The Boinás Cenozoic thrust (Cantabrian Mountains, Spain)

The opencast gold mine of Boinás, has allowed to outcrops the contact between the variscan basement and the Cenozoic sediments. It is observable that the contact is a post - Lower Oligocene thrust, with a N40ºE trend. From a macrostructural point of view, Boinás thrust spreads along more than 10 km with a constant orientation, a vertical gap that reaches 400 m, and a NW vergence. Northwestwards another Alpine thrust develops (Tineo, A l o n s o y Pulgar , 2004) with a parallel orientation an opposite vergence. Between both thrusts a tectonic pop-down appears (Narcea Pop-down). The dynamic analysis shows that this structure was activated by a paleostress tensor with an horizontal s1 trending N139ºE, with a stress regime close to uniaxial compression (R=0.06). This stress allows the geometrical interchanges between s2 and s3. The outcrop also allows to observe a secondary population of normal faults, that fits to an extensional stress tensor (R=0.01) with s3 trending N146ºE, that is coaxial with the main compressive stress tensor. We interpret both fault populations as generated by the tectonic thrust emplacemen

Plasma Levels of Transforming Growth Factor-β1 Reflect Left Ventricular Remodeling in Aortic Stenosis

Background: TGF-b1 is involved in cardiac remodeling through an auto/paracrine mechanism. The contribution of TGF-b1 from plasmatic source to pressure overload myocardial remodeling has not been analyzed. We investigated, in patients with valvular aortic stenosis (AS), and in mice subjected to transverse aortic arch constriction (TAC), whether plasma TGF-b1 relates with myocardial remodeling, reflected by LV transcriptional adaptations of genes linked to myocardial hypertrophy and fibrosis, and by heart morphology and function. Methodology/Principal Findings: The subjects of the study were: 39 patients operated of AS; 27 healthy volunteers; 12 mice subjected to TAC; and 6 mice sham-operated. Myocardial samples were subjected to quantitative PCR. Plasma TGF-b1 was determined by ELISA. Under pressure overload, TGF-b1 plasma levels were significantly increased both in AS patients and TAC mice. In AS patients, plasma TGF-b1 correlated directly with aortic transvalvular gradients and LV mass surrogate variables, both preoperatively and 1 year after surgery. Plasma TGF-b1 correlated positively with the myocardial expression of genes encoding extracellular matrix (collagens I and III, fibronectin) and sarcomeric (myosin light chain-2, b-myosin heavy chain) remodelling targets of TGF-b1, in TAC mice and in AS patients. Conclusions/Significance: A circulating TGF-b1-mediated mechanism is involved, in both mice and humans, in the excessive deposition of ECM elements and hypertrophic growth of cardiomyocytes under pressure overload. The possible value of plasma TGF-b1 as a marker reflecting preoperative myocardial remodeling status in AS patients deserves further analysis in larger patient cohorts

MALDI Profiling of Human Lung Cancer Subtypes

Proteomics is expected to play a key role in cancer biomarker discovery. Although it has become feasible to rapidly analyze proteins from crude cell extracts using mass spectrometry, complex sample composition hampers this type of measurement. Therefore, for effective proteome analysis, it becomes critical to enrich samples for the analytes of interest. Despite that one-third of the proteins in eukaryotic cells are thought to be phosphorylated at some point in their life cycle, only a low percentage of intracellular proteins is phosphorylated at a given time.In this work, we have applied chromatographic phosphopeptide enrichment techniques to reduce the complexity of human clinical samples. A novel method for high-throughput peptide profiling of human tumor samples, using Parallel IMAC and MALDI-TOF MS, is described. We have applied this methodology to analyze human normal and cancer lung samples in the search for new biomarkers. Using a highly reproducible spectral processing algorithm to produce peptide mass profiles with minimal variability across the samples, lineal discriminant-based and decision tree–based classification models were generated. These models can distinguish normal from tumor samples, as well as differentiate the various non–small cell lung cancer histological subtypes.A novel, optimized sample preparation method and a careful data acquisition strategy is described for high-throughput peptide profiling of small amounts of human normal lung and lung cancer samples. We show that the appropriate combination of peptide expression values is able to discriminate normal lung from non-small cell lung cancer samples and among different histological subtypes. Our study does emphasize the great potential of proteomics in the molecular characterization of cancer

