Submitted by Alessandra Portugal (alessandradf@ioc.fiocruz.br) on 2013-09-17T13:17:37Z No. of bitstreams: 1 Hugo Leonardo2 OK.docx.pdf: 1727936 bytes, checksum: 9b422dec3434e2e337a66ba7ab57e26b (MD5) / Made available in DSpace on 2013-09-17T13:17:37Z (GMT). No. of bitstreams: 1 Hugo Leonardo2 OK.docx.pdf: 1727936 bytes, checksum: 9b422dec3434e2e337a66ba7ab57e26b (MD5) Previous issue date: 2012-08-30 / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil / Os enterovírus humanos ( Picornaviridae ) são vírus de transmissão predominantemente ent érica, possuem distribuição cosmopolita, estando entre os agentes mais prevalentes como causadores de patogenias em humanos. Atualmente, já foram descritos mais de 100 sorotipos para os enterovírus humanos e em grande parte dos casos as infecções associada s são assintomáticas. Surtos e casos esporádicos de enteroviroses são frequentemente notificados em diversas regiões do mundo causando conjuntivite hemorrágica aguda, meningite asséptica, doença de mão pé e boca e poliomielite. A poliomielite é uma doença infecciosa de caráter agudo, que pode assumir desde formas assintomáticas até formas paralíticas (paralisia flácida aguda ou PFA), causada em geral por um dos três sorotipos de poliovírus (PV). O PV selvagem está eliminado do Brasil desde 1989, atualmente sendo restrito a apenas quatro países (Nigéria, Afeganistão, Paquistão, Índia). Entretanto surtos de PFA associados à PV de origem vacinal e a enterovírus não pólio recombinantes tem sido notificados. A caracterização de EVNP é de extrema importância para a investigação da diversidade de vírus co - circulantes, e para relacionar os sintomas clínicos com o sorotipo viral envolvido, incluindo a investigação de vias de transmissão de enterovírus, durante a ocorrência de surtos, além de contribuir para estudos ep idemiológicos e com a evolução de enterovírus. Neste estudo foram analisadas amostras relacionadas à PFAs, utilizando RT - PCR e PCR com o objetivo de identificar quais são as espécies de enterovírus humanos associadas. Os membros da espécie C foram sequenci ados para a identificação de sorotipo. De um total de 190 amostras, 79 eram da espécie C, 78 da espécie B, 32 da espécie A e 1 amostra era correspondente as espécies A e C,não sendo encontradas amostras da espécie D. Entre as amostras da espécie C,58 cor respondiam a PV.Os dados obtidos apresentam similaridades com estudos similares na Europa e Ásia, cobrindo um aspecto pouco observado na epidemiologia dos enterovírus em território brasileiro. / The human enterovirus es (Picornaviridae) are predominantly enteric virus transmission, have a cosmopolitan distribution, being among the most prevalent agents as causing pathogens in humans. Currently, have been described more than 100 serotypes for human enteroviruses and in mo st cases associated infections are asymptomatic. Outbreaks and sporadic cases of enteroviruses are frequently reported in several regions of the world causing acute hemorrhagic conjunctivitis, aseptic meningitis, hand foot and mouth disease and poliomyelit es. Poliomyelites is an infectious disease of acute character, which may take from asymptomatic to paralytic form (acute flaccid paralysis or PFA), usually caused by one of three poliovirus serotypes (PV). The PV is eliminated wild in Brazil since 1989, cu rrently restricted to only four countries (Nigeria, Afghanistan, Pakistan and India). However PFA outbreaks associated with PV source vaccine and recombinant Non - polio enteroviruses has been reported. The characterization of EVNP is extremely important to investigate the diversity of co - circulating viruses, and to correlate clinical symptoms with viral serotype involved, including the investigation of routes of transmission of enteroviruses, during outbreaks, besides contributing for epidemiological studies and the evolution of enteroviruses. We analyzed samples related to AFP, using RT - PCR and PCR in order to identify which species of human enteroviruses associated. Members of the species C were sequenced for identification of serotype. From a total of 190 samples, 79 were of type C, 78 type B, 32 type A and one sample was corresponding for A and C, were not found samples of type D. Among the samples of species C, 58 corresponded to PV.Os data show similarities with similar studies in Europe and Asia, coveri ng a little noticed aspect of the epidemiology of enteroviruses in Brazilian territory.

The present study focuses on the biological functions of the transcription factor EMA/E2F-6, a member of the E2F-family of transcription factors that play an import role in cell cycle progression, differentiation and apoptosis. EMA/E2F-6 functions as a transcriptional repressor by recruiting a large protein complex, that includes polycomb group proteins, to specific target genes in order to silence their expression. To identify the biological functions of EMA/E2F-6 mice lacking this factor were developed and subsequently analysed. EMA/E2F6-/- mice are born with the expected frequency, are fertile and develop normally up to 18 months of age. Then about 25 % of these mice develop a paralysis of the hind limbs and present with a severe primary myelination defect of the spinal cord (and in part of peripheral nerves, too) that is accompanied by a massive infiltration of macrophages. Importantly, the histological findings were also detected in EMA/E2F-6-/- mice lacking clinical symptoms albeit to a lesser extend. With respect to EMA/E2F-6 association with polycomb group (Pc-G) proteins there were no significant findings such as skeletal transformations. In addition, only a mild proliferation defect of T-lymphocytes was observed that, in a more severe form, is typical for Pc-G mutations in the mice. Surprisingly, embryonic fibroblasts from EMA/E2F-6-/- mice have no obvious cell cycle defects. Accordingly, gene expression profiles showed that classical E2F target genes were normally regulated in these cells. However, EMA/E2F-6-/- fibroblasts ubiquitously express genes like alpha-tubulin-3 and -7 that are normally expressed in a strictly testis-specific manner. All EMA/E2F-6-dependent target genes identified contain a conserved E2F-binding site in their promoters that is required both for EMA/E2F-6 binding and regulation.