Thursday, August 4, 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 - 10 of 14

1. PLoS Negl Trop Dis. 2011 Jul;5(7):e1253. Epub 2011 Jul 19.

A Screen against Leishmania Intracellular Amastigotes: Comparison to a Promastigote Screen and Identification of a Host Cell-Specific Hit.

De Muylder G, Ang KK, Chen S, Arkin MR, Engel JC, McKerrow JH.

Source

Department of Pathology, Sandler Center for Drug Discovery, University of California San Francisco, San Francisco, California, United States of America.

Abstract

The ability to screen compounds in a high-throughput manner is essential in the process of small molecule drug discovery. Critical to the success of screening strategies is the proper design of the assay, often implying a compromise between ease/speed and a biologically relevant setting. Leishmaniasis is a major neglected disease with limited therapeutic options. In order to streamline efforts for the design of productive drug screens against Leishmania, we compared the efficiency of two screening methods, one targeting the free living and easily cultured promastigote (insect-infective) stage, the other targeting the clinically relevant but more difficult to culture intra-macrophage amastigote (mammal-infective) stage. Screening of a 909-member library of bioactive compounds against Leishmania donovani revealed 59 hits in the promastigote primary screen and 27 in the intracellular amastigote screen, with 26 hits shared by both screens. This suggested that screening against the promastigote stage, although more suitable for automation, fails to identify all active compounds and leads to numerous false positive hits. Of particular interest was the identification of one compound specific to the infective amastigote stage of the parasite. This compound affects intracellular but not axenic parasites, suggesting a host cell-dependent mechanism of action, opening new avenues for anti-leishmanial chemotherapy.

PMID:
21811648
[PubMed - in process]
2. PLoS One. 2011;6(7):e22463. Epub 2011 Jul 21.

Alba-Domain Proteins of Trypanosoma brucei Are Cytoplasmic RNA-Binding Proteins That Interact with the Translation Machinery.

Mani J, Güttinger A, Schimanski B, Heller M, Acosta-Serrano A, Pescher P, Späth G, Roditi I.

Source

Institute of Cell Biology, University of Bern, Bern, Switzerland.

Abstract

Trypanosoma brucei and related pathogens transcribe most genes as polycistronic arrays that are subsequently processed into monocistronic mRNAs. Expression is frequently regulated post-transcriptionally by cis-acting elements in the untranslated regions (UTRs). GPEET and EP procyclins are the major surface proteins of procyclic (insect midgut) forms of T. brucei. Three regulatory elements common to the 3' UTRs of both mRNAs regulate mRNA turnover and translation. The glycerol-responsive element (GRE) is unique to the GPEET 3' UTR and regulates its expression independently from EP. A synthetic RNA encompassing the GRE showed robust sequence-specific interactions with cytoplasmic proteins in electromobility shift assays. This, combined with column chromatography, led to the identification of 3 Alba-domain proteins. RNAi against Alba3 caused a growth phenotype and reduced the levels of Alba1 and Alba2 proteins, indicative of interactions between family members. Tandem-affinity purification and co-immunoprecipitation verified these interactions and also identified Alba4 in sub-stoichiometric amounts. Alba proteins are cytoplasmic and are recruited to starvation granules together with poly(A) RNA. Concomitant depletion of all four Alba proteins by RNAi specifically reduced translation of a reporter transcript flanked by the GPEET 3' UTR. Pulldown of tagged Alba proteins confirmed interactions with poly(A) binding proteins, ribosomal protein P0 and, in the case of Alba3, the cap-binding protein eIF4E4. In addition, Alba2 and Alba3 partially cosediment with polyribosomes in sucrose gradients. Alba-domain proteins seem to have exhibited great functional plasticity in the course of evolution. First identified as DNA-binding proteins in Archaea, then in association with nuclear RNase MRP/P in yeast and mammalian cells, they were recently described as components of a translationally silent complex containing stage-regulated mRNAs in Plasmodium. Our results are also consistent with stage-specific regulation of translation in trypanosomes, but most likely in the context of initiation.

PMID:
21811616
[PubMed - in process]
3. J Trop Med. 2012;2012:639304. Epub 2011 Jul 21.

Differential Regulation of the Immune Response in the Spleen and Liver of Mice Infected with Leishmania donovani.

Bankoti R, Stäger S.

