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 Wednesday, 2011 Feb 16
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 12

1.	Indian J Med Res. 2011 Jan;133(1):27-39. Visceral leishmaniasis: Experimental models for drug discovery. Gupta S; Nishi. Division of Parasitology, Central Drug Research Institute (CSIR), Lucknow, India. Abstract Visceral leishmaniasis (VL) or kala-azar is a chronic protozoan infection in humans associated with significant global morbidity and mortality. The causative agent is a haemoflagellate protozoan Leishmania donovani, an obligate intracellular parasite that resides and multiplies within macrophages of the reticulo-endothelial system. Most of the existing anti-leishmanial drugs have serious side effects that limit their clinical application. As an alternate strategy, vaccination is also under experimental and clinical trials. The in vitro evaluation designed to facilitate rapid testing of a large number of drugs has been focussed on the promastigotes milt little attention on the clinically relevant parasite stage, amastigotes. Screening designed to closely reflect the situation in vivo is currently time consuming, laborious, and expensive, since it requires intracellular amastigotes and animal model. The ability to select transgenic Leishmania expressing reporter proteins, such as the green fluorescent proteins (GFP) or the luciferase opened up new possibilities for the development of drug screening models. Many experimental animal models like rodents, dogs and monkeys have been developed, each with specific features, but none accurately reproduces what happens in humans. Available in vitro and in vivo methodologies for antileishmanial drug screening and their respective advantages and disadvantages are reviewed.
	PMID: 21321417 [PubMed - in process]
	Related citations

2.	Proc Natl Acad Sci U S A. 2011 Feb 14. [Epub ahead of print] Trypanosome REH1 is an RNA helicase involved with the 3'-5' polarity of multiple gR NA-guided uridine insertion/deletion RNA editing. Li F, Herrera J, Zhou S, Maslov DA, Simpson L. Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, CA 90095. Abstract Uridine insertion/deletion RNA editing in kinetoplastid mitochondria corrects encoded frameshifts in mRNAs. The genetic information for editing resides in small guide RNAs (gRNAs), which form anchor duplexes just downstream of an editing site and mediate editing within a single editing "block." Many mRNAs require multiple gRNAs; the observed overall 3' to 5' polarity of editing is determined by the formation of upstream mRNA anchors by downstream editing. Hel61, a mitochondrial DEAD-box protein, was previously shown to be involved in RNA editing, but the functional role was not clear. Here we report that down-regulation of Hel61 [renamed REH1 (RNA editing helicase 1)] expression in Trypanosoma brucei selectively affects editing mediated by two or more overlapping gRNAs but has no effect on editing within a single block. Down-regulation produces an increased abundance of the gRNA/edited mRNA duplex for the first editing block of the A6 mRNA. Recombinant REH1 has an ATP-dependent double strand RNA unwinding activity in vitro with a model gRNA-mRNA duplex. These data indicate that REH1 is involved in gRNA displacement either directly by unwinding the gRNA/edited mRNA duplex or indirectly, to allow the 5' adjacent upstream gRNA to form an anchor duplex with the edited mRNA to initiate another block of editing. Purified tagged REH1 is associated with the RNA editing core complex by RNA linkers and a colocalization of REH1, REL1, and two kinetoplast ribosomal proteins with the kinetoplast DNA was observed by immunofluorescence, suggesting that editing, transcription, and translation may be functionally linked.
	PMID: 21321231 [PubMed - as supplied by publisher]
	Related citations

3.	Proc Natl Acad Sci U S A. 2011 Feb 14. [Epub ahead of print] Identification of the meiotic life cycle stage of Trypanosoma brucei in the tsetse fly. Peacock L, Ferris V, Sharma R, Sunter J, Bailey M, Carrington M, Gibson W. School of Biological Sciences, University of Bristol, Bristol BS8 1UG, United Kingdom. Abstract Elucidating the mechanism of genetic exchange is fundamental for understanding how genes for such traits as virulence, disease phenotype, and drug resistance are transferred between pathogen strains. Genetic exchange occurs in the parasitic protists Trypanosoma brucei, T. cruzi, and Leishmania major, but the precise cellular mechanisms are unknown, because the process has not been observed directly. Here we exploit the identification of homologs of meiotic genes in the T. brucei genome and demonstrate that three functionally distinct, meiosis-specific proteins are expressed in the nucleus of a single specific cell type, defining a previously undescribed developmental stage occurring within the tsetse fly salivary gland. Expression occurs in clonal and mixed infections, indicating that the meiotic program is an intrinsic but hitherto cryptic part of the developmental cycle of trypanosomes. In experimental crosses, expression of meiosis-specific proteins usually occurred before cell fusion. This is evidence of conventional meiotic division in an excavate protist, and the functional conservation of the meiotic machinery in these divergent organisms underlines the ubiquity and basal evolution of meiosis in eukaryotes.
	PMID: 21321215 [PubMed - as supplied by publisher]
	Related citations

