Tuesday, October 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 16

1. PLoS One. 2011;6(9):e25381. Epub 2011 Sep 22.

Profiling the Trypanosoma cruzi Phosphoproteome.

Marchini FK, de Godoy LM, Rampazzo RC, Pavoni DP, Probst CM, Gnad F, Mann M, Krieger MA.

Source

Instituto Carlos Chagas, Fiocruz, Curitiba, Paraná, Brazil.

Abstract

Protein phosphorylation is a reversible post-translational modification essential for the regulation of several signal transduction pathways and biological processes in the living cell. Therefore, the identification of protein phosphorylation sites is crucial to understand cell signaling control at the molecular level. Based on mass spectrometry, recent studies have reported the large-scale mapping of phosphorylation sites in various eukaryotes and prokaryotes. However, little is known about the impact of phosphorylation in protozoan parasites. To in depth characterize the phosphoproteome of Trypanosoma cruzi, a parasite of the Kinetoplastida class, protein samples from cells at different phases of the metacyclogenesis - differentiation process of the parasites from non-infective epimastigotes to infective metacyclic trypomastigotes - were enriched for phosphopeptides using TiO(2) chromatography and analyzed on an LTQ-Orbitrap mass spectrometer. In total, 1,671 proteins were identified, including 753 phosphoproteins, containing a total of 2,572 phosphorylation sites. The distribution of phosphorylated residues was 2,162 (84.1%) on serine, 384 (14.9%) on threonine and 26 (1.0%) on tyrosine. Here, we also report several consensus phosphorylation sequence motifs and as some of these conserved groups have enriched biological functions, we can infer the regulation by protein kinases of this functions. To our knowledge, our phosphoproteome is the most comprehensive dataset identified until now for Kinetoplastida species. Here we also were able to extract biological information and infer groups of sites phosphorylated by the same protein kinase. To make our data accessible to the scientific community, we uploaded our study to the data repositories PHOSIDA, Proteome Commons and TriTrypDB enabling researchers to access information about the phosphorylation sites identified here.

PMID:
21966514
[PubMed - in process]
2. PLoS One. 2011;6(9):e25356. Epub 2011 Sep 23.

Differential Modulation of ATP-Induced P2X7-Associated Permeabilities to Cations and Anions of Macrophages by Infection with Leishmania amazonensis.

Marques-da-Silva C, Chaves MM, Rodrigues JC, Corte-Real S, Coutinho-Silva R, Persechini PM.

Source

Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.

Abstract

Leishmania and other parasites display several mechanisms to subvert host immune cell function in order to achieve successful infection. The ATP receptor P2X7, an agonist-gated cation channel widely expressed in macrophages and other cells of the immune system, is also coupled to inflammasome activation, IL-1 beta secretion, production of reactive oxygen species, cell death and the induction of the permeabilization of the plasma membrane to molecules of up to 900 Da. P2X7 receptors can function as an effective microbicidal triggering receptor in macrophages infected with several microorganisms including Mycobacteria tuberculosis, Chlamydia and Leishmania. We have previously shown that its expression is up-regulated in macrophages infected with L.amazonensis and that infected cells also display an increase in P2X7-induced apoptosis and membrane permeabilization to some anionic fluorescent dyes. In an independent study we recently showed that the phenomenon of macrophage membrane permeabilization can involve at least two distinct pathways for cations and anions respectively. Here, we re-addressed the effects of ATP-induced P2X7-associated phenomena in macrophages infected with L.amazonensis and demonstrated that the P2X7-associated dye uptake mechanisms are differentially modulated. While the membrane permeabilization for anionic dyes is up-modulated, as previously described, the uptake of cationic dyes is strongly down-modulated. These results unveil new characteristics of two distinct permeabilization mechanisms associated with P2X7 receptors in macrophages and provide the first evidence indicating that these pathways can be differentially modulated in an immunologically relevant situation. The possible importance of these results to the L.amazonensis escape mechanism is discussed.

PMID:
21966508
[PubMed - in process]
3. PLoS One. 2011;6(9):e25273. Epub 2011 Sep 23.

CYP5122A1, a Novel Cytochrome P450 Is Essential for Survival of Leishmania donovani.

Verma S, Mehta A, Shaha C.

Source

Cell Death and Differentiation Research Laboratory, Centre for Molecular Medicine National Institute of Immunology, New Delhi, India.

