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.

Cartas enviadas por Ramón María de Aldasoro a Justo Garate en 1940

8 cartas (mecanografiadas) ; 225x285 mmm. Ubicación: Caja 1 - Carpeta 20

Cartas enviadas por José Angel Ascunde a Justo Garate entre 1991 y 1994

9 cartas y 1 tarjeta de visita (mecanografiadas y manuscritas) ; 210x295mm. Ubicación: Caja 1 - Carpeta 70

Carta enviada por Angel Ayestarán a Justo Garate en 1982

1 carta (mecanografiada) ; 219x277mm. Ubicación: Caja 1 - Carpeta 78

Carta enviada por José María de Azcárraga a Justo Garate en 1964

1 carta (manuscrita) : 275x214mm. Ubicación: Caja 1 - Carpeta 81

Cartas enviadas por José María Azcona a Justo Garate entre 1930 y 1936

7 cartas (mecanografiadas y manuscritas) ; entre 180x130mm y 214x139mm. Ubicación: Caja 1 - Carpeta 82

Cartas enviadas por José María Bengoa a Justo Garate entre 1940 y 1945

10 cartas (mecanografiadas); entre 210x255mm y 210x310mm. [La carta fechada el 10-11-1942 esta incompleta, falta la primera hoja]

Cartas enviadas por José María Bengoa a Justo Garate entre 1947 y 1961

11 cartas (mecanografiadas y manuscritas); entre 170x225mm y 215x275mm

Cartas enviadas por José María Bengoa a Justo Garate entre 1962 y 1992

8 cartas (mecanografiadas y manuscritas); entre 150x210mm y 215x275mm .- 1 Felicitación de Navidad (manuscrita y sin fecha) ; 110mmx160mm

Cartas enviadas por María Milagros Bidegain a Justo Garate entre 1971 y 1972

2 cartas (mecanografiada y manuscrita); entre 215x155mm y 210x315mm.

Cosméticos María D'uol: Gulliver en el país de los gigantes

Duración (en horas): De 21 a 30 horas Destinatario: Estudiante y Docente

Effect of the A cation size disorder and synthesis conditions on the properties of an iron perovskite series

Póster presentado en The Energy and Materials Research Conference - EMR2015 celebrado en Madrid (España) entre el 25-27 de febrero de 2015

Ictiólogos de la Argentina: María Isabel Hylton Scott

This series will include all those people who, by means of their contributions, great and small, played a part in the consolidation of ichthyology in Argentina. The general plan of this work consists of individual factsheets containing a list of works by each author, along with reference bibliography and, whenever possible, personal pictures and additional material. The datasheets will be published primarily in chronological order, although this is subject to change by the availability of materials for successive editions. This work represents another approach for the recovery and revalorization of those who set the foundations of Argentine ichthyology while in diverse historical circumstances. I expect this to be the beginning of a major work that achieves the description of such a significant part of the history of natural sciences in Argentina.

As razões do direito: um estudo da razão pública a partir do modelo liberal-igualitário de John Rawls

Em 1993, John Rawls, notável filósofo e professor da distinta Harvard University, publicou seu Political Liberalism, um livro em que pela primeira vez sintetiza sistematicamente o conceito de razão pública, uma ideia chave de sua teoria da justiça como equidade (justice as fairness). Segundo Rawls, a razão pública consiste fundamentalmente no modo e conteúdo adequados ao debate e à fundamentação de escolhas essenciais de justiça no espaço público de uma democracia constitucional. Nesse sentido, Rawls advoga que o único meio razoável de justificação da coerção estatal reside no reconhecimento e/ou obtenção de consensos (overlapping consensus) em relação às escolhas essenciais de uma sociedade democrática, o que só é possível se atores públicos e privados se despojarem de suas respectivas doutrinas filosóficas ou morais abrangentes ao debater e decidir tais questões essenciais de justiça. A presente dissertação tem por objetivo analisar a proposta de razão pública de Rawls, dentro do contexto de sua teoria da justiça como equidade, propondo-se a verificar se o pensamento rawlsiano procede no contexto jurídico-filosófico da pós-modernidade e se a sua teoria pode ser concretamente aplicada aos ordenamentos jurídicos contemporâneos, em especial no que tange ao conteúdo e pleno exercício da liberdade religiosa pelos cidadãos de um estado constitucional democrático.