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[PMID]: 29422501 [Au] Autor: Collopy LC; Ware TL; Goncalves T; Í Kongsstovu S; Yang Q; Amelina H; Pinder C; Alenazi A; Moiseeva V; Pearson SR; Armstrong CA; Tomita K [Ad] Endereço: Chromosome Maintenance Group, UCL Cancer Institute, University College London, London, WC1E 6DD, UK. [Ti] Título: LARP7 family proteins have conserved function in telomerase assembly. [So] Source: Nat Commun;9(1):557, 2018 02 08. [Is] ISSN: 2041-1723 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Understanding the intricacies of telomerase regulation is crucial due to the potential health benefits of modifying its activity. Telomerase is composed of an RNA component and reverse transcriptase. However, additional factors required during biogenesis vary between species. Here we have identified fission yeast Lar7 as a member of the conserved LARP7 family, which includes the Tetrahymena telomerase-binding protein p65 and human LARP7. We show that Lar7 has conserved RNA-recognition motifs, which bind telomerase RNA to protect it from exosomal degradation. In addition, Lar7 is required to stabilise the association of telomerase RNA with the protective complex LSm2-8, and telomerase reverse transcriptase. Lar7 remains a component of the mature telomerase complex and is required for telomerase localisation to the telomere. Collectively, we demonstrate that Lar7 is a crucial player in fission yeast telomerase biogenesis, similarly to p65 in Tetrahymena, and highlight the LARP7 family as a conserved factor in telomere maintenance. [Mh] Termos MeSH primário: Proteínas Nucleares/genética Fosfoproteínas/genética Proteínas de Protozoários/genética RNA Fúngico/genética DNA Polimerase Dirigida por RNA/genética RNA/genética Ribonucleoproteínas/genética Schizosaccharomyces/genética Telomerase/genética [Mh] Termos MeSH secundário: Motivos de Aminoácidos Sequência Conservada Expressão Gênica Seres Humanos Isoenzimas/genética Isoenzimas/metabolismo Proteínas Nucleares/metabolismo Fosfoproteínas/metabolismo Ligação Proteica Proteínas de Protozoários/metabolismo RNA/metabolismo Estabilidade de RNA RNA Fúngico/metabolismo DNA Polimerase Dirigida por RNA/metabolismo Ribonucleoproteínas/metabolismo Schizosaccharomyces/metabolismo Telomerase/metabolismo Telômero/química Telômero/ultraestrutura Tetrahymena thermophila/genética Tetrahymena thermophila/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Isoenzymes); 0 (Larp7 protein, human); 0 (Nuclear Proteins); 0 (Pdd1 protein, Tetrahymena); 0 (Phosphoproteins); 0 (Protozoan Proteins); 0 (RNA, Fungal); 0 (Ribonucleoproteins); 0 (Ter1 telomerase subunit, S pombe); 63231-63-0 (RNA); EC 2.7.7.49 (RNA-Directed DNA Polymerase); EC 2.7.7.49 (Telomerase) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180307 [Lr] Data última revisão: 180307 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180210 [St] Status: MEDLINE [do] DOI: 10.1038/s41467-017-02296-4

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[PMID]: 28460112 [Au] Autor: Aponte S; Guerra ÁP; Álvarez-Larrotta C; Bernal SD; Restrepo C; González C; Yasnot MF; Knudson-Ospina A [Ad] Endereço: Grupo de Bioquímica y Biología Celular, Instituto Nacional de Salud, Bogotá, D.C., Colombia. [Ti] Título: Baseline in vivo, ex vivo and molecular responses of Plasmodium falciparum to artemether and lumefantrine in three endemic zones for malaria in Colombia. [So] Source: Trans R Soc Trop Med Hyg;111(2):71-80, 2017 02 01. [Is] ISSN: 1878-3503 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Background: Colombia began using artemisinin-based combination therapies for the treatment of uncomplicated Plasmodium falciparum malaria in 2006. It is necessary to implement resistance surveillance to antimalarial drugs in order to promptly detect changes in parasite susceptibility. The aim of this study was to establish a susceptibility baseline of P. falciparum to artemether-lumefantrine using three monitoring tools. Methods: Patients with