What's new for 'Trypanosomatids' in PubMed

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Sent on Tuesday, 2010 Dec 28
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.	Nucleic Acids Res. 2010 Dec 23. [Epub ahead of print] ATP independent type IB topoisomerase of Leishmania donovani is stimulated by ATP: an insight into the functional mechanism. Sengupta S, Ganguly A, Roy A, Bosedasgupta S, D'Annessa I, Desideri A, Majumder HK. Molecular Parasitology Laboratory, Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata 700032, India, Biophysical Chemistry, Infection Biology, Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland and Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, Rome 00133, Italy. Abstract Most type IB topoisomerases do not require ATP and Mg(2+) for activity. However, as shown previously for vaccinia topoisomerase I, we demonstrate that ATP stimulates the relaxation activity of the unusual heterodimeric type IB topoisomerase from Leishmania donovani (LdTOP1L/S) in the absence of Mg(2+). The stimulation is independent of ATP hydrolysis but requires salt as a co-activator. ATP binds to LdTOP1L/S and increases its rate of strand rotation. Docking studies indicate that the amino acid residues His93, Tyr95, Arg188 and Arg190 of the large subunit may be involved in ATP binding. Site directed mutagenesis of these four residues individually to alanine and subsequent relaxation assays reveal that the R190A mutant topoisomerase is unable to exhibit ATP-mediated stimulation in the absence of Mg(2+). However, the ATP-independent relaxation activities of all the four mutant enzymes remain unaffected. Additionally, we provide evidence that ATP binds LdTOP1L/S and modulates the activity of the otherwise ATP-independent enzyme. This study establishes ATP as an activator of LdTOP1L/S in the absence of Mg(2+).
	PMID: 21186185 [PubMed - as supplied by publisher]

2.	Protein Expr Purif. 2010 Dec 22. [Epub ahead of print] Comparative expression of wild-type and highly soluble mutant His103Leu of hydroxynitrile lyase from Manihot esculenta in prokaryotic and eukaryotic expression systems. Dadashipour M, Fukuta Y, Asano Y. Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan. Abstract Low protein solubility and inclusion body formation represent big challenges in production of recombinant proteins in Escherichia coli. We have recently reported functional expression of hydroxynitrile lyase from Manihot esculenta, MeHNL, in E. coli with high in vivo solubility and activity using directed evolution. As a part of attempts to clarify the mechanism of this phenomenon, we have described the possibility of expression of the highly active and soluble mutant MeHNL-His103Leu as well as wild-type enzyme in several expression systems. Methylotrophic yeast Pichia pastoris, protozoan host Leishmania tarentolae and two cell-free translations, including an E. coli lysate (WakoPURE system) and wheat germ translation system were used to compare expression profiles of the genes. Two distinguishable protein expression patterns were observed in prokaryotic and eukaryotic-based systems. The wild-type and mutant enzyme showed high activity for both genes (up to 10 U/ ml) in eukaryotic hosts P. pastoris and L. tarentolae, while those of E. coli exhibited about 1 and 15 U/ml, respectively. The different activity level in prokaryotic systems but the same level among the eukaryotic hosts indicate the phenomenon is specific to the E. coli system. Both the wild-type and mutant enzymes were functionally expressed in eukaryotic systems, probably using the folding assistants such as chaperones. Properties of expression systems used in this study were precisely compared, too. Copyright © 2010. Published by Elsevier Inc.
	PMID: 21185385 [PubMed - as supplied by publisher]

3.	Mol Biochem Parasitol. 2010 Dec 22. [Epub ahead of print] Glucose-6-phosphate dehydrogenase is the target for the trypanocidal action of human steroids. Gupta S, Cordeiro AT, Michels PA. Research Unit for Tropical Diseases, de Duve Institute, TROP 74.39, Avenue Hippocrate 74, B-1200 Brussels, Belgium. Abstract Steroids such as dehydroepiandrosterone (DHEA) and epiandrosterone (EA) exert multiple effects in mammals including the inhibition of glucose-6-phosphate dehydrogenase (G6PDH). Initially, the inhibition was considered specific for the mammalian enzyme. The beneficial effect of these steroids on infections by protists and nematodes was attributed to stimulation of the immune system. However, we showed previously that DHEA and EA also inhibit Trypanosoma brucei and T. cruzi G6PDH, with low micromolar K(i)' values, but not the enzyme from Leishmania species, and kill in vitro cultured trypanosomes. We report here that, contrary to wild-type trypanosomes, mutant bloodstream-form T. brucei cells expressing L. mexicana G6PDH are not susceptible to the steroids, proving that G6PDH is the in situ target. Moreover, bromo-derivatives of the steroids show 50-100 fold lower K(i)' values for the enzyme and display an increased potency to kill the parasites. Therefore, the compounds offer promise for use in development of parasite-selective drugs. Copyright © 2010. Published by Elsevier B.V.
	PMID: 21185333 [PubMed - as supplied by publisher]

