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https://www.readbyqxmd.com/read/28429321/euglena-transcript-processing
#1
David C McWatters, Anthony G Russell
RNA transcript processing is an important stage in the gene expression pathway of all organisms and is subject to various mechanisms of control that influence the final levels of gene products. RNA processing involves events such as nuclease-mediated cleavage, removal of intervening sequences referred to as introns and modifications to RNA structure (nucleoside modification and editing). In Euglena, RNA transcript processing was initially examined in chloroplasts because of historical interest in the secondary endosymbiotic origin of this organelle in this organism...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28397756/anti-trypanosomatid-elemanolide-sesquiterpene-lactones-from-vernonia-lasiopus-o-hoffm
#2
Njogu M Kimani, Josphat C Matasyoh, Marcel Kaiser, Reto Brun, Thomas J Schmidt
Sleeping sickness or human African trypanosomiasis (HAT) is a neglected tropical disease (NTD) threatening millions of peoples' lives with thousands infected. The disease is endemic in poorly developed regions of sub-Saharan Africa and is caused by the kinetoplastid "protozoan" parasite Trypanosoma brucei. The parasites are transmitted to humans through bites of infected tsetse flies of the genus Glossina. The few available drugs for treatment of this disease are highly toxic, difficult to administer, costly and unavailable to poor rural communities bearing the major burden of this infection...
April 8, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28381627/characterization-of-rbp9-and-rbp10-two-developmentally-regulated-rna-binding-proteins-in-trypanosoma-brucei
#3
Luis Miguel De Pablos, Steve Kelly, Janaina de Freitas Nascimento, Jack Sunter, Mark Carrington
The fate of an mRNA is determined by its interaction with proteins and small RNAs within dynamic complexes called ribonucleoprotein complexes (mRNPs). In Trypanosoma brucei and related kinetoplastids, responses to internal and external signals are mainly mediated by post-transcriptional processes. Here, we used proximity-dependent biotin identification (BioID) combined with RNA-seq to investigate the changes resulting from ectopic expression of RBP10 and RBP9, two developmentally regulated RNA-binding proteins (RBPs)...
April 2017: Open Biology
https://www.readbyqxmd.com/read/28369657/origin-and-evolutionary-alteration-of-the-mitochondrial-import-system-in-eukaryotic-lineages
#4
Yoshinori Fukasawa, Toshiyuki Oda, Kentaro Tomii, Kenichiro Imai
Protein transport systems are fundamentally important for maintaining mitochondrial function. Nevertheless, mitochondrial protein translocases such as the kinetoplastid ATOM complex have recently been shown to vary in eukaryotic lineages. Various evolutionary hypotheses have been formulated to explain this diversity. To resolve any contradiction, estimating the primitive state and clarifying changes from that state are necessary. Here, we present more likely primitive models of mitochondrial translocases, specifically the translocase of the outer membrane (TOM) and translocase of the inner membrane (TIM) complexes, using scrutinized phylogenetic profiles...
March 20, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28336470/bioassay-guided-isolation-of-active-principles-from-nigerian-medicinal-plants-identifies-new-trypanocides-with-low-toxicity-and-no-cross-resistance-to-diamidines-and-arsenicals
#5
Godwin Unekwuojo Ebiloma, John Ogbaji Igoli, Evangelos Katsoulis, Anne-Marie Donachie, Anthonius Eze, Alexander Ian Gray, Harry P de Koning
ETHNOPHARMACOLOGICAL RELEVANCE: Leaves from the plant species studied herein are traditionally used in northern Nigeria against various protozoan infections. However, none of these herbal preparations have been standardized, nor have their toxicity to mammalian cells been investigated. In search of improved and non-toxic active antiprotozoal principles that are not cross-resistant with current anti-parasitics, we here report the results of the in vitro screening of extracts from seven selected medicinal plant species (Centrosema pubescens, Moringa oleifera, Tridax procumbens, Polyalthia longifolia, Newbouldia laevis, Eucalyptus maculate, Jathropha tanjorensis), used traditionally to treat kinetoplastid infections in Nigeria, and the isolation of their bioactive principles...
March 20, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28334821/in-vivo-cleavage-specificity-of-trypanosoma-brucei-editosome-endonucleases
#6
Jason Carnes, Suzanne McDermott, Atashi Anupama, Brian G Oliver, D Noah Sather, Kenneth Stuart
RNA editing is an essential post-transcriptional process that creates functional mitochondrial mRNAs in Kinetoplastids. Multiprotein editosomes catalyze pre-mRNA cleavage, uridine (U) insertion or deletion, and ligation as specified by guide RNAs. Three functionally and compositionally distinct editosomes differ by the mutually exclusive presence of the KREN1, KREN2 or KREN3 endonuclease and their associated partner proteins. Because endonuclease cleavage is a likely point of regulation for RNA editing, we elucidated endonuclease specificity in vivo...
