What's new for 'Trypanosomatids' in PubMed

This message contains My NCBI what's new results from the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).
Do not reply directly to this message.

Sender's message:

Sent on Tuesday, 2010 Oct 26
Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
Click here to view complete results in PubMed. (Results may change over time.)
To unsubscribe from these e-mail updates click here.

PubMed Results

Items 1 - 10 of 10

1.	Am J Respir Cell Mol Biol. 2010 Oct 22. [Epub ahead of print] Identification of the Mhc region as an Asthma Susceptibility Locus in Recombinant Congenic Mice. Nawijn MC, Piavaux BJ, Jeurink PV, Gras R, Reinders MA, Stearns T, Foote S, Hylkema MN, Groot PC, Korstanje R, van Oosterhout AJ. Laboratory of Allergology & Pulmonary Diseases, Department of Pathology and Medical Biology, GRIAC Research Institute, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands. Abstract Allergic asthma is a complex disease characterized by airway hyperreactivity (AHR), Th2 driven eosinophilic airway inflammation, high allergen-specific IgE (anti-OVA IgE) levels in serum and airway remodeling. Since asthma susceptibility has a strong genetic component, we aimed to identify new asthma susceptibility genes in the mouse by analyzing the asthma phenotypes of the Leishmania major resistant (lmr) recombinant congenic (RC) strains. The lmr RC strains are derived from C57BL/6 and BALB/c intercrosses and carry congenic loci on chromosome 17 (lmr1) and 9 (lmr2) in both backgrounds. Whereas the lmr2 locus on chromosome 9 only contributes to a small background-specific effect on anti-OVA IgE and AHR, the lmr1 locus on chromosome 17 mediates a strong effect on Th2-driven eosinophilic airway inflammation as well as background-specific effects on anti-OVA IgE and AHR. The lmr1 locus contains almost 600 polymorphic genes. To narrow down this number of candidate genes, we performed genome-wide transcriptional profiling on lung tissue from C.lmr1 RC mice and BALB/c controls. We identify a small number of differentially expressed genes located within the congenic fragment, including a number of Mhc genes, polymorphic between BALB/c and C57Bl/6. The analysis of asthma phenotypes in the C.B10-H2b RC strain, carrying the C57Bl/6 haplotype of the Mhc locus in a BALB/c genetic background, reveals a strikingly similar asthma phenotype compared to C.lmr1, indicating that the differentially expressed genes located within the C.B10-H2b congenic fragment are the most likely candidate genes to contribute to the reduced asthma phenotypes associated with the C57Bl/6 allele of lmr1.
	PMID: 20971879 [PubMed - as supplied by publisher]
	Related citations

2.	Travel Med Infect Dis. 2010 Sep;8(5):305-10. Epub 2010 Oct 12. Rapid detection of human Leishmania infa ntum infection: A comparative field study using the fast agglutination screening test and the direct agglutination test. Akhoundi B, Mohebali M, Babakhan L, Edrissian GH, Eslami MB, Keshavarz H, Malekafzali H. Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, P.O. Box: 14155-6446, Tehran, Iran. Abstract This study aimed to evaluate the performance of a fast agglutination screening test (FAST) for serodiagnosis of human Leishmania infantum infection in Iran. FAST is based on the direct agglutination test (DAT) but combines with a higher parasite concentration and is performed with only one serum dilution. The validity of FAST for the detection of L. infantum infection in the field was compared with the direct agglutination test on 110 confirmed or patients suspected of infection with leishmaniasis, 177 healthy individuals and 41 patients with other infectious diseases who were from northwestern and southern parts of Iran. In this study, we found a 1:1600 cut-off point empirically by seeking the best correlation (90.8) between sera confirmed with visceral leishmaniasis and healthy control sera. A sensitivity of 95.4% (95% CI, 91.4-99.4) and specificity of 88.5% (95% CI, 84.2-92.8) were found with 1:1600 as a cut-off titer when DAT-confirmed cases were compared with the control groups. A good degree of agreement was found between FAST and DAT (90.8%) by Kappa analysis. FAST requires 2 h for reading the results versus the 12-18 h needed for DAT. As FAST is simple, rapid, sensitive and non-invasive and does not require a higher volume of antigens or much expertise, it can be used for screening and serodiagnosis of human L. infantum infection. Copyright © 2010 Elsevier Ltd. All rights reserved.
	PMID: 20971441 [PubMed - in process]
	Related citations