4.	Trans R Soc Trop Med Hyg. 2010 Dec 22. [Epub ahead of print] Pharmacovigilance methods in public health programmes: the example of miltefosine and visceral leishmaniasis. Kshirsagar N, Ferner R, Figueroa BA, Ghalib H, Lazdin J. Department of Clinical Pharmacology, Seth GS Medical College and King Edward Memorial Hospital, Parel, Mumbai, India. Abstract Pharmacovigilance is concerned with the assessment of benefit and harm. Disease burden, status of healthcare delivery through government centres and practitioners, existing pharmacovigilance programmes, relevant pre-marketing studies and the likely effectiveness and risks of drugs must be considered for planning pharmacovigilance activity. The risk of a drug may be known, unknown, potential or specific to the context of the programme. The potential benefits of a public health programme aimed at reducing or eliminating a specific condition will depend on the health burden due to that condition, which is a function of the seriousness of the condition and its frequency, as well as the likely efficacy of the programme in reaching its goals. The present article has outlined an approach to pharmacovigilance for such a donor-funded programme, using pharmacovigilance in leishmaniasis as an example. Copyright © 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.
	PMID: 21185045 [PubMed - as supplied by publisher]

5.	Rev Bras Parasitol Vet. 2010 Oct-Dec;19(4):256-8. Occurrence of Leishmania (Leishmania) chagasi in a domestic cat (Felis catus) in Andradina, São Paulo, Brazil: case report. Coelho WM, Lima VM, Amarante AF, Langoni H, Pereira VB, Abdelnour A, Bresciani KD. Departamento de Higiene Veterinária e Saúde Pública, Faculdade de Medicina Veterinária e Zootecnia, Universidade Estadual Paulista - UNESP,Distrito Rubião Jr., s/n CEP 18618-970, Botucatu - SP, Brazil. hlangoni@fmvz.unesp.br. Abstract This work describes natural infection by Leishmania in a domestic cat where amastigote forms of the parasite were observed in the popliteal lymph node imprint. Positive and negative serological reactions were observed by enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence assay (IFA), respectively. Polymerase chain reaction (PCR) revealed that the nucleotide sequence of the sample was identical to Leishmania (L.) chagasi. This is the first report of the disease in felines of the city of Andradina, SP, an area considered endemic for canine and human visceral leishmaniasis.
	PMID: 21184705 [PubMed - in process]

6.	Rev Bras Parasitol Vet. 2010 Oct-Dec;19(4):233-7. Sandflies (Psychodidae: Phlebotominae) survey in an urban transmission area of visceral leishmaniasis, Northeastern Brazil. Amóra SS, Bevilaqua CM, Feijó FM, Oliveira PG, Peixoto GC, Sousa RN, Alves ND, Oliveira LM, Macedo IT. Laboratório de Doenças Parasitárias, Programa de Pós-graduação em Ciências Veterinárias, Universidade Estadual do Ceará - UECE, Campus do Itaperi,Av. Paranjana, 1700, CEP 60740-000, Fortaleza - CE, Brazil. claudiamlb@yahoo.com.br. Abstract Visceral leishmaniasis (VL) is a major public health challenge in Brazil, especially in states where it is endemic. The aim of this study was to investigate the relationship of sand fly population density with environmental variables (temperature, rainfall and relative humidity) in urban areas of the city of Mossoró, Rio Grande do Norte, Northeastern Brazil. Sand flies were captured with Center Disease Control (CDC) traps installed monthly in the intra and peridomicile of three houses. Data analysis was based on the chi-square test and linear regression. A total of 7,347 sand flies were captured, being 93.85% Lutzomyia longipalpis and 6.15% Lutzomyia evandroi. Sand flies were more commonly found in the peridomicile and there was no difference between the number of males and females. The variables rainy season as well as relative humidity and rainfall, alone or together, did not have an effect on sand fly population density. However, high temperatures had a negative effect. The study of the behavior of sand flies in specific units of endemic areas can provide input to public health authorities for planning appropriate VL vector control measures.
	PMID: 21184700 [PubMed - in process]