Tuesday, May 5, 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 -10 of 11

1: Indian J Pediatr. 2009 Apr;76(4):436-7.

Multiple relapses of Visceral Leishmaniasis in a patient treated with liposomal amphotericin.

Department of Pediatric Haematology, Pamukkale University, Postal Code-20100, Denizli, Turkey, drmakin80@hotmail.com.

PMID: 19412589 [PubMed - in process]

2: J Pediatr Gastroenterol Nutr. 2009 May;48(5):639-642.

Visceral Leishmaniasis Mimicking Autoimmune Hepatitis.

*IsMeTT, University of Pittsburgh Medical Center, Palermo, Italy daggerUnità di Gastroenterologia ed Epatologia, Dipartimento di Pediatria, Italy double daggerUnità di Anatomia Patologica, Dipartimento di Oncologia, dei Trapianti e delle nuove Tecnologie in Medicina, Azienda Ospedaliera-Universitaria Pisana, Pisa, Italy.

PMID: 19412014 [PubMed - as supplied by publisher]

3: Cell Cycle. 2009 Jun 27;8(11). [Epub ahead of print]

Prediction of novel families of enzymes involved in oxidative and other complex modifications of bases in nucleic acids.

National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.

Modified bases in nucleic acids present a layer of information that directs biological function over and beyond the coding capacity of the conventional bases. While a large number of modified bases have been identified, many of the enzymes generating them still remain to be discovered. Recently, members of the 2-oxoglutarate- and iron(II)-dependent dioxygenase super-family, which modify diverse substrates from small molecules to biopolymers, were predicted and subsequently confirmed to catalyze oxidative modification of bases in nucleic acids. Of these, two distinct families, namely the AlkB and the kinetoplastid base J binding proteins (JBP) catalyze in situ hydroxylation of bases in nucleic acids. Using sensitive computational analysis of sequences, structures and contextual information from genomic structure and protein domain architectures, we report five distinct families of 2-oxoglutarate- and iron(II)-dependent dioxygenase that we predict to be involved in nucleic acid modifications. Among the DNA-modifying families, we show that the dioxygenase domains of the kinetoplastid base J-binding proteins belong to a larger family that includes the Tet proteins, prototyped by the human oncogene Tet1, and proteins from basidiomycete fungi, chlorophyte algae, heterolobosean amoeboflagellates and bacteriophages. We present evidence that some of these proteins are likely to be involved in oxidative modification of the 5-methyl group of cytosine leading to the formation of 5-hydroxymethylcytosine. The Tet/JBP homologs from basidiomycete fungi such as Laccaria and Coprinopsis show large lineage-specific expansions and a tight linkage with genes encoding a novel and distinct family of predicted transposases, and a member of the Maelstrom-like HMG family. We propose that these fungal members are part of a mobile transposon. To the best of our knowledge, this is the first report of a eukaryotic transposable element that encodes its own DNA-modification enzyme with a potential regulatory role. Through a wider analysis of other poorly characterized DNA-modifying enzymes we also show that the phage Mu Mom-like proteins, which catalyze the N6-carbamoylmethylation of adenines, are also linked to diverse families of bacterial transposases, suggesting that DNA modification by transposable elements might have a more general presence than previously appreciated. Among the other families of 2-oxoglutarate- and iron(II)-dependent dioxygenases identified in this study, one which is found in algae, is predicted to mainly comprise of RNA-modifying enzymes and shows a striking diversity in protein domain architectures suggesting the presence of RNA modifications with possibly unique adaptive roles. The results presented here are likely to provide the means for future investigation of unexpected epigenetic modifications, such as hydroxymethyl cytosine, that could profoundly impact our understanding of gene regulation and processes such as DNA demethylation.

PMID: 19411852 [PubMed - as supplied by publisher]

4: Travel Med Infect Dis. 2009 May;7(3):125-46. Epub 2009 Apr 11.

A practical approach to common skin problems in returning travellers.

Worldwise Traveller's Health, 72 Remuera Road, Newmarket, Auckland, New Zealand.