3.	Exp Parasitol. 2010 Oct 21. [Epub ahead of print] Quercetin, a fluorescent bioflavanoid, inhibits Trypanosoma brucei hexokinase 1. Dodson HC, Lyda TL, Chambers JW, Morris MT, Christensen KA, Morris JC. Department of Genetics and Biochemistry. Abstract Hexokinases from the African trypanosome, Trypanosoma brucei, are attractive targets for the development of anti-parasitic drugs, in part because the parasite utilizes glycolysis exclusively for ATP production during the mammalian infection. Here, we have demonstrated that the bioflavanoid quercetin (QCN), a known trypanocide, is a mixed inhibitor of Trypanosoma brucei hexokinase 1 (TbHK1) (IC(50) = 4.1 ± 0.8 μM). Spectroscopic analysis of QCN binding to TbHK1, taking advantage of the intrinsically fluorescent single tryptophan (Trp177) in TbHK1, revealed that QCN quenches emission of Trp177, which is located near the hinge region of the enzyme. ATP similarly quenched Trp177 emission, while glucose had no impact on fluorescence. Supporting the possibility that QCN toxicity is a consequence of inhibition of the essential hexokinase, in live parasites QCN fluorescence localizes to glycosomes, the subcellular home of TbHK1. Additionally, RNAi-mediated silencing of TbHK1 expression expedited QCN induced death, while over-expressing TbHK1 protected trypanosomes from the compound. In summary, these observations support the suggestion that QCN toxicity is in part attributable to inhibition of the essential TbHK1. Copyright © 2010. Published by Elsevier Inc.
	PMID: 20971104 [PubMed - as supplied by publisher]
	Related citations

4.	Travel Med Infect Dis. 2010 Jul;8(4):263-8. Epub 2010 Jun 2. Time to put out the lights on sleeping sickness? Nimmo C. University College London Medical School, Gower Street, London WC1E 6BT, UK. Abstract Sleeping sickness (or Human African Trypanosomiasis, HAT) is a potentially fatal parasitic disease that affects a large proportion of sub-Saharan Africa. It was epidemic in the early 20th century before being nearly eradicated through a variety of control programmes. Despite this, there was a resurgence in the 1980s and 90s following relaxation of these programmes. Recent advances are reversing this trend once more. However, more research is required to improve diagnosis and treatment, and to better understand the epidemiology of HAT if complete eradication is to be achieved in the future. Copyright © 2010 Elsevier Ltd. All rights reserved.
	PMID: 20970729 [PubMed - in process]
	Related citations