uncomplicated malaria treated with artemether-lumefantrine underwent clinical and parasitological follow-up over 28 days. Ex vivo test was performed using the microtest technique for chloroquine, arthemeter, dihydroartemisinin and lumefantrine. Pfmdr1 copy number and polymorphisms in Pfk13, Pfatp6, Pfcrt and Pfmdr1 genes were analyzed. Results: From a total of 150 screened patients, 49 completed follow-up for 28 days. All treated patients had adequate clinical and parasitological responses. Parasitic clearance showed a drastic reduction of parasite biomass at 24 hours and complete elimination at 48 hours. One hundred eleven isolates were processed, all exhibited high susceptibility to artemisinins and a slight decrease in susceptibility to lumefantrine. No genetic polymorphisms associated with resistance to artemisinin were found. Conclusion: This study generated a susceptibility baseline in response to therapy with Coartem (artemether-lumefantrine) with numerical reference values, which will allow data comparison with future studies to systematically monitor changes in the parasite and to provide an early alert to the health authorities. [Mh] Termos MeSH primário: Antimaláricos/uso terapêutico Artemisininas/uso terapêutico Etanolaminas/uso terapêutico Fluorenos/uso terapêutico Malária/tratamento farmacológico Plasmodium falciparum/efeitos dos fármacos [Mh] Termos MeSH secundário: Adolescente Adulto Idoso Antimaláricos/farmacologia Artemisininas/farmacologia Criança Colômbia Variações do Número de Cópias de DNA Combinação de Medicamentos Resistência a Medicamentos/efeitos dos fármacos Resistência a Medicamentos/genética Quimioterapia Combinada Etanolaminas/farmacologia Feminino Fluorenos/farmacologia Seres Humanos Malária/parasitologia Masculino Meia-Idade Parasitemia/tratamento farmacológico Plasmodium falciparum/isolamento & purificação Polimorfismo Genético Proteínas de Protozoários/genética Adulto Jovem [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Antimalarials); 0 (Artemisinins); 0 (Drug Combinations); 0 (Ethanolamines); 0 (Fluorenes); 0 (Protozoan Proteins); 0 (artemether-lumefantrine combination); C7D6T3H22J (artemether); F38R0JR742 (lumefantrine) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180308 [Lr] Data última revisão: 180308 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170502 [St] Status: MEDLINE [do] DOI: 10.1093/trstmh/trx021

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[PMID]: 29180487 [Au] Autor: Pierog PL; Zhao Y; Singh S; Dai J; Yap GS; Fitzgerald-Bocarsly P [Ad] Endereço: Department of Pathology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103. [Ti] Título: Inactivates Human Plasmacytoid Dendritic Cells by Functional Mimicry of IL-10. [So] Source: J Immunol;200(1):186-195, 2018 01 01. [Is] ISSN: 1550-6606 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Plasmacytoid dendritic cells (pDCs) are the major producers of IFN-α, an antiviral cytokine involved in immunomodulation and control of HIV type 1 replication, whereas is a life-threatening opportunistic infection in AIDS patients. During infection with HIV type 1, human pDCs decrease in circulation and remaining pDC produce lower amounts of IFN-α in response to viral stimulation. In this study, we investigated the impact of coinfection with on the innate virus-directed responses of human pDCs. Using intracellular flow cytometry and fluorescence microscopy, we determined that invaded but did not induce IFN-α or TNF-α in human pDC. However, inhibited IFN-α and TNF-α produced in response to HSV and HIV, thus functionally inactivating pDC. IFN-α production was inhibited only in cells infected by , which inhibited neither uptake of GFP-HSV nor localization of TLR9 in CD71 endosomes, directing us to investigate downstream events. Using imaging flow cytometry, we found that both and IL-10 inhibited virus-induced nuclear translocation, but not phosphorylation, of IFN response factor 7. Blockade of IFN response factor 7 nuclear translocation and