Wednesday, July 8, 2009

What's new for 'Trypanosomatids' in PubMed

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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 -7 of 7

1: Parasitol Res. 2009 Jul 7. [Epub ahead of print]

Trans-sialidase from Trypanosoma brucei as a potential target for DNA vaccine development against African trypanosomiasis.

Silva MS, Prazeres DM, Lança A, Atouguia J, Monteiro GA.

Unidade de Ensino e Investigação de Clínica das Doenças Tropicais-Centro de Malária e Outras Doenças Tropicais (CMDT), Instituto de Higiene e Medicina Tropical-IHMT, Av. da Junqueira, 96, 1349-008, Lisboa, Portugal, mssilva@ihmt.unl.pt.

African trypanosomiasis (AT), also known as sleeping sickness in humans and Nagana in animals, is a disease caused by the protozoan parasite Trypanosoma brucei. AT is an extremely debilitating disease in human, cattle, and wild animals, and the treatment is difficult with frequent relapses. This work shows that BALB-c mice immunized intramuscularly with a single dose (100 mug) of a plasmid DNA encoding the 5'-terminal region of the trans-sialidase (nTSA) gene of T. brucei brucei are able to produce IgG antibodies that bind to the bloodstream form of T. brucei-protein extract and recognize the recombinant nTSA protein, expressed in Escherichia coli. Furthermore, this DNA vaccination process was able to protect 60% of mice submitted to a challenge assay with the infective form of T. brucei brucei parasites. These results demonstrate that a DNA vaccine coding for trans-sialidase from T. brucei is potentially useful in the prophylaxis of AT.

PMID: 19582478 [PubMed - as supplied by publisher]

2: PLoS Negl Trop Dis. 2009 Jul 7;3(7):e476.

Comparative Expression Profiling of Leishmania: Modulation in Gene Expression between Species and in Different Host Genetic Backgrounds.

Depledge DP, Evans KJ, Ivens AC, Aziz N, Maroof A, Kaye PM, Smith DF.

Centre for Immunology and Infection, Department of Biology/Hull York Medical School, University of York, York, United Kingdom.

BACKGROUND: Genome sequencing of Leishmania species that give rise to a range of disease phenotypes in the host has revealed highly conserved gene content and synteny across the genus. Only a small number of genes are differentially distributed between the three species sequenced to date, L. major, L. infantum and L. braziliensis. It is not yet known how many of these genes are expressed in the disease-promoting intracellular amastigotes of these species or whether genes conserved between the species are differentially expressed in the host. METHODS/PRINCIPAL FINDINGS: We have used customised oligonucleotide microarrays to confirm that all of the differentially distributed genes identified by genome comparisons are expressed in intracellular amastigotes, with only a few of these subject to regulation at the RNA level. In the first large-scale study of gene expression in L. braziliensis, we show that only approximately 9% of the genes analysed are regulated in their RNA expression during the L. braziliensis life cycle, a figure consistent with that observed in other Leishmania species. Comparing amastigote gene expression profiles between species confirms the proposal that Leishmania transcriptomes undergo little regulation but also identifies conserved genes that are regulated differently between species in the host. We have also investigated whether host immune competence influences parasite gene expression, by comparing RNA expression profiles in L. major amastigotes derived from either wild-type (BALB/c) or immunologically compromised (Rag2(-/-) gamma(c) (-/-)) mice. While parasite dissemination from the site of infection is enhanced in the Rag2(-/-) gamma(c) (-/-) genetic background, parasite RNA expression profiles are unperturbed. CONCLUSION/SIGNIFICANCE: These findings support the hypothesis that Leishmania amastigotes are pre-adapted for intracellular survival and undergo little dynamic modulation of gene expression at the RNA level. Species-specific parasite factors contributing to virulence and pathogenicity in the host may be limited to the products of a small number of differentially distributed genes or the differential regulation of conserved genes, either of which are subject to translational and/or post-translational controls.

PMID: 19582145 [PubMed - in process]

3: Eukaryot Cell. 2009 Jul 6. [Epub ahead of print]

The Role of AP-1 in Developmentally Regulated Lysosomal Trafficking in Trypanosoma brucei.

Tazeh NN, Silverman JS, Schwartz KJ, Sevova ES, Sutterwala SS, Bangs JD.

Department of Medical Microbiology & Immunology, University of Wisconsin School of Medicine and Public Health, 1550 Linden Drive, Madison, 53706.

