Involvement of ANXA5 and ILKAP in Susceptibility to Malignant Melanoma

Single nucleotide-polymorphisms (SNPs) are a source of diversity among human population, which may be responsible for the different individual susceptibility to diseases and/or response to drugs, among other phenotypic traits. Several low penetrance susceptibility genes associated with malignant melanoma (MM) have been described, including genes related to pigmentation, DNA damage repair and oxidative stress pathways. In the present work, we conducted a candidate gene association study based on proteins and genes whose expression we had detected altered in melanoma cell lines as compared to normal melanocytes. The result was the selection of 88 loci and 384 SNPs, of which 314 fulfilled our quality criteria for a case-control association study. The SNP rs6854854 in ANXA5 was statistically significant after conservative Bonferroni correction when 464 melanoma patients and 400 controls were analyzed in a discovery Phase I. However, this finding could not be replicated in the validation phase, perhaps because the minor allele frequency of SNP rs6854854 varies depending on the geographical region considered. Additionally, a second SNP (rs6431588) located on ILKAP was found to be associated with melanoma after considering a combined set of 1,883 MM cases and 1,358 disease-free controls. The OR was 1.29 (95% CI 1.12-1.48; p-value= 4x10(-4)). Both SNPs, rs6854854 in ANXA5 and rs6431588 in ILKAP, show population structure, which, assuming that the Spanish population is not significantly structured, suggests a role of these loci on a specific genetic adaptation to different environmental conditions. Furthermore, the biological relevance of these genes in MM is supported by in vitro experiments, which show a decrease in the transcription levels of ANXA5 and ILKAP in melanoma cells compared to normal melanocytes.

¿Por qué siguen existiendo los paraísos fiscales?

El TFG realizado trata de investigar los motivos por los cuales siguen existiendo los paraísos fiscales, a pesar de la gran variedad de perjuicios que estos provocan. Para ello, se han analizado las definiciones y características que existen, así como su evolución histórica, su tipología y clasificación. Junto con esto, se han analizado los aspectos negativos y positivos que provocan los paraísos fiscales, así como los agentes que se benefician de la existencia y uso de estos. Posteriormente, se ha realizado un balance entre los aspectos negativos y positivos concluyendo finalmente, con la identificación de los motivos que apoyan la continuidad de estas jurisdicciones. Este trabajo ha sido realizado en castellano.

Regulación bancaria

[ES] Se realiza un estudio sobre la necesidad de que exista una regulación en el sector bancario, así como la explicación de los diferentes riesgo que se asumen. Finalmente, se habla de la trayectoria de Basilea para llegar a la conclusión de si es necesario o merece la pena mantenerla para una estabilidad futura.

Pharmacogenetics of MicroRNAs and MicroRNAs Biogenesis Machinery in Pediatric Acute Lymphoblastic Leukemia

Despite the clinical success of acute lymphoblastic leukemia (ALL) therapy, toxicity is frequent. Therefore, it would be useful to identify predictors of adverse effects. In the last years, several studies have investigated the relationship between genetic variation and treatment-related toxicity. However, most of these studies are focused in coding regions. Nowadays, it is known that regions that do not codify proteins, such as microRNAs (miRNAs), may have an important regulatory function. MiRNAs can regulate the expression of genes affecting drug response. In fact, the expression of some of those miRNAs has been associated with drug response. Genetic variations affecting miRNAs can modify their function, which may lead to drug sensitivity. The aim of this study was to detect new toxicity markers in pediatric B-ALL, studying miRNA-related polymorphisms, which can affect miRNA levels and function. We analyzed 118 SNPs in pre-miRNAs and miRNA processing genes in association with toxicity in 152 pediatric B-ALL patients all treated with the same protocol (LAL/SHOP). Among the results found, we detected for the first time an association between rs639174 in DROSHA and vomits that remained statistically significant after FDR correction. DROSHA had been associated with alterations in miRNAs expression, which could affect genes involved in drug transport. This suggests that miRNA-related SNPs could be a useful tool for toxicity prediction in pediatric B-ALL.

