What's new for 'Trypanosomatids' in PubMed

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Sent on Thursday, 2012 April 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 - 8 of 8

1.	PLoS One. 2012;7(4):e35167. Epub 2012 Apr 12. A New Generation of T7 RNA Polymerase-Independent Inducible Expression Plasmids for Trypanosoma brucei. Sunter J, Wickstead B, Gull K, Carrington M. Source Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom. Abstract Expression of transgenes is central to forward and reverse genetic analysis in Trypanosoma brucei. The inducible expression of transgenes in trypanosomes is based on the tetracycline repressor binding to a tetracycline operator to prevent transcription in the absence of tetracycline. The same inducible system is used to produce double-stranded RNA for RNAi knockdown of target genes. This study describes a new plasmid pSPR2.1 that drives consistent high-level expression of tetracycline repressor in procyclic form trypanosomes. A complementary expression plasmid, p3227, was constructed. The major difference between this and current plasmids is the separation of the inducible transgene and selectable marker promoters by the plasmid backbone. The plasmid p3227 was able to support inducible expression in cell lines containing pSPR2.1 as well as the established Lister 427 29-13 cell line. p3666, a derivative of p3227, was made for inducible expression of stem loop RNAi constructs and was effective for knockdown of DRBD3, which had proved problematic using existing RNAi plasmids with head-to-head promoters. The plasmid system was also able to support inducible transgene expression and DRBD3 RNAi knockdown in bloodstream form cells expressing tetracycline repressor from an integrated copy of the plasmid pHD1313.
	PMID: 22511983 [PubMed - in process]

2.	PLoS Pathog. 2012 Apr;8(4):e1002646. Epub 2012 Apr 12. TLR4 and NKT Cell Synergy in Immunotherapy against Visceral Leishmaniasis. Karmakar S, Bhaumik SK, Paul J, De T. Source Division of Infectious Disease and Immunology, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, Kolkata, India. Abstract NKT cells play an important role in autoimmune diseases, tumor surveillance, and infectious diseases, providing in most cases protection against infection. NKT cells are reactive to CD1d presented glycolipid antigens. They can modulate immune responses by promoting the secretion of type 1, type 2, or immune regulatory cytokines. Pathogen-derived signals to dendritic cells mediated via Toll like Receptors (TLR) can be modulated by activated invariant Natural Killer T (iNKT) cells. The terminal β-(1-4)-galactose residues of glycans can modulate host responsiveness in a T helper type-1 direction via IFN-γ and TLRs. We have attempted to develop a defined immunotherapeutic, based on the cooperative action of a TLR ligand and iNKT cell using a mouse model of visceral leishmaniasis. We evaluated the anti-Leishmania immune responses and the protective efficacy of the β-(1-4)-galactose terminal NKT cell ligand glycosphingophospholipid (GSPL) antigen of L. donovani parasites. Our results suggest that TLR4 can function as an upstream sensor for GSPL and provoke intracellular inflammatory signaling necessary for parasite killing. Treatment with GSPL was able to induce a strong effective T cell response that contributed to effective control of acute parasite burden and led to undetectable parasite persistence in the infected animals. These studies for the first time demonstrate the interactions between a TLR ligand and iNKT cell activation in visceral leishmaniasis immunotherapeutic.
	PMID: 22511870 [PubMed - in process]

3.	Mem Inst Oswaldo Cruz. 2012 May;107(3):416-9. The stepwise selection for ketoconazole resistance induces upregulation of C14-demethylase (CYP51) in Leishmania amazonensis. Andrade-Neto VV, Matos-Guedes HL, Gomes DC, Canto-Cavalheiro MM, Rossi-Bergmann B, Torres-Santos EC. Source Laboratório de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro, RJ, Brasil, 21040-900. Abstract Ketoconazole is a clinically safe antifungal agent that also inhibits the growth of Leishmania spp. A study was undertaken to determine whether Leishmania parasites are prone to becoming resistant to ketoconazole by upregulating C14-demethylase after stepwise pharmacological pressure. Leishmania amazonensis promastigotes [inhibitory concentration (IC)50 = 2 µM] were subjected to stepwise selection with ketoconazole and two resistant lines were obtained, La8 (IC50 = 8 µM) and La10 (IC50 = 10 µM). As a result, we found that the resistance level was directly proportional to the C14-demethylase mRNA expression level; we also observed that expression levels were six and 12 times higher in La8 and La10, respectively. This is the first demonstration that L. amazonensis can up-regulate C14-demethylase in response to drug pressure and this report contributes to the understanding of the mechanisms of parasite resistance.
	PMID: 22510839 [PubMed - in process]

