Control of the induction of type I interferon by Peste des petits ruminants virus.

Peste des petits ruminants virus (PPRV) is a morbillivirus that produces clinical disease in goats and sheep. We have studied the induction of interferon-β (IFN-β) following infection of cultured cells with wild-type and vaccine strains of PPRV, and the effects of such infection with PPRV on the induction of IFN-β through both MDA-5 and RIG-I mediated pathways. Using both reporter assays and direct measurement of IFN-β mRNA, we have found that PPRV infection induces IFN-β only weakly and transiently, and the virus can actively block the induction of IFN-β. We have also generated mutant PPRV that lack expression of either of the viral accessory proteins (V&C) to characterize the role of these proteins in IFN-β induction during virus infection. Both PPRV_ΔV and PPRV_ΔC were defective in growth in cell culture, although in different ways. While the PPRV V protein bound to MDA-5 and, to a lesser extent, RIG-I, and over-expression of the V protein inhibited both IFN-β induction pathways, PPRV lacking V protein expression can still block IFN-β induction. In contrast, PPRV C bound to neither MDA-5 nor RIG-I, but PPRV lacking C protein expression lost the ability to block both MDA-5 and RIG-I mediated activation of IFN-β. These results shed new light on the inhibition of the induction of IFN-β by PPRV

Turismo rural, empreendedorismo e gênero: um estudo de caso na comunidade autônoma da Galiza

Neste trabalho indagamos sobre possíveis diferenças no comportamento empreendedor em turismo rural; estabelecemos características e dimensões motivadoras em função do gênero. Num exemplo representativo de estabelecimentos de turismo rural da Comunidade Autônoma da Galiza (Espanha), encontramos relação entre gênero e importância da compatibilização de atividades agrárias e tumrísticas, e entre gênero e perfil das motivações para empreender atividades de turismo rural. As mulheres estão mais motivadas por elementos do âmbito econômico e, portanto, na tomada de decisões, têm mais relevância os critérios de racionalidade econômica unidos à estratégia de diversificação da atividade agrária em favor da sobrevivência financeira. Ao contrário do estabelecido na maior parte da literatura, os fatores de índole social, familiar ou institucional têm a mesma importância para homens e mulheres. Aliás, verificase a ausência de relação entre gênero e características pessoais (como idade e formação e necessidades financeiras do empreendedor)

Two different neurodegenerative diseases caused by proteins with similar structures

The downstream prion-like protein (doppel, or Dpl) is a paralog of the cellular prion protein, PrP(C). The two proteins have ≈25% sequence identity, but seem to have distinct physiologic roles. Unlike PrP(C), Dpl does not support prion replication; instead, overexpression of Dpl in the brain seems to cause a completely different neurodegenerative disease. We report the solution structure of a fragment of recombinant mouse Dpl (residues 26–157) containing a globular domain with three helices and a small amount of β-structure. Overall, the topology of Dpl is very similar to that of PrP(C). Significant differences include a marked kink in one of the helices in Dpl, and a different orientation of the two short β-strands. Although the two proteins most likely arose through duplication of a single ancestral gene, the relationship is now so distant that only the structures retain similarity; the functions have diversified along with the sequence

LEF1 supports metastatic brain colonization by regulating glutathione metabolism and increasing ROS resistance in breast cancer

More than half of all brain metastases show infiltrating rather than displacing growth at the macro-metastasis/brain parenchyma interface (MMPI), a finding associated with shorter survival. The Lymphoid Enhancer-binding Factor-1 (LEF1) is an epithelial-mesenchymal transition (EMT) transcription factor that is commonly overexpressed in brain-colonizing cancer cells. Here, we overexpressed LEF1 in an in vivo breast cancer brain colonization model. It shortened survival, albeit without engaging EMT at the MMPI. By differential proteome analysis, we identified a novel function of LEF1 as a regulator of the glutathione (GSH) system, the principal cellular redox buffer. LEF1 overexpression also conferred resistance against therapeutic GSH depletion during brain colonization and improved management of intracellular ROS. We conclude that besides EMT, LEF1 facilitates metastasis by improving the anti-oxidative capacity of epithelial breast cancer cells, in particular during colonization of the brain parenchyma