Abstract

BACKGROUND:

Cytochrome P450s (CYP450s) are hemoproteins catalysing diverse biochemical reactions important for metabolism of xenobiotics and synthesis of physiologically important compounds such as sterols. Therefore, they are functionally important for survival of invading pathogens. One such opportunistic pathogen Leishmania donovani causes visceral leishmaniasis worldwide, which is an important public health problem due to significant disease burden. The parasite genome database, Gene DB, annotates 3 CYP450s in Leishmania, however, the functional role of cytochrome P450 enzymes in Leishmania spp. remains elusive.

METHODOLOGY/PRINCIPAL FINDINGS:

A CYP450-like gene cloned from Leishmania donovani was identified as a novel CYP450, the CYP5122A1. Upon co-localization with organelle specific markers, CYP5122A1 distribution was shown to be localized in the promastigote ER, mitochondria and the glycosomes. Replacement of one allele of CYP5122A1 with either neomycin or hygromycin gene by homologous recombination in Leishmania promastigotes induced substantial reduction of CYP5122A1 expression. These parasites showed impaired growth, lower mitochondrial Ca(2+) and membrane potential resulting in low ATP generation. Also, these parasites were less infective in vitro and in vivo than their wild-type counterparts as assessed by incubation of Leishmania promastigotes with macrophages in vitro as well as through administration of parasites into hamsters. The HKOs were more susceptible to drugs like miltefosine and antimony, but showed reduced sensitivity to amphotericin B. Removal of two alleles of CYP5122A1 did not allow the parasites to survive. The mutant parasites showed 3.5 times lower ergosterol level as compared to the wild-type parasites when estimated by Gas chromatography/mass spectrometry. Complementation of CYP5122A1 through episomal expression of protein by using pXG-GFP+2 vector partially rescued CYP5122A1 expression and restored ergosterol levels by 1.8 times. Phenotype reversal included restored growth pattern and lesser drug susceptibility.

CONCLUSIONS/SIGNIFICANCE:

In summary, this study establishes CYP5122A1 as an important molecule linked to processes like cell growth, infection and ergosterol biosynthesis in Leishmania donovani.

PMID:
21966477
[PubMed - in process]
4. Indian J Dermatol. 2011 Jul;56(4):428-9.

Auricular enlargement: an atypical presentation of old world cutaneous leishmaniasis.

Robati RM, Qeisari M, Saeedi M, Karimi M.

Source

Skin Research Center, Shahid Beheshti University, M.C. Shohada-e Tajrish Hospital, Tehran, Iran .

Abstract

The auricle is an extremely rare site for cutaneous leishmaniasis (CL) in Old World, which tends to be a benign disease with self-healing small nodules such as the "oriental sore". However, in the New World, there is a type of CL of the ear, named as "chiclero's ulcer" which is caused by Leishmania mexicana. Herein, we describe a case of massive auricular enlargement due to Old World CL.

PMID:
21965856
[PubMed - in process]
5. Mol Biol Cell. 2011 Sep 30. [Epub ahead of print]

ALBA Proteins are Stage-Regulated during Trypanosome Development in the Tsetse Fly and Participate in Differentiation.

Subota I, Rotureau B, Blisnick T, Ngwabyt S, Durand-Dubief M, Engstler M, Bastin P.

Source

Trypanosome Cell Biology Unit, CNRS URA 2581, Parasitology & Mycology Department, Institut Pasteur, Paris, France Department of Cell and Developmental Biology, Theodor-Boveri-Institute, University of Wuerzburg, Wuerzburg, Germany.

Abstract

The protozoan parasite Trypanosoma brucei is responsible for sleeping sickness and alternates between mammal and tsetse fly hosts, where it has to adapt to different environments. In this report, we investigated the role of two members of the ALBA family that encodes hypothetical RNA-binding proteins conserved in most eukaryotes. We show that ALBA3/4 proteins colocalize with the DHH1 RNA-binding protein and with a subset of poly (A+) RNA in stress granules upon starvation. Depletion of ALBA3/4 proteins by RNA interference in the cultured procyclic stage produces cell modifications mimicking several morphogenetic aspects of trypanosome differentiation that usually take place in the fly midgut. A combination of immunofluorescence data and video-microscopy analysis of live trypanosomes expressing endogenously ALBA fused with fluorescent proteins revealed that ALBA3/4 are present throughout the development of the parasite in the tsetse fly, with the striking exception of the transition stages found in the proventriculus region. This involves migration of the nucleus towards the posterior end of the cell, a phenomenon that is perturbed upon forced expression of ALBA3 during the differentiation process, showing for the first time the involvement of an RNA-binding protein in trypanosome development in vivo.

