Tuesday, June 7, 2011

What's new for 'Trypanosomatids' in PubMed

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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 - 5 of 5

1. Eukaryot Cell. 2011 Jun 3. [Epub ahead of print]

RAB11 FUNCTION IN TRYPANOSOMA BRUCEI; IDENTIFICATION OF CONSERVED AND NOVEL INTERACTION PARTNERS.

Gabernet-Castello C, Dubois KN, Nimmo C, Field MC.

Source

Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK.

Abstract

The Ras-like GTPase Rab11 is implicated in multiple aspects of intracellular transport, including maintenance of plasma membrane composition and cytokinesis. In metazoa these functions are mediated in part via coiled-coil Rab11-interacting proteins (FIPs) acting as Rab11 effectors. Additional interaction between Rab11 and the exocyst subunit Sec15 connects Rab11 with exocytosis. We find that FIPs are metazoan-specific, suggesting that other factors mediate Rab11 functions in non-metazoa. We examined Rab11 interactions in Trypanosoma brucei, where endocytosis is well studied and the role of Rab11 in recycling well documented. TbSec15 and TbRab11 interact, demonstrating evolutionarily conservation. By yeast two-hybrid we identified additional Rab11-interaction partners; Tb927.5.1640 (designated RBP74) interacted with both Rab11 and Rab5. RBP74 shares a coiled-coil architecture with metazoan FIPs but is unrelated by sequence and appears to play a role in coordinating endocytosis and recycling. A second coiled-coil protein, Tb09.211.4830 (TbAZI1), orthologous to AZI1 in Homo sapiens, interacts exclusively with Rab11. AZI1 is restricted to taxa with motile cilia/flagella. These data suggest that Rab11 functions are mediated by evolutionarily conserved (i.e. AZI1 and Sec15) and potentially lineage-specific (RBP74) interactions essential for the integration of the endomembrane system.

PMID:
21642507
[PubMed - as supplied by publisher]
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2. Fitoterapia. 2011 May 27. [Epub ahead of print]

New cassane diterpenes from Caesalpinia echinata.

Cota BB, de Oliveira DM, de Siqueira EP, Souza-Fagundes EM, Pimenta AM, Santos DM, Rabello A, Zani CL.

Source

Laboratório de Química de Produtos Naturais, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Av. Augusto de Lima, 1715, Belo Horizonte, MG, 30190-002, Brazil.

Abstract

An investigation of the ethanolic extract from stems of Caesalpinia echinata Lam (Leguminosae-Caesalpinioideae) led to the isolation of five new cassane diterpenes along with known lambertianic acid. Their structures were determined based on spectroscopic methods. A preliminary study on leishmanicidal activity demonstrated that compounds 1, 2 and 6 were found to inhibit the growth of amastigote-like forms of Leishmania amazonensis without affecting mononuclear cells obtained from human peripheral blood.

Copyright © 2011. Published by Elsevier B.V.

PMID:
21641971
[PubMed - as supplied by publisher]
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3. Vet Parasitol. 2011 May 14. [Epub ahead of print]

Evaluation of miltefosine for the treatmen t of dogs naturally infected with L. infantum (=L. chagasi) in Brazil.

Andrade HM, Toledo VP, Pinheiro MB, Guimarães TM, Oliveira NC, Castro JA, Silva RN, Amorim AC, Brandão RM, Yoko M, Silva AS, Dumont K, Ribeiro ML Jr, Bartchewsky W, Monte SJ.

Source

Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Departamento de Parasitologia, Belo Horizonte, MG, Brazil.

