Uncovering tumour heterogeneity through PKR and nc886 analysis in metastatic colon cancer patients treated with 5-FU-based chemotherapy

Colorectal cancer treatment has advanced over the past decade. The drug 5-fluorouracil is still used with a wide percentage of patients who do not respond. Therefore, a challenge is the identification of predictive biomarkers. The protein kinase R (PKR also called EIF2AK2) and its regulator, the non-coding pre-mir-nc886, have multiple effects on cells in response to numerous types of stress, including chemotherapy. In this work, we performed an ambispective study with 197 metastatic colon cancer patients with unresectable metastases to determine the relative expression levels of both nc886 and PKR by qPCR, as well as the location of PKR by immunohistochemistry in tumour samples and healthy tissues (plasma and colon epithelium). As primary end point, the expression levels were related to the objective response to first-line chemotherapy following the response evaluation criteria in solid tumours (RECIST) and, as the second end point, with survival at 18 and 36 months. Hierarchical agglomerative clustering was performed to accommodate the heterogeneity and complexity of oncological patients\u27 data. High expression levels of nc886 were related to the response to treatment and allowed to identify clusters of patients. Although the PKR mRNA expression was not associated with chemotherapy response, the absence of PKR location in the nucleolus was correlated with first-line chemotherapy response. Moreover, a relationship between survival and the expression of both PKR and nc886 in healthy tissues was found. Therefore, this work evaluated the best way to analyse the potential biomarkers PKR and nc886 in order to establish clusters of patients depending on the cancer outcomes using algorithms for complex and heterogeneous data

The p38 MAPK Components and Modulators as Biomarkers and Molecular Targets in Cancer

This research was funded by MCIN/AEI/10.13039/501100011033/FEDER, grant number RTI2018-101309-B-C22 and by the Chair Doctors Galera-Requena in cancer stem cell research.The mitogen-activated protein kinase (MAPK) family is an important bridge in the transduction of extracellular and intracellular signals in different responses at the cellular level. Within this MAPK family, the p38 kinases can be found altered in various diseases, including cancer, where these kinases play a fundamental role, sometimes with antagonistic mechanisms of action, depending on several factors. In fact, this family has an immense number of functionalities, many of them yet to be discovered in terms of regulation and action in different types of cancer, being directly involved in the response to cancer therapies. To date, three main groups of MAPKs have been identified in mammals: the extracellular signal-regulated kinases (ERK), Jun N-terminal kinase (JNK), and the different isoforms of p38 (alpha, beta, gamma, delta). In this review, we highlight the mechanism of action of these kinases, taking into account their extensive regulation at the cellular level through various modifications and modulations, including a wide variety of microRNAs. We also analyze the importance of the different isoforms expressed in the different tissues and their possible role as biomarkers and molecular targets. In addition, we include the latest preclinical and clinical trials with different p38-related drugs that are ongoing with hopeful expectations in the present/future of developing precision medicine in cancer.MCIN/AEI/10.13039/501100011033/FEDER RTI2018-101309-B-C22Chair Doctors Galera-Requena in cancer stem cell researc

Inhibition of VEGF-Induced VEGFR-2 Activation and HUVEC Migration by Melatonin and Other Bioactive Indolic Compounds

Excessive concentrations of vascular endothelial growth factor (VEGF) trigger angiogenesis, which causes complications such as the destabilization of atherosclerotic plaques and increased growth of tumors. This work focuses on the determination of the inhibitory activity of melatonin and other indolic related compounds on VEGF-induced VEGF receptor-2 (VEGFR-2) activation and an approximation to the molecular mechanism underlying the inhibition. Quantification of phosphorylated VEGFR-2 was measured by ELISA. Migration wound-healing assay was used to determine cell migration of human umbilical vein endothelial cells (HUVECs). This is the first time that melatonin, 3-indolacetic acid, 5-hydroxytryptophol, and serotonin are proved to significantly inhibit VEGF-induced VEGFR-2 activation in human umbilical vein endothelial cells and subsequent angiogenesis. 3-Indolacetic acid showed the highest inhibitory effect (IC50 value of 0.9704 mM), followed by 5-hydroxytryptophol (35% of inhibition at 0.1 mM), melatonin (30% of inhibition at 1 mM), and serotonin (24% of inhibition at 1 mM). An approximation to the molecular mechanism of the inhibition has been proposed, suggesting that indolic compounds might interact with the cell surface components of the endothelial membrane in a way that prevents VEGF from activating the receptor. Additionally, wound-healing assay revealed that exposure of HUVECs to melatonin and 3-indolacetic acid in the presence of VEGF significantly inhibited cell migration by 87% and 99%, respectively, after 24 h. These data demonstrate that melatonin, 3-indolacetic acid, 5-hydroxytryptophol, and serotonin would be good molecules for future exploitation as anti-VEGF signaling agents.España, Ministerio de Ciencia e Innovación AGL2013-47300-C3-2-

