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https://www.readbyqxmd.com/read/28727848/the-nuclear-proteome-of-trypanosoma-brucei
#1
Carina Goos, Mario Dejung, Christian J Janzen, Falk Butter, Susanne Kramer
Trypanosoma brucei is a protozoan flagellate that is transmitted by tsetse flies into the mammalian bloodstream. The parasite has a huge impact on human health both directly by causing African sleeping sickness and indirectly, by infecting domestic cattle. The biology of trypanosomes involves some highly unusual, nuclear-localised processes. These include polycistronic transcription without classical promoters initiated from regions defined by histone variants, trans-splicing of all transcripts to the exon of a spliced leader RNA, transcription of some very abundant proteins by RNA polymerase I and antigenic variation, a switch in expression of the cell surface protein variants that allows the parasite to resist the immune system of its mammalian host...
2017: PloS One
https://www.readbyqxmd.com/read/28727769/small-subunit-ribosomal-metabarcoding-reveals-extraordinary-trypanosomatid-diversity-in-brazilian-bats
#2
Maria Augusta Dario, Ricardo Moratelli Mendonça da Rocha, Philipp Schwabl, Ana Maria Jansen, Martin S Llewellyn
BACKGROUND: Bats are a highly successful, globally dispersed order of mammals that occupy a wide array of ecological niches. They are also intensely parasitized and implicated in multiple viral, bacterial and parasitic zoonosis. Trypanosomes are thought to be especially abundant and diverse in bats. In this study, we used 18S ribosomal RNA metabarcoding to probe bat trypanosome diversity in unprecedented detail. METHODOLOGY/PRINCIPAL FINDINGS: Total DNA was extracted from the blood of 90 bat individuals (17 species) captured along Atlantic Forest fragments of Espírito Santo state, southeast Brazil...
July 20, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28724794/apol1-variants-change-c-terminal-conformational-dynamics-and-binding-to-snare-protein-vamp8
#3
Sethu M Madhavan, John F O'Toole, Martha Konieczkowski, Laura Barisoni, David B Thomas, Santhi Ganesan, Leslie A Bruggeman, Matthias Buck, John R Sedor
APOL1 variants in African populations mediate resistance to trypanosomal infection but increase risk for kidney diseases through unknown mechanisms. APOL1 is expressed in glomerular podocytes and does not vary with underlying kidney disease diagnoses or APOL1 genotypes, suggesting that the kidney disease-associated variants dysregulate its function rather than its localization or abundance. Structural homology searches identified vesicle-associated membrane protein 8 (VAMP8) as an APOL1 protein interactor. VAMP8 colocalizes with APOL1 in the podocyte, and the APOL1:VAMP8 interaction was confirmed biochemically and with surface plasmon resonance...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28724725/protein-diversity-in-discrete-structures-at-the-distal-tip-of-the-trypanosome-flagellum
#4
Vladimir Varga, Flavia Moreira-Leite, Neil Portman, Keith Gull
The distal end of the eukaryotic flagellum/cilium is important for axonemal growth and signaling and has distinct biomechanical properties. Specific flagellum tip structures exist, yet their composition, dynamics, and functions are largely unknown. We used biochemical approaches to identify seven constituents of the flagella connector at the tip of an assembling trypanosome flagellum and three constituents of the axonemal capping structure at the tips of both assembling and mature flagella. Both tip structures contain evolutionarily conserved as well as kinetoplastid-specific proteins, and component assembly into the structures occurs very early during flagellum extension...
July 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716154/new-insights-from-gorongosa-national-park-and-niassa-national-reserve-of-mozambique-increasing-the-genetic-diversity-of-trypanosoma-vivax-and-trypanosoma-vivax-like-in-tsetse-flies-wild-ungulates-and-livestock-from-east-africa
#5
Carla Mf Rodrigues, Herakles A Garcia, Adriana C Rodrigues, André G Costa-Martins, Carlos L Pereira, Dagmar L Pereira, Zakaria Bengaly, Luis Neves, Erney P Camargo, Patrick B Hamilton, Marta Mg Teixeira
BACKGROUND: Trypanosoma (Duttonella) vivax is a major pathogen of livestock in Africa and South America (SA), and genetic studies limited to small sampling suggest greater diversity in East Africa (EA) compared to both West Africa (WA) and SA. METHODS: Multidimensional scaling and phylogenetic analyses of 112 sequences of the glycosomal glyceraldehyde phosphate dehydrogenase (gGAPDH) gene and 263 sequences of the internal transcribed spacer of rDNA (ITS rDNA) were performed to compare trypanosomes from tsetse flies from Gorongosa National Park and Niassa National Reserve of Mozambique (MZ), wild ungulates and livestock from EA, and livestock isolates from WA and SA...
