Una reflexión acerca del problema del desempleo en la C.A.P.V.

La Comunidad Autónoma Vasca presenta una realidad socio-económica compleja sobre la que inciden multitud de variables políticas,económicas y culturales que han mediatizado nuestro desarrollo en los últimos años. Partiendo de que el principal problema que tiene la economía vasca y también la española es el paro,nos planteamos qué líneas de actuación deberían darse, si no para solucionarlo totalmente, sí al menos para reducirlo de una forma significativa.

Evidence for classification of c.1852_1853AA > GC in MLH1 as a neutral variant for Lynch syndrome

Background: Lynch syndrome (LS) is an autosomal dominant inherited cancer syndrome characterized by early onset cancers of the colorectum, endometrium and other tumours. A significant proportion of DNA variants in LS patients are unclassified. Reports on the pathogenicity of the c.1852_1853AA>GC (p.Lys618Ala) variant of the MLH1 gene are conflicting. In this study, we provide new evidence indicating that this variant has no significant implications for LS. Methods: The following approach was used to assess the clinical significance of the p.Lys618Ala variant: frequency in a control population, case-control comparison, co-occurrence of the p.Lys618Ala variant with a pathogenic mutation, co-segregation with the disease and microsatellite instability in tumours from carriers of the variant. We genotyped p.Lys618Ala in 1034 individuals (373 sporadic colorectal cancer [CRC] patients, 250 index subjects from families suspected of having LS [revised Bethesda guidelines] and 411 controls). Three well-characterized LS families that fulfilled the Amsterdam II Criteria and consisted of members with the p.Lys618Ala variant were included to assess co-occurrence and co-segregation. A subset of colorectal tumour DNA samples from 17 patients carrying the p.Lys618Ala variant was screened for microsatellite instability using five mononucleotide markers. Results: Twenty-seven individuals were heterozygous for the p.Lys618Ala variant; nine had sporadic CRC (2.41%), seven were suspected of having hereditary CRC (2.8%) and 11 were controls (2.68%). There were no significant associations in the case-control and case-case studies. The p.Lys618Ala variant was co-existent with pathogenic mutations in two unrelated LS families. In one family, the allele distribution of the pathogenic and unclassified variant was in trans, in the other family the pathogenic variant was detected in the MSH6 gene and only the deleterious variant co-segregated with the disease in both families. Only two positive cases of microsatellite instability (2/17, 11.8%) were detected in tumours from p.Lys618Ala carriers, indicating that this variant does not play a role in functional inactivation of MLH1 in CRC patients. Conclusions: The p.Lys618Ala variant should be considered a neutral variant for LS. These findings have implications for the clinical management of CRC probands and their relatives.

Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

The synthesis of a GSK 2(nd) generation inhibitor of the hepatitis C virus, by enantioselective 1,3-dipolar cycloaddition between a leucine derived iminoester and tert-butyl acrylate, was studied. The comparison between silver(I) and gold(I) catalysts in this reaction was established by working with chiral phosphoramidites or with chiral BINAP. The best reaction conditions were used for the total synthesis of the hepatitis C virus inhibitor by a four step procedure affording this product in 99% ee and in 63% overall yield. The origin of the enantioselectivity of the chiral gold(I) catalyst was justified according to DFT calculations, the stabilizing coulombic interaction between the nitrogen atom of the thiazole moiety and one of the gold atoms being crucial.

The MLH1 c.1852_1853delinsGC (p.K618A) Variant in Colorectal Cancer: Genetic Association Study in 18,723 Individuals

Colorectal cancer is one of the most frequent neoplasms and an important cause of mortality in the developed world. Mendelian syndromes account for about 5% of the total burden of CRC, being Lynch syndrome and familial adenomatous polyposis the most common forms. Lynch syndrome tumors develop mainly as a consequence of defective DNA mismatch repair associated with germline mutations in MLH1, MSH2, MSH6 and PMS2. A significant proportion of variants identified by screening these genes correspond to missense or noncoding changes without a clear pathogenic consequence, and they are designated as "variants of uncertain significance'', being the c.1852_1853delinsGC (p.K618A) variant in the MLH1 gene a clear example. The implication of this variant as a low-penetrance risk variant for CRC was assessed in the present study by performing a case-control study within a large cohort from the COGENT consortium-COST Action BM1206 including 18,723 individuals (8,055 colorectal cancer cases and 10,668 controls) and a case-only genotype-phenotype correlation with several clinical and pathological characteristics restricted to the Epicolon cohort. Our results showed no involvement of this variant as a low-penetrance variant for colorectal cancer genetic susceptibility and no association with any clinical and pathological characteristics including family history for this neoplasm or Lynch syndrome.

A chemically inert Rashba split interface electronic structure of C-60, FeOEP and PTCDA on BiAg2/Ag(111) substrates

The fields of organic electronics and spintronics have the potential to revolutionize the electronics industry. Finding the right materials that can retain their electrical and spin properties when combined is a technological and fundamental challenge. We carry out the study of three archetypal organic molecules in intimate contact with the BiAg2 surface alloy. We show that the BiAg2 alloy is an especially suited substrate due to its inertness as support for molecular films, exhibiting an almost complete absence of substrate-molecular interactions. This is inferred from the persistence of a completely unaltered giant spin-orbit split surface state of the BiAg2 substrate, and from the absence of significant metallic screening of charged molecular levels in the organic layer. Spin-orbit split states in BiAg2 turn out to be far more robust to organic overlayers than previously thought.

Estudio de una serie musteriense de La Quina (Charente, Francia): el ejemplo de la trinchera C (excavaciones DR. L. y G. Henri-Martin)

[ES] El análisis de una serie industrial correspondiente a los cinco niveles arqueológicos de la trinchera C de La Quina (Charente, Francia), proveniente de las excavaciones del Dr. L. Henri-Martin y de G. Henri-Martin, pone de manifiesto, junto a la caracterización del conjunto estratigráfico por la presencia de raederas, el progresivo incremento de los denticulados en el devenir temporal. Este hecho asociado a otros particulares fenómenos secundarios (en el alargamiento de las formas, en la tipología de las raederas, en la elaboración del retoque, ... ) traducen una complicación diacrónica creciente en la dinámica de este complejo musteroide, presagiando, quizás, su relativa afinidad con el proceso leptolitizante de las series industriales evolucionadas del Paleolítico medio.

Técnicas de metalistería en una moneda romana del siglo 1 d. C.

[ES] Se analiza un sestercio de Nerón usado como elemento ornamental. Un artesano hizo en el reverso de la moneda algunos radios curvos y cinco agujeros. En el artículo se hacen una serie de consideraciones sobre la realización de este inusual trabajo y su posible función. Por otro lado, también se examinan ciertos aspectos de los usos ornamentales de la moneda y la evaluación moral de la figura de Nerón.