What's new for 'Trypanosomatids' in PubMed

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Sent on Friday, 2010 Jul 16
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 11

1.	J Clin Microbiol. 2010 Jul 14. [Epub ahead of print] Comparison of Leishmania OligoC-TesT PCR with conventional and real-time PCR for the detection of canine Leishmania infection. Carson C, Quinnell RJ, Holden J, Garcez LM, Deborggraeve S, Courtenay O. Populations and Disease Research Group, Department of Biological Sciences, University of Warwick, Coventry, UK; Institute of Integrative and Comparative Biology, University of Leeds, Leeds, UK; Departamento de Parasitologia, Instituto Evandro Chagas, Fundação Nacional de Saude, Belém, Brazil; Department of Parasitology, Institute of Tropical Medicine, Antwerp, Belgium. Abstract There is a need for standardization and simplification of the existing methods for molecular detection of Leishmania infantum in the canine reservoir host. The commercially available OligoC-TesT kit incorporates standardized PCR reagents with rapid oligochromatographic dipstick detection of PCR products, and is highly sensitive in humans, but not yet independently validated in dogs. Here we compare the sensitivity of the OligoC-TesT with that of nested kinetoplast DNA (kDNA) PCR, nested internal transcribed spacer-1 (ITS-1) PCR, and a PCR/hybridization protocol, in longitudinal naturally infected canine bone marrow samples for which parasite burdens were measured by real-time quantitative PCR (qPCR). Sensitivity of the OligoC-TesT in infected dogs was 70% (95% C.I. 63-78%), similar to that of kDNA PCR (72%; 95% C.I. 65-80%; P=0.69), but significantly greater than PCR/hybridization (61%; 95% C.I. 53-69%; P=0.007) and ITS-1 nested PCR (54%; 95% C.I. 45-62%; P<0.001); real-time qPCR had the highest sensitivity (91%; 95% C.I. 85-95%; P<0.001). OligoC-TesT sensitivity was greater in polysymptomatic and oligosymptomatic dogs compared to asymptomatic dogs (93%, 74%, and 61%, respectively; P=0.005), a trend also observed in the other qualitative PCR methods tested (P</=0.05). Test positivity increased with increasing parasite burden measured by real-time qPCR: OligoC-TesT and kDNA PCR detected 100% and 99% of positive samples when parasite burden exceeded 74 and 49 parasites/ml, respectively. The OligoC-TesT has high sensitivity for detection of canine Leishmania infections; ease of operation and interpretation are further advantages for veterinary diagnostic laboratories, and for large-scale survey work in developing countries.
	PMID: 20631112 [PubMed - as supplied by publisher]

2.	BMC Int Health Hum Rights. 2010 Jul 14;10(1):20. [Epub ahead of print] One step forward, one step sideways? Expanding research capacity for neglected diseases. Lexchin J. Abstract ABSTRACT: BACKGROUND: There is general agreement, including from the pharmaceutical industry, that current market based methods of generating research into the development of pharmaceutical products that are relevant for developing countries do not work. This conclusion is relevant not just for the most neglected diseases such as leishmaniasis but even for global diseases such as cancer and cardiovascular disease. DISCUSSION: Stimulating research will mean overcoming barriers such as patent thickets, poor coordination of research activities, exclusive licensing of new technologies by universities and the structural problems that inhibit conducting appropriate clinical trials in developing countries. In addition, it is necessary to ensure that the priorities for research reflect the needs of developing countries and not just donors. This article will explore each of these issues and then look at three emerging approaches to stimulating research -paying for innovation, priority review sales or vouchers and public-private partnerships, - and evaluate their strengths and weaknesses. SUMMARY: All of the stakeholders agree that there is a pressing need for a major expansion in the level of R&D. Whatever that new model turns out to be, it will have to deal with the 5 barriers outlined in this paper. Finally, none of the three proposals considered here for expanding research is free from major limitations.
