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Trypanosome

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https://www.readbyqxmd.com/read/29148062/flagellar-incorporation-of-proteins-follows-at-least-two-different-routes-in-trypanosomes
#1
Laetitia Vincensini, Thierry Blisnick, Eloïse Bertiaux, Sebastian Hutchinson, Christina Georgikou, Cher-Pheng Ooi, Philippe Bastin
BACKGROUND INFORMATION: Eukaryotic cilia and flagella are sophisticated organelles composed of several hundreds of proteins that need to be incorporated at the right time and the right place during assembly. RESULTS: Two methods were used to investigate this process in the model protist Trypanosoma brucei: inducible expression of epitope-tagged labelled proteins and fluorescence recovery after photobleaching (FRAP) of fluorescent fusion proteins. This revealed that skeletal components of the radial spokes (RSP3), the central pair (PF16) and the outer dynein arms (DNAI1) are incorporated at the distal end of the growing flagellum...
November 16, 2017: Biology of the Cell
https://www.readbyqxmd.com/read/29121981/intrinsic-dna-curvature-in-trypanosomes
#2
Pablo Smircich, Najib M El-Sayed, Beatriz Garat
BACKGROUND: Trypanosoma cruzi and Trypanosoma brucei are protozoan parasites causing Chagas disease and African sleeping sickness, displaying unique features of cellular and molecular biology. Remarkably, no canonical signals for RNA polymerase II promoters, which drive protein coding genes transcription, have been identified so far. The secondary structure of DNA has long been recognized as a signal in biological processes and more recently, its involvement in transcription initiation in Leishmania was proposed...
November 9, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29114487/prevalence-of-trypanosome-infection-in-tsetse-flies-from-oji-river-and-emene-axis-of-enugu-state-nigeria-a-preliminary-report
#3
Kenechukwu Chibuike Onyekwelu, Fidelis Ebele Ejezie, Anthonius Anayochukwu Eze, Joy Ebele Ikekpeazu, Richard Chukwunonye Ezeh, Godknows Chizurumoke Edeh
Introduction: Trypanosomes are protozoan parasites of vertebrates transmitted by blood-sucking tsetse fly. Trypanosomes remain a constant threat to the lives of humans and animals throughout large regions of Africa. Aims and Objectives: This study investigated the presence, prevalence, and species of trypanosome parasite in tsetse flies caught in two areas of no previous documented history of trypanosome infection. Materials and Methods: For this purpose, 63 and 77 nonterenal tsetse flies were collected from Oji River and Emene areas of Enugu State Nigeria, respectively...
July 2017: Tropical Parasitology
https://www.readbyqxmd.com/read/29113731/oral-fexinidazole-for-late-stage-african-trypanosoma-brucei-gambiense-trypanosomiasis-a-pivotal-multicentre-randomised-non-inferiority-trial
#4
Victor Kande Betu Ku Mesu, Wilfried Mutombo Kalonji, Clélia Bardonneau, Olaf Valverde Mordt, Séverine Blesson, François Simon, Sophie Delhomme, Sonja Bernhard, Willy Kuziena, Jean-Pierre Fina Lubaki, Steven Lumeya Vuvu, Pathou Nganzobo Ngima, Hélène Mahenzi Mbembo, Médard Ilunga, Augustin Kasongo Bonama, Josué Amici Heradi, Jean Louis Lumaliza Solomo, Guylain Mandula, Lewis Kaninda Badibabi, Francis Regongbenga Dama, Papy Kavunga Lukula, Digas Ngolo Tete, Crispin Lumbala, Bruno Scherrer, Nathalie Strub-Wourgaft, Antoine Tarral
BACKGROUND: Few therapeutic options are available to treat late-stage human African trypanosomiasis, a neglected tropical disease caused by Trypanosoma brucei gambiense (g-HAT). The firstline treatment nifurtimox eflornithine combination therapy needs to be administered intravenously in a hospital setting by trained personnel, which is not optimal, given that patients often live in remote areas with few health resources. Therefore, we aimed to assess the safety and efficacy of an oral regimen of fexinidazole (a 2-substituted 5-nitroimidazole with proven trypanocidal activity) versus nifurtimox eflornithine combination therapy in patients with late-stage g-HAT...