Source

Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract

Immunity to pathogens requires generation of effective innate and adaptive immune responses. Leishmania donovani evades these host defense mechanisms to survive and persist in the host. A better understanding and identification of mechanisms that L. donovani employs for its survival is critical for developing novel therapeutic interventions that specifically target the parasite. This paper will highlight some of the mechanisms that the parasite utilizes for its persistence and also discuss how the immune response is regulated.

PMID:
21811511
[PubMed - in process]
4. J Trop Med. 2011;2011:876742. Epub 2011 Jul 27.

Toolkit for monitoring and evaluation of indoor residual spraying for visceral leishmaniasis control in the Indian subcontinent: application and results.

Huda MM, Mondal D, Kumar V, Das P, Sharma SN, Das ML, Roy L, Gurung CK, Banjara MR, Akhter S, Maheswary NP, Kroeger A, Chowdhury R.

Source

Laboratory Sciences Division, International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka 1212, Bangladesh.

Abstract

Background. We field tested and validated a newly developed monitoring and evaluation (M&E) toolkit for indoor residual spraying to be used by the supervisors at different levels of the national kala-azar elimination programs in Bangladesh, India and Nepal. Methods. Methods included document analysis, in-depth interviews, direct observation of spraying squads, and entomological-chemical assessments (bioassay, susceptibility test, chemical analysis of insecticide residues on sprayed surfaces, vector density measurements at baseline, and three follow-up surveys). Results. We found that the documentation at district offices was fairly complete; important shortcomings included insufficient training of spraying squads and supervisors, deficient spray equipment, poor spraying performance, lack of protective clothing, limited coverage of houses resulting in low bioavailability of the insecticide on sprayed surfaces, and reduced vector susceptibility to DDT in India, which limited the impact on vector densities. Conclusion. The M&E toolkit is a useful instrument for detecting constraints in IRS operations and to trigger timely response.

PMID:
21811510
[PubMed - in process]
5. RNA. 2011 Aug 2. [Epub ahead of print]

Guide RNA biogenesis involves a novel RNase III family endoribonuclease in Trypanosoma brucei.

Madina BR, Kuppan G, Vashisht AA, Liang YH, Downey KM, Wohlschlegel JA, Ji X, Sze SH, Sacchettini JC, Read LK, Cruz-Reyes J.

Source

Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843, USA.

Abstract

The mitochondrial genome of kinetoplastids, including species of Trypanosoma and Leishmania, is an unprecedented DNA structure of catenated maxicircles and minicircles. Maxicircles represent the typical mitochondrial genome encoding components of the respiratory complexes and ribosomes. However, most mRNA sequences are cryptic, and their maturation requires a unique U insertion/deletion RNA editing. Minicircles encode hundreds of small guide RNAs (gRNAs) that partially anneal with unedited mRNAs and direct the extensive editing. Trypanosoma brucei gRNAs and mRNAs are transcribed as polycistronic precursors, which undergo processing preceding editing; however, the relevant nucleases are unknown. We report the identification and functional characterization of a close homolog of editing endonucleases, mRPN1 (mitochondrial RNA precursor-processing endonuclease 1), which is involved in gRNA biogenesis. Recombinant mRPN1 is a dimeric dsRNA-dependent endonuclease that requires Mg(2+), a critical catalytic carboxylate, and generates 2-nucleotide 3' overhangs. The cleavage specificity of mRPN1 is reminiscent of bacterial RNase III and thus is fundamentally distinct from editing endonucleases, which target a single scissile bond just 5' of short duplexes. An inducible knockdown of mRPN1 in T. brucei results in loss of gRNA and accumulation of precursor transcripts (pre-gRNAs), consistent with a role of mRPN1 in processing. mRPN1 stably associates with three proteins previously identified in relatively large complexes that do not contain mRPN1, and have been linked with multiple aspects of mitochondrial RNA metabolism. One protein, TbRGG2, directly binds mRPN1 and is thought to modulate gRNA utilization by editing complexes. The proposed participation of mRPN1 in processing of polycistronic RNA and its specific protein interactions in gRNA expression are discussed.

PMID:
21810935
[PubMed - as supplied by publisher]
6. Parasitology. 2011 Aug 3:1-10. [Epub ahead of print]

Leishmanicidal effect of Spiranthera odoratíssima (Rutaceae) and its isolated alkaloid skimmianine occurs by a nitric oxide dependent mechanism.