February 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28320630/early-polymerase-chain-reaction-detection-of-chagas-disease-reactivation-in-heart-transplant-patients
#7
Priscilla Almeida da Costa, Marcela Segatto, Danielle Fernandes Durso, Wagson José de Carvalho Moreira, Lucas Lodi Junqueira, Fábio Morato de Castilho, Silvio Amadeu de Andrade, Cláudio Léo Gelape, Egler Chiari, Andréa Teixeira-Carvalho, Sergio Danilo Junho Pena, Carlos Renato Machado, Gloria Regina Franco, Geraldo Brasileiro Filho, Maria da Consolação Vieira Moreira, Andréa Mara Macedo
BACKGROUND: Heart transplantation is a valuable therapeutic option for Chagas disease patients with severe cardiomyopathy. During patient follow-up, the differential diagnosis between cardiac transplant rejection and Chagas disease infection reactivation remains a challenging task, which hinders rapid implementation of the appropriate treatment. Herein we investigate whether polymerase chain reaction (PCR) strategies could facilitate early detection of Trypanosoma cruzi (T cruzi) in transplanted endomyocardial biopsies (EMBs)...
February 24, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28285595/evaluation-of-four-molecular-methods-to-detect-leishmania-infection-in-dogs
#8
Andreia Albuquerque, Lenea Campino, Luís Cardoso, Sofia Cortes
BACKGROUND: Canine leishmaniasis, a zoonotic disease caused by Leishmania infantum vectored by phlebotomine sand flies, is considered a relevant veterinary and public health problem in various countries, namely in the Mediterranean basin and Brazil, where dogs are considered the main reservoir hosts. Not only diseased dogs but also those subclinically infected play a relevant role in the transmission of L. infantum to vectors; therefore, early diagnosis is essential, under both a clinical and an epidemiological perspective...
March 13, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28246372/a-novel-stage-specific-glycosomal-nucleoside-diphosphate-kinase-from-trypanosoma-cruzi
#9
Maria de Los Milagros Camara, Leon Bouvier, Chantal Reigada, Fabio A Digirolamo, Melisa Saye, Claudio A Pereira
Nucleoside diphosphate kinases (NDPK) are key enzymes involved in the intracellular nucleotide maintenance in all living organisms, especially in trypanosomatids which are unable to synthesise purines de novo. Four putative NDPK isoforms were identified in the Trypanosoma cruzi Chagas, 1909 genome but only two of them were characterised so far. In this work, we studied a novel isoform from T. cruzi called TcNDPK3. This enzyme presents an atypical N-terminal extension similar to the DM10 domains. In T. cruzi, DM10 sequences targeted other NDPK isoform (TcNDPK2) to the cytoskeleton, but TcNDPK3 was localised in glycosomes despite lacking a typical peroxisomal targeting signal...
February 17, 2017: Folia Parasitologica
https://www.readbyqxmd.com/read/28242550/desing-and-synthesis-of-potent-anti-trypanosoma-cruzi-agents-new-thiazoles-derivatives-which-induce-apoptotic-parasite-death
#10
Elany Barbosa da Silva, Dayane Albuquerque Oliveira E Silva, Arsênio Rodrigues Oliveira, Carlos Henrique da Silva Mendes, Thiago André Ramos Dos Santos, Aline Caroline da Silva, Maria Carolina Acioly de Castro, Rafaela Salgado Ferreira, Diogo Rodrigo Magalhães Moreira, Marcos Veríssimo de Oliveira Cardoso, Carlos Alberto de Simone, Valéria Rêgo Alves Pereira, Ana Cristina Lima Leite
Chagas disease, caused by the kinetoplastid protozoan parasite Trypanosoma cruzi, remains a relevant cause of illness and premature death and it is estimated that 6 million to 7 million people are infected worldwide. Although chemotherapy options are limited presenting serious problems, such as low efficacy and high toxicity. T. cruzi is susceptible to thiazoles, making this class of compounds appealing for drug development. Previously, thiazoles resulted in an increase in anti-T. cruzi activity in comparison to thiosemicarbazones...
April 21, 2017: European Journal of Medicinal Chemistry
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
#11
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
#12
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...
March 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
#13
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...
May 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
#14
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
#15
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...
May 5, 2017: Gene
https://www.readbyqxmd.com/read/28185724/simplifying-nature-towards-the-design-of-broad-spectrum-kinetoplastid-inhibitors-inspired-by-acetogenins
#16
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
#17
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
#18
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
#19
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 because of 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
#20
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
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