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Sent on Thursday, 2010 Sep 09Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Anal Bioanal Chem. 2010 Sep 8. [Epub ahead of print]Towards an unbiased metabolic profiling of protozoan parasites: optimisation of a Leishmania sampling protocol for HILIC-orbitrap analysis.T'kindt R, Jankevics A, Scheltema RA, Zheng L, Watson DG, Dujardin JC, Breitling R, Coombs GH, Decuypere S.Department of Parasitology, Unit of Molecular Parasitology, Institute of Tropical Medicine, 2000, Antwerp, Belgium. AbstractComparative metabolomics of Leishmania species requires the simultaneous identification and quantification of a large number of intracellular metabolites. Here, we describe the optimisation of a comprehensive metabolite extraction protocol for Leishmania parasites and the subsequent optimisation of the analytical approach, consisting of hydrophilic interaction liquid chromatography coupled to LTQ-orbitrap mass spectrometry. The final optimised protocol starts with a rapid quenching of parasite cells to 0 degrees C, followed by a triplicate washing step in phosphate-buffered saline. The intracellular metabolome of 4 x 10(7) parasites is then extracted in cold chloroform/methanol/water 20/60/20 (v/v/v) for 1 h at 4 degrees C, resulting in both cell disruption and comprehensive metabolite dissolution. Our developed metabolomics platform can detect approximately 20% of the predicted Leishmania metabolome in a single experiment in positive and negative ionisation mode. Figure Final optimized protocol for the study of the intracellular metabolome of Leishmania parasites. Following HILIC-orbitrap analysis of obtained metabolite extracts, 20% of the predicted metabolome is covered, involving metabolites from many different pathways. |
| PMID: 20824428 [PubMed - as supplied by publisher] | |
| 2. | PLoS Negl Trop Dis. 2010 Aug 31;4(8). pii: e810.Functional Genome Annotation by Combined Analysis across Microarray Studies of Trypanosoma brucei.Shateri Najafabadi H, Salavati R.Institute of Parasitology, McGill University, Ste. Anne de Bellevue, Quebec, Canada. AbstractBACKGROUND: Functional annotation of trypanosomatid genomes has been a daunting task due to the low similarity of their genes with annotated genes of other organisms. Three recent studies have provided gene expression profiles in several different conditions and life stages for one of the main disease-causing trypanosomatids, Trypanosoma brucei. These data can be used to study the gene functions and regulatory mechanisms in this organism. METHODOLOGY/PRINCIPAL FINDINGS: Combining the data from three different microarray studies of T. brucei, we show that functional linkages among T. brucei genes can be identified based on gene coexpression, leading to a powerful approach for gene function prediction. These predictions can be further improved by considering the expression profiles of orthologous genes from other trypanosomatids. Furthermore, gene expression profiles can be used to discover potential regulatory elements within 3' untranslated regions. CONCLUSIONS/SIGNIFICANCE: These results suggest that although trypanosomatids do not regulate genes at transcription level, trypanosomatid genes with related functions are coregulated post-transcriptionally via modulation of mRNA stability, implying the presence of complex regulatory networks in these organisms. Our analysis highlights the demand for a thorough transcript profiling of T. brucei genome in parallel with other trypanosomatid genomes, which can provide a powerful means to improve their functional annotation. |
| PMID: 20824174 [PubMed - in process] | |
| 3. | Pediatr Infect Dis J. 2010 Sep 3. [Epub ahead of print]CUMULATIVE CARDIAC TOXICITY OF SODIUM STIBOGLUCONATE AND AMPHOTERICIN B IN TREATMENT OF KALA-AZAR.Maheshwari A, Seth A, Kaur S, Aneja S, Rath B, Basu S, Patel R, Dutta AK.From the Department of Pediatrics, Lady Hardinge Medical College, New Delhi, India. AbstractKala-azar or visceral leishmaniasis is a disseminated protozoal infection caused by parasites of the genus Leishmania (Leishmania donovani in India). Conventional therapy for visceral leishmaniasis continues to be pentavalent antimony (sodium antimony gluconate [SAG]). Amphotericin B is widely used for SAG-unresponsive cases and sometimes even as a first-line drug, especially in endemic areas. With the conventional regimen of SAG, cardiac toxicity has been reported in 8% to 17% of cases with 5% to 7% of them having fatal toxicity. Cardiac toxicity is uncommon with amphotericin B with only few isolated reports. We report some patients with kala-azar in whom coadministration of SAG and amphotericin B led to arrhythmia and sudden death. |
| PMID: 20823781 [PubMed - as supplied by publisher] | |
| 4. | Essays Biochem. 2010 Sep 20;48(1):201-19.Epigenetics and transcriptional control in African trypanosomes.Rudenko G.Division of C ell and Molecular Biology, Sir Alexander Fleming Building, Imperial College, South Kensington, London SW7 2AZ, U.K. AbstractThe African trypanosome Trypanosoma brucei is a unicellular parasite which causes African sleeping sickness. Transcription in African trypanosomes displays some unusual features, as most of the trypanosome genome is transcribed as extensive polycistronic RNA Pol II (polymerase II) transcription units that are not transcriptionally regulated. In addition, RNA Pol I is used for transcription of a small subset of protein coding genes in addition to the rDNA (ribosomal DNA). These Pol I-transcribed protein coding genes include the VSG (variant surface glycoprotein) genes. Although a single trypanosome has many hundreds of VSG genes, the active VSG is transcribed in a strictly monoalleleic fashion from one of approx. 