Saturday, June 13, 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: Nat Prod Res. 2009;23(10):909-15.Click here to read

A novel 1-indanone isolated from Uvaria afzelii roots.

Okpekon T, Millot M, Champy P, Gleye C, Yolou S, Bories C, Loiseau P, Laurens A, Hocquemiller R.

Laboratoire de Chimie Analytique, UFR des Sciences Pharmaceutiques et Biologiques, 22 BP 714Abidjan 22, République de Côte d'Ivoire.

Bioactivity-guided fractionations of chloromethylenic extract of the roots of U. afzelii (Annonaceae), using Leishmania donovani and Trypanosoma brucei brucei bioassay, resulted in the isolation of the two known compounds, emorydone (1) and demethoxymatteucinol (2), previously isolated from the stems, which were characterised from this source. In addition, the novel 1-indanone, afzeliindanone (3), was also isolated. The structure determination of afzeliindanone (3) was elucidated on the basis of spectral data as 4-[4-hydroxy-3-methoxyphenyl]-indan-1-one. This compound is the first 1-indanone derivative isolated from plants.

PMID: 19521904 [PubMed - in process]

2: Int J Parasitol. 2009 Jun 8. [Epub ahead of print]Click here to read

Trypanosoma vivax displays a clonal population structure.

Duffy CW, Morrison LJ, Black A, Pinchbeck GL, Christley RM, Schoenefeld A, Tait A, Turner CM, Macleod A.

Glasgow Biomedical Research Centre, Wellcome Centre for Molecular Parasitology, Faculty of Veterinary Medicine, University of Glasgow, 120 University Place, Glasgow G12 8TA, United Kingdom.; Division of Infection and Immunity, Faculty of Biomedical and Life Sciences, University of Glasgow, Biomedical Research Centre, 120 University Place, Glasgow G12 8TA, United Kingdom.

African animal trypanosomiasis, or Nagana, is a debilitating and economically costly disease with a major impact on animal health in sub-Saharan Africa. Trypanosoma vivax, one of the principal trypanosome species responsible for the disease, infects a wide host range including cattle, goats, horses and donkeys and is transmitted both cyclically by tsetse flies and mechanically by other biting flies, resulting in a distribution covering large swathes of South America and much of sub-Saharan Africa. While there is evidence for mating in some of the related trypanosome species, Trypanosoma brucei, Trypanosoma congolense and Trypanosoma cruzi, very little work has been carried out to examine this question in T. vivax. Understanding whether mating occurs in T. vivax will provide insight into the dynamics of trait inheritance, for example the spread of drug resistance, as well as examining the origins of meiosis in the order Kinetoplastida. With this in mind we have identified orthologues of eight core meiotic genes within the genome, the presence of which imply that the potential for mating exists in this species. In order to address whether mating occurs, we have investigated a sympatric field population of T. vivax collected from livestock in The Gambia, using microsatellite markers developed specifically for this species. Our analysis has identified a clonal population structure showing significant linkage disequilibrium, homozygote deficits and disagreement with Hardy-Weinberg predictions at six microsatellite loci, indicative of a lack of mating in this population of T. vivax.

PMID: 19520081 [PubMed - as supplied by publisher]

3: Mini Rev Med Chem. 2009 Jun;9(6):674-86.

Novel findings on trypanosomatid chemotherapy using DNA topoisomerase inhibitors.

Díaz-González R, Pérez-Pertejo Y, Prada CF, Fernández-Rubio C, Balaña-Fouce R, Reguera RM.

Dpto. Farmacología y Toxicología, Universidad de León, Campus de Vegazana s/n, 24071 León, Spain. rbalf@unileon.es.

Trypanosomatid (order Kinetoplastida)-borne neglected tropical diseases - African and American trypanosomiasis and leishmaniasis - are amongst the most devastating health threats of underdeveloped, developing and poor countries. Climatic changes due to global warming, tourism exchange and increasing migratory fluxes are re-distributing the endemic subtropical location of these diseases to a new scenario with a rising presence in developed countries during the last decades. In addition, the proved opportunistic transmission of these diseases through contaminated syringes shared by drug users, in combination with immunosuppression processes linked to HIV infections and the poor response to the typical treatments, point to AIDS patients as a sensitive sub-population prone to suffer from these diseases. DNA topoisomerases are the "molecular engineers" that unravel the DNA during replication and transcription. The mechanism of DNA unwinding includes the scission of a single DNA strand - type I topoisomerases - or both DNA strands - type II topoisomerases - establishing transient covalent bonds with the scissile end. Camptothecin and etoposide - two natural drugs whose semi-synthetic derivatives are currently used in cancer chemotherapy - target types I and II DNA-topoisomerases respectively, stabilizing ternary topoisomerase-DNA-drug covalent complexes, which irreversibly poison the enzymes. Several differences between parasite and host DNA topoisomerases have pointed to these enzymes as potential drug targets in Trypanosomatids. The unusual localization inside the mitochondria-like organellum - the kinetoplast - linked to mini and maxicircles, as well as the uncommon heterodimeric structure of the DNA topoisomerase IB subfamily, make these proteins unquestionable targets for drug intervention against trypanosomatids.

PMID: 19519493 [PubMed - in process]

4: Infect Disord Drug Targets. 2009 Jun;9(3):366-74.

Interactive Text Mining with Pipeline Pilot: A Bibliographic Web-Based Tool for PubMed.

