What's new for 'Trypanosomatids' in PubMed

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Sent on Thursday, 2010 Sep 30
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 - 9 of 9

1.	Phytother Res. 2010 Oct;24(10):1468-72. Antiprotozoal activity of drimane and coloratane sesquiterpenes towards Trypanosoma brucei rhodesiense and Plasmodium falciparum in vitro. Wube AA, Bucar F, Gibbons S, Asres K, Rattray L, Croft SL. Department of Pharmacognosy, Institute of Pharmaceutical Sciences, Karl-Franzens University Graz, Universitaetsplatz 4/1, A-8010 Graz, Austria. Abstract The extracts and 12 sesquiterpenes obtained from the East African medicinal plant Warburgia ugandensis Sprague (Canellaceae) were assessed for their antiplasmodial activity against the chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum and antitrypanosomal activity against Trypanosoma brucei rhodesiense. The dichloromethane extract displayed strong antiplasmodial and antitrypanosomal activities with IC(50) values of 8.10 and 1.10 µg/mL against K1 strain of the malaria parasite and STlB900 strain of T. b. rhodesiense, respectively. Among the compounds evaluated for inhibition of trypomastigotes, both drimane and coloratane sesquiterpenes possessing aldehyde groups at positions 8 and 9 were found to show most antitrypanosomal activity with IC(50) values in the range 0.56-6.4 µM. The antiplasmodial assays also revealed that the six coloratane and six drimane sesquiterpenes isolated from this extract exhibited significant antitrypanosomal activity with IC(50) values ranged from 0.45 to ?114 µM. Among the compounds tested against the malarial parasite P. falciparum 11?-hydroxymuzigadiolide (3) was most active with an IC(50) value of 6.40 µM. Copyright © 2010 John Wiley & Sons, Ltd.
	PMID: 20878696 [PubMed - in process]

2.	Korean J Parasitol. 2010 Sep;48(3):245-6. Epub 2010 Sep 15. A case of post kala-azar dermal leishmaniasis in India. Tripathy K, Misra A, Mallik R, Misra D, Rout N, Rath J. Department of Pathology, S.C.B. Medical College, Cuttack, Orissa, India. Abstract Post kala-azar dermal leishmaniasis (PKDL) is a rare disease. This is a solitary case report from Orissa, India. We describe a case of PKDL in a 55-year-old male who presented with multiple nodular lesions over face, trunk, and extremities. The patient had been to an endemic area of kala-azar and had a previous history of leishmaniasis. Fine needle aspiration cytology samples from skin nodules revealed Leishmania amastigotes.
	PMID: 20877504 [PubMed - in process]

3.	J Cell Sci. 2010 Sep 28. [Epub ahead of print] CMF70 is a subunit of the dynein regulatory complex. Kabututu ZP, Thayer M, Melehani JH, Hill KL. Abstract Flagellar motility drives propulsion of several important pathogens and is essential for human development and physiology. Motility of the eukaryotic flagellum requires coordinate regulation of thousands of dynein motors arrayed along the axoneme, but the proteins underlying dynein regulation are largely unknown. The dynein regulatory complex, DRC, is recognized as a focal point of axonemal dynein regulation, but only a single DRC subunit, trypanin/PF2, is currently known. The component of motile flagella 70 protein, CMF70, is broadly and uniquely conserved among organisms with motile flagella, suggesting a role in axonemal motility. Here we demonstrate that CMF70 is part of the DRC from Trypanosoma brucei. CMF70 is located along the flagellum, co-sediments with trypanin in sucrose gradients and co-immunoprecipitates with trypanin. RNAi knockdown of CMF70 causes motility defects in a wild- type background and suppresses flagellar paralysis in cells with central pair defects, thus meeting the functional definition of a DRC subunit. Trypanin and CMF70 are mutually conserved in at least five of six extant eukaryotic clades, indicating that the DRC was probably present in the last common eukaryotic ancestor. We have identified only the second known subunit of this ubiquitous dynein regulatory system, highlighting the utility of combined genomic and functional analyses for identifying novel subunits of axonemal sub-complexes.
	PMID: 20876659 [PubMed - as supplied by publisher]

