Thursday, March 10, 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 - 6 of 6

1. J Leukoc Biol. 2011 Mar 8. [Epub ahead of print]

Technical Advance: Amine-reactive OVA multimers for auto-vaccination against cytokines and other mediators: perspectives illustrated for GCP-2 in L. major infection.

Uyttenhove C, Marillier RG, Tacchini-Cottier F, Charmoy M, Caspi RR, Damsker JM, Goriely S, Su D, Van Damme J, Struyf S, Opdenakker G, Van Snick J.

*Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium;

Abstract

Anticytokine auto-vaccination is a powerful tool for the study of cytokine functions in vivo but has remained rather esoteric as a result of numerous technical difficulties. We here describe a two-step procedure based on the use of OVA multimers purified by size exclusion chromatography after incubation with glutaraldehyde at pH 6. When such polymers are incubated with a target protein at pH 8.5 to deprotonate reactive amines, complexes are formed that confer immunogenicity to self-antigens. The chemokine GCP-2/CXCL6, the cytokines GM-CSF, IL-17F, IL-17E/IL-25, IL-27, and TGF-β1, and the MMP-9/gelatinase B are discussed as examples. mAb, derived from such immunized mice, have obvious advantages for in vivo studies of the target proteins. Using a mAb against GCP-2, obtained by the method described here, we provide the first demonstration of the major role played by this chemokine in rapid neutrophil mobilization after Leishmania major infection. Pre-activated OVA multimers reactive with amine residues thus provide an efficient carrier for auto-vaccination against 9-90 kDa autologous proteins.

PMID: 21385949 [PubMed - as supplied by publisher]
2. Mol Biol Evol. 2011 Mar 8. [Epub ahead of print]

Experimental examination of EFL and MATX eukaryotic horizontal gene transfers: co-existence of mutually exclusive transcripts predates functional rescue.

Szabová J, Ruzicka P, Verner Z, Hampl V, Lukes J.

Faculty of Science, Charles University in Prague, 128 44 Prague, Czech Republic.

Abstract

Many eukaryotic genes do not follow simple vertical inheritance. Elongation factor 1α (EF-1α) and methionine adenosyl transferase (MAT) are enzymes with complicated evolutionary histories and, interestingly, the two cases have several features in common. These essential enzymes occur as two relatively divergent paralogs (EF-1α/EFL, MAT/MATX) that have patchy distributions in eukaryotic lineages that are nearly mutually exclusive. To explain such distributions, we must invoke either multiple eukaryote-to-eukaryote horizontal gene transfers (HGTs) followed by functional replacement, or presence of both paralogs in the common ancestor followed by long-term co-existence and differential losses in various eukaryotic lineages. To understand the evolution of these paralogs, we have performed in vivo experiments in Trypanosoma brucei addressing the consequences of long-term co-expression and functional replacement. In the first experiment of its kind, we have demonstrated that EF-1α and MAT can be simultaneously expressed with EFL and MATX, respectively, without affecting the growth of the flagellates. After the endogenous MAT or EF-1α was down-regulated by RNA interference, MATX immediately substituted for its paralog, while EFL was not able to substitute for EF-1α, leading to mortality. We conclude that MATX is naturally capable of evolving patchy paralog distribution via HGTs and/or long term co-expression and differential losses. The capability of EFL to spread by HGT is lower and so the patchy distribution of EF-1α/EFL paralogs was probably shaped mainly by deep paralogy followed by long term co-existence and differential losses.

PMID: 21385829 [PubMed - as supplied by publisher]
3. Science. 2011 Mar 4;331(6021):1149-53.

Controlling and coordinating development in vector-transmitted parasites.

Matthews KR.

Centre for Immunity, Infection, and Evolution, Institute for Immunology and Infection Research, Ashworth Laboratories, School of Biological Sciences, King's Buildings, University of Edinburgh, Edinburgh EH9 3JT, UK.