Libro de Resúmenes del Congreso Euro-Latinoamericano de Intervención en Justicia Juvenil

Libro de Resúmenes del Congreso Euro-Latinoamericano de Intervención en Justicia Juvenil celebrado en la Universidad de Almería del 21/10/15 al 23/10/15

Optimización de la gestión de residuos informáticos en la EINA.

El presente trabajo se centra en la gestión de residuos de equipos eléctricos y electrónicos de carácter informático en la EINA. Una vez conocida la normativa que se aplica a este tipo de residuos, se investiga acerca de cómo se deben gestionar y se analiza una encuesta realizada a los 15 departamentos con presencia en la EINA. Se resalta la importancia que tiene alargar la vida útil de todos los RAEE. Se describen posibles reutilizaciones que tienen algunos componentes que conforman las torres de ordenador, y cómo se recicla en una planta de tratamiento. Analizando tanto el plan de gestión actual que tiene UNIZAR como las encuestas realizadas se detectan las carencias que tiene dicho plan, y se propone uno nuevo que mejora aquellos puntos que se han encontrado deficientes o que no aparecían y que, además, se apoya en las solicitudes que han aportado los departamentos. Como se describe en el trabajo, existe una dificultad a la hora de investigar sobre este tema en la EINA debido a la escasa documentación y a la falta de información sobre cómo gestionar los equipos informáticos cuando se convierten en residuos. Además, se pretende contribuir a los ODS 7,8,9,12 y 13 para ayudar en la implantación de los ODS en la EINA.<br /

Histone H3E73Q and H4E53A mutations cause recombinogenic DNA damage

The stability and function of eukaryotic genomes is closely linked to histones and to chromatin structure. The state of the chromatin not only affects the probability of DNA to undergo damage but also DNA repair. DNA damage can result in genetic alterations and subsequent development of cancer and other genetic diseases. Here, we identified two mutations in conserved residues of histone H3 and histone H4 (H3E73Q and H4E53A) that increase recombinogenic DNA damage. Our results suggest that the accumulation of DNA damage in these histone mutants is largely independent on transcription and might arise as a consequence of problems occurring during DNA replication. This study uncovers the relevance of H3E73 and H4E53 residues in the protection of genome integrity.European Research Council ERC2014 AdG669898 TARLOOPMinisterio de Economía y Competitividad BFU2016-75058-

The assessment of the ASD (Autism Spectrum Disorder) classrooms in early children’s education: the voice of teachers and families

