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Sent on Tuesday, 2010 Aug 24Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Mol Biochem Parasitol. 2010 Aug 19. [Epub ahead of print]The role of the Kinesin-13 family protein TbKif13-2 in flagellar length control of Trypanosoma brucei.Chan KY, Ersfeld K.Department of Biological Sciences. AbstractTbKif13-2, a member of the microtubule-depolymerising Kinesin-13 family was localized at the tip of the flagellum in Trypanosoma brucei. Its predicted activity suggested a role in the regulation of axonemal length. However, using gene deletion and overexpression of TbKif13-2 we show that, in procyclic T. brucei, this kinesin has only a very limited effect on flagellar length. Gene deletion resulted in no significant elongation of the flagellum and overexpression only slightly decreased flagellar length and the rate of growth of a new flagellum during cell division. This is in contrast to studies in Leishmania major, where overexpression of the TbKif13-2 homologue resulted in a significant length reduction of the flagellum. Knock-out of TbKif13-2 has, however, an effect on the initial growth of the emerging new flagellum. In conclusion, we show that TbKif13-2 has only a marginal impact on flagellar length in T. brucei. |
| PMID: 20728476 [PubMed - as supplied by publisher] | |
| 2. | Int J Antimicrob Agents. 2010 Aug 19. [Epub ahead of print]Leishmaniasis in the World Health Organization Eastern Mediterranean Region.Postigo JA.World Health Organization, Eastern Mediterranean Regional Office, Abdel Razak El Sanhouri St., Cairo, Egypt. AbstractLeishmaniasis represents a major public health problem in the Eastern Mediterranean Region (EMR) of the World Health Organization (WHO). Cutaneous and visceral leishmaniasis are mainly seen in 14 of the 22 countries of the region. In several of these countries outbreaks have an apparent tendency to occur at around 10-year intervals. In 2008, some 100000 new cases of cutaneous leishmaniasis were reported. Foci of zoonotic cutaneous leishmaniasis, caused by Leishmania major, occur in Afghanistan, Egypt, Iran, Iraq, Jordan, Libya, Morocco, Palestine, Pakistan, Saudi Arabia, Sudan, Syria, Tunisia and Yemen. Anthroponotic cutaneous leishmaniasis, caused by L. tropica, occurs in Afghanistan, Iran, Iraq, Morocco, Pakistan, Saudi Arabia, Syria and Yemen. Anthroponotic visceral leishmaniasis, caused by L. donovani, occurs mainly in Sudan and Somalia. Zoonotic visceral leishmaniasis, caused by L. infantum, occurs in most countries of the region. In order to address the problem of leishmaniasis in the EMR, WHO is supporting ministries of health through a strategic plan focusing on (a) training programme managers and health workers on diagnosis and case management; (b) establishing a harmonized regional surveillance system; (c) creating a regional network of experts; (d) promoting political commitment of national governments. |
| PMID: 20728317 [PubMed - as supplied by publisher] | |
| 3. | Eur J Med Chem. 2010 Aug 7. [Epub ahead of print]QSAR and docking studies of novel antileishmanial diaryl sulfides and sulfonamides.Goodarzi M, da Cunha EF, Freitas MP, Ramalho TC.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), UNLP, CCT La Plata-CONICET, Diag. 113 y 64, C.C. 16, Suc.4, 1900 La Plata, Argentina. AbstractLeishmaniasis is a neglected disease transmitted in many tropical and sub-tropical countries, with few studies devoted to its treatment. In this work, the activities of two antileishmanial compound classes were modeled using Dragon descriptors, and multiple linear (MLR) and support vector machines (SVM) as linear and nonlinear regression methods, respectively. Both models were highly predictive, with calibration, leave-one-out validation and external validation R(2) of 0.79, 0.72 and 0.78, respectively, for the MLR-based model, improving significantly to 0.98, 0.93 and 0.90 when using SVM modeling. Therefore, novel compounds were proposed using the QSAR models built by combining the substructures of the main active compounds of both classes. The most promising structures were docked into the active site of Leishmania donovani alpha,beta tubulin (Ld-Tub), demonstrating the high affinity of some new structures when compared to existing antileishmanial compounds. |
| PMID: 20728249 [PubMed - as supplied by publisher] | |
