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Sent on Tuesday, 2009 Nov 10Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Pathol Biol (Paris). 2009 Nov 4. [Epub ahead of print][Choice of primers: A determining element in molecular diagnosis of cutaneous leishmaniasis.][Article in French] Neffati A, Kallel K, Anene S, Kaouech E, Belhadj S, Ennigrou S, Chaker E.Laboratoire de parasitologie-mycologie, La Rabta, Jebbari, 1007 Tunis, Tunisie. The cutaneous leishmaniasis (CL) is a parasitic disease which represents a serious problem for the public health not only in Tunisia but also all over the world. Its diagnosis is based on the techniques which are usually used, direct examination and in vitro culture. Because of several factors, these techniques lack sensitivity. The molecular biology, which is indeed more rapid and more sensitive, has proved its effectiveness in diagnosis of the CL. There are two main aims for our research work. First, to show the contribution of the Polymerase Chain Reaction (PCR) during the diagnosis of CL (of course by comparing the results obtained when using this technique with those found through the direct examination); second, to compare the two pairs of primers which amplify the leishmanien gene coding for the 18s ribosomal sub-unit: the pair R221/R332 (PCR1) and the pair Lei70L/Lei70R (PCR2). Our work was carried out upon 299 samples. One hundred and eighty-eight of them were positive using the direct examination and/or the PCR and 111 were negative. Only two samples were positive using of course the direct examination in comparison with 74 which were positive when using only the PCR (PCR1 and/or PCR2). Among these 74 samples, 64 where positive using only PCR2 in comparison with two samples which were positive using only PCR1. The eight remaining samples were at once positive for the PCR1 and the PCR2. The PCR (notably the PCR2) has proved a more significant percentage of positivity in comparison with direct examination: 98.98% for the PCR and 60.6% for direct examination. |
| PMID: 19896289 [PubMed - as supplied by publisher] | |
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| 2. | FEBS J. 2009 Nov 6. [Epub ahead of print]Side chain specificity of ADP-ribosylation by a sirtuin.Fahie K, Hu P, Swatkoski S, Cotter RJ, Zhang Y, Wolberger C.Department of Biophysics and Biophysical Chemistry, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Endogenous mono-ADP-ribosylation in eukaryotes is involved in regulating protein synthesis, signal transduction, cytoskeletal integrity, and cell proliferation, although few cellular ADP-ribosyltransferases have been identified. The sirtuins constitute a highly conserved family of protein deacetylases, and several family members have also been reported to perform protein ADP-ribosylation. We characterized the ADP-ribosylation reaction of the nuclear sirtuin homolog Trypanosoma brucei SIR2-related protein 1 (TbSIR2RP1) on both acetylated and unacetylated substrates. We demonstrated that an acetylated substrate is not required for ADP-ribosylation to occur, indicating that the reaction performed by TbSIR2RP1 is a genuine enzymatic reaction and not a side reaction of deacetylation. Biochemical and MS data showed that arginine is the major ADP-ribose acceptor for unacetylated substrates, whereas arginine does not appear to be the major ADP-ribose acceptor in reactions with acetylated histone H1.1. We performed combined ab initio quantum mechanical/molecular mechanical molecular dynamics simulations, which indicated that sirtuin ADP-ribosylation at arginine is energetically feasible, and involves a concerted mechanism with a highly dissociative transition state. In comparison with the corresponding nicotinamide cleavage in the deacetylation reaction, the simulations suggest that sirtuin ADP-ribosylation would be several orders slower but less sensitive to nicotinamide inhibition, which is consistent with experimental results. These results suggest that TbSIR2RP1 can perform ADP-ribosylation using two distinct mechanisms, depending on whether or not the substrate is acetylated. Structured digital abstract * MINT-7288298: TbSIR2 (uniprotkb:O96670) adp ribosylates (MI:0557) histone H1.1 (uniprotkb:Q02539) by enzymatic studies (MI:0415) * MINT-7288305, MINT-7288325, MINT-7288338, MINT-7288352, MINT-7288370, MINT-7288395, MINT-7288412: TbSIR2 (uniprotkb:O96670) adp ribosylates (MI:0557) histone H1.1 (uniprotkb:P02253) by enzymatic studies (MI:0415) * MINT-7288385: TbSIR2 (uniprotkb:O96670) deacetylates (MI:0197) histone H1.1 (uniprotkb:Q02539) by deacetylase assay (MI:0406) * MINT-7288424: hADPRH (uniprotkb:P54922) cleaves (MI:0194) histone H1.1 (uniprotkb:Q02539) by enzymatic studies (MI:0415). |
