Functional signatures in non-small-cell lung cancer: a systematic review and meta-analysis of sex-based differences in transcriptomic studies

While studies have established the existence of differences in the epidemiological and clinical patterns of lung adenocarcinoma between male and female patients, we know relatively little regarding the molecular mechanisms underlying such sex-based differences. In this study, we explore said differences through a meta-analysis of transcriptomic data. We performed a meta-analysis of the functional profiling of nine public datasets that included 1366 samples from Gene Expression Omnibus and The Cancer Genome Atlas databases. Meta-analysis results from data merged, normalized, and corrected for batch effect show an enrichment for Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways related to the immune response, nucleic acid metabolism, and purinergic signaling. We discovered the overrepresentation of terms associated with the immune response, particularly with the acute inflammatory response, and purinergic signaling in female lung adenocarcinoma patients, which could influence reported clinical differences. Further evaluations of the identified differential biological processes and pathways could lead to the discovery of new biomarkers and therapeutic targets. Our findings also emphasize the relevance of sex-specific analyses in biomedicine, which represents a crucial aspect influencing biological variability in diseaseThis work was supported by Fondo de Investigación Sanitaria (ISCIII PI15-00209), GV/2020/ 186, and ISCIII PT17/0009/0015 FEDE

Spirometry and respiratory oscillometry: Feasibility and concordance in schoolchildren with asthma

Producción CientíficaObjective:The purpose of this study was to describe the feasibility of respiratory oscillometry (RO) in schoolchildren with asthma, and the concordance of its results with those of spirometry, to determine its clinical usefulness. Methods:RO and spirometry were performed in 154 children (6 to 14-year-old) with asthma, following strict quality criteria for the tests. Their feasibility (probability of valid test, time of execution, number of maneuvers needed to achieve a valid test, and perceived difficulty) was compared. The factors that influence feasibility were analyzed with multivariate methods. FEV1, FEV1/FVC, FVC and FEF25-75 for spirometry, and R5, AX and R5-19 for RO, were converted into z-scores and their concordance was investigated through intraclass correlation coefficients (ICC) and kappa indices for normal/abnormal values. Results:There were no differences in the probability of obtaining a valid RO or spirometry (83.1% vs. 81.8%, p = 0.868). RO required a lower number of maneuvers [mean (SD) 4.2 (1.8) versus 6.0 (1.6), p < 0.001] and less execution time [5.1 (2.7) versus 7.6 (2.4) minutes, p < 0.001], and patients considered it less difficult. Age increased the probability of obtaining valid RO and spirometry. The concordance of results between RO and spirometry was low, and only between zFEV1 and zAX could it be considered moderate (ICC = 0.412, kappa = 0.427). Conclusion:RO and spirometry are feasible in children with asthma. RO has some practical advantages, but the concordance of its results with spirometry is low.Junta de Castilla y León (Gerencia Regional de Salud - Grant/Award Number: 2191/A/2020

Xarxa de literatura catalana infantil (Grau d’Educació Infantil)

En aquesta memòria descrivim el treball en xarxa elaborat pels membres del projecte d’innovació docent “Xarxa de literatura catalana infantil (Grau d’Educació Infantil)” que, durant el curs 2014-2015, ha dut a terme diverses reunions presencials i virtuals per a modernitzar i millorar el procés d’ensenyament-aprenentatge relacionat amb la matèria objecte d’estudi. L’eix vertebral del projecte es basa l’ús de les TIC com a recurs motivador i dinàmic que cal implementar en la metodologia docent de les assignatures relacionades amb la literatura infantil del grau en Educació Infantil. En aquest sentit, s’hi descriuen els avantatges dels recursos relacionats amb l’univers Google (sobretot, Calendar, Sites, Drive i Youtube) i Prezi, la pàgina web que proporciona un entorn de presentacions en línia dinàmiques i interactives, molt en consonància amb les interessos de l’alumnat i els nous processos de comunicació i interacció docent. Per a il·lustrar el projecte, s’hi mostren imatges representatives dels materials que han sigut elaborats amb aquestos recursos

