RESUMO
BACKGROUND: The fungal genus Aspergillus is of critical importance to humankind. Species include those with industrial applications, important pathogens of humans, animals and crops, a source of potent carcinogenic contaminants of food, and an important genetic model. The genome sequences of eight aspergilli have already been explored to investigate aspects of fungal biology, raising questions about evolution and specialization within this genus. RESULTS: We have generated genome sequences for ten novel, highly diverse Aspergillus species and compared these in detail to sister and more distant genera. Comparative studies of key aspects of fungal biology, including primary and secondary metabolism, stress response, biomass degradation, and signal transduction, revealed both conservation and diversity among the species. Observed genomic differences were validated with experimental studies. This revealed several highlights, such as the potential for sex in asexual species, organic acid production genes being a key feature of black aspergilli, alternative approaches for degrading plant biomass, and indications for the genetic basis of stress response. A genome-wide phylogenetic analysis demonstrated in detail the relationship of the newly genome sequenced species with other aspergilli. CONCLUSIONS: Many aspects of biological differences between fungal species cannot be explained by current knowledge obtained from genome sequences. The comparative genomics and experimental study, presented here, allows for the first time a genus-wide view of the biological diversity of the aspergilli and in many, but not all, cases linked genome differences to phenotype. Insights gained could be exploited for biotechnological and medical applications of fungi.
Assuntos
Adaptação Biológica , Aspergillus/classificação , Aspergillus/genética , Biodiversidade , Genoma Fúngico , Genômica , Aspergillus/metabolismo , Biomassa , Carbono/metabolismo , Biologia Computacional/métodos , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Metilação de DNA , Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica , Redes Reguladoras de Genes , Genômica/métodos , Humanos , Redes e Vias Metabólicas , Anotação de Sequência Molecular , Família Multigênica , Oxirredutases/metabolismo , Filogenia , Plantas/metabolismo , Plantas/microbiologia , Metabolismo Secundário/genética , Transdução de Sinais , Estresse Fisiológico/genéticaRESUMO
A synthetic peptide representing the receptor-binding domain of human thrombin (TP508) promotes angiogenesis and accelerates wound healing in animal models. However, the mechanisms underlying the therapeutic effects of TP508 have not been clearly defined. In this study, we set out to determine whether TP508 could stimulate stem cell proliferation. Adipose tissue-derived stem cells (ASCs) were incubated with TP508 (5 microg/ml) and cell proliferation was determined by bromodeoxyuridine (BrdU) incorporation. Our data showed that TP508 treatment significantly stimulated BrdU incorporation in ASCs (p < 0.01). The increased BrdU incorporation induced by TP508 was abolished by the PI3 kinase (PI3K) inhibitor LY294002 at 50 microM. Western blot analysis of ASCs revealed increased phosphorylation of Akt in response to TP508 when compared to unstimulated controls. These results indicate that TP508 exerts proliferative effects on ASCs via the PI3K/Akt pathway.