Tuesday, August 25, 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 -6 of 6

1: J Struct Funct Genomics. 2009 Aug 22. [Epub ahead of print]Click here to read

Heterologous expression of L. major proteins in S. cerevisiae: a test of solubility, purity, and gene recoding.

Quartley E, Alexandrov A, Mikucki M, Buckner FS, Hol WG, Detitta GT, Phizicky EM, Grayhack EJ.

Center for Pediatric Biomedical Research, University of Rochester Medical School, Rochester, NY, 14642, USA.

High level expression of many eukaryotic proteins for structural analysis is likely to require a eukaryotic host since many proteins are either insoluble or lack essential post-translational modifications when expressed in E. coli. The well-studied eukaryote Saccharomyces cerevisiae possesses several attributes of a good expression host: it is simple and inexpensive to culture, has proven genetic tractability, and has excellent recombinant DNA tools. We demonstrate here that this yeast exhibits three additional characteristics that are desirable in a eukaryotic expression host. First, expression in yeast significantly improves the solubility of proteins that are expressed but insoluble in E. coli. The expression and solubility of 83 Leishmania major ORFs were compared in S. cerevisiae and in E. coli, with the result that 42 of the 64 ORFs with good expression and poor solubility in E. coli are highly soluble in S. cerevisiae. Second, the yield and purity of heterologous proteins expressed in yeast is sufficient for structural analysis, as demonstrated with both small scale purifications of 21 highly expressed proteins and large scale purifications of 2 proteins, which yield highly homogeneous preparations. Third, protein expression can be improved by altering codon usage, based on the observation that a codon-optimized construct of one ORF yields three-fold more protein. Thus, these results provide direct verification that high level expression and purification of heterologous proteins in S. cerevisiae is feasible and likely to improve expression of proteins whose solubility in E. coli is poor.

PMID: 19701618 [PubMed - as supplied by publisher]

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2: J Am Acad Dermatol. 2009 Sep;61(3):441-50.

More experiences with the Tzanck smear test: cytologic findings in cutaneous granulomatous disorders.

Durdu M, Baba M, Seçkin D.

Department of Dermatology, Başkent University Faculty of Medicine, Adana, Turkey.

BACKGROUND: Granulomatous dermatitis is a distinctive histopathologic cutaneous reaction pattern against various infectious and noninfectious agents. Cytologically, granulomatous dermatitis shows granulomas and multinucleated giant cells. Various etiologic agents of granulomatous diseases can also be identified. OBJECTIVE: We aimed to investigate Tzanck smear findings in granulomatous skin diseases. METHODS: Patients who had granulomas and/or multinucleated giant cells of Langhans, foreign body- and/or Touton type in Tzanck smear tests were included in the study. In these patients, Tzanck preparations were then further evaluated for additional cytologic findings. Samples stained with May-Grünwald-Giemsa stain were evaluated by the same dermatologist throughout the study. In some patients, methylene blue, Gram and/or Erlich-Ziehl-Nielsen stains were also performed. In all of the study cases, the final diagnosis was established after the evaluation of clinical and laboratory findings (including, when appropriate, potassium hydroxide examination; bacterial, leishmanial, and fungal cultures; histopathology; tuberculosis and leishmania polymerase chain reaction). We also calculated the sensitivity and specificity of the Leishman-Donovan body for cutaneous leishmaniasis. RESULTS: Over a 2-year period, 94 of 950 patients (9.9%) in whom Tzanck smear tests were performed had cytologic findings consistent with a granulomatous reaction. In 74 (78.7%) and 20 (21.3%) patients, the granulomatous reaction was due to infectious and noninfectious causes, respectively. Infectious causes included cutaneous leishmaniasis in 65 patients (87.8%), candidal granuloma in two patients, botyromycosis in two patients, and aspergillosis, blastomycosis, mucormycosis, leprosy, and cutaneous tuberculosis in one patient each. In 58 of 74 patients (78.4%) with infectious granulomatous dermatitis, the causes of the granulomas were identified. Noninfectious granulomatous reactions were due to granuloma annulare in 7 patients, sarcoidosis in 5 patients, a foreign body in 4 patients, necrobiosis lipoidica in 2 patients, and juvenile xanthogranuloma in 2 patients. In 17 of 20 patients (85%) with noninfectious granulomatous reactions, the cytologic findings were characteristic of the final diagnoses. The sensitivity and specificity of Leishman-Donovan bodies for cutaneous leishmaniasis were 76.9% and 100%, respectively. LIMITATIONS: All of the samples were evaluated by the same dermatologist throughout the study; therefore no comment could be made regarding the reliability of the Tzanck smear test. In addition, the sensitivity and specificity of Tzanck smear test findings for diseases other than cutaneous leishmaniasis could not be calculated because of an insufficient number of patients. CONCLUSION: The Tzanck smear test may be a useful diagnostic tool for certain granulomatous skin diseases.

