What's new for 'Trypanosomatids' in PubMed

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Sent on Thursday, 2010 May 06
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 - 5 of 5

1.	PLoS Pathog. 2010 Apr 29;6(4):e1000871. Keratinocytes determine Th1 immunity during early experimental leishmaniasis. Ehrchen JM, Roebrock K, Foell D, Nippe N, von Stebut E, Weiss JM, Münck NA, Viemann D, Varga G, Müller-Tidow C, Schuberth HJ, Roth J, Sunderkötter C. Institute of Immunology, University of Muenster, Muenster, Germany. Abstract Experimental leishmaniasis is an excellent model system for analyzing Th1/Th2 differentiation. Resistance to Leishmania (L.) major depends on the development of a L. major specific Th1 response, while Th2 differentiation results in susceptibility. There is growing evidence that the microenvironment of the early affected tissue delivers the initial triggers for Th-cell differentiation. To analyze this we studied differential gene expression in infected skin of resistant and susceptible mice 16h after parasite inoculation. Employing microarray technology, bioinformatics, laser-microdissection and in-situ-hybridization we found that the epidermis was the major source of immunomodulatory mediators. This epidermal gene induction was significantly stronger in resistant mice especially for several genes known to promote Th1 differentiation (IL-12, IL-1beta, osteopontin, IL-4) and for IL-6. Expression of these cytokines was temporally restricted to the crucial time of Th1/2 differentiation. Moreover, we revealed a stronger epidermal up-regulation of IL-6 in the epidermis of resistant mice. Accordingly, early local neutralization of IL-4 in resistant mice resulted in a Th2 switch and mice with a selective IL-6 deficiency in non-hematopoietic cells showed a Th2 switch and dramatic deterioration of disease. Thus, our data indicate for the first time that epidermal cytokine expression is a decisive factor in the generation of protective Th1 immunity and contributes to the outcome of infection with this important human pathogen.
	PMID: 20442861 [PubMed - in process]
	Publication Types: Research Support, Non-U.S. Gov't

2.	J Biol Chem. 2010 May 4. [Epub ahead of print] The Fe/S cluster assembly protein Isd11 is essential for tRNA thiolation in Trypanosoma brucei. Paris Z, Changmai P, Rubio MA, Zikova A, Stuart KD, Alfonzo JD, Lukes J. Institute of Parasitology, Czech Republic; Abstract Fe/S clusters are part of the active site of many enzymes and are essential for cell viability. In eukaryotes the cysteine desulfurase Nfs (IscS) donates the sulfur during Fe/S cluster assembly and was thought sufficient for this reaction. Moreover, Nfs is indispensable for tRNA thiolation, a modification generally required for tRNA function and protein synthesis. Recently, Isd11 was discovered as an integral part of the Nfs activity at an early step of Fe/S cluster assembly. Here we show, using a combination of genetic, molecular and biochemical approaches, that Isd11, in line with its strong association with Nfs, is localized in the mitochondrion of T. brucei. In addition to its involvement in Fe/S assembly, Isd11 also partakes in both cytoplasmic and mitochondrial tRNA thiolation, whereas Mtu1, another protein proposed to collaborate with Nfs in tRNA thiolation, is required for this process solely within the mitochondrion. Taken together these data places Isd11 at the center of these sulfur transactions and raises the possibility of a connection between Fe/S metabolism and protein synthesis, helping integrate two seemingly unrelated pathways.
	PMID: 20442400 [PubMed - as supplied by publisher]

3.	Parasitology. 2010 May 5:1-11. [Epub ahead of print] Current status of vaccination against African trypanosomiasis. Magez S, Caljon G, Tran T, Stijlemans B, Radwanska M. Unit of Cellular and Molecular Immunology, Vrije Universiteit Brussel (VUB), Pleinlaan 2, B-1050 Brussels, Belgium. Abstract SUMMARYAnti-trypanosomiasis vaccination still remains the best theoretical option in the fight against a disease that is continuously hovering between its wildlife reservoir and its reservoir in man and livestock. While antigentic variation of the parasite surface coat has been considered the major obstacle in the development of a functional vaccine, recent research into the biology of B cells has indicated that the problems might go further than that. This paper reviews past and current attempts to design both anti-trypanosome vaccines, as well as vaccines directed towards the inhibition of infection-associated pathology.
	PMID: 20441680 [PubMed - as supplied by publisher]

4.	Parasitology. 2010 May 5:1-10. [Epub ahead of print] Heat-shock protein 70 PCR-RFLP: a universal simple tool for Leishmania species discrimination in the New and Old World. Montalvo AM, Fraga J, Monzote L, Montano I, DE Doncker S, Dujardin JC, VAN DER Auwera G. Instituto de Medicina Tropical Pedro Kourí, Departamento de Parasitología, La Habana, Cuba. Abstract SUMMARYIntroduction. Species typing in leishmaniasis gains importance in diagnostics, epidemiology, and clinical studies. A restriction fragment length polymorphism (RFLP) assay of PCR amplicons from a partial heat-shock protein 70 gene (hsp70) had been described for the New World, allowing identification of some species. Methods. Based on an initial in silico analysis of 51 hsp70 sequences, most of which we recently determined in the frame of a phylogenetic study, species-specific restriction sites were identified. These were tested by PCR-RFLP on 139 strains from 14 species, thereby documenting both inter- and intra-species variability. Results. Our assay could identify Leishmania infantum, L. donovani, L. tropica, L. aethiopica, L. major, L. lainsoni, L. naiffi, L. braziliensis, L. peruviana, L. guyanensis, and L. panamensis by applying 2 subsequent digests. L. mexicana, L. amazonensis, and L. garnhami did not generate species-specific restriction fragment patterns. Conclusion. Currently no assay is available for global Leishmania species discrimination. We present a universal PCR-RFLP method allowing identification of most medically relevant Old and New World Leishmania species on the basis of a single PCR, obviating the need to perform separate PCRs. The technique is simple to perform and can be implemented in all settings where PCR is available.
	PMID: 20441679 [PubMed - as supplied by publisher]

5.	J Med Chem. 2010 May 4. [Epub ahead of print] Almiramides A-C: Discovery and Development of a New Class of Leishmaniasis Lead Compounds. Sanchez LM, Lopez D, Vesely BA, Della Togna G, Gerwick WH, Kyle DE, Linington RG. Department of Chemistry and Biochemistry, University of California Santa Cruz, 1156 High Street, Santa Cruz, California 95064. Abstract Leishmaniasis is a debilitating disease caused by protozoan parasites of the genus Leishmania, which affects an estimated 12 million people worldwide. The discovery of new lead compounds for leishmaniasis is therefore a pressing concern for global health programs. The organic extract of a Panamanian collection of the marine cyanobacterium Lyngbya majuscula showed strong in vitro activity in two complementary screens against the tropical parasite Leishmania donovani, the causative agent of visceral leishmaniasis. Chromatographic separation of this complex mixture led to the isolation of the highly N-methylated linear lipopeptides, almiramides A-C (1-3). Comparison with the biological activities of a number of related metabolites and semisynthetic derivatives revealed key features required for activity and afforded one new compound (11) with superior in vitro activity. Subsequent synthesis of a library of simplified analogues led to the discovery of several compounds with improved therapeutic indices to the natural products.
	PMID: 20441198 [PubMed - as supplied by publisher]