346 research outputs found

    Lipid metabolite biomarkers in cardiovascular disease: discovery and biomechanism translation from human studies

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    Lipids represent a valuable target for metabolomic studies since altered lipid metabolism is known to drive the pathological changes in cardiovascular disease (CVD). Metabolomic technologies give us the ability to measure thousands of metabolites providing us with a metabolic fingerprint of individual patients. Metabolomic studies in humans have supported previous findings into the pathomechanisms of CVD, namely atherosclerosis, apoptosis, inflammation, oxidative stress, and insulin resistance. The most widely studied classes of lipid metabolite biomarkers in CVD are phospholipids, sphingolipids/ceramides, glycolipids, cholesterol esters, fatty acids, and acylcarnitines. Technological advancements have enabled novel strategies to discover individual biomarkers or panels that may aid in the diagnosis and prognosis of CVD, with sphingolipids/ceramides as the most promising class of biomarkers thus far. In this review, application of metabolomic profiling for biomarker discovery to aid in the diagnosis and prognosis of CVD as well as metabolic abnormalities in CVD will be discussed with particular emphasis on lipid metabolites

    Calibrachoa: Plagas y manejo

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    Calibrachoa es un género exclusivamente americano, afín a Petunia, de distribución predominan temente sub-tropical atlántica entre los paralelos 18 y 37 ºS. En la Argentina existen 13 especies nativas presentes principalmente en la Mesopotamia. Se las encuentra creciendo en ambientes abiertos con suelo arenoso o pedregoso de buen drenaje de Entre Ríos y Corrientes, o en suelos rojizos ácidos de Misiones o norte de Corrientes. Desde su creación, el Instituto de Floricultura de INTA ha trabajado en el desarrollo de variedades nacionales de calibrachoa como fruto del mejoramiento genético de germoplasma nativo. Tanto es así, que el mercado florícola argentino cuenta con tres variedades nacionales: Overá fucsia INTA y Pampa salmón INTA (inscriptas en el Registro Nacional de Cultivares del Instituto Nacional de Semillas) e INTA 06575 (patentada en la Patent and Trademark Office de Estados Unidos). Las variedades de calibrachoa desarrolladas por INTA son plan tas herbáceas perennes, de pleno sol y comportamiento anual. Florecen constantemente desde la primavera hasta el otoño en forma muy abundante, con un pico entre el fin de la primavera y el inicio del verano. Ofrecen néctar a visitantes florales, son vigo rosas y con amplia cobertura del espacio, recomendables para ser plantadas en macetas colgantes o macetas grandes (Figura 1) o utilizadas en espacios abiertos a pleno sol, en canteros y borduras (Figura 2). Son de fácil mantenimiento. La variedad Overá fucsia INTA (Figura 3) es de porte erecto, compacta, con floración abundante. Sus flores son de color fucsia y aparecen en forma temprana, independientemente del fotoperio do. Prefiere suelos o sustratos levemente ácidos (pH 5,5-6,5). Es ideal para cultivo en macetas, pero también presenta un buen comportamiento en canteros o borduras. La variedad Pampa salmón INTA (Figura 4) es de porte semierecto. Sus flores son de color salmón. La floración es más tardía que en otras variedades, requiere de fotoperiodo mayor a 12 horas y alta iluminación para florecer plenamente. Es ideal para espacios abiertos como canteros o borduras a pleno sol. A diferencia de las otras variedades, no es tan exigente de suelos o sustratos ácidos. La variedad INTA 06575 (Figura 5) es la de crecimiento más vigoroso. Sus flores son de color púr pura. Al igual que las de Overá fucsia INTA, aparecen en forma temprana, independientemente del fotoperiodo. Prefiere suelos o sustratos mediana a ligeramente ácidos (pH 5,5-6,5) y tolera las altas temperatura del verano. Es ideal para espacios abiertos, en canteros o borduras a pleno sol.Fil: Borrelli, N.P. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Floricultura; ArgentinaFil: Martinez, M.A. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Concordia; ArgentinaFil: Rivera, Marta Carolina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Floricultura; ArgentinaFil: Alderete, Marisol. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Floricultura; ArgentinaFil: Hagiwara, Juan Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Floricultura; ArgentinaFil: Diaz, Beatriz Maria. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Concordia; ArgentinaFil: Karlanian, Mónica N. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Floricultura; ArgentinaFil: Fernández, Martín Nicolás. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Floricultura; ArgentinaFil: Garcia Lager, Eduardo Antonio. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Floricultura; ArgentinaFil: Tombion, Leticia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Floricultura; Argentin

    Update on the correlation of the highest energy cosmic rays with nearby extragalactic matter

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    Data collected by the Pierre Auger Observatory through 31 August 2007 showed evidence for anisotropy in the arrival directions of cosmic rays above the Greisen-Zatsepin-Kuz'min energy threshold, \nobreak{6×10196\times 10^{19}eV}. The anisotropy was measured by the fraction of arrival directions that are less than 3.13.1^\circ from the position of an active galactic nucleus within 75 Mpc (using the V\'eron-Cetty and V\'eron 12th12^{\rm th} catalog). An updated measurement of this fraction is reported here using the arrival directions of cosmic rays recorded above the same energy threshold through 31 December 2009. The number of arrival directions has increased from 27 to 69, allowing a more precise measurement. The correlating fraction is (386+7)(38^{+7}_{-6})%, compared with 2121% expected for isotropic cosmic rays. This is down from the early estimate of (6913+11)(69^{+11}_{-13})%. The enlarged set of arrival directions is examined also in relation to other populations of nearby extragalactic objects: galaxies in the 2 Microns All Sky Survey and active galactic nuclei detected in hard X-rays by the Swift Burst Alert Telescope. A celestial region around the position of the radiogalaxy Cen A has the largest excess of arrival directions relative to isotropic expectations. The 2-point autocorrelation function is shown for the enlarged set of arrival directions and compared to the isotropic expectation.Comment: Accepted for publication in Astroparticle Physics on 31 August 201

