Saturday, September 19, 2009

What's new for 'Trypanosomatids' in PubMed

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Sent on Saturday, 2009 Sep 19
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: Methods Mol Biol. 2009;573:329-45.

A systematic strategy for the discovery of candidate genes responsible for phenotypic variation.

Fisher P, Noyes H, Kemp S, Stevens R, Brass A.

School of Computer Science, University of Manchester, Manchester, UK.

It is increasingly common to combine genome-wide expression data with quantitative trait mapping data to aid in the search for sequence polymorphisms responsible for phenotypic variation. By joining these complex but different data types at the level of the biological pathway, we can take advantage of existing biological knowledge to systematically identify possible mechanisms of genotype-phenotype interaction. With the development of web services and workflows, this process can be made rapid and systematic. Our methodology was applied to a use case of resistance to African trypanosomiasis in mice. Workflows developed in this investigation, including a guide to loading and executing them with example data, are available at http://www.myexperiment.org/users/43/workflows .

PMID: 19763936 [PubMed - in process]

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2: Genetica. 2009 Sep 10. [Epub ahead of print]

A transposon toolkit for gene transfer and mutagenesis in protozoan parasites.

Damasceno JD, Beverley SM, Tosi LR.

Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, SP, 14049-900, Brazil.

Protozoan parasites affect millions of people around the world. Treatment and control of these diseases are complicated partly due to the intricate biology of these organisms. The interactions of species of Plasmodium, Leishmania and trypanosomes with their hosts are mediated by an unusual control of gene expression that is not fully understood. The availability of the genome sequence of these protozoa sets the stage for using more comprehensive, genome-wide strategies to study gene function. Transposons are effective tools for the systematic introduction of genetic alterations and different transposition systems have been adapted to study gene function in these human pathogens. A mariner transposon toolkit for use in vivo or in vitro in Leishmania parasites has been developed and can be used in a variety of applications. These modified mariner elements not only permit the inactivation of genes, but also mediate the rescue of translational gene fusions, bringing a major contribution to the investigation of Leishmania gene function. The piggyBac and Tn5 transposons have also been shown to mobilize across Plasmodium spp. genomes circumventing the current limitations in the genetic manipulation of these organisms.

PMID: 19763844 [PubMed - as supplied by publisher]

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3: J Infect Dev Ctries. 2009 Jul 1;3(6):479-83.

Septic shock due to visceral leishmaniasis, probably transmitted from blood transfusion.

Mpaka MA, Daniil Z, Kyriakou DS, Zakynthinos E.

Critical Care Department, School of Medicine, University Hospital of Thessaly, Greece.

A case of visceral leishmaniasis (VL) in a 77-year-old woman, with renal failure on haemodialysis, admitted in the intensive care unit (ICU) with vascular instability requiring vassopressor treatment, is presented. Initially, no co-infection could be detected. The patient initially responded well when liposomal amphotericin B was administered, after bone marrow demonstrated multiple intra-cellular Leishmania amastigotes and extra-cellular promastigotes. However, the patient died from uncontrolled septic shock from a secondary bacterial infection, the tenth day of admission. To our knowledge, vascular instability has not been reported in VL. Moreover, non-vector transmission was also suspected in this case. The patient had undergone cholecystectomy three months earlier, during which two blood units had been transfused; IgG anti-Leishmania antibodies at a high titer were detected in one of the two healthy blood donors, later.

PMID: 19762964 [PubMed - in process]

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4: Trends Parasitol. 2009 Sep 15. [Epub ahead of print]

Are neutrophils important host cells for Leishmania parasites?

Ritter U, Frischknecht F, van Zandbergen G.

Department of Immunology, University of Regensburg, Franz-Josef-Strauss-Allee 11, D93053 Regensburg, Germany.

Neutrophils are the most crucial cells for early defence against infections. When appropriately activated, they can kill obligate intracellular pathogens such as Leishmania. However, once the phagocytotic killing has been evaded, neutrophils can serve as host cells for Leishmania. Parasitized neutrophils were suggested to function as a 'Trojan horse', to transfer Leishmania silently to macrophages. In vivo imaging has contributed a second evasion mechanism. We termed it the 'Trojan rabbit' strategy, whereby parasites escape dying neutrophils to infect macrophages. Here, we discuss the different experimental models used to study neutrophil function in leishmaniasis. We suggest that the capacity of neutrophils to function as an immune evasion target depends on the genetic background of the host and the parasite strain used for the experiments.

PMID: 19762280 [PubMed - as supplied by publisher]

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5: Phytomedicine. 2009 Sep 15. [Epub ahead of print]

Leishmanicidal activity of benzophenones and extracts from Garcinia brasiliensis Mart. fruits.

Pereira IO, Marques MJ, Pavan AL, Codonho BS, Barbiéri CL, Beijo LA, Doriguetto AC, D'Martin EC, Dos Santos MH.

Department of Pharmacy, Laboratory of Phytochemistry and Medicinal Chemistry, Federal University of Alfenas, MG, Brazil.

Infections by protozoans of the genus Leishmania are the major worldwide health problem, with high endemicity in developing countries. The drugs of choice for the treatment of leishmaniasis are the pentavalent antimonials, which exert renal and cardiac toxicity. Thus, there is a strong need for safer and more effective treatments against leishmaniasis. The present study was designated to evaluate, by a bioguided assay, the leishmanicidal activity of extracts (hexane, ethyl-acetate and ethanolic) and molecules both obtained by means of extraction from pericarps of Garcinia brasiliensis fruits. The hexane extract presented the best activity on the extracellular (promastigotes) and intracellular (amastigotes) forms of Leishmania (L.) amazonensis, when compared to the other extracts. Based on these findings, this extract was fractionated by silica gel column chromatography, affording nine fractions then resulting in three purified prenylated benzophenones - 7-epi-clusianone (1), garciniaphenone (2) and guttiferone-a (3). They showed significant activity on Leishmania (L.) amazonensis, and little toxicity for mammalian cells. Structure-activity relationships were evaluated showing that the IC(50) value displayed is dependent of prenyl groups and phenolic hydroxyls number, and inversely proportional to the hydrophobicity. Our results are promising, showing that these compounds are biologically active on Leishmania (L.) amazonensis.

PMID: 19762221 [PubMed - as supplied by publisher]

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