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Recovery rates for baleen whales that were decimated by exploitation vary between species and populations. Age determination is critical for the understanding of recovery trends and population structure, but determining age in free-ranging individuals remains challenging. Recent research has suggested that the methylation level of some genes in skin samples may provide age determinations with accuracy. We selected nine CpG sites from three genes (TET2, CDKN2A, and GRIA2) and analyzed them in 40 skin samples from known-age individuals pertaining to two different populations of fin whales from the North Atlantic. We observed significant correlations with age in five CpG sites. We used three of these CpG sites to perform an epigenetic age estimation. Predictions had a standard deviation of 2.94, but regression between observed and predicted ages showed a clear underestimation for older fin whales. For further development, we suggest: (1) screening for new CpG sites associated with age that exhibit higher variability between individuals, and (2) including older animals whenever the sampling allows it. We also observed subtle, but significant differences between the two populations studied in one of the CpG sites (TET2_CpG + 21). We attributed these differences to genetic differences or to the dissimilar environments that affect both populations.

Histone deacetylase 11 (HDAC11) is the latest identified member of the histone deacetylase family of enzymes. It is highly expressed in brain, heart, testis, kidney, and skeletal muscle, although its role in these tissues is poorly understood. Here, we investigate for the first time the consequences of HDAC11 genetic impairment on skeletal muscle regeneration, a process principally dependent on its resident stem cells (satellite cells) in coordination with infiltrating immune cells and stromal cells. Our results show that HDAC11 is dispensable for adult muscle growth and establishment of the satellite cell population, while HDAC11 deficiency advances the regeneration process in response to muscle injury. This effect is not caused by differences in satellite cell activation or proliferation upon injury, but rather by an enhanced capacity of satellite cells to differentiate at early regeneration stages in the absence of HDAC11. Infiltrating HDAC11-deficient macrophages could also contribute to this accelerated muscle regenerative process by prematurely producing high levels of IL-10, a cytokine known to promote myoblast differentiation. Altogether, our results show that HDAC11 depletion advances skeletal muscle regeneration and this finding may have potential implications for designing new strategies for muscle pathologies coursing with chronic damage. Database Data were deposited in NCBI's Gene Expression Omnibus accessible through GEO Series accession number .

Alu repeats constitute a major fraction of human genome and for a small subset of them a role in gene regulation has been described. The number of studies focused on the functional characterization of particular Alu elements is very limited. Most Alu elements are DNA methylated and then assumed to lie in repressed chromatin domains. We hypothesize that Alu elements with low or variable DNA methylation are candidates for a functional role. In a genome-wide study in normal and cancer tissues, we pinpointed an Alu repeat (AluSq2) with differential methylation located upstream of the promoter region of the DIEXF gene. DIEXF encodes a highly conserved factor essential for the development of zebrafish digestive tract. To characterize the contribution of the Alu element to the regulation of DIEXF we analysed the epigenetic landscapes of the gene promoter and flanking regions in different cell types and cancers. Alternate epigenetic profiles (DNA methylation and histone modifications) of the AluSq2 element were associated with DIEXF transcript diversity as well as protein levels, while the epigenetic profile of the CpG island associated with the DIEXF promoter remained unchanged. These results suggest that AluSq2 might directly contribute to the regulation of DIEXF transcription and protein expression. Moreover, AluSq2 was DNA hypomethylated in different cancer types, pointing out its putative contribution to DIEXF alteration in cancer and its potential as tumoural biomarker.