4.	Mol Cell Biol. 2011 Feb 14. [Epub ahead of print] Epigenetic regulation of transcription and virulence in Trypanosoma cruzi by O-linked thymine glucosylation of DNA. Ekanayake DK, Minning T, Weatherly B, Gunasekera K, Nilsson D, Tarleton R, Ochsenreiter T, Sabatini R. Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA; Center for Tropical and Emerging Global Infectious Diseases and Department of Cellular Biology, University of Georgia, Athens, GA; Institute of Cell Biology, University of Bern, Bern, Switzerland. Abstract Unlike other eukaryotes, the protein coding genes of Trypanosoma cruzi are arranged into large polycistronic gene clusters transcribed by polymerase II (Pol II). Thus, it is thought that trypanosomes rely solely on post-transcriptional processes to regulate gene expression. Here, we show that the glucosylated thymine DNA base (Beta-D-glucosyl hydroxymethyluracil or base J) is present within sequences flanking the polycistronic units (PTU) in T. cruzi. The loss of base J at sites of transcription initiation, via deletion of the two enzymes that regulate J synthesis (JBP1 and JBP2), correlates with an increased rate of Pol II transcription and subsequent genome-wide increase in gene expression. Affected genes include virulence genes and the resulting parasites are defective in host cell invasion and egress. These studies indicate that base J represents an epigenetic factor regulating Pol II transcription initiation in kinetoplastids, and provides the first biological role of the only hyper-modified DNA base in eukaryotes.
	PMID: 21321080 [PubMed - as supplied by publisher]
	Related citations

5.	Vet Parasitol. 2011 Jan 19. [Epub ahead of print] In vitro effect of Aloe vera, Coriandrum sativum and Ricinus communis fractions on Leishmania infantum and on murine monocytic cells. Rondon FC, Bevilaqua CM, Accioly MP, Morais SM, Andrade-Junior HF, Machado LK, Cardoso RP, Almeida CA, Queiroz-Junior EM, Rodrigues AC. Laboratório de Doença Parasitárias/Universidade Estadual do Ceará, Brazil. Abstract In South America, visceral leishmaniasis is a zoonosis caused by the protozoan species Leishmania infantum (syn. L. chagasi) and is primarily transmitted through the bite of the female Lutzomyia longipalpis. Its main reservoir in urban areas is the dog. The application of control measures recommended by health agencies have not achieved significant results in reducing the incidence of human cases, and the lack of effective drugs to treat dogs resulted in the prohibition of this course of action in Brazil. Therefore, it is necessary to search new alternatives for the treatment of canine and human visceral leishmaniasis. The objectives of this study were to evaluate the in vitro effect of fractions from Aloe vera (aloe), Coriandrum sativum (coriander), and Ricinus communis (castor) on promastigotes and amastigotes of L. infantum and to analyze the toxicity against the murine monocytic cells RAW 264.7. To determine the viability of these substances on 50% parasites (IC50), we used a tetrazolium dye (MTT) colorimetric assay (bromide 3-4.5-dimethylthiazol-2-yl-2,5-dephenyltetrazolium), and on amastigotes we performed an in situ ELISA. All fractions were effective against L. infantum promastigotes and did not differ from the positive control pentamidine (p>0.05). However, the R. communis ethyl acetate and chloroform fractions, as well as the C. sativum methanol fraction, were the most effective against amastigotes and did not differ from the positive control amphotericin B (p>0.05). The R. communis ethyl acetate fraction was the least toxic, presenting 83.5% viability of RAW 264.7 cells, which was similar to the results obtained with amphotericin B (p>0.05). Based on these results, we intend to undertake in vivo studies with R. communis ethyl acetate fractions due the high effectiveness against amastigotes and promastigotes of L. infantum and the low cytotoxicity towards murine monocytic cells. Copyright © 2011. Published by Elsevier B.V.
	PMID: 21320755 [PubMed - as supplied by publisher]
	Related citations

