What's new for 'Trypanosomatids' in PubMed

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Sent on Saturday, 2010 Aug 21
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 - 6 of 6

1.	Mol Cell Proteomics. 2010 Aug 19. [Epub ahead of print] Discovery and verification of osteopontin and beta-2-microglobulin as promising markers for staging human African trypanosomiasis. Tiberti N, Hainard A, Lejon V, Robin X, Mumba Ngoyi D, Turck N, Matovu E, Enyaru J, Mathu Ndung U J, Scherl A, Dayon L, Sanchez JC. Geneva University, Switzerland; Abstract Human African trypanosomiasis (HAT), or sleeping sickness, is a parasitic disease endemic in sub-Saharan Africa, transmitted to humans through the bite of a tsetse fly. The first or haemolymphatic stage of the disease (S1) is associated with presence of parasites in the bloodstream, lymphatic system and body tissues. If patients are left untreated, parasites cross the blood-brain barrier (BBB) and invade the cerebrospinal fluid (CSF) and the brain parenchyma, giving rise to the second or meningoencephalitic stage (S2). Stage determination is a crucial step in guiding the choice of treatment, as drugs used for S2 are potentially dangerous. Current staging methods, based on counting white blood cells (WBC) and demonstrating trypanosomes in CSF, lack specificity and/or sensitivity. In the present study, we used a number of proteomic strategies to discover new markers with potential for staging HAT. CSF samples were collected from patients infected with Trypanosoma brucei gambiense in the Democratic Republic of Congo. The stage was determined following the guidelines of the national control program. The proteome of the samples was analysed by two-dimensional gel electrophoresis (n=9), and by sixplex tandem mass tag (TMT) isobaric labeling (n=6) quantitative mass spectrometry. Overall, 73 proteins were over-expressed in patients presenting the second stage of disease. Two of these, osteopontin and beta-2-microglobulin, were confirmed to be potential markers for staging HAT by Western blot and ELISA. The two proteins significantly discriminated between S1 and S2 patients with high sensitivity (68% and 78%, respectively) for 100% specificity, and a combination of both improved the sensitivity to 91%. The levels of osteopontin and beta-2-microglobulin in CSF of S2 patients (microg/ml range), as well as the fold increased concentration in S2 compared to S1 (3.8 and 5.5 respectively) make the two markers good candidates for the development of a test for staging HAT patients.
	PMID: 20724469 [PubMed - as supplied by publisher]
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2.	Glycobiology. 2010 Aug 19. [Epub ahead of print] Identification, subcellular localization, biochemical properties and high-resolution crystal structure of Trypanosoma brucei UDP-glucose pyrophosphorylase. Mariño K, Sampaio-Güther ML, Wernimont AK, Amani M, Hui R, Ferguson MA. Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, United Kingdom. Abstract The protozoan parasite Trypanosoma brucei is the causative agent of the cattle disease Nagana and human African sleeping sickness. Glycoproteins play key roles in the parasite's survival and infectivity and the de novo biosyntheses of the sugar nucleotides UDP-galactose, UDP-N-acetylglucosamine and GDP-fucose have been shown to be essential for the growth. The only route to UDP-galactose in T.brucei is through the epimerization of UDP-glucose by UDP-glucose 4'-epimerase. UDP-glucose is also the glucosyl donor for the unfolded glycoprotein glucosyltransferase (UGGT) involved in glycoprotein quality control in the endoplasmic reticulum and is the presumed donor for the synthesis of base J (beta-D-glucosylhydroxymethyluracil), a rare deoxynucleotide found in telomere-proximal DNA in the bloodstream form of T.brucei. Considering that UDP-glucose plays such a central role in carbohydrate metabolism, we decided to characterize UDP-glucose biosynthesis in T.brucei. We identified and characterized the parasite UDP-glucose pyrophosphorylase (TbUGP), responsible for the formation of UDP-glucose from glucose-1-phosphate and UTP, and localized the enzyme to the peroxisome-like glycosome organelles of the parasite. Recombinant TbUGP was shown to be enzymatically active and specific for glucose-1-phosphate. The high-resolution crystal structure was also solved, providing a framework for the design of potential inhibitors against the parasite enzyme.
	PMID: 20724435 [PubMed - as supplied by publisher]
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3.	Trop Med Int Health. 2010 Aug 16. [Epub ahead of print] Challenges in HIV and visceral Leishmania co-infection: future research directions. Ejara ED , Lynen L, Boelaert M, van Griensven J. University of Gondar, Gondar, Ethiopia.
	PMID: 20723183 [PubMed - as supplied by publisher]
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4.	FEMS Microbiol Lett. 2010 Jul 23. [Epub ahead of print] Cloning, overexpression and characterization of Leishmania donovani squalene synthase. Bhargava P, Kumar K, Chaudhaery SS, Saxena AK, Roy U. Division of Biochemistry, Central Drug Research Institute, Lucknow, UP, India. Abstract Abstract Squalene synthase (SSN, EC 2.5.1.21), a major enzyme in the sterol biosynthetic pathway, catalyses an unusual head-to-head reductive dimerization of two molecules of farnesyl-pyrophosphate (FPP) in a two-step reaction to form squalene. FPP serves as a metabolic intermediate in the formation of sterols, dolichols, ubiquinones and farnesylated proteins. Here, we report cloning, expression and purification of a catalytically active recombinant squalene synthase of Leishmania donovani (LdSSN). The pH and temperature optima of LdSSN were 7.4 and 37 degrees C, respectively. Biochemical studies revealed that the K(m) and V(max) for the substrate FPP were 3.8 muM and 0.59 nM min(-1) mg(-1) and for NADPH were 43.23 muM and 0.56 nM min(-1) mg(-1). LdSSN was found to be sensitive towards denaturants as manifested by a loss of enzyme activity at the concentration of 1 M urea or 0.25 M guanidine hydrochloride. Zaragozic acid A, a potent inhibitor of mammalian SSN, was also a competitive inhibitor of recombinant LdSSN, with a K(i) of 74 nM. This is the first report on the purification and characterization of full-length recombinant SSN from L. donovani. Studies on recombinant LdSSN will help in evaluating this enzyme as a potential drug target for visceral leishmaniasis.
	PMID: 20722739 [PubMed - as supplied by publisher]
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5.	Plast Reconstr Surg. 1963 Apr;31:370-84. The triad of Columella deformit ies. MILLARD DR.
	PMID: 20712082 [PubMed - indexed for MEDLINE]

