Friday, April 24, 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: Nucleic Acids Res. 2009 Apr 22. [Epub ahead of print]Click here to read

Transcriptionally active TFIIH of the early-diverged eukaryote Trypanosoma brucei harbors two novel core subunits but not a cyclin-activating kinase complex.

Lee JH, Jung HS, Günzl A.

Department of Genetics and Developmental Biology, Department of Molecular, Microbial and Structural Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-3301 and Department of Cell Biology, University of Massachusetts, 55 Lake Ave, North, Worcester, MA 01655, USA.

Trypanosoma brucei is a member of the early-diverged, protistan family Trypanosomatidae and a lethal parasite causing African Sleeping Sickness in humans. Recent studies revealed that T. brucei harbors extremely divergent orthologues of the general transcription factors TBP, TFIIA, TFIIB and TFIIH and showed that these factors are essential for initiating RNA polymerase II-mediated synthesis of spliced leader (SL) RNA, a trans splicing substrate and key molecule in trypanosome mRNA maturation. In yeast and metazoans, TFIIH is composed of a core of seven conserved subunits and the ternary cyclin-activating kinase (CAK) complex. Conversely, only four TFIIH subunits have been identified in T. brucei. Here, we characterize the first protistan TFIIH which was purified in its transcriptionally active form from T. brucei extracts. The complex consisted of all seven core subunits but lacked the CAK sub-complex; instead it contained two trypanosomatid-specific subunits, which were indispensable for parasite viability and SL RNA gene transcription. These findings were corroborated by comparing the molecular structures of trypanosome and human TFIIH. While the ring-shaped core domain was surprisingly congruent between the two structures, trypanosome TFIIH lacked the knob-like CAK moiety and exhibited extra densities on either side of the ring, presumably due to the specific subunits.

PMID: 19386623 [PubMed - as supplied by publisher]

2: J Biol Chem. 2009 Apr 22. [Epub ahead of print]Click here to read

Dual targeting of a tRNA ASP requires two different aspartyl-tRNA synthetases in Trypanosoma brucei.

Charriere F, O'Donoghue P, Helgadottir S, Marechal-Drouard L, Cristodero M, Horn EK, Soll D, Schneider A.

University of Bern, Switzerland;

The mitochondrion of the parasitic protozoon Trypanosoma brucei does not encode any tRNAs. This deficiency is compensated for by partial import of nearly all of its cytosolic tRNAs. Most trypanosomal aminoacyl-tRNA synthetases are encoded by single copy genes suggesting the use of the same enzyme in the cytosol and in the mitochondrion. However, the T. brucei genome encodes two distinct genes for eukaryotic aspartyl-tRNA synthetase (AspRS) even though the cell has a single tRNA(Asp) isoacceptor only. Phylogenetic anaylsis showed that the two T. brucei AspRSs evolved from a duplication early in kinetoplastid evolution and also revealed that 8 other major duplications of AspRS occurred in the eukaryotic domain. RNAi analysis established that both Tb-AspRS1 and Tb-AspRS2 are essential for growth and required for cytosolic and mitochondrial Asp-tRNA(Asp) formation, respectively. In vitro charging assays demonstrated that the mitochondrial Tb-AspRS2 aminoacylates both cytosolic and mitochondrial tRNA(Asp), whereas the cytosolic Tb-AspRS1 selectively recognizes cytosolic but not mitochondrial tRNA(Asp). This indicates that cytosolic and mitochondrial tRNA(Asp), even though derived from the same nuclear gene, are physically different most likely due to a mitochondria-specific nucleotide modification. Mitochondrial Tb-AspRS2 defines a novel group of eukaryotic AspRSs with an extended substrate specificity that are restricted to trypanosomatids and therefore may be exploited as a novel drug target.

PMID: 19386587 [PubMed - as supplied by publisher]

3: Vet Parasitol. 2009 Mar 31. [Epub ahead of print]Click here to read

Selection of appropriate serological tests to measure the incidence of natural Leishmania infantum infection during DNA/MVA prime/boost canine vaccine trials.

Carson C, Antoniou M, Christodoulou V, Messaritakis I, Quinnell RJ, Blackwell JM, Courtenay O.

Populations and Disease Research Group, Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK.