Abstract

Vector-borne parasites cause major human diseases of the developing world, including malaria, human African trypanosomiasis, Chagas disease, leishmaniasis, filariasis, and schistosomiasis. Although the life cycles of these parasites were defined over 100 years ago, the strategies they use to optimize their successful transmission are only now being understood in molecular terms. Parasites are now known to monitor their environment in both their host and vector and in response to other parasites. This allows them to adapt their developmental cycles and to counteract any unfavorable conditions they encounter. Here, I review the interactions that parasites engage in with their hosts and vectors to maximize their survival and spread.

PMID: 21385707 [PubMed - in process]
4. Eur J Med Chem. 2011 Feb 22. [Epub ahead of print]

Synthesis and evaluation of new furanyl and thiophenyl azoles as antileishmanial agents.

Marrapu VK, Mittal M, Shivahare R, Gupta S, Bhandari K.

Medicinal and Process Chemistry Division, Central Drug Research Institute, CSIR, Lucknow 226 001, India.

Abstract

A series of benzyloxy furanyl and benzyloxy thiophenyl azoles were synthesized and screened for their in vitro antileishmanial activity against Leishmania donovani. Among all, 16 compounds have shown more than 90% inhibition against promastigotes at 20 μM while 11 compounds exhibited IC(50) in the range of 3.04-9.39 μM against amastigotes. Compound 4, a 3-chlorobenzyloxy furanyl imidazole emerged as the most active compound in the series with IC(50) value of 3.04 μM and SI value of 19.80, and was several folds more potent than the reference drugs miltefosine and miconazole.

Copyright © 2011 Elsevier Masson SAS. All rights reserved.
PMID: 21385661 [PubMed - as supplied by publisher]
5. Parasite Immunol. 2011 Mar 8. doi: 10.1111/j.1365-3024.2011.01287.x. [Epub ahead of print]

Human host determinants influencing the outcome of T. b. gambiense infections.

Bucheton B, Macleod A, Jamonneau V.

Institut de Recherche pour le Développement (IRD), Unité Mixte de Recherche IRD-CIRAD 177, TA A-17/G, Campus International de Baillarguet, F-34398 Montpellier, France. Centre International de Recherche-Développement sur l'Elevage en zones Subhumides (CIRDES), Unité de recherches sur les bases biologiques de la lutte intégrée, 01 BP 454 Bobo-Dioulasso 01, Burkina Faso. Wellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, Sir Henry Wellcome Building for Comparative Medical Sciences, 464 Bearsden Road, Glasgow, G61 1QH, UK.

Abstract

Since first identified, Human African trypanosomiasis (HAT) or sleeping sickness has been described as invariably fatal. Increasing data however argue that infection by Trypanosoma brucei gambiense, the causative agent of HAT, results in a wide range of outcomes in its human host and importantly that a number of subjects in endemic areas are apparently able to control infection to low levels, undetectable by the classical parasitological tests used in the field. Thus trypanotolerance seems to occur in humans as has already been described in cattle or in the rodent experimental models of infection. This review focuses on the description of the diversity of outcomes resulting from T.b. gambiense in humans and on the host factors involved. The consequences/impacts on HAT epidemiology resulting from this diversity are also discussed with regard to implementing sustainable HAT control strategies.

Copyright © 2011 Blackwell Publishing Ltd.
PMID: 21385185 [PubMed - as supplied by publisher]
6. Org Lett. 2011 Mar 8. [Epub ahead of print]

A Fluorous Phosphate Protecting Group with Applications to Carbohydrate Synthesis.

Liu L, Pohl NL.

Department of Chemistry, Department of Chemical and Biological Engineering, and the Plant Sciences Institute, Hach Hall, Iowa State University, Ames, Iowa 50011-3111, United States.

Abstract

The first fluorous protecting group for phosphate is reported. This group can be used as a facile tag for purification and be removed under mild reducing conditions using zinc and ammonium formate. Synthesis of a disaccharide from Leishmania using this fluorous protecting group demonstrated the group's stability to the acidic conditions necessary for glycosylation as well as its orthogonality to several other common protecting groups.

PMID: 21384825 [PubMed - as supplied by publisher]

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