5.	Trans R Soc Trop Med Hyg. 2010 Oct 20. [Epub ahead of print] Multi-centric prospective evaluation of rk39 rapid test and direct agglutination test for the diagnosis of visceral leishman iasis in Brazil. de Assis TS, Braga AS, Pedras MJ, Oliveira E, Barral A, de Siqueira IC, Costa CH, Costa DL, Holanda TA, Soares VY, Biá M, Caldas AD, Romero GA, Rabello A. Laboratório de Pesquisas Clínicas, Centro de Pesquisas René Rachou (CPqRR), Fundação Oswaldo Cruz (FIOCRUZ), Belo Horizonte, Minas Gerais, Brazil. Abstract The diagnosis of visceral leishmaniasis (VL) is still a major problem in Brazil and several other countries where the disease is endemic. The use of an easy-to-use and interpret, sensitive, and specific method that requires no complex infrastructure or specialized professionals, such as direct agglutination test (DAT) and the rK39-based rapid immunochromatographic test may enhance the diagnosis of disease. This study evaluated the performance of a rapid test (DiaMed- IT-LEISH(®)) and the DAT for the diagnosis of VL in 213 parasitologically confirmed cases and 119 controls with clinical suspicion of VL and confirmation of another etiology. The sensitivities and specificities of the rapid test were 93% and 97%, respectively and those of the DAT were 90% and 96%, respectively. The positive predictive values of the rapid test and the DAT were 98% and 97%, respectively and the negative predictive values were 89% and 84%, respectively. The Kappa index showed agreement between both methods classified as substantial (0.77). This study showed that the DAT and the rapid test can be used to diagnose VL in Brazil, following a pilot study for implementation of the rapid test in the health services. Copyright © 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.
	PMID: 20970152 [PubMed - as supplied by publisher]
	Related citations

6.	J Struct Biol. 2010 Oct 19. [Epub ahead of print] Structures of a key interaction protein from the Trypanosoma brucei editosome in complex with single domain antibodies. Wu M, Park YJ, Pardon E, Turley S, Hayhurst A, Deng J, Steyaert J, Hol WG. Biomolecular Structure Center, Department of Biochemistry, School of Medicine, University of Washington, Seattle, WA 98195, USA. Abstract Several major global diseases are caused by single-cell parasites called trypanosomatids. These organisms exhibit many unusual features including a unique and essential U-insertion-deletion RNA editing process in their single mitochondrion. Many key RNA editing steps occur in ∼ 20S editosomes, which have a core of 12 proteins. Among these, the "interaction protein" KREPA6 performs a central role in maintaining the integrity of the editosome core and also binds to ssRNA. The use of llama single domain antibodies (VHH domains) accelerated crystal growth of KREPA6 from Trypanosoma brucei dramatically. All three structures obtained are heterotetramers with a KREPA6 dimer in the center, and one VHH domain bound to each KREPA6 subunit. Two of the resultant heterotetramers use complementarity determining region 2 (CDR2) and framework residues to form a parallel pair of beta strands with KREPA6 - a mode of interaction not seen before in VHH domain-antigen complexes. The third type of VHH domain binds in a totally different manner to KREPA6. Intriguingly, while KREPA6 forms tetramers in solution adding either one of the three VHH domains results in the formation of a heterotetramer in solution, in perfect agreement with the crystal structures. Biochemical solution studies indicate that the C-terminal tail of KREPA6 is involved in the dimerization of KREPA6 dimers to form tetramers. The implications of these crystallographic and solution studies for possible modes of interaction of KREPA6 with its many binding partners in the editosome are discussed. Copyright © 2010. Published by Elsevier Inc.
	PMID: 20969962 [PubMed - as supplied by publisher]
	Related citations

7.	Free Radic Biol Med. 2010 Oct 19. [Epub ahead of print] Functional characterization of methionine sulfoxide reductase A from Trypanosoma spp. Arias DG, Cabeza MS, Erben ED, Carranza PG, Lujan HD, Iñón MT, Iglesias AA, Guerrero SA. Instituto de Agrobiotecnología del Litoral, UNL-CONICET, Santa Fe, (3000), Argentina. Abstract Methionine is an amino acid susceptible to be oxidized to methionine sulfoxide (MetSO). The reduction of MetSO to methionine is catalyzed by methionine sulfoxide reductase (MSR), an enzyme present in almost all organisms. In trypanosomatids, the study of antioxidant systems has been mainly focused in the involvement of trypanothione, a specific redox component for these organisms. However, no information is available concerning mechanisms for repairing oxidized proteins, which would be relevant for survival of these pathogens in the different stages of their life cycle. We report the molecular cloning of three genes codifying for putative A-type MSR in trypanosomatids. The genes were expressed in Escherichia coli, and the corresponding recombinant proteins were purified and functionally characterized. The enzymes were specific for the L-Met(S)SO reduction, using Trypanosomacruzi tryparedoxin I as reducing substrate. Each enzyme migrated in electrophoresis with particular profiles migration after differences they exhibit in superficial charge. The in vivo presence of the enzymes was evidenced by immunological detection in replicative stages of T. cruzi and Trypanosoma brucei. Results support the occurrence of a metabolic pathway in Trypanosoma spp, involved in the critical function of repairing oxidized macromolecules. Copyright © 2010. Published by Elsevier Inc.
	PMID: 20969952 [PubMed - as supplied by publisher]
	Related citations