Do s Santos RA, Batista J, Rosa SI, Torquato HF, Bassi CL, Ribeiro TA, DE Sousa PT, Bessera AM, Fontes CJ, DA Silva LE, Piuvezam MR.

Source

Laboratório de Imunofarmacologia, Laboratório de Tecnologia Farmacêutica- LTF, Departamento de Fisiologia e Patologia, Universidade Federal da Paraíba - UFPB, Campus I, João Pessoa, Paraíba, Brazil.

Abstract

SUMMARYLeishmaniasis is one of the neglected diseases. High cost, systemic toxicity, and diminished efficacy due to development of resistance by the parasites has a negative impact on the current treatment options. Thus, the search for a new, effective and safer anti-leishmanial drug becomes of paramount importance. Compounds derived from natural products may be a better and cheaper source in this regard. This study evaluated the in vitro anti-leishmanial activity of Spiranthera odoratíssima (Rutaceae) fractions and isolated compounds, using promastigote and amastigote forms of different Leishmania species. J774 A.1 macrophage was used as the parasite host cell for the in vitro assays. Evaluations of cytoxicity, nitric oxide (NO), interleukin-10 and in silico analysis were carried out. In vitro experiments showed that the fruit hexanic fraction (Fhf) and its alkaloid skimmianine (Skm) have a significant (P<0·001) effect against L. braziliensis. This anti-L. braziliensis activity of Fhf and Skm was due to increased production of NO and attenuation of IL-10 production in the macrophages at concentrations ranging from 1·6 to 40·0 μg/ml. The in silico assay demonstrated significant interaction between Skm and amino acid residues of NOS2. Skm is thus a promising drug candidate for L. braziliensis due to its potent immunomodulatory activity.

PMID:
21810308
[PubMed - as supplied by publisher]
7. Chem Res Toxicol. 2011 Aug 2. [Epub ahead of print]

Synthetic Chromanol Derivatives and their Interaction with Complex III in Mitochondria from Bovine, Yeast and Leishmania.

Monzote L, Stamberg W, Patel A, Rosenau T, Maes L, Cos P, Gille L.

Abstract

Synthetic chromanol derivatives (TMC4O, 6-hydroxy-4,4,7,8-tetramethyl-chroman-4-one; TMC2O, 6-hydroxy-4,4,7,8-tetramethyl-chroman-2-one; Twin, 1,3,4,8,9,11-hexamethyl-6,12-methano-12H-dibenzo[d,g][1,3]dioxocin-2,10-diol) share structural elements with the potent inhibitor of the mitochondrial cytochrome (cyt) bc1 complex stigmatellin. Studies with isolated bovine cyt bc1 complex demonstrated that these compounds partially inhibit the mammalian enzyme. The aim of this work was to comparatively investigate these toxicological aspects of synthetic vitamin E derivatives in mitochondria of different species. The chromanols and atovaquone as reference compound were evaluated for their inhibition of the cyt bc1 activity in mitochondrial fractions from bovine hearts, yeast and Leishmania. In addition, compounds were evaluated in vitro for their inhibitory activity against whole-cell Leishmania and mouse peritoneal macrophages. In these organisms, the chromanols show a species-selective inhibition of the cyt bc1 activity different from atovaquone. While in atovaquone the side chain mediates species-selectivity, the marked differences for TMC2O and TMC4O in cyt bc1 inhibition suggests that direct substitution of the chromanol head group will control selectivity in these compounds. Low micromolar concentrations of TMC2O (IC50 = 9.5 ± 0.5 µM) inhibited the growth of Leishmania and an esterified TMC2CO derivative inhibited the cyt bc1 activity with an IC50 of 4.9 ± 0.9 µM. These findings suggest that certain chromanols exhibit beyond their antioxidative properties also antileishmanial activities and that TMC2O derivatives could be useful towards the development more active antiprotozoal compounds.

PMID:
21809846
[PubMed - as supplied by publisher]
8. Clin Dermatol. 2011 Mar-Apr;29(2):130-9.

Common acrally distributed dermatoses.

Oumeish OY.

