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https://www.readbyqxmd.com/read/28095298/molecular-identification-and-genotyping-of-trypanosoma-cruzi-dna-in-autochthonous-chagas-disease-patients-from-texas-usa
#1
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 14, 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
#2
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
#3
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
#4
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...
December 29, 2016: 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
#5
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...
December 14, 2016: Acta Tropica
https://www.readbyqxmd.com/read/27940065/identification-of-trypanosoma-cruzi-discrete-typing-units-dtus-in-latin-american-migrants-in-barcelona-spain
#6
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...
December 7, 2016: Parasitology International
https://www.readbyqxmd.com/read/27911702/the-unconventional-kinetoplastid-kinetochore-from-discovery-toward-functional-understanding
#7
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
#8
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
https://www.readbyqxmd.com/read/27829476/murine-models-susceptibility-to-distinct-trypanosoma-cruzi-i-genotypes-infection
#9
Cielo M León, Marleny Montilla, Ricardo Vanegas, Maria Castillo, Edgar Parra, Juan David Ramírez
Chagas disease is a complex zoonosis that affects around 8 million people worldwide. This pathology is caused by Trypanosoma cruzi, a kinetoplastid parasite that shows tremendous genetic diversity evinced in six distinct Discrete Typing Units (TcI-TcVI) including a recent genotype named as TcBat and associated with anthropogenic bats. TcI presents a broad geographical distribution and has been associated with chronic cardiomyopathy. Recent phylogenetic studies suggest the existence of two genotypes (Domestic (TcIDom) and sylvatic TcI) within TcI...
November 10, 2016: Parasitology
https://www.readbyqxmd.com/read/27820863/pyrimidine-salvage-enzymes-are-essential-for-de-novo-biosynthesis-of-deoxypyrimidine-nucleotides-in-trypanosoma-brucei
#10
Christopher Leija, Filipa Rijo-Ferreira, Lisa N Kinch, Nick V Grishin, Nicole Nischan, Jennifer J Kohler, Zeping Hu, Margaret A Phillips
The human pathogenic parasite Trypanosoma brucei possess both de novo and salvage routes for the biosynthesis of pyrimidine nucleotides. Consequently, they do not require salvageable pyrimidines for growth. Thymidine kinase (TK) catalyzes the formation of dTMP and dUMP and is one of several salvage enzymes that appear redundant to the de novo pathway. Surprisingly, we show through analysis of TK conditional null and RNAi cells that TK is essential for growth and for infectivity in a mouse model, and that a catalytically active enzyme is required for its function...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27760563/evolution-of-the-tim17-protein-family
#11
Vojtěch Žárský, Pavel Doležal
BACKGROUND: The Tim17 family of proteins plays a fundamental role in the biogenesis of mitochondria. Three Tim17 family proteins, Tim17, Tim22, and Tim23, are the central components of the widely conserved multi-subunit protein translocases, TIM23 and TIM22, which mediate protein transport across and into the inner mitochondrial membrane, respectively. In addition, several Tim17 family proteins occupy the inner and outer membranes of plastids. RESULTS: We have performed comprehensive sequence analyses on 5631 proteomes from all domains of life deposited in the Uniprot database...
October 19, 2016: Biology Direct
https://www.readbyqxmd.com/read/27752045/structures-and-stabilization-of-kinetoplastid-specific-split-rrnas-revealed-by-comparing-leishmanial-and-human-ribosomes
#12
Xing Zhang, Mason Lai, Winston Chang, Iris Yu, Ke Ding, Jan Mrazek, Hwee L Ng, Otto O Yang, Dmitri A Maslov, Z Hong Zhou
The recent success in ribosome structure determination by cryoEM has opened the door to defining structural differences between ribosomes of pathogenic organisms and humans and to understand ribosome-targeting antibiotics. Here, by direct electron-counting cryoEM, we have determined the structures of the Leishmania donovani and human ribosomes at 2.9 Å and 3.6 Å, respectively. Our structure of the leishmanial ribosome elucidates the organization of the six fragments of its large subunit rRNA (as opposed to a single 28S rRNA in most eukaryotes, including humans) and reveals atomic details of a unique 20 amino acid extension of the uL13 protein that pins down the ends of three of the rRNA fragments...
October 18, 2016: Nature Communications
https://www.readbyqxmd.com/read/27744351/rna-editing-tutase-1-structural-foundation-of-substrate-recognition-complex-interactions-and-drug-targeting
#13
Lional Rajappa-Titu, Takuma Suematsu, Paola Munoz-Tello, Marius Long, Özlem Demir, Kevin J Cheng, Jason R Stagno, Hartmut Luecke, Rommie E Amaro, Inna Aphasizheva, Ruslan Aphasizhev, Stéphane Thore
Terminal uridyltransferases (TUTases) execute 3' RNA uridylation across protists, fungi, metazoan and plant species. Uridylation plays a particularly prominent role in RNA processing pathways of kinetoplastid protists typified by the causative agent of African sleeping sickness, Trypanosoma brucei In mitochondria of this pathogen, most mRNAs are internally modified by U-insertion/deletion editing while guide RNAs and rRNAs are U-tailed. The founding member of TUTase family, RNA editing TUTase 1 (RET1), functions as a subunit of the 3' processome in uridylation of gRNA precursors and mature guide RNAs...