	PMID: 20630063 [PubMed - as supplied by publisher]

3.	FEBS J. 2010 Jul 12. [Epub ahead of print] Protein and mRNA content of TcDHH1-containing mRNPs in Trypanosoma cruzi. Holetz FB, Alves LR, Probst CM, Dallagiovanna B, Marchini FK, Manque P, Buck G, Krieger MA, Correa A, Goldenberg S. Instituto Carlos Chagas/FIOCRUZ, Curitiba, Brazil. Abstract In trypanosomatids, the regulation of gene expression occurs mainly at the post-transcriptional level. Previous studies have revealed nontranslated mRNA in the Trypanosoma cruzi cytoplasm. Previously, we have identified and cloned the TcDHH1 protein, a DEAD box RNA helicase. It has been reported that Dhh1 is involved in multiple RNA-related processes in various eukaryotes. It has also been reported to accumulate in stress granules and processing bodies of yeast, animal cells, Trypanosoma brucei and T. cruzi. TcDHH1 is localized to discrete cytoplasmic foci that vary depending on the life cycle status and nutritional conditions. To study the composition of mRNPs containing TcDHH1, we carried out immunoprecipitation assays with anti-TcDHH1 using epimastigote lysates. The protein content of mRNPs was determined by MS and pre-immune serum was used as control. We also carried out a ribonomic approach to identify the mRNAs present within the TcDHH1 immunoprecipitated complexes. For this purpose, competitive microarray hybridizations were performed against negative controls, the nonprecipitated fraction. Our results showed that mRNAs associated with TcDHH1 in the epimastigote stage are those mainly expressed in the other forms of the T. cruzi life cycle. These data suggest that mRNPs containing TcDHH1 are involved in mRNA metabolism, regulating the expression of at least epimastigote-specific genes. Structured digital abstract * MINT-7909478: DHH1 (uniprotkb:Q4DIE1) physically interacts (MI:0915) with PABP2 (uniprotkb:Q27335) by anti bait coimmunoprecipitation (MI:0006) * MINT-7909338: DHH1 (uniprotkb:Q4DIE1) physically interacts (MI:0914) with ATP-dependent DEAD/H RNA helicase, putative (uniprotkb:Q4DIE1), Actin, putative (uniprotkb:Q4D7A6), Actin, putative (uniprotkb:Q4CLA9), Chaperonin HSP60, mitochondrial (uniprotkb:Q4DYP6), ATP-dependent Clp protease subunit, heat shock protein 100 (HSP100), putative (uniprotkb:Q4CNM5), Elongation factor 2, putative (uniprotkb:Q4D5X0), Elongation factor 1-alpha (EF-1-alpha), putative (uniprotkb:Q4CU73), Heat shock protein 85, putative (uniprotkb:Q4CQS6), Glutamate dehydrogenase, putative (uniprotkb:Q4DWV8), Putative uncharacterized protein (uniprotkb:Q4CNI8), 40S ribosomal protein S11, putative (uniprotkb:Q4CRH9), Sterol 24-c-methyltransferase, putative (uniprotkb:Q4CMB7), Heat shock protein 70 (HSP70), putative (uniprotkb:Q4DTM9), Glutamate dehydrogenase, putative (uniprotkb:Q4D5C2) and Calpain-like cysteine peptidase, putative (uniprotkb:Q4CYU3) by anti bait coimmunoprecipitation (MI:0006) * MINT-7909469: DHH1 (uniprotkb:Q4DIE1) physically interacts (MI:0915) with PABP1 (uniprotkb:Q4E4I9) by anti bait coimmunoprecipitation (MI:0006).
	PMID: 20629747 [PubMed - as supplied by publisher]

4.	PLoS Pathog. 2010 Jul 8;6(7):e1000992. TOPO3alpha Influences Antigenic Variation by Monitoring Expression-Site-Associated VSG Switching in Trypanosoma brucei. Kim HS, Cross GA. Laboratory of Molecular Parasitology, The Rockefeller University, New York, New York, United States of America. Abstract Homologous recombination (HR) mediates one of the major mechanisms of trypanosome antigenic variation by placing a different variant surface glycoprotein (VSG) gene under the control of the active expression site (ES). It is believed that the majority of VSG switching events occur by duplicative gene conversion, but only a few DNA repair genes that are central to HR have been assigned a role in this process. Gene conversion events that are associated with crossover are rarely seen in VSG switching, similar to mitotic HR. In other organisms, TOPO3alpha (Top3 in yeasts), a type IA topoisomerase, is part of a complex that is involved in the suppression of crossovers. We therefore asked whether a related mechanism might suppress VSG recombination. Using a set of reliable recombination and switching assays that could score individual switching mechanisms, we discovered that TOPO3alpha function is conserved in Trypanosoma brucei and that TOPO3alpha plays a critical role in antigenic switching. Switching frequency increased 10-40-fold in the absence of TOPO3alpha and this hyper-switching phenotype required RAD51. Moreover, the preference of 70-bp repeats for VSG recombination was mitigated, while homology regions elsewhere in ES were highly favored, in the absence of TOPO3alpha. Our data suggest that TOPO3alpha may remove undesirable recombination intermediates constantly arising between active and silent ESs, thereby balancing ES integrity against VSG recombination.
