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Sent on Wednesday, 2010 May 12Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | J Biol Chem. 2010 May 10. [Epub ahead of print]Cell-free synthesis and functional characterization of sphingolipid synthases from parasitic trypanosomatid protozoa.Sevova ES, Goren MA, Schwartz KJ, Hsu FF, Turk J, Fox BG, Bangs JD.University of Wisconsin-Madison, United States; AbstractThe Trypanosoma brucei genome has four highly similar genes encoding sphingolipid synthases (TbSLS1-4). TbSLSs are polytopic membrane proteins that are essential for viability of the pathogenic bloodstream stage of this human protozoan parasite, and consequently can be considered as potential drug targets. TbSLS4 was previously shown to be a bifunctional sphingomyelin/ethanolamine phosphorylceramide synthase, while functions of the others were not characterized. Using a recently described liposome-supplemented cell-free synthesis system, which eliminates complications from background cellular activities, we now unambiguously define the enzymatic specificity of the entire gene family. TbSLS1 produces inositol phosphorylceramide, TbSLS2 produces ethanolamine phosphorylceramide, and TbSLS3 is bifunctional like TbSLS4. These findings indicate that TbSLS1 is uniquely responsible for synthesis of inositol phosphorylceramide in insect stage parasites, in agreement with published expression array data. This approach also revealed that the T. cruzi ortholog (TcSLS1) is a dedicated inositol phosphorylceramide synthase. The cell-free synthesis system allowed rapid optimization of the reaction conditions for these enzymes, and site-specific mutagenesis to alter end product specificity. A single residue at position 252 (TbSLS1, Ser252; TbSLS3, Phe252) strongly influences enzymatic specificity. We have also used this system to demonstrate that aureobasidin A, a potent inhibitor of fungal inositol phosphorylceramide synthases, does not significantly affect any of the TbSLS activities, consistent with the phylogenetic distance of these two clades of sphingolipid synthases. These results represent the first application of cell-free synthesis for the rapid preparation and functional annotation of integral membrane proteins, and thus illustrate its utility in studying otherwise intractable enzyme systems. |
| PMID: 20457606 [PubMed - as supplied by publisher] | |
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| 2. | Eur J Med Chem. 2010 Apr 14. [Epub ahead of print]Synthesis of 2-(pyrimidin-2-yl)-1-phenyl-2,3,4,9-tetrahydro-1H-beta-carbolines as antileishmanial agents.Kumar R, Khan S, Verma A, Srivastava S, Viswakarma P, Gupta S, Meena S, Singh N, Sarkar J, Chauhan PM.Medicinal & Process Chemistry Division, Central Drug Research Institute, CSIR, Lucknow, India. AbstractA series of 2-(pyrimidin-2-yl)-1-phenyl-2,3,4,9-tetrahydro-1H-beta-carboline derivatives has been synthesized and evaluated for antileishmanial activity against Leishmania donovani. Compound 8 exhibited best antileishmanial activity with IC(50) value of 1.93 mug/ml against amastigotes, high selectivity index, and was more active than reference drugs sodium stilbogluconate and pentamidine. Copyright © 2010 Elsevier Masson SAS. All rights reserved. |
| PMID: 20457476 [PubMed - as supplied by publisher] | |
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| 3. | J Microbiol Immunol Infect. 2010 Apr;43(2):138-146.Evaluation of the Effects of a New Formulation of Leishmania Major Antig en in Balb/C and Conventional White Laboratory Mice.Latifynia A, Hazrati SM.Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. AbstractBACKGROUND/PURPOSE: Leishmaniasis is currently a threat in 80 countries around the world, and cutaneous Leishmaniasis accounts for more than 5% of new cases. It is a problematic disease in Iran, and preparing a protective vaccine has been a major goal of medical investigations. The objective of this study was to compare the protective effects of a cocktail vaccine candidate encoding various Leishmania major antigens in highly susceptible (Balb/C, or type I mice) and resistant (laboratory small white, or type II) mice. METHODS: A new antigen formulation was evaluated in type I and II mice. Leishmania major promastigotes was cultured and harvested at different growth stages, and a cocktail made from the harvested organisms. The preparations were tested for sterility and contamination by endotoxin. Five different methods were utilized to produce a crude antigen preparation. The protein levels of the antigen preparations were measured using the Lowry method, and the antigens were intradermally injected using different protocols for type I and II mice. After 38 days, all mice were euthanized with diethyl ether, and spleens were removed. Histological sections were prepared, stained with hematoxylin and eosin and changes to the splenic white pulp (SWP) were studied microscopically. RESULTS: Compared with the control groups, there was a drastic change in white pulp structure. The size increases of the SWP were dependent on the injection group and mouse strain. There was a remarkable expansion of lymphoid follicles in the treated groups in both mice strains. CONCLUSION: The new antigen formulation was able to stimulate and expand the lymphoid constituents of spleen tissue. The SWP is where immune responses and antibodies are produced. Therefore, the effect of the antigen preparations on secondary immune responses, adaptive immunity, and antibody production is important in determining the susceptibility of mice to cutaneous Leishmaniasis and the induction of immunity. Copyright © 2010 Taiwan Society of Microbiology. Published by Elsevier B.V. All rights reserved. |
