Adrenal gland tumorigenesis after gonadectomy in mice is a complex genetic trait driven by epistatic loci

Postgonadectomy adrenocortical tumorigenesis is a strain-specific phenomenon in inbred mice, assumed to be caused by elevated LH secretion and subsequent ectopic LH receptor (LHR) overexpression in adrenal gland. However, the molecular mechanisms of this cascade of events remain unknown. In this study, we took advantage of the mouse strain dependency of the phenotype to unravel its genetic basis. Our results present the first genome-wide screening related to this pathology in two independent F2 and backcross populations generated between the neoplastic DBA/2J and the nonsusceptible C57BL/6J strains. Surprisingly, the postgonadectomy elevation of serum LH was followed by similar up-regulation of adrenal LHR expression in both parental strains and their crosses, irrespective of their tumor status, indicating that it is not the immediate cause of the tumorigenesis. Linkage analysis revealed one major significant locus for the tumorigenesis on chromosome 8, modulated by epistasis with another quantitative trait locus on chromosome 18. Weight gain, a secondary phenotype after gonadectomy, showed a significant but separate quantitative trait locus on chromosome 7. Altogether, postgonadectomy adrenocortical tumorigenesis in DBA/2J mice is a dominant trait that is not a direct consequence of adrenal LHR expression but is driven by a complex genetic architecture. Analysis of candidate genes in the tumorigenesis linkage region showed that Sfrp1 (secreted frizzled-related protein 1), a tumor suppressor gene, is differentially expressed in the neoplastic areas. These findings may have relevance to the human pathogenesis of macronodular adrenal hyperplasia and adrenocortical tumors in postmenopausal women and why some of them develop obesity

Carmen i Ultima Thule: fyra nordiska tolkningar av en spansk zigenerska under sent 1800-tal

Carmen (composed by Georges Bizet) had its Nordic première at the Royal Swedish Theatre in Stockholm in 1878, only three years after its first performance at the Opéra-Comique in Paris. Olefine Moe-Torssell (1850–1933), a relatively high soprano, sung the role in Stockholm, thus becoming the first Carmen in Norden. Thirteen years later the opera had already been staged all over the Nordic countries: in Denmark (1887) with the young female singer Elisabeth Dons (1864–1942) in Carmen’s role, in Finland (1889) with Emma Engdahl (1852–1930) in the title role, and in Norway (1891) with the expressive singer Gina Oselio (Ingeborg Aas, 1858–1937) as Carmen. In my article, I argue that Carmen arrived in Norden in the middle of an artistic paradigm shift, which manifested itself as a public polemic between advocates for a conservative aesthetic idealism, and those defending new and modern art movements, such as realism and naturalism. A main concern among the debaters was how the woman and especially the changed behaviour of the modern woman should be represented in art. As a realistic opera with a female character who neither sacrifices herself nor dies for love, Carmen can be construed as one comment on this debate, whether this was the authors’ intention or not. My analysis reveals that since Carmen could never be linked to the traditional chain of self-sacrificing female characters, most newspaper critics, as well as the singer Gina Oselio, turned to the reverse formula: if a female character could not be idealised, she should be demonised (Moi 2006). Hence the Nordic critics unanimously defined Carmen as a femme fatale who destroys the innocent Don José, the actual hero of the opera. &nbsp