Vellay SG, Latimer NE, Paillard G.

Accelrys Ltd, 334 Cambridge Science Park, Cambridge CB4 0WN, UK. svellay@accelrys.com.

Text mining has become an integral part of all research in the medical field. Many text analysis software platforms support particular use cases and only those. We show an example of a bibliographic tool that can be used to support virtually any use case in an agile manner. Here we focus on a Pipeline Pilot web-based application that interactively analyzes and reports on PubMed search results. This will be of interest to any scientist to help identify the most relevant papers in a topical area more quickly and to evaluate the results of query refinement. Links with Entrez databases help both the biologist and the chemist alike. We illustrate this application with Leishmaniasis, a neglected tropical disease, as a case study.

PMID: 19519489 [PubMed - in process]

5: Mol Biochem Parasitol. 2009 Aug;166(2):190-3. Epub 2009 Apr 5.Click here to read LinkOut

Identification of core components of the exon junction complex in trypanosomes.

Bercovich N, Levin MJ, Clayton C, Vazquez MP.

INGEBI-CONICET, Vuelta de Obligado 2490, 2P, Buenos Aires, Argentina.

In animal cells, the exon junction complex (EJC) is deposited onto mRNAs during the second step of splicing, 20-24 nt upstream of the exon-exon junction. The EJC core contains four proteins: Mago, Y14, eIF4AIII and Btz. In trypanosomes, cis-splicing is very rare but all mRNAs are subject to 5'trans-splicing of a 39-nt RNA sequence. Here we show that trypanosomes have a conserved Mago and a divergent Y14 protein, but we were unable to identify a Btz orthologue. We demonstrate that Mago and Y14 form a stable heterodimer using yeast two hybrid analyses. We also show that this complex co-purifies in vivo in trypanosomes with a protein containing an NTF2 domain, typically involved in mRNA transport.

PMID: 19450736 [PubMed - indexed for MEDLINE]

6: PLoS ONE. 2009;4(4):e5113. Epub 2009 Apr 1.Click here to read Click here to read References for this PMC Article, Free in PMC, LinkOut

The MHC gene region of murine hosts influences the differential tissue tropism of infecting Trypanosoma cruzi strains.

Freitas JM, Andrade LO, Pires SF, Lima R, Chiari E, Santos RR, Soares M, Machado CR, Franco GR, Pena SD, Macedo AM.

Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

We have previously demonstrated that both parasite genetic variability and host genetic background were important in determining the differential tissue distribution of the Col1.7G2 and JG T. cruzi monoclonal strains after artificial infections in mice. We observed that the JG strain was most prevalent in hearts of mouse lineages with the MHC haplotype H-2(d) (BALB/c and DBA2), while Col1.7G2 was predominant in hearts from C57BL/6 mice, which have the H-2(b) haplotype. To assess whether the MHC gene region indeed influenced tissue tropism of T. cruzi, we used the same two parasite strains to infect C57BL/6 (H-2(b)) and C57BLKS/J (H-2(d)) mice; the latter strain results from the introgression of DBA2 MHC region into the C57BL/6 background. We also performed ex vivo infections of cardiac explants from four congenic mice lineages with the H-2(b) and H-2(d) haplotypes arranged in two different genetic backgrounds: C57BLKS/J (H-2(d)) versus C57BL/6 (H-2(b)) and BALB/c (H-2(d)) versus BALB/B10-H2(b) (H-2(b)). In agreement with our former observations, Col1.7G2 was predominant in hearts from C57BL/6 mice (H-2(b)), but we observed a clear predominance of the JG strain in hearts from C57BLKS/J animals (H-2(d)). In the ex vivo experiments Col1.7G2 also prevailed in explants from H-2(b) animals while no predominance of any of the strains was observed in H-2(d) mice explants, regardless of the genetic background. These observations clearly demonstrate that the MHC region influences the differential tissue distribution pattern of infecting T. cruzi strains, which by its turn may be in a human infection the determinant for the clinical forms of the Chagas disease.

PMID: 19337367 [PubMed - indexed for MEDLINE]

PMCID: PMC2659742

7: Bioorg Med Chem. 2009 Apr 1;17(7):2673-9. Epub 2009 Mar 5.Click here to read LinkOut

Molecular modeling studies and in vitro bioactivity evaluation of a set of novel 5-nitro-heterocyclic derivatives as anti-T. cruzi agents.

Paula FR, Jorge SD, de Almeida LV, Pasqualoto KF, Tavares LC.

Departmento de Tecnologia Bioquímico-Farmacêutica, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Avenida Lineu Prestes, 580, Bloco 16, São Paulo, 05508-900, SP, Brazil.

In this study, in vitro anti-T. cruzi activity assays of nifuroxazide (NX) analogues, such as 5-nitro-2-furfuryliden and 5-nitro-2-theniliden derivatives, were performed. A molecular modeling approach was also carried out to relate the lipophilicity potential (LP) property and biological activity data. The majority of the NX derivatives showed increased anti-T. cruzi activity in comparison to the reference drug, benznidazole (BZN). Additionally, the 5-nitro-2-furfuryliden derivatives presented better pharmacological profile than the 5-nitro-2-theniliden analogues. The LP maps and corresponding ClogP values indicate that there is an optimum lipophilicity value, which must be observed in the design of new potential anti-T. cruzi agents.

PMID: 19303308 [PubMed - indexed for MEDLINE]

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