Área de PDI em Pesquisa, Desenvolvimento e Inovação em Genômica Funcional 2013
Veja, abaixo, a relação de artigos científicos publicados pelo IOC, na referida Área Temática, organizados em ordem alfabética crescente:
| Branquinha MH, Marinho FA, Sangenito LS, Oliveira SSC, Goncalves KC, Ennes-Vidal V, d'Avila Levy CM and Santos ALS (2013), "Calpains: Potential Targets for Alternative Chemotherapeutic Intervention Against Human Pathogenic Trypanosomatids", Current Medicinal Chemistry., August, 2013. Vol. 20(25), pp. 3174-3185. Bentham Science Publ Ltd. [DOI] |
| Abstract: The treatment for both leishmaniasis and trypanosomiasis, which are severe human infections caused by trypanosomatids belonging to Leishmania and Trypanosoma genera, respectively, is extremely limited because of concerns of toxicity and efficacy with the available anti-protozoan drugs, as well as the emergence of drug resistance. Consequently, the urgency for the discovery of new trypanosomatid targets and novel bioactive compounds is particularly necessary. In this context, the investigation of changes in parasite gene expression between drug resistant/sensitive strains and in the up-regulation of virulence-related genes in infective forms has brought to the fore the involvement of calpain-like proteins in several crucial pathophysiological processes performed by trypanosomatids. These studies were encouraged by the publication of the complete genome sequences of three human pathogenic trypanosomatids, Trypanosoma brucei, Trypanosoma cruzi and Leishmania major, which allowed in silico analyses that in turn directed the identification of numerous genes with interesting chemotherapeutic characteristics, including a large family of calpain-related proteins, in which to date 23 genes were assigned as calpains in T. brucei, 40 in T. cruzi and 33 in L. braziliensis. In the present review, we intend to add to these biochemical/biological reports the investigations performed upon the inhibitory capability of calpain inhibitors against human pathogenic trypanosomatids. |
BibTeX: @article{Branquinha2013, author = {Branquinha, M. H. and Marinho, F. A. and Sangenito, L. S. and Oliveira, S. S. C. and Goncalves, K. C. and Ennes-Vidal, V. and d'Avila-Levy, C. M. and Santos, A. L. S.}, title = {Calpains: Potential Targets for Alternative Chemotherapeutic Intervention Against Human Pathogenic Trypanosomatids}, journal = {Current Medicinal Chemistry}, publisher = {Bentham Science Publ Ltd}, year = {2013}, volume = {20}, number = {25}, pages = {3174--3185}, doi = {10.2174/0929867311320250010} } |
| De Oliveira L, Pereira R and Brandao A (2013), "An analysis of trypanosomatids kDNA minicircle by absolute dinucleotide frequency", Parasitology International., August, 2013. Vol. 62(4), pp. 397-403. Elsevier Ireland Ltd. [DOI] |
| Abstract: Trypanosomatid mitochondrial DNA (kDNA) possesses thousands of copies of small circular molecules called minicircles. Due to a high level of nucleotide polymorphism among copies, sequence alignment for species or strain characterization is not appropriate. In this work we report dinucleotide absolute frequency as a method to analyze minicircle sequences heterogeneity in trypanosomatids. Using Trypanosoma rangeli and Leishmania guyanensis minicircles as example of sequence length heterogeneity, we show that dinucleotide frequency of minicircles whose length variation is less than to 10% is relatively constant. Dinucleotide frequencies in Leishmania genus point out three clusters of predominant dinucleotide profiles: GG/TT/TG for Old World species; ii) Tr/AA/TA for New World species and iii) TT/GG(AA) TA(AT) for Sauroleishmania. Trypanosoma species displayed broad range composition and the highest frequency values. Their dinucleotide profile appears to be species specific, except for African trypanosomes which exhibit similar composition. The low number of sequences from Crithidia, Herpetomonas, Phytomonas and Wallaceina did not allow a generalized analysis, however some species present highly similar compositional profile, e.g., Wallaceina species. Distinct signatures for Trypanosomatidae family members can be generated by using values of absolute frequencies, range and composition of most/least frequent dinucleotides from minicircles. Each species can be graphically represented by a diagram of frequencies along with a box plot of summary statistics. (C) 2013 Elsevier Ireland Ltd. All rights reserved. |
