations developed between 2000-2002 in Sidrón's Cave, according to the three main objectives that concern the human fossil record: the anthropological characteristics, how and when they arrived there and the relation between fossils and culture. We conclude preliminarily that the record belongs to Horno Neanderthalensis, archeological remains to the Middle Paleolithic techno-complex, and they are in a secondary [email protected]

    Manganese oxides as biominerals in a granitic subterranean environment

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    Black coatings were detected on granite surfaces in groundwater catch work tunnels from Porto city (NW Portugal). XRD, FTIR, Micro-Raman, ICP-MS, TEM-EDS, SEM-EDS and SEM-FIB were the analytical procedures carried out to investigate the origin of the black coatings. In this subterranean environment, the enrichment in metals and other trace elements, such as Mn and Fe, and clay minerals characterize the black microbial mats, mainly composed of Mn/Fe-oxidising bacteria.Fundação para a Ciência e a Tecnologia (FCT
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