November 3, 2017: Lancet
https://www.readbyqxmd.com/read/29113599/haemoparasites-of-the-pied-flycatcher-inter-population-variation-in-the-prevalence-and-community-composition
#5
Anna Dubiec, Edyta Podmokła, Iga Harnist, Tomasz D Mazgajski
The prevalence and community composition of haemoparasites can substantially differ among avian host populations, which may lead to different selection pressures. Therefore, information about these parameters is crucial for understanding, e.g. the inter-population variation in host life history traits. Here, we molecularly screened a population of a long-distance migrant, the pied flycatcher Ficedula hypoleuca, from central Poland for the presence of three genera of blood parasites: Haemoproteus, Plasmodium and Trypanosoma...
November 8, 2017: Parasitology
https://www.readbyqxmd.com/read/29110762/apol1-nephrotoxicity-what-does-ion-transport-have-to-do-with-it
#6
REVIEW
Opeyemi A Olabisi, John F Heneghan
Apolipoprotein L1 (APOL1) protein is the human serum factor that protect human beings against Trypanosoma brucei brucei, the cause of trypanosomiasis. Subspecies of T b brucei that cause human sleeping sickness-T b gambiense and T b rhodesiense evolved molecular mechanisms that enabled them to evade killing by APOL1. Sequence changes (termed G1 and G2) in the APOL1 gene that restored its ability to kill T b rhodesiense also increase the risk of developing glomerular diseases and accelerate progression to end-stage kidney disease...
November 2017: Seminars in Nephrology
https://www.readbyqxmd.com/read/29110761/the-cell-biology-of-apol1
#7
REVIEW
John F O'Toole, Leslie A Bruggeman, Sethu Madhavan, John R Sedor
The association of variants in the APOL1 gene, which encodes apolipoprotein L1 (APOL1), with progressive nondiabetic kidney diseases in African Americans has prompted intense investigation into the function(s) of APOL1. APOL1 is an innate immune effector that protects human beings from infection by some trypanosomal parasites. We review the data characterizing APOL1 trypanolytic function, which has been a basis for studies of APOL1 function in mammalian cells. Subsequently, we discuss the studies that use animal models, mammalian cell culture models, and kidney biopsy tissue to discover the mechanisms of variant APOL1-associated kidney diseases...
November 2017: Seminars in Nephrology
https://www.readbyqxmd.com/read/29110757/a-brief-history-of-apol1-a-gene-evolving
#8
REVIEW
David J Friedman
APOL1 kidney risk variants lead to high rates of kidney disease in people of recent African ancestry. These risk variants are very common and confer a large increase in risk of kidney disease. This unusual combination of high frequency and large effect size occurs because the risk variants also appear to have beneficial properties. The risk variants show enhanced protective effects against certain pathogens, particularly the trypanosomes that cause African sleeping sickness. Here, we consider the origins and evolution of the primate-only APOL1 gene...
November 2017: Seminars in Nephrology
https://www.readbyqxmd.com/read/29108932/improving-anti-trypanosomal-activity-of-alkamides-isolated-from-achillea-fragrantissima
#9
Joseph Skaf, Omar Hamarsheh, Michael Berninger, Srikkanth Balasubramanian, Tobias A Oelschlaeger, Ulrike Holzgrabe
In previous studies the aerial parts of Achillea fragrantissima were found to have substantial antileishmanial and antitrypanosomal activity. A bioassay-guided fractionation of a dichloromethane extract yielded the isolation of the essential anti-trypanosomal compounds of the plant. Seven sesquiterpene lactones (including Achillolide-A), two flavonoids, chrysosplenol-D and chrysosplenetine, and four alkamides (including pellitorine) were identified. This is the first report for the isolation of the sesquiterpene lactones 3 and 4, chrysosplenetine and the group of alkamides from this plant...
November 3, 2017: Fitoterapia
https://www.readbyqxmd.com/read/29107420/african-trypanosomiasis-synthesis-sar-enabling-novel-drug-discovery-of-ubiquinol-mimics-for-trypanosome-alternative-oxidase
#10
Ryan A West, Oran G O'Doherty, Trevor Askwith, John Atack, Paul Beswick, Jamie Laverick, Michael Paradowski, Lewis E Pennicott, Srinivasa P S Rao, Gareth Williams, Simon E Ward
African trypanosomiasis is a parasitic disease affecting 5000 humans and millions of livestock animals in sub-Saharan Africa every year. Current treatments are limited, difficult to administer and often toxic causing long term injury or death in many patients. Trypanosome alternative oxidase is a parasite specific enzyme whose inhibition by the natural product ascofuranone (AF) has been shown to be curative in murine models. Until now synthetic methods to AF analogues have been limited, this has restricted both understanding of the key structural features required for binding and also how this chemotype could be developed to an effective therapeutic agent...
