RESUMO
Loneliness is associated with impaired mental and physical health. Studies of lonely individuals reported differential expression of inflammatory genes in peripheral leukocytes and diminished activation in brain reward regions such as nucleus accumbens, but could not address gene expression in the human brain. Here, we examined genome-wide RNA expression in post-mortem nucleus accumbens from donors (N=26) with known loneliness measures. Loneliness was associated with 1710 differentially expressed transcripts and genes from 1599 genes (DEGs; false discovery rate P<0.05, fold change ⩾|2|, controlling for confounds) previously associated with behavioral processes, neurological disease, psychological disorders, cancer, organismal injury and skeletal and muscular disorders, as well as networks of upstream RNA regulators. Furthermore, a number of DEGs were associated with Alzheimer's disease (AD) genes (that was correlated with loneliness in this sample, although gene expression analyses controlled for AD diagnosis). These results identify novel targets for future mechanistic studies of gene networks in nucleus accumbens and gene regulatory mechanisms across a variety of diseases exacerbated by loneliness.
Assuntos
Solidão , Núcleo Accumbens/química , Idoso de 80 Anos ou mais , Autopsia , Encéfalo/metabolismo , Feminino , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes/genética , Genoma/genética , Estudo de Associação Genômica Ampla , Humanos , Solidão/psicologia , Masculino , Núcleo Accumbens/metabolismo , Transcriptoma/genéticaRESUMO
We previously reported the isolation of PR2257, a novel avian sarcoma retrovirus which transduced the c-src protooncogene. The v-src gene of PR2257 differs from the c-src gene by a sequence change after amino acid 525, resulting in the replacement of tyrosine 527 by a valine, and an extension of the open reading frame into the non coding region of c-src. We investigated the respective roles of Tyr527 mutation and of the C-terminal extension in activating the oncogenic properties of c-src. Therefore we overexpressed the wild type c-src gene and c-src variants, carrying either a substitution of tyrosine 527 or an extension of the C-terminus or both modifications in combination, in chicken embryo fibroblasts and post mitotic neuroretina (NR) cells, using replication defective retroviruses. We also used in vivo inoculation of plasmid DNA to assess the tumorigenicity of the various c-src genes. We report that, in contrast to previous results, overexpression of c-src is sufficient to induce NR cell division. While mutation of tyrosine 527 alone significantly activates c-src transforming and tumorigenic properties, its combination with the C-terminal extension of PR2257 confers to this gene full oncogenic properties and increased metastatic potential as compared to the v-src of Rous sarcoma virus strains.
Assuntos
Diferenciação Celular/genética , Divisão Celular/genética , Transformação Celular Neoplásica/genética , Genes src/genética , Quinases da Família src/genética , Animais , Galinhas , Vetores Genéticos , Neoplasias Experimentais/genética , Neoplasias Experimentais/patologia , Fenótipo , Retroviridae/genética , Transfecção , Quinases da Família src/metabolismoRESUMO
The env and v-src genes of a duck-adapted variant of Rous sarcoma virus were replaced for corresponding genes from parental chick-derived virus. The generation of viral constructs with replaced genes is described. DNAs of viruses with replaced genes were assayed on chick and duck embryo fibroblasts by transfection assays. Transformation efficiency was measured by the focus assay and multiplication of virus by the reverse transcriptase assay. Duck-adapted virus with replaced env gene lost the higher transformation efficiency for duck cells, whereas replacement of the v-src gene had no effect on its host-specific transformation activity.