Registro Español de Trasplante Cardiaco. XXXI Informe Oficial de la Asociación de Insuficiencia Cardiaca de la Sociedad Española de Cardiología

Introducción y objetivos Se presentan las características clínicas y los resultados de los trasplantes cardiacos realizados en España con la actualización correspondiente a 2019. Métodos Se describen las características clínicas y los resultados de los trasplantes cardiacos realizados en 2019, así como las tendencias de estos en el periodo 2010-2018. Resultados En 2019 se realizaron 300 trasplantes (8.794 desde 1984; 2.745 entre 2010 y 2019). Respecto a años previos, los cambios más llamativos son el descenso hasta el 38% de los trasplantes realizados en código urgente, y la consolidación en el cambio de asistencia circulatoria pretrasplante, con la práctica desaparición del balón de contrapulsación (0, 7%), la estabilización del uso del oxigenador extracorpóreo de membrana (9, 6%) y el aumento de los dispositivos de asistencia ventricular (29%). La supervivencia en el trienio 2016-2018 es similar a la del trienio 2013-2015 (p = 0, 34), y ambas mejores que la del trienio 2010-2012 (p = 0, 002 y p = 0, 01 respectivamente). Conclusiones Se mantienen estables tanto la actividad del trasplante cardiaco en España como los resultados en supervivencia en los últimos 2 trienios. Hay una tendencia a realizar menos trasplantes urgentes, la mayoría con dispositivos de asistencia ventricular. Introduction and objectives: The present report describes the clinical characteristics and outcomes of heart transplants in Spain and updates the data to 2019. Methods: We describe the clinical characteristics and outcomes of heart transplants performed in Spain in 2019, as well as trends in this procedure from 2010 to 2018. Results: In 2019, 300 transplants were performed (8794 since 1984; 2745 between 2010 and 2019). Compared with previous years, the most notable findings were the decreasing rate of urgent transplants (38%), and the consolidation of the type of circulatory support prior to transplant, with an almost complete disappearance of counterpulsation balloon (0.7%), stabilization in the use of extracorporeal membrane oxygenation (9.6%), and an increase in the use of ventricular assist devices (29.0%). Survival from 2016 to 2018 was similar to that from 2013 to 2015 (P = .34). Survival in both these periods was better than that from 2010 to 2012 (P = .002 and P = .01, respectively). Conclusions: Heart transplant activity has remained stable during the last few years, as have outcomes (in terms of survival). There has been a trend to a lower rate of urgent transplants and to a higher use of ventricular assist devices prior to transplant

El cabalgamiento cenozoico de Boinás (Cordillera Cantábrica, España)

The opencast gold mine of Boinás, has allowed to outcrops the contact between the variscan basement and the Cenozoic sediments. It is observable that the contact is a post - Lower Oligocene thrust, with a N40ºE trend. From a macrostructural point of view, Boinás thrust spreads along more than 10 km with a constant orientation, a vertical gap that reaches 400 m, and a NW vergence. Northwestwards another Alpine thrust develops (Tineo, A l o n s o y Pulgar , 2004) with a parallel orientation an opposite vergence. Between both thrusts a tectonic pop-down appears (Narcea Pop-down). The dynamic analysis shows that this structure was activated by a paleostress tensor with an horizontal s1 trending N139ºE, with a stress regime close to uniaxial compression (R=0.06). This stress allows the geometrical interchanges between s2 and s3. The outcrop also allows to observe a secondary population of normal faults, that fits to an extensional stress tensor (R=0.01) with s3 trending N146ºE, that is coaxial with the main compressive stress tensor. We interpret both fault populations as generated by the tectonic thrust emplacement

Targeting Signaling Pathway Downstream of RIG-I/MAVS in the CNS Stimulates Production of Endogenous Type I IFN and Suppresses EAE