	PMID: 20628569 [PubMed - in process]
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5.	Bioorg Med Chem. 2010 May 7. [Epub ahead of print] Synthesis, structural elucidation and in vitro antiparasitic activity against Trypanosoma cruzi and Leishmania chagasi parasites of novel tetrahydro-1-benzazepine derivatives. Gómez-Ayala S, Castrillón JA, Palma A, Leal SM, Escobar P, Bahsas A. Laboratorio de Síntesis Orgánica, Escuela de Química, Universidad Industrial de Santander, A. A. 678, Bucaramanga, Santander, Colombia. Abstract Forty six new 1,4-epoxy-2-exo-aryl- and cis-2-aryl-4-hydroxytetrahydro-1-benzazepine derivatives were synthesized and fully characterized. All compounds were tested in vitro against both Trypanosoma cruzi and Leishmania chagasi parasites and also for cytotoxicity using Vero and THP-1 mammalian cell lines. Many of the evaluated compounds showed remarkable activity against the epimastigote and intracellular amastigote forms of T. cruzi, with IC(50) values comparable with that of control drug nifurtimox, a nitrofuran derivative currently used in the treatment of Chagas' disease. Other derivatives were found to have good activity against L. chagasi promastigotes, with low toxicity against the mammalian cells, but neither of them was active on intracellular amastigotes of L. chagasi infecting THP-1 macrophages. Copyright © 2010 Elsevier Ltd. All rights reserved.
	PMID: 20627590 [PubMed - as supplied by publisher]
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6.	Vet Parasitol. 2010 May 19. [Epub ahead of print] Canine leishmaniasis in Algeria: True prevalence and diagnostic test characteristics in groups of dogs of different functio nal type. Adel A, Saegerman C, Speybroeck N, Praet N, Victor B, De Deken R, Soukehal A, Berkvens D. BP 179 Cité Malki Ben Aknoun, Alger, Algeria; University of Liege, Faculty of Veterinary Medicine, Department of Infectious and Parasitic Diseases, Epidemiology and Risk Analysis Applied to Veterinary Sciences, Boulevard de Colonster, 20, B43b, B-4000 Liege, Belgium; Institute of Tropical Medicine, Department of Animal Health, Nationalestraat 155, B-2000 Antwerp, Belgium. Abstract A Bayesian approach was used to assess the prevalence of Canine leishmaniasis and evaluate three serological diagnostic tests: indirect fluorescent antibody test (IFAT), direct agglutination test, and particle gel immuno-assay (PaGIA) for Canine leishmaniasis (CL) in Algiers. Four hundred and sixty-two dogs were involved in this study and divided in four groups according to their functional type: stray dogs, farm dogs, national guard dogs and pet dogs. The stray dog group showed the highest prevalence of leishmaniasis (11.7%), followed by the national guard dogs (9.7%) and the farm dogs (5.9%). IFAT was shown to be the most sensitive test in all groups. However, IFAT specificity was considerably lowered in the farm dog group: 65.2% versus 94.5% for the stray dogs. A considerable drop in PaGIA specificity was noted in the stray dogs group. The results of the current study demonstrate the variability of test characteristics in different situations and underline the danger of using standard values, without verifying their appropriateness for the specific purposes. Copyright © 2010 Elsevier B.V. All rights reserved.
	PMID: 20627416 [PubMed - as supplied by publisher]
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7.	J Neuroimmunol. 2010 Jun 4. [Epub ahead of print] CD200 receptors are differentially expressed and modulated by minocycline in the brain during Trypanosoma brucei infection. Masocha W. Department of Applied Therapeutics, Faculty of Pharmacy, Kuwait University, Kuwait. Abstract Infection with Trypanosoma brucei, which causes African trypanosomiasis, activates microglia, which are constitutively maintained in a quiescent state through CD200-CD200 receptor interactions. C57BL/6 mice have one inhibitory receptor, CD200R and three activating members, CD200 receptor-like (RL)a-c. Infection increased MAC-1 (microglia marker), CD200RLa and CD200RLb, but not CD200, CD200R or CD200RLc, transcript levels in the brains. Minocycline treatment inhibited the infection-induced elevation of MAC-1 and CD200RLa transcripts, but had no significant effect on CD200 or the other receptors. This suggests that CD200RLa might play a role in microglia/macrophage activation during trypanosome infection. Copyright © 2010 Elsevier B.V. All rights reserved.