4.	Mol Cell Biol. 2010 Sep 27. [Epub ahead of print] A TFIIH-associated mediator head is a basal factor of small nuclear spliced leader RNA gene transcription in early-diverged trypanosomes. Lee JH, Cai G, Panigrahi AK, Dunham-Ems S, Nguyen TN, Radolf JD, Asturias FJ, Günzl A. Department of Genetics and Developmental Biology, Department of Molecular, Microbial and Structural Biology, University of Connecticut Health Center, 400 Farmington Avenue, Farmington, CT 06030, USA; Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Seattle Biomedical Research Institute, 307 Westlake Avenue N, Seattle, WA 98109, USA; Department of Medicine and Department of Pediatrics, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA. Abstract Genome annotation suggested that early-diverged kinetoplastids possess a reduced set of basal transcription factors. More recent work, however, on the lethal parasite Trypanosoma brucei identified extremely divergent orthologs of TBP, TFIIA, TFIIB and TFIIH which, together with the small nuclear RNA activating protein complex, form a transcription pre-initiation complex (PIC) at the spliced leader (SL) RNA gene (SLRNA) promoter. The SL RNA is a small nuclear RNA and a trans splicing substrate for the maturation of all pre-mRNAs which is metabolized continuously to sustain gene expression. Here, we identified and biochemically characterized a novel TFIIH-associated protein complex in T. brucei (Med-T) consisting of nine subunits whose amino acid sequences are conserved only among kinetoplastid organisms. Functional analyses in vivo and in vitro demonstrated that the complex is essential for cell viability, SLRNA transcription, and PIC integrity. Molecular structure analysis of purified Med-T and Med-T/TFIIH complexes by electron microscopy revealed that Med-T corresponds to the mediator head module of higher eukaryotes. These data therefore show that mediator is a basal factor for small nuclear SL RNA gene transcription in trypanosomes and that the basal transcription function of mediator head is a characteristic feature of eukaryotes which developed early in their evolution.
	PMID: 20876299 [PubMed - as supplied by publisher]

5.	Dermatol Online J. 2010 Sep 15;16(9):1. Nodular lymphangitis: Report of a case with pres entation of a diagnostic paradigm. Giordano CN, Kalb RE, Brass C, Lin L, Helm TN. University at Buffalo School of Medicine and Biomedical Sciences. Abstract A 54-year-old man with asthma, mitral valve prolapse, and a back injury developed erythematous nodules that progressed along the lymphatic drainage of his right arm. Skin biopsy revealed granulomatous inflammation with microabscess formation. Culture confirmed Mycobacterium marinum infection. The patient was treated with clarithromycin, ethambutol, rifampin, and topical silver sulfadiazine. Oral doxycycline hyclate was later added because of slow healing. Mycobacterium marinum is one of a group of infectious agents that can cause nodular lymphangitis. Sporotrichoid lesions most commonly develop after cutaneous inoculation with Sporothrix schenckii, Leishmania species, Nocardia species, and Mycobacterium marinum. A thorough clinical history and physical examination can narrow the differential diagnosis by eliciting information about the etiologic setting, incubation time, clinical appearance of the lesions, and presence or absence of systemic involvement for each of the causative organisms. Skin biopsy and microbiological tissue cultures are essential for diagnostic confirmation. The differential diagnosis and a suggested diagnostic paradigm will be reviewed.
	PMID: 20875322 [PubMed - in process]

6.	BMC Bioinformatics. 2010 Sep 27;11(1):484. [Epub ahead of print] Protein network prediction and topological analysis in Leishmania major as a tool for drug target selection. Florez AF, Park D, Bhak J, Kim BC, Kuchinsky A, Morris JH, Espinosa J, Muskus C. Abstract ABSTRACT: BACKGROUND: Leishmaniasis is a virulent parasitic infection that causes a worldwide disease burden. Most treatments have toxic side-effects and efficacy has decreased due to the emergence of resistant strains. The outlook is worsened by the absence of promising drug targets for this disease. We have taken a computational approach to the detection of new drug targets, which may become an effective strategy for the discovery of new drugs for this tropical disease. RESULTS: We have predicted the protein interaction network of Leishmania major by using three validated methods: PSIMAP, PEIMAP, and iPfam. Combining the results from these methods, we calculated a high confidence network (confidence score > 0.70) with 1,366 nodes and 33,861 interactions. We were able to predict the biological process for 263 interacting proteins by doing enrichment analysis of the clusters detected. Analyzing the topology of the network with metrics such as connectivity and betweenness centrality, we detected 142 potential drug targets after homology filtering with the human proteome. Further experiments can be done to validate these targets. CONCLUSION: We have constructed the first protein interaction network of the Leishmania major parasite by using a computational approach. The topological analysis of the protein network enabled us to identify a set of candidate proteins that may be both (1) essential for parasite survival and (2) without human orthologs. These potential targets are promising for further experimental validation. This strategy, if validated, may augment established drug discovery methodologies, for this and possibly other tropical diseases, with a relatively low additional investment of time and resources.
	PMID: 20875130 [PubMed - as supplied by publisher]

