3,390 research outputs found

    JM-20, a Benzodiazepine-Dihydropyridine Hybrid Molecule, Inhibits the Formation of Alpha-Synuclein-Aggregated Species

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    \ua9 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Studies showed that JM-20, a benzodiazepine-dihydropyridine hybrid molecule, protects against rotenone and 6-hydroxydopamine neurotoxicity. However, its protective effects against cytotoxicity induced by endogenous neurotoxins involved in Parkinson’s disease (PD) pathogenesis have never been investigated. In this study, we evaluated the ability of JM-20 to inhibit alpha-synuclein (aSyn) aggregation. We also evaluated the interactions of JM-20 with aSyn by molecular docking and molecular dynamics and assessed the protective effect of JM-20 against aminochrome cytotoxicity. We demonstrated that JM-20 induced the formation of heterogeneous amyloid fibrils, which were innocuous to primary cultures of mesencephalic cells. Moreover, JM-20 reduced the average size of aSyn positive inclusions in H4 cells transfected with SynT wild-type and synphilin-1-V5, but not in HEK cells transfected with synphilin-1-GFP. In silico studies showed the interaction between JM-20 and the aSyn-binding site. Additionally, we showed that JM-20 protects SH-SY5Y cells against aminochrome cytotoxicity. These results reinforce the potential of JM-20 as a neuroprotective compound for PD and suggest aSyn as a molecular target for JM-20

    Investigation of the CRT performance of a PET scanner based in liquid xenon: a Monte Carlo study

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    The measurement of the time of flight of the two 511 keV gammas recorded in coincidence in a PET scanner provides an effective way of reducing the random background and therefore increases the scanner sensitivity, provided that the coincidence resolving time (CRT) of the gammas is sufficiently good. Existing commercial systems based in LYSO crystals, such as the GEMINIS of Philips, reach CRT values of 600 ps (FWHM). In this paper we present a Monte Carlo investigation of the CRT performance of a PET scanner exploiting the scintillating properties of liquid xenon. We find that an excellent CRT of 60 70 ps (depending on the PDE of the sensor) can be obtained if the scanner is instrumented with silicon photomultipliers (SiPMs) sensitive to the ultraviolet light emitted by xenon. Alternatively, a CRT of 120 ps can be obtained instrumenting the scanner with (much cheaper) blue-sensitive SiPMs coated with a suitable wavelength shifter. These results show the excellent time of flight capabilities of a PET device based in liquid xenon.The authors acknowledge support from the following agencies and institutions: the European Research Council (ERC) under the Advanced Grant 339787-NEXT, the Ministerio de Economia y Competitividad and FEDER of Spain, the Severo Ochoa Program SEV-2014-0398 and GVA under grant PROMETEO/2016/120; we acknowledge enlightening discussions with J. Varela and C. Lerche.Gómez-Cadenas, JJ.; Benlloch-Rodriguez, JM.; Ferrario, P.; Monrabal, F.; Rodriguez-Samaniego, J.; Toledo Alarcón, JF. (2016). Investigation of the CRT performance of a PET scanner based in liquid xenon: a Monte Carlo study. Journal of Instrumentation. 11(P09011). https://doi.org/10.1088/1748-0221/11/09/P09011S11P0901

    Radiative properties for astrophysical plasma mixtures in nonlocal thermodynamic equilibrium

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    Radiative properties play a pivotal role in astrophysical plasma flows and are needed in radiation-hydrodynamic simulations in order to understand their behavior and also to interpret the plasma emission spectra, which are valuable diagnostic tools. Radiative properties of astrophysical plasma mixtures have been commonly calculated for low-density optically thin plasmas assuming coronal equilibrium and for high density assuming local thermodynamic equilibrium. However, there are wide ranges of conditions in which these thermodynamic regimes are not achieved and the plasma is in the nonlocal thermodynamic equilibrium regime. In the present work, a study of the plasma radiative properties of oxygen and iron and an astrophysical plasma mixture in nonlocal thermodynamic steady-state equilibrium is carried out. The ranges of electron temperatures and densities considered are 1-1000 eV and 10(11)-10(20) cm(-3), respectively. In the study, departures from coronal and local thermodynamic equilibria in terms of the density and temperature are also analyzed. Large differences in the radiative properties that can reach two orders of magnitude when the plasma is far from these thermodynamic regimes are obtained. These analyses are done assuming the plasma to be optically thin. A brief study of the influence of the plasma self-absorption in the radiative properties of oxygen and iron is made. For that purpose, the plasma is assumed with planar geometry and the study is performed in terms of the width of the plasma slab and electron temperature and density.0,9922,353Q1Q1SCI

    CONGENITAL 11-BETA-HYDROXYSTEROID DEHYDROGENASE-DEFICIENCY ASSOCIATED WITH JUVENILE HYPERTENSION - CORTICOSTEROID METABOLITE PROFILES OF 4 PATIENTS AND THEIR FAMILIES

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    Four children with 11 .beta.-hydroxysteroid dehydrogenase deficiency are described. All patients had severe hypertension, hypokalemia, and low plasma aldosterone and renin activities. Two of the patients were siblings and 2 were unrelated. The most noticable biochemical feature of these individuals was the extremely low excretion of cortisol metabolites containing on 11-carbonyl group compared to the excretion of the 11 .beta.-hydroxyl containing metabolites. Although this condition is readily diagnosed in affected individuals by urinary steroid analysis, carriers of the defect do not differ from normal in their urinary steroids. Both parents of the affected siblings had normal 11-oxo-steroid/11 .beta.-hydroxysteroid ratios under baseline conditions and the lesions could not be revealed by ACTH administration