    The exposure of the hybrid detector of the Pierre Auger Observatory

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    The Pierre Auger Observatory is a detector for ultra-high energy cosmic rays. It consists of a surface array to measure secondary particles at ground level and a fluorescence detector to measure the development of air showers in the atmosphere above the array. The "hybrid" detection mode combines the information from the two subsystems. We describe the determination of the hybrid exposure for events observed by the fluorescence telescopes in coincidence with at least one water-Cherenkov detector of the surface array. A detailed knowledge of the time dependence of the detection operations is crucial for an accurate evaluation of the exposure. We discuss the relevance of monitoring data collected during operations, such as the status of the fluorescence detector, background light and atmospheric conditions, that are used in both simulation and reconstruction.Comment: Paper accepted by Astroparticle Physic

    Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C: A prospective observational study

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    Background: Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. Methods: In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with =2 clinical signs/symptoms of NP-C were considered ''suspected NP-C'' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI =70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. Results: In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores =70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. Conclusion: This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis

    The comparative responsiveness of Hospital Universitario Princesa Index and other composite indices for assessing rheumatoid arthritis activity

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    Objective To evaluate the responsiveness in terms of correlation of the Hospital Universitario La Princesa Index (HUPI) comparatively to the traditional composite indices used to assess disease activity in rheumatoid arthritis (RA), and to compare the performance of HUPI-based response criteria with that of the EULAR response criteria. Methods Secondary data analysis from the following studies: ACT-RAY (clinical trial), PROAR (early RA cohort) and EMECAR (pre-biologic era long term RA cohort). Responsiveness was evaluated by: 1) comparing change from baseline (Delta) of HUPI with Delta in other scores by calculating correlation coefficients; 2) calculating standardised effect sizes. The accuracy of response by HUPI and by EULAR criteria was analyzed using linear regressions in which the dependent variable was change in global assessment by physician (Delta GDA-Phy). Results Delta HUPI correlation with change in all other indices ranged from 0.387 to 0.791); HUPI's standardized effect size was larger than those from the other indices in each database used. In ACT-RAY, depending on visit, between 65 and 80% of patients were equally classified by HUPI and EULAR response criteria. However, HUPI criteria were slightly more stringent, with higher percentage of patients classified as non-responder, especially at early visits. HUPI response criteria showed a slightly higher accuracy than EULAR response criteria when using Delta GDA-Phy as gold standard. Conclusion HUPI shows good responsiveness in terms of correlation in each studied scenario (clinical trial, early RA cohort, and established RA cohort). Response criteria by HUPI seem more stringent than EULAR''s

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

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    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

    Quantum gravity phenomenology at the dawn of the multi-messenger era—A review

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    The exploration of the universe has recently entered a new era thanks to the multi-messenger paradigm, characterized by a continuous increase in the quantity and quality of experimental data that is obtained by the detection of the various cosmic messengers (photons, neutrinos, cosmic rays and gravitational waves) from numerous origins. They give us information about their sources in the universe and the properties of the intergalactic medium. Moreover, multi-messenger astronomy opens up the possibility to search for phenomenological signatures of quantum gravity. On the one hand, the most energetic events allow us to test our physical theories at energy regimes which are not directly accessible in accelerators; on the other hand, tiny effects in the propagation of very high energy particles could be amplified by cosmological distances. After decades of merely theoretical investigations, the possibility of obtaining phenomenological indications of Planck-scale effects is a revolutionary step in the quest for a quantum theory of gravity, but it requires cooperation between different communities of physicists (both theoretical and experimental). This review, prepared within the COST Action CA18108 “Quantum gravity phenomenology in the multi-messenger approach”, is aimed at promoting this cooperation by giving a state-of-the art account of the interdisciplinary expertise that is needed in the effective search of quantum gravity footprints in the production, propagation and detection of cosmic messengers.publishedVersio

    Techniques for measuring aerosol attenuation using the Central Laser Facility at the Pierre Auger Observatory

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    The Pierre Auger Observatory in Malargüe, Argentina, is designed to study the properties of ultra-high energy cosmic rays with energies above 10(18) eV. It is a hybrid facility that employs a Fluorescence Detector to perform nearly calorimetric measurements of Extensive Air Shower energies. To obtain reliable calorimetric information from the FD, the atmospheric conditions at the observatory need to be continuously monitored during data acquisition. In particular, light attenuation due to aerosols is an important atmospheric correction. The aerosol concentration is highly variable, so that the aerosol attenuation needs to be evaluated hourly. We use light from the Central Laser Facility, located near the center of the observatory site, having an optical signature comparable to that of the highest energy showers detected by the FD. This paper presents two procedures developed to retrieve the aerosol attenuation of fluorescence light from CLF laser shots. Cross checks between the two methods demonstrate that results from both analyses are compatible, and that the uncertainties are well understood. The measurements of the aerosol attenuation provided by the two procedures are currently used at the Pierre Auger Observatory to reconstruct air shower data
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