Consecuentemente con la firme determinación adoptada por parte del Gobierno de España de respaldar un modelo educativo bilingüe así como el compromiso asumido por la Región Murcia de conseguir que todos sus centros educativos sean bilingües para 2020, los centros docentes nos vemos en la necesidad de profundizar y asumir la metodología propuesta por la Unión Europea denominada: Content and Language Integrated Learning (CLIL). Por dicha metodología (CLIL o AICLE en español) se entiende el aprendizaje de materias del currículo no correspondientes con Lengua Extranjera. Este giro metodológico sumado al pobre seguimiento por parte de la Comunidad Autónoma de los Centros Bilingües de la Región de Murcia (CBM), demandó en nuestro centro educativo la necesidad de diseñar una serie de actuaciones que cohesionaran a todos los miembros implicados para facilitar una implantación efectiva y con identidad propia. Para ello, se determinó crear un Departamento de Investigación y Tecnología educativa bilingüe que coordinara todas las actividades a lo largo del estudio, fijándose los siguientes objetivos: • Formar a los docentes tanto en metodología AICLE como en otras técnicas que implementaran el proceso de enseñanza-aprendizaje (E-A), así como lograr un número adecuado de docentes habilitados en lengua extranjera. • Llegar a conocer los logros adquiridos por parte del alumnado en ANL en comparativa con el resto de materias del currículo así como su adquisición de la lengua no-materna (L2) propia del programa. • Responder a las demandas surgidas por parte de los padres que se enfrentaban a un programa donde todo está en inglés. Para responder a estas necesidades, se ha empleado una metodología mixta cuyo método ha sido la Investigación Basada en Diseño (IBD) que nos ha permitido generar ciclos continuos de diseño, desarrollo, análisis y rediseño en cada uno de los siete años que ha durado este estudio longitudinal dividido en dos fases: trabajo previo para lograr ser centro CBM (3 años iniciales) y trabajo siendo centro autorizado CBM (4 años finales). La muestra empleada para este estudio responderá al seguimiento de la totalidad del alumnado que inició el programa CBM en 2012 así como sus respectivos padres y docentes que se han ido incorporando anualmente al mismo. Como conclusiones principales del presente estudio, podemos extraer las siguientes: • El empleo de la metodología bilingüe (AICLE) en combinación con el aprendizaje cooperativo, el uso diario de Pizarra Digital Interactiva (PDI) en el aula y el trabajo con materiales de edición propia, facilitan la plena integración del programa. • Los materiales de elaboración propia diseñados para la web escolar y las diversas ANL han enriquecido notoriamente el proceso de E-A aportando situaciones significativas para el alumnado y captando su atención favoreciendo así el logro de conocimientos de orden superior. • Las actividades formativas planificadas han dotado al docente de los conocimientos y destrezas necesarias para afrontar el bilingüismo en el aula de manera exitosa además de lograr más docentes habilitados de los realmente necesarios. • Las calificaciones obtenidas por los alumnos en las ANL en comparación con otras materias no pertenecientes al programa, son ligeramente superiores y además se ha comprobado que mejoran la adquisición del segundo idioma. • El grado de satisfacción de los alumnos, docentes y padres con el programa CBM, ha ido mejorando a lo largo del proceso de implantación y finalmente describen más ventajas que inconvenientes en el empleo del programa. Finalmente, tras nuestra experiencia investigadora, y dada la complejidad del programa, queremos remarcar la idoneidad de incluir en el organigrama del centro un Departamento específico que articule todo el proceso de implantación e implementación de este tipo de programas educativos. According to the government’s strong determination to backing a bilingual educational model and the commitment made by the Region of Murcia, (whereby all education centres must work under the aforementioned programme by 2020), each and every learning institution and personnel working in them see ourselves obligated to work under and deepen the application and understanding of CLIL (Content and Language Integrated Learning) method proposed by the European Union. Under said method (known in Spanish as AICLE), are contained the learning of curricular subjects not included in Second Language Acquisition. This methodological shift, in addition to the inadequate following from the Autonomous Community of the CBM institutions (Centros Bilingues de la Region de Murcia by its Spanish acronym), required a need to design a course of action in our educational centre and demanded all involved parties to converge to facilitate an effective and genuine implementation of the program. To that end, it was decided to create a bilingual Research and Technology Department which would coordinate all activities throughout the study, with the following goals: • Instruct the teaching staff in CLIL methodology and in several other techniques to help in the teaching/learning process as well as reaching an adequate figure of educational personnel proficient in foreign languages. • Acknowledge the achievements of the pupils in non-linguistic subjects when compared to the rest of curricular subjects and the acquisition of L2 inside of the programme. • Answer the parental demands when facing a programme using English in its entirety. To meet these goals, we employed a mixed methodology which the investigatory method used was Design Based Research (BDR by its acronym) which allowed us to create continuous design, development, analysis and redesign cycles in each and every one of the seven years this two-phase longitudinal study has lasted: preliminary work to be able to become a CBM centre (first 3 years) and work under CBM authorised centre (4 last years). The sample used for this study will match the tracking of the entirety of the students starting the CBM method in 2012 as well as their parents and teaching staff being brought into the programme by each year. The main conclusions of this here study extracted are: • The use of bilingual methodology (CLIL) in combination with collaborative learning, the daily usage of the interactive digital whiteboard in the classroom and also self-edited materials ease the full integration of the programme. • The self-edited materials for the school website and the various non-linguistic subjects have significantly enriched the teaching/learning process, adding meaningful situations for the student body, therefore improving higher order concept. • Planned educational activities have supplied the teaching personnel with the necessary skills and abilities to cope with the implementation of bilingualism in the classroom in a successful manner, in addition to the gain a greater number of qualified teachers than needed. • The scores achieved by the students in non-linguistic subjects were found to be higher in comparison with other subjects not included in the programme. Furthermore, an improvement in Second Language Acquisition has been noted. • The degree of satisfaction of pupils, parents and teaching staff with the CBM programme has soared throughout the process of implementation and eventually recognize more advantages than the alternative in the use of the programme. Finally, after our research experience, and given the complexity of the program, we would like to highlight the appropriateness of including in the organization chart of the center a specific Department which articulates the whole process of deployment and implementation of this type of educational programs.