4.	Mem Inst Oswaldo Cruz. 2012 May;107(3):402-9. A morphologically distinct Phlebotomus argentipes population from active cutaneous leishmaniasis foci in central Sri Lanka. Ranasinghe S, Maingon RD, Bray DP, Ward RD, Udagedara C, Dissanayake M, Jayasuriya V, Silva NK. Source Department of Parasitology, University of Sri Jayewardenepura, Gangodawila, Nugegoda, Sri Lanka. Abstract Although the reported aetiological agent of cutaneous leishmaniasis (CL) in Sri Lanka is Leishmania donovani, the sandfly vector remains unknown. Ninety-five sandflies, 60 females and 35 males, collected in six localities in the district of Matale, central Sri Lanka, close to current active transmission foci of CL were examined for taxonomically relevant characteristics. Eleven diagnostic morphological characters for female sandflies were compared with measurements described for Indian and Sri Lankan sandflies, including the now recognised Phlebotomus argentipes sensu lato species complex. The mean morphometric measurements of collected female sandflies differed significantly from published values for P. argentipes morphospecies B, now re-identified as Phlebotomus annandalei from Delft Island and northern Sri Lanka, from recently re-identified P. argentipes s.s. sibling species and from Phlebotomus glaucus. Furthermore, analysis of underlying variation in the morphometric data through principal component analysis also illustrated differences between the population described herein and previously recognised members of the P. argentipes species complex. Collectively, these results suggest that a morphologically distinct population, perhaps most closely related to P. glaucus of the P. argentipess. I. species complex, exists in areas of active CL transmission. Thus, research is required to determine the ability of this population of flies to transmit cutaneous leishmaniasis.
	PMID: 22510837 [PubMed - in process]

5.	Mem Inst Oswaldo Cruz. 2012 May;107(3):396-401. Biotic factors and occurrence of Lutzomyia longipalpis in endemic area of visceral leishmaniasis, Mato Grosso do Sul, Brazil. Oliveira EF, Silva EA, Fernandes CE, Paranhos Filho AC, Gamarra RM, Ribeiro AA, Brazil RP, Oliveira AG. Source Faculdade de Medicina Dr Hélio Mandetta. Abstract The relationships between environmental exposure to risk agents and health conditions have been studied with the aid of remote sensing imagery, a tool particularly useful in the study of vegetation cover. This study aims to evaluate the influence of environmental variables on the spatial distribution of the abundance of Lutzomyia longipalpis and the reported canine and human visceral leishmaniasis (VL) cases at an urban area of Campo Grande, state of Mato Grosso do Sul. The sandfly captures were performed in 13 residences that were selected by raffle considering four residences or collection station for buffer. These buffers were generated from the central house with about 50, 100 and 200 m from it in an endemic area of VL. The abundance of sandflies and human and canine cases were georreferenced using the GIS software PCI Geomatica. The normalized difference vegetation index (NDVI) and percentage of land covered by vegetation were the environmental variables extracted from a remote sensing IKONOS-2 image. The average NDVI was considered as the complexity of habitat and the standard deviation as the heterogeneity of habitat. One thousand three hundred sixty-seven specimens were collected during the catch. We found a significant positive linear correlation between the abundance of sandflies and the percentage of vegetation cover and average NDVI. However, there was no significant association between habitat heterogeneity and the abundance of these flies.
	PMID: 22510836 [PubMed - in process]