| PMID: 19895577 [PubMed - as supplied by publisher] | |
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| 3. | FEBS J. 2009 Nov 6. [Epub ahead of print]Alanine aminotransferase of Trypanosoma brucei- a key role in proline metabolism in procyclic life forms.Spitznagel D, Ebikeme C, Biran M, Nic A Bháird N, Bringaud F, Henehan GT, Nolan DP.School of Biochemistry and Immunology, Trinity College Dublin, Ireland. African trypanosomes possess high levels of alanine aminotransferase (EC 2.6.1.2), although the function of their activity remains enigmatic, especially in slender bloodstream forms where the metabolism of ketoacids does not occur. Therefore, the gene for alanine aminotransferase enzyme in Trypanosoma brucei (TbAAT) was characterized and its function assessed using a combination of RNA interference and gene knockout approaches. Surprisingly, as much as 95% or more of the activity appears to be unnecessary for growth of either bloodstream or procyclic forms respiring on glucose. A combination of RNA interference and NMR spectroscopy revealed an important role for the activity in procyclic forms respiring on proline. Under these conditions, the major end product of proline metabolism is alanine, and a reduction in TbAAT activity led to a proportionate decrease in the amount of alanine excreted along with an increase in the doubling time of the cells. These results provide evidence of a role for alanine aminotransferase in the metabolism of proline in African trypanosomes by linking glutamate produced by the initial oxidative steps of the pathway with pyruvate produced by the final oxidative step of the pathway. This step appears to be essential when proline is the primary carbon source, which is likely to be the physiological situation in the tsetse fly vector. |
| PMID: 19895576 [PubMed - as supplied by publisher] | |
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| 4. | J Med Chem. 2009 Nov 6. [Epub ahead of print]Fluorinated Rhodacyanine (SJL-01) Possessing High Efficacy for Visceral Leishmaniasis (VL).Yang M, Arai C, Bakar Md A, Lu J, Ge JF, Pudhom K, Takasu K, Kasai K, Kaiser M, Brun R, Yardley V, Itoh I, Ihara M.Drug Discovery Science Research Center, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan. Anti-Leishmania in vitro and in vivo activities of various rhodacyanine derivatives have been examined. Among them, the fluorinatied variant SJL-01 (8) showed IC(50) of 0.011 muM against Leishmania donovani strain MHOM/ET/67/L82 (selective index of >15000) and 95-97% inhibition against L. donovani strain MHOM/ET/67/HU in female BALB/c mice by 1.3-12.5 mg/kg x 5 iv administrations. Negative results on chromosomal aberration test and in vitro micronucleus test suggest that compound 8 is a hopeful candidate for visceral leishmaniasis (VL). |
| PMID: 19894726 [PubMed - as supplied by publisher] | |
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| 5. | Curr Drug Metab. 2009 Jun;10(5):459-69.Amphotericin B and its new derivatives - mode of action.Baginski M, Czub J.Department of Pharmaceutical Technology and Biochemistry, Gdansk University of Technology, Poland. maciekb@hypnos.chem.pg.gda.pl Amphotericin B (AmB) is a well known antifungal and antiprotozoal antibiotic used in the clinic for several decades. Clinical applications of AmB, however, are limited by its nephrotoxicity and many other acute side effects which are not acceptable by patients when their life is not threaten. In order to improve the therapeutic index of this drug, lipid formulations have been introduced and many efforts have been made to obtain less toxic AmB derivatives by chemical modifications of the parent drug. This review presents concise knowledge about this fascinating compound and a critical review of the data published within last few years about the mechanism of action of this antibiotic. In particular, in the present work we discuss: i) structure and properties of AmB and its recently synthesized new derivatives; ii) antifungal and antileishmanial activity and toxicity of these compounds; and iii) mode of action of AmB and its derivatives at cellular and molecular levels, with particular attention paid to interactions of AmB and different components of cellular membranes. |
| PMID: 19689243 [PubMed - indexed for MEDLINE] | |
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