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https://www.readbyqxmd.com/read/28212935/dissecting-biochemical-peculiarities-of-the-atpase-activity-of-tcsub2-a-component-of-the-mrna-export-pathway-in-trypanosoma-cruzi
#1
Ize de Aguiar Bittencourt, Mariana Serpeloni, Priscila Mazzochi Hiraiwa, Tatiana de Arruda Campos Brasil de Souza, Andréa Rodrigues Ávila
The RNA helicase DEAD-box protein Sub2 (yeast)/UAP56 (mammals) is conserved across eukaryotes and is essential for mRNA export in trypanosomes. Despite the high conservation of Sub2 in lower eukaryotes such as Trypanosoma cruzi, the low conservation of other mRNA export factors raises questions regarding whether the mode of action of TcSub2 is similar to that of orthologs from other eukaryotes. Mutation of the conserved K87 residue of TcSub2 abolishes ATPase activity, showing that its ATPase domain is functional...
February 14, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28194625/trypanosomiasis-challenge-estimation-using-the-diminazene-aceturate-berenil-index-in-zebu-in-gabon
#2
Brieuc G A Cossic, Brice Adjahoutonon, Pierre Gloaguen, Gui Lov Dibanganga, Gael Maganga, Pascal Leroy, Ewan T MacLeod, Kim Picozzi
A longitudinal study was conducted within a cattle ranch in Gabon to determine the diminazene aceturate (Berenil) index (DAI) in a group of Zebu, raised under low tsetse density; this measure providing an assessment of trypanosomiasis risk. The objective was to evaluate the trypanosomiasis pressure thus informing trypanosomiasis control methods and cattle management. Twenty female adult Zebu were monitored for 24 weeks during the dry season. Blood samples were collected on a weekly basis and subjected to parasitological and haematological analysis (n = 480), using the buffy-coat method and the packed cell volume value (PCV), respectively, infected animals were treated with a single intramuscular injection of diminazene aceturate (8 mg/kg)...
February 14, 2017: Tropical Animal Health and Production
https://www.readbyqxmd.com/read/28177042/microbial-control-of-arthropod-borne-disease
#3
Miguel A Saldaña, Shivanand Hegde, Grant L Hughes
Arthropods harbor a diverse array of microbes that profoundly influence many aspects of host biology, including vector competence. Additionally, symbionts can be engineered to produce molecules that inhibit pathogens. Due to their intimate association with the host, microbes have developed strategies that facilitate their transmission, either horizontally or vertically, to conspecifics. These attributes make microbes attractive agents for applied strategies to control arthropod-borne disease. Here we discuss the recent advances in microbial control approaches to reduce the burden of pathogens such as Zika, Dengue and Chikungunya viruses, and Trypanosome and Plasmodium parasites...
February 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/28167559/anti-trypanosomal-activity-of-sterol-14%C3%AE-demethylase-cyp51-inhibitors-vni-and-vfv-in-the-swiss-mouse-models-of-chagas-disease-induced-by-the-y-strain-trypanosoma-cruzi
#4
F H Guedes-da-Silva, D G J Batista, C F Da Silva, J S De Araújo, B P Pavão, M R Simões-Silva, M B Meuser, K C Demarque, O C Moreira, C Britto, G I Lepesheva, M N C Soeiro
Chagas disease is a life-threatening infection caused by a variety of genetically diverse strains of the protozoan parasite Trypanosoma cruzi The current treatment (benznidazole and nifurtimox) is unsatisfactory, and potential alternatives include inhibitors of sterol 14α-demethylase (CYP51), the cytochrome P450 enzyme essential for biosynthesis of sterols in eukaryotes and the major target for clinical and agricultural antifungals. Here we performed a comparative investigation of two protozoa-specific CYP51 inhibitors, VNI and its CYP51 structure-based derivative VFV, in the murine models of infection caused by the Y strain T...
February 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28166845/let-s-get-fissical-fast-in-silico-synchronization-as-a-new-tool-for-cell-division-cycle-analysis
#5
Brooke Morriswood, Markus Engstler
Cell cycle progression is a question of fundamental biological interest. The coordinated duplication and segregation of all cellular structures and organelles is however an extremely complex process, and one which remains only partially understood even in the most intensively researched model organisms. Trypanosomes are in an unusual position in this respect - they are both outstanding model systems for fundamental questions in eukaryotic cell biology, and pathogens that are the causative agents of three of the neglected tropical diseases...