African trypanosomes are the causative agents of human trypanosomiasis (sleeping sickness). The pathogenic stage of this parasite has unique adaptations to life in the bloodstream of the mammalian host, including up-regulation of endocytic and lysosomal activities. We investigate stage specific requirements for cytoplasmic adaptor/clathrin machinery in post-Golgi biosynthetic sorting to the lysosome using RNAi silencing of the Tbmicro1 subunit of Adaptor Complex 1 (AP-1), in conjunction with immunolocalization, kinetic analyses of reporter transport, and quantitative endocytosis assays. Tbmicro1 silencing is lethal in both stages indicating critical function(s) for the AP-1 machinery. Transport of soluble and membrane-bound secretory cargo is Tbmicro1 independent in both stages. In procyclics trafficking of the lysosomal membrane protein, p67, is disrupted leading to cell surface mislocalization. The lysosomal protease trypanopain is also secreted, suggesting a transmembrane sorting receptor for this soluble hydrolase. In bloodstream trypanosomes both p67 and trypanopain trafficking are unaffected by Tbmicro1 silencing suggesting that AP-1 is not necessary for biosynthetic lysosomal trafficking. Endocytosis in bloodstream cells is also unaffected, indicating that AP-1 does not function at the flagellar pocket. These results indicate that post-Golgi sorting to the lysosome is critically dependent on the AP-1/clathrin machinery in procyclic trypanosomes, but that this machinery is not necessary in bloodstream parasites. We propose a simple model for stage specific default secretory trafficking in trypanosomes that is consistent with the behavior of other soluble and GPI-anchored cargos, and which is influenced by up-regulation of endocytosis in bloodstream parasites as an adaptation to life in the mammalian bloodstream.

PMID: 19581441 [PubMed - as supplied by publisher]

4: Biochim Biophys Acta. 2009 Jul 3. [Epub ahead of print]

Analyses of Non-Leucine Rich Repeat (Non-LRR) Regions Intervening Between LRRs in Proteins.

Matsushima N, Mikami T, Tanaka T, Miyashita H, Yamada K, Kuroki Y.

Sapporo Medical University Center for Medical Education, Sapporo, Hokkaido 060-8556, Japan.

BACKROUND: Many proteins have LRR (leucine rich repeat) units interrupted by non-LRRs which we call IR (Non-LRR Island Region). METHODS: We identified proteins containing LRR@IRs (LRRs having IR) by using a new method and then analyzed their natures and distributions. RESULTS: LRR@IR proteins were found in over two hundred proteins from prokaryotes and from eukaryotes. These are divided into twenty-one different protein families. The IRs occur one to four times in LRR regions and range in length from 5 to 11,265 residues. The IR lengths in Fungi adenylate cyclases (acys) range from 5 to 116 residues; there are 22 LRR repeats. The IRs in Leishmania proteophosphoglycans (ppgs) vary from 105 to 11,265 residues. These results indicate that the IRs evolved rapidly. A group of LRR@IR proteins - LRRC17, chondroadherin-like protein, ppgs, and four Pseudomonas proteins - have a super motif consisting of an LRR block and its adjacent LRR@IR region. This indicates that the entire super motif experienced duplication. The sequence analysis of IRs offer functional similarity in some LRR@IR protein families. GENERAL SIGNIFICANCE: This study suggests that various IRs and super-motifs provide a great variety of structures and functions for LRRs.

PMID: 19580846 [PubMed - as supplied by publisher]

5: J Commun Dis. 2008 Dec;40(4):273-6.

Clinical and laboratory comparison of different brands of amphotericin B used for the treatment of Kala-azar: an observational study.

Narayan S, Gupta AK, Singh Subhankar K, Lal CS, Singh VP, Sinha PK, Das P, Thakur CP.

Rajendra Memorial Research Institute of Medical Sciences, Patna-800007, India. drshyamnarayan@rediffmail.com

The communication presents clinical response of cases of visceral leishmaniasis to treatment by two different brands of Amphotericin B. Fungizone was found to be slightly better than Amphotericin B, however, the difference is not statistically significant.

PMID: 19579720 [PubMed - in process]

6: New Microbiol. 2009 Apr;32(2):223-7.

Visceral leishmaniasis in a patient with common variable immunodeficiency and evans syndrome: clinical remarks.

Maio P, Leone S, Volpe S, dell'Aquila G, Giglio S, Magliocca M, Nigro FS, Pacifico P, Acone N.

Infectious Diseases Department, A.O.R.N. S.G. Moscati, Avellino, Italy. patriziamaio@yahoo.it

Visceral Leishmaniasis (VL) is a vector-borne zoonosis endemic in Southern Italy whose usual clinical features include fever, splenomegaly, pancytopenia and hypergammaglobulinemia. The clinical and biochemical picture may be misleading in patients with immunodeficiency diseases hampering the diagnosis. We describe a VL case in a patient whose spleen had been removed and who had Common Variable Immunodeficiency and Evans syndrome.

PMID: 19579705 [PubMed - in process]

7: Phytomedicine. 2009 Jun;16(6-7):659-64. Epub 2009 Apr 2.Click here to read LinkOut

Antitrypanosomal activity of some pregnane glycosides isolated from Caralluma species.

Abdel-Sattar E, Shehab NG, Ichino C, Kiyohara H, Ishiyama A, Otoguro K, Omura S, Yamada H.

Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia. abdelsattar@yahoo.com

Pregnane glycosides previously isolated from genus Caralluma (C. Penicillata, C. tuberculata and C. russelliana) were tested for their antitrypanosomal activity. Penicilloside E showed the highest antitrypanosomal activity (IC(50) 1.01 microg/ml) followed by caratuberside C (IC(50) 1.85 microg/ml), which exhibited the highest selectivity index (SI 12.04). It was noticed that acylation is required for the antitrypanosomal activity while glycosylation at C-20 has no significant effect on the activity.

PMID: 19345077 [PubMed - indexed for MEDLINE]

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