6.	Mem Inst Oswaldo Cruz. 2012 May;107(3):377-86. Characterization of anti-silencing factor 1 in Leishmania major. Scher R, Garcia JB, Pascoalino B, Schenkman S, Cruz AK. Source Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil, 14049-904. Abstract Anti-silencing factor 1 (ASF1) is a histone chaperone that contributes to the histone deposition during nucleosome assembly in newly replicated DNA. It is involved in chromatin disassembly, transcription activation and in the cellular response to DNA damage. In Leishmania major the ASF1 gene (LmASF1) is located in chromosome 20 and codes for a protein showing 67% of identity with the Trypanosoma brucei TbASF1a. Compared to orthologous proteins, LmASF1 conserves the main residues relevant for its various biological functions. To study ASF1 in Leishmania we generated a mutant overexpressing LmASF1 in L. major. We observed that the excess of LmASF1 impaired promastigotes growth rates and had no impact on cell cycle progress. Differently from yeast, ASF1 overproduction in Leishmania did not affect expression levels of genes located on telomeres, but led to an upregulation of proteins involved in chromatin remodelling and physiological stress, such as heat shock proteins, oxidoreductase activity and proteolysis. In addition, we observed that LmASF1 mutant is more susceptible to the DNA damaging agent, methyl methane sulphonate, than the control line. Therefore, our study suggests that ASF1 from Leishmania pertains to the chromatin remodelling machinery of the parasite and acts on its response to DNA damage.
	PMID: 22510834 [PubMed - in process]

7.	Mem Inst Oswaldo Cruz. 2012 May;107(3):370-6. In vitro evaluation of new terpenoid derivatives against Leishmania infantum and Leishmania braziliensis. Ramírez-Macías I, Marín C, Chahboun R, Olmo F, Messouri I, Huertas O, Rosales MJ, Gutierrez-Sánchez R, Alvarez-Manzaneda E, Sánchez-Moreno M. Source Department of Parasitology, University of Granada, Granada, Spain. Abstract The activity of five (1-5) abietane phenol derivatives against Leishmania infantum and Leishmania braziliensis was studied using promastigotes and axenic and intracellular amastigotes. Infectivity and cytotoxicity tests were performed with J774.2 macrophage cells using Glucantime as a reference drug. The mechanisms of action were analysed by performing metabolite excretion and transmission electron microscopy ultrastructural studies. Compounds 1-5 were more active and less toxic than Glucantime. The infection rates and mean number of parasites per cell observed in amastigote experiments showed that derivatives 2, 4 and 5 were the most effective against both L. infantum and L. braziliensis. The ultrastructural changes observed in the treated promastigote forms confirmed that the greatest cell damage was caused by the most active compound (4). Only compound 5 caused changes in the nature and amounts of catabolites excreted by the parasites, as measured by ¹H nuclear magnetic resonance spectroscopy. All of the assayed compounds were active against the two Leishmania species in vitro and were less toxic in mammalian cells than the reference drug.
	PMID: 22510833 [PubMed - in process]

8.	Bioorg Med Chem Lett. 2011 Dec 1;21(23):7197-200. Epub 2011 Sep 29. Identification of small-molecule inhibitors of Trypansoma cruzi replication. Germain AR, Carmody LC, Dockendorff C, Galan-Rodriguez C, Rodriguez A, Johnston S, Bittker JA, MacPherson L, Dandapani S, Palmer M, Schreiber SL, Munoz B. Source Chemical Biology Platform and Probe Development Center, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Abstract We report the outcome of a high-throughput small-molecule screen to identify novel, nontoxic, inhibitors of Trypansoma cruzi, as potential starting points for therapeutics to treat for both the acute and chronic stages of Chagas disease. Two compounds were identified that displayed nanomolar inhibition of T. cruzi and an absence of activity against host cells at the highest tested dose. These compounds have been registered with NIH Molecular Libraries Program (probes ML157 and ML158). Copyright © 2011 Elsevier Ltd. All rights reserved.
	PMID: 22018462 [PubMed - indexed for MEDLINE]
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