February 7, 2017: Parasitology
https://www.readbyqxmd.com/read/28162093/evaluating-the-impact-of-targeting-livestock-for-the-prevention-of-human-and-animal-trypanosomiasis-at-village-level-in-districts-newly-affected-with-t-b-rhodesiense-in-uganda
#6
Louise Hamill, Kim Picozzi, Jenna Fyfe, Beatrix von Wissmann, Sally Wastling, Nicola Wardrop, Richard Selby, Christine Amongi Acup, Kevin L Bardosh, Dennis Muhanguzi, John D Kabasa, Charles Waiswa, Susan C Welburn
BACKGROUND: Uganda has suffered from a series of epidemics of Human African Trypanosomiasis (HAT), a tsetse transmitted disease, also known as sleeping sickness. The area affected by acute Trypanosoma brucei rhodesiense HAT (rHAT) has been expanding, driven by importation of infected cattle into regions previously free of the disease. These regions are also affected by African Animal Trypanosomiasis (AAT) demanding a strategy for integrated disease control. METHODS: In 2008, the Public Private Partnership, Stamp Out Sleeping Sickness (SOS) administered a single dose of trypanocide to 31 486 head of cattle in 29 parishes in Dokolo and Kaberamaido districts...
February 6, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28145221/molecular-identification-of-trypanosome-species-in-trypanotolerant-cattle-from-the-south-of-gabon
#7
Gaël Darren Maganga, Jacques-François Mavoungou, Nadine N'dilimabaka, Ivan Cyr Moussadji Kinga, Bertrand Mvé-Ondo, Illich Manfred Mombo, Barthélémy Ngoubangoye, Brieuc Cossic, Clency Sylde Mikala Okouyi, Alain Souza, Eric Maurice Leroy, Brice Kumulungui, Benjamin Ollomo
The aim of this study was to provide information on trypanosome species infecting trypanotolerant cattle from southern Gabon. The study was conducted on 224 trypanotolerant cattle from three regions located in southern Gabon, using ITS1 primer-based PCR. Seventy-two (32%) N'dama cattle were found polymerase chain reaction (PCR) positive with trypanosomes. The overall prevalence of trypanosomosis was 57% (63/110), 4% (4/100), and 36% (5/14) in the Gala section of the Nyanga ranch, the Miyama ranch, and Ossiele, respectively...
2017: Parasite: Journal de la Société Française de Parasitologie
https://www.readbyqxmd.com/read/28143982/differential-binding-of-mitochondrial-transcripts-by-mrb8170-and-mrb4160-regulates-distinct-editing-fates-of-mitochondrial-mrna-in-trypanosomes
#8
Sameer Dixit, Michaela Müller-McNicoll, Vojtěch David, Kathi Zarnack, Jernej Ule, Hassan Hashimi, Julius Lukeš
: A dozen mRNAs are edited by multiple insertions and/or deletions of uridine residues in the mitochondrion of Trypanosoma brucei Several protein complexes have been implicated in performing this type of RNA editing, including the mitochondrial RNA-binding complex 1 (MRB1). Two paralogous novel RNA-binding proteins, MRB8170 and MRB4160, are loosely associated with the core MRB1 complex. Their roles in RNA editing and effects on target mRNAs are so far not well understood. In this study, individual-nucleotide-resolution UV-cross-linking and affinity purification (iCLAP) revealed a preferential binding of both proteins to mitochondrial mRNAs, which was positively correlated with their extent of editing...
January 31, 2017: MBio
https://www.readbyqxmd.com/read/28142188/phosphatidylserine-synthase-2-and-phosphatidylserine-decarboxylase-are-essential-for-aminophospholipid-synthesis-in-trypanosoma-brucei
#9
Luce Farine, Jennifer Jelk, Jae-Yeon Choi, Dennis R Voelker, Jon Nunes, Terry K Smith, Peter Bütikofer
Phosphatidylethanolamine (PE) and phosphatidylserine (PS) are ubiquitously expressed and metabolically interconnected glycerophospholipids in eukaryotes and prokaryotes. In Trypanosoma brucei, PE synthesis has been shown to occur mainly via the Kennedy pathway, one of the three routes leading to PE synthesis in eukaryotes, while PS synthesis has not been studied experimentally. We now reveal the importance of T. brucei PS synthase 2 (TbPSS2) and T. brucei PS decarboxylase (TbPSD), two key enzymes involved in aminophospholipid synthesis, for trypanosome viability...