July 17, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28713858/life-stage-specific-cargo-receptors-facilitate-glycosylphosphatidylinositol-anchored-surface-coat-protein-transport-in-trypanosoma-brucei
#6
Emilia K Kruzel, George P Zimmett, James D Bangs
The critical virulence factor of bloodstream-form Trypanosoma brucei is the glycosylphosphatidylinositol (GPI)-anchored variant surface glycoprotein (VSG). Endoplasmic reticulum (ER) exit of VSG is GPI dependent and relies on a discrete subset of COPII machinery (TbSec23.2/TbSec24.1). In other systems, p24 transmembrane adaptor proteins selectively recruit GPI-anchored cargo into nascent COPII vesicles. Trypanosomes have eight putative p24s (TbERP1 to TbERP8) that are constitutively expressed at the mRNA level...
July 2017: MSphere
https://www.readbyqxmd.com/read/28713367/nanobodies-as-tools-to-understand-diagnose-and-treat-african-trypanosomiasis
#7
REVIEW
Benoit Stijlemans, Patrick De Baetselier, Guy Caljon, Jan Van Den Abbeele, Jo A Van Ginderachter, Stefan Magez
African trypanosomes are strictly extracellular protozoan parasites that cause diseases in humans and livestock and significantly affect the economic development of sub-Saharan Africa. Due to an elaborate and efficient (vector)-parasite-host interplay, required to complete their life cycle/transmission, trypanosomes have evolved efficient immune escape mechanisms that manipulate the entire host immune response. So far, not a single field applicable vaccine exists, and chemotherapy is the only strategy available to treat the disease...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28706597/an-infrequent-cause-of-apical-ventricular-aneurysm-in-the-united-states
#8
Mohammed M Taleb
Chronic Chagas cardiomyopathy (CCC) is a late complication of Chagas disease with various manifestations including arrhythmia, heart failure, thromboembolism, and stroke. In a patient with symptoms of heart failure and left ventricular apical aneurysm unexplained by structural heart or coronary vascular abnormalities, CCC should be strongly considered and inquiry made about exposure status. Typical electrocardiographic findings of bundle branch block, complete heart blocks, and ventricular arrhythmia are helpful clues...
April 2017: Heart Views: the Official Journal of the Gulf Heart Association
https://www.readbyqxmd.com/read/28704541/increased-genetic-diversity-and-prevalence-of-co-infection-with-trypanosoma-spp-in-koalas-phascolarctos-cinereus-and-their-ticks-identified-using-next-generation-sequencing-ngs
#9
Amanda D Barbosa, Alexander W Gofton, Andrea Paparini, Annachiara Codello, Telleasha Greay, Amber Gillett, Kristin Warren, Peter Irwin, Una Ryan
Infections with Trypanosoma spp. have been associated with poor health and decreased survival of koalas (Phascolarctos cinereus), particularly in the presence of concurrent pathogens such as Chlamydia and koala retrovirus. The present study describes the application of a next-generation sequencing (NGS)-based assay to characterise the prevalence and genetic diversity of trypanosome communities in koalas and two native species of ticks (Ixodes holocyclus and I. tasmani) removed from koala hosts. Among 168 koalas tested, 32...
2017: PloS One
https://www.readbyqxmd.com/read/28701485/gt-rich-promoters-can-drive-rna-pol-ii-transcription-and-deposition-of-h2a-z-in-african-trypanosomes
#10
Carolin Wedel, Konrad U Förstner, Ramona Derr, T Nicolai Siegel
Genome-wide transcription studies are revealing an increasing number of "dispersed promoters" that, unlike "focused promoters", lack well-conserved sequence motifs and tight regulation. Dispersed promoters are nevertheless marked by well-defined chromatin structures, suggesting that specific sequence elements must exist in these unregulated promoters. Here, we have analyzed regions of transcription initiation in the eukaryotic parasite Trypanosoma brucei, in which RNA polymerase II transcription initiation occurs over broad regions without distinct promoter motifs and lacks regulation...
