What's new for 'Trypanosomatids' in PubMed

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Sent on Wednesday, 2011 Feb 02
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.	RNA Biol. 2011 Jan 1;8(1). [Epub ahead of print] snRNA-specific role of SMN in trypanosome snRNP biogenesis in vivo. Jaé N, Preußer C, Krüger T, Tkacz ID, Engstler M, Michaeli S, Bindereif A. Institut für Biochemie, Justus-Liebig-Universität Gießen, Gießen, Germany. Abstract Pre-mRNA splicing in trypanosomes requires the SMN-mediated assembly of small nuclear ribonucleoproteins (snRNPs). In contrast to higher eukaryotes, the cellular localization of snRNP biogenesis and the involvement of nuclear-cytoplasmic trafficking in trypanosomes are controversial. By using RNAi knockdown of SMN in T.brucei to investigate its functional role in snRNP assembly, we found dramatic changes in the steady-state levels of snRNAs and snRNPs: The SL RNA accumulates, whereas U1, U4, and U5 snRNA levels decrease, and Sm core assembly in particular of the SL RNA is strongly reduced. In addition, SMN depletion blocks U4/U6 di-snRNP formation; the variant Sm core of the U2 snRNP, however, still forms efficiently after SMN knockdown. Concerning the longstanding question, whether nuclear-cytoplasmic trafficking is involved in trypanosomal snRNP biogenesis, fluorescence in situ hybridization (FISH) and immunofluorescence assays revealed that the SL RNA genes and transcripts colocalize with SMN. Remarkably, SMN silencing leads to a nucleoplasmic accumulation of both SL RNA and the Sm proteins. In sum, our data demonstrate an essential and snRNAselective role of SMN in snRNP biogenesis in vivo and strongly argue for a nucleoplasmic Sm core assembly of the SL RNP.
	PMID: 21282982 [PubMed - as supplied by publisher]

2.	Antimicrob Agents Chemother. 2011 Jan 31. [Epub ahead of print] Successful treatment of Old World cutaneous leishmaniasis due to L. infantum with Posaconazole. Paniz Mondolfi AE, Stavropoulos C, Gelanew T, Loucas E, Perez Alvarez AM, Benaim G, Polsky B, Schoenian G, Sordillo EM. Department of Pathology and Laboratory Medicine, St. Luke's-Roosevelt Hospital Center (University Hospital of Columbia University College of Physicians and Surgeons), New York NY-USA; Laboratorio de Bioquímica. Instituto de Biomedicina, Universidad Central de Venezuela/Ministerio de Salud y Desarrollo Social/IVSS, Caracas-Venezuela; Division of Infectious Diseases, St. Luke's-Roosevelt Hospital Center (University Hospital of Columbia University College of Physicians and Surgeons); Institut fuer Mikrobiologie und Hygiene, Charité Universitaetsmedizin Berlin, Berlin-Germany; Faculty of Medicine, Addis Ababa University, P.O. Box 9086, Addis Ababa, Ethiopia; Department of Dermatology, Mount Sinai School of Medicine, New York NY-USA; Instituto de Estudios Avanzados (IDEA), Caracas-Venezuela & Instituto de Biologia Experimetal, Facultad de Ciencias. Universidad Central de Venezuela, Caracas-Venezuela. Abstract Leishmania infantum is a known cause of Old World cutaneous leishmaniasis (OWCL). In acute OWCL, the lesion is usually limited to one or a few papules, plaques or nodules that evolve during a period of months to the ulcerous form (1, 2). Treatment options for OWCL include topical paromomycin ointment, local infiltration with antimonials, thermotherapy, or miltefosine (3). However, except for thermotherapy, these treatments are not Food and Dug Administration (FDA)-approved. Use of these therapies is also limited by variable efficacy and local and systemic side effects that affect tolerability and compliance (1, 3). We describe a patient with OWCL successfully treated with posaconazole, an oral drug typically considered an antifungal agent, but which also targets specific metabolic pathways of the parasite.
	PMID: 21282455 [PubMed - as supplied by publisher]

