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Lemos A.E.G.,Fundacao Oswaldo Cruz | Ferreira L.B.,University of Porto | Batoreu N.M.,Fundacao Oswaldo Cruz | de Freitas P.P.,Fundacao Centro Universitario Estadual da Zona Oeste | And 5 more authors.
Tumor Biology | Year: 2016

Prostate cancer antigen 3 (PCA3) is a prostate-specific long noncoding RNA (lncRNA) involved in the control of prostate cancer (PCa) cell survival, through modulating androgen receptor (AR) signaling. To further comprehend the mechanisms by which PCA3 modulates LNCaP cell survival, we characterized the expression patterns of several cancer-related genes, including those involved in epithelial-mesenchymal transition (EMT) and AR cofactors in response to PCA3 silencing. We also aimed to develop a strategy to stably silence PCA3. Small interfering RNA (siRNA) or short hairpin RNA (shRNA) was used to knock down PCA3 in LNCaP cells. The expression of 84 cancer-related genes, as well as those coding for AR cofactors and EMT markers, was analyzed by quantitative real-time PCR (qRT-PCR). LNCaP-PCA3 silenced cells differentially expressed 16 of the 84 cancer genes tested, mainly those involved in gene expression control and cell signaling. PCA3 knockdown also induced the upregulation of several transcripts coding for AR cofactors and modulated the expression of EMT markers. LNCaP cells transduced with lentivirus vectors carrying an shRNA sequence targeting PCA3 stably downregulated PCA3 expression, causing a significant drop (60 %) in the proportion of LNCaP cells expressing the transgene. In conclusion, our data provide evidence that PCA3 silencing modulates the expression of key cancer-related genes, including those coding for AR cofactors and EMT markers. Transducing LNCaP cells with an shRNA sequence targeting PCA3 led to loss of viability of the cells, supporting the proposal of PCA3 knockdown as a putative therapeutic approach to inhibit PCa growth. © 2016 International Society of Oncology and BioMarkers (ISOBM) Source

Barros L.C.,Fundacao Centro Universitario Estadual da Zona Oeste | Hirakawa A.R.,University of Sao Paulo
IEEE Latin America Transactions | Year: 2014

The representation and mapping of unknown environments for robot navigation is a focus of research that presents great challenges, especially regarding the amount of data involved and the difficulty of dynamically performing computational structures updating. This paper innovates by applying the Adaptive Digitized Straight Line Segment (ADSLS) technique to reduce the amount of data for representing trajectories through the Adaptive Finite Automata (AFA), improving positive results of state of the art works. © 2003-2012 IEEE. Source

Santoro D.O.,Instituto Nacional Of Controle Of Qualidade Em Saude | Cardoso A.M.,Fundacao Centro Universitario Estadual da Zona Oeste | Coutinho F.H.,Federal University of Rio de Janeiro | Coutinho F.H.,Radboud University Nijmegen | And 4 more authors.
Journal of Applied Microbiology | Year: 2015

Aims: To evaluate the diversity of Pseudomonads and antibiotic resistance profiles of Pseudomonas aeruginosa in a hospital wastewater treatment plant (HWTP) located in Rio de Janeiro city, Brazil. Due its intrinsic multidrug resistance and its ability to colonize several environments, we selected Ps. aeruginosa isolates as indicator of antimicrobial resistance frequency. Methods and Results: Twenty-seven Ps. aeruginosa strains isolated from five stages of HWTP identified by rrs 16S rDNA sequencing were submitted against 12 antimicrobials through disc diffusion method. Among these isolates, 62·9% showed aztreonam resistance, followed by ticarcillin/clavulanic acid (33·3%) and cefepime (22·2%). Of these isolates, 22·2% were classified as multidrug-resistant (MDR ≥ 3 classes). Five 16S rRNA gene libraries of Pseudomonas genus were constructed, one for each stages of the plant, yielding 93 sequences clustered in 41 Operational Taxonomic Units (OTUs). Each treatment step showed unique OTU's composition, suggesting changes in Pseudomonas spp. communities during the process. Several Pseudomonas species involved in biodegradation and bioremediation of xenobiotics were detected suggesting a positive impact in the wastewater treatment. Conclusions: Our strategy using metagenomics associated with the isolation of Ps. aeruginosa strains as bio-indicator allowed us to assess their antimicrobial susceptibility, the viability and diversity of Pseudomonas species in the hospital wastewater. Significance and Impact of the Study: The presence of MDR bacteria from treated effluents alerts for the need to improve these systems to avoid the spreading of resistance genes in aquatic ecosystems. This has special relevance in Brazil, where a significant portion of the population has no access to treated water. © 2015 The Society for Applied Microbiology. Source

Jordao A.K.,Federal University of Fluminense | Jordao A.K.,Fundacao Centro Universitario Estadual da Zona Oeste | Vargas M.D.,Federal University of Fluminense | Pinto A.C.,Federal University of Rio de Janeiro | And 2 more authors.
RSC Advances | Year: 2015

Lawsone (1) is a special naphthoquinone that is useful for many applications in various scientific and technological fields. For over 100 years, it has been used as the starting material for the synthesis of a variety of biologically active compounds and materials with interesting properties. In organic synthesis, it has been used in many reactions. This review aims to address the various aspects of its use in organic synthesis. This journal is © The Royal Society of Chemistry. Source

Carvalho S.T.,Institute Biofisica Carlos Chagas Filho | Oliveira I.A.,Institute Biofisica Carlos Chagas Filho | Pita S.,Institute Biofisica Carlos Chagas Filho | Goncalves A.S.,Institute Biofisica Carlos Chagas Filho | And 11 more authors.
Glycobiology | Year: 2010

One of the most interesting aspects of Trypanosoma cruzi is its adaptation to obtain sialic acid from its host, fulfilling this need exclusively through the reaction catalyzed by enzymatically active trans-sialidase (aTS), thought to play an important role in the pathogenesis of Chagas' disease. Herein, we report that 2-difluoromethyl-4-nitrophenyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosid acid (NeuNAcFNP) inactivates aTS time-and dose-dependently, and this inhibition was not relieved removing the inhibitor. Also, NeuNAcFNP causes a decrease in infection of mammalian cells. Characterization of labeled aTS by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry revealed that inactivation of the enzyme occurs through formation of a covalent bond between Arg245 and Asp247 and the inhibitor aglycone. Participation of Asp247 in the catalytic mechanism was proved by constructing a TSD247A mutant, which presents only residual activity. Molecular dynamic simulations indicate that the D247A mutation results in a more open catalytic cleft. In summary, NeuNAcFNP is the first reported mechanism-based inhibitor of aTS, representing a new template for drug design and opening new possibilities for chemotherapy of Chagas' disease, as well as for the elucidation of aTS function in T. cruzi pathogenesis and biology. © The Author 2010. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org. Source

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