Read by QxMD icon Read


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
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)...
September 15, 2016: European Journal of Protistology
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
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
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
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
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...
October 15, 2016: Nucleic Acids Research
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
Sarah Crunkhorn
No abstract text is available yet for this article.
September 29, 2016: Nature Reviews. Drug Discovery
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
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
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
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
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
Shilpi Khare, Advait S Nagle, Agnes Biggart, Yin H Lai, Fang Liang, Lauren C Davis, S Whitney Barnes, Casey J N Mathison, Elmarie Myburgh, Mu-Yun Gao, J Robert Gillespie, Xianzhong Liu, Jocelyn L Tan, Monique Stinson, Ianne C Rivera, Jaime Ballard, Vince Yeh, Todd Groessl, Glenn Federe, Hazel X Y Koh, John D Venable, Badry Bursulaya, Michael Shapiro, Pranab K Mishra, Glen Spraggon, Ansgar Brock, Jeremy C Mottram, Frederick S Buckner, Srinivasa P S Rao, Ben G Wen, John R Walker, Tove Tuntland, Valentina Molteni, Richard J Glynne, Frantisek Supek
Chagas disease, leishmaniasis and sleeping sickness affect 20 million people worldwide and lead to more than 50,000 deaths annually1. The diseases are caused by infection with the kinetoplastid parasites Trypanosoma cruzi, Leishmania spp. and Trypanosoma brucei spp., respectively. These parasites have similar biology and genomic sequence, suggesting that all three diseases could be cured with drug(s) modulating the activity of a conserved parasite target2. However, no such molecular targets or broad spectrum drugs have been identified to date...
August 8, 2016: Nature
Marco A Sanchez, Khoa D Tran, Jessica Valli, Sam Hobbs, Errin Johnson, Eva Gluenz, Scott M Landfear
African trypanosomes and related kinetoplastid parasites selectively traffic specific membrane proteins to the flagellar membrane, but the mechanisms for this trafficking are poorly understood. We show here that KHARON, a protein originally identified in Leishmania parasites, interacts with a putative trypanosome calcium channel and is required for its targeting to the flagellar membrane. KHARON is located at the base of the flagellar axoneme, where it likely mediates targeting of flagellar membrane proteins, but is also on the subpellicular microtubules and the mitotic spindle...
September 16, 2016: Journal of Biological Chemistry
Henry M Kariithi, Sjef Boeren, Edwin K Murungi, Just M Vlak, Adly M M Abd-Alla
BACKGROUND: Glossina m. morsitans is the primary vector of the Trypanosoma brucei group, one of the causative agents of African trypanosomoses. The parasites undergo metacyclogenesis, i.e. transformation into the mammalian-infective metacyclic trypomastigote (MT) parasites, in the salivary glands (SGs) of the tsetse vector. Since the MT-parasites are largely uncultivable in vitro, information on the molecular processes that facilitate metacyclogenesis is scanty. METHODS: To bridge this knowledge gap, we employed tandem mass spectrometry to investigate protein expression modulations in parasitized (T...
2016: Parasites & Vectors
Dazhi Zhao, Kezia Lizardo, Min Hui Cui, Kamalakar Ambadipudi, Jose Lora, Linda A Jelicks, Jyothi F Nagajyothi
Chagasic cardiomyopathy, which is seen in Chagas disease, is the most severe and life-threatening manifestation of infection by the kinetoplastid Trypanosoma cruzi. Adipose tissue and diet play a major role in maintaining lipid homeostasis and regulating cardiac pathogenesis during the development of Chagas cardiomyopathy. We have previously reported that T. cruzi has a high affinity for lipoproteins and that the invasion rate of this parasite increases in the presence of cholesterol, suggesting that drugs that inhibit cholesterol synthesis, such as statins, could affect infection and the development of Chagasic cardiomyopathy...
November 2016: Microbes and Infection
Éverton Dias D'Andréa, Anne Diehl, Peter Schmieder, Hartmut Oschkinat, José Ricardo Pires
Trypanosoma cruzi, Trypanosma brucei and Leishmania spp. are kinetoplastid protozoa causative agents of Chagas disease, sleeping sickness and leishmaniasis, respectively, neglected tropical diseases estimated to infect millions of people worldwide. Their genome sequencing has revealed approximately 50 % of genes encoding hypothetical proteins of unknown function, opening possibilities for novel target identification and drug discovery. Q4DY78 is a putative essential protein from T. cruzi conserved in the related kinetoplastids and divergent from mammalian host proteins...
October 2016: Biomolecular NMR Assignments
Oliver C F Orban, Ricarda S Korn, Diego Benítez, Andrea Medeiros, Lutz Preu, Nadège Loaëc, Laurent Meijer, Oliver Koch, Marcelo A Comini, Conrad Kunick
Trypanothione synthetase is an essential enzyme for kinetoplastid parasites which cause highly disabling and fatal diseases in humans and animals. Inspired by the observation that N(5)-substituted paullones inhibit the trypanothione synthetase from the related parasite Leishmania infantum, we designed and synthesized a series of new derivatives. Although none of the new compounds displayed strong inhibition of Trypanosoma brucei trypanothione synthetase, several of them caused a remarkable growth inhibition of cultivated Trypanosoma brucei bloodstream forms...
August 15, 2016: Bioorganic & Medicinal Chemistry
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"