inhibition of the IFN-α response was partially reversed by a deficiency in the -derived ROP16 kinase, known to directly phosphorylate STAT3, a critical mediator of IL-10's anti-inflammatory effects. Taken together, our results indicate that suppresses pDC activation by mimicking IL-10's regulatory effects through an ROP16 kinase-dependent mechanism. Our findings further imply a convergent mechanism of inhibition of TLR signaling by and IL-10 and suggest potential negative consequences of HIV/ coinfection. [Mh] Termos MeSH primário: Células Dendríticas/imunologia Infecções por HIV/imunologia HIV-1/imunologia Interleucina-10/metabolismo Infecções Oportunistas/imunologia Proteínas Tirosina Quinases/metabolismo Proteínas de Protozoários/metabolismo Toxoplasma/imunologia Toxoplasmose/imunologia [Mh] Termos MeSH secundário: Diferenciação Celular Células Cultivadas Coinfecção Células Dendríticas/parasitologia Seres Humanos Imunidade Inata Imunomodulação Fator Regulador 7 de Interferon/metabolismo Interferon-alfa/metabolismo Fator de Transcrição STAT3/metabolismo Transdução de Sinais Receptor Toll-Like 9/metabolismo Fator de Necrose Tumoral alfa/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL [Nm] Nome de substância: 0 (IRF7 protein, human); 0 (Interferon Regulatory Factor-7); 0 (Interferon-alpha); 0 (Protozoan Proteins); 0 (STAT3 Transcription Factor); 0 (Toll-Like Receptor 9); 0 (Tumor Necrosis Factor-alpha); 130068-27-8 (Interleukin-10); EC 2.7.10.1 (Protein-Tyrosine Kinases); EC 2.7.10.1 (Rop16 protein, Toxoplasma gondii) [Em] Mês de entrada: 1801 [Cu] Atualização por classe: 180307 [Lr] Data última revisão: 180307 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 171129 [St] Status: MEDLINE [do] DOI: 10.4049/jimmunol.1701045

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[PMID]: 28468674 [Au] Autor: Cunningham DA; Lin JW; Brugat T; Jarra W; Tumwine I; Kushinga G; Ramesar J; Franke-Fayard B; Langhorne J [Ad] Endereço: The Francis Crick Institute, London, NW1 1AT, UK. Deirdre.Cunningham@crick.ac.uk. [Ti] Título: ICAM-1 is a key receptor mediating cytoadherence and pathology in the Plasmodium chabaudi malaria model. [So] Source: Malar J;16(1):185, 2017 05 03. [Is] ISSN: 1475-2875 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: BACKGROUND: Parasite cytoadherence within the microvasculature of tissues and organs of infected individuals is implicated in the pathogenesis of several malaria syndromes. Multiple host receptors may mediate sequestration. The identity of the host receptor(s), or the parasite ligand(s) responsible for sequestration of Plasmodium species other than Plasmodium falciparum is largely unknown. The rodent malaria parasites may be useful to model interactions of parasite species, which lack the var genes with their respective hosts, as other multigene families are shared between the species. The role of the endothelial receptors ICAM-1 and CD36 in cytoadherence and in the development of pathology was investigated in a Plasmodium chabaudi infection in C57BL/6 mice lacking these receptors. The schizont membrane-associated cytoadherence (SMAC) protein of Plasmodium berghei has been shown to exhibit reduced CD36-associated cytoadherence in P. berghei ANKA-infected mice. METHODS: Parasite tissue sequestration and the development of acute stage pathology in P. chabaudi infections of mice lacking CD36 or ICAM-1, their respective wild type controls, and in infections with mutant P. chabaudi parasites lacking the smac gene were compared. Peripheral blood parasitaemia, red blood cell numbers and weight change were monitored throughout the courses of infection. Imaging of bioluminescent parasites in isolated tissues (spleen, lungs, liver, kidney and gut) was used to measure tissue parasite load. RESULTS: This study shows that neither the lack of CD36 nor the deletion of the smac gene from P. chabaudi significantly impacted on acute-stage pathology or parasite sequestration. By contrast, in the absence of ICAM-1, infected