Tuesday, September 1, 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: Eukaryot Cell. 2009 Aug 28. [Epub ahead of print]

Trypanosoma pre-replication machinery contains a single functional Orc1/Cdc6 protein as typical of Archaea.

Godoy PD, Nogueira-Junior LA, Paes LS, Cornejo A, Martins RM, Silber AM, Schenkman S, Elias MC.

Laboratório de Parasitologia, Instituto Butantan, São Paulo; Departamento de Parasitologia, Universidade de São Paulo, São Paulo; Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, Brasil.

In unicellular eukaryotes, such as yeast, and in multicellular organisms, the replication origin is recognized by the heterohexamer origin recognition complex (ORC) containing six proteins Orc1-Orc6, while in Archaea the replication origin is recognized by just one protein, Orc1/Cdc6, which is highly sequence-related to Orc1 and Cdc6. Similar to Archaea, trypanosomatid genomes contain the only one gene annotated as Orc1. Since trypanosome Orc1 is also homologous to Cdc6, Orc1 from trypanosome were named here as Orc1/Cdc6. Here we show that the recombinant Orc1/Cdc6 from Trypanosoma cruzi (TcOrc1/Cdc6) and from Trypanosoma brucei (TbOrc1/Cdc6) present ATPase activity, typical from pre-replication machinery components. Also, TcOrc1/Cdc6 and TbOrc1/Cdc6 replaced yeast Cdc6 but not Orc1 in a phenotypic complementation assay. The induction of Orc1/Cdc6 silencing by RNAi in T. brucei resulted in enucleated cells, strong suggesting the involvement of Orc1/Cdc6 in DNA replication. Orc1/Cdc6 is expressed during the entire cell cycle in the nucleus of trypanosomes, remaining associated with chromatin in all stages of the cell cycle. These results allowed us to conclude that Orc1/Cdc6 is indeed a member of the trypanosome pre-replication machinery and point out that trypanosomes carry a pre-replication machinery that is less complex than other eukaryotes and closer to archaea.

PMID: 19717742 [PubMed - as supplied by publisher]

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2: Travel Med Infect Dis. 2009 Jul;7(4):215-8. Epub 2009 Jun 13.

A traveler with neurobrucellosis.

Van den Enden E, Vlieghe E, Demeester R, Ieven G, Jansens H, Van den Hauwe L.

Institute of Tropical Medicine, Department of Clinical Sciences, Nationalestraat 155, 2000 Antwerp, Belgium. evdenden@itg.be

An Indian traveler developed fever and neurological symptoms after a visit to East Africa. He was treated with suramin, melarsoprol and prednisolone for presumed East African trypanosomiasis. His condition deteriorated and cerebral lesions developed. Neurobrucellosis was diagnosed. Combination antibiotic therapy led to gradual clinical improvement and regression of the brain lesions. Misdiagnosis of East African trypanosomiasis followed by treatment with potentially lethal medication should be avoided by not relying on insufficient evidence during the diagnostic process.

PMID: 19717103 [PubMed - in process]

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3: Biochim Biophys Acta. 2009 Aug 27. [Epub ahead of print]

3D Entropy and Moments Prediction of Enzyme Classes and Experimental-Theoretic Study of Peptide Fingerprints in Leishmania Parasites.

Concu R, Dea-Ayuela MA, Perez-Montoto LG, Prado-Prado FJ, Uriarte E, Bolás-Fernández F, Podda G, Pazos A, Munteanu CR, Ubeira FM, González-Díaz H.

Department of Microbiology & Parasitology, Faculty of Pharmacy, USC, 15782 Santiago de Compostela, Spain; Dipartimento Farmaco Chimico Tecnologico, Facoltá di Farmacia, UNICA, Cagliari 09124, Italy.

