174 research outputs found

    Colonic adenocarcinoma an underlying malignancy of dermatomyositis: case report

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    Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of chronic, autoimmune connective tissue disorders that affect muscles primarily. A few cases have reported the correlation between IIM and paraneoplastic manifestations, primarily dermatomyositis (DM). We described the case of a 47-year-old woman with dermatomyositis and the finding of a colonic adenocarcinoma, who presented alternating diarrhoea and hematochezia. The immunoassay for myositis-specific antibodies showed anti-Mi-2a, anti-MDA5, and anti-Ro52 antibodies, while the colonoscopy showed a one-centimetre mass in the sigmoid. Literature reviews have contemplated an underlying malignancy in patients with dermatomyositis, particularly in those with anti-Mi-2 antibodies and atypical features or unexplained symptoms. A correlation between DM and colonic adenocarcinoma has-been documented in a few reports, particularly in patients with unexplained gastrointestinal symptoms or weight loss. The mechanisms of the association of dermatomyositis and malignancies, especially colonic malignancies, are still unknown and need more research for better strategies

    Retinal pigment epithelium degeneration caused by aggregation of PRPF31 and the role of HSP70 family of proteins

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    Background Mutations in pre-mRNA splicing factor PRPF31 can lead to retinitis pigmentosa (RP). Although the exact disease mechanism remains unknown, it has been hypothesized that haploinsufficiency might be involved in the pathophysiology of the disease. Methods In this study, we have analyzed a mouse model containing the p.A216P mutation in Prpf31 gene. Results We found that mutant Prpf31 protein produces cytoplasmic aggregates in the retinal pigment epithelium and decreasing the protein levels of this splicing factor in the nucleus. Additionally, normal protein was recruited in insoluble aggregates when the mutant protein was overexpressed in vitro. In response to protein aggregation, Hspa4l is overexpressed. This member of the HSP70 family of chaperones might contribute to the correct folding and solubilization of the mutant protein, allowing its translocation to the nucleus. Conclusions Our data suggests that a mechanism haploinsufficiency and dominant-negative is involved in retinal degeneration due to mutations in PRPF31. HSP70 over-expression might be a new therapeutic target for the treatment of retinal degeneration due to PRPF31 mutations.This project has been financed through a) The ISCIII (Miguel Servet-I, 2015), co-financed by the European Regional Development Fund (ERDF), No CP15/00071. b) The European Union’s Horizon 2020 research and innovation program, under grant agreement No 634479. c) Regional Ministry of Economy, Innovation and Science of the Junta de Andalucía, No P09-CTS-04967.info:eu-repo/semantics/publishedVersio

    Producción recombinante de la enteroquinasa de cadena ligera bovina en el periplasma de Escherichia coli.

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    La enteroquinasa es una peptidasa que se produce en la mucosa duodenal bovina, la cual consiste de dos cadenas: una pesada (115 kDa) y una ligera (35 kDa) la cual posee la actividad catilítica. Esta enzima activa el tripsinógeno reconociendo la secuencia (Asp)4-Lis y cortando en el extremo C-terminal de esta secuencia. Esto la convierte en un reactivo esencial en la producción de proteínas recombinantes en Escherichia coli ya que colocando esta secuencia entre una proteína de fusión y la proteína de interés permitiría la separación de ambas. Para producir la enteroquinasa se utilizará la secuencia de amioácidos del péptido señal de la enzima PelB, una pectato liasa de la bacteria Erwinia carotovora, la cual se encargará de dirigir la expresión al periplasma de Escherichia coli. Se produce aquí ya que es rara la formación de cuerpos de inclusión, favorece la formación de puentes disulfuro para el correcto plegamiento, además hay menos proteínas y esto hace que la fracción sea más pura. Esta proteína se usará en el Laboratorio de Biotecnología de la FCQ para separar proteínas de fusión de las proteínas recombinantes de interé

    Characterization and Decomposition of the Natural van der Waals SnSb2Te4 under Compression