3.	Antimicrob Agents Chemother. 2011 Jan 31. [Epub ahead of print] Selective inhibitors of methionyl-tRNA synthetase have potent activity on Trypanosoma brucei infection in mice. Shibata S, Gillespie JR, Kelley AM, Napuli AJ, Zhang Z, Kovzun KV, Pefley RM, Lam J, Zucker F, Van Voorhis WC, Merritt EA, Hol WG, Verlinde CL, Fan E, Buckner FS. Department of Biochemistry and Department of Medicine, University of Washington, Seattle, Washington 98195, USA. Abstract Human African trypanosomiasis continues to be an important public health threat in extensive regions of Sub-Saharan Africa. Treatment options for infected patients are unsatisfactory due to toxicity, difficult administration regimes, and poor efficacy of available drugs. The aminoacyl-tRNA synthetases were selected as attractive drug targets due to their essential roles in protein synthesis and cell survival. Comparative sequence analysis disclosed differences between the trypanosome and mammalian methionyl-tRNA synthetases (MetRS) that suggested opportunities for selective inhibition using drug-like molecules. Experiments using RNA interference on the single MetRS of Trypanosoma brucei demonstrated that this gene product was essential for normal cell growth. Small molecules (diaryl diamines) similar to those shown to have potent activity on prokaryotic MetRS enzymes were synthesized and observed to have inhibitory activity on the T. brucei MetRS (IC50 <50 nM) and on bloodstream forms of T. brucei cultures (EC50 as low 4 nM). Twenty-one compounds had a close correlation between enzyme binding/inhibition and T. brucei growth inhibition indicating that they were likely to be acting on the intended target. The compounds had minimal effects on mammalian cell growth at 20 μM, demonstrating a wide therapeutic index. The most potent compound was tested in the murine model of trypanosomiasis and demonstrated profound parasite suppression and delayed mortality. A homology model of the T. brucei MetRS based on other MetRS structures was used to model binding of the lead diaryl diamine compounds. Future studies will focus on improving the pharmacological properties of the MetRS inhibitors.
	PMID: 21282428 [PubMed - as supplied by publisher]

4.	J Infect Dis. 2011 Mar;203(5):715-25. Epub 2011 Jan 31. Leishmania major Attenuates Host Immunity by Stimulating Local Indoleamin e 2,3-Dioxygenase Expression. Makala LH, Baban B, Lemos H, El-Awady AR, Chandler PR, Hou DY, Munn DH, Mellor AL. Immunotherapy Center. Abstract Inflammation stimulates immunity but can create immune privilege in some settings. Here, we show that cutaneous Leishmania major infection stimulated expression of the immune regulatory enzyme indoleamine 2,3 dioxygenase (IDO) in local lymph nodes. Induced IDO attenuated the T cell stimulatory functions of dendritic cells and suppressed local T cell responses to exogenous and nominal parasite antigens. IDO ablation reduced local inflammation and parasite burdens, as did pharmacologic inhibition of IDO in mice with established infections. IDO ablation also enhanced local expression of proinflammatory cytokines and induced some CD4(+) T cells to express interleukin (IL) 17. These findings showed that IDO induced by L. major infection attenuated innate and adaptive immune responses. Thus, IDO acts as a molecular switch regulating host responses, and IDO inhibitor drugs are a potential new approach to enhance host immunity to established leishmania infections.
	PMID: 21282196 [PubMed - in process]