8.	Mol Microbiol. 2010 Nov;78(3):757-69. doi: 10.1111/j.1365-2958.2010.07368.x. Epub 2010 Sep 24. Mitochondrial translation is essential in bloodstream forms of Trypanosoma brucei. Cristodero M, Seebeck T, Schneider A. Department of Chemistry and Biochemistry, University of Bern, Freiestr. 3, CH-3012 Bern, Switzerland Institute of Cell Biology, University of Bern, Baltzerstrasse 4, CH-3012 Bern, Switzerland. Abstract The parasitic protozoa Trypanosoma brucei has a complex life cycle. Oxidative phosphorylation is highly active in the procyclic form but absent from bloodstream cells. The mitochondrial genome encodes several gene products that are required for oxidative phosphorylation, but it completely lacks tRNA genes. For mitochondrial translation to occur, the import of cytosolic tRNAs is therefore essential for procyclic T. brucei. Whether the same is true for the bloodstream form has not been studied so far. Here we show that the steady-state levels of mitochondrial tRNAs are essentially the same in both life stages. Editing of the imported tRNA(Trp) also occurs in both forms as well as in mitochondria of Trypanosoma evansi, which lacks a genome and a translation system. These results show that mitochondrial tRNA import is a constitutive process that must be mediated by proteins that are expressed in both forms of the life cycle and that are not encoded in the mitochondrial genome. Moreover, bloodstream cells lacking either mitochondria-specific translation elongation factor Tu or mitochondrial tryptophanyl-tRNA synthetase are not viable indicating that mitochondrial translation is also essential in this stage. Both of these proteins show trypanosomatid-specific features and may therefore be excellent novel drug targets. © 2010 Blackwell Publishing Ltd.
	PMID: 20969649 [PubMed - in process]
	Related citations

9.	Acta Cytol. 2010 Sep-Oct;54(5):743-6. Visceral leishmaniasis in a case of acute lymphoblastic leukemia at both remission and relapse, diagnosed by bone marrow aspiration. Daneshbod Y, Dehghani SJ, Nikzad M, Daneshbod K.
	PMID: 20968169 [PubMed - in process]
	Related citations

10.	Antioxid Redox Signal. 2010 Mar 15;12(6):787-92. Cloning, expression, and characterization of a dithiol glutaredoxin from Trypanosoma cruzi. Marquez VE, Arias DG, Piattoni CV, Robello C, Iglesias AA, Guerrero SA. Instituto de Agrobiotecnología del Litoral, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral., Ciudad Universitaria-Paraje El Pozo, S3000ZAA Santa Fe, Argentina. Abstract Glutaredoxins play an important role in cellular functionality. A putative dithiol glutaredoxin is encoded in the genome of Trypanosoma cruzi. We cloned the gene and obtained the recombinant protein, which behaved as a typical thioltransferase. Activity was variable and dependent on the nature of reducer or oxidant agent used, or both. Epimastigote extracts exhibited similar activity, suggesting the occurrence of the protein in the parasite. Results support a redox scenario in T. cruzi, with glutaredoxin being involved mainly in reduction of glutathione disulfide as well as in deglutathionylation of target proteins.
	PMID: 19769456 [PubMed - indexed for MEDLINE]
	Related citations