July 12, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28698807/the-2d-structure-of-the-t-brucei-preedited-rps12-mrna-is-not-affected-by-macromolecular-crowding
#11
W-Matthias Leeder, Stephan Voskuhl, H Ulrich Göringer
Mitochondrial transcript maturation in African trypanosomes requires RNA editing to convert sequence-deficient pre-mRNAs into translatable mRNAs. The different pre-mRNAs have been shown to adopt highly stable 2D folds; however, it is not known whether these structures resemble the in vivo folds given the extreme "crowding" conditions within the mitochondrion. Here, we analyze the effects of macromolecular crowding on the structure of the mitochondrial RPS12 pre-mRNA. We use high molecular mass polyethylene glycol as a macromolecular cosolute and monitor the structure of the RNA globally and with nucleotide resolution...
2017: Journal of Nucleic Acids
https://www.readbyqxmd.com/read/28697609/differential-virulence-and-tsetse-fly-transmissibility-of-i-trypanosoma-congolense-i-and-i-trypanosoma-brucei-i-strains
#12
Purity K Gitonga, Kariuki Ndung'u, Grace A Murilla, Paul C Thande, Florence N Wamwiri, Joanna E Auma, Geoffrey N Ngae, James K Kibugu, Richard Kurgat, John K Thuita
African animal trypanosomiasis causes significant economic losses in sub-Saharan African countries because of livestock mortalities and reduced productivity. Trypanosomes, the causative agents, are transmitted by tsetse flies (Glossina spp.). In the current study, we compared and contrasted the virulence characteristics of five Trypanosoma congolense and Trypanosoma brucei isolates using groups of Swiss white mice (n = 6). We further determined the vectorial capacity of Glossina pallidipes, for each of the trypanosome isolates...
June 27, 2017: Onderstepoort Journal of Veterinary Research
https://www.readbyqxmd.com/read/28688979/remarkable-richness-of-trypanosomes-in-tsetse-flies-glossina-morsitans-morsitans-and-glossina-pallidipes-from-the-gorongosa-national-park-and-niassa-national-reserve-of-mozambique-revealed-by-fluorescent-fragment-length-barcoding-fflb
#13
Herakles A Garcia, Carla M F Rodrigues, Adriana C Rodrigues, Dagmar L Pereira, Carlos L Pereira, Erney P Camargo, P B Hamilton, Marta M G Teixeira
Trypanosomes of African wild ungulates transmitted by tsetse flies can cause human and livestock diseases. However, trypanosome diversity in wild tsetse flies remains greatly underestimated. We employed FFLB (fluorescent fragment length barcoding) for surveys of trypanosomes in tsetse flies (3086) from the Gorongosa National Park (GNP) and Niassa National Reserve (NNR) in Mozambique (MZ), identified as Glossina morsitans morsitans (GNP/NNR=77.6%/90.5%) and Glossina pallidipes (22.4%/9.5%). Trypanosomes were microscopically detected in 8...
July 5, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28684718/steroid-alkaloids-from-holarrhena-africana-with-strong-activity-against-trypanosoma-brucei-rhodesiense
#14
Charles Okeke Nnadi, Ngozi Justina Nwodo, Marcel Kaiser, Reto Brun, Thomas J Schmidt
In our continued search for natural compounds with activity against Trypanosoma brucei, causative agent of human African trypanosomiasis (HAT, "sleeping sickness"), we have investigated extracts from the leaves and bark of the West African Holarrhenaafricana (syn. Holarrhena floribunda; Apocynaceae). The extracts and their alkaloid-enriched fractions displayed promising in vitro activity against bloodstream forms of T. brucei rhodesiense (Tbr; East African HAT). Bioactivity-guided chromatographic fractionation of the alkaloid-rich fractions resulted in the isolation of 17 steroid alkaloids, one nitrogen-free steroid and one alkaloid-like non-steroid...
July 6, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28684539/ppr-polyadenylation-factor-defines-mitochondrial-mrna-identity-and-stability-in-trypanosomes
#15
Liye Zhang, Francois M Sement, Takuma Suematsu, Tian Yu, Stefano Monti, Lan Huang, Ruslan Aphasizhev, Inna Aphasizheva
In Trypanosoma brucei, most mitochondrial mRNAs undergo internal changes by RNA editing and 3' end modifications. The temporally separated and functionally distinct modifications are manifested by adenylation prior to editing, and by post-editing extension of a short A-tail into a long A/U-heteropolymer. The A-tail stabilizes partially and fully edited mRNAs, while the A/U-tail enables mRNA binding to the ribosome. Here, we identify an essential pentatricopeptide repeat-containing RNA binding protein, kinetoplast polyadenylation factor 3 (KPAF3), and demonstrate its role in protecting pre-mRNA against degradation by the processome...