7.	MLO Med Lab Obs. 2010 Aug;42(8):10-2, 14-5; quiz 16-7. Diseases without borders. Handle exotic diseases with this lab pocket guide. Bersch C, DiRamio D.
	PMID: 20734895 [PubMed - indexed for MEDLINE]
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8.	Cell Tissue Res. 2010 Jul;341(1):173-80. Epub 2010 May 22. Differential apoptosis-like cell death in amastigote and trypomastigote forms from Trypanosoma cruzi-infected heart cells in vitro. De Souza EM, Nefertiti AS, Bailly C, Lansiaux A, Soeiro MN. Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ, Brasil. emello@ioc.fiocruz.br Abstract Apoptosis, type-I of programmed cell death (PCD-I), is not restricted to multicellular organisms since many apoptotic features have been described in different trypanosomatids, including Trypanosoma cruzi. Our present aim was to monitor, by different morphological markers, the occurrence of apoptosis-like death in amastigotes and trypomastigotes of T.cruzi (Y strain) during the infection of heart culture cells. We documented the differential occurrence of PCD-I in amastigotes and trypomastigotes, with distinct death rates noticed between these two parasite-distinct forms. Fluorescence microscopy and flow cytometry analysis using different hall markers of apoptosis (phosphatidylserine exposure, collapse of mitochondrial membrane potential and DNA fragmentation) showed that amastigotes present higher levels of apoptosis-like cell death as compared to trypomastigotes. It is possible that the higher levels of PCD-I in these highly multiplicative forms may contribute to the control of the parasite burden within the host cells. On the other hand, the apoptosis-like occurrence in the infective but non-proliferative stage of the parasite (trypomastigotes) may play a role in parasite evasion mechanisms as suggested for other parasites.
	PMID: 20495825 [PubMed - indexed for MEDLINE]
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9.	Mol Microbiol. 2010 Apr;76(1):78-91. Epub 2010 Feb 10. A high-affinity putrescine-cadaverine transporter from Trypanosoma cruzi. Hasne MP, Coppens I, Soysa R, Ullman B. Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, OR 97239-3098, USA. Abstract Whereas mammalian cells and most other organisms can synthesize polyamines from basic amino acids, the protozoan parasite Trypanosoma cruzi is incapable of polyamine biosynthesis de novo and therefore obligatorily relies upon putrescine acquisition from the host to meet its nutritional requirements. The cell surface proteins that mediate polyamine transport into T. cruzi, as well as most eukaryotes, however, have by-in-large eluded discovery at the molecular level. Here we report the identification and functional characterization of two polyamine transporters, TcPOT1.1 and TcPOT1.2, encoded by alleles from two T. cruzi haplotypes. Overexpression of the TcPOT1.1 and TcPOT1.2 genes in T. cruzi epimastigotes revealed that TcPOT1.1 and TcPOT1.2 were high-affinity transporters that recognized both putrescine and cadaverine but not spermidine or spermine. Furthermore, the activities and subcellular locations of both TcPOT1.1 and TcPOT1.2 in intact parasites were profoundly influenced by extracellular putrescine availability. These results establish TcPOT1.1 and TcPOT1.2 as key components of the T. cruzi polyamine transport pathway, an indispensable nutritional function for the parasite that may be amenable to therapeutic manipulation.
	PMID: 20149109 [PubMed - indexed for MEDLINE]
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