BibTeX: @article{Oliveira2013, author = {De Oliveira, L. and Pereira, R. and Brandao, A.}, title = {An analysis of trypanosomatids kDNA minicircle by absolute dinucleotide frequency}, journal = {Parasitology International}, publisher = {Elsevier Ireland Ltd}, year = {2013}, volume = {62}, number = {4}, pages = {397--403}, doi = {10.1016/j.parint.2013.04.005} } |
| Felicio DF, Vidal LD, Irineu RS, Leitao AC, von Kruger WA, Britto CD, Cardoso A, Cardoso JS and Lage C (2013), "Overexpression of Escherichia coli nucleotide excision repair genes after cisplatin-induced damage", Dna Repair., January, 2013. Vol. 12(1), pp. 63-72. Elsevier Science Bv. [DOI] |
| Abstract: Cisplatin is currently used in tumor chemotherapy to induce the death of malignant cells through blockage of DNA replication. It is a commonly used chemotherapeutic agent binding mono- or bifunctionally to guanines in DNA. Escherichia coli K12 mutant strains deficient in nucleotide excision repair (NER) were submitted to increasing concentrations of cisplatin, and the results revealed that uvrA and uvrB mutants are sensitive to this agent, while uvrC and cho mutants remain as the wild type strain. The time required for both gene expression turn-off and return to normal weight DNA in wild-type E. coli was not accomplished even after 4 h post-treatment with cisplatin, while the same process takes place within 1.5 h after ultraviolet radiation (UV). Besides, a heavily damaging action of cisplatin can be seen not only by persistent nicks on genomic DNA, but also by NER gene expression exceeding manifold that seen after equivalent lethal doses of UV. Moreover, cisplatin caused an increase in uvrB gene expression from its putative upstream promoter P3 in an SOS-independent manner. (C) 2012 Elsevier B.V. All rights reserved. |
BibTeX: @article{Felicio2013, author = {Felicio, D. F. and Vidal, L. D. and Irineu, R. S. and Leitao, A. C. and von Kruger, W. A. and Britto, C. D. and Cardoso, A. and Cardoso, J. S. and Lage, C.}, title = {Overexpression of Escherichia coli nucleotide excision repair genes after cisplatin-induced damage}, journal = {Dna Repair}, publisher = {Elsevier Science Bv}, year = {2013}, volume = {12}, number = {1}, pages = {63--72}, doi = {10.1016/j.dnarep.2012.10.009} } |
| Gomez A, Cardoso C, Genta FA, Terra WR and Ferreira C (2013), "Active site characterization and molecular cloning of Tenebrio molitor midgut trehalase and comments on their insect homologs", Insect Biochemistry and Molecular Biology., August, 2013. Vol. 43(8), pp. 768-780. Pergamon-elsevier Science Ltd. [DOI] |
| Abstract: The soluble midgut trehalase from Tenebrio molitor (TmTre1) was purified after several chromatographic steps, resulting in an enzyme with 58 kDa and pH optimum 5.3 (ionizing active groups in the free enzyme: pK(e1) = 3.8 +/- 0.2 pK(e2) = 7.4 +/- 0.2). The purified enzyme corresponds to the deduced amino acid sequence of a cloned cDNA (TmTre1-cDNA), because a single cDNA coding a soluble trehalase was found in the T. molitor midgut transcriptome. Furthermore, the mass of the protein predicted to be coded by TmTre1-cDNA agrees with that of the purified enzyme. TmTre1 has the essential catalytic groups Asp 315 and Glu 513 and the essential Arg residues R164, R217, R282. Carbodiimide inactivation of the purified enzyme at different pH values reveals an essential carboxyl group with pKa = 3.5 +/- 0.3. Phenylglyoxal modified a single Arg residue with pKa = 7.5 +/- 0.2, as observed in the soluble trehalase from Spodoptera frugiperda (SfTre1). Diethylpyrocarbonate modified a His residue