animals experience less anaemia and weight loss, reduced parasite accumulation in both spleen and liver and higher peripheral blood parasitaemia during acute stage malaria. The reduction in parasite tissue sequestration in infections of ICAM-1 null mice is maintained after mosquito transmission. CONCLUSIONS: These results indicate that ICAM-1-mediated cytoadherence is important in the P. chabaudi model of malaria and suggest that for rodent malarias, as for P. falciparum, there may be multiple host and parasite molecules involved in sequestration. [Mh] Termos MeSH primário: Antígenos CD36/genética Molécula 1 de Adesão Intercelular/genética Malária/parasitologia Plasmodium chabaudi/fisiologia Proteínas de Protozoários/genética [Mh] Termos MeSH secundário: Animais Antígenos CD36/metabolismo Feminino Molécula 1 de Adesão Intercelular/metabolismo Camundongos Camundongos Endogâmicos C57BL Plasmodium chabaudi/genética Proteínas de Protozoários/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (CD36 Antigens); 0 (Icam1 protein, mouse); 0 (Protozoan Proteins); 126547-89-5 (Intercellular Adhesion Molecule-1) [Em] Mês de entrada: 1801 [Cu] Atualização por classe: 180223 [Lr] Data última revisão: 180223 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170505 [St] Status: MEDLINE [do] DOI: 10.1186/s12936-017-1834-8

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[PMID]: 28450175 [Au] Autor: Madamet M; Kounta MB; Wade KA; Lo G; Diawara S; Fall M; Bercion R; Nakoulima A; Fall KB; Benoit N; Gueye MW; Fall B; Diatta B; Pradines B [Ad] Endereço: Unité de parasitologie et d'entomologie, Département des maladies infectieuses, Institut de recherche biomédicale des armées, Marseille, France; Aix-Marseille Université, Unité de recherche sur les maladies infectieuses et tropicales emergentes (URMITE), UM 63, CNRS 7278, IRD 198, Inserm 1095, Marse [Ti] Título: Absence of association between polymorphisms in the K13 gene and the presence of Plasmodium falciparum parasites at day 3 after treatment with artemisinin derivatives in Senegal. [So] Source: Int J Antimicrob Agents;49(6):754-756, 2017 Jun. [Is] ISSN: 1872-7913 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: In 2006, the Senegalese National Malaria Control Programme recommended artemisinin-based combination therapy as first-line treatment for uncomplicated malaria. In addition, intravenous (i.v.) injection of artesunate and artemether has gradually replaced quinine for the treatment of severe malaria. Mutations in the propeller domain of the Kelch 13 gene (K13-propeller, PF3D71343700), such as Y493H, R539T, I543T and C580Y, were recently associated with in vivo and in vitro resistance to artemisinin in Southeast Asia. However, these mutations were not identified in Africa. In total, 181 isolates of Plasmodium falciparum from 161 patients from Dakar, Senegal, were collected between August 2015 and January 2016. The K13-propeller gene of the isolates was sequenced. A search for non-synonymous mutations in the propeller region of K13 was performed in the 181 isolates collected from Dakar from 2015 to 2016. Three synonymous mutations were detected (D464D, C469C and R471R). Of 119 patients treated with i.v. artesunate or intramuscular artemether followed by artemether/lumefantrine, 9 patients were still parasitaemic on Day 3. Parasites from these nine patients were wild-type for K13-propeller. None of the polymorphisms known to be involved in artemisinin resistance in Asia were detected. These results suggest that K13 is not the best predictive marker for artemisinin resistance in Africa. More isolates from clinical failure cases or patients with delayed parasite clearance after treatment with artemisinin derivatives are necessary to identify new molecular markers. [Mh] Termos MeSH primário: Antimaláricos/uso terapêutico Artemisininas/uso terapêutico Malária Falciparum/tratamento farmacológico Malária Falciparum/parasitologia Plasmodium falciparum/efeitos dos fármacos Polimorfismo Genético Proteínas de Protozoários/genética [Mh] Termos MeSH secundário: Animais Seres Humanos Mutação de Sentido Incorreto Plasmodium falciparum/genética Plasmodium falciparum/isolamento & purificação Mutação Puntual Senegal Análise de Sequência de DNA Fatores de Tempo Resultado do Tratamento [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antimalarials); 0 (Artemisinins); 0 (Protozoan Proteins); 9RMU91N5K2 (artemisinine) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180220 [Lr] Data última revisão: 180220 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170429 [St] Status: MEDLINE

