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https://www.readbyqxmd.com/read/28644986/designing-novel-inhibitors-against-histone-acetyltransferase-hat-%C3%A2-gcn5-of-plasmodium-falciparum
#1
Amarjeet Kumar, Krishanu Bhowmick, Kunwar Somesh Vikramdeo, Neelima Mondal, Naidu Subbarao, Suman Kumar Dhar
During active proliferation phase of intra-erythrocytic cycle, the genome of P. falciparum is regulated epigenetically and evolutionary conserved parasite-specific histone proteins are extensively acetylated. The reversible process of lysine acetylation, causing transcriptional activation and its deacetylation, causing transcriptional repression is regulated by balanced activities of HATs and HDACs. They are also known to regulate antigenic variations and gametocytic conversion in P. falciparum. These histone modifying enzymes have been identified as potential targets for development of anitmalarials in literature...
June 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28644560/identification-and-characterization-of-ars-like-sequences-as-putative-origin-s-of-replication-in-human-malaria-parasite-plasmodium-falciparum
#2
Meetu Agarwal, Krishanu Bhowmick, Kushal Shah, Annangarachari Krishnamachari, Suman Kumar Dhar
DNA replication is a fundamental process in genome maintenance, and initiates from several genomic sites (origins) in eukaryotes. In S. cerevisiae, conserved sequences known as Autonomously Replicating Sequences (ARSs) provide a landing pad for the Origin Recognition Complex (ORC), leading to replication initiation. Although origins from higher eukaryotes share some common sequence features, the definitive genomic organization of these sites remains elusive. The human malaria parasite Plasmodium falciparum undergoes multiple rounds of DNA replication; therefore, control of initiation events is crucial to ensure proper replication...
June 23, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28643631/the-anopheles-gambiae-2la-chromosome-inversion-is-associated-with-susceptibility-to-plasmodium-falciparum-in-africa
#3
Michelle M Riehle, Tullu Bukhari, Awa Gneme, Wamdaogo M Guelbeogo, Boubacar Coulibaly, Abdrahamane Fofana, Adrien Pain, Emmanuel Bischoff, Francois Renaud, Abdoul H Beavogui, Sekou F Traore, N'Fale Sagnon, Kenneth D Vernick
Chromosome inversions suppress genetic recombination and establish co-adapted gene complexes, or supergenes. The 2La inversion is a widespread polymorphism in the Anopheles gambiae species complex, the major African mosquito vectors of human malaria. Here we show that alleles of the 2La inversion are associated with natural malaria infection levels in wild-captured vectors from West and East Africa. Mosquitoes carrying the more-susceptible allele (2L+(a)) are also behaviorally less likely to be found inside houses...
June 23, 2017: ELife
https://www.readbyqxmd.com/read/28642573/characterisation-of-plasmodium-falciparum-populations-selected-on-the-human-endothelial-receptors-p-selectin-e-selectin-cd9-and-cd151
#4
Nahla Galal Metwally, Ann-Kathrin Tilly, Pedro Lubiana, Lisa K Roth, Michael Dörpinghaus, Stephan Lorenzen, Kathrin Schuldt, Susanne Witt, Anna Bachmann, Henning Tidow, Thomas Gutsmann, Thorsten Burmester, Thomas Roeder, Egbert Tannich, Iris Bruchhaus
The ability of the parasite Plasmodium falciparum to evade the immune system and be sequestered within human small blood vessels is responsible for severe forms of malaria. The sequestration depends on the interaction between human endothelial receptors and P. falciparum erythrocyte membrane protein 1 (PfEMP1) exposed on the surface of the infected erythrocytes (IEs). In this study, the transcriptomes of parasite populations enriched for parasites that bind to human P-selectin, E-selectin, CD9 and CD151 receptors were analysed...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642094/investigation-of-the-component-in-artemisia-annua-l-leading-to-enhanced-antiplasmodial-potency-of-artemisinin-via-regulation-of-its-metabolism
#5
Tian-Yu Cai, Yun-Rui Zhang, Jian-Bo Ji, Jie Xing
ETHNOPHARMACOLOGICAL RELEVANCE: The chemical matrix of the herb Artemisia annua L. (A. annua), from which artemisinin (QHS) is isolated, can enhance both the bioavailability and efficacy of QHS. However, the exact mechanism of this synergism remains unknown. The biotransformation of QHS and potential "enzyme inhibitors" in plant matrix could be of great importance in understanding the improved efficacy of QHS in A. annua, which has been limited to the synergism with flavonoid components...