| PMID: 20457431 [PubMed - as supplied by publisher] | |
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| 4. | Acta Trop. 2010 May 7. [Epub ahead of print]Natural Leishmania infantum infection in Migonemyia migonei (França, 1920) (Diptera:Psychodidae:Phlebotominae) the putative vector of visceral leishmaniasis in Pernambuco State, Brazil.Carvalho MR, Valença HF, Silva FJ, de Pita-Pereira D, Pereira TD, Britto C, Brazil RP, Filho SB.Departamento de Imunologia Centro de Pesquisas Aggeu Magalhães, FIOCRUZ, Recife, PE 50670-420, Brazil; Laboratório de Bioquímica e Fisiologia de Insetos, Instituto Oswaldo Cruz, FIOCRUZ, Manguinhos, 21045-900, Rio de Janeiro, RJ, Brazil. AbstractA study of the natural infection of phlebotomine sand flies by Leishmania (Leishmania) infantum was conducted in an area of visceral leishmaniasis in São Vicente Férrer, located in the northern part of the Atlantic rain forest region in the State of Pernambuco, Brazil. In a previous study, Migonemyia migonei have been found predominantly in peridomiciles and houses in this endemic area. The analysis of Mi. migonei, collected by CDC light trap, by multiplex PCR assay coupled to non-isotopic hybridization showed that 2 females out of 50 were infected by L. infantum. This is the first finding of natural infection of Mi. migonei by L. infantum suggesting that Mi. migonei may be the vector of Leishmaniainfantum in areas of visceral leishmaniasis where Lutzomyia longipalpis, the usual vector, is absent. Copyright © 2010. Published by Elsevier B.V. |
| PMID: 20457120 [PubMed - as supplied by publisher] | |
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| 5. | Vet J. 2010 Apr 22. [Epub ahead of print]Prevalence of anti-platelet antibodies in dogs naturally co-infected by Leishmania infantum and Ehrlichia canis.Cortese L, Terrazzano G, Piantedosi D, Sica M, Prisco M, Ruggiero G, Ciaramella P.Department of Veterinary Clinical Science, Section of Internal Medicine, University of Naples Federico II, Via Delpino, 1, 80137 Naples, Italy. AbstractThirty naturally infected dogs were divided into three groups (10 animals each): group I (canine leishmaniosis), group II (canine ehrlichiosis) and group III (dogs co-infected by both infectious agents). Ten clinically healthy dogs were used as controls. A haematological profile was obtained and dog sera were assessed for the presence of platelet-bound IgM and IgG antibodies (PBIgM, PBIgG) using flow cytometry. Eight of the naturally co-infected dogs (80%), five of the leishmaniotic dogs (50%) and six of the ehrlichiotic dogs (60%) had detectable levels of platelet-bound antibodies (PBIg). No PBIg were observed in the control group. The hypothesis that Leishmania and Ehrlichia co-infection could more severely affect the immune response of infected dogs is discussed. Copyright © 2010 Elsevier Ltd. All rights reserved. |
| PMID: 20456989 [PubMed - as supplied by publisher] | |
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| 6. | Clin Exp Dermatol. 2010 Apr 27. [Epub ahead of print]Cutaneous leishmaniasis: advances in disease pathogenesis, diagnostics and therapeutics.Ameen M.Royal Free Hospital, Royal Free Hampstead NHS Trust, London, UK. AbstractSummary Cutaneous leishmaniasis is one of the most common tropical dermatoses worldwide and is of major public health importance. It is caused by numerous Leishmania protozoa species, which are responsible for its clinical diversity. With changes in vector (sandfly) habitat and increased travel among human populations, its incidence is rising, and in nonendemic countries, including the UK, it is increasingly diagnosed in migrants, returned travellers, and military personnel. Diagnostic tests have not always been sufficiently sensitive, and despite a wide range of treatments, poor therapeutic responses and adverse effects are common. In the past decade, there have been notable advances in molecular diagnostics, in the understanding of host immune responses to infection, and in new therapeutic interventions and vaccine development. |
| PMID: 20456404 [PubMed - as supplied by publisher] | |
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| 7. | Lancet. 2010 Mar 27;375(9720):1080.Research capacity strengthening in the DRC.Lutumba P, Kande V, Boelaert M, Kayembe JM, Mampunza S. |
| PMID: 20346811 [PubMed - indexed for MEDLINE] | |
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