PMID: 19700014 [PubMed - in process]

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3: Bioorg Med Chem. 2009 Aug 7. [Epub ahead of print]Click here to read

Synthesis and activity of azaterphenyl diamidines against Trypanosoma brucei rhodesiense and Plasmodium falciparum.

Hu L, Arafa RK, Ismail MA, Patel A, Munde M, Wilson WD, Wenzler T, Brun R, Boykin DW.

Department of Chemistry, Georgia State University, Atlanta, GA 30303-3083, USA.

A series of azaterphenyl diamidines has been synthesized and evaluated for in vitro antiprotozoal activity against both Trypanosoma brucei rhodesiense (T. b. r.) and Plasmodium falciparum (P. f.) and in vivo efficacy in the STIB900 acute mouse model for T. b. r. Six of the 13 compounds showed IC(50) values less than 7nM against T. b. r. Twelve of those exhibited IC(50) values less than 6nM against P. f. and six of those showed IC(50) values 0.6nM, which are more than 25-fold as potent as furamidine. Moreover, two of them showed more than 40-fold selectivity for P. f. versus T. b. r. Three compounds 15b, 19d and 19e exhibited in vivo efficacy against T. b. r. much superior to furamidine, and equivalent to or better than azafuramidine. The antiparasitic activity of these diamidines depends on the ring nitrogen atom(s) location relative to the amidine groups and generally correlates with DNA binding affinity.

PMID: 19699098 [PubMed - as supplied by publisher]

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4: Parasitol Int. 2009 Aug 18. [Epub ahead of print]Click here to read

Challenges and perspectives in vaccination against leishmaniasis.

de Oliveira CI, Nascimento IP, Barral A, Soto M, Barral-Netto M.

Centro de Pesquisas Gonçalo Muniz-FIOCRUZ, Salvador, BA, Brazil.

The leishmaniases are a group of diseases caused by protozoa of the genus Leishmania which affect millions of people worldwide. The leishmaniases are transmitted to the vertebrate hosts by phlebotomine sand flies. In this review, we focus on areas poorly addressed in the ongoing efforts to develop a vaccine against Leishmania, namely: vaccination with antigens present in sand fly saliva, vaccines based on intracellular Leishmania antigens and use of recombinant BCG as a vehicle for vaccination. Additionally, we address the differences between L. major and L. braziliensis and the impact that it may have on strategies for immunoprophylaxis.

PMID: 19698801 [PubMed - as supplied by publisher]

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5: Biochem J. 2009 Aug 27;422(3):571.Click here to read

Biochemical characterization of the initial steps of the Kennedy pathway in Trypanosoma brucei: the ethanolamine and choline kinases.

Gibellini F, Hunter WN, Smith TK.

PMID: 19698088 [PubMed - in process]

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6: Molecules. 2009 Jun 22;14(6):2256-72.LinkOut

Heterocyclic-2-carboxylic acid (3-cyano-1,4-di-N-oxidequinoxalin-2-yl)amide derivatives as hits for the development of neglected disease drugs.

Ancizu S, Moreno E, Torres E, Burguete A, Pérez-Silanes S, Benítez D, Villar R, Solano B, Marín A, Aldana I, Cerecetto H, González M, Monge A.

Unidad en Investigación y Desarrollo de Medicamentos, Centro de Investigación en Farmacobiología Aplicada, University of Navarra, C/Irunlarrea s/n, 31008 Pamplona, Spain.

Neglected diseases represent a major health problem. It is estimated that one third of the world population is infected with tuberculosis (TB). Besides TB, Chagas disease, affects approximately 20 million people. Quinoxalines display great activities against TB and Chagas. Forty new quinoxaline 1,4-di-N-oxide derivatives have been prepared and tested against M. tuberculosis and T. cruzi. Carboxylic acid quinoxaline 1,4-di-N-oxides (CAQDOs) 5 and 17 showed MIC values on the same order as the reference antituberculosis drug, rifampicin. Meanwhile, CAQDOs 12 and 22 presented IC(50) values in the same order as the anti-chagasic drug, nifurtimox.

PMID: 19553897 [PubMed - indexed for MEDLINE]

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