In response to the increasing need for field trials of experimental DNA vaccines against zoonotic visceral leishmaniasis in dogs, our aim was to validate the use of ELISA protocols which will be suitable for detection of natural infection in vaccinated dogs. We have previously demonstrated that DNA/modified vaccinia virus Ankara (MVA) vaccine expressing tryparedoxin peroxidase (TRYP) induced high titres of TRYP antigen-specific IgG in immunized dogs. Here we report our findings that seroconversion to an unrelated diagnostic antigen rK39 did not occur in vaccinated dogs, and that responses to crude Leishmania infantum promastigote antigen (CLA) were weak and short-lived. This is in contrast to strong responses to both antigens shown in naturally infected dogs. To select an appropriate serological test for measurement of infection incidence, we also tested longitudinal samples from an immunologically well-characterized cohort of naturally infected dogs. The sensitivity of CLA ELISA was superior to that of rK39 in early stage infection (from 2 months before, to 2 months after the first detection of infection by PCR or parasitological culture), and more sensitive than rK39 in cross-sectional sampling (81.0% vs 61.9%). We conclude that CLA ELISA will provide sensitive estimates of L. infantum infection incidence in DNA/MVA vaccinated dogs, though optimal testing would include rK39, or a similar recombinant antigen, to improve overall specificity.

PMID: 19386420 [PubMed - as supplied by publisher]

4: Acta Dermatovenerol Croat. 2009 Apr;17(1):88-89.

Bolivarian Association of Dermatology, Cartagena, Colombia, November 10-11, 2008.

Lipozenčić J.

This joyful meeting of the Bolivarian Association of Dermatology, ebulliently celebrating its 15th anniversary, was coordinated adroitly by distinguished dermatologist Gonzalo Marrugo Guardo, Association President Blanca Peña Zapata, Association Vice President and founding President Alfonso Navarro Cesar, and Secretary Erick Alvarez Pereira (Fig 1). It was held in romantic Cartagena, an enchanting walled city founded in 1533 on the Caribbean coast in this nation named after Christopher Columbus. Liberated from colonial rule by Simón Bolivar in 1819, Colombia today is the size of Spain, France and Portugal combined and contains extraordinary geographic diversity with more plant and animal species per square kilometer than any other country in the entire world. The academic program consisted mainly of a featured address entitled "Dermatitis Atópica: un Desafío Clinico" (Atopic Dermatitis: a Clinical Challenge) by Robert A. Schwartz (USA), who was elected to honorary membership (Fig 2). Professor Schwartz noted that Gonzalo Marrugo and so many other superb Colombian dermatologists had trained with the legendary Professor Fernando Latapí (1902-1989), a shared mentor since Dr. Schwartz had spent a month rotating with him in 1976 at the Centro Dermatológico Pascua in Mexico City. At the University of Cartagena Hospital dedicated chief of dermatology Francisco Camacho Chaljub and talented dermatology faculty member Maria José Guerrero examined patients with Dr. Schwartz, including some with verrucous leishmaniasis, tuberous sclerosis complex, and leprosy (Fig 3). Additionally, Dr. Marrugo was joined by Dr. Schwartz in examining patients at the former's Bocagrande private office adjacent to Bocagrande Hospital, including a challenging one with a dystrophic form of epidermolysis bullosa. We saluted the traditions established by Gonzalo Marrugo's illustrious dermatologist father, Rubén Marrugo (1911-1989), Titular Professor at the University of Cartagena Faculty of Medicine, who was renowned for his work on leprosy, and look to a bright tomorrow with Gonzalo Marruago's children Gonzalo and Jacqueline Marrugo Lara, future third generation dermatologists, both currently medical students at the Pontifical Xaverian University Faculty of Medicine in Bogotá. The wonderful Colombian hospitality of Gonzalo Marrugo and his elegant and eminent periodonist wife Jacqueline Lara will be remembered with affection (Fig 4). An enjoyable noteworthy Sunday outing with them was to a medicinal mud volcano, Volcán de Lodo El Totumo, on the way to Barranquilla to see Antonio Jaller Raad (President, Dermocaribe Congress 2009), his graceful wife Maria Luisa Granados, lawyer daughter Maria Luisa and budding dermatologist son José Antonio. We thought of the inspiring leader of Colombian dermatology, Rafael Falabella, Professor and Founding Head, Dermatology, University del Valle, Cali, who has earned our admiration, gratitude, and respect.