December 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29100526/serological-tests-for-gambiense-human-african-trypanosomiasis-detect-antibodies-in-cattle
#11
Enock Matovu, Annah Kitibwa, Albert Picado, Sylvain Biéler, Paul R Bessell, Joseph Mathu Ndung'u
BACKGROUND: Serological tests for gambiense human African trypanosomiasis (gHAT) detect antibodies to antigens on the cell surface of bloodstream trypanosomes. As trypanosomes that cause animal African trypanosomiasis (AAT) also express related antigens, we have evaluated two rapid diagnostic tests (RDTs) on cattle in trypanosomiasis endemic and non-endemic regions, to determine whether gHAT serological tests could also be used to screen for AAT. METHODS: Two RDTs, 1G RDT, made with native antigens, and p2G RDT, made with recombinant antigens, were tested on 121 cattle in a trypanosomiasis-free region, and on 312 cattle from a rhodesiense HAT and AAT endemic region...
November 3, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/29089615/genome-wide-mutagenesis-and-multi-drug-resistance-in-american-trypanosomes-induced-by-the-front-line-drug-benznidazole
#12
Mônica C Campos, Jody Phelan, Amanda F Francisco, Martin C Taylor, Michael D Lewis, Arnab Pain, Taane G Clark, John M Kelly
Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and affects 5-8 million people in Latin America. Although the nitroheterocyclic compound benznidazole has been the front-line drug for several decades, treatment failures are common. Benznidazole is a pro-drug and is bio-activated within the parasite by the mitochondrial nitroreductase TcNTR-1, leading to the generation of reactive metabolites that have trypanocidal activity. To better assess drug action and resistance, we sequenced the genomes of T...
October 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29084172/benzoic-acid-derivatives-with-trypanocidal-activity-enzymatic-analysis-and-molecular-docking-studies-toward-trans-sialidase
#13
Muhammad Kashif, Antonio Moreno-Herrera, Juan Carlos Villalobos-Rocha, Benjamín Nogueda-Torres, Jaime Pérez-Villanueva, Karen Rodríguez-Villar, José Lius Medina-Franco, Peterson de Andrade, Ivone Carvalho, Gildardo Rivera
Chagas, or American trypanosomiasis, remains an important public health problem in developing countries. In the last decade, trans-sialidase has become a pharmacological target for new anti-Chagas drugs. In this work, the aims were to design and find a new series of benzoic acid derivatives as trans-sialidase (TS) inhibitors and anti-trypanosomal agents. Three compounds (14, 18, and 19) sharing a para-aminobenzoic acid moiety showed more potent trypanocidal activity than the commercially available drugs nifurtimox and benznidazole in both strains: the lysis concentration of 50% of the population (LC50) was <0...
October 30, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29078807/relationship-between-trypanosoma-brucei-rhodesiense-genetic-diversity-and-clinical-spectrum-among-sleeping-sickness-patients-in-uganda
#14
Charles D Kato, Claire M Mugasa, Ann Nanteza, Enock Matovu, Vincent P Alibu
OBJECTIVE: Human African trypanosomiasis (HAT) due to Trypanosoma brucei rhodesiense in East and southern Africa is reported to be clinically diverse. We tested the hypothesis that this clinical diversity is associated with a variation in trypanosome genotypes. RESULTS: Trypanosome DNA isolated from HAT patients was genotyped using 7 microsatellite markers directly from blood spotted FTA cards following a whole genome amplification. All markers were polymorphic and identified 17 multi-locus genotypes with 56% of the isolates having replicate genotypes...
October 27, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29074577/functional-analyses-of-the-cif1-cif2-complex-in-trypanosome-identify-the-structural-motifs-required-for-cytokinesis
#15
Huiqing Hu, Paul Majneri, Dielan Li, Yasuhiro Kurasawa, Tai An, Gang Dong, Ziyin Li
Cytokinesis in trypanosome occurs uni-directionally along the longitudinal axis from the cell anterior towards the cell posterior and requires a trypanosome-specific CIF1-CIF2 protein complex. However, little is known about the contribution of the structural motifs in CIF1 and CIF2 to complex assembly and cytokinesis. Here, we demonstrated that the two zinc-finger motifs but not the coiled-coil motif in CIF1 are required for interaction with the EF-hand motifs in CIF2. We further showed that localization of CIF1 depends on the coiled-coil motif and the first zinc-finger motif and that localization of CIF2 depends on the EF-hand motifs...