that resulted in a less active enzyme with pKe1 changed to 4.8 +/- 0.2. In TmTre1 the modified His residue (putatively His 336) is more exposed than the His modified in SfTre1 (putatively His 210) and that affects the ionization of an Arg residue. The architecture of the active site of TmTre1 and SfTre1 is different, as shown by multiple inhibition analysis, the meaning of which demands further research. Trehalase sequences obtained from midgut transcriptomes (pyrosequencing and Illumina data) from 8 insects pertaining to 5 different orders were used in a cladogram, together with other representative sequences. The data suggest that the trehalase gene went duplication and divergence prior to the separation of the paraneopteran and holometabolan orders and that the soluble trehalase derived from the membrane-bound one by losing the C-terminal transmembrane loop. (C) 2013 Elsevier Ltd. All rights reserved. |
BibTeX: @article{Gomez2013, author = {Gomez, A. and Cardoso, C. and Genta, F. A. and Terra, W. R. and Ferreira, C.}, title = {Active site characterization and molecular cloning of Tenebrio molitor midgut trehalase and comments on their insect homologs}, journal = {Insect Biochemistry and Molecular Biology}, publisher = {Pergamon-elsevier Science Ltd}, year = {2013}, volume = {43}, number = {8}, pages = {768--780}, doi = {10.1016/j.ibmb.2013.05.010} } |
| Miguel RB, Coura JR, Samudio F and Suarez-Mutis MC (2013), "EVALUATION OF THREE DIFFERENT DNA EXTRACTION METHODS FROM BLOOD SAMPLES COLLECTED IN DRIED FILTER PAPER IN Plasmodium SUBPATENT INFECTIONS FROM THE AMAZON REGION IN BRAZIL", Revista Do Instituto De Medicina Tropical De Sao Paulo., May, 2013. Vol. 55(3), pp. 205-208. Inst Medicina Tropical Sao Paulo. [DOI] |
| Abstract: Asymptomatic Plasmodium infection is a new challenge for public health in the American region. The polymerase chain reaction (PCR) is the best method for diagnosing subpatent parasitemias. In endemic areas, blood collection is hampered by geographical distances and deficient transport and storage conditions of the samples. Because DNA extraction from blood collected on filter paper is an efficient method for molecular studies in high parasitemic individuals, we investigated whether the technique could be an alternative for Plasmodium diagnosis among asymptomatic and pauciparasitemic subjects. In this report we compared three different methods (Chelex (R)-saponin, methanol and TRIS-EDTA) of DNA extraction from blood collected on filter paper from asymptomatic Plasmodium-infected individuals. Polymerase chain reaction assays for detection of Plasmodium species showed the best results when the Chelex (R)-saponin method was used. Even though the sensitivity of detection was approximately 66% and 31% for P. falciparum and P. vivax, respectively, this method did not show the effectiveness in DNA extraction required for molecular diagnosis of Plasmodium. The development of better methods for extracting DNA from blood collected on filter paper is important for the diagnosis of subpatent malarial infections in remote areas and would contribute to establishing the epidemiology of this form of infection. |
BibTeX: @article{Miguel2013, author = {Miguel, R. B. and Coura, J. R. and Samudio, F. and Suarez-Mutis, M. C.}, title = {EVALUATION OF THREE DIFFERENT DNA EXTRACTION METHODS FROM BLOOD SAMPLES COLLECTED IN DRIED FILTER PAPER IN Plasmodium SUBPATENT INFECTIONS FROM THE AMAZON REGION IN BRAZIL}, journal = {Revista Do Instituto De Medicina Tropical De Sao Paulo}, publisher = {Inst Medicina Tropical Sao Paulo}, year = {2013}, volume = {55}, number = {3}, pages = {205--208}, doi = {10.1590/S0036-46652013000300012} } |
| Santos LO, Garcia-Gomes AS, Catanho M, Sodre CL, Santos ALS, Branquinha MH and d'Avila Levy CM (2013), "Aspartic peptidases of human pathogenic trypanosomatids: perspectives and trends for chemotherapy.", Curr Med Chem. Vol. 20(25), pp. 3116-3133. [DOI] |