Hypothyroidism confers tolerance to cerebral malaria

The modulation of the host’s metabolism to protect tissue from damage induces tolerance to infections increasing survival. Here, we examined the role of the thyroid hormones, key metabolic regulators, in the outcome of malaria. Hypothyroidism confers protection to experimental cerebral malaria by a disease tolerance mechanism. Hypothyroid mice display increased survival after infection with Plasmodium berghei ANKA, diminishing intracranial pressure and brain damage, without altering pathogen burden, blood-brain barrier disruption, or immune cell infiltration. This protection is reversed by treatment with a Sirtuin 1 inhibitor, while treatment of euthyroid mice with a Sirtuin 1 activator induces tolerance and reduces intracranial pressure and lethality. This indicates that thyroid hormones and Sirtuin 1 are previously unknown targets for cerebral malaria treatment, a major killer of children in endemic malaria areas.This work was funded by grants SAF2017-83289-R to S.A. and A.A., SAF2017-90604REDT to A.A. supported by the The European Regional Development Fund (FEDER) and BIO2016-77430-R to J.M.B. from the Ministerio de Economía y Competitividad; B2017/BMD-3724 to S.A. and A.A. from the Comunidad de Madrid; and CIBERONC CB/16/00228 to A.A. from the Instituto de Salud Carlos III

Curso abierto de ayuda para la elaboración del Trabajo Fin de Grado en los Grados en Química e Ingeniería Química

Este proyecto llevará a cabo el desarrollo de un curso abierto que sirva a los estudiantes como guía de ayuda a la hora de elaborar su Trabajo Fin de Grado (TFG) en los Grados de Química e Ingeniería Química. Se incluirá una descripción de herramientas que los estudiantes puedan emplear en el desarrollo de sus TFG. Éstas serán seleccionadas de acuerdo con la experiencia de los miembros del Grupo y en función de las necesidades de los estudiantes. El curso resultante se editará para libre acceso a través del portal iTunes U, de ámbito internacional, convirtiéndose en el primer curso UCM ofertado en esta plataforma (tras consulta y aprobación del Vicerrectorado de Innovación; de no ser así, se alojará en alguna otra plataforma de amplia difusión). Se aprovechará la accesibilidad ofertada a los estudiantes por iTunes U para poner a su disposición el material elaborado logrando una gran difusión, incrementándose la visibilidad internacional de la UCM. El material de ayuda elaborado para el curso se presentará tanto en español como en inglés, para facilitar su uso por alumnos visitantes de la UCM, favoreciendo la movilidad de los estudiantes en el marco del EEES. Este material también se adaptará para poder ser empleado de forma directa, totalmente o en forma de módulos, en el Campus Virtual UCM