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[PMID]: 29342212 [Au] Autor: Chaorattanakawee S; Nuchnoi P; Hananantachai H; Tumkosit U; Saunders D; Naka I; Ohashi J; Patarapotikul J [Ad] Endereço: Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Rangsit, Patumthani, Thailand. [Ti] Título: Sequence variation in Plasmodium falciparum merozoite surface protein-2 is associated with virulence causing severe and cerebral malaria. [So] Source: PLoS One;13(1):e0190418, 2018. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Parasite virulence, an important factor contributing to the severity of Plasmodium falciparum infection, varies among P. falciparum strains. Relatively little is known regarding markers of virulence capable of identifying strains responsible for severe malaria. We investigated the effects of genetic variations in the P.f. merozoite surface protein 2 gene (msp2) on virulence, as it was previously postulated as a factor. We analyzed 300 msp2 sequences of single P. falciparum clone infection from patients with uncomplicated disease as well as those admitted for severe malaria with and without cerebral disease. The association of msp2 variations with disease severity was examined. We found that the N allele at codon 8 of Block 2 in the FC27-like msp2 gene was significantly associated with severe disease without cerebral complications (odds ratio = 2.73, P = 0.039), while the K allele at codon 17 of Block 4 in the 3D7-like msp2 gene was associated with cerebral malaria (odds ratio = 3.52, P = 0.024). The data suggests possible roles for the associated alleles on parasite invasion processes and immune-mediated pathogenicity. Multiplicity of infection was found to associate with severe disease without cerebral complications, but not cerebral malaria. Variations in the msp2-FC27-block 2-8N and 3D7-block 4-17K allele appear to be parasite virulence markers, and may be useful in determining the likelihood for severe and cerebral malaria. Their interactions with potential host factors for severe diseases should also be explored. [Mh] Termos MeSH primário: Antígenos de Protozoários/genética Malária Cerebral/parasitologia Plasmodium falciparum/genética Proteínas de Protozoários/genética [Mh] Termos MeSH secundário: Sequência de Aminoácidos Animais Antígenos de Protozoários/química Sequência de Bases Seres Humanos Plasmodium falciparum/patogenicidade Proteínas de Protozoários/química Alinhamento de Sequência Virulência [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Antigens, Protozoan); 0 (Protozoan Proteins); 0 (merozoite surface protein 2, Plasmodium) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180215 [Lr] Data última revisão: 180215 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180118 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0190418