January 31, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28141804/use-of-chiral-cell-shape-to-ensure-highly-directional-swimming-in-trypanosomes
#10
Richard John Wheeler
Swimming cells typically move along a helical path or undergo longitudinal rotation as they swim, arising from chiral asymmetry in hydrodynamic drag or propulsion bending the swimming path into a helix. Helical paths are beneficial for some forms of chemotaxis, but why asymmetric shape is so prevalent when a symmetric shape would also allow highly directional swimming is unclear. Here, I analyse the swimming of the insect life cycle stages of two human parasites; Trypanosoma brucei and Leishmania mexicana. This showed quantitatively how chirality in T...
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28127369/molecular-identification-of-hemoprotozoan-parasites-in-camels-camelus-dromedarius-of-iran
#11
Alireza Sazmand, Barbara Eigner, Mohammad Mirzaei, Seyed Hossein Hekmatimoghaddam, Josef Harl, Georg Gerhard Duscher, Hans-Peter Fuehrer, Anja Joachim
BACKGROUND: Although camels represent a valuable source of food, wool and hide in many countries, in-depth information about their vector-borne pathogens is scarce compared to other animals. The aim of the current study was to characterize vector-borne protozoa in the blood of dromedaries from Iran by molecular tools. METHODS: From June to July 2014, 200 peripheral blood samples were collected from asymptomatic one-humped camels in two provinces of Kerman and Sistan- va-Baloochestan in central and southeastern Iran...
October 2016: Iranian Journal of Parasitology
https://www.readbyqxmd.com/read/28125726/a-receptor-s-tale-an-eon-in-the-life-of-a-trypanosome-receptor
#12
REVIEW
Matthew K Higgins, Harriet Lane-Serff, Paula MacGregor, Mark Carrington
African trypanosomes have complex life cycles comprising at least ten developmental forms, variously adapted to different niches in their tsetse fly vector and their mammalian hosts. Unlike many other protozoan pathogens, they are always extracellular and have evolved intricate surface coats that allow them to obtain nutrients while also protecting them from the immune defenses of either insects or mammals. The acquisition of macromolecular nutrients requires receptors that function within the context of these surface coats...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28119024/antiparasitic-lethality-of-sulfonamidebenzamides-in-kinetoplastids
#13
Amber Hackler, Stephen L Patrick, Elizabeth W Kahney, Daniel P Flaherty, Elizabeth R Sharlow, James C Morris, Jennifer E Golden
A sulfonamidebenzamide series was assessed for anti-kinetoplastid parasite activity based on structural similarity to the antiparasitic drug, nifurtimox. Through structure-activity optimization, derivatives with limited mammalian cell toxicity and increased potency toward African trypanosomes and Leishmania promastigotes were developed. Compound 22 had the best potency against the trypanosome (EC50=0.010μM) while several compounds showed ∼10-fold less potency against Leishmania promastigotes without impacting mammalian cells (EC50>25μM)...
February 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28118556/investigation-into-individual-health-and-exposure-to-infectious-agents-of-platypuses-ornithorhynchus-anatinus-in-two-river-catchments-in-northwest-tasmania
#14
James W Macgregor, Carly S Holyoake, Sarah A Munks, Joanne H Connolly, Ian D Robertson, Patricia A Fleming, Kristin S Warren
Changes in the health of individuals within wildlife populations can be a cause or effect of population declines in wildlife species. Aspects of individual platypus ( Ornithorhynchus anatinus ) health have been reported. However, holistic studies investigating potential synergistic effects of both pathogens and environmental factors are needed to expand understanding of platypus individual health. We collected baseline data on the health of platypuses in two Tasmanian river catchments (including evidence of the potentially fatal fungal disease mucormycosis) and on individual, demographic, geographic, and temporal patterns associated with health data results...
January 24, 2017: Journal of Wildlife Diseases
https://www.readbyqxmd.com/read/28117773/xenopus-oocytes-optimized-methods-for-microinjection-removal-of-follicular-cell-layers-and-fast-solution-changes-in-electrophysiological-experiments
#15
Maria C Maldifassi, Nisa Wongsamitkul, Roland Baur, Erwin Sigel
The Xenopus oocyte as a heterologous expression system for proteins, was first described by Gurdon et al.(1) and has been widely used since its discovery (References 2 - 3, and references therein). A characteristic that makes the oocyte attractive for foreign channel expression is the poor abundance of endogenous ion channels(4). This expression system has proven useful for the characterization of many proteins, among them ligand-gated ion channels. The expression of GABAA receptors in Xenopus oocytes and their functional characterization is described here, including the isolation of oocytes, microinjections with cRNA, the removal of follicular cell layers, and fast solution changes in electrophysiological experiments...