Cadomian and Variscan sutures of Iberia: a comparison

p.11-12. -A meeting held as a tribute to Teodoro Palacios on his retirement as Professor of Palaeontology at the University of Extremadura, Badajoz, Spain, 26th & 27th January, 2022, University of Extremadura, Badajoz. Edited by Sören Jensen[EN] The Iberian Massif holds evidence of two pre-Mesozoic orogenies, namely the Cadomian and Variscan. The Cadomian Orogeny resulted from long-lived subduction under the periphery of Gondwana during the Neoproterozoic and early Paleozoic. The Variscan Orogen resulted from the progressive collision of Gondwana, Laurussia and their pericontinental terranes during the Devonian and Carboniferous, after the closure of the Rheic Ocean and other marginal basins located along their mainlands. Despite these two orogens differ from one another in the global context from which they emerged, in Iberia they share some characteristics that make them intriguingly alike. The Variscan Orogen contains two major sutures zones. One that separates mainland Gondwana from peri-Gondwanan terranes (intra-Gondwana suture), and another one separating Laurussia from the latter terranes (Rheic suture). The Variscan intra-Gondwana suture is Tectonically dismembered and separates a collection of terranes with continental crust affinity that were transported inland from the periphery of Gondwana during the closure of a (Devonian) marginal basin opened during ongoing convergence between Gondwana and Laurussia (e.g., Careón Ophiolite), ⁓15 million years after the onset of the Variscan Orogen. This process was the result of subduction polarity towards Laurussia, i.e. away from mainland Gondwana. The exhumation of the ophiolites and high-P rocks in this suture was largely controlled by syn-convergence extensional tectonics. The current structure of the Rheic suture, on the other hand, is the result of reworking after the opening of an ephemeral oceanic basin (Beja-Acebuches Ophiolite). Subduction polarity during both the closure of the primary suture zone and the closure of the ephemeral basin were beneath mainland Gondwana. However, the closure of the ephemeral basin developed flake tectonics and obduction of pieces of the ocean basin onto the upper plate. Suture zones in the Cadomian Orogen went unnoticed until few years ago. Despite being intensely reworked by Variscan deformation, the ongoing structural, tectonometamorphic, geochemical and geochronological studies provide first-order constrains on their primary (Cadomian) geometry as well as insight on the paleogeographic location of subduction zones that led to their formation. A collective, yet preliminary analysis of these sutures, pictures a major architecture of the Cadomian Orogen that contain, at least, two sutures zones. One Cadomian suture is identified in the Mérida Ophiolite, which separates an upper and lower plate, both with continental crust affinity and likely Gondwanan derivation (intra-Gondwana suture). This intra-Gondwana suture was formed after the closure by subduction away from mainland Gondwana of a marginal basin that opened during ongoing convergence between Gondwana and an oceanic plate, millions of years after the onset of the Cadomian Orogen. The exhumation of the ophiolite and mid-P rocks that make this suture was largely controlled by syn-convergence extensional tectonics. Another Cadomian suture is represented by the Calzadilla Ophiolite, whose protoliths formed in a fore-arc basin to the most external part of Gondwana. The location of this suture zone is explained by flake tectonics, which contributed to the obduction of the ophiolite onto the upper plate while ongoing subduction was beneath mainland Gondwana. Cadomian and Variscan sutures share fundamental characteristics regarding the paleolocation of the ocean basins they derive from and the overall resulting geometry and tectonic processes involved in their formation. The suture zones that represent the closure of basins located at the outermost section of peri-Gondwana, and closely facing subduction underneath Gondwana (Calzadilla and Beja-Acebuches ophiolites), were obducted inwards onto mainland Gondwana (upper plate). The intra-Gondwana suture zones (Careón and Mérida ophiolites) formed after subduction of a marginal basin beneath the periphery of Gondwana, and the exhumation of rock units of the subduction system was largely assisted by syn-convergence extensional tectonics following subduction-accretion. The Variscan and Cadomian orogens, despite being formed in different contexts (oceanic subduction vs. continental collision), share two major features. Both are (i) mostly built by Gondwanan lithosphere, and (ii) occupy the upper plate of a subduction zone that consumed a large ocean. These two orogens alternate phases of contraction and extension (mostly concentrated in the upper plate). In both cases, extension was intense enough as to create marginal ocean basins and to favor exhumation of deep-seated rocks (quite common in upper plates). Perhaps, these major features they share may explain the resemblance of the final global architecture of these two orogens, and provide additional arguments to consider Gondwana as resistant to subduction and recycling in the mantle and prone to crustal growth, being the upper plate to the orogenic systems it was involved in during at least 300 m.y.Peer reviewe

An optimized MNK1b aptamer, apMNKQ2, and its potential use as a therapeutic agent in breast cancer