6.	Exp Parasitol. 2011 Feb 11. [Epub ahead of print] Effect of the Syn adenium carinatum latex lectin (ScLL) on Leishmania (Leishmania) amazonensis infection in murine macrophages. Afonso-Cardoso SR, Silva CV, Ferreira MS, Souza MA. Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, MG, Brazil. Abstract Anti parasitic effect of a lectin isolated from Synadenium carinatum latex (ScLL) was evaluated against Leishmania (Leishmania) amazonensis promastigotes/amastigotes. Pretreatment of murine inflammatory peritoneal macrophages with ScLL reduced by 65.5 % the association index of macrophages and L. (L) amazonensis promastigotes. Expression of cytokines (IL-12, IL-1 and TNF-α) was detected in infected macrophages pretreated with ScLL (10 μg/mL). ScLL also reduced the growth of L. (L) amazonensis amastigote intracellular forms, showing no in vitro cytotoxic effects in mammalian host cells. ScLL treatment in infected murine inflammatory peritoneal macrophages did not induce nitric oxide production, suggesting that a nitric oxide independent pathway is activated to decrease the number of intracellular Leishmania. Copyright © 2011 Elsevier Inc. All rights reserved.
	PMID: 21320493 [PubMed - as supplied by publisher]
	Related citations

7.	Parasit Vectors. 2011 Feb 14;4(1):19. [Epub ahead of print] Temporal stability of Glossina fuscipes fuscipes populations in Uganda. Echodu R, Beadell JS, Okedi LM, Hyseni C, Aksoy S, Caccone A. Abstract ABSTRACT: BACKGROUND: Glossina fuscipes, a riverine species of tsetse, is the major vector of human African trypanosomiasis (HAT) in sub-Saharan Africa. Understanding the population dynamics, and specifically the temporal stability, of G. fuscipes will be important for informing vector control activities. We evaluated genetic changes over time in seven populations of the subspecies G. f. fuscipes distributed across southeastern Uganda, including a zone of contact between two historically isolated lineages. A total of 667 tsetse flies were genotyped at 16 microsatellite loci and at one mitochondrial locus. RESULTS: Results of an AMOVA indicated that time of sampling did not explain a significant proportion of the variance in allele frequencies observed across all samples. Estimates of differentiation between samples from a single population ranged from approximately 0 to 0.019, using Jost's DEST. Effective population size estimates using momentum-based and likelihood methods were generally large. We observed significant change in mitochondrial haplotype frequencies in just one population, located along the zone of contact. The change in haplotypes was not accompanied by changes in microsatellite frequencies, raising the possibility of asymmetric mating compatibility in this zone. CONCLUSION: Our results suggest that populations of G. f. fuscipes were stable over the 8-12 generations studied. Future studies should aim to reconcile these data with observed seasonal fluctuations in the apparent density of tsetse.
	PMID: 21320301 [PubMed - as supplied by publisher]
	Related citations

8.	Mol Microbiol. 2011 Feb 14. doi: 10.1111/j.1365-2958.2011.07584.x. [Epub ahead of print] Calcineurin is required for Leishmania major stress response pathways and for virulence in the mammalian host. Naderer T, Dandash O, McConville MJ. Department of Biochemistry and Molecular Biology, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, Victoria 3010, Australia. Abstract Leishmania parasites must adapt to elevated temperatures and other environmental stresses during infection of their mammalian hosts. How these environmental cues are sensed is poorly understood. In this study we show that calcium uptake is required for parasite thermotolerance at 34 - 37(o) C. To identify potential down-stream targets of calcium influx, a L. major mutant lacking the essential regulatory subunit (CnB) of the Ca(2+) /calmodulin-dependent serine/threonine-specific phosphatase, calcineurin, was generated. The Δcnb mutant grew as well as wild type parasites at 27(o) C and differentiated normally to infective metacyclic promastigotes. However, Δcnb parasites lost viability when exposed to increased temperature (34°C) and were hypersensitive to endoplasmic reticulum and membrane stress, induced by tunicamycin and inhibitors of sterol and sphingolipid biosynthesis, respectively. Δcnb promastigotes were internalized by macrophages, but their differentiation to the heat adapted amastigote stage was delayed and the resulting parasites failed to proliferate. Strikingly, the Δcnb parasites were completely cleared by susceptible BALB/c mice. Complementation of Δcnb parasites with CnB restored thermotolerance and infectivity in both macrophages and animal models. Our results suggest that Ca(2+) influx and calcineurin signaling are required for both early and long term adaptive parasite responses to environmental stresses encountered in the mammalian host. © 2011 Blackwell Publishing Ltd.
	PMID: 21320183 [PubMed - as supplied by publisher]
	Related citations

