Fine mapping and functional analysis of the multiple sclerosis risk gene CD6

CD6 has recently been identified and validated as risk gene for multiple sclerosis (MS), based on the association of a single nucleotide polymorphism (SNP), rs17824933, located in intron 1. CD6 is a cell surface scavenger receptor involved in T-cell activation and proliferation, as well as in thymocyte differentiation. In this study, we performed a haptag SNP screen of the CD6 gene locus using a total of thirteen tagging SNPs, of which three were non-synonymous SNPs, and replicated the recently reported GWAS SNP rs650258 in a Spanish-Basque collection of 814 controls and 823 cases. Validation of the six most strongly associated SNPs was performed in an independent collection of 2265 MS patients and 2600 healthy controls. We identified association of haplotypes composed of two non-synonymous SNPs [rs11230563 (R225W) and rs2074225 (A257V)] in the 2nd SRCR domain with susceptibility to MS (Pmax(T) permutation=161024). The effect of these haplotypes on CD6 surface expression and cytokine secretion was also tested. The analysis showed significantly different CD6 expression patterns in the distinct cell subsets, i.e. – CD4+ naı¨ve cells, P = 0.0001; CD8+ naı¨ve cells, P,0.0001; CD4+ and CD8+ central memory cells, P = 0.01 and 0.05, respectively; and natural killer T (NKT) cells, P = 0.02; with the protective haplotype (RA) showing higher expression of CD6. However, no significant changes were observed in natural killer (NK) cells, effector memory and terminally differentiated effector memory T cells. Our findings reveal that this new MS-associated CD6 risk haplotype significantly modifies expression of CD6 on CD4+ and CD8+ T cells.

De samurais a empresarios. La industrialización de Japón

En este trabajo se analiza el proceso de industrialización de Japón, así como los factores que influyeron en el mismo a finales del siglo XIX. En una primera parte se estudia el cambio de régimen político tras la caida del shogunato Tokugawa y el ascenso al poder del emperador Meiji. En una segunda parte se analizan los principales sectores económicos del pais y los efectos que la nueva política gubernamental tuvo sobre ellos. Por último se dedica un apartado a los zaibatsu, conglomerado empresarial característico del Japón de la época.

Eginhardo, Suetonio y la "perfidia" de los vascones

[ES] Las referencias a los vascones que Eginhardo incluye en su célebre «Vita Karoli» asocian a este pueblo con la perfidia, entendida ésta como parte del estereotipo de la barbarie forjado a lo largo de la Antigüedad Clásica. Esta imagen se ve reforzada, además, por la dependencia que esta biografía de Carlomagno muestra con respecto a las Vidas de los Césares de Suetonio.