Background: Papillary thyroid cancer (PTC) is the most common type of thyroid cancer. Unlike most cancers, its incidence has dramatically increased in the last decades mainly due to increased diagnosis of indolent PTCs. Adequate risk stratification is crucial to avoid the over-treatment of low-risk patients, as well as the under-treatment of high-risk patients, but the currently available markers are still insufficient. Kallikreins (KLKs) are emergent biomarkers in cancer, but their involvement in PTC is unknown. Methods: This study analyzed DNA methylation (HumanMethylation arrays) and gene expression (RNA-Seq) of KLKs, BRAF and RAS mutations, and clinical data from four published thyroid cancer data sets including normal and tumor tissues (n = 73, n = 475, n = 20, and n = 82) as discovery, training, and validation series. The C4.5 classification algorithm was used to generate a decision tree. Disease-free survival was estimated using Kaplan-Meier and Cox approaches. Specific analyses were performed using real-time polymerase chain reaction and immunohistochemistry. Results: The entire KLK family was deregulated in PTC, displaying a specific epigenetic and transcriptional profile strongly associated with BRAF(V600E) or RAS mutations. Thus, a decision-tree algorithm was developed based on three KLKs with >80% sensitivity and >95% specificity, identifying BRAF- and RAS-mutated tumors. Notably, tumors lacking these mutations were classified as BRAF- or RAS-like. Most importantly, the KLK algorithm uncovered a novel PTC subtype showing favorable prognostic features. Conclusions: The KLK algorithm could lead to a new clinically applicable strategy with important implications for the risk stratification of PTC and the management of patients.

Item does not contain fulltext BACKGROUND: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (< or=20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. MATERIALS AND METHODS: TP53 mutations within a large, international database of CRC (n = 3583) were classified according to functional status for transactivation. RESULTS: Inactive TP53 mutations were found in 29% of all CRCs and were more frequent in rectal (32%) than proximal colon (22%) tumours (P < 0.001). Higher frequencies of inactive TP53 mutations were also seen in advanced stage tumours (P = 0.0003) and in tumours with the poor prognostic features of vascular (P = 0.006) and lymphatic invasion (P = 0.002). Inactive TP53 mutations were associated with significantly worse outcome only in patients with Dukes' stage D tumours (RR = 1.71, 95%CI 1.25-2.33, P < 0.001). Patients with Dukes' C stage tumours appeared to gain a survival benefit from 5-fluorouracil-based chemotherapy regardless of TP53 functional status for transactivation ability. CONCLUSIONS: Mutations that inactivate the transactivational ability of TP53 are more frequent in advanced CRC and are associated with worse prognosis in this stage of disease.

