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de Oliveira L.L.,University of Sao Paulo | de Oliveira P.S.L.,Brazilian Biosciences National Laboratory | Tinos R.,University of Sao Paulo
BMC Bioinformatics

The organization of the canonical code has intrigued researches since it was first described. If we consider all codes mapping the 64 codes into 20 amino acids and one stop codon, there are more than 1.51×10 possible genetic codes. The main question related to the organization of the genetic code is why exactly the canonical code was selected among this huge number of possible genetic codes. Many researchers argue that the organization of the canonical code is a product of natural selection and that the code's robustness against mutations would support this hypothesis. In order to investigate the natural selection hypothesis, some researches employ optimization algorithms to identify regions of the genetic code space where best codes, according to a given evaluation function, can be found (engineering approach). The optimization process uses only one objective to evaluate the codes, generally based on the robustness for an amino acid property. Only one objective is also employed in the statistical approach for the comparison of the canonical code with random codes. We propose a multiobjective approach where two or more objectives are considered simultaneously to evaluate the genetic codes. Results: In order to test our hypothesis that the multiobjective approach is useful for the analysis of the genetic code adaptability, we implemented a multiobjective optimization algorithm where two objectives are simultaneously optimized. Using as objectives the robustness against mutation with the amino acids properties polar requirement (objective 1) and robustness with respect to hydropathy index or molecular volume (objective 2), we found solutions closer to the canonical genetic code in terms of robustness, when compared with the results using only one objective reported by other authors. Conclusions: Using more objectives, more optimal solutions are obtained and, as a consequence, more information can be used to investigate the adaptability of the genetic code. The multiobjective approach is also more natural, because more than one objective was adapted during the evolutionary process of the canonical genetic code. Our results suggest that the evaluation function employed to compare genetic codes should consider simultaneously more than one objective, in contrast to what has been done in the literature. © de Oliveira et al. Source

De Souza E Silva J.M.,University of Campinas | De Souza E Silva J.M.,Brazilian Synchrotron Light Laboratory (LNLS) | Pastorello M.,University of Campinas | Kobarg J.,Brazilian Biosciences National Laboratory | And 2 more authors.

Silver-based nanocomposites are known to act as biocides against a series of microorganisms and are largely studied as an alternative to substitute conventional antibiotics that show decreasing efficacy. In this work, an eco-friendly method to synthesize silver nanoparticles assembled on the surface of hexaniobate crystals is reported. By means of ion exchange, K+ ions of layered potassium hexaniobate were partially substituted by Ag + ions and the resulting material was exposed to UV light. The irradiation allowed the reduction of silver ions with consequent formation of silver nanoparticles located only on the hexaniobate surface, whereas Ag + ions located in the interlayer space remained in the ionic form. Increasing UV-light exposure times allowed controlling of the silver nanoparticle size. The antibacterial effects of the pristine potassium hexaniobate and of silver-containing hexaniobate samples were tested against Escherichia coli (E. coli). The antibacterial efficacy was determined to be related to the presence of silver in hexaniobate. An increasing activity against E. coli was observed with the decrease in silver nanoparticles size, suggesting that silver nanoparticles of distinct sizes interact differently with bacterial cell walls. The right size to kill: Silver nanoparticles decorating the surface of hexaniobate crystals are prepared by an eco-friendly method. According to tests against E. coli, silver nanoparticles of distinct sizes interact differently with bacterial cell walls. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Oliveira-Paula G.H.,University of Sao Paulo | Lacchini R.,University of Sao Paulo | Fontana V.,Brazilian Biosciences National Laboratory | Silva P.S.,Federal University of Juiz de fora | And 2 more authors.
European Journal of Clinical Pharmacology

Purpose: Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that affects blood pressure by promoting vasodilation mediated by nitric oxide. Angiotensin-converting enzyme inhibitors (ACEi) up-regulate the VEGF expression; thus, genetic polymorphisms in the VEGFA gene could affect the antihypertensive responses to these drugs. Methods: Hypertensive patients (n=102) were prospectively treated only with the ACEi enalapril for 60 days. We compared the effect of VEGFA polymorphisms on changes in blood pressure after enalapril treatment. In addition, multiple linear regression analysis was carried out to assess the effect of covariates on blood pressure. Genotypes for g.-2578C>A (rs699947), g.-1154G>A (rs1570360), and g.-634G>C (rs2010963) VEGFA polymorphisms were determined, and haplotype frequencies were estimated. Results: Individuals carrying the CA and AA genotypes for the g.-2578C>A polymorphism and the AGG haplotype showed more intense decrease in blood pressure in response to enalapril 20 mg/day. A multiple linear regression analysis showed that the AA genotype for the g.-2578C>A polymorphism and the AGG haplotype are associated with more intense decrease in blood pressure in response to enalapril 20 mg/day, while the CC genotype for the g.-2578C>A polymorphism and the CGG haplotype are associated with the opposite effect. Conclusions: These findings suggest that polymorphisms in VEGFA gene may affect the antihypertensive responses to enalapril. © 2015 Springer-Verlag. Source

