What's new for 'Trypanosomatids' in PubMed

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Sent on Thursday, 2012 May 10
Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"

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PubMed Results

Items 1 - 10 of 11

1.	J Parasitol Res. 2012;2012:203818. Epub 2012 Apr 12. Reactive oxygen species and nitric oxide in cutaneous leishmaniasis. Horta MF, Mendes BP, Roma EH, Noronha FS, Macêdo JP, Oliveira LS, Duarte MM, Vieira LQ. Source Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil. Abstract Cutaneous leishmaniasis affects millions of people around the world. Several species of Leishmania infect mouse strains, and murine models closely reproduce the cutaneous lesions caused by the parasite in humans. Mouse models have enabled studies on the pathogenesis and effector mechanisms of host resistance to infection. Here, we review the role of nitric oxide (NO), reactive oxygen species (ROS), and peroxynitrite (ONOO(-)) in the control of parasites by macrophages, which are both the host cells and the effector cells. We also discuss the role of neutrophil-derived oxygen and nitrogen reactive species during infection with Leishmania. We emphasize the role of these cells in the outcome of leishmaniasis early after infection, before the adaptive T(h)-cell immune response.
	PMID: 22570765 [PubMed - in process]
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2.	PLoS One. 2012;7(5):e36233. Epub 2012 May 3. Selective Blockade of Trypanosomatid Protein Synthesis by a Recombinant Antibody Anti-Trypanosoma cruzi P2β Protein. Juri Ayub M, Nyambega B, Simonetti L, Duffy T, Longhi SA, Gómez KA, Hoebeke J, Levin MJ, Smulski CR. Source Laboratorio de Biología Molecular de la Enfermedad de Chagas, Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina. Abstract The ribosomal P proteins are located on the stalk of the ribosomal large subunit and play a critical role during the elongation step of protein synthesis. The single chain recombinant antibody C5 (scFv C5) directed against the C-terminal region of the Trypanosoma cruzi P2β protein (TcP2β) recognizes the conserved C-terminal end of all T. cruzi ribosomal P proteins. Although this region is highly conserved among different species, surface plasmon resonance analysis showed that the scFv C5 possesses very low affinity for the corresponding mammalian epitope, despite having only one single amino-acid change. Crystallographic analysis, in silico modelization and NMR assays support the analysis, increasing our understanding on the structural basis of epitope specificity. In vitro protein synthesis experiments showed that scFv C5 was able to specifically block translation by T. cruzi and Crithidia fasciculata ribosomes, but virtually had no effect on Rattus norvegicus ribosomes. Therefore, we used the scFv C5 coding sequence to make inducible intrabodies in Trypanosoma brucei. Transgenic parasites showed a strong decrease in their growth rate after induction. These results strengthen the importance of the P protein C terminal regions for ribosomal translation activity and suggest that trypanosomatid ribosomal P proteins could be a possible target for selective therapeutic agents that could be derived from structural analysis of the scFv C5 antibody paratope.
	PMID: 22570698 [PubMed - in process]
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3.	J Biomed Biotechnol. 2012;2012:673458. Epub 2012 Apr 10. Application of Serial Analysis of Gene Expression to the Study of the Gene Expression Profile of Leishmania infantum chagasi Promastigote. Lima Neto AS, de Melo Neto OP, Costa CH. Source Laboratório de Pesquisas em Leishmanioses, Instituto de Doenças Tropicais Natan Portella (IDTNP), Rua Gov. Artur de Vasconcelos 151, Centro/Sul, 64.001-450 Teresina, PI, Brazil. Abstract This study describes the application of the LongSAGE methodology to study the gene expression profile in promastigotes of Leishmania infantum chagasi. A tag library was created using the LongSAGE method and consisted of 14,208 tags of 17 bases. Of these, 8,427 (59.3%) were distinct. BLAST research of the 1,645 most abundant tags showed that 12.8% of them identified the coding sequences of genes, while 82% (1,349/1,645) identified one or more genomic sequences that did not correspond with open reading frames. Only 5.2% (84/1,645) of the tags were not aligned to any position in the L. infantum genome. The UTR size of Leishmania and the lack of CATG sites in some transcripts were decisive for the generation of tags in these regions. Additional analysis will allow a better understanding of the expression profile and discovering the key genes in this life cycle.
