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Manuel Fresno, Núria Gironès
Chagas disease is a multisystemic disorder caused by the protozoan parasite Trypanosoma cruzi , which affects ~8 million people in Latin America, killing 7,000 people annually. Chagas disease is one of the main causes of death in the endemic area and the leading cause of infectious myocarditis in the world. T. cruzi infection induces two phases, acute and chronic, where the infection is initially asymptomatic and the majority of patients will remain clinically indeterminate for life. However, over a period of 10-30 years, ~30% of infected individuals will develop irreversible, potentially fatal cardiac syndromes (chronic chagasic cardiomyopathy [CCC]), and/or dilatation of the gastro-intestinal tract (megacolon or megaesophagus)...
2018: Frontiers in Microbiology
Godwin U Ebiloma, Evangelos Katsoulis, John O Igoli, Alexander I Gray, Harry P De Koning
Natural products have made remarkable contributions to drug discovery and therapy. In this work we exploited various biochemical approaches to investigate the mode of action of 16-α-hydroxy-cleroda-3,13 (14)-Z-dien-15,16-olide (HDK-20), which we recently isolated from Polyalthia longifolia, on Trypanosoma brucei bloodstream trypomastigotes. HDK20 at concentrations ≥ EC50 (0.4 μg/ml) was trypanocidal, with its effect irreversible after only a brief exposure time (<1 h). Fluorescence microscopic assessment of DNA configuration revealed severe cell cycle defects after 8 h of incubation with the compound, the equivalent of a single generation time...
March 15, 2018: Scientific Reports
Natalia Anahí Juiz, Irma Torrejón, Marianela Burgos, Ana María Fernanda Torres, Tomás Duffy, Nelly Melina Cayo, Anahí Tabasco, Miriam Salvo, Silvia Andrea Longhi, Alejandro Gabriel Schijman
Infection with Trypanosoma cruzi in women at reproductive age is associated with congenital transmission and adverse pregnancy outcome. The placenta is a key barrier to infection. We characterized gene expression profiles of term placental environment from T. cruzi seropositive (SP) and seronegative (SN) mothers performing RNA-seq. Nine pools of placental RNA paired samples were used: three from SN and six from SP tissues. Each pool consisted of female/male newborns and vaginal/caesarean deliveries binomials...
March 12, 2018: American Journal of Pathology
Oneida Espinosa-Álvarez, Paola A Ortiz, Luciana Lima, André G Costa-Martins, Myrna G Serrano, Stephane Herder, Gregory A Buck, Erney P Camargo, Patrick B Hamilton, Jamie R Stevens, Marta M G Teixeira
Trypanosoma rangeli and Trypanosoma cruzi are generalist trypanosomes sharing a wide range of mammalian hosts; they are transmitted by triatomine bugs, and are the only trypanosomes infecting humans in the Neotropics. Their origins, phylogenetic relationships, and emergence as human parasites have long been subjects of interest. In the present study, taxon-rich analyses (20 trypanosome species from bats and terrestrial mammals) using ssrRNA, glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH), heat shock protein-70 (HSP70) and Spliced Leader (SL) RNA sequences, and multilocus phylogenetic analyses using 11 single copy genes from 15 selected trypanosomes, provide increased resolution of relationships between species and clades, strongly supporting two main sister lineages: lineage Schizotrypanum, comprising T...
March 12, 2018: International Journal for Parasitology
Laura Jeacock, Joana Faria, David Horn
Protein abundance differs from a few to millions of copies per cell. Trypanosoma brucei presents an excellent model for studies on codon bias and differential gene expression because transcription is broadly unregulated and uniform across the genome. T. brucei is also a major human and animal protozoal pathogen. Here, an experimental assessment, using synthetic reporter genes, revealed that GC3 codons have a major positive impact on both mRNA and protein abundance. Our estimates of relative expression, based on coding sequences alone (codon usage and sequence length), are within 2-fold of the observed values for the majority of measured cellular mRNAs (n>7000) and proteins (n>2000)...
March 15, 2018: ELife
Teresa Cruz-Bustos, Silvia N J Moreno, Roberto Docampo
Membrane proteins in trypanosomatids are, in general, weakly expressed and confirmation of their subcellular localization frequently requires their overexpression with epitope tags. However, overexpression can lead to mislocalization of the probes. Viswanathan et al. (Nat. Methods, 2015) described high performance tags for localization of weakly expressed proteins. We report here the use of these protein tags, named "spaghetti monster", for CRISPR /Cas9-mediated C-terminal endogenous tagging of Trypanosoma cruzi to localize two weakly expressed transient receptor potential (TRP) channels to acidic compartments...