| Abstract: Aspartic peptidases are proteolytic enzymes present in many organisms like vertebrates, plants, fungi, protozoa and in some retroviruses such as human immunodeficiency virus (HIV). These enzymes are involved in important metabolic processes in microorganisms/virus and play major roles in infectious diseases. Although few studies have been performed in order to identify and characterize aspartic peptidase in trypanosomatids, which include the etiologic agents of leishmaniasis, Chagas' disease and sleeping sickness, some beneficial properties of aspartic peptidase inhibitors have been described on fundamental biological events of these pathogenic agents. In this context, aspartic peptidase inhibitors (PIs) used in the current chemotherapy against HIV (e.g., amprenavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir) were able to inhibit the aspartic peptidase activity produced by different species of Leishmania. Moreover, the treatment of Leishmania promastigotes with HIV PIs induced several perturbations on the parasite homeostasis, including loss of the motility and arrest of proliferation/growth. The HIV PIs also induced an increase in the level of reactive oxygen species and the appearance of irreversible morphological alterations, triggering parasite death pathways such as programed cell death (apoptosis) and uncontrolled autophagy. The blockage of physiological parasite events as well as the induction of death pathways culminated in its incapacity to adhere, survive and escape of phagocytic cells. Collectively, these results support the data showing that parasites treated with HIV PIs have a significant reduction in the ability to cause in vivo infection. Similarly, the treatment of Trypanosoma cruzi cells with pepstatin A showed a significant inhibition on both aspartic peptidase activity and growth as well as promoted several and irreversible morphological changes. These studies indicate that aspartic peptidases can be promising targets in trypanosomatid cells and aspartic proteolytic inhibitors can be benefic chemotherapeutic agents against these human pathogenic microorganisms. |
BibTeX: @article{Santos2013a, author = {Santos, L. O. and Garcia-Gomes, A. S. and Catanho, M. and Sodre, C. L. and Santos, A L S. and Branquinha, M. H. and d'Avila-Levy, C. M.}, title = {Aspartic peptidases of human pathogenic trypanosomatids: perspectives and trends for chemotherapy.}, journal = {Curr Med Chem}, year = {2013}, volume = {20}, number = {25}, pages = {3116--3133}, doi = {10.2174/0929867311320250007} } |
| Santos LO, Vitorio BS, Branquinha MH, Silva CMPE, Santos ALS and d'Avila Levy CM (2013), "Nelfinavir is effective in inhibiting the multiplication and aspartic peptidase activity of Leishmania species, including strains obtained from HIV-positive patients", Journal of Antimicrobial Chemotherapy., February, 2013. Vol. 68(2), pp. 348-353. Oxford Univ Press. [DOI] |
| Abstract: There is a general lack of effective and non-toxic chemotherapeutic agents for leishmaniasis and there is as yet no study about the effect of HIV peptidase inhibitors (HIV PIs) on Leishmania/HIV-coinfected patients. In the present work, we performed a comparative analysis of the spectrum of action of HIV PIs on different Leishmania spp., including strains obtained from HIV-positive patients receiving or not receiving antiretroviral treatment. The effects of nelfinavir and saquinavir on Leishmania proliferation were assessed by means of a colorimetric assay (MTT). Subsequently, the effect of nelfinavir on aspartic peptidase activity from Leishmania spp. was assessed by following the degradation of the fluorogenic substrate MCA-G-K-P-I-L-F-F-R-L-K-DNP-Arg-NH2. Nelfinavir was capable of significantly reducing the multiplication of many Leishmania reference strains and isolates obtained from HIV-positive patients receiving or not receiving antiretroviral treatment. Leishmania major growth was inhibited by approximate to 50, while all other flagellates were strongly inhibited (at least 94), except for a Leishmania chagasi strain obtained from an HIV-positive patient under treatment with highly active antiretroviral therapy (HAART). Culture of this isolate in the presence of nelfinavir induced a considerable reduction in the aspartic peptidase activity. In addition, nelfinavir was also capable of inhibiting the aspartic peptidase activity of all Leishmania strains tested. The present data contribute to the study of the effect of HIV PIs on Leishmania infection and add new insights into the possibility of exploiting aspartic peptidases as promising targets in order to generate novel medications to treat leishmaniasis. |