El futuro del estado del bienestar

En este Trabajo fin de Grado se hace una reflexión interesante en torno al modelo social europeo, sus características en los distintos países, y, en comparación con el modelo americano. Se subrayan los pilares del Estado del Bienestar y su debilidad actual provocada por la crisis económica, proponiéndose posibles alternativas para su viabilidad. La Unión Europea se encuentra actualmente, en un momento crucial de su historia, donde las dudas sobre la viabilidad de su modelo social aumentan cada día, frente a las cuales tendrá que actuar adecuadamente para seguir garantizando el bienestar de su sociedad así como su crecimiento económico. Se explica las características del modelo social europeo; sus diferencias entre los países miembros, y, con otros modelos como el americano. Analizamos también el impacto de la crisis en el mercado de trabajo en los distintos escenarios y sus consecuencias sobre la pobreza, la cohesión social y la desigualdad, valorando el efecto negativo tanto en el crecimiento económico como en la democracia. En base a esos datos, que son distintos para cada país dependiendo de su historia y modelo social, se perfilan posibles medidas para superar la crisis económica y la supervivencia de bienestar europeo.

Differential Neuroprotective Effects of 5 '-Deoxy-5 '-Methylthioadenosine

Background: 5'-deoxy-5'-methylthioadenosine (MTA) is an endogenous compound produced through the metabolism of polyamines. The therapeutic potential of MTA has been assayed mainly in liver diseases and, more recently, in animal models of multiple sclerosis. The aim of this study was to determine the neuroprotective effect of this molecule in vitro and to assess whether MTA can cross the blood brain barrier (BBB) in order to also analyze its potential neuroprotective efficacy in vivo. Methods: Neuroprotection was assessed in vitro using models of excitotoxicity in primary neurons, mixed astrocyte-neuron and primary oligodendrocyte cultures. The capacity of MTA to cross the BBB was measured in an artificial membrane assay and using an in vitro cell model. Finally, in vivo tests were performed in models of hypoxic brain damage, Parkinson's disease and epilepsy. Results: MTA displays a wide array of neuroprotective activities against different insults in vitro. While the data from the two complementary approaches adopted indicate that MTA is likely to cross the BBB, the in vivo data showed that MTA may provide therapeutic benefits in specific circumstances. Whereas MTA reduced the neuronal cell death in pilocarpine-induced status epilepticus and the size of the lesion in global but not focal ischemic brain damage, it was ineffective in preserving dopaminergic neurons of the substantia nigra in the 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP)-mice model. However, in this model of Parkinson's disease the combined administration of MTA and an A(2A) adenosine receptor antagonist did produce significant neuroprotection in this brain region. Conclusion: MTA may potentially offer therapeutic neuroprotection.

Euskarazko denbora-egiturak etiketatzeko gidalerroak v2.0

[EN]To interpret the temporal information on texts, a mark-up language that will code that information is needed, in order to make that information automatically reachable. The most used mark-up language is TimeML (Pustejovsky et al., 2003), which has also been choosen for Basque. In this guidelines we present the Basque version of ISO-TimeML (ISO-TimeML working group, 2008). After having analysed the tags, attributes and values created for English, we describe the most appropriate ones to represent Basque time structures’ information.

Proposta Metodológica de Análise Quantitativa da Sustentabilidade de Estabelecimentos Agropecuários Fluminenses

O presente trabalho consistiu em realizar uma proposta metodológica de análise quantitativa da sustentabilidade de estabelecimentos agropecuários fluminenses através do emprego do marco metodológico proposto por Sauvenier et al. (2006) e van Cauwenbergh et al. (2007), denominado SAFE (Sustainability Assessment of Farming and the Environment Framework). Conforme a aplicação para sistemas agrários realizada por Sánchez-Fernández (2009) e por sua vez, incorporando a quarta dimensão da sustentabilidade (dimensão institucional), ademais das três dimensões clássicas neste tipo de análise (econômica, social e ambiental), seguindo a sugestão do IBGE (2010), com base nas recomendações do Livro Azul da ONU (1996). Esse procedimento contou com a colaboração e validação de um painel composto por 16 especialistas em agricultura fluminense o que permitiu selecionar 20 indicadores de sustentabilidade, derivados de 17 critérios, 8 princípios e 4 dimensões. Dos resultados alcançados e de seus possíveis desdobramentos, a proposta metodológica sugerida pode ser considerada uma ferramenta potencialmente útil para guiar as políticas públicas que incidem sobre o setor.

