RESUMO
Bioinformatics is challenged by the fact that traditional analysis tools have difficulty in processing large-scale data from high-throughput sequencing. The open source Apache Hadoop project, which adopts the MapReduce framework and a distributed file system, has recently given bioinformatics researchers an opportunity to achieve scalable, efficient and reliable computing performance on Linux clusters and on cloud computing services. In this article, we present MapReduce frame-based applications that can be employed in the next-generation sequencing and other biological domains. In addition, we discuss the challenges faced by this field as well as the future works on parallel computing in bioinformatics.
Assuntos
Biologia Computacional , Coleta de Dados , Linguagens de ProgramaçãoRESUMO
The essential role of mechanical signals in regulating the function of living cells is universally observed. However, how mechanical signals are transduced in cells to regulate gene expression is largely unknown. We previously demonstrated that the gene encoding h2-calponin (Cnn2) is sensitively regulated by mechanical tension. In the present study, mouse genomic DNA containing the Cnn2 promoter was cloned, and a nested set of 5' truncations was studied. Transcriptional activity of the Cnn2 promoter-reporter constructs was examined in transfected NIH/3T3, HEK293, and C2C12 cells for their responses to the stiffness of culture substrate. The results showed significant transcriptional activities of the -1.00- and -1.24-kb promoter constructs, whereas the -0.61-kb construct was inactive. The -1.38-, -1.57-, and -2.12-kb constructs showed higher transcriptional activity, whereas only the -1.57- and -2.12-kb constructs exhibited repression of expression when the host cells were cultured on low stiffness substrate. Internal deletion of the segment between -1.57 and -1.38 kb in the -2.12-kb promoter construct abolished the low substrate stiffness-induced repression. Site-specific deletion or mutation of an HES-1 transcription factor binding site in this region also abolished this repression effect. The level of HES-1 increased in cells cultured under a low tension condition, corresponding to the down-regulation of h2-calponin. h2-Calponin gene expression is further affected by the treatment of cells with Notch inhibitor and activator, suggesting an upstream signaling mechanism.
Assuntos
Regulação da Expressão Gênica/fisiologia , Proteínas dos Microfilamentos/biossíntese , Regiões Promotoras Genéticas/fisiologia , Receptores Notch/metabolismo , Transdução de Sinais/fisiologia , Transcrição Gênica/fisiologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proteínas de Ligação ao Cálcio , Deleção de Genes , Células HEK293 , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Células K562 , Camundongos , Proteínas dos Microfilamentos/genética , Células NIH 3T3 , Receptores Notch/genética , Fatores de Transcrição HES-1 , CalponinasRESUMO
BACKGROUND: Evidence has shown that autoantibodies against M2 muscarinic acetylcholine receptors may play a role in the development of atrial fibrillation. The goal of this study was to evaluate the effects of anti-M2 receptor autoantibodies on rabbit atria in vivo. METHODS: Rabbits were immunized monthly with a synthetic peptide corresponding to the M2 receptor. The atrial electrophysiology of the isolated perfused rabbit hearts was studied. Western blots and RT-PCR were performed to determine the expression of the atrial muscarinic receptor and the acetylcholine-activated potassium channel. Atrial tissue was stained with Masson's trichrome stain for fibrosis detection. RESULTS: Autoantibodies were persistently detected in immunized rabbits. M2 rabbits showed a significantly shorter atrial effective refractory period and a longer intra-atrial activation time than control rabbits. Electrical stimuli induced a significantly larger number of repetitive atrial responses in M2 rabbits. The protein levels of the M2 receptor and GIRK4 were upregulated in M2 rabbits. The mRNA levels of GIRK1 and GIRK4 were also upregulated. Histological examination revealed significantly increased diffuse fibrotic deposition in M2 rabbit atria compared with control rabbits. CONCLUSION: The M2 receptor autoantibody-positive rabbits showed altered atrial electrophysiology, overexpression of the M2 receptor-I(K,ACh) pathway and atrial fibrosis, which indicates that the autoantibodies against M2 receptors may participate in the induction and perpetuation of atrial fibrillation.
