Análise de propriedades topológicas das redes biológicas integradas da Escherichia coli e da Saccharomyces cerevisiae

Biological processes are complex and possess emergent properties that can not be explained or predict by reductionism methods. To overcome the limitations of reductionism, researchers have been used a group of methods known as systems biology, a new interdisciplinary eld of study aiming to understand the non-linear interactions among components embedded in biological processes. These interactions can be represented by a mathematical object called graph or network, where the elements are represented by nodes and the interactions by edges that link pair of nodes. The networks can be classi- ed according to their topologies: if node degrees follow a Poisson distribution in a given network, i.e. most nodes have approximately the same number of links, this is a random network; if node degrees follow a power-law distribution in a given network, i.e. small number of high-degree nodes and high number of low-degree nodes, this is a scale-free network. Moreover, networks can be classi ed as hierarchical or non-hierarchical. In this study, we analised Escherichia coli and Saccharomyces cerevisiae integrated molecular networks, which have protein-protein interaction, metabolic and transcriptional regulation interactions. By using computational methods, such as MathematicaR , and data collected from public databases, we calculated four topological parameters: the degree distribution P(k), the clustering coe cient C(k), the closeness centrality CC(k) and the betweenness centrality CB(k). P(k) is a function that calculates the total number of nodes with k degree connection and is used to classify the network as random or scale-free. C(k) shows if a network is hierarchical, i.e. if the clusterization coe cient depends on node degree. CC(k) is an indicator of how much a node it is in the lesse way among others some nodes of the network and the CB(k) is a pointer of how a particular node is among several ...(Complete abstract click electronic access below)

Determinação de genes mórbidos e drogáveis a partir da construção e análise da rede integrada de interações moleculares entre genes humanos

The discovering process of new morbid genes and new target proteins for drugs have been shown to be very costly and laborious. Having in view cutting costs and speeding up this process, we propose, in this work, a new method to determine the gene druggability score and morbidity score, the probabilities of the protein encoded by the gene have the characteristics that make it a new target for drugs and in case of an alteration in that gene, we observed a phenotype that characterizes a genetic based illness. To determine these characteristics, we built, analyzed and determined the characteristics of the topology of the integrated molecular interactions network among human genes containing physical interactions between proteins, metabolic interactions and interactions of transcriptional regulation, and included other data such as level of gene transcription and cellular localization of the protein encoded by the gene. We tested our model in training sets and achieved results equal or better than the ones achieved by similar methods in the literature. Finally, with the purpose of investigating whether the assigned scores resembles the potential druggabilities and morbities of the previously unclassi ed genes, we looked for evidences in biomedical literature supporting the potential druggability and morbidity status of genes with the 10 highest scores. We found clear evidences for 73% and 90% of potential druggable and morbid genes respectively

PHF21B as a candidate tumor suppressor gene in head and neck squamous cell carcinomas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Flow sorting and exome sequencing reveal the oncogenome of primary Hodgkin and Reed-Sternberg cells

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

MicroRNAs targeting the immunomodulatory HLA-G gene: a new survey searching for microRNAs with potential to regulate HLA-G

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Transcriptome response signatures associated with the overexpression of a mitochondrial uncoupling protein (AtUCP1) in tobacco

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Expressão diferencial de microRNAs no câncer de próstata

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Regulation of glycogen metabolism by the CRE-1, RCO-1 and RCM-1 proteins in Neurospora crassa. The role of CRE-1 as the central transcriptional regulator

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Aspects of gene regulation in the diploid and tetraploid Odontophrynus americanus (Amphibia, Anura, Leptodactylidae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Transcriptional activation of MMP-13 by periodontal pathogenic LPS requires p38 MAP kinase

Matrix metal loprotease-13 (MMP-13) is induced by pro-inflammatory cytokines and increased expression is associated with a number of pathological conditions such as tumor metastasis, osteoarthritis, rheumatoid arthritis and periodontal diseases. MMP-13 gene regulation and the signal transduction pathways activated in response to bacterial LPS are largely unknown. In these studies, the role of the mitogen-activated protein kinase (MAPK) pathways in the regulation of MMP-13 induced by lipopolysaccharide was investigated. Lipopolysaccharide from Escherichia coli and Actinobacillus actinomycetemcomitans significantly (P < 0.05) increased MMP-13 steady-state mRNA (average of 27% and 46% increase, respectively) in murine periodontal ligament fibroblasts. MMP-13 mRNA induction was significantly reduced by inhibition of p38 MAP kinase. Immunoblot analysis indicated that p38 signaling was required for LPS-induced MMP-13 expression. Lipopolysaccharide induced proximal promoter reporter (-660/+32 mMMP-13) gene activity required p38 signaling. Collectively, these results indicate that lipopolysaccharide-induced murine MMP-13 is regulated by p38 signaling through a transcriptional mechanism.

Transcriptional and Posttranscriptional Regulations of the HLA-G Gene

HLA-G has a relevant role in immune response regulation. The overall structure of the HLA-G coding region has been maintained during the evolution process, in which most of its variable sites are synonymous mutations or coincide with introns, preserving major functional HLA-G properties. The HLA-G promoter region is different from the classical class I promoters, mainly because (i) it lacks regulatory responsive elements for IFN-gamma and NF-kappa B, (ii) the proximal promoter region (within 200 bases from the first translated ATG) does not mediate transactivation by the principal HLA class I transactivation mechanisms, and (iii) the presence of identified alternative regulatory elements (heat shock, progesterone and hypoxia-responsive elements) and unidentified responsive elements for IL-10, glucocorticoids, and other transcription factors is evident. At least three variable sites in the 3' untranslated region have been studied that may influence HLA-G expression by modifying mRNA stability or microRNA binding sites, including the 14-base pair insertion/deletion, +3142C/G and +3187A/G polymorphisms. Other polymorphic sites have been described, but there are no functional studies on them. The HLA-G coding region polymorphisms might influence isoform production and at least two null alleles with premature stop codons have been described. We reviewed the structure of the HLA-G promoter region and its implication in transcriptional gene control, the structure of the HLA-G 3' UTR and the major actors of the posttranscriptional gene control, and, finally, the presence of regulatory elements in the coding region.

Transcriptional Activity, Chromosomal Distribution and Expression Effects of Transposable Elements in Coffea Genomes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Differences in transcriptional activity of human papillomavirus type 6 molecular variants in recurrent respiratory papillomatosis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)