Type I interferons (IFN), including IFNβ, play a protective role in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Type I IFNs are induced by the stimulation of innate signaling, including via cytoplasmic RIG-I-like receptors. In the present study, we investigated the potential effect of a chimeric protein containing the key domain of RIG-I signaling in the production of CNS endogenous IFNβ and asked whether this would exert a therapeutic effect against EAE. We intrathecally administered an adeno-associated virus vector (AAV) encoding a fusion protein comprising RIG-I 2CARD domains (C) and the first 200 amino acids of mitochondrial antiviral-signaling protein (MAVS) (M) (AAV-CM). In vivo imaging in IFNβ/luciferase reporter mice revealed that a single intrathecal injection of AAV-CM resulted in dose-dependent and sustained IFNβ expression within the CNS. IFNβ expression was significantly increased for 7 days. Immunofluorescent staining in IFNβ-YFP reporter mice revealed extraparenchymal CD45+ cells, choroid plexus, and astrocytes as sources of IFNβ. Moreover, intrathecal administration of AAV-CM at the onset of EAE induced the suppression of EAE, which was IFN-I-dependent. These findings suggest that accessing the signaling pathway downstream of RIG-I represents a promising therapeutic strategy for inflammatory CNS diseases, such as MS

Deposition of carbon nanotubes onto aramid fibers using as-received and chemically modified fibers

Multiwall carbon nanotubes (MWCNTs) oxidized by an acid treatment were deposited on the surface of as-received commercial aramid fibers containing a surface coating ("sizing"), and fibers modified by either a chlorosulfonic treatment or a mixture of nitric and sulfuric acids. The surface of the aramid fiber activated by the chemical treatments presents increasing density of CO, COOH and OH functional groups. However, these chemical treatments reduced the tensile mechanical properties of the fibers, especially when the nitric and sulfuric acid mixture was used. Characterization of the MWCNTs deposited on the fiber surface was conducted by scanning electron microscopy, Raman spectroscopy mapping and X-ray photoelectron spectroscopy. These characterizations showed higher areal concentration and more homogeneous distribution of MWCNTs over the aramid fibers for as-received fibers and for those modified with chlorosulfonic acid, suggesting the existence of interaction between the oxidized MWCNTs and the fiber coating. The electrical resistance of the MWCNT-modified aramid yarns comprising 1000 individual fibers was in the order of M Omega/cm, which renders multifunctional properties.CONACYT-CIAM (Mexico) 188089 CONICYT (Chile) 120003 "Fondo Mixto CONACYT-Gobierno del Estado de Yucatan" 24704

MKP1/CL100 controls tumor growth and sensitivity to cisplatin in non-small-cell lung cancer

Non-small-cell lung cancer (NSCLC) represents the most frequent and therapy-refractive sub-class of lung cancer. Improving apoptosis induction in NSCLC represents a logical way forward in treating this tumor. Cisplatin, a commonly used therapeutic agent in NSCLC, induces activation of N-terminal-c-Jun kinase (JNK) that, in turn, mediates induction of apoptosis. In analysing surgical tissue samples of NSCLC, we found that expression of MKP1/CL100, a negative regulator of JNK, showed a strong nuclear staining for tumor cells, whereas, in normal bronchial epithelia, MKP1 was localized in the cytoplasm as well as in nuclei. In the NSCLC-derived cell lines H-460 and H-23, we found that MKP1 was constitutively expressed. Expressing a small-interfering RNA (siRNA) vector for MKP1 in H-460 cells resulted in a more efficient activation by cisplatin of JNK and p38 than in the parental cells, and this correlated with a 10-fold increase in sensitivity to cisplatin. A similar response was also observed in H-460 and H-23 cells when treated with the MKP1 expression inhibitor RO-31-8220. Moreover, expression of a siRNA-MKP2, an MKP1-related phosphatase, had no effect on H-460 cell viability response to cisplatin. Tumors induced by H-460 cells expressing MKP1 siRNA grew slower in nu-/nu- mice and showed more susceptibility to cisplatin than parental cells, and resulted in an impaired growth of the tumor in mice. On the other hand, overexpression of MKP1 in the H-1299 NSCLC-derived cell line resulted in further resistance to cisplatin. Overall, the results showed that inhibition of MKP1 expression contributes to a slow down in cell growth in mice and an increase of cisplatin-induced cell death in NSCLC. As such, MKP1 can be an attractive target in sensitizing cells to cisplatin to increase the effectiveness of the drug in treating NSCLC. © 2006 Nature Publishing Group All rights reserved.This work was supported by the following grants: no. 08.1/0048.1/2003 from the Comunidad Autónoma de Madrid; no. 01/1094, no. 02/0774 and no. 02/1094 from the Fondo de Investigación Sanitaria; no. RTICC C03/10 from Instituto de Salud Carlos III. The investigators RM-P and CM-G are supported by Grant no. RTICC C03/10.Peer Reviewe