PMID:
21965287
[PubMed - as supplied by publisher]
6. Acta Trop. 2011 Sep 22. [Epub ahead of print]

Transmission of Leishmania infantum MON-98 to hamsters by the bite of Phlebotomus langeroni Nitzulescu (Diptera: Psychodidae).

El Sawaf BM, Doha SA, Imam MI.

Source

Department of Entomology, Faculty of Science, Ain Shams University, Cairo, Egypt.

Abstract

The ability of Phlebotomus langeroni to successfully acquire and transmit Leishmania infantum MON-98 to hamsters was demonstrated. Sand flies and Leishmania both originated from an infantile visceral leishmaniasis focus in El Agamy Egypt. P. langeroni females were infected by feeding on lesions of needle-inoculated hamster and on infected blood suspension using a chick-skin membrane apparatus. Infection rate of sand flies fed on membrane was 88% compared to 7.8% for flies fed on leishmanial lesion. The transmission to hamster took place by the bites of infective flies taking a second blood meal, on the 8th to 10th day post-feeding. Furthermore, successful transmission was by the bites of flies that took no blood or that took partial blood meal. Whereas flies that took partial blood meal were not infective as indicated by dissection. In three hamsters, lesions developed after three months. Leishmania amastigotes were demonstrated from the lesion as well as from the liver and spleen of infected hamsters.

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

PMID:
21964050
[PubMed - as supplied by publisher]
7. Anal Chim Acta. 2011 Oct 31;705(1-2):72-80. Epub 2011 Apr 20.

Non-linear modeling of (1)H NMR metabonomic data using kernel-based orthogonal projections to latent structures optimized by simulated annealing.

Fonville JM , Bylesjö M, Coen M, Nicholson JK, Holmes E, Lindon JC, Rantalainen M.

Source

Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, South Kensington, London SW7 2AZ, UK.

Abstract

Linear multivariate projection methods are frequently applied for predictive modeling of spectroscopic data in metabonomic studies. The OPLS method is a commonly used computational procedure for characterizing spectral metabonomic data, largely due to its favorable model interpretation properties providing separate descriptions of predictive variation and response-orthogonal structured noise. However, when the relationship between descriptor variables and the response is non-linear, conventional linear models will perform sub-optimally. In this study we have evaluated to what extent a non-linear model, kernel-based orthogonal projections to latent structures (K-OPLS), can provide enhanced predictive performance compared to the linear OPLS model. Just like its linear counterpart, K-OPLS provides separate model components for predictive variation and response-orthogonal structured noise. The improved model interpretation by this separate modeling is a property unique to K-OPLS in comparison to other kernel-based models. Simulated annealing (SA) was used for effective and automated optimization of the kernel-function parameter in K-OPLS (SA-K-OPLS). Our results reveal that the non-linear K-OPLS model provides improved prediction performance in three separate metabonomic data sets compared to the linear OPLS model. We also demonstrate how response-orthogonal K-OPLS components provide valuable biological interpretation of model and data. The metabonomic data sets were acquired using proton Nuclear Magnetic Resonance (NMR) spectroscopy, and include a study of the liver toxin galactosamine, a study of the nephrotoxin mercuric chloride and a study of Trypanosoma brucei brucei infection. Automated and user-friendly procedures for the kernel-optimization have been incorporated into version 1.1.1 of the freely available K-OPLS software package for both R and Matlab to enable easy application of K-OPLS for non-linear prediction modeling.

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

PMID:
21962350
[PubMed - in process]
8. Rev Bras Parasitol Vet. 2011 Jul;20(3):228-34.

Phlebotomine sand flies and canine infection in areas of human visceral leishmaniasis, Cuiabá, Mato Grosso.

Mestre GL, Ribeiro AL, Miyazaki RD, Rodrigues JS, Almeida Ado B, Sousa VR, Missawa NA.

Source

Centro de Controle de Zoonoses, Secretaria Municipal de Saúde de Cuiabá,R. Cel. Evaristo da Costa e Silva, 66, Bairro CPA 1,CEP 78055-181, Cuiabá - MT, Brazil. gmestre@brturbo.com.br.