16 pags., 8 figs.Breast cancer is the most commonly diagnosed and leading cause of cancer death among women worldwide. Mitogen-activated protein kinase-interacting kinases (MNKs) promote the expression of several oncogenic proteins and are overexpressed in several types of cancer. In human cells, there are four isoforms of MNKs. The truncated isoform MNK1b, first described in our laboratory, has a higher basal activity and is constitutively active. Aptamers are emerging in recent years as potential therapeutic agents that show significant advantages over drugs of other nature. We have previously obtained and characterized a highly specific aptamer against MNK1b, named apMNK2F, with a dissociation constant in the nanomolar range, which produces significant inhibition of proliferation, migration, and colony formation in breast cancer cells. Furthermore, its sequence analysis predicted two G-quadruplex structures. In this work, we show the optimization process of the aptamer to reduce its size, improving its stability. The obtained aptamer, named apMNKQ2, is able to inhibit proliferation, colony formation, migration, and invasion in breast cancer cells. In murine models of breast cancer, apMNKQ2 has demonstrated its efficacy in reducing tumor volume and the number of metastases. In conclusion, apMNKQ2 could be used as an anti-tumor drug in the future.C.P.-D. was supported by grant RTC-2014-1986-1 from the Ministry of Economy and Competitiveness (Spain). R.F.-M... by predoctoral contract (PEJD-2018-BMD-4416) from the Community of Madrid (Spain) and FPU19/02929 from the Ministry of Science, Innovation and Universities (Spain). R.C.-B. for predoctoral contracts (PEJD 2016-BMD-2145 and 2018-BMD-9201) from the Community of Madrid and grant RTC2019-07227-1. M. EM., and V.M.G. are researchers at FIBio-HRC. Supported by grants RTC2019-07227-1, PID2020-116620GB-T.I.00, and PID2019-105417RB-I00, funded by MCIN/ AEI /10.13039/501100011033 (Ministry of Economy and Competitiveness, Spain).Peer reviewe

Zinc-Doped Iron Oxide Nanoparticles as a Proton-Activatable Agent for Dose Range Verification in Proton Therapy

Proton therapy allows the treatment of specific areas and avoids the surrounding tissues. However, this technique has uncertainties in terms of the distal dose fall-off. A promising approach to studying the proton range is the use of nanoparticles as proton-activatable agents that produce detectable signals. For this, we developed an iron oxide nanoparticle doped with Zn (IONP@Zn-cit) with a hydrodynamic size of 10 nm and stability in serum. Cytotoxicity, defined as half of the surveillance, was 100 &mu;g Zn/mL in the U251 cell line. The effect on clonogenic cell death was tested after X-ray irradiation, which suggested a radioprotective effect of these nanoparticles at low concentrations (1&ndash;10 &mu;g Zn/mL). To evaluate the production of positron emitters and prompt-gamma signals, IONP@Zn-cit was irradiated with protons, obtaining prompt-gamma signals at the lowest measured concentration (10 mg Zn/mL). Finally, 67Ga-IONP@Zn-cit showed accumulation in the liver and spleen and an accumulation in the tumor tissue of 0.95% ID/g in a mouse model of U251 cells. These results suggest the possibility of using Zn nanoparticles as proton-activatable agents to verify the range by prompt gamma detection and face the challenges of prompt gamma detection in a specific biological situation, opening different avenues to go forward in this field

The Courel Mountains UNESCO Global Geopark: An Amazing Geological History Extended Along 600 Million Years

[EN] The Courel Mountains UNESCO Global Geopark (2019) stands out in SW of Europe because of its geoheritage, its biodiversity and its cultural heritage, all of it considered of international interest. These aspects shape the local development economic and cultural improvement and development. The geoheritage is the result of three geological cycles since the Proterozoic, involving the Cadomian-Avalonian-Pan-African orogeny, the opening of the Rheic Ocean and the Variscan orogeny, and finally the Permian-Mesozoic continental expansion and the Alpine orogeny. The geological history of Courel Mountains is one of singular rocks, huge recumbent folds, valuable metallic mineralization, and invertebrate fossils preserved within metamorphic rocks. This long history is recorded in an exceptional Variscan basement that we can ravel thanks to the exhumation during the Alpine uplifting, when the present-day Courel Mountains were built.Peer reviewe

Design of a GIS-database for the management of the Courel Mountains UNESCO Global Geopark (Spain)

X Congreso Geológico de España, 5-7 Julio 2021, Vitoria - GasteizSe ha desarrollado una base de datos en un sistema de información geográfica (SIG) para la gestión del Geoparque Mundial de la UNESCO Montañas do Courel (NO de España). El SIG incluye 66 capas de información topográfica, geológica, minera, biológica, arqueológica y etnográfica, que pueden ser combinadas entre sí para elaborar mapas temáticos adaptados a la finalidad y al usuario. Los mapas generados son empleados en actividades de divulgación, en el diseño de cartografías técnicas de apoyo a los gestores del Geoparque, en el desarrollo de estudios científicos y en acciones de geoconservació