BibTeX: @article{Santos2013, author = {Santos, L. O. and Vitorio, B. S. and Branquinha, M. H. and Silva, C. M. P. E. and Santos, A. L. S. and d'Avila-Levy, C. M.}, title = {Nelfinavir is effective in inhibiting the multiplication and aspartic peptidase activity of Leishmania species, including strains obtained from HIV-positive patients}, journal = {Journal of Antimicrobial Chemotherapy}, publisher = {Oxford Univ Press}, year = {2013}, volume = {68}, number = {2}, pages = {348--353}, doi = {10.1093/jac/dks410} } |
| Silveira LB, Marchi-Salvador DP, Santos NA, Silva FP, Marcussi S, Fuly AL, Nomizo A, da Silva SL, Stabeli RG, Arantes EC and Soares AM (2013), "Isolation and expression of a hypotensive and anti-platelet acidic phospholipase A(2) from Bothrops moojeni snake venom", Journal of Pharmaceutical and Biomedical Analysis., January, 2013. Vol. 73, pp. 35-43. Elsevier Science Bv. [DOI] |
| Abstract: Phospholipases A(2) are important components of snake venoms, the basic isoforms have been more extensively studied than the acidic groups, maybe due to their higher toxicity. Trying to better understand the role of the acidic isoforms on the envenomation process, an acidic phospholipase A(2) was purified from Bothrops moojeni snake venom through two chromatographic steps (BmooPLA(2)). The enzyme showed a relative molecular mass of 13,601 Da, pI 5.2, high phospholipase activity, bactericidal effect, moderate cytotoxic activity and was able to inhibit platelet aggregation. Moreover, BmooPLA(2) induced moderate in vivo edema and hypotensive effect. The 414 bp cDNA encoding the BmooPLA(2) was cloned and expressed in Escherichia coil. The recombinant BmooPLA(2) showed phospholipase and inhibitory activities on platelet aggregation similar to those of the native protein. A comparative study between BmooPLA(2), the acidic (BthA-I) and basic (BthTX-II) PLA(2) from B. jararacussu venom showed that the effects of BmooPLA(2) and BthA-I-PLA(2) are similar. BmooPLA(2) is the first isolated and characterized non-myotoxic PLA(2) from B. moojeni snake venom. The recombinant PLA(2) can substitute the native toxin in studies aiming its biotechnological application in order to help the preservation of this endangered species. These data along with the preliminary structural studies here reported will provide a better understanding of this important class of proteins. (C) 2012 Elsevier B.V. All rights reserved. |
BibTeX: @article{Silveira2013, author = {Silveira, L. B. and Marchi-Salvador, D. P. and Santos, N. A. and Silva, F. P. and Marcussi, S. and Fuly, A. L. and Nomizo, A. and da Silva, S. L. and Stabeli, R. G. and Arantes, E. C. and Soares, A. M.}, title = {Isolation and expression of a hypotensive and anti-platelet acidic phospholipase A(2) from Bothrops moojeni snake venom}, journal = {Journal of Pharmaceutical and Biomedical Analysis}, publisher = {Elsevier Science Bv}, year = {2013}, volume = {73}, pages = {35--43}, doi = {10.1016/j.jpba.2012.04.008} } |
| Trindade LS, Aigaki T, Peixoto AA, Balduino A, Mânica da Cruz IB and Heddle JG (2013), "A novel classification system for evolutionary aging theories.", Front Genet. Vol. 4, pp. 25. [DOI] |
