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1.
Cell Rep ; 18(6): 1395-1409, 2017 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-28178518

RESUMO

SoxB transcription factors and histone deacetylases (HDACs) are each major players in the regulation of neurogenesis, but a functional link between them has not been previously demonstrated. Here, we show that SoxB2 and Hdac2 act together to regulate neurogenesis in the cnidarian Hydractinia echinata during tissue homeostasis and head regeneration. We find that misexpression of SoxB genes modifies the number of neural cells in all life stages and interferes with head regeneration. Hdac2 was co-expressed with SoxB2, and its downregulation phenocopied SoxB2 knockdown. We also show that SoxB2 and Hdac2 promote each other's transcript levels, but Hdac2 counteracts this amplification cycle by deacetylating and destabilizing SoxB2 protein. Finally, we present evidence for conservation of these interactions in human neural progenitors. We hypothesize that crosstalk between SoxB transcription factors and Hdac2 is an ancient feature of metazoan neurogenesis and functions to stabilize the correct levels of these multifunctional proteins.


Assuntos
Cnidários/metabolismo , Cnidários/fisiologia , Histona Desacetilase 2/metabolismo , Neurogênese/fisiologia , Fatores de Transcrição SOXB2/metabolismo , Animais , Evolução Biológica , Regulação para Baixo/fisiologia , Humanos , Neurônios/metabolismo , Neurônios/fisiologia , Regeneração/fisiologia , Células-Tronco/metabolismo , Células-Tronco/fisiologia
2.
PLoS Negl Trop Dis ; 11(8): e0005831, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28846678

RESUMO

BACKGROUND: Leptospirosis is a bacterial zoonosis caused by pathogenic Leptospira for which rats are considered as the main reservoir. Disease incidence is higher in tropical countries, especially in insular ecosystems. Our objectives were to determine the current burden of leptospirosis in Seychelles, a country ranking first worldwide according to historical data, to establish epidemiological links between animal reservoirs and human disease, and to identify drivers of transmission. METHODS: A total of 223 patients with acute febrile symptoms of unknown origin were enrolled in a 12-months prospective study and tested for leptospirosis through real-time PCR, IgM ELISA and MAT. In addition, 739 rats trapped throughout the main island were investigated for Leptospira renal carriage. All molecularly confirmed positive samples were further genotyped. RESULTS: A total of 51 patients fulfilled the biological criteria of acute leptospirosis, corresponding to an annual incidence of 54.6 (95% CI 40.7-71.8) per 100,000 inhabitants. Leptospira carriage in Rattus spp. was overall low (7.7%) but dramatically higher in Rattus norvegicus (52.9%) than in Rattus rattus (4.4%). Leptospira interrogans was the only detected species in both humans and rats, and was represented by three distinct Sequence Types (STs). Two were novel STs identified in two thirds of acute human cases while noteworthily absent from rats. CONCLUSIONS: This study shows that human leptospirosis still represents a heavy disease burden in Seychelles. Genotype data suggests that rats are actually not the main reservoir for human disease. We highlight a rather limited efficacy of preventive measures so far implemented in Seychelles. This could result from ineffective control measures of excreting animal populations, possibly due to a misidentification of the main contaminating reservoir(s). Altogether, presented data stimulate the exploration of alternative reservoir animal hosts.


Assuntos
Reservatórios de Doenças , Leptospira interrogans/isolamento & purificação , Leptospirose/epidemiologia , Leptospirose/veterinária , Zoonoses/epidemiologia , Adolescente , Adulto , Animais , Efeitos Psicossociais da Doença , Transmissão de Doença Infecciosa , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Incidência , Leptospirose/transmissão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ratos , Reação em Cadeia da Polimerase em Tempo Real , Seicheles/epidemiologia , Adulto Jovem , Zoonoses/transmissão
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