La retórica latino-cristiana: Agustín de Hipona

[EN] The "Christian Scientia" as it is presented in "De Doctrina Christiana" has two aspects: inventio, which corresponds to intellectio, to the understanding of the Holy Writings, and, on other hand, the exposition of the results obtained. These two sides are closely linked in his ideal of oratory: "dicere sapienter et eloquenter". On trying to acquire eloquence the main point is the "familiaritas" with the models, and these are the Writings and the Christian authors, the only models, as for content and form, that must be of any interest to the Christian orator. From this point of view the place left for standard rhetoric is very small.

Geochemical characterization of the fire-fountain fed deposits of Las Herrerias volcano (Campo de Calatrava Volcanic Field, Ciudad Real)

The Las Herrerias volcano (Bolanos de Calatrava, Campo de Calatrava Volcanic Field) is characterized by the great amount and variety of fire-fountain fed deposits. All these deposits are compositionally similar, being constituted by magnesium-rich (MgO = 11.58-4.19%), aluminium-poor (Al2O3 = 9.64-10.99%) highly sodic (Na2O = 2.24-3.81%) melanephelinites, with high contents in rare earth-elements (10x-200x chondrite), particularly in light-rare earth elements with respect to the heavy ones [(La/Lu)(N) = 32-35]. Contrary to the equivalent melanephelinites of this volcanic field, the relatively low contents in Ni (233-286 ppm), Cr (393-520 ppm) and magnesium number (Mg* = 45-54) indicate that these rocks do not correspond with primary melts. On the other hand, the variable distribution of clinopyroxene in the magma during eruption would be responsible for the slight compositional differences observed in the studied samples. Finally, we argue that these fire fountains were developed in a continental intraplate setting.

Optimizing the Curie temperature of pseudo-binary RxR2-x ' Fe-17 (R, R ' = rare earth) for magnetic refrigeration

Several pseudo-binary RxR2-x'Fe-17 alloys (with R = Y, Ce, Pr, Gd and Dy) were synthesized with rhombohedral Th2Zn17-type crystal structure determined from x-ray and neutron powder diffraction. The choice of compositions was done with the aim of tuning the Curie temperature (T-C) in the 270 +/- 20 K temperature range, in order to obtain the maximum magneto-caloric effect around room temperature. The investigated compounds exhibit broad isothermal magnetic entropy changes, Delta S-M(T), with moderate values of the refrigerant capacity, even though the values of Delta S-M(Peak) are relatively low compared with those of the R2Fe17 compounds with R = Pr or Nd. The reduction on the Delta S-M(Peak) is explained in terms of the diminution in the saturation magnetization value. Furthermore, the Delta S-M(T) curves exhibit a similar caret-like behavior, suggesting that the magneto-caloric effect is mainly governed by the Fe-sublattice. A single master curve for Delta S-M/Delta S-M(Peak)(T) under different values of the magnetic field change are obtained for each compound by rescaling of the temperature axis.

El sacrificio de Alcestis

[ES] La tragedia griega exige, para su comprensión, remitirse al contexto social y cultural en que fue compuesta. Tomar como referente el conocimiento que nosotros tenemos del modo de vida y pensamiento de entonces es algo fundamental, si se quiere entender la forma de actuar de las mujeres y de los hombres trágicos, como Alcestis y Admeto. Vistos bajo esta perspectiva, dejan de ser la heroína romántica y el pérfido esposo, para convertirse ella en el paradigma del ideal femenino en una sociedad donde el padre es el miembro más preciado de la familia, y él en el varón irreprochable. Todo esto bajo un discurso, el trágico, que se complace en difuminar la frontera mediadora entre lo masculino y lo femenino.