| Abstract: Theories of lifespan evolution are a source of confusion amongst aging researchers. After a century of aging research the dispute over whether the aging process is active or passive persists and a comprehensive and universally accepted theoretical model remains elusive. Evolutionary aging theories primarily dispute whether the aging process is exclusively adapted to favor the kin or exclusively non-adapted to favor the individual. Interestingly, contradictory data and theories supporting both exclusively programmed and exclusively non-programmed theories continue to grow. However, this is a false dichotomy; natural selection favors traits resulting in efficient reproduction whether they benefit the individual or the kin. Thus, to understand the evolution of aging, first we must understand the environment-dependent balance between the advantages and disadvantages of extended lifespan in the process of spreading genes. As described by distinct theories, different niches and environmental conditions confer on extended lifespan a range of fitness values varying from highly beneficial to highly detrimental. Here, we considered the range of fitness values for extended lifespan and develop a fitness-based framework for categorizing existing theories. We show that all theories can be classified into four basic types: secondary (beneficial), maladaptive (neutral), assisted death (detrimental), and senemorphic aging (varying between beneficial to detrimental). We anticipate that this classification system will assist with understanding and interpreting aging/death by providing a way of considering theories as members of one of these classes rather than consideration of their individual details. |
BibTeX: @article{Trindade2013, author = {Trindade, Lucas S. and Aigaki, Toshiro and Peixoto, Alexandre A. and Balduino, Alex and Mânica da Cruz, Ivana B. and Heddle, Jonathan G.}, title = {A novel classification system for evolutionary aging theories.}, journal = {Front Genet}, year = {2013}, volume = {4}, pages = {25}, url = {http://dx.doi.org/10.3389/fgene.2013.00025}, doi = {10.3389/fgene.2013.00025} } |
| Trindade-Silva AE, Rua CPJ, Andrade BGN, Vicente ACP, Silva GGZ, Berlinck RGS and Thompson FL (2013), "Polyketide Synthase Gene Diversity within the Microbiome of the Sponge Arenosclera brasiliensis, Endemic to the Southern Atlantic Ocean", Applied and Environmental Microbiology., March, 2013. Vol. 79(5), pp. 1598-1605. Amer Soc Microbiology. [DOI] |
| Abstract: Microbes associated with marine sponges are considered important producers of bioactive, structurally unique polyketides. The synthesis of such secondary metabolites involves type I polyketide synthases (PKSs), which are enzymes that reach a maximum complexity degree in bacteria. The Haplosclerida sponge Arenosclera brasiliensis hosts a complex microbiota and is the source of arenosclerins, alkaloids with cytotoxic and antibacterial activity. In the present investigation, we performed high-throughput sequencing of the ketosynthase (KS) amplicon to investigate the diversity of PKS genes present in the metagenome of A. brasiliensis. Almost 4,000 ketosynthase reads were recovered, with about 90% annotated automatically as bacterial. A total of 235 bacterial KS contigs was rigorously assembled from this sequence pool and submitted to phylogenetic analysis. A great diversity of six type I PKS groups has been consistently detected in our phylogenetic reconstructions, including a novel and A. brasiliensis-exclusive group. Our study is the first to reveal the diversity of type I PKS genes in A. brasiliensis as well as the potential of its microbiome to serve as a source of new polyketides. |
BibTeX: @article{Trindade-Silva2013, author = {Trindade-Silva, A. E. and Rua, C. P. J. and Andrade, B. G. N. and Vicente, A. C. P. and Silva, G. G. Z. and Berlinck, R. G. S. and Thompson, F. L.}, title = {Polyketide Synthase Gene Diversity within the Microbiome of the Sponge Arenosclera brasiliensis, Endemic to the Southern Atlantic Ocean}, journal = {Applied and Environmental Microbiology}, publisher = {Amer Soc Microbiology}, year = {2013}, volume = {79}, number = {5}, pages = {1598--1605}, doi = {10.1128/AEM.03354-12} } |
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