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[PMID]: 29293520 [Au] Autor: Padgett LR; Lentini JM; Holmes MJ; Stilger KL; Fu D; Sullivan WJ [Ad] Endereço: Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America. [Ti] Título: Elp3 and RlmN: A tale of two mitochondrial tail-anchored radical SAM enzymes in Toxoplasma gondii. [So] Source: PLoS One;13(1):e0189688, 2018. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Radical S-adenosylmethionine (rSAM) enzymes use a 5'-deoxyadensyl 5'-radical to methylate a wide array of diverse substrates including proteins, lipids and nucleic acids. One such enzyme, Elongator protein-3 (TgElp3), is an essential protein in Toxoplasma gondii, a protozoan parasite that can cause life-threatening opportunistic disease. Unlike Elp3 homologues which are present in all domains of life, TgElp3 localizes to the outer mitochondrial membrane (OMM) via a tail-anchored trafficking mechanism in Toxoplasma. Intriguingly, we identified a second tail-anchored rSAM domain containing protein (TgRlmN) that also localizes to the OMM. The transmembrane domain (TMD) on Toxoplasma Elp3 and RlmN homologues is required for OMM localization and has not been seen beyond the chromalveolates. Both TgElp3 and TgRlmN contain the canonical rSAM amino acid sequence motif (CxxxCxxC) necessary to form the 4Fe-4S cluster required for tRNA modifications. In E. coli, RlmN is responsible for the 2-methlyadenosine (m2A) synthesis at purine 37 in tRNA while in S. cerevisiae, Elp3 is necessary for the formation of 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U) at the wobble tRNA position. To investigate why these two rSAM enzymes localize to the mitochondrion in Toxoplasma, and whether or not TgRlmN and TgElp3 possess tRNA methyltransferase activity, a series of mutational and biochemical studies were performed. Overexpression of either TgElp3 or TgRlmN resulted in a significant parasite replication defect, but overexpression was tolerated if either the TMD or rSAM domain was mutated. Furthermore, we show the first evidence that Toxoplasma tRNAGlu contains the mcm5s2U modification, which is the putative downstream product generated by TgElp3 activity. [Mh] Termos MeSH primário: Enzimas/metabolismo Proteínas de Protozoários/metabolismo Toxoplasma/enzimologia [Mh] Termos MeSH secundário: Toxoplasma/crescimento & desenvolvimento [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, U.S. GOV'T, P.H.S. [Nm] Nome de substância: 0 (Enzymes); 0 (Protozoan Proteins) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180215 [Lr] Data última revisão: 180215 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180103 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0189688

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[PMID]: 29309786 [Au] Autor: Hijjawi N; Yang R; Hatmal M; Yassin Y; Mharib T; Mukbel R; Mahmoud SA; Al-Shudifat AE; Ryan U [Ad] Endereço: Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, The Hashemite University, PO Box 150459, Zarqa, 13115, Jordan. [Ti] Título: Comparison of ELISA, nested PCR and sequencing and a novel qPCR for detection of Giardia isolates from Jordan. [So] Source: Exp Parasitol;185:23-28, 2018 Feb. [Is] ISSN: 1090-2449 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Little is known about the prevalence of Giardia duodenalis in human patients in Jordan and all previous studies have used direct microscopy, which lacks sensitivity. The present study developed a novel quantitative PCR (qPCR) assay at the ß-giardin (bg) locus and evaluated its use as a frontline test for the diagnosis of giardiasis in comparison with a commercially available ELISA using nested PCR and sequencing of the glutamate dehydrogenase (gdh) locus (gdh nPCR) as the gold standard. A total of 96 human faecal samples were collected from 96 patients suffering from diarrhoea from 5 regions of Jordan and were screened using the ELISA and qPCR. The analytical specificity of the bg qPCR assay revealed no cross-reactions with other genera and detected all the Giardia isolates tested. Analytical sensitivity was 1 Giardia cyst per µl of DNA extract. The overall prevalence of Giardia was 64.6%. The clinical sensitivity and specificity of the bg qPCR was 89.9% and 82.9% respectively compared to 76.5 and 68.0% for the ELISA. This study is the first to compare three different methods (ELISA, bg qPCR, nested PCR and sequencing at the gdh locus) to diagnose Jordanian patients suffering from giardiasis and to analyze their demographic data. [Mh] Termos MeSH primário: Diarreia/parasitologia Giardia lamblia/isolamento & purificação