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    This document is the Accepted Manuscript version of a Published Work that appeared in final form in Inorganic Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.inorgchem.0c01086.[EN] High pressure X-ray diffraction, Raman scattering, and electrical measurements, together with theoretical calculations, which include the analysis of the topological electron density and electronic localization function, evidence the presence of an isostructural phase transition around 2 GPa, a Fermi resonance around 3.5 GPa, and a pressure-induced decomposition of SnSb2Te4 into the high-pressure phases of its parent binary compounds (alpha-Sb2Te3 and SnTe) above 7 GPa. The internal polyhedral compressibility, the behavior of the Raman-active modes, the electrical behavior, and the nature of its different bonds under compression have been discussed and compared with their parent binary compounds and with related ternary materials. In this context, the Raman spectrum of SnSb2Te4 exhibits vibrational modes that are associated but forbidden in rocksalt-type SnTe; thus showing a novel way to experimentally observe the forbidden vibrational modes of some compounds. Here, some of the bonds are identified with metavalent bonding, which were already observed in their parent binary compounds. The behavior of SnSb2Te4 is framed within the extended orbital radii map of BA(2)Te(4) compounds, so our results pave the way to understand the pressure behavior and stability ranges of other "natural van der Waals" compounds with similar stoichiometry.This work has been performed under financial support from the Spanish MINECO under Project MALTA-CONSOLIDER TEAM network (RED2018-102612-T) and Project FIS2017-83295-P, from Generalitat Valenciana under Project PROMETEO/2018/123. This publication is a product of the "Programa de Valoracion y Recursos Conjuntos de I+D+i VLC/CAMPUS and has been financed by the Spanish Ministerio de Educacion, Cultura y Deporte, as part of "Programa Campus de Excelencia Internacional". Supercomputer time has been provided by the Red Espanola de Supercomputacion (RES) and the MALTA cluster. J.A.S. acknowledges a "Ramon y Cajal" fellowship (RYC-2015-17482) for financial support, and E.L.D.S. acknowledges Marie Sklodowska-Curie Grant No. 785789-COMEX from the European Union's Horizon 2020 research and innovation program. We also thank ALBA synchrotron and DIAMOND light source for funded experiments.Sans-Tresserras, JÁ.; Vilaplana Cerda, RI.; Da Silva, EL.; Popescu, C.; Cuenca-Gotor, VP.; Andrada-Chacón, A.; Sánchez-Benitez, J.... (2020). Characterization and Decomposition of the Natural van der Waals SnSb2Te4 under Compression. Inorganic Chemistry. 59(14):9900-9918. https://doi.org/10.1021/acs.inorgchem.0c01086S990099185914Mellnik, A. R., Lee, J. S., Richardella, A., Grab, J. L., Mintun, P. J., Fischer, M. H., … Ralph, D. C. (2014). Spin-transfer torque generated by a topological insulator. Nature, 511(7510), 449-451. doi:10.1038/nature13534Chen, Y. L., Analytis, J. G., Chu, J.-H., Liu, Z. K., Mo, S.-K., Qi, X. L., … Shen, Z.-X. (2009). 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    Experimental and Theoretical Study of SbPO4 under Compression

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    This document is the Accepted Manuscript version of a Published Work that appeared in final form in Inorganic Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.inorgchem.9b02268.[EN] SbPO4 is a complex monoclinic layered material characterized by a strong activity of the nonbonding lone electron pair (LEP) of Sb. The strong cation LEP leads to the formation of layers piled up along the a axis and linked by weak SbO electrostatic interactions. In fact, Sb has 4-fold coordination with O similarly to what occurs with the P-O coordination, despite the large difference in ionic radii and electronegativity between both elements. Here we report a joint experimental and theoretical study of the structural and vibrational properties of SbPO4 at high pressure. We show that SbPO4 is not only one of the most compressible phosphates but also one of the most compressible compounds of the ABO(4) family. Moreover, it has a considerable anisotropic compression behavior, with the largest compression occurring along a direction close to the a axis and governed by the compression of the LEP and the weak interlayer Sb-O bonds. The strong compression along the a axis leads to a subtle modification of the monoclinic crystal structure above 3 GPa, leading from a 2D to a 3D material. Moreover, the onset of a reversible pressure-induced phase transition is observed above 9 GPa, which is completed above 20 GPa. We propose that the high-pressure phase is a triclinic distortion of the original monoclinic phase. The understanding of the compression mechanism of SbPO4 can aid to improve the ion intercalation and catalytic properties of this layered compound.The authors acknowledge financial support from the Brazilian Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq - 159754/2018-6, 307199/2018-5, 422250/20163, 201050/2012-9), FAPESP (2013/07793-6), Spanish Ministerio de Economia y Competitividad (MINECO) under projects MALTA Consolider Ingenio 2010 network (MAT2015-71070-REDC and RED2018-102612-T), MAT2016-75586-C4-1/2/3-P, PGC2018-097520-A-I00, FIS2017-83295-P, and PGC2018-094417-B-I00 from Generalitat Valenciana under project PROMETEO/2018/123, and the European Comission under project COMEX. D.S.-P., JA.S., and A.O.d.l.R. acknowledge "Ramim y Cajal" Fellowships for financial support (RyC-2014-15643, RYC-2015-17482, and RyC-2016-20301, respectively). E.L.d. 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    Utilization of mechanical power and associations with clinical outcomes in brain injured patients: a secondary analysis of the extubation strategies in neuro-intensive care unit patients and associations with outcome (ENIO) trial

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    Background: There is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes. Methods: In this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale ≤ 12 before intubation) who required mechanical ventilation (MV) ≥ 24 h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS). Results: We included 1217 patients (mean age 51.2 years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9 J/min [IQR 9.2-15.1], 13 J/min [IQR 10-17], and 14 J/min [IQR 11-20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9 J/min, aRR at 17 J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22). Conclusions: Exposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation

    Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

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    A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

    First results from the AugerPrime Radio Detector

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    Update of the Offline Framework for AugerPrime

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    Outreach activities at the Pierre Auger Observatory

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