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Kinetoplastids

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https://www.readbyqxmd.com/read/28216511/global-kinetoplastea-phylogeny-inferred-from-a-large-scale-multigene-alignment-including-parasitic-species-for-better-understanding-transitions-from-a-free-living-to-a-parasitic-lifestyle
#1
Euki Yazaki, Sohta A Ishikawa, Keitaro Kume, Akira Kumagai, Takashi Kamaishi, Goro Tanifuji, Tetsuo Hashimoto, Yuji Inagaki
All members of the order Trypanosomatida known to date are parasites that are most likely descendants of a free-living ancestor. Trypanosomatids are an excellent model to assess the transition from a free-living to a parasitic lifestyle, because a large amount of experimental data has been accumulated for well-studied members that are harmful to humans and livestock (Trypanosoma spp. and Leishmania spp.). However, recent advances in our understanding of the diversity of trypanosomatids and their close relatives (i...
February 20, 2017: Genes & Genetic Systems
https://www.readbyqxmd.com/read/28210761/the-evolutionary-loss-of-rnai-key-determinants-in-kinetoplastids-as-a-multiple-sporadic-phenomenon
#2
Andrey V Matveyev, João M P Alves, Myrna G Serrano, Vladimir Lee, Ana M Lara, William A Barton, André G Costa-Martins, Stephen M Beverley, Erney P Camargo, Marta M G Teixeira, Gregory A Buck
We screened the genomes of a broad panel of kinetoplastid protists for genes encoding proteins associated with the RNA interference (RNAi) system using probes from the Argonaute (AGO1), Dicer1 (DCL1), and Dicer2 (DCL2) genes of Leishmania brasiliensis and Crithidia fasciculata. We identified homologs for all the three of these genes in the genomes of a subset of these organisms. However, several of these organisms lacked evidence for any of these genes, while others lacked only DCL2. The open reading frames encoding these putative proteins were structurally analyzed in silico...
February 16, 2017: Journal of Molecular Evolution
https://www.readbyqxmd.com/read/28209553/intraspecific-genetic-variability-in-a-population-of-moroccan-leishmania-infantum-revealed-by-pcr-rflp-of-kdna-minicircles
#3
Adil El Hamouchi, Rajaa Ejghal, Moustapha Hida, Meryem Lemrani
In Morocco, Leishmania infantum is the main etiologic agent of human and canine visceral leishmaniasis (VL). This species has been proven to be an opportunistic agent in HIV+ patients and is also responsible of sporadic cutaneous leishmaniasis (CL).This work aims to evaluate the genetic variability of Moroccan L. infantum strains based on PCR-RFLP analysis of the kinetoplastid DNA (kDNA) minicircles. A total of 75 DNA samples extracted from positive Giemsa-stained smears (n=32) and from L. infantum cultures (n=43) was studied...
February 14, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28193658/in-vitro-ex-vivo-and-in-vivo-activity-of-diamidines-against-trypanosoma-congolense-and-trypanosoma-vivax
#4
Kirsten Gillingwater, Christina Kunz, Christiane Braghiroli, David W Boykin, Richard R Tidwell, Reto Brun
African Animal Trypanosomosis (AAT) is caused by the tsetse-transmitted protozoans, Trypanosoma congolense and T. vivax, leading to huge agricultural losses throughout sub-Saharan Africa. Three drugs are available to treat Nagana in cattle (diminazene diaceturate, homidium- and isometamidium chloride). With increasing reports of drug-resistant populations, new molecules should be investigated as potential candidates to combat Nagana. Dicationic compounds have demonstrated excellent efficacy against different kinetoplastid parasites...
February 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28188871/cloning-characterization-and-subcellular-localization-of-nuclear-lim-interactor-interacting-factor-gene-from-leishmania-donovani
#5
R Ravinder, N Goyal
LIM domains are zinc-binding motifs that mediate protein-protein interactions and are found in a wide variety of cytoplasmic and nuclear proteins. The nuclear LIM domain family members have a number of different functions including transcription factors, gene regulation, cell fate determination, organization of the cytoskeleton and tumour formation exerting their function through various LIM domain interacting protein partners/cofactors. Nuclear LIM domain interacting proteins/factors have not been reported in any protozoan parasites including Leishmania...
February 7, 2017: Gene
https://www.readbyqxmd.com/read/28185724/simplifying-nature-towards-the-design-of-broad-spectrum-kinetoplastid-inhibitors-inspired-by-acetogenins
#6
Eoin R Gould, Elizabeth F B King, Stefanie K Menzies, Andrew L Fraser, Lindsay B Tulloch, Marija K Zacharova, Terry K Smith, Gordon J Florence
The need for new treatments for the neglected tropical diseases African sleeping sickness, Chagas disease and Leishmaniasis remains urgent with the diseases widespread in tropical regions, affecting the world's very poorest. We have previously reported bis-tetrahydropyran 1,4-triazole analogues designed as mimics of the annonaceous acetogenin natural product chamuvarinin, which maintained trypanocidal activity. Building upon these studies, we here report related triazole compounds with pendant heterocycles, mimicking the original butenolide of the natural product...