9.	Methods Mol Biol. 2011;696:327-37. Distributions of ion series in ETD and CID spectra: making a comparison. Hart SR, Lau KW, Gaskell SJ, Hubbard SJ. Michael Barber Centre for Mass Spectrometry, School of Chemistry, Manchester Interdisciplinary Biocentre, University of Manchester, Manchester, UK. Abstract Databases which capture proteomic data for subsequent interrogation can be extremely useful for our understanding of peptide ion behaviour in the mass spectrometer, leading to novel hypotheses and mechanistic understanding of the underlying mechanisms determining peptide fragmentation behaviour. These, in turn, can be used to improve database searching algorithms for use in automated and unbiased interpretation of peptide product ion spectra. Here, we examine a previously published dataset using our established methods, in order to discover differences in the observation of product ions of different types, following ion activation and unimolecular dissociation either by collisional dissociation or the ion/ion reaction, electron transfer dissociation. Using a target-decoy database searching strategy, a large data set of precursor ions, were confidently predicted as peptide sequence matches (PSMs) at either a 1% or 5% peptide false discovery rate, as reported in our previous study. Using these high quality PSMs, we have conducted a more detailed and novel analysis of the global trends in observed product ions present/absent in these spectra, examining both CID and ETD data. We uncovered underlying trends for an increased propensity for the observation of higher members of the ion series in ETD product ion spectra in comparison to their CID counterparts. Such data-mining efforts will prove useful in the generation of new database searching algorithms which are well suited to the analysis of ETD product ion spectra.
	PMID: 21063958 [PubMed - indexed for MEDLINE]
	Related citations

10.	Exp Parasitol. 2011 Feb;127(2):475-80. Epub 2010 Oct 29. Trypanosoma evansi: immune response and acetylcholinesterase activity in lymphocyte s from infected rats. Da Silva AS, Monteiro SG, Gonçalves JF, Spanevello R, Schmatz R, Oliveira CB, Costa MM, França RT, Jaques JA, Schetinger MR, Mazzanti CM, Lopes ST. Department of Microbiology and Parasitology, Universidade Federal de Santa Maria, Brazil. aleksandro_ss@yahoo.com.br Abstract The existence of cholinergic receptors in the immune system cells is well documented. This study aimed to evaluate the acetylcholinesterase activity (AChE) in lymphocytes from rats infected with Trypanosoma evansi in acute and chronic phase disease. Twenty animals were infected with 10(6) trypomastigotes forms each and 10 were used as negative controls. The two groups of inoculated rats were formed according to the degree of parasitemia and the period post-infection (PI). Group A: rats with 4 days PI and between 24 and 45 parasites/field (1000×); group B: rats with 30 days PI and parasitemia with jagged peaks between 0 and 1 parasites/field; group C: not-infected animals. At 4 days PI (acute phase) and 30 days PI (chronic phase) the rats were anesthetized to collect blood for hemogram and separation of lymphocytes. After separation, the AChE activity was measured in lymphocytes. It was observed that the number of lymphocytes increased significantly in group A compared to group C. The activity of AChE in lymphocytes significantly increased in acute phase and decreased in chronic phase in the infected rats when compared to not-infected (P<0.05). Statistical analysis showed a positive correlation between the number of lymphocytes and AChE activity in lymphocytes in 4 days PI (r(2): 0.59). Therefore, the infection by T. evansi influences AChE activity in lymphocytes of rats indicating changes in the responses of cholinergic system in acute phase, possibly due to immune functions performed by these enzymes. Copyright © 2010 Elsevier Inc. All rights reserved.
	PMID: 21036170 [PubMed - indexed for MEDLINE]
	Related citations