6.	Nat Prod Commun. 2010 Jun;5(6):853-8. Antimicrobial and antiparasitic abietane diterpenoids from the roots of Clerodendrum eriophyllum. Machumi F, Samoylenko V, Yenesew A, Derese S, Midiwo JO, Wiggers FT, Jacob MR, Tekwani BL, Khan SI, Walker LA, Muhammad I. Department of Chemistry, University of Nairobi, P.O. Box 30197 (00100), Nairobi, Kenya. Abstract Chromatographic separation of the roots of a Kenyan medicinal plant, Clerodendrum eriophyllum, led to the isolation of ten abietane diterpenoids (1-10), one of which (1) was isolated for the first time from a natural source. Using spectroscopic data, the structure of 1 was determined to be 12-hydroxy-8,12-abietadiene-3,11,14-trione. Circular dichroism (CD) spectra showed that the stereochemistry of compounds 1, 3, and 6-8 belongs to the normal series of abietane diterpenes, which confirmed the absolute stereochemistry of the isolated compounds. Compounds 1-10 were evaluated for their in vitro antiplasmodial, antileishmanial, antifungal and antibacterial activities. Compounds 3 and 7 exhibited potent antifungal activity (IC50/MIC 0.58/1.25 and 0.96/2.5 microg/mL, respectively) against C. neoformans, whereas 3, 6 and 7 showed strong antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus with IC50/MIC values between 1.33-1.75/2.5-5 and 0.96-1.56/2.5 microg/mL, respectively. In addition, compounds 3 and 9 exhibited potent antileishmanial activity (IC50 0.08 and 0.20 microg/mL, respectively) against L. donovani, while 3 and 7 displayed weak antimalarial activity against Plasmodium falciparum, but 9 was inactive.
	PMID: 20614808 [PubMed - indexed for MEDLINE]
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