July 6, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28674747/oral-administration-of-azithromycin-ameliorates-trypanosomosis-in-trypanosoma-congolense-infected-mice
#16
Nthatisi Innocentia Molefe, Shino Yamasaki, Adrian Miki C Macalanda, Keisuke Suganuma, Kenichi Watanabe, Xuenan Xuan, Noboru Inoue
Animal trypanosomosis is a devastating parasitic disease that is of economic importance to livestock production. The infection includes animal African trypanosomosis, surra, and dourine. The treatment is based solely on few compounds that were discovered decades ago and which are associated with severe toxicity. Furthermore, it is likely that the parasite has developed resistance towards them. Thus, there is an urgent need for new, accessible, and less toxic drugs. Azithromycin is an antibiotic with documented efficacy against Toxoplasma, Babesia, and Plasmodium...
July 4, 2017: Parasitology Research
https://www.readbyqxmd.com/read/28672001/host-seeking-efficiency-can-explain-population-dynamics-of-the-tsetse-fly-glossina-morsitans-morsitans-in-response-to-host-density-decline
#17
Jennifer S Lord, Zinhle Mthombothi, Vitalis K Lagat, Fatumah Atuhaire, John W Hargrove
Females of all blood-feeding arthropod vectors must find and feed on a host in order to produce offspring. For tsetse-vectors of the trypanosomes that cause human and animal African trypanosomiasis-the problem is more extreme, since both sexes feed solely on blood. Host location is thus essential both for survival and reproduction. Host population density should therefore be an important driver of population dynamics for haematophagous insects, and particularly for tsetse, but the role of host density is poorly understood...
July 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28659447/unravelling-the-relationship-between-the-tsetse-fly-and-its-obligate-symbiont-wigglesworthia-transcriptomic-and-metabolomic-landscapes-reveal-highly-integrated-physiological-networks
#18
XiaoLi Bing, Geoffrey M Attardo, Aurelien Vigneron, Emre Aksoy, Francesca Scolari, Anna Malacrida, Brian L Weiss, Serap Aksoy
Insects with restricted diets rely on obligate microbes to fulfil nutritional requirements essential for biological function. Tsetse flies, vectors of African trypanosome parasites, feed exclusively on vertebrate blood and harbour the obligate endosymbiont Wigglesworthia glossinidia. Without Wigglesworthia, tsetse are unable to reproduce. These symbionts are sheltered within specialized cells (bacteriocytes) that form the midgut-associated bacteriome organ. To decipher the core functions of this symbiosis essential for tsetse's survival, we performed dual-RNA-seq analysis of the bacteriome, coupled with metabolomic analysis of bacteriome and haemolymph collected from normal and symbiont-cured (sterile) females...
June 28, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/28657594/the-cytological-events-and-molecular-control-of-life-cycle-development-of-trypanosoma-brucei-in-the-mammalian-bloodstream
#19
REVIEW
Eleanor Silvester, Kirsty R McWilliam, Keith R Matthews
African trypanosomes cause devastating disease in sub-Saharan Africa in humans and livestock. The parasite lives extracellularly within the bloodstream of mammalian hosts and is transmitted by blood-feeding tsetse flies. In the blood, trypanosomes exhibit two developmental forms: the slender form and the stumpy form. The slender form proliferates in the bloodstream, establishes the parasite numbers and avoids host immunity through antigenic variation. The stumpy form, in contrast, is non-proliferative and is adapted for transmission...
June 28, 2017: Pathogens
https://www.readbyqxmd.com/read/28656524/identification-of-potential-trypanothione-reductase-inhibitors-among-commercially-available-formula-see-text-carboline-derivatives-using-chemical-space-lead-like-and-drug-like-filters-pharmacophore-models-and-molecular-docking
#20
Jorge Rodríguez-Becerra, Lizethly Cáceres-Jensen, José Hernández-Ramos, Lorena Barrientos
American trypanosomiasis or Chagas disease caused by the protozoan Trypanosoma cruzi (T. cruzi) is an important endemic trypanosomiasis in Central and South America. This disease was considered to be a priority in the global plan to combat neglected tropical diseases, 2008-2015, which indicates that there is an urgent need to develop more effective drugs. The development of new chemotherapeutic agents against Chagas disease can be related to an important biochemical feature of T. cruzi: its redox defense system...
June 27, 2017: Molecular Diversity
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