El proceso de globalización en el cual están inmersos la mayoría de los países de la actualidad conlleva la necesidad imperiosa de dominar un idioma que satisfaga las necesidades comunicativas entre los mismos. Es por ello que se hace patente la necesidad de formación en un idioma diferente al materno, que sirva de vínculo de unión entre pueblos. Y entre los países occidentales, sin duda alguna, este idioma es el inglés (idioma hablado por 335 millones de personas en todo el mundo). Como respuesta a esta necesidad, en algunos colegios españoles se han creado diversos programas de actuación para ser llevados a cabo desde el curso primero de la etapa educativa de Educación Primaria. Mi TFM se centra en el programa bilingüe llevado a cabo en la región de Murcia y pretende investigar el desarrollo y resultados de una experiencia de innovación apoyada en TIC. Para comenzar, realizaremos una fundamentación teórica que servirá de base y punto de partida para poder planificar nuestra experiencia innovadora de acorde con las demandas exigidas según el modelo del programa bilingüe en el cual estamos centrados. A continuación plantearemos e ilustraremos la parte empírica de nuestra intervención y posteriormente presentaremos y analizaremos los resultados obtienidos de esta experiencia innovadora así como las conclusiones y perspectivas de futuro que se extraen de la misma

Olive oil (OO) is the most representative food of the traditional Mediterranean Diet (MedDiet). Increasing evidence suggests that monounsaturated fatty acids (MUFA) as a nutrient, OO as a food, and the MedDiet as a food pattern are associated with a decreased risk of cardiovascular disease, obesity, metabolic syndrome, type 2 diabetes and hypertension. A MedDiet rich in OO and OO per se has been shown to improve cardiovascular risk factors, such as lipid profiles, blood pressure, postprandial hyperlipidemia, endothelial dysfunction, oxidative stress, and antithrombotic profiles. Some of these beneficial effects can be attributed to the OO minor components. Therefore, the definition of the MedDiet should include OO. Phenolic compounds in OO have shown antioxidant and anti-inflammatory properties, prevent lipoperoxidation, induce favorable changes of lipid profile, improve endothelial function, and disclose antithrombotic properties. Observational studies from Mediterranean cohorts have suggested that dietary MUFA may be protective against age-related cognitive decline and Alzheimer's disease. Recent studies consistently support the concept that the OO-rich MedDiet is compatible with healthier aging and increased longevity. In countries where the population adheres to the MedDiet, such as Spain, Greece and Italy, and OO is the principal source of fat, rates of cancer incidence are lower than in northern European countries. Experimental and human cellular studies have provided new evidence on the potential protective effect of OO on cancer. Furthermore, results of case-control and cohort studies suggest that MUFA intake including OO is associated with a reduction in cancer risk (mainly breast, colorectal and prostate cancers). (C) 2009 Elsevier B.V. All rights reserved.

Genomic alterations have been analysed in 65 non-small-cell lung cancer (NSCLC) tissue samples by using the arbitrarily primed polymerase chain reaction (AP-PCR), which is a PCR-based genomic fingerprinting. We have shown that AP-PCR may be applied as a useful and feasible practical method for detection of the genomic alterations that accompany malignancy in NSCLC. Genomic changes detected by us consisted of: allelic losses or gains in anonymous DNA sequences, homozygously deleted DNA sequences and polymorphic DNA sequences. According to these genomic changes, lung tumours evaluated in the present study have been scored into three groups: low, moderate and high genomic damage tumours. The aim of this study was to investigate the effect of genomic damage on patient survival. Survival analysis was carried out in 51 NSCLC patients. Our results revealed that high genomic damage patients showed a poorer prognosis than those with low or moderate genomic damage (P = 0.038). Multivariate Cox regression analysis showed that patients with higher genomic alterations displayed an adjusted-by-stage risk ratio 4.26 times higher than the remaining patients (95% CI = 1.03-17.54). We can conclude that genomic damage has an independent prognostic value of poor clinical evolution in NSCLC. Images Figure 1 Figure 2