Source

Amman Clinic, The Leishmania Project, Prince Rashid Suburb, P.O. Box 65, Amman 11831, Jordan. oumeishdermatol@hotmail.com

Abstract

Acral, referring to the peripheral parts of the body, includes arms and hands, legs and feet, and nails, plus the ears and nose. This contribution, in dealing with the advances in diagnosis of common acrally distributed dermatologic lesions, covers the distribution, localization, shape, and patterns of such lesions. Knowing the morphology of skin lesions is an art that requires not only good observation but also a reasonable classification. For this reason, I have established the "Oumeish classification" to include (1) genodermatoses, (2) physically induced dermatoses, (3) temperature-induced dermatoses, (4) viral disease, (5) vascular entities, (6) neoplasms, and (7) miscellaneous conditions.

Copyright © 2011. Published by Elsevier Inc.

PMID:
21396552
[PubMed - indexed for MEDLINE]
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9. Vet Parasitol. 2011 May 11;177(3-4):199-202. Epub 2011 Feb 15.

Abnormal biochemical and haematological indices in trypanosomiasis as a threat to herd production.

Ohaeri CC, Eluwa MC.

Source

Department of Biological Sciences, Michael Okpara University of Agriculture Umudike, PMB 7267 Umuahia Abia State, Nigeria. ohaeric2000@yahoo.co.uk

Abstract

Blood samples were collected from 46 domestic ruminants comprising of 23 trypanosomiasis infected and 23 uninfected control groups to study some biochemical and haematological effects of trypanosomiasis under natural condition. The effect of trypanosome infection in ruminant animals showed that infected animals had significantly lower (P<0.05) packed cell volume, erythrocyte count and higher (P<0.01) mean cell volumes than uninfected animals. Leucocytosis, reticulocytosis and thrombocytopenia were also observed. The infection also produced a decrease in albumin (P<0.001), significant increase in total protein and bilirubin levels. These changes were not seen in the animals that were not infected. The outcome of the work shows that herds are severely affected by the disease, and therefore supports the prospect of routine check as an epidemiologic tool in trypanosomiasis based on its abnormal effects in blood.

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

PMID:
21382664
[PubMed - indexed for MEDLINE]
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10. PLoS One. 2011 Jan 31;6(1):e15986.

A novel soluble immune-type receptor (SITR) in teleost fish: carp SITR is involved in the nitric oxi de-mediated response to a protozoan parasite.

Ribeiro CM, Bird S, Raes G, Ghassabeh GH, Schijns VE, Pontes MJ, Savelkoul HF, Wiegertjes GF.

Source

Cell Biology and Immunology Group, Department of Animal Sciences, Wageningen University, Wageningen, The Netherlands.

Abstract

BACKGROUND:

The innate immune system relies upon a wide range of germ-line encoded receptors including a large number of immunoglobulin superfamily (IgSF) receptors. Different Ig-like immune receptor families have been reported in mammals, birds, amphibians and fish. Most innate immune receptors of the IgSF are type I transmembrane proteins containing one or more extracellular Ig-like domains and their regulation of effector functions is mediated intracellularly by distinct stimulatory or inhibitory pathways.

METHODOLOGY/PRINCIPAL FINDINGS:

Carp SITR was found in a substracted cDNA repertoire from carp macrophages, enriched for genes up-regulated in response to the protozoan parasite Trypanoplasma borreli. Carp SITR is a type I protein with two extracellular Ig domains in a unique organisation of a N-proximal V/C2 (or I-) type and a C-proximal V-type Ig domain, devoid of a transmembrane domain or any intracytoplasmic signalling motif. The carp SITR C-proximal V-type Ig domain, in particular, has a close sequence similarity and conserved structural characteristics to the mammalian CD300 molecules. By generating an anti-SITR antibody we could show that SITR protein expression was restricted to cells of the myeloid lineage. Carp SITR is abundantly expressed in macrophages and is secreted upon in vitro stimulation with the protozoan parasite T. borreli. Secretion of SITR protein during in vivo T. borreli infection suggests a role for this IgSF receptor in the host response to this protozoan parasite. Overexpression of carp SITR in mouse macrophages and knock-down of SITR protein expression in carp macrophages, using morpholino antisense technology, provided evidence for the involvement of carp SITR in the parasite-induced NO production.

CONCLUSION/SIGNIFICANCE:

We report the structural and functional characterization of a novel soluble immune-type receptor (SITR) in a teleost fish and propose a role for carp SITR in the NO-mediated response to a protozoan parasite.

PMCID: PMC3031540
Free PMC Article
PMID:
21305002
[PubMed - indexed for MEDLINE]
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