PMID: 19386222 [PubMed - as supplied by publisher]

5: Expert Rev Proteomics. 2009 Apr;6(2):199-211.Click here to read

Protozoan parasite aquaporins.

Fadiel A, Isokpehi RD, Stambouli N, Hamza A, Benammar-Elgaaied A, Scalise TJ.

Department of OBGYN, New York University School of Medicine, New York, NY 10016, USA; and, Bellevue Hospital Center, New York University School of Medicine, 462 First Avenue, New York, NY 10016, USA. fadiea01@nyu.edu.

Protozoan parasites are a major threat to human health with millions of fatalities worldwide, especially in nonindustrialized countries. Currently, there is no cure for many of these parasitic diseases. Consequently, there is an imperative to find treatment targets and develop novel drugs based on the proteins encoded in the genomes of these parasites. Aquaporins, members of membrane proteins discovered and characterized within the past 20 years, are the mechanism through which water is transported through living membranes. The presence of aquaporins explains disease etiology related to water physiology and presents new pharmacogenomic targets. In this article, we review the literature on aquaporins found in Apicomplexan, Kinetoplastida and Microsporidia parasites as potential drug targets. Furthermore, by analyzing protein motion dynamics, we identify impediments that need to be surmounted for developing effective drugs targeting the aquaglyceroporin of Plasmodium falciparum, the causative agent of the most fatal form of human malaria.

PMID: 19385945 [PubMed - as supplied by publisher]

6: J Biomol Struct Dyn. 2009 Jun;26(6):755-762.Click here to read

A Cost-effective Amino-acid-type Selective Isotope Labeling of Proteins Expressed in Leishmania tarentolae.

Foldynova-Trantirkova S, Matulova J, Dotsch V, Lohr F, Cirstea I, Alexandov K, Breitling R, Lukes J, Trantirek L.

Faculty of Sciences, University of South Bohemia, Ceske Budejovice, Czech Republic. trant@paru.cas.cz.

We report a cost efficient approach for amino-acid-type selective isotope labeling of proteins expressed in Leishmania tarentolae. The method provides an economically advantageous alternative to recently established protocol for isotopic labeling using expensive synthetic media. The method is based on cultivation of the L. tarentolae expression strain in a cheap complex medium supplemented with labeled amino acid(s). In this protocol, a labeled amino acid is deliberately diluted in the medium of undefined composition, which leads to a low-level isotope enrichment upon protein over-expression. The economic advantage of the protocol is achieved by avoiding large volumes of expensive synthetic medium. Decreased sensitivity of a NMR experiment due to low-level isotope enrichment is compensated by a five- to seven-fold increase of the yield of the recombinant protein in complex medium as compared to that in the synthetic medium. In addition, the decreased sensitivity can be compensated by using a higher magnetic field, cryo-detection system or higher number of transients during the NMR data acquisition. We show that enrichment as low as 5% does not compromise a NMR experiment and makes preparation of the recombinant proteins over-expressed in L. tarentolae economically viable. The method is demonstrated by selective labeling of the ~27 kDa enhanced green fluorescent protein (EGFP) with (15)N-labeled valine.

PMID: 19385703 [PubMed - as supplied by publisher]

7: Org Lett. 2009 May 7;11(9):1975-1978.Click here to read

The Aignopsanes, a New Class of Sesquiterpenes from Selected Chemotypes of the Sponge Cacospongia mycofijiensis.

Johnson TA, Amagata T, Sashidhara KV, Oliver AG, Tenney K, Matainaho T, Ang KK, McKerrow JH, Crews P.

Department of Chemistry and Biochemistry & Institute for Marine Sciences, University of California, Santa Cruz, California 95064, University of Papua New Guinea, National Captical District, Papua New Guinea, Sandler Center for Basic Research in Parasitic Disease, University of California, San Francisco, California 94143, and Small Molecule Discovery Center, University of California, San Francisco, California 94158.

A survey of individual specimens of northern Papua New Guinea derived Cacospongia mycofijiensis has yielded novel sesquiterpenes, aignopsanoic acid A (1), methyl aignopsanoate A (2), and isoaignopsanoic acid A (3). The structures and absolute configurations of 1-3 were established using NMR data, X-ray crystallography results, and an analysis of CD properties. Two of these metabolites, 1 and 2, were moderately active against Trypanosoma brucei, the parasite responsible for sleeping sickness.

PMID: 19385671 [PubMed - as supplied by publisher]

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