Es sabido que el avance hacia culturas, políticas y prácticas más inclusivas es un proceso complejo y dilemático. Los obstáculos se acrecientan cuando se trata de alumnado con mayores dificultades como es el caso del Trastorno del Espectro del Autismo (TEA). La Comunidad de Madrid, al igual que otras comunidades autónomas, viene desarrollando un programa de escolarización preferente para este alumnado, en un intento de incluir al alumnado con TEA, que hasta el momento se situaba en centros específicos, en centros educativos ordinarios. La investigación desarrollada trata de identificar y analizar la concreción de las dimensiones de la inclusión en Educación Infantil (Booth y Ainscow, 2006) en el marco de la propuesta educativa que desarrollan estos centros. Para ello, una estrategia necesaria es tener muy presentes “las voces” (Susinos y Ceballos, 2012) de familias y docentes como expresión de sus anhelos y expectativas, y también de sus logros, dificultades y propuestas de mejora que subyacen en la labor que realizan diariamente. Conocer la percepción por parte de familias y docentes en relación a las características que definen la inclusión en los centros, la importancia de un liderazgo pedagógico en los equipos directivos, el alto compromiso y satisfacción del profesorado con el trabajo que desarrolla, así como los altos índices en la participación de las familias en los centros son algunos de los resultados que se muestran en el artículo como indicadores clave para favorecer los procesos de inclusión educativa.It is well known that progress towards more inclusive cultures, policies and practices is a complex and dilemmatic process. The obstacles increase when dealing with students with greater difficulties as is the case of Autism Spectrum Disorder (ASD). The Community of Madrid, like other Autonomous Communities, has developed a preferential schooling program for these students, in an attempt to include students with ASD, which until now was located in specific centers, in ordinary educational centers. The research developed aims to identify and analyze the concretion of the dimensions of inclusion in Early Childhood Education (Booth and Ainscow, 2006) within the framework of the educational proposal developed by these centers. For this, a necessary strategy is to keep in mind “the voices” (Susinos and Ceballos, 2012) of families and teachers as an expression of their desires and expectations, and also of their achievements, difficulties and proposals for improvement that underlie the work they perform daily. The fact of knowing the perception by families and teachers in relation to the characteristics that define inclusion in the centers, the importance of a pedagogical leadership in the management teams, teacher’s high commitment and satisfaction with the work they develop, as well as the high rates in the participation of families in the centers are some of the results that are shown in the article as key indicators to favor the processes of educational inclusion

Hospitalisation cost of patients with diabetic foot ulcers in Valencia (Spain) in the period 2009-2013 : a retrospective descriptive analysis

Ulcers are the main cause of hospitalisation and clinical complications in patients with diabetes. We analyse the length and cost of hospital stay of patients with diabetic foot ulcers, taking into consideration that hospitalisation and, if necessary, amputation represent the greatest area of expense to the healthcare system for such patients. This analysis focuses on the treatment provided to these patients in public hospitals in the region of Valencia (Spain), registered in the Spanish Minimum Basic Data Set, during the period 2009-2013. The number of acute hospital admissions in this respect is increasing and has a high socioeconomic cost. During the study period, there were over 2700 hospital admissions, an average of nearly 550 per year. The total hospital stay for these patients was 30,886 days, with an average of 11.4 days and a cost of 7633 per admission. Preventive policies and the deployment of multidisciplinary teams are essential to reduce these costs and avoid future complications such as amputation

143 PRINCIPAL COMPONENT CLUSTERING OF FRONTAL PLANE KNEE KINEMATICS

Replication forks stall at different DNA obstacles such as those originated by transcription. Fork stalling can lead to DNA double-strand breaks (DSBs) that will be preferentially repaired by homologous recombination when the sister chromatid is available. The Rrm3 helicase is a replisome component that promotes replication upon fork stalling, accumulates at highly transcribed regions and prevents not only transcription-induced replication fork stalling but also transcription-associated hyper-recombination. This led us to explore the possible role of Rrm3 in the repair of DSBs when originating at the passage of the replication fork. Using a mini-HO system that induces mainly single-stranded DNA breaks, we show that rrm3Δ cells are defective in DSB repair. The defect is clearly seen in sister chromatid recombination, the major repair pathway of replication-born DSBs. Our results indicate that Rrm3 recruitment to replication-born DSBs is crucial for viability, uncovering a new role for Rrm3 in the repair of broken replication forks.This work was supported by grants from the Spanish Ministry of Economy and Innovation (BFU2013-42918), the European Union (FEDER), the European Research Council (ERC2014 AdG669898 TARLOOP), and the Junta de Andalucía (BIO1238). SMG was funded by a predoctoral training fellowship from the Spanish National Research Council (CSIC) and BGG by a postdoctoral grant from the Scientific Foundation of the Spanish Association Against Cancer (AECC). Funding for open access charge: Grants from the Spanish Ministry of Economy and Innovation (BFU2013-42918).Peer Reviewe

4000 years of climate change in Northern Spain from speleothem records

Depto. de Geodinámica, Estratigrafía y PaleontologíaFac. de Ciencias GeológicasTRUEpu