5.	Vet Parasitol. 2011 Jan 11. [Epub ahead of print] Leishmania chagasi infection in cats with dermatologic lesions from an endemic area of visceral leishmaniosis in Brazil. Vides JP, Schwardt TF, Sobrinho LS, Marinho M, Laurenti MD, Biondo AW, Leutenegger C, Marcondes M. Department of Veterinary Clinics, Surgery and Reproduction, São Paulo State University, Araçatuba, São Paulo, 16050-680, Brazil. Abstract Although dogs are considered the main domestic reservoirs for Visceral Leishmaniosis (VL), which is caused in the Americas by Leishmania chagasi, infected cats have also been recently found in endemic areas of several countries and became a public health concern. Accordingly, the purpose of this study was to evaluate cats with dermatologic lesions from an endemic area of VL and the natural infection of L. chagasi. A total of 55 cats were selected between April 2008 and November 2009 from two major animal shelters of Araçatuba, Southeastern Brazil. All cats underwent general and dermatologic examinations, followed by direct parasitological examination of lymphoid organs, immunosorbent assay (ELISA) and indirect immunofluorescence (IFAT). In addition, detection of amastigotes was performed by immunohistochemistry (IHC) in skin lesions of all cats. VL was diagnosed in 27/55 (49.1%) cats with dermatological problems. Amastigotes were found in lymphoid organs of 10/27 (37.0%) cats; serology of 14/27 (51.9%), 6/27 (22.2%) and 5/27 (18.5%) cats was positive for ELISA, IFAT and both, respectively. The IHC identified 9/27 (33.3%) cats; 5/27 (18.5%) were positive only for IHC and therefore increased the overall sensitivity. Specific FIV antibodies were found in 6/55 (10.9%) cats, of which 5/6 (83.3%) had leishmaniosis. Real time PCR followed by amplicon sequencing successfully confirmed L. chagasi infection. In conclusion, dermatological lesions in cats from endemic areas was highly associated to visceral leishmaniosis, and therefore skin IHC and differential diagnosis of LV should be always conducted in dermatological patients in such areas. Copyright © 2011 Elsevier B.V. All rights reserved.
	PMID: 21282011 [PubMed - as supplied by publisher]

6.	Transpl Infect Dis. 2011 Jan 31. doi: 10.1111/j.1399-3062.2011.00598.x. [Epub ahead of print] Recurrent leishmaniasis in kidney transplant recipients: report of 2 cases and systematic review of the literature. Simon I, Wissing KM, Del Marmol V, Antinori S, Remmelink M, Nilufer Broeders E, Nortier JL, Corbellino M, Abramowicz D, Cascio A. Department of Nephrology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium Department of Nephrology, Universitair Ziekenhuis, Brussels, Belgium Department of Dermatology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium Department of Clinical Sciences, Section of Infectious Diseases and Immunopathology, Università degli Studi di Milano, Milano, Italy Department of Pathology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium Department of Human Pathology, Tropical and Parasitological Diseases Unit, University of Messina, Messina, Italy AILMI (Associazione Italiana per la Lotta contro le Malattie Infettive; Italian Association for the Control of Infectious Diseases), University of Messina, Messina, Italy. Abstract I. Simon, K.M. Wissing, V. Del Marmol, S. Antinori, M. Remmelink, E. Nilufer Broeders, J.L. Nortier, M. Corbellino, D. Abramowicz, A. Cascio. Recurrent leishmaniasis in kidney transplant recipients: report of 2 cases and systematic review of the literature. Transpl Infect Dis 2011. All rights reserved Abstract: The characteristics of 8 episodes of leishmaniasis with atypical manifestations in 2 Italian kidney transplant recipients are analyzed and contextualized among those of 52 other episodes of leishmaniasis observed in 19 transplant recipients found through a systematic review of the international literature. In all the patients, the initial episode was visceral leishmaniasis, which was associated with mucocutaneous involvement in 2 cases. With the exception of 1 case of post kala-azar dermal leishmaniasis, 2 episodes of Leishmania endophthalmitis, and 3 episodes of mucocutaneous leishmaniasis, all the recurrences were characterized by visceral involvement. The potential role of polymerase chain reaction in monitoring the infection, the importance of a long follow-up, the potential benefit of chemoprophylaxis, and the therapeutic challenges are discussed. © 2011 John Wiley & Sons A/S.
	PMID: 21281418 [PubMed - as supplied by publisher]