	PMID: 20627327 [PubMed - as supplied by publisher]
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8.	J Struct Biol. 2010 Jul 10. [Epub ahead of print] Solution structure and dynamics of ADF/cofilin from Leishmania donovani. Pathak PP, Pulavarti SV, Jain A, Sahasrabuddhe AA, Gupta CM, Arora A. Molecular and Structural Biology Division, Central Drug Research Institute, Lucknow - 226 001, India. Abstract Leishmania donovani ADF/cofilin (LdCof) is a novel member of ADF/cofilin family. LdCof depolymerizes, but does not co-sediment with, rabbit muscle actin filaments. Its F-actin depolymerizing activity is pH independent. Further, it possesses weak F-actin severing activity. In order to better understand its characteristic properties, we have determined the solution NMR structure of LdCof and have analyzed protein backbone dynamics from (15)N-relaxation measurements. The structure of LdCof possesses a conserved ADF/cofilin fold with a central mixed beta-sheet consisting of six beta-strands which is surrounded by five alpha-helices. LdCof structure has conserved G/F-actin binding site, and consists of the characteristic long kinked alpha-helix (alpha3) and it binds to rabbit muscle ADP-G-actin with 1:1 stoichiometry (K(d) approximately 0.2 muM). The F-actin binding site is not well formed and analysis of (15)N-relaxation data shows that residues in the beta4-beta5 loop region and C-terminal are relatively flexible, which seems to be a determinant for the low F-actin severing activity of LdCof. Copyright © 2010. Published by Elsevier Inc.
	PMID: 20627129 [PubMed - as supplied by publisher]
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9.	Parasite Immunol. 2010 Aug;32(8):599-606. Host and parasite genomics, an Australasian perspective. Peacock C. Discipline of Microbiology and Immunology, School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, Crawley, WA, Australia and Telethon Institute for Child Health Research, Subiaco, WA, Australia. Abstract The last decade has seen rapid advances in the genetic technology that is allowing researchers to examine host-pathogen interactions at a whole organism level. The advent of 'affordable' post-genomic technology has opened up a world of proteomic, transcriptomic and metabolomic methodologies that have been utilized by research groups in the Australasian region to examine the hosts' response to parasitic infections. Significant contributions have been made to many areas of parasitic infections with particular strengths being in malaria vaccine development, genetic susceptibility to leishmaniasis, genomic and proteomic analysis of schistosomiasis and genetic determination of resistance to helminthes in domestic animals. This review highlights some of these studies that have made significant contributions to our knowledge of the pathogenesis of parasitic diseases with a particular emphasis placed on studies reported in the last couple of years.
	PMID: 20626815 [PubMed - in process]
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10.	Southeast Asian J Trop Med Public Health. 2010 Jan;41(1):1-12. Awareness about kala-azar disease and related preventive attitudes and practices in a highly endemic rural area of India. Siddiqui NA, Kumar N, Ranjan A, Pandey K, Das VN, Verma RB, Das P. Rajendra Memorial Research Institute of Medical Sciences (ICMR), Agam-Kuan, Patna, Bihar, India. niyamatalisiddiqui@yahoo.com Abstract This study was undertaken to assess the extent of community awareness and related practices about kala-azar undertaken by them to control the disease, in an highly endemic focus of Bihar, India. A household-based cross-sectional knowledge, attitude, and practices (KAP) survey consisting of quantitative components on knowledge, attitude, and practices concerning kala-azar was administered to heads-of-household through a semi-structured questionnaire. Data indicated that 61% respondents were illiterate, 4% had correct knowledge that sandfly bites caused kala-azar, 26% do not know any specific transmission agents for kala-azar. A majority (72%) of respondents were not able to recognize sandfly, 33% had no specific knowledge about the symptoms. All of them (100%) believed that this disease could affect his or her family income. Nearly all (95%) were positive that the kala-azar cases could be reduced with implementation of proper health measures. A few (11%) suggested isolation of patients to avoid contacting kala-azar while a high proportion (93%) of respondents favored specific allopathic medicine, and a majority (72%) favored the utilization of the services offered by primary health centers or government hospitals. Just over half (66%) of the respondents were not using any prevention measures to avoid contacting disease. These results could prove to be useful for health planners in developing suitable control strategies.
	PMID: 20578475 [PubMed - indexed for MEDLINE]
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