Abstract

Dogs naturally infected with Leishmania Infantum (=L. chagasi) were treated with miltefosine using different therapeutic regimens. The animals were evaluated for clinical evolution, biochemical parameters, parasite load (by real-time PCR), cytokine levels and humoral response. After treatment and during the following 24 months, there was progressive clinical improvement and complete recovery in 50% (7/14) of the treated animals. There was a decrease in the smear positivity of the bone marrow after treatment, and there was also a gradual and constant decrease in positive cultures at the end of the follow-up period. However, the PCR detection of parasite DNA remained positive. In general, all animals presented a significant increase in parasite load 6 months after treatment. The IFN-γ levels in all the groups tended to increase during follow-up period, regardless of the miltefosine dose administered. The IL-4 and IL-10 levels of the animals tended to decrease during follow-up, except after 300 days when only IL-10 increased. The serum antibodies identified antigens that ranged from 116kDa to less than 29kDa in the Western blot assay. Furthermore, 300 days after treatment, qualitative and quantitative differences in the antigen profiles were observed. Antigens of 97 and 46kDa were the most intensely recognized. Higher levels of antigen-specific Leishmania IgG were detected before and 300 days after treatment in all groups. Taking together, the improvement in the clinical symptoms was not followed by parasitological clearance, suggesting that treatment with miltefosine is not recommended, especially in endemic areas like Brazil, where children are the major victims and dogs are involved in the maintenance of the parasite cycle.

Copyright © 2011 Elsevier B.V. All rights reserved.

PMID:
21641721
[PubMed - as supplied by publisher]
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4. Free Radic Biol Med. 2011 May 20. [Epub ahead of print]

A tryparedoxin-dependent peroxidase protects African trypanosomes from membrane damage.Diechtierow M, Krauth-Siegel RL.

Abstract

Hydroperoxide detoxification in African trypanosomes is achieved by 2-Cys-peroxiredoxin (TXNPx)- and non-selenium glutathione peroxidase (Px)-type enzymes which both obtain their reducing equivalents from the unique trypanothione/tryparedoxin system. Previous RNA interference approaches revealed that the cytosolic TXNPx and the Px-type enzymes are essential for Trypanosoma brucei. Because of partially overlapping in vitro substrate specificities and subcellular localisation the physiological function of the individual enzymes was not yet clear. As shown here, TXNPx and Px are expressed at comparable levels and in their active reduced state. Px-overexpressing parasites were less sensitive toward linoleic acid hydroperoxide but not hydrogen peroxide. Kinetic studies confirmed that Px-but not TXNPx-reduces lipophilic hydroperoxides including phospholipids with high efficiency. Most interestingly, the severe proliferation defect of Px-depleted bloodstream cells could be rescued by Trolox, but not by hydrophilic antioxidants, in the medium. This allowed us to knock-out the three Px genes individually and thus to distinguish their in vivo role. Deletion of the cytosolic Px I and II resulted in extremely fast membrane peroxidation followed by cell lysis. Cells lacking specifically the mitochondrial Px III showed a transient growth retardation and cardiolipin peroxidation but adapted within 24h to normal proliferation.

Copyright © 2011. Published by Elsevier Inc.

PMID:
21640819
[PubMed - as supplied by publisher]
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5. Exp Parasitol. 2011 May 27. [Epub ahead of print]

Efficacy of Leishmania donovani ribosomal P1 gene as DNA vaccine in experimental visceral leishmaniasis.

Arora SK, Masih S, Vasishta RK.

Source

Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.

Abstract

The acidic ribosomal proteins of the protozoan parasites have been described as prominent antigens during human disease. We present here data showing the molecular cloning and protective efficacy of P1 gene of Leishmaniadonovani as DNA vaccine. The PCR amplified complete ORF cloned in either pQE or pVAX vector was used either as peptide or DNA vaccine against experimentally induced visceral leishmaniasis in hamsters. The recombinant protein rLdP1 was given along with Freund's adjuvant and the plasmid DNA vaccine, pVAX-P1 was used alone either as single dose or double dose (prime and boost) in different groups of hamsters which were subsequently challenged with a virulent dose of 1×10(7)L.donovani (MHOM/IN/DD8/1968 strain) promastigotes by intra-cardiac route. While the recombinant protein rLdP1 or DNA vaccine pVAX-P1 in single dose format were not found to be protective, DNA vaccine in a prime-boost mode was able to induce protection with reduced mortality, a significant (75.68%) decrease in splenic parasite burden and increased expression of Th1 type cytokines in immunized hamsters. Histopathology of livers and spleens from these animals showed formation of mature granulomas with compact arrangement of lymphocytes and histiocytes, indicating its protective potential as vaccine candidate.

Copyright © 2011. Published by Elsevier Inc.

PMID:
21640106
[PubMed - as supplied by publisher]
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