The number of protein 3D structures without function annotation in Protein Data Bank (PDB) has been steadily increased. This fact has led in turn to an increment of demand for theoretical models to give a quick characterization of these proteins. In this work, we present a new and fast Markov Chain Model (MCM) to predict the Enzyme Classification (EC) number. We used both Linear Discriminant Analysis (LDA) and/or Artificial Neural Networks (ANN) in order to compare linear vs. non-linear classifiers. The LDA model found is very simple (three variables) and at the same time is able to predict the first EC number with an overall accuracy of 79% for a dataset of 4755 proteins (859 enzymes and 3896 non-enzymes) divided into both training and external validation series. In addition, the best non-linear ANN model is notably more complex but has an overall accuracy of 98.85%. It is important to emphasize that this method may help us to predict not only new enzyme proteins but also to select peptide candidates found on the Peptide Mass Fingerprints (PMFs) of new proteins that may improve enzyme activity. In order to illustrate the use of the model in this regard, we first report the 2D-Electrophoresis (2DE) and MADLI-TOF Mass Spectra characterization of the PMF of a new possible malate dehydrogenase sequence from Leishmania infantum. Next, we used the models to predict the contribution to a specific enzyme action of 30 peptides found in the PMF of the new protein. We implemented the present model in a server at portal Bio-AIMS (http://miaja.tic.udc.es/Bio-AIMS/EnzClassPred.php). This free on-line tool is based on PHP/HTML/Python and MARCH-INSIDE routines. This combined strategy may be used to identify and predict peptides of prokaryote and eukaryote parasites and their hosts, as well as other superior organisms; which may be of interest in drug development or target identification.

PMID: 19716935 [PubMed - as supplied by publisher]

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4: Acta Trop. 2009 Aug 27. [Epub ahead of print]

Lutzomyia migonei as putative vector of Visceral Leishmaniasis in La Banda. Argentina.

Salomón OD, Quintana MG, Bezzi G, Morán ML, Betbeder E, Valdéz DV.

Centro Nacional de Diagnóstico e Investigación en Endemo-epidemias, ANLIS, Ministerio de Salud de la Nación.

Four autochthonous cases of human visceral leishmaniasis (VL) were reported in La Banda, Santiago del Estero from June 2007 to May 2008. In the vicinity of these cases there were 3/47 rK39 sero-positive dogs, and another 4 dogs with VL were reported by passive surveillance. The sero-positive dogs and infected humans lived within a 3.1km radius. Phebotomine sand fly captures were performed twice during November/December 2007 and April 2008. In 20 of the 59 sampled sites in the areas of the human and canine cases (220 night/traps) 151 phlebotomine sand flies were collected and consisted of: Lutzomyia migonei 93%, Lu. cortelezzii: 5.6% and Lu. neivai: 1.4%. We propose that there was an enzootic cycle of VL with accidental human transmission due to Lu. migonei and suggest that there be a surveillance of human isolated cases of VL within the Lu. migonei dispersion area.

PMID: 19716797 [PubMed - as supplied by publisher]

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5: Transplant Proc. 2009 Jul-Aug;41(6):2363-5.

Renal transplantation in emigrants from Africa in Spain: similar results but different infectious profile compared with spanish people.

Mérida E, Rodríguez A, Hernandez G, Huerta A, Gonzalez J, Hernández A, González E, Morales E, Praga M, Andrés A, Morales JM.

Nephrology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.