	PMID: 22570533 [PubMed - in process]
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4.	Braz J Med Biol Res. 2012 May 10. pii: S0100-879X2012007500073. [Epub ahead of print] Interleukin-10-dependent down-regulation of interferon-gamma response to Leishmania by Mycobacterium leprae antigens during the clinical course of a coinfection. Azeredo-Coutinho RB, Matos DC, Nery JA, Valete-Rosalino CM, Mendonça SC. Source Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil.
	PMID: 22570089 [PubMed - as supplied by publisher]
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5.	Appl Microbiol Biotechnol. 2012 May 10. [Epub ahead of print] Improvement of N-glycan site occupancy of therapeutic glycoproteins produced in Pichia pastoris. Choi BK, Warburton S, Lin H, Patel R, Boldogh I, Meehl M, d'Anjou M , Pon L, Stadheim TA, Sethuraman N. Source GlycoFi, Biologics Discovery, Merck & Co., Inc, 21 Lafayette St. Suite 200, Lebanon, NH, 03766, USA. Abstract Yeast is capable of performing posttranslational modifications, such as N- or O-glycosylation. It has been demonstrated that N-glycans play critical biological roles in therapeutic glycoproteins by modulating pharmacokinetics and pharmacodynamics. However, N-glycan sites on recombinant glycoproteins produced in yeast can be underglycosylated, and hence, not completely occupied. Genomic homology analysis indicates that the Pichia pastoris oligosaccharyltransferase (OST) complex consists of multiple subunits, including OST1, OST2, OST3, OST4, OST5, OST6, STT3, SWP1, and WBP1. Monoclonal antibodies produced in P. pastoris show that N-glycan site occupancy ranges from 75-85 % and is affected mainly by the OST function, and in part, by process conditions. In this study, we demonstrate that N-glycan site occupancy of antibodies can be improved to greater than 99 %, comparable to that of antibodies produced in mammalian cells (CHO), by overexpressing Leishmania major STT3D (LmSTT3D) under the control of an inducible alcohol oxidase 1 (AOX1) promoter. N-glycan site occupancy of non-antibody glycoproteins such as recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) was also significantly improved, suggesting that LmSTT3D has broad substrate specificity. These results suggest that the glycosylation status of recombinant proteins can be improved by heterologous STT3 expression, which will allow for the customization of therapeutic protein profiles.
	PMID: 22569635 [PubMed - as supplied by publisher]
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6.	Mol Biochem Parasitol. 2012 May 5. [Epub ahead of print] Importance of enolase in Giardia lamblia differentiation. Castillo-Romero A, Davids BJ, Lauwaet T, Gillin FD. Source Department of Pathology, University of California, San Diego, California 92103-8416, U. S. A. Abstract The ability of Giardia to differentiate into cysts which survive in the environment and release the virulent trophozoites after ingestion in the small intestine is essential for transmission and disease. We examined the role of enolase, a glycolytic enzyme, in Giardia differentiation. The sequence of Giardia lamblia enolase (gEno) is most similar to enolases in Homo sapiens and Leishmania mexicana, and shows the conserved catalytic and metal-binding residues. We used an integration vector to stably express wild type and mutant gEno. In trophozoites, wild type gEno localized to the cell membrane, caudal flagella and cytosol. gEno is present on the wall of mature cysts, but not in encystation secretory vesicles (ESV). The expression of gEno with a deletion of residues G167-K169, or mutations H389Q/R390S significantly inhibited excystation while mutation of residue D257K had no effect. These results suggest a role for enolase in regulation of Giardia excystation. Copyright © 2012. Published by Elsevier B.V.