Skin diseases are the third most common cause of morbidity in returning travellers and may affect 8% of travellers during travel. Classic tropical diseases account for one quarter and the remainder are cosmopolitan diseases. The majority are of infectious origin, and of these bacterial infections are the most common and lead to the most hospitalisations. The ten most frequently encountered diagnoses comprise four classical tropical infections (cutaneous larva migrans, myiasis, tungiasis and cutaneous leishmaniasis) and six nontropical diseases (bacterial skin infections, arthropod bites, allergic reactions, scabies, animal bites and superficial fungal infections). Other notable skin problems include swimmer's itch, dengue fever presenting with a rash and rickettsial infections presenting with a rash or eschar. Delayed diagnosis, especially of tropical diseases, is common and may be reduced by improved knowledge and a systematic approach to skin problems. This involves a thorough travel specific, traveller specific and skin problem based history, combined with targeted examination and investigations. A frequency weighted differential diagnosis of the most common skin lesions is presented. An increased emphasis on preventative advice in relation to skin disease is encouraged during pre-travel consultations.

PMID: 19411040 [PubMed - in process]

5: Prog Histochem Cytochem. 2009 Jun;44(2):67-124. Epub 2009 Apr 5.

Electron microscopy and cytochemistry analysis of the endocytic pathway of pathogenic protozoa.

Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, bloco G subsolo, Cidade Universitária, Ilha do Fundão, Rio de Janeiro 21941-902, Brazil; Diretoria de Programas, Instituto Nacional de Metrologia, Normalização e Qualidade Industrial-INMETRO, Av. Nossa Senhora das Graças, 50, Xerém, Duque de Caxias - Rio de Janeiro 25250-020, Brazil.

Endocytosis is essential for eukaryotic cell survival and has been well characterized in mammal and yeast cells. Among protozoa it is also important for evading from host immune defenses and to support intense proliferation characteristic of some life cycle stages. Here we focused on the contribution of morphological and cytochemical studies to the understanding of endocytosis in Trichomonas, Giardia, Entamoeba, Plasmodium, and trypanosomatids, mainly Trypanosoma cruzi, and also Trypanosoma brucei and Leishmania.

PMID: 19410686 [PubMed - as supplied by publisher]

6: Vet Parasitol. 2009 Mar 31. [Epub ahead of print]

Effects of melarsamine hydrochloride (Cymelarsan((R))) and diminazene aceturate (Berenil((R))) on the pathology of experimental Trypanosoma brucei infection in red fronted gazelles (Gazella rufifrons).

Department of Veterinary Microbiology & Parasitology, University of Maiduguri, Nigeria.

An experimental infection of red fronted gazelles (Gazella rufifrons) with Trypanosoma brucei strain MKAR/84/NITR/6 was carried out. Two waves of parasitaemia which corresponded with a significant decline (p<0.05) in packed cell volume (PCV) was encountered in the infected untreated controls and those treated at day 8 post-infection with a sub-optimal dosage of diminazene aceturate (Berenil((R))) at 3.5mg/kg body weight. At postmortem, hepatomegally, splenomegally, lymphadenopathy, nephritis, myocardial degeneration with pulmonary oedema was observed in the two groups. Similarly, histopathological studies of some organs revealed interstitial haemorrhages, severe degenerative changes with cellular infiltrations. On the other hand, those treated by day 8 post-infection with melarsamine hydrochloride (Cymelarsan((R))) at 0.3mg/kg, 0.6mg/kg or diminazene aceturate (Berenil((R))) at 7.0mg/kg body weight had apparently normal organs at the end of the experiment. These results suggest that, T. brucei can cause severe pathological changes in untreated red fronted gazelles (Gazellarufifrons). However, treatments at the onset of parasitaemia, by day 8 post-infection with melarsamine hydrochloride (Cymelarsan((R))) at 0.3 and 0.6mg/kg or diminazene aceturate (Berenil((R))) at 7.0mg/kg body weight ameliorated the deleterious effects of the infection in the gazelles.

PMID: 19410371 [PubMed - as supplied by publisher]

7: Int J Antimicrob Agents. 2009 Apr 29. [Epub ahead of print]

Artesunate plus sulfamethoxypyrazine/pyrimethamine for the treatment of cutaneous leishmaniasis: a double-blind, placebo-controlled clinical trial.

P.O. Box 102, Faculty of Medicine, University of Khartoum, Khartoum, Sudan.