March 15, 2018: Journal of Eukaryotic Microbiology
Alexis Bonfim-Melo, Éden R Ferreira, Renato A Mortara
This study evaluated the participation of host cell Rho-family GTPases and their effector proteins in the actin-dependent invasion by Trypanosoma cruzi extracellular amastigotes (EAs). We observed that all proteins were recruited and colocalized with actin at EA invasion sites in live or fixed cells. EA internalization was inhibited in cells depleted in Rac1, N-WASP, and WAVE2. Time-lapse experiments with Rac1, N-WASP and WAVE2 depleted cells revealed that EA internalization kinetics is delayed even though no differences were observed in the proportion of EA-induced actin recruitment in these groups...
2018: Frontiers in Microbiology
Sara Silva Pereira, Andrew P Jackson
BACKGROUND: Trypanosomatid parasites such as Trypanosoma spp. and Leishmania spp. are a major source of infectious disease in humans and domestic animals worldwide. Fundamental to the host-parasite interactions of these potent pathogens are their cell surfaces, which are highly decorated with glycosylated proteins and other macromolecules. Trypanosomatid genomes contain large multi-copy gene families encoding UDP-dependent glycosyltransferases (UGTs), the primary role of which is cell-surface decoration...
March 14, 2018: BMC Evolutionary Biology
Claudia Laperchia, Yuan-Zhong Xu, Dieudonné Mumba Ngoyi, Tiziana Cotrufo, Marina Bentivoglio
Neuron populations of the lateral hypothalamus which synthesize the orexin (OX)/hypocretin or melanin-concentrating hormone (MCH) peptides play crucial, reciprocal roles in regulating wake stability and sleep. The disease human African trypanosomiasis (HAT), also called sleeping sickness, caused by extracellular Trypanosoma brucei ( T. b .) parasites, leads to characteristic sleep-wake cycle disruption and narcoleptic-like alterations of the sleep structure. Previous studies have revealed damage of OX and MCH neurons during systemic infection of laboratory rodents with the non-human pathogenic T...
2018: Frontiers in Neuroanatomy
Colleen Edith Archer, M Corrie Schoeman, Christopher Charles Appleton, Samson Mukaratirwa, Karen J Hope, Glenda Beverly Matthews
This study investigated associations between Trypanosoma lewisi; Xenopsylla cheopis, a common cyclical vector of T. lewisi; Polyplax spinulosa, a reported mechanical vector; and Laelaps ecidnina and L. lamborni, two rodent mites of Rattus norvegicus in Durban. Three hundred and seventy nine R. norvegicus were live-trapped at 48 sites in 4 locality types of Durban during a one year period. Rats were euthanized, cardiac blood was taken to check for hemoparasites and ectoparasites were removed for identification...
March 13, 2018: Journal of Parasitology
Cher-Pheng Ooi, Terry K Smith, Eva Gluenz, Nadina Vasileva Wand, Sue Vaughan, Gloria Rudenko
The predominant secretory cargo of bloodstream form Trypanosoma brucei is Variant Surface Glycoprotein (VSG), comprising ~10% total protein and forming a dense protective layer. Blocking VSG translation using Morpholino oligonucleotides triggered a precise pre-cytokinesis arrest. We investigated the effect of blocking VSG synthesis on the secretory pathway. The number of Golgi decreased, particularly in post-mitotic cells, from 3.5 ± 0.6 to 2.0 ± 0.04 per cell. Similarly, the number of ER exit sites (ERES) in post-mitotic cells dropped from (3...
March 13, 2018: Traffic
Hanako Hayashi, Bungo Akiyoshi
Kinetoplastids have a nucleus that contains the nuclear genome and a kinetoplast that contains the mitochondrial genome. These single-copy organelles must be duplicated and segregated faithfully to daughter cells at each cell division. In Trypanosoma brucei , although duplication of both organelles starts around the same time, segregation of the kinetoplast precedes that of the nucleus. Cytokinesis subsequently takes place so that daughter cells inherit a single copy of each organelle. Very little is known about the molecular mechanism that governs the timing of these events...
March 12, 2018: Biology Open
E Quintero-Troconis, N Buelvas, C Carrasco-López, M R Domingo-Sananes, L González-González, R Ramírez-Molina, L Osorio, A Lobo-Rojas, A J Cáceres, P A Michels, H Acosta, W Quiñones, J L Concepción
Purification of enolase (ENO) from the cytosol of Trypanosoma cruzi indicated that it may interact with at least five other proteins. Two of them were identified as metallocarboxypeptidase-1 (TcMCP-1) and a putative acireductone dioxygenase (ARDp). Subcellular localization studies confirmed the presence of ARDp in the cytosol, as is the case for ENO and TcMCP-1. Analysis of the ARDp sequence showed that this protein has two domains, an N-terminal ARD and a C-terminal TRP14 (thioredoxin-related protein) domain...