	PMID: 22569588 [PubMed - as supplied by publisher]
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7.	Mol Biochem Parasitol. 2012 May 5. [Epub ahead of print] Leishmania (l.) amazonensis peptidase activities inside the living cells and in their lysates. Caroselli EE, Assis DM, Barbieri CL, Júdice WA, Juliano MA, Gazarini ML, Juliano L. Source Department of Biophysics, Universidade Federal de São Paulo, SP, Brazil. Abstract In this study we investigated the peptidase activity in Leishmania (L.) amazonensis live amastigote by confocal microscopy using peptidyl-MCA as substrates, the hydrolysis of which releases the MCA fluorophore inside the cells. Cell pre-treatment with peptidase inhibitors indicated the presence of cysteine and serine peptidases. It was noteworthy that Leishmania amastigotes incorporate only substrates (Z-FR-MCA, Z-RR-MCA) or inhibitors (E64, TLCK) containing positively charged groups. The peptidase activities in the supernatants of amastigotes and promastigotes lysates were also evaluated with the same peptidyl-MCA substrates and inhibitors in the pH range 4.5-9.0. The effects of temperature and different salts were also included in this study. The hydrolytic activities of supernatants on Z-FR-MCA clearly indicate the presence of different cysteine peptidases that adapted to work in different environment conditions. Intact Leishmania cells incorporated Z-RR-MCA, the hydrolysis of which was inhibited only by TLCK indicating the presence of at least one serine peptidase. The pH profile of Z-RR-MCA hydrolysis by amastigotes and promastigotes lysate supernatants, and the hydrolysis time course of the FRET peptide Abz-AGRRRAQ-EDDnp at R-A bond, followed by removal of the two C-termini R to yield Abz-AGR-OH that is a unique characteristic of oligopeptidase B, indicate its presence in the parasite. Copyright © 2012. Published by Elsevier B.V.
	PMID: 22569587 [PubMed - as supplied by publisher]
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8.	Mol Biochem Parasitol. 2012 May 5. [Epub ahead of print] Disparate phenotypic effects from the knockdown of various Trypanosoma brucei cytochrome c oxidase subunits. Gnipová A, Panicucci B, Paris Z, Verner Z, Horváth A, Lukeš J, Zíková A. Source Institute of Parasitology, Biology Centre, České Budějovice, Czech Republic; Faculty of Science, Comenius University, Bratislava, Slovakia. Abstract The Trypanosoma brucei cytochrome c oxidase (respiratory complex IV) is a very divergent complex containing a surprisingly high number of trypanosomatid-specific subunits with unknown function. To gain insight into the functional organization of this large protein complex, the expression of three novel subunits (TbCOX VII, TbCOX X and TbCOX 6080) were down-regulated by RNA interference. We demonstrate that all three subunits are important for the proper function of complex IV and the growth of the procyclic stage of T. brucei. These phenotypes were manifested by the structural instability of the complex when these indispensible subunits were repressed. Furthermore, the impairment of cytochrome c oxidase resulted in other severe mitochondrial phenotypes, such as a decreased mitochondrial membrane potential, reduced ATP production via oxidative phoshorylation and redirection of oxygen consumption to the trypanosome-specific alternative oxidase, TAO. Interestingly, the inspected subunits revealed some disparate phenotypes, particularly regarding the activity of cytochrome c reductase (respiratory complex III). While the activity of complex III was down-regulated in RNAi induced cells for TbCOX X and TbCOX 6080, the TbCOX VII silenced cell line actually exhibited higher levels of complex III activity and elevated levels of ROS formation. This result suggests that the examined subunits may have different functional roles within complex IV of T. brucei, perhaps involving the ability to communicate between sequential enzymes in the respiratory chain. In summary, by characterizing the function of three hypothetical components of complex IV, we are able to assign these proteins as genuine and indispensable subunits of the procyclic T. brucei cytochrome c oxidase, an essential component of the respiratory chain in these evolutionary ancestral and medically important parasites. Copyright © 2012. Published by Elsevier B.V.