January 28, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28179142/rna-seq-in-kinetoplastids-a-powerful-tool-for-the-understanding-of-the-biology-and-host-pathogen-interactions
#7
REVIEW
Luz Helena Patino, Juan David Ramírez
The kinetoplastids include a large number of parasites responsible for serious diseases in humans and animals (Leishmania and Trypanosoma brucei) considered endemic in several regions of the world. These parasites are characterized by digenetic life cycles that undergo morphological and genetic changes that allow them to adapt to different microenvironments on their vertebrates and invertebrates hosts. Recent advances in ´omics´ technology, specifically transcriptomics have allowed to reveal aspects associated with such molecular changes...
February 4, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28179112/glucose-6-phosphate-dehydrogenase-and-trypanothione-reductase-interaction-protects-leishmania-donovani-from-metalloid-mediated-oxidative-stress
#8
Ayan Kumar Ghosh, Savita Saini, Sushmita Das, Abhishek Mandal, Abul Hasan Sardar, Md Yousuf Ansari, Kumar Abhishek, Ajay Kumar, Ruby Singh, Sudha Verma, Asif Equbal, Vahab Ali, Pradeep Das
Exploration of metabolons as viable drug target is rare in kinetoplastid biology. Here we present a novel protein-protein interaction among Glucose-6-phosphate dehydrogenase (LdG6PDH) and Trypanothione reductase (LdTryR) of Leishmania donovani displaying interconnection between central glucose metabolism and thiol metabolism of this parasite. Digitonin fractionation patterns observed through immunoblotting indicated localisation of both LdG6PDH and LdTryR in cytosol. In-silico and in-vitro interaction observed by size exclusion chromatography, co-purification, pull-down assay and spectrofluorimetric analysis revealed LdG6PDH and LdTryR physically interact with each other in a NADPH dependent manner...
February 4, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28150358/diversity-and-evolution-of-paramoeba-spp-and-their-kinetoplastid-endosymbionts
#9
Shannon J Sibbald, Ugo Cenci, Morgan Colp, Yana Eglit, Charles J O'Kelly, John M Archibald
Members of the genus Paramoeba (including Neoparamoeba) (Amoebozoa) are single-celled eukaryotes of economic and ecological importance due to their association with disease in a variety of marine animals including fish, sea urchins, and lobster. Interestingly, they harbor a eukaryotic endosymbiont of kinetoplastid ancestry, Perkinsela sp. To investigate the complex relationship between Paramoeba spp. and Perkinsela sp., as well as the relationships between different Paramoeba species, molecular data was obtained for four novel isolates...
February 1, 2017: Journal of Eukaryotic Microbiology
https://www.readbyqxmd.com/read/28119024/antiparasitic-lethality-of-sulfonamidebenzamides-in-kinetoplastids
#10
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/28108523/all-that-is-old-does-not-wither-conservation-of-outer-kinetochore-proteins-across-all-eukaryotes
#11
Aruni P Senaratne, Ines A Drinnenberg
The kinetochore drives faithful chromosome segregation in all eukaryotes, yet the underlying machinery is diverse across species. D'Archivio and Wickstead (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201608043) apply sensitive homology predictions to identify proteins in kinetoplastids with similarity to canonical outer kinetochore proteins, suggesting some degree of universality in the eukaryotic kinetochore.
February 2017: Journal of Cell Biology
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
#12
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/28095298/molecular-identification-and-genotyping-of-trypanosoma-cruzi-dna-in-autochthonous-chagas-disease-patients-from-texas-usa
#13
Melissa N Garcia, Hadley Burroughs, Rodion Gorchakov, Sarah M Gunter, Eric Dumonteil, Kristy O Murray, Claudia P Herrera
The parasitic protozoan Trypanosoma cruzi, the causative agent of Chagas disease, is widely distributed throughout the Americas, from the southern United States (US) to northern Argentina, and infects at least 6 million people in endemic areas. Much remains unknown about the dynamics of T. cruzi transmission among mammals and triatomine vectors in sylvatic and peridomestic eco-epidemiological cycles, as well as of the risk of transmission to humans in the US. Identification of T. cruzi DTUs among locally-acquired cases is necessary for enhancing our diagnostic and clinical prognostic capacities, as well as to understand parasite transmission cycles...