Campanhon I.B.,Federal University of Rio de Janeiro | Domingues R.R.,Brazilian Biosciences National Laboratory | Paes Leme A.F.,Brazilian Biosciences National Laboratory | Soares Da Silva M.R.,Federal University of Rio de Janeiro

Hepatitis B and C virus (HBV and HCV) infections are an important cause of cirrhosis and hepatocellular carcinoma. The natural history has a prominent latent phase, and infected patients may remain undiagnosed; this situation may lead to the continuing spread of these infections in the community. Compelling reasons exist for using saliva as a diagnostic fluid because it meets the demands of being an inexpensive, noninvasive and easy-to-use diagnostic method. Indeed, comparative analysis of the salivary proteome using mass spectrometry is a promising new strategy for identifying biomarkers. Our goal is to apply an Orbitrap-based quantitative approach to explore the salivary proteome profile in HBV- and HCV-infected patients. In the present study, whole saliva was obtained from 20 healthy, (control) 20 HBV-infected and 20 HCV-infected subjects. Two distinct pools containing saliva from 10 subjects of each group were obtained. The samples were ultracentrifuged and fractionated, and all fractions were hydrolyzed (trypsin) and injected into an LTQ-VELOS ORBITRAP. The identification and analyses of peptides were performed using Proteome Discoverer1.3 and ScaffoldQ + v.3.3.1. From a total of 362 distinct proteins identified, 344 proteins were identified in the HBV, 326 in the HCV and 303 in the control groups. Some blood proteins, such as flavin reductase (which converts biliverdin to bilirubin), were detected only in the HCV group. The data showed a reduced presence of complement C3, ceruloplasmin, alpha(1)-acid glycoprotein and alpha(2)-acid glycoprotein in the hepatitis-infected patients. Peptides of serotransferrin and haptoglobin were less detected in the HCV group. This study provides an integrated perspective of the salivary proteome, which should be further explored in future studies targeting specific disease markers for HBV and HCV infection. © 2014 Gonc¸alves et al. Source

Hansen H.P.,University of Cologne | Engels H.-M.,University of Cologne | Dams M.,University of Cologne | Paes Leme A.F.,Brazilian Biosciences National Laboratory | And 10 more authors.
Journal of Pathology

Classical Hodgkin's lymphoma (cHL)-affected lymphoid tissue contains only a few malignant Hodgkin and Reed-Sternberg (HRS) cells, which are disseminated within a massive infiltrate of reactive cells. In particular, the innate immune infiltrate is deemed to support tumour growth by direct cell-cell interaction. Since they are rarely found in close proximity to the malignant cells in situ, we investigated whether cHL-derived extracellular vesicles might substitute for a direct cell-cell contact. We studied the crosstalk of the transmembrane proteins CD30 and CD30 ligand (CD30L) because they are selectively expressed on HRS and innate immune cells, respectively. Here, we showed that HRS cells released both the ectodomain as a soluble molecule (sCD30) and the entire receptor on the surface of extracellular vesicles. The vesicle diameter was 40-800 nm, as determined by cryo- and immune electron microscopy. In addition to CD30, typical extracellular vesicle markers were detected by mass spectrometry and flow cytometry, including tetraspanins, flotillins, heat shock proteins and adhesion molecules. In contrast to sCD30, vesicles caused a CD30-dependent release of interleukin-8 in CD30L+ eosinophil-like EoL-1 cells and primary granulocytes from healthy donors, underscoring the functionality of CD30 on vesicles. In extracellular matrix (ECM)-embedded culture of HRS cells, a network of actin and tubulin-based protrusions guided CD30+ vesicles into the micro-environment. This network targeted CD30+ vesicles towards distant immune cells and caused a robust polarization of CD30L. Confocal laser scanning microscopy of 30 μm sections showed a CD30 vesicle-containing network also in cHL-affected lymphoid tissue of both mixed-cellularity and nodular sclerosing subtypes. This network might facilitate the communication between distant cell types in cHL tissue and allow a functional CD30-CD30L interaction in trans. The tubulin backbone of the network may provide a target for the therapy of cHL with antitubulin-based CD30 antibody constructs. Copyright © 2013 Pathological Society of Great Britain and Ireland. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Source

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