| 4. | J Control Release. 2010 Aug 18. [Epub ahead of print]Sunlight triggered photodynamic ultradeformable liposomes against Leishmania braziliensis are also leishmanicidal in the dark.Montanari J, Maidana C, Esteva MI, Salomon C, Morilla MJ, Romero EL.Programa de Nanomedicinas, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Roque Saenz Peña 352, Bernal, B1876 BXD, Buenos Aires, Argentina. AbstractBeing independent of artificial power sources, self administered sunlight triggered photodynamic therapy could be suitable alternative treatment for cutaneous leishmaniasis, that avoids the need for injectables and the toxic side effects of pentavalent antimonials. In this work we have determined the in vitro leishmanicidal activity of sunlight triggered photodynamic ultradeformable liposomes (UDL). ZnPc is a hydrophobic Zn phthalocyanine that showed 20 % anti-promastigote activity (APA) and 20 % anti-amastigote activity (AA) against Leishmania braziliensis (strain 2903) after 15min sunlight irradiation (15J/cm(2)). However, when loaded in UDL as UDL-ZnPc (1.25muM ZnPc-1mM phospholipids) elicited 100 % APA and 80 % AA at the same light dose. In the absence of host cells toxicity, UDL and UDL-ZnPc also showed non-photodynamic leishmanicidal activity. Confocal laser scanning microscopy of cryosectioned human skin mounted in non-occlusive Saarbrücken Penetration Model, showed that upon transcutaneous administration ZnPc penetrated nearly 10 folds deeper as UDL-ZnPc that if loaded in conventional liposomes. Quantitative determination of ZnPc confirmed that UDL-ZnPc penetrated homogeneously in the stratum corneum, carrying 7 folds higher amount of ZnPc 8 folds deeper than L-ZnPc. It is envisioned that the multiple leishmanicidal effects of UDL-ZnPc could play a synergistic role in prophylaxis or therapeutic at the first stages of the infection. |
| PMID: 20727925 [PubMed - as supplied by publisher] | |
| 5. | J Biomol Struct Dyn. 2010 Aug;28(1):51-70.Conformational and oligomeric effects on the cysteine pK(a) of tryparedoxin peroxidase.Yuan Y, Knaggs MH, Poole LB, Fetrow JS, Salsbury FR Jr.Departments of Physics and Wake Forest University, 1834 Reynold Road, Winston-Salem, North Carolina 27106, USA. AbstractTypical 2-Cys peroxiredoxins (Prxs) are peroxidases which regulate cell signaling pathways, apoptosis, and differentiation. These enzymes are obligate homodimers, and can form decamers in solution. During catalysis, Prxs exhibit cysteine-dependent reactivity which requires the deprotonation of the peroxidatic cysteine (C(p)) supported by a lowered pK(a) in the initial step. We present the results of molecular dynamics simulations combined with pKa calculations on the monomeric, dimeric and decameric forms of one typical 2-Cys Prx, the tryparedoxin peroxidase from Trypanosoma cruzi (PDB id, 1uul). The calculations indicate that C(p) (C52) pK(a) values are highly affected by oligomeric state; an unshifted C(p) pK(a) (approximately 8.3, comparable to the pK(a) of isolated cysteine) is calculated for the monomer. In the dimers, starting with essentially identical structures, the C(p)s evolve dynamically asymmetric pK(a)s during the simulations; one subunit's C(p) pK(a) is shifted downward at a time, while the other is unshifted. However, when averaged over time, or multiple simulations, the two subunits within a dimer exhibit the same C(p), showing no preference for a lowered pK(a) in either subunit. Two conserved pathways that communicate the asymmetric pK(a)s between C(p)s of different subunits can be identified. In the decamer, all the C(p) pK(a)s are shifted downward, with slight asymmetry in the dimers which form the decamers. Structural analyses implicate oligomerization effects as responsible for these oligomeric state-dependent C(p) pK(a) shifts. The intra-dimer and the inter-dimer subunit contacts in the decamer restrict the conformations of the side chains of several residues (T49, T54 and E55) calculated to be key in shifting the C(p) pK(a). In addition, the backbone fluctuations of a few residues (M46, D47 and F48) result in a different electrostatic environment for the C(p) in dimers relative to the monomers. These side chain and backbone interactions which contribute to pK(a) modulation indicate the importance of oligomerization to the function of the typical 2-Cys Prxs. |
| PMID: 20476795 [PubMed - indexed for MEDLINE] | |
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