Methylation alterations are not a major cause of PTTG1 missregulation

Background: On its physiological cellular context, PTTG1 controls sister chromatid segregation during mitosis. Within its crosstalk to the cellular arrest machinery, relies a checkpoint of integrity for which gained the over name of securin. PTTG1 was found to promote malignant transformation in 3T3 fibroblasts, and further found to be overexpressed in different tumor types. More recently, PTTG1 has been also related to different processes such as DNA repair and found to trans-activate different cellular pathways involving c-myc, bax or p53, among others. PTTG1 over-expression has been correlated to a worse prognosis in thyroid, lung, colorectal cancer patients, and it can not be excluded that this effect may also occur in other tumor types. Despite the clinical relevance and the increasing molecular characterization of PTTG1, the reason for its up-regulation remains unclear. Method: We analysed PTTG1 differential expression in PC-3, DU-145 and LNCaP tumor cell lines, cultured in the presence of the methyl-transferase inhibitor 5-Aza-2'-deoxycytidine. We also tested whether the CpG island mapping PTTG1 proximal promoter evidenced a differential methylation pattern in differentiated thyroid cancer biopsies concordant to their PTTG1 immunohistochemistry status. Finally, we performed whole-genome LOH studies using Affymetix 50 K microarray technology and FRET analysis to search for allelic imbalances comprising the PTTG1 locus. Conclusion: Our data suggest that neither methylation alterations nor LOH are involved in PTTG1 over-expression. These data, together with those previously reported, point towards a post-transcriptional level of missregulation associated to PTTG1 over-expression.This project was funded by The Fundación de Investigación Biomédica Mutua Madrileña Automovilista. Neocodex have been partially funded by the Ministerio de Educación y Ciencia of Spain (FIT-010000-2004-69, PTQ04-1-0006, PTQ2003-0549, PTQ2003-0546 and PTQ2003-0783). MAJ was also supported by SAF2005- 07713-C03-03 and CS by FIS 06/757

The Châtelperronian Neanderthals of Cova Foradada (Calafell, Spain) used imperial eagle phalanges for symbolic purposes

Evidence for the symbolic behavior of Neanderthals in the use of personal ornaments is relatively scarce. Among the few ornaments documented, eagle talons, which were presumably used as pendants, are the most frequently recorded. This phenomenon appears concentrated in a specific area of southern Europe during a span of 80 thousand years. Here, we present the analysis of one eagle pedal phalange recovered from the Châtelperronian layer of Foradada Cave (Spain). Our research broadens the known geographical and temporal range of this symbolic behavior, providing the first documentation of its use among the Iberian populations, as well as of its oldest use in the peninsula. The recurrent appearance of large raptor talons throughout the Middle Paleolithic time frame, including their presence among the last Neanderthal populations, raises the question of the survival of some cultural elements of the Middle Paleolithic into the transitional Middle to Upper Paleolithic assemblages and beyond

Biochemical and structural characterization of a novel thermophilic esterase EstD11 provide catalytic insights for the HSL family

[Abstract]: A novel esterase, EstD11, has been discovered in a hot spring metagenomic library. It is a thermophilic and thermostable esterase with an optimum temperature of 60 C. A detailed substrate preference analysis of EstD11 was done using a library of chromogenic ester substrate that revealed the broad substrate specificity of EstD11 with significant measurable activity against 16 substrates with varied chain length, steric hindrance, aromaticity and flexibility of the linker between the carboxyl and the alcohol moiety of the ester. The tridimensional structures of EstD11 and the inactive mutant have been determined at atomic resolutions. Structural and bioinformatic analysis, confirm that EstD11 belongs to the family IV, the hormone-sensitive lipase (HSL) family, from the α/β-hydrolase superfamily. The canonical a/b hydrolase domain is completed by a cap domain, composed by two subdomains that can unmask of the active site to allow the substrate to enter. Eight crystallographic complexes were solved with different substrates and reaction products that allowed identification of the hot-spots in the active site underlying the specificity of the protein. Crystallization and/or incubation of EstD11 at high temperature provided unique information on cap dynamics and a first glimpse of enzymatic activity in vivo. Very interestingly, we have discovered a unique Met zipper lining the active site and the cap domains that could be essential in pivotal aspects as thermo-stability and substrate promiscuity in EstD11Ministerio de Ciencia e Innovación; BFU2017-90030-

ERK5/BMK1 is a novel target of the tumor suppressor VHL: implication in clear cell renal carcinoma