Giardíase/parasitologia [Mh] Termos MeSH secundário: Adolescente Adulto Antígenos de Protozoários/análise Criança Pré-Escolar Cólica/parasitologia Proteínas do Citoesqueleto/genética DNA de Protozoário/química DNA de Protozoário/isolamento & purificação Ensaio de Imunoadsorção Enzimática Fezes/parasitologia Feminino Giardia lamblia/genética Giardia lamblia/imunologia Giardíase/epidemiologia Glutamato Desidrogenase Seres Humanos Lactente Jordânia/epidemiologia Masculino Meia-Idade Reação em Cadeia da Polimerase Prevalência Proteínas de Protozoários/genética Reação em Cadeia da Polimerase em Tempo Real Sensibilidade e Especificidade Vômito/parasitologia Adulto Jovem [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antigens, Protozoan); 0 (Cytoskeletal Proteins); 0 (DNA, Protozoan); 0 (Protozoan Proteins); 0 (giardin protein, Giardia lamblia); EC 1.4.1.2 (Glutamate Dehydrogenase) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180214 [Lr] Data última revisão: 180214 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180109 [St] Status: MEDLINE

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[PMID]: 29309783 [Au] Autor: Picchio MS; Sánchez VR; Arcon N; Soto AS; Perrone Sibilia M; Aldirico MLA; Urrutia M; Moretta R; Fenoy IM; Goldman A; Martin V [Ad] Endereço: Laboratorio de Inmunología, Vacunas y Alergia, CESyMA, Escuela de Ciencia y Tecnología, Universidad Nacional de San Martín, Campus Migueletes, Martín de Irigoyen 3100 C.P., 1650 San Martín, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Godoy Cruz 2290 [Ti] Título: Vaccine potential of antigen cocktails composed of recombinant Toxoplasma gondii TgPI-1, ROP2 and GRA4 proteins against chronic toxoplasmosis in C3H mice. [So] Source: Exp Parasitol;185:62-70, 2018 Feb. [Is] ISSN: 1090-2449 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: The development of an effective and safe vaccine to prevent Toxoplasma gondii infection is an important aim due to the great clinical and economic impact of this parasitosis. We have previously demonstrated that immunization with the serine protease inhibitor-1 (TgPI-1) confers partial protection to C3H/HeN and C57BL/6 mice. In order to improve the level of protection, in this work, we combined this novel antigen with ROP2 and/or GRA4 recombinant proteins (rTgPI-1+rROP2, rTgPI-1+rGRA4, rTgPI-1+rROP2+rGRA4) to explore the best combination against chronic toxoplasmosis in C3H/HeN mice. All tested vaccine formulations, administered following a homologous prime-boost protocol that combines intradermal and intranasal routes, conferred partial protection as measured by the reduction of brain cyst burden following oral challenge with tissue cysts of Me49 T. gondii strain. The highest level of protection was achieved by the mixture of rTgPI-1 and rROP2 proteins with an average parasite burden reduction of 50% compared to the unvaccinated control group. The vaccine-induced protective effect was related to the elicitation of systemic cellular and humoral immune responses that included antigen-specific spleen cell proliferation, the release of Th1/Th2 cytokines, and the generation of antigen-specific antibodies in serum. Additionally, mucosal immune responses were also induced, characterized by secretion of antigen-specific IgA antibodies in intestinal lavages and specific mesenteric lymph node cell proliferation. Our results demonstrate that rTgPI-1+rROP2 antigens seem a promising mixture to be combined with other immunogenic proteins in a multiantigenic vaccine formulation against toxoplasmosis. [Mh] Termos MeSH primário: Antígenos de Protozoários/imunologia Vacinas Protozoárias/normas Toxoplasma/imunologia Toxoplasmose Animal/prevenção & controle [Mh] Termos MeSH secundário: Animais Anticorpos Antiprotozoários/sangue Linhagem Celular Doença Crônica Citocinas/metabolismo Feminino Fibroblastos/parasitologia Prepúcio do Pênis/citologia Seres Humanos Imunoglobulina A Secretora/análise Imunoglobulina G/sangue Mucosa Intestinal/imunologia Masculino