December 31, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28114403/proline-metabolism-is-essential-for-trypanosoma-brucei-brucei-survival-in-the-tsetse-vector
#16
Brian S Mantilla, Letícia Marchese, Aitor Casas-Sánchez, Naomi A Dyer, Nicholas Ejeh, Marc Biran, Frédéric Bringaud, Michael J Lehane, Alvaro Acosta-Serrano, Ariel M Silber
Adaptation to different nutritional environments is essential for life cycle completion by all Trypanosoma brucei sub-species. In the tsetse fly vector, L-proline is among the most abundant amino acids and is mainly used by the fly for lactation and to fuel flight muscle. The procyclic (insect) stage of T. b. brucei uses L-proline as its main carbon source, relying on an efficient catabolic pathway to convert it to glutamate, and then to succinate, acetate and alanine as the main secreted end products. Here we investigated the essentiality of an undisrupted proline catabolic pathway in T...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28114397/the-trypanosome-exocyst-a-conserved-structure-revealing-a-new-role-in-endocytosis
#17
Cordula M Boehm, Samson Obado, Catarina Gadelha, Alexandra Kaupisch, Paul T Manna, Gwyn W Gould, Mary Munson, Brian T Chait, Michael P Rout, Mark C Field
Membrane transport is an essential component of pathogenesis for most infectious organisms. In African trypanosomes, transport to and from the plasma membrane is closely coupled to immune evasion and antigenic variation. In mammals and fungi an octameric exocyst complex mediates late steps in exocytosis, but comparative genomics suggested that trypanosomes retain only six canonical subunits, implying mechanistic divergence. We directly determined the composition of the Trypanosoma brucei exocyst by affinity isolation and demonstrate that the parasite complex is nonameric, retaining all eight canonical subunits (albeit highly divergent at the sequence level) plus a novel essential subunit, Exo99...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28112515/conjugates-of-2-4-dihydroxybenzoate-and-salicylhydroxamate-and-lipocations-display-potent-anti-parasite-effects-by-efficiently-targeting-the-trypanosoma-brucei-and-trypanosoma-congolense-mitochondrion
#18
Francisco José Fueyo González, Godwin U Ebiloma, Carolina Izquierdo García, Victor Bruggeman, José María Sánchez Villamañán, Anne Donachie, Emmanuel Oluwadare Balogun, Daniel Ken Inaoka, Tomoo Shiba, Shigeharu Harada, Kiyoshi Kita, Harry P de Koning, Christophe Dardonville
We investigated a chemical strategy to boost the trypanocidal activity of 2,4-dihydroxybenzoic acid (2,4-DHBA)- and salicylhydroxamic acid (SHAM)-based trypanocides with triphenylphosphonium and quinolinium lipophilic cations (LC). Three series of LC conjugates were synthesized that were active in the submicromolar (5a-d and 10d-f) to low nanomolar (6a-f) range against wild-type and multi-drug resistant strains of African trypanosomes (Trypanosoma brucei brucei and T. congolense). This represented an improvement in trypanocidal potency of at least 200-fold, and up to >10,000-fold, compared with the non-LC coupled parent compounds 2,4-DHBA and SHAM...
January 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28100781/biogenesis-of-a-mitochondrial-outer-membrane-protein-in-trypanosoma-brucei-targeting-signal-and-dependence-on-an-unique-biogenesis-factor
#19
Julia Bruggisser, Sandro Käser, Jan Mani, Andre Schneider
The mitochondrial outer membrane (OM) contains single and multiple membrane-spanning proteins which need to contain signals that ensure correct targeting and insertion into the OM. The biogenesis of such proteins has so far essentially only been studied in yeast and related organisms. Here we show that POMP10, an OM protein of the early diverging protozoan Trypanosoma brucei, is signal-anchored. Transgenic cells expressing variants of POMP10 fused to GFP demonstrate that the N-terminal membrane-spanning domain flanked by a few positively charged or neutral residues is both necessary and sufficient for mitochondrial targeting...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28096380/in-situ-structure-of-trypanosomal-atp-synthase-dimer-reveals-a-unique-arrangement-of-catalytic-subunits
#20
Alexander W Mühleip, Caroline E Dewar, Achim Schnaufer, Werner Kühlbrandt, Karen M Davies
We used electron cryotomography and subtomogram averaging to determine the in situ structures of mitochondrial ATP synthase dimers from two organisms belonging to the phylum euglenozoa: Trypanosoma brucei, a lethal human parasite, and Euglena gracilis, a photosynthetic protist. At a resolution of 32.5 Å and 27.5 Å, respectively, the two structures clearly exhibit a noncanonical F1 head, in which the catalytic (αβ)3 assembly forms a triangular pyramid rather than the pseudo-sixfold ring arrangement typical of all other ATP synthases investigated so far...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
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