Shigella sonnei genome sequencing and phylogenetic analysis indicate recent global dissemination from Europe

Shigella are human-adapted Escherichia coli that have gained the ability to invade the human gut mucosa and cause dysentery1,2, spreading efficiently via low-dose fecal-oral transmission3,4. Historically, S. sonnei has been predominantly responsible for dysentery in developed countries, but is now emerging as a problem in the developing world, apparently replacing the more diverse S. flexneri in areas undergoing economic development and improvements in water quality4-6. Classical approaches have shown S. sonnei is genetically conserved and clonal7. We report here whole-genome sequencing of 132 globally-distributed isolates. Our phylogenetic analysis shows that the current S. sonnei population descends from a common ancestor that existed less than 500 years ago and has diversified into several distinct lineages with unique characteristics. Our analysis suggests the majority of this diversification occurred in Europe, followed by more recent establishment of local pathogen populations in other continents predominantly due to the pandemic spread of a single, rapidly-evolving, multidrug resistant lineage

Characterization of a Novel Fusion Protein from IpaB and IpaD of Shigella spp. and Its Potential as a Pan-Shigella Vaccine

Shigellosis is an important disease in the developing world, where about 90 million people become infected with Shigella spp. each year. We previously demonstrated that the type three secretion apparatus (T3SA) proteins IpaB and IpaD are protective antigens in the mouse lethal pulmonary model. In order to simplify vaccine formulation and process development, we have evaluated a vaccine design that incorporates both of these previously tested Shigella antigens into a single polypeptide chain. To determine if this fusion protein (DB fusion) retains the antigenic and protective capacities of IpaB and IpaD, we immunized mice with the DB fusion and compared the immune response to that elicited by the IpaB/IpaD combination vaccine. Purification of the DB fusion required coexpression with IpgC, the IpaB chaperone, and after purification it maintained the highly α-helical characteristics of IpaB and IpaD. The DB fusion also induced comparable immune responses and retained the ability to protect mice against Shigella flexneri and S. sonnei in the lethal pulmonary challenge. It also offered limited protection against S. dysenteriae challenge. Our results show the feasibility of generating a protective Shigella vaccine comprised of the DB fusion

Induction of erythroferrone in healthy humans by micro-dose recombinant erythropoietin or high-altitude exposure

The erythropoietin (Epo)-erythroferrone (ERFE)-hepcidin axis coordinates erythropoiesis and iron homeostasis. While mouse studies have established that Epo-induced ERFE production represses hepcidin synthesis by inhibiting hepatic BMP/SMAD signaling, evidence for the role of ERFE in humans is limited. To investigate the role of ERFE as a physiological erythroid regulator in humans, we conducted two studies: first, 24 males received six injections of saline (placebo), recombinant Epo (rhEpo) 20 UI kg-1 (micro-dose) or 50 UI kg-1 (low-dose). Second, we quantified ERFE in 22 subjects exposed to high altitude (3800 m) for 15 hours. In the first study, total hemoglobin mass (Hbmass) increased after low- but not after micro-dose injections, when compared to placebo. Serum ERFE levels were enhanced by rhEpo, remaining higher than after placebo for 48 (micro-dose) or 72 hours (low-dose) post-injections. Conversely, hepcidin levels decreased when Epo and ERFE arose, before any changes in serum iron parameters occurred. In the second study, serum Epo and ERFE increased at high altitude. The present results demonstrate that in healthy humans ERFE responds to slightly increased Epo levels not associated with Hbmass expansion and down-regulates hepcidin in an apparently iron-independent way. Notably, ERFE flags micro-dose Epo, thus holding promise as novel anti-doping biomarker

Veterans League Rio Grande: forms of leisure and singularities football

Neste trabalho, tratamos do futebol sob sua forma menos espetacularizada, que ?? praticada, prioritariamente, como lazer. Embora este seja jogado por uma grande parte da popula????o, principalmente no Brasil, n??o possui a mesma visibilidade midi??tica do profissional. O foco de an??lise foi o futebol de veteranos, atrav??s do campeonato organizado pela Liga de Veteranos do Rio Grande (LVRG) no ano de 2010, em sua 15?? edi????o. Nossos objetivos foram: compreender as formas de organiza????o e funcionamento da Liga; descrever e analisar acontecimentos futebol??sticos do campeonato de 2010 e estudar as pr??ticas que constituem esse futebol de veteranos dentro e fora de campo. Isso, atrav??s de uma metodologia inspirada tanto na etnografia como na hist??ria oral, composta por 43 di??rios de campo, 460 imagens, documentos oficiais (atas, estatutos, regulamentos) e not??cias do ??nico jornal di??rio da cidade, o Jornal Agora. Al??m disso, realizamos duas entrevistas e a coleta de um depoimento oral, bem como o registro de anota????es das conversas informais com os integrantes da Liga. Observamos que os participantes se apropriam desse futebol com diferentes objetivos, os quais lhes exigem dedica????o mesmo fora daquele espa??o-tempo formal dos jogos promovidos pela Liga de Veteranos. Identificamos a LVRG enquanto ambiente de lazer que propicia o encontro de seus integrantes em diferentes ocasi??es, promovendo sociabilidades. Constatamos, ainda, que essa Liga apresentou algumas singularidades futebol??sticas, principalmente na distribui????o de fun????es espec??ficas, como a de treinador, e na valoriza????o da organiza????o e da disciplina futebol??sticaIn this work we treat football not as a spectacle form, but as leisure. Although this is played by a large population, mainly in Brazil, does not have the same visibility of the professional football in the media. The focus of analysis was the veterans football, through the championship organized by the Liga de Veteranos do Rio Grande (LVRG) in the year 2010 in its 15th edition. Our objectives were: to understand the organization and functioning of the League, describe and analyze football s events championship in 2010 and study the practices that constitute this veterans football on and off the field. This, through a methodology inspired both ethnography and oral history, composed of 43 field diaries, 460 images, official documents (acts, statutes, regulations) and news of the city's only daily newspaper, the Journal Agora. In addition, we conducted two interviews and the collection of oral testimony and the record notes of informal conversations with members of the League. We observed that participants take ownership of football with different goals, which they require dedication that even outside space-time formal games promoted by the Liga de Veteranos. We identified the LVRG while leisure environment that promotes the meeting of its members on different occasions, promoting sociability. We also had noted that this league presented some singularities in their football, particularly in the distribution of specific functions, such as coaching, and promote the organization and discipline footbal