October 26, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29072526/rab-gtpases-in-cilium-formation-and-function
#16
Oliver E Blacque, Noemie Scheidel, Stefanie Kuhns
Cilia are microtubule-based organelles extending from a basal body at the surface of eukaryotic cells. Cilia regulate cell and fluid motility, sensation and developmental signaling, and ciliary defects cause human diseases (ciliopathies) affecting the formation and function of many tissues and organs. Over the past decade, various Rab and Rab-like membrane trafficking proteins have been shown to regulate cilia-related processes such as basal body maturation, ciliary axoneme extension, intraflagellar transport and ciliary signaling...
October 26, 2017: Small GTPases
https://www.readbyqxmd.com/read/29063677/transporters-of-trypanosoma-brucei-phylogeny-physiology-pharmacology
#17
REVIEW
Remo S Schmidt, Juan P Macêdo, Michael E Steinmann, Amaia González Salgado, Peter Bütikofer, Erwin Sigel, Doris Rentsch, Pascal Mäser
Trypanosoma brucei comprise the causative agents of sleeping sickness, T. b. gambiense and T. b. rhodesiense, as well as the livestock-pathogenic T. b. brucei. The parasites are transmitted by the tsetse fly and occur exclusively in sub-Saharan Africa. T. brucei are not only lethal pathogens, but have also become model organisms for molecular parasitology. We focus here on membrane transport proteins of T. brucei, their contribution to homeostasis and metabolism in the context of a parasitic lifestyle, and their pharmacological role as potential drug targets or routes of drug entry...
October 24, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29062898/essential-assembly-factor-rpf2-forms-novel-interactions-within-the-5s-rnp-in-trypanosoma-brucei
#18
Anyango D Kamina, Daniel Jaremko, Linda Christen, Noreen Williams
Ribosome biogenesis is a highly complex and conserved cellular process that is responsible for making ribosomes. During this process, there are several assembly steps that function as regulators to ensure proper ribosome formation. One of these steps is the assembly of the 5S ribonucleoprotein particle (5S RNP) in the central protuberance of the 60S ribosomal subunit. In eukaryotes, the 5S RNP is composed of 5S rRNA, ribosomal proteins L5 and L11, and assembly factors Rpf2 and Rrs1. Our laboratory previously showed that in Trypanosoma brucei, the 5S RNP is composed of 5S rRNA, L5, and trypanosome-specific RNA binding proteins P34 and P37...
September 2017: MSphere
https://www.readbyqxmd.com/read/29061160/molecular-prevalence-of-trypanosome-infections-in-cattle-and-tsetse-flies-in-the-maasai-steppe-northern-tanzania
#19
Mary Simwango, Anibariki Ngonyoka, Happiness J Nnko, Linda P Salekwa, Moses Ole-Neselle, Sharadhuli I Kimera, Paul S Gwakisa
BACKGROUND: African trypanosomosis is a disease of public health and economic importance that poses a major threat to the livelihoods of people living in the Maasai Steppe, where there is a significant interaction between people, livestock and wildlife. The vulnerability of the Maasai people to the disease is enhanced by the interaction of their cattle, which act as vehicles for trypanosomes, and tsetse flies close to wildlife in protected areas. This study was aimed at identification of trypanosome infections circulating in cattle and tsetse flies in order to understand their distribution and prevalence in livestock/wildlife interface areas in the Maasai Steppe...
October 23, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/29049963/optimization-of-physicochemical-properties-for-4-anilinoquinazoline-inhibitors-of-trypanosome-proliferation
#20
Jennifer L Woodring, Kelly A Bachovchin, Kimberly G Brady, Mitchell F Gallerstein, Jessey Erath, Scott Tanghe, Susan E Leed, Ana Rodriguez, Kojo Mensa-Wilmot, Richard J Sciotti, Michael P Pollastri
Human African trypanosomiasis (HAT) is a deadly disease in need of new chemotherapeutics that can cross into the central nervous system. We previously reported the discovery of 2 (NEU-617), a small molecule with activity against T. brucei bloodstream proliferation. Further optimization of 2 to improve the physicochemical properties (LogP, LLE, [1], and MPO score) [2] have led us to twelve sub-micromolar compounds, most importantly the headgroup variants 9i and 9j, and the linker variant 18. Although these 3 compounds had reduced potency compared to 2, they all had improved LogP, LLE and MPO scores...
December 1, 2017: European Journal of Medicinal Chemistry
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