    Economic evaluation of three populational screening strategies for cervical cancer in the county of Valles Occidental: CRICERVA clinical trial

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    Copyright @ 2011 Acera et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.A high percentage of cervical cancer cases have not undergone cytological tests within 10 years prior to diagnosis. Different population interventions could improve coverage in the public system, although costs will also increase. The aim of this study was to compare the effectiveness and the costs of three types of population interventions to increase the number of female participants in the screening programmes for cancer of the cervix carried out by Primary Care in four basic health care areas.Fondo de Investigación Sanitaria del Instituto Carlos III de Madri

    Phosphoproteomics data classify hematological cancer cell lines according to tumor type and sensitivity to kinase inhibitors

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    This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

    Study protocol of cost-effectiveness and cost-utility of a biopsychosocial multidisciplinary intervention in the evolution of non-specific sub-acute low back pain in the working population: cluster randomised trial.

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    This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain (LBP), with high incidence and prevalence rate, is one of the most common reasons to consult the health system and is responsible for a significant amount of sick leave, leading to high health and social costs. The objective of the study is to assess the cost-effectiveness and cost-utility analysis of a multidisciplinary biopsychosocial educational group intervention (MBEGI) of non-specific sub-acute LBP in comparison with the usual care in the working population recruited in primary healthcare centres. Methods/design: The study design is a cost-effectiveness and cost-utility analysis of a MBEGI in comparison with the usual care of non-specific sub-acute LBP.Measures on effectiveness and costs of both interventions will be obtained from a cluster randomised controlled clinical trial carried out in 38 Catalan primary health care centres, enrolling 932 patients between 18 and 65 years old with a diagnosis of non-specific sub-acute LBP. Effectiveness measures are: pharmaceutical treatments, work sick leave (% and duration in days), Roland Morris disability, McGill pain intensity, Fear Avoidance Beliefs (FAB) and Golberg Questionnaires. Utility measures will be calculated from the SF-12. The analysis will be performed from a social perspective. The temporal horizon is at 3 months (change to chronic LBP) and 12 months (evaluate the outcomes at long term. Assessment of outcomes will be blinded and will follow the intention-to-treat principle. Discussion: We hope to demonstrate the cost-effectiveness and cost-utility of MBEGI, see an improvement in the patients' quality of life, achieve a reduction in the duration of episodes and the chronicity of non-specific low back pain, and be able to report a decrease in the social costs. If the intervention is cost-effectiveness and cost-utility, it could be applied to Primary Health Care Centres. Trial registration: ISRCTN: ISRCTN5871969

    Kinetic Study of Oxidative Dehydrogenation of Ethane over MoVTeNb Mixed-Oxide Catalyst

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    This document is the Accepted Manuscript version of a Published Work that appeared in final form in Industrial & Engineering Chemistry Research, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see [insert ACS Articles on Request author-directed link to Published Work, see http://doi.org/10.1021/ie402447h[EN] A MoVTeNb multimetallic mixed oxide was studied for the oxidative dehydrogenation of ethane, a promising alternative for catalytic ethylene production. Lab-scale steady-state experimental reaction data were obtained according to a 3(k) experimental design to investigate the simultaneous effect of temperature (400-480 degrees C) and space time [23-70 g(cat) h (mol of ethane) I]. A fixed-bed reactor at atmospheric pressure was employed, feeding a mixture of ethane, oxygen, and nitrogen. Ethane conversion varied from 17 to 85%, whereas selectivity for ethylene and COx varied from 94 to 76% and from 4.0 to 24%, respectively. These types of analyses are useful for determining the optimum reaction conditions to enhance the catalytic performance of the mixed oxides presented herein.This work was financially supported by the Instituto Mexicano del Petroleo. Technical support from Eng. G. Alonso-Ramirez is gratefully acknowledged.Valente, J.; Quintana-Solorzano, R.; Armendariz-Herrera, H.; Barragan-Rodriguez, G.; López Nieto, JM. (2014). Kinetic Study of Oxidative Dehydrogenation of Ethane over MoVTeNb Mixed-Oxide Catalyst. Industrial and Engineering Chemistry Research. 53(5):1775-1786. doi:10.1021/ie402447hS1775178653

    Protocol for Metatranscriptomic analysis of Intestinal Microbiota

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    The objective of this publication is to provide the detailed protocol for metartancriptomisc studies of animal intestinal microbiota. The protocol describes isolation of high quality microbial community RNA from the mammalian intestinal content, subsequent mRNA enrichment, cDNA synthesis and sequencing. Twelve libraries were prepared, pooled in equimolar concentrations into a single library and sequenced on one GS Titanium 70×75 picotiter plate, following this protocol. The total number of reads obtained for 12 libraries was 1,155,062 (average 96,000 per library) and the combined size of 12 libraries was 521 million bases (average 43 million bases per library). The reported size of non-ribosomal RNA library fraction is ~15%, the fraction of non-ribosomal reads is ~17%. Hence we described a robust technique for metranscriptomic studies of animal intestinal microbiota. The double stranded cDNAs, prepared following this protocol, are suitable for pyrosequencing (454, Illumina), clone library construction or could be used to archive and store metaranscriptomic samples
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