PMID: 19409761 [PubMed - as supplied by publisher]

8: Eur J Med Chem. 2009 Mar 24. [Epub ahead of print]

Synthesis and antiprotozoal activities of dicationic bis(phenoxymethyl)benzenes, bis(phenoxymethyl)naphthalenes, and bis(benzyloxy)naphthalenes.

Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC 27599-7525, USA.

A series of 37 dicationically substituted bis(phenoxymethyl)benzene bis(phenoxymethyl)naphthalene, and bis(benzyloxy)naphthalene analogues of pentamidine was prepared and evaluated for antiprotozoal activities and cytotoxicity in in vitro. 1,3-Bis(4-amidinophenoxymethyl)benzene (1) was the most active against Trypanosoma brucei rhodesiense (IC(50)=2.1nM). 1,3-Bis[4-(N-isopropylamidino)phenoxymethyl]benzene (2) was most active against Plasmodium falciparum (IC(50)=3.6nM) and displayed a selectivity index more than 50 times greater than that of pentamidine. Several other compounds displayed lower antiplasmodial IC(50) values and higher selectivity indices relative to pentamidine. 1,4-Bis(4-amidinophenoxymethyl)benzene (14) was the most active against Leishmania donovani (IC(50)=1.3muM). Compound 2 displayed the greatest activity against T. b. rhodesiense in vivo, curing three of four infected mice dosed intraperitoneally at 5mg/kgx4 days.

PMID: 19409677 [PubMed - as supplied by publisher]

9: Mol Biochem Parasitol. 2009 Apr 28. [Epub ahead of print]

Kinetoplastid papain-like cysteine peptidases.

Sandler Center for Basic Research in Parasitic Diseases, California Institute for Quantitative Biosciences, Byers Hall, University of California San Francisco, 1700 4(th) Street, San Francisco, CA 94158, U.S.A.

Cysteine peptidases are important for growth and survival of kinetoplastid parasites. The best characterised are those homologous to mammalian cathepsins B and L. To address a somewhat confusing terminology, we introduce a unifying nomenclature for kinetoplastid CATB and CATL peptidases. We review their evolutionary relatedness, genomic organisation, developmental expression, subcellular location and physiological functions. In addition, the applications of kinetoplastid CATB and CATL enzymes as vaccine candidates, diagnostic markers and drug targets are discussed.

PMID: 19409421 [PubMed - as supplied by publisher]

10: Mol Ecol. 2009 Apr;18(8):1801-13. Epub 2009 Mar 17.Click here to read LinkOut

Detection of selection signatures within candidate regions underlying trypanotolerance in outbred cattle populations.

Institut de Recherche pour le Développement, Unité Mixte de Recherche Trypanosomes, TA A-17/A Campus international de Baillarguet, Montpellier cedex 5, France.

Breeding indigenous African taurine cattle tolerant to trypanosomosis is a straightforward approach to control costs generated by this disease. A recent study identified quantitative trait loci (QTL) underlying trypanotolerance traits in experimental crosses between tolerant N'Dama and susceptible Boran zebu cattle. As trypanotolerance is thought to result from local adaptation of indigenous cattle breeds, we propose an alternative and complementary approach to study the genetic architecture of this trait, based on the identification of selection signatures within QTL or candidate genes. A panel of 92 microsatellite markers was genotyped on 509 cattle belonging to four West African trypanotolerant taurine breeds and 10 trypanosusceptible European or African cattle breeds. Some of these markers were located within previously identified QTL regions or candidate genes, while others were chosen in regions assumed to be neutral. A detailed analysis of the genetic structure of these different breeds was carried out to confirm a priori grouping of populations based on previous data. Tests based on the comparison of the observed heterozygosities and variances in microsatellite allelic size among trypanotolerant and trypanosusceptible breeds led to the identification of two significantly less variable microsatellite markers. BM4440, one of these two outlier loci, is located within the confidence interval of a previously described QTL underlying a trypanotolerance-related trait. Detection of selection signatures appears to be a straightforward approach for unravelling the molecular determinism of trypanosomosis pathogenesis. We expect that a whole genome approach will help confirm these results and achieve a higher resolving power.

PMID: 19302350 [PubMed - indexed for MEDLINE]

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