January 15, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28091623/comparative-genomics-of-canine-isolated-leishmania-leishmania-amazonensis-from-an-endemic-focus-of-visceral-leishmaniasis-in-governador-valadares-southeastern-brazil
#14
Hugo O Valdivia, Laila V Almeida, Bruno M Roatt, João Luís Reis-Cunha, Agnes Antônia Sampaio Pereira, Celia Gontijo, Ricardo Toshio Fujiwara, Alexandre B Reis, Mandy J Sanders, James A Cotton, Daniella C Bartholomeu
Leishmaniasis is a highly diverse group of diseases caused by kinetoplastid of the genus Leishmania. These parasites are taxonomically diverse, with human pathogenic species separated into two subgenera according to their development site inside the alimentary tract of the sand fly insect vector. The disease encompasses a variable spectrum of clinical manifestations with tegumentary or visceral symptoms. Among the causative species in Brazil, Leishmania (Leishmania) amazonensis is an important etiological agent of human cutaneous leishmaniasis that accounts for more than 8% of all cases in endemic regions...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28077462/bromodomains-in-protozoan-parasites-evolution-function-and-opportunities-for-drug-development
#15
REVIEW
Victoria Jeffers, Chunlin Yang, Sherri Huang, William J Sullivan
Parasitic infections remain one of the most pressing global health concerns of our day, affecting billions of people and producing unsustainable economic burdens. The rise of drug-resistant parasites has created an urgent need to study their biology in hopes of uncovering new potential drug targets. It has been established that disrupting gene expression by interfering with lysine acetylation is detrimental to survival of apicomplexan (Toxoplasma gondii and Plasmodium spp.) and kinetoplastid (Leishmania spp...
March 2017: Microbiology and Molecular Biology Reviews: MMBR
https://www.readbyqxmd.com/read/28034897/trypanosome-outer-kinetochore-proteins-suggest-conservation-of-chromosome-segregation-machinery-across-eukaryotes
#16
Simon D'Archivio, Bill Wickstead
Kinetochores are multiprotein complexes that couple eukaryotic chromosomes to the mitotic spindle to ensure proper segregation. The model for kinetochore assembly is conserved between humans and yeast, and homologues of several components are widely distributed in eukaryotes, but key components are absent in some lineages. The recent discovery in a lineage of protozoa called kinetoplastids of unconventional kinetochores with no apparent homology to model organisms suggests that more than one system for eukaryotic chromosome segregation may exist...
February 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/27988178/a-novel-protein-coding-potential-of-long-intergenic-non-coding-rnas-lincrnas-in-the-kinetoplastid-protozoan-parasite-leishmania-major
#17
Harsh Pawar, Kalpana Pai, Milind S Patole
Cutaneous leishmaniasis (CL) is caused by a kinetoplastid protozoan parasite Leishmania major, as a skin ulcer at the site of the sandfly bite. CL is curable and in most cases ulcers heal spontaneously within three to six months leaving a scar and disfiguration. Complete genome of L. major was reported in 2005 at the very initial phase of kinetoplastid parasite genome sequencing project. Presently, L. major genome is most studied and comprehensively annotated genome and therefore, it is being used as a reference genome for annotating recently sequenced Leishmanial genomes...
March 2017: Acta Tropica
https://www.readbyqxmd.com/read/27940065/identification-of-trypanosoma-cruzi-discrete-typing-units-dtus-in-latin-american-migrants-in-barcelona-spain
#18
Alba Abras, Montserrat Gállego, Carmen Muñoz, Natalia A Juiz, Juan Carlos Ramírez, Carolina I Cura, Silvia Tebar, Anna Fernández-Arévalo, María-Jesús Pinazo, Leonardo de la Torre, Elizabeth Posada, Ferran Navarro, Paula Espinal, Cristina Ballart, Montserrat Portús, Joaquim Gascón, Alejandro G Schijman
Trypanosoma cruzi, the causative agent of Chagas disease, is divided into six Discrete Typing Units (DTUs): TcI-TcVI. We aimed to identify T. cruzi DTUs in Latin-American migrants in the Barcelona area (Spain) and to assess different molecular typing approaches for the characterization of T. cruzi genotypes. Seventy-five peripheral blood samples were analyzed by two real-time PCR methods (qPCR) based on satellite DNA (SatDNA) and kinetoplastid DNA (kDNA). The 20 samples testing positive in both methods, all belonging to Bolivian individuals, were submitted to DTU characterization using two PCR-based flowcharts: multiplex qPCR using TaqMan probes (MTq-PCR), and conventional PCR...
April 2017: Parasitology International
https://www.readbyqxmd.com/read/27911702/the-unconventional-kinetoplastid-kinetochore-from-discovery-toward-functional-understanding
#19
REVIEW
Bungo Akiyoshi
The kinetochore is the macromolecular protein complex that drives chromosome segregation in eukaryotes. Its most fundamental function is to connect centromeric DNA to dynamic spindle microtubules. Studies in popular model eukaryotes have shown that centromere protein (CENP)-A is critical for DNA-binding, whereas the Ndc80 complex is essential for microtubule-binding. Given their conservation in diverse eukaryotes, it was widely believed that all eukaryotes would utilize these components to make up a core of the kinetochore...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27889663/higher-classification-and-phylogeny-of-euglenozoa
#20
Thomas Cavalier-Smith
Discoveries of numerous new taxa and advances in ultrastructure and sequence phylogeny (including here the first site-heterogeneous 18S rDNA trees) require major improvements to euglenozoan higher-level taxonomy. I therefore divide Euglenozoa into three subphyla of substantially different body plans: Euglenoida with pellicular strips; anaerobic Postgaardia (class Postgaardea) dependent on surface bacteria and with uniquely modified feeding apparatuses; and new subphylum Glycomonada characterised by glycosomes (Kinetoplastea, Diplonemea)...
October 2016: European Journal of Protistology
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