December 15, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27715485/constructive-edge-of-uridylation-induced-rna-degradation
#14
Ruslan Aphasizhev, Takuma Suematsu, Liye Zhang, Inna Aphasizheva
RNA uridylation is a significant transcriptome-shaping factor in protists, fungi, metazoans, and plants. The 3' U-additions are catalyzed by terminal uridyltransferases (TUTases), a diverse group of enzymes that along with non-canonical poly(A) polymerases form a distinct group in the superfamily of DNA polymerase β-like nucleotidyl transferases. Within and across studied organisms and subcellular compartments, TUTases differ in nucleotide triphosphate selectivity, interacting partners, and RNA targets. A general premise linking RNA uridylation to 3'-5' degradation received support from several studies of small RNAs and mRNA turnover...
October 7, 2016: RNA Biology
https://www.readbyqxmd.com/read/27681791/antiparasitic-drugs-proteasome-inhibition-combats-kinetoplastid-infections
#15
Sarah Crunkhorn
No abstract text is available yet for this article.
September 29, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27615028/sending-a-message-extracellular-vesicles-of-pathogenic-protozoan-parasites
#16
Anthony J Szempruch, Lauren Dennison, Rudo Kieft, John M Harrington, Stephen L Hajduk
Parasitic unicellular eukaryotes use extracellular vesicles (EVs) as vehicles for intercellular communication and host manipulation. By using various mechanisms to generate EVs and by transferring a wide range of molecules through EVs, pathogenic protozoans are able to establish infective niches, modulate the immune system of the host and cause disease. In addition to effects on the host, EVs are able to transfer virulence factors, drug-resistance genes and differentiation factors between parasites. In this Progress article, we explore recent insights into the biology of EVs from human infectious protozoan parasites, including Trichomonas vaginalis, Plasmodium spp...
November 2016: Nature Reviews. Microbiology
https://www.readbyqxmd.com/read/27540714/evaluation-of-a-novel-lentiviral-vaccine-expressing-kmp11-haspb-fusion-protein-against-leishmania-infantum-in-balb-c-mice
#17
N Mortazavidehkordi, A Farjadfar, H Khanahmad, Z Ghayour Najafabadi, N Hashemi, A Fallah, A Najafi, V Kia, S H Hejazi
Hydrophilic acylated surface protein B (HASPB) is an immunogenic Leishmania protein against which antibodies are produced in the sera of cutaneous and visceral Leishmaniasis (VL) patients. Kinetoplastid membrane protein 11 (KMP11) is another protein antigen of Leishmania which is reported as a promising candidate for vaccination of VL. It is a highly conserved surface protein present in all members of kinetoplastid family and is expressed in both promastigotes and amastigotes. In this study, the coding sequence of KMP11 and HASPB was cloned into a pCDH-cGFP lentiviral vector as a fusion protein...
October 6, 2016: Parasite Immunology
https://www.readbyqxmd.com/read/27540585/deah-rha-helicase%C3%A2-znf-cofactor-systems-in-kinetoplastid-rna-editing-and-evolutionarily-distant-rna-processes
#18
Jorge Cruz-Reyes, Blaine H M Mooers, Zakaria Abu-Adas, Vikas Kumar, Shelly Gulati
Multi-zinc finger proteins are an emerging class of cofactors in DEAH-RHA RNA helicases across highly divergent eukaryotic lineages. DEAH-RHA helicase•zinc finger cofactor partnerships predate the split of kinetoplastid protozoa, which include several human pathogens, from other eukaryotic lineages 100-400 Ma. Despite a long evolutionary history, the prototypical DEAH-RHA domains remain highly conserved. This short review focuses on a recently identified DEAH-RHA helicase•zinc finger cofactor system in kinetoplastid RNA editing, and its potential functional parallels with analogous systems in embryogenesis control in nematodes and antivirus protection in humans...
2016: RNA & Disease
https://www.readbyqxmd.com/read/27536007/rna-damage-in-biological-conflicts-and-the-diversity-of-responding-rna-repair-systems
#19
A Maxwell Burroughs, L Aravind
RNA is targeted in biological conflicts by enzymatic toxins or effectors. A vast diversity of systems which repair or 'heal' this damage has only recently become apparent. Here, we summarize the known effectors, their modes of action, and RNA targets before surveying the diverse systems which counter this damage from a comparative genomics viewpoint. RNA-repair systems show a modular organization with extensive shuffling and displacement of the constituent domains; however, a general 'syntax' is strongly maintained whereby systems typically contain: a RNA ligase (either ATP-grasp or RtcB superfamilies), nucleotidyltransferases, enzymes modifying RNA-termini for ligation (phosphatases and kinases) or protection (methylases), and scaffold or cofactor proteins...
October 14, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27527618/synthesis-screening-and-in-silico-simulations-of-anti-parasitic-propamidine-benzimidazole-derivatives
#20
Carlos A Méndez-Cuesta, Miguel Ángel Herrera-Rueda, Sergio Hidalgo-Figueroa, Hugo Tlahuext, Rosa Moo-Puc, Juan Bautista Chale-Dzul, Manuel Chan-Bacab, Benjamín Otto Ortega-Morales, Emanuel Hernández-Núñez, Oscar Méndez-Lucio, José L Medina-Franco, Gabriel Navarrete-Vazquez
BACKGROUND: Propamidine, an antiseptic aromatic diamidine is a toxic compound with potential use as antiprotozoal drug. On the other hand, benzimidazole derivatives have shown excellent antiparasitic effects. We designed hybrid molecules between propamidine and benzimidazole in order to retain the antiprotozoal action, but decreasing the toxic effect of the molecule. Objetive: Design and prepare 12 hybrids from propamidine and benzimidazole for testing their antiparasitic effect over three protozoa: Giardia intestinalis, Trichomonas vaginalis and Leishmania Mexicana, as well as conduct several in silico simulations such as toxicological profile, molecular docking and molecular dynamics in order to understand their potential mode of action...
August 11, 2016: Medicinal Chemistry
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