March 9, 2018: Biochimica et Biophysica Acta
Fernando Araujo Monteiro, Christiane Weirauch, Márcio Felix, Cristiano Lazoski, Fernando Abad-Franch
In this chapter, we review and update current knowledge about the evolution, systematics, and biogeography of the Triatominae (Hemiptera: Reduviidae)-true bugs that feed primarily on vertebrate blood. In the Americas, triatomines are the vectors of Trypanosoma cruzi, the etiological agent of Chagas disease. Despite declining incidence and prevalence, Chagas disease is still a major public health concern in Latin America. Triatomines occur also in the Old World, where vector-borne T. cruzi transmission has not been recorded...
2018: Advances in Parasitology
Esteban Yefi-Quinteros, Catalina Muñoz-San Martín, Antonella Bacigalupo, Juana P Correa, Pedro E Cattan
BACKGROUND: Trypanosoma cruzi is the agent of Chagas disease, a major public health problem in Latin America. Many wild and domestic animals are naturally infected with T. cruzi; rodents are one of the groups which have been consistently detected infected in different countries. The aim of this work was to characterize blood T. cruzi load in naturally infected rodents from a Chagas disease endemic region in Chile. METHODS: Baited traps were set in domestic and peridomestic areas of rural dwellings...
March 12, 2018: Parasites & Vectors
Clement Isaac, Benjamin Igho Igbinosa, John Asekhaen Ohiolei, Catherine Eki Osimen
Some small mammals occur as household pests and harbour a number of parasites that could be of public health importance. This study profiled the helminth and protozoan parasites in trapped small mammals within and around human dwelling places (houses) located across 4 major towns (Auchi, Benin, Ekpoma, and Uromi) and environs in Edo state, Nigeria. Six genera ( Apodemus sp., Crocidura sp., Mastomys natalensis , Mus musculus , Rattus sp., and Sorex sp.) were identified from 502 trapped small mammals. Overall, M...
February 2018: Korean Journal of Parasitology
Laura-Isobel McCall, Anupriya Tripathi, Fernando Vargas, Rob Knight, Pieter C Dorrestein, Jair L Siqueira-Neto
Trypanosoma cruzi parasites are the causative agents of Chagas disease. These parasites infect cardiac and gastrointestinal tissues, leading to local inflammation and tissue damage. Digestive Chagas disease is associated with perturbations in food absorption, intestinal traffic and defecation. However, the impact of T. cruzi infection on the gut microbiota and metabolome have yet to be characterized. In this study, we applied mass spectrometry-based metabolomics and 16S rRNA sequencing to profile infection-associated alterations in fecal bacterial composition and fecal metabolome through the acute-stage and into the chronic stage of infection, in a murine model of Chagas disease...
March 12, 2018: PLoS Neglected Tropical Diseases
Sujogya Kumar Panda, Walter Luyten
The purpose of this review is to survey the antiparasitic plants of the Asteraceae family and their applicability in the treatment of parasites. This review is divided into three major parts: (a) literature on traditional uses of Asteraceae plants for the treatment of parasites; (b) description of the major classes of chemical compounds from Asteraceae and their antiparasitic effects; and (c) antiparasitic activity with special reference to flavonoids and terpenoids. This review provides detailed information on the reported Asteraceae plant extracts found throughout the world and on isolated secondary metabolites that can inhibit protozoan parasites such as Plasmodium, Trypanosoma, Leishmania, and intestinal worms...
2018: Parasite: Journal de la Société Française de Parasitologie
I Matetovici, J Van Den Abbeele
Thioester-containing proteins (TEPs) are conserved proteins with a role in innate immune immunity. In the current study, we characterized the TEP family in the genome of six tsetse fly species (Glossina spp.). Tsetse flies are the biological vectors of several African trypanosomes, which cause sleeping sickness in humans or nagana in livestock. The analysis of the tsetse TEP sequences revealed information about their structure, evolutionary relationships and expression profiles under both normal and trypanosome infection conditions...
March 12, 2018: Insect Molecular Biology
O Villafraz, R Rondón-Mercado, A J Cáceres, J L Concepción, W Quiñones
T. rangeli epimastigotes contain only a single detectable phosphoglycerate kinase (PGK) enzyme in their cytosol. However, analysis of this parasite's recently sequenced genome showed a gene predicted to code for a PGK with the same molecular mass as the natural enzyme, and with a cytosolic localization as well. In this work, we have partially purified the natural PGK from T. rangeli epimastigotes. Furthermore, we cloned the predicted PGK gene and expressed it as a recombinant active enzyme. Both purified enzymes were kinetically characterized and displayed similar substrate affinities, with KmATP values of 0...
March 8, 2018: Experimental Parasitology
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