Allelic imbalances are common events in cancer cells. Quantitative alterations in specific chromosomal loci have been linked to activation (gain) or inactivation (loss) of genes with a proven impact on tumor cell biology. The aim of this study was to detect new chromosomal regions recurrently altered in colorectal tumorigenesis and with a potential effect on patient's outcome. We have analyzed a series of human colorectal tumor biopsy specimens by using the DNA fingerprinting technique arbitrarily primed PCR. This approach provided information on 95 different loci randomly selected and distributed through out the cell's genome. Eight sequences displayed recurrent alterations associated with diminished patient survival. Four of them (showing allelic losses) were located in chromosome 4, one sequence in chromosome 2, and one sequence in chromosome 17. The chromosomal origin of the two remaining sequences could not be determined. Fine mapping of chromosome 4 bands suggested that there are at least two regions in chromosome 4 (4p14-16 and 4q21-28) susceptible to containing tumor suppressor genes the loss of which may affect tumor aggressiveness.

RNA arbitrarily primed (RAP)-PCR is a powerful tool for studying differential gene expression in cancer cells. Systematic analysis of human tumor samples may provide a list of markers with potential application to the diagnosis, prognostic assessment, and treatment of the disease. Nevertheless, because of characteristics inherent to the samples and technique, artifactual results are likely. We have assessed the effects of several factors on RAP-PCR performance to determine the sensitivity and reproducibility of the technique, as well as the accuracy of its results, under different conditions in human cell lines and in a series of 129 paired human normal colonic mucosa-colorectal carcinoma samples. Our results show that RAP-PCR provides reliable fingerprints in a relatively wide spectrum of circumstances, including variations in RNA concentration and contamination by DNA. Densitometric analysis indicated that relative band-intensity variations more than 20% were reproducible in 95% of the cases. Serial analysis of paired normal-tumor cases yielded a number of bands that were recurrently either underexpressed or overexpressed in tumor relative to normal mucosa. These differentially expressed bands are prime targets of research because they represent candidate tumor-specific up- or down-regulated genes with a relevant role in carcinogenesis.

Olive oil (OO) is the most representative food of the traditional Mediterranean Diet (MedDiet). Increasing evidence suggests that monounsaturated fatty acids (MUFA) as a nutrient, OO as a food, and the MedDiet as a food pattern are associated with a decreased risk of cardiovascular disease, obesity, metabolic syndrome, type 2 diabetes and hypertension. A MedDiet rich in OO and OO per se has been shown to improve cardiovascular risk factors, such as lipid profiles, blood pressure, postprandial hyperlipidemia, endothelial dysfunction, oxidative stress, and antithrombotic profiles. Some of these beneficial effects can be attributed to the OO minor components. Therefore, the definition of the MedDiet should include OO. Phenolic compounds in OO have shown antioxidant and anti-inflammatory properties, prevent lipoperoxidation, induce favorable changes of lipid profile, improve endothelial function, and disclose antithrombotic properties. Observational studies from Mediterranean cohorts have suggested that dietary MUFA may be protective against age-related cognitive decline and Alzheimer's disease. Recent studies consistently support the concept that the OO-rich MedDiet is compatible with healthier aging and increased longevity. In countries where the population adheres to the MedDiet, such as Spain, Greece and Italy, and OO is the principal source of fat, rates of cancer incidence are lower than in northern European countries. Experimental and human cellular studies have provided new evidence on the potential protective effect of OO on cancer. Furthermore, results of case-control and cohort studies suggest that MUFA intake including OO is associated with a reduction in cancer risk (mainly breast, colorectal and prostate cancers)., CIBEROBN is an initiative of ISCIII and CEAS Foundation, Spain.