	PMID: 22569586 [PubMed - as supplied by publisher]
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9.	Acta Trop. 2012 Apr 30. [Epub ahead of print] Natural infection of cortelezzii complex (Diptera: Psychodidae: Phlebotominae) with Leishmania braziliensis in Chaco, Argentina. Rosa J, Pereira DP, Brazil RP, Filho JD, Salomón O, Szelag E. Source Área Entomología, Instituto de Medicina Regional, Universidad Nacional del Nordeste, Av. Las Heras 727, (CP 3500) Resistencia, Chaco, Argentina. Abstract In Argentina, American Cutaneous Leishmaniasis (ACL) extends up to 29°S in the phytogeographic regions of the Yungas (west), Chaco (center) and Paranaense (east). Since the Phlebotominae vectors of this disease in the western Chaco (dry Chaco) are unknown, in the present work, we studied the natural infection in Phlebotominae by PCR-ERFLP and Dot blot in order to incriminate these organisms as potential vectors. Captures with CDC-type traps were performed monthly in the domicile, the peridomicile and the forest in the Municipio Misión Nueva Pompeya, Chaco, Argentina, in two sites with human cases of ACL: Los Pozos (24°54'S, 61°22'W) and Fortín Arenales (24°58'S, 61°21'W), from November 2006 to December 2007. A total of 1702 Phlebotominae were captured: Mygonemyia migonei (83.8%), cortelezzii complex (11.1%), Mycropigomyia peresi (3.3%), Mycropygomy quinquefer (1.2%), Pintomyia torresi (0.2%) and Nyssomyia neivai (0.2%). Although no significant differences were found in species diversity, there were significant differences in abundance between both sites studied. A total of 80 phlebotomine females were analyzed: 50 of the cortelezzii complex and 30 My. migonei. No intestinal flagellates were observed by light microscopy. Two pools of 10 individuals of the cortelezzii complex of the peridomicile and forest of Fortín Arenales were reactive by PCR and Dot blot for Leishmania (Viannia) braziliensis. In Argentina, Evandromyia cortelezzii has been incriminated as a likely vector of ACL because of its abundance in areas of sporadic outbreaks. In the present work, Ev. cortelezzii females were found naturally infected, thus reinforcing the hypothesis that the members of the cortelezzii complex act as vectors of the disease. Copyright © 2012. Published by Elsevier B.V.
	PMID: 22569560 [PubMed - as supplied by publisher]
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10.	Int J Biol Macromol. 2012 May 5. [Epub ahead of print] Fumarate hydratase isoforms of Leishmania major: subcellular localization, structural and kinetic properties. Feliciano PR, Gupta S, Dyszy F, Dias-Baruffi M, Costa-Filho AJ, Michels PA, Nonato MC. Source Laboratório de Cristalografia de Proteínas, FCFRP, Universidade de São Paulo, Ribeirão Preto 14040-903, Brazil. Abstract Fumarate hydratases (FHs; EC 4.2.1.2) are enzymes that catalyze the reversible hydration of fumarate to S-malate. Parasitic protists that belong to the genus Leishmania and are responsible for a complex of vector-borne diseases named leishmaniases possess two genes that encode distinct putative FH enzymes. Genome sequence analysis of Leishmania major Friedlin reveals the existence of genes LmjF24.0320 and LmjF29.1960 encoding the putative enzymes LmFH-1 and LmFH-2, respectively. In the present work, the FH activity of both L. major enzymes has been confirmed. Circular dichroism studies suggest important differences in terms of secondary structure content when comparing LmFH isoforms and even larger differences when comparing them to the homologous human enzyme. CD melting experiments revealed that both LmFH isoforms are thermolabile enzymes. The catalytic efficiency under aerobic and anaerobic environments suggests that they are both highly sensitive to oxidation and damaged by oxygen. Intracellular localization studies located LmFH-1 in the mitochondrion, whereas LmFH-2 was found predominantly in the cytosol with possibly also some in glycosomes. The high degree of sequence conservation in different Leishmania species, together with the relevance of FH activity for the energy metabolism in these parasites suggest that FHs might be exploited as targets for broad-spectrum antileishmanial drugs. Copyright © 2012. Published by Elsevier B.V.
	PMID: 22569531 [PubMed - as supplied by publisher]
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