Hi ha quatre pàgines de material suplementari sense numeracióExtracellular signal-regulated kinase 5 (ERK5), also known as big mitogen-activated protein kinase (MAPK) 1, is implicated in a wide range of biologic processes, which include proliferation or vascularization. Here, we show that ERK5 is degraded through the ubiquitin-proteasome system, in a process mediated by the tumor suppressor von Hippel-Lindau (VHL) gene, through a prolyl hydroxylation-dependent mechanism. Our conclusions derive from transient transfection assays in Cos7 cells, as well as the study of endogenous ERK5 in different experimental systems such as MCF7, HMEC, or Caki-2 cell lines. In fact, the specific knockdown of ERK5 in pVHL-negative cell lines promotes a decrease in proliferation and migration, supporting the role of this MAPK in cellular transformation. Furthermore, in a short series of fresh samples from human clear cell renal cell carcinoma, high levels of ERK5 correlate with more aggressive and metastatic stages of the disease. Therefore, our results provide new biochemical data suggesting that ERK5 is a novel target of the tumor suppressor VHL, opening a new field of research on the role of ERK5 in renal carcinomas

The importance of regional differences in vulnerability to climate change for demersal fisheries

Regional differences in climate vulnerability are particularly important in many countries with socio-ecological gradients or geographical and environmental spatial segregation. Many studies are regularly performed at the national level, but regional assessments can provide more detailed information and important insights into intra-national vulnerabilities. They require detailed information of many socio-ecological components that are often neglected at the regional scale but are meaningful and operational at national and international levels. In this work, we developed a climate vulnerability assessment (CVA) to investigate the vulnerability of demersal fisheries based on 19 indicators covering exposure, fisheries sensitivity, species sensitivity (SS) and adaptive capacity (AC) for nine coastal regions of Spain, contrasting the Mediterranean to Atlantic areas. Exposure was consistently larger in the Mediterranean than Atlantic regions, while AC showed the opposite trend. While fisheries and SS did not display a clear Atlantic-Mediterranean pattern, they were critical for capturing regional differences that have an impact on fisheries vulnerability. Our results highlight the generally higher vulnerability of Mediterranean demersal fisheries, mainly due to the lower AC and higher exposure of Mediterranean regions, while providing key regional elements for guiding national and international actions for adaptation. This study demonstrates that the spatial scale considered in the development of CVAs must recognise the spatial heterogeneity in the socio-ecological system within its unit of analysis in order to be a relevant tool for management and policy makers.Preprint2,27

Episodios sedimentarios en el Alcudiense Superior (Proterozoico) y su tránsito al Cámbrico en la zona centro meridional del Macizo Ibérico

The evolution of the Upper Alcudian-Lower Cambrian basin is studied in the eastern lusitanian-Alcudian Zone. Five sedimentary episodes with distinctive characteristics are considered

Coordinación entre las asignaturas del área de ingeniería térmica y energía de los grados y el Máster Universitario en Ingeniería Naval y Oceánica de la Universidad Politécnica de Madrid

El trabajo que se presenta tiene por objetivo establecer la coordinación existente entre los objetivos y actividades de las asignaturas del área de ingeniería térmica, energía y propulsión del Máster en Ingeniería Naval y Oceánica, y los objetivos y actividades del mismo tipo de asignaturas en los Grados en Ingeniería Marítima y en Arquitectura Naval de la ETSI Navales de la Universidad Politécnica de Madrid. Igualmente, se plantea estudiar la coordinación de estas materias entre sí dentro de los Grados. Pueden mencionarse asignaturas obligatorias tales como Termodinámica, Ingeniería Térmica, Energía y Propulsión, Motores Diésel Marinos, Turbomáquinas Térmicas y Diseño integral de plantas de Energía y Propulsión. Entre las asignaturas optativas se encuentran Refrigeración y Climatización en Buques y Tecnología de las Pilas de Combustible y Energía del Hidrógeno. Para poder coordinar dos especialidades de Grado universitario con campos tan dispares, pero a la vez tan relacionados, con el Máster Universitario que se cursará en ambos casos, se deben exigir unas pautas muy marcadas para no solapar las actividades y/o habilidades necesarias para alcanzar dichas capacidades. De la necesidad de comprender mejor y con mayor exactitud las necesidades de cada uno de los planes de estudios en el área de ingeniería térmica, energía y propulsión, y más concretamente, las relaciones que existen entre ellos, nace este trabajo. Para mejorar la eficacia de la enseñanza de los actuales y futuros alumnos, será fundamental desarrollar, entre otras, una serie de acciones que incluyen un estudio a fondo de los objetivos del Máster y de los Grados en relación con estas materias; el diseño y aplicación de una plantilla de descripción de las asignaturas en Máster y en Grado, que permita la elaboración de árboles de relación entre Máster-Grados; partiendo del Máster que vinculen los objetivos, las competencias generales, específicas y transversales (y el nivel de desarrollo propuesto) y los conocimientos previos; la confección y análisis de encuestas dirigidas a alumnos egresados, profesores y empresas, que emplean a estos alumnos con el fin de evaluar el nivel de consecución de los objetivos planteados. Esto permitirá determinar, en cuanto al área de ingeniería térmica, energía y propulsión, la viabilidad de la consecución de los objetivos del Máster en función de los objetivos planteados en los Grados al identificar vacíos y redundancias en cuanto a los objetivos, las competencias y los conocimientos previos del Máster en relación con los Grados. Con todo ello será posible proponer las modificaciones oportunas, en los casos en los que se consideren necesarias.Los autores desean agradecer a la Universidad Politécnica de Madrid su soporte y ayuda en este trabajo, en el marco del Proyecto de Innovación Educativa IE1415-08002