The number of renal transplantation of emigrants from Africa in Europe is increasing. However, there is little information about the results. The aim of this study was to compare the results of renal transplantation among this African emigrant population compared with a matched group of Spanish patients. From 1996-2006, 27 African emigrants (from Morocco, Guinea, and Nigeria) received renal transplants in Madrid. We compared their results with a matched cohort, including 69% who received a kidney from the same donors to 49 Caucasian Spanish patients. Demographic data were similar except that retransplantation was more frequent (32% vs 0%; P = .02) among Spanish patients and hepatitis B was more frequent among the African group (22% vs 2%; P = .004). For both groups the most frequent regimen was steroids, tacrolimus, and mycophenolate mofetil. Acute rejection incidence was similar (Africans 26% vs Spanish 22%), but rejection as a cause of graft loss was numerically more frequent in Africans (4 of 6). Patient and graft survival rates were identical in both groups (96% and 80%, respectively) at a mean follow-up of 76 months in Africans versus 68 months in Spanish people. Characteristically African patients required higher dose of tacrolimus to maintain the same levels; and notably, they suffered rare opportunistic infections, such as Phonopsis longicolla and visceral Leishmania. In summary, renal transplantation in African emigrant patients in Spain showed excellent results similar to those obtained with a Spanish population. However, these patients needed higher doseses of Tacrolimus and experienced more rare opportunistic infections.

PMID: 19715920 [PubMed - in process]

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Patient Drug Information

  • Tacrolimus (Prograf®)

    Tacrolimus is used along with other medications to prevent rejection (attack of a transplanted organ by the immune system of a person receiving the organ) in people who have received kidney, liver, or heart transplants. ...

  • Mycophenolate (CellCept®, Myfortic®)

    Mycophenolate (CellCept) is used with other medications to help prevent transplant organ rejection (attack of the transplanted organ by the immune system of the person receiving the organ) in people who have received kid...

  • Source: AHFS Consumer Medication Information
6: J Med Chem. 2009 Aug 31. [Epub ahead of print]

On-Bead Screening of a Combinatorial Fumaric Acid Derived Peptide Library Yields Antiplasmodial Cysteine Protease Inhibitors with Unusual Peptide Sequences.

Machon U, Büchold C, Stempka M, Schirmeister T, Gelhaus C, Leippe M, Gut J, Rosenthal PJ, Kisker C, Leyh M, Schmuck C.

Institute of Organic Chemistry, University of Duisburg-Essen, Universitatstrasse 7, 45141 Essen, Germany.

A new class of cysteine protease inhibitors based on fumaric acid derived oligopeptides was successfully identified from a high-throughput screening of a solid-phase bound combinatorial library. As target enzymes falcipain and rhodesain were used, which play important roles in the life cycles of the parasites which cause malaria (Plasmodium falciparum) and African sleeping sickness (Trypanosoma brucei rhodesiense). The best inhibitors with unusual amino acid sequences not reported before for this type of enzyme were also fully analyzed in detail in solution. K(i) values in the lower micromolar and even nanomolar region were found. Some inhibitors are even active against plasmodia and show good selectivity relative to other enzymes. Also the mechanism of action was studied and could be shown to be irreversible inhibition.

PMID: 19715342 [PubMed - as supplied by publisher]

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7: Trop Med Int Health. 2009 Jul;14(7):732-5. Epub 2009 Apr 23.Click here to read LinkOut

Sensitivity and specificity of Chagas Stat-Pak test in Bolivia.

Chippaux JP, Santalla JA, Postigo JR, Romero M, Salas Clavijo NA, Schneider D, Brutus L.

Institut de Recherche pour le Développement, La Paz, Bolivia. jean-philippe.chippaux@ird.fr

OBJECTIVE: To compare the results of an immunochromatographic test performed on whole blood, Chagas Stat-Pak, with those of an ELISA test using recombinant antigens. METHOD: We tested 995 subjects of a rural population of all ages in the south of Bolivia, 459 pregnant women of the same population and 1030 urban women giving birth from the east of Bolivia. RESULTS: The sensitivity of the CSP test for the entire studied population (n = 2484) was 94.73% [93.35-96.10]; the specificity was 97.33% [96.50-98.15]. However, the specificity differed significantly between rural pregnant and urban birthing women, which could be attributed either to differences of parasite strain or Chagas prevalence. CONCLUSION: The test is simple of use, reliable, relatively inexpensive (<2 US$ each test) and its performances are compatible with a field use for large-scale screenings.

PMID: 19392737 [PubMed - indexed for MEDLINE]

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