15 telomeric VSG ESs (expression sites). Originally, it was thought that chromatin was not involved in the transcriptional control of ESs; however, this view is now being re-evaluated. It has since been shown that the active ES is depleted of nucleosomes compared with silent ESs. In addition, a number of proteins involved in chromatin remodelling or histone modification and which play a role in ES silencing {including TbISWI [T. brucei ISWI (imitation-switch protein)] and DOT1B} have recently been identified. Lastly, the telomere-binding protein TbRAP1 (T. brucei RAP1) has been shown to establish a repressive gradient extending from the ES telomere end up to the ES promoter. We still need to determine which epigenetic factors are involved in 'marking' the active ES as part of the counting mechanism of monoallelic exclusion. The challenge will come in determining how these multiple regulatory layers contribute to ES control. |
| PMID: 20822495 [PubMed - in process] | |
| 5. | Am J Trop Med Hyg. 2010 Aug;83(2):382-7.Community participation and domiciliary occurrence of infected Meccus longipennis in two Mexican village s in Jalisco state.Brenière SF, Bosseno MF, Gastélum EM, Soto Gutiérrez MM, de Jesús Kasten Monges M, Barraza Salas JH, Romero Paredes JJ, de Jesús Lozano Kasten F.Département Sociétés et Santé, UR 016 Caractérisation et Contrôle des Populations de Vecteurs, Montpellier, France. frederique.breniere@ird.fr AbstractThe entomological features of Chagas disease in two western Mexican villages were analyzed through triatomines collection by the inhabitants and active research in the peridomicile. The inhabitant collections have the following comparable characteristics: 1) Meccus longipennis was the dominant species (> 91%), 2) around 43% of the insects were collected indoors, 3) about 70% of triatomines were adults, 4) cumulated rates of infestation of the dwellings reached 40-50%, 5) the triatomine infection rate by Trypanosoma cruzi was > 50%, and 6) the indoor triatomines frequently feed on humans (range 38.5-56.2%). However, the collection was twice as abundant in the first village and the peridomicile infestation, evaluated by the active collection, reached up to 60% and only 4.9% in the other village. Furthermore, females predominated in the first village, whereas males in the other. The current results allow discussing the course of action to prevent Chagas disease in this region. |
| PMID: 20682887 [PubMed - indexed for MEDLINE] | |
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| 6. | Am J Trop Med Hyg. 2010 Aug;83(2):380-1.Temporal fluctuation of infection with different Trypanosoma cruzi g enotypes in the wild rodent Octodon degus.Campos R, Botto-Mahan C, Ortiz S, Coronado X, Solari A.Departamento de Ciencias Ecológicas, Universidad de Chile, Santiago, Chile. AbstractWe identified and followed-up for two years Octodon degus rodents infected with Trypanosoma cruzi genotypes by using xenodiagnosis with two vector species (Mepraia spinolai and Triatoma infestans), polymerase chain reaction DNA-based detection of insect dejections, Southern blot analysis, and minicircle hybridization with genotype-specific probes. Results show temporal fluctuations of infection with four parasite lineages (TCI, TCII, TCV, and TCVI) in one co-infected O. degus. Results are discussed in the context of parasitemia level and infection control in mammal hosts. |
| PMID: 20682886 [PubMed - indexed for MEDLINE] | |
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| 7. | J Mol Biol. 2010 Jun 25;399(5):696-706. Epub 2010 Apr 24.Mechanism of U-insertion RNA editing in trypanosom e mitochondria: characterization of RET2 functional domains by mutational analysis.Ringpis GE, Stagno J, Aphasizhev R.Department of Microbiology and Molecular Genetics, School of Medicine, University of California Irvine, B240 Medical Sciences I, Irvine, CA 92697, USA. Abstract3'-Terminal uridylyl transferases (TUTases) selectively bind uridine 5'-triphosphate (UTP) and catalyze the addition of uridine 5'-monophosphate to the 3'-hydroxyl of RNA substrates in a template-independent manner. RNA editing TUTase 1 and RNA editing TUTase 2 (RET2) play central roles in uridine insertion/deletion RNA editing, which is an essential part of mitochondrial RNA processing in trypanosomes. Although the conserved N-terminal (catalytic) domain and C-terminal (nucleotide base recognition) domain are readily distinguished in all known TUTases, nucleotide specificity, RNA substrate preference, processivity, quaternary structures, and auxiliary domains vary significantly among enzymes of divergent biological functions. RET2 acts as a subunit of the RNA editing core complex to carry out guide-RNA-dependent U-insertion into mitochondrial mRNA. By correlating mutational effects on RET2 activity as recombinant protein and as RNA editing core complex subunit with RNAi-based knock-in phenotypes, we have assessed the UTP and RNA binding sites in RET2. Here we demonstrate functional conservation of key UTP-binding and metal-ion-coordinating residues and identify amino acids involved in RNA substrate recognition. Invariant arginine residues 144 and 435 positioned in the vicinity of the UTP binding site are critical for RET2 activity on single-stranded and double-stranded RNAs, as well as function in vivo. Recognition of a double-stranded RNA, which resembles a guide RNA/mRNA duplex, is further facilitated by multipoint contacts across the RET2-specific middle domain. |
| PMID: 20417643 [PubMed - indexed for MEDLINE] | |
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