Characteristics and Outcome of Acute Heart Failure in Infective Endocarditis: Focus on Cardiogenic Shock

Spanish Collaboration on Endocarditis—Grupo de Apoyo al Manejo de la Endocarditis Infecciosa en España (GAMES).[Background] Studies investigating the impact of cardiogenic shock (CS) on endocarditis are lacking.[Methods] Prospectively collected cohort from 35 Spanish centers (2008-2018). Logistic regression analyses were performed to identify risk factors for developing CS and predictors of mortality.[Results] Among 4856 endocarditis patients, 1652 (34%) had acute heart failure (AHF) and 244 (5%) CS. Compared with patients without AHF and AHF but no CS, patients with CS presented higher rates of surgery (40.5%, 52.5%, and 68%; P < .001) and in-hospital mortality (16.3%, 39.1%, and 52.5%). Compared with patients with septic shock, CS patients presented higher rates of surgery (42.5% vs 68%; P < .001) and lower rates of in-hospital and 1-year mortality (62.3% vs 52.5%, P = .008, and 65.3% vs 57.4%, P = .030). Severe aortic and mitral regurgitation (OR [95% CI], 2.47 [1.82-3.35] and 3.03 [2.26-4.07]; both P < .001), left-ventricle ejection fraction <60% (1.72; 1.22-2.40; P = .002), heart block (2.22; 1.41-3.47; P = .001), tachyarrhythmias (5.07; 3.13-8.19; P < .001), and acute kidney failure (2.29; 1.73-3.03; P < .001) were associated with higher likelihood of developing CS. Prosthetic endocarditis (2.03; 1.06 -3.88; P = .032), Staphylococcus aureus (3.10; 1.16 -8.30; P = .024), tachyarrhythmias (3.09; 1.50-10.13; P = .005), and not performing cardiac surgery (11.40; 4.83-26.90; P < .001) were associated with a higher risk of mortality.[Conclusions] AHF is common among patients with endocarditis. CS is associated with high mortality and should be promptly identified and assessed for cardiac surgery.This work was supported by the Ministerio de Sanidad y Consumo of Spain (grant number FIS NCT00871104; Instituto de Salud Carlos III). Institut d’Investigacions Biomèdiques Pi i Sunyer (IDIBAPS) provided J. M. M. with a persobal IDIBAPS 80:20 research grant during 2017–2021. M. H. M. held a Rio Hortega Research Grant (CM17/00062) from the Instituto de Salud Carlos III” and the Ministerio de Economia y Competitividad, Madrid (Spain) in 2018–2020.Peer reviewe

Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression

Background: This report provides histopathological evidence to support prior neuroimaging findings of decreased volume and altered metabolism in the frontal cortex in major depressive disorder. Methods: Computer-assisted three-dimensional cell counting was used to reveal abnormal cytoarchitecture in left rostral and caudal orbitofrontal and dorsolateral prefrontal cortical regions in subjects with major depression as compared to psychiatrically normal controls. Results: Depressed subjects had decreases in cortical thickness, neuronal sizes, and neuronal and glial densities in the upper (II–IV) cortical layers of the rostral orbitofrontal region. In the caudal orbitofrontal cortex in depressed subjects, there were prominent reductions in glial densities in the lower (V–VI) cortical layers that were accompanied by small but significant decreases in neuronal sizes. In the dorsolateral prefrontal cortex of depressed subjects marked reductions in the density and size of neurons and glial cells were found in both supra- and infragranular layers. Conclusions: These results reveal that major depression can be distinguished by specific histopathology of both neurons and glial cells in the prefrontal cortex. Our data will contribute to the interpretation of neuroimaging findings and identification of dysfunctional neuronal circuits in major depression