RESUMO
The amphipod crustacean Parhyale hawaiensis is a blossoming model system for studies of developmental mechanisms and more recently regeneration. We have sequenced the genome allowing annotation of all key signaling pathways, transcription factors, and non-coding RNAs that will enhance ongoing functional studies. Parhyale is a member of the Malacostraca clade, which includes crustacean food crop species. We analysed the immunity related genes of Parhyale as an important comparative system for these species, where immunity related aquaculture problems have increased as farming has intensified. We also find that Parhyale and other species within Multicrustacea contain the enzyme sets necessary to perform lignocellulose digestion ('wood eating'), suggesting this ability may predate the diversification of this lineage. Our data provide an essential resource for further development of Parhyale as an experimental model. The first malacostracan genome will underpin ongoing comparative work in food crop species and research investigating lignocellulose as an energy source.
Assuntos
Anfípodes/genética , Proteínas de Artrópodes/genética , Genoma , Estágios do Ciclo de Vida/genética , Lignina/metabolismo , Redes e Vias Metabólicas/genética , Anfípodes/classificação , Anfípodes/crescimento & desenvolvimento , Anfípodes/metabolismo , Animais , Aquicultura , Proteínas de Artrópodes/imunologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Ontologia Genética , Sequenciamento de Nucleotídeos em Larga Escala , Imunidade Inata , Cariótipo , Estágios do Ciclo de Vida/imunologia , Masculino , Redes e Vias Metabólicas/imunologia , Anotação de Sequência Molecular , Filogenia , RNA não Traduzido/genética , RNA não Traduzido/imunologia , Regeneração , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/imunologiaRESUMO
Paroxysmal nocturnal haemoglobinuria (PNH) clones are frequently detected in patients with aplastic anaemia (AA). To evaluate the prognostic role of PNH clone presence we conducted a prospective study in 125 AA patients treated with combined immunosuppressive therapy (IST). Seventy-four patients (59%) had a PNH clone (PNH+ patients) at diagnosis, with a median clone size of 0·60% in granulocytes and 0·15% in red blood cells. The response rate at 6 months was higher in PNH+ patients than that in PNH- patients, both after first- and second-line IST: 68% vs. 45%, P = 0·0164 and 53% vs. 13%, P = 0·0502 respectively. Moreover, 42% of PNH+ patients achieved complete remission compared with only 16% of PNH- patients (P = 0·0029). In multivariate logistic regression analysis, PNH clone presence (odds ratio 2·56, P = 0·0180) and baseline absolute reticulocyte count (ARC) ≥30 × 10(9) /l (odds ratio 5·19, P = 0·0011) were independent predictors of response to treatment. Stratification according to PNH positivity and ARC ≥30 × 10(9) /l showed significant distinctions for cumulative incidence of response, overall and failure-free survival. The results of this prospective study confirmed the favourable prognostic value of PNH clone presence in the setting of IST for AA.