Proteínas de Membrana/imunologia Camundongos Camundongos Endogâmicos C3H Proteínas de Protozoários/imunologia Baço/citologia Baço/imunologia Vacinas Sintéticas/normas [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antibodies, Protozoan); 0 (Antigens, Protozoan); 0 (Cytokines); 0 (GRA4 protein, Toxoplasma gondii); 0 (Immunoglobulin A, Secretory); 0 (Immunoglobulin G); 0 (Membrane Proteins); 0 (Protozoan Proteins); 0 (Protozoan Vaccines); 0 (ROP 2 protein, Toxoplasma gondii); 0 (TgPI protein, Toxoplasma gondii); 0 (Vaccines, Synthetic) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180214 [Lr] Data última revisão: 180214 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180109 [St] Status: MEDLINE

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MEDLINE

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[PMID]: 29307564 [Au] Autor: Niikura M; Inoue SI; Fukutomi T; Yamagishi J; Asahi H; Kobayashi F [Ad] Endereço: Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo 181-8611, Japan. [Ti] Título: Comparative genomics and proteomic analyses between lethal and nonlethal strains of Plasmodium berghei. [So] Source: Exp Parasitol;185:1-9, 2018 Feb. [Is] ISSN: 1090-2449 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Plasmodium berghei (Pb) XAT, a rodent malaria parasite, is an irradiation-attenuated variant derived from the lethal strain Pb NK65. Differences in genome sequence, protein structure and function between Pb XAT and Pb NK65 are currently unknown. In this study, to investigate genetic alterations in Pb XAT, we performed comparative genomics and proteomics analyses of nonlethal and lethal strains of Pb. We found mutations, such as a deletion mutation in rhoptry-associated protein (rap) 1, and deletion of rap2/3 and skeleton-binding protein 1 (sbp1), in Pb XAT. RAP1 is required for targeting of RAP2 to the rhoptries. However, the contribution of RAP2/3 to the lethality of Plasmodium is unclear. Therefore, we generated RAP1- and RAP2/3-deficient mutants of Pb ANKA, a reference strain of P. berghei. Furthermore, we investigated the effect of RAP1 and RAP2/3 deficiency on the outcome of infection. The parasitemia in mice infected with RAP1-deficient parasites was increased compared to that in control parasite-infected mice during the early phase of infection. However, mice infected with RAP1-deficient parasites survived longer than did control parasite-infected mice. Moreover, mice infected with RAP2/3-deficient parasites showed low levels of parasitemia and ultimately recovered from the infection The aim of this study was to investigate the effect of RAP2/3 expression on the outcome of infection with Pb XAT using a RAP2/3-expressing Pb XAT. Results showed that complementation of RAP2/3 expression in Pb XAT partially restored virulence. Our findings suggest that RAP1 and RAP2/3 contribute to virulence and a decrease in their expression explains the loss of virulence of the Pb XAT strain. [Mh] Termos MeSH primário: Genômica Malária/parasitologia Plasmodium berghei/patogenicidade Proteômica [Mh] Termos MeSH secundário: Animais Cromatografia Líquida DNA de Protozoário/química DNA de Protozoário/genética Eritrócitos/parasitologia Feminino Malária/mortalidade Camundongos Camundongos Endogâmicos C57BL Parasitemia/parasitologia Plasmodium berghei/genética Plasmodium berghei/metabolismo Reação em Cadeia da Polimerase/métodos Proteínas de Protozoários/genética Transcrição Reversa Deleção de Sequência Organismos Livres de Patógenos Específicos Espectrometria de Massas em Tandem Virulência [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE [Nm] Nome de substância: 0 (DNA, Protozoan); 0 (Protozoan Proteins); 0 (rhoptry associated protein, Plasmodium); 145184-78-7 (rhoptry-associated antigen-2, Plasmodium) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180214 [Lr] Data última revisão: 180214 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180109 [St] Status: MEDLINE

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