Abstract

Visceral leishmaniasis is a systemic infectious disease that can cause to a severe, potentially life-threatening chronic condition in humans. Risk factors for infection in urban areas have been associated with poor living conditions, the presence of sand fly vectors and infected pets. This study aimed to describe sand fly and canine infection in the neighborhoods of human visceral leishmaniasis occurrence in the city of Cuiabá, Mato Grosso State, central-western Brazil, reported between January 2005 and December 2006. A total of 1,909 sand flies were collected. They were predominantly males and the most frequent species were Lutzomyia cruzi (81.25%), Lutzomyia whitmani (13.88%) and Lutzomyia longipalpis (2.62%). The sand fly density was not significantly correlated with the variation of environmental factors. The prevalence of canine visceral leishmaniasis in the neighborhoods studied was 26.82% and it was found that areas with high density of vectors coincided with areas of high prevalence of dogs and those with the highest rates of human cases. The study of vectors and other potential hosts are essential for a good understanding of visceral leishmaniasis and the related public health concerns, aiming at the prevention and control of leishmaniasis in the city of Cuiabá, Mato Grosso State.

PMID:
21961754
[PubMed - in process]
9. Rev Bras Parasitol Vet. 2011 Jul;20(3):219-22.

Molecular and serological detection of Leishmania spp. in captive wild animals from Ilha Solteira, SP, Brazil.

Jusi MM, Starke-Buzetti WA, Oliveira TM, Tenório Mda S, Sousa Lde O, Machado RZ.

Source

Departamento de Patologia Veterinária,Universidade Estadual Paulista - UNESP, Rod. Prof. Paulo Donato Castellane,s/n, zona rural, CEP 14890-000, Jaboticabal - SP, Brazil. zacarias@fcav.unesp.br.

Abstract

Leishmaniasis is a zoonotic disease that affects 12 million people worldwide. Several mammalian species can serve as a reservoir for this disease. Dogs are the main reservoir for visceral leishmaniasis in urban areas, which has become a serious public health concern in Brazil. The aim of this study was to evaluate the presence of Leishmania spp. in captive wild animals from Ilha Solteira, São Paulo, Brazil. Blood and various tissues samples were collected from animals of five different species: Speothos venaticus, Chrysocyon brachyurus, Cerdocyon thous, Pseudalopex vetulus, and Procyon cancrivorus. Antibodies against Leishmania spp. were detected in three wild canids by indirect fluorescent antibody test (IFAT) and enzyme-linked immunosorbent assay (ELISA). PCR analyses of blood and bone marrow from all animals were negative, but Leishmania DNA was found in the tissues and skin of seropositive animals. Positive PCR samples were also positive for Leishmania donovani complex. Analysis of sequenced PCR products showed similarities with different regions of Leishmania (Leishmania) infantum and Leishmania (Leishmania) chagasi kinetoplastids. Measures to control visceral leishmaniasis in wild animals kept in Brazilian zoos should be established, as no disease control programs are currently available.

PMID:
21961752
[PubMed - in process]
10. Acta Trop. 2011 Sep 16. [Epub ahead of print]

Lutzomyia (Pintomyia) fischeri (Diptera: Psychodidae: Phlebotominae), a probable vector of American Cutaneous Leishmaniasis: Detection of natural infection by Leishmania (Viannia) DNA in specimens from the municipality of Porto Alegre (RS), Brazil, using multiplex PCR assay.

Pita-Pereira DD, Souza GD, Pereira TD, Zwetsch A, Britto C, Rangel EF.

Source

Laboratório de Biologia Molecular e Doenças Endêmicas - IOC, Rio de Janeiro, RJ, Brazil.

Abstract

In order to determine natural Leishmania (Viannia) infection in Lutzomyia (Pintomyia) fischeri, a multiplex PCR methodology coupled to non-isotopic hybridization was adopted for the analysis of sand fly samples collected by CDC light traps in an endemic area of American Cutaneous Leishmaniasis (ACL) in the periurban region of the municipality of Porto Alegre, Rio Grande do Sul State, Brazil. We analyzed by PCR methodology 560 specimens of Lutzomyia (Pintomyia) fischeri (520 females and 40 males). The wild sand flies were grouped into 56 pools (52 females and 4 males) of 10 each, and positive results were detected in 2 of the 52 female pools, representing a minimum infection rate of 0.38% based on the presence of at least 1 infected insect in the pool. This result associated with some local evidence such as anthopophily, spatial distribution in accordance with the transmission area and human case incidence, suggests that L. (P.)fischeri may be considered as a secondary vector of ACL in the studied locality.

Copyright © 2011. Published by Elsevier B.V.

PMID:
21939631
[PubMed - as supplied by publisher]
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