June 19, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28641558/bis-2-aminoimidazolines-and-bisguanidines-synthetic-approaches-antiparasitic-activity-and-dna-binding-properties
#6
Christophe Dardonville, J Jonathan Nué Martínez
BACKGROUND: Parasitic diseases caused by protozoan parasites of the genus Trypanosoma and Plasmodium cause some of the deadliest and disabling human infections in tropical and subtropical areas. Diphenyl-based bis(2-phenylimino)imidazolidines and bisguanidines are extremely potent antiparasitic agents against Trypanosoma brucei (etiological agent of African trypanosomiasis) and Plasmodium falciparum (etiological agent of severe malaria). Many of these compounds are also curative in mouse models of stage 1 African trypanosomiasis representing promising leads for the development of antitrypanosomal drugs...
June 22, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28639487/mrp2-abcc2-c1515y-polymorphism-modulates-exposure-to-lumefantrine-during-artemether-lumefantrine-antimalarial-therapy
#7
Karin Vos, Carlotta Lo Sciuto, Rita Piedade, Michael Ashton, Anders Björkman, Billy Ngasala, Andreas Mårtensson, José Pedro Gil
AIM: To investigate the potential involvement of the hepatic ATP-binding cassette transporters MRP2 and MDR1 in the disposition of lumefantrine (LUM) among patients with uncomplicated Plasmodium falciparum malaria. MATERIALS & METHODS: The tag SNPs MDR1/ABCB1 C3435T and MRP2/ABCC2 C1515Y were determined in two artemether-LUM clinical trials, including a pharmacokinetic/pharmacodynamic study focused on the treatment phase (72 h), and an efficacy trial where day 7 (D7) LUM levels were measured...
June 22, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28638769/deeper-insight-into-the-six-step-domino-reaction-of-aldehydes-with-malononitrile-and-evaluation-of-antiviral-and-antimalarial-activities-of-the-obtained-bicyclic-products
#8
Christina M Bock, Gangajji Parameshwarappa, Simon Bönisch, Walter Bauer, Corina Hutterer, Maria Leidenberger, Oliver Friedrich, Manfred Marschall, Barbara Kappes, Andreas Görling, Svetlana B Tsogoeva
The straightforward and efficient synthesis of complex aza- and carbobicyclic compounds, which are of importance for medicinal chemistry, is a challenge for modern chemical methodology. An unprecedented metal-free six-step domino reaction of aldehydes with malononitrile was presented in our previous study to provide, in a single operation, these bicyclic nitrogen-containing molecules. Presented here is a deeper investigation of this atom-economical domino process by extending the scope of aldehydes, performing post-modifications of domino products, applying bifunctional organocatalysts and comprehensive NMR studies of selected domino products...
June 2017: ChemistryOpen
https://www.readbyqxmd.com/read/28638076/single-molecule-analysis-reveals-that-dna-replication-dynamics-vary-across-the-course-of-schizogony-in-the-malaria-parasite-plasmodium-falciparum
#9
Slavica Stanojcic, Nada Kuk, Imran Ullah, Yvon Sterkers, Catherine J Merrick
The mechanics of DNA replication and cell cycling are well-characterized in model organisms, but less is known about these basic aspects of cell biology in early-diverging Apicomplexan parasites, which do not divide by canonical binary fission but undergo unconventional cycles. Schizogony in the malaria parasite, Plasmodium, generates ~16-24 new nuclei via independent, asynchronous rounds of genome replication prior to cytokinesis and little is known about the control of DNA replication that facilitates this...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637923/infectivity-of-plasmodium-falciparum-sporozoites-determines-emerging-parasitemia-in-infected-volunteers
#10
Matthew B B McCall, Linda J Wammes, Marijke C C Langenberg, Geert-Jan van Gemert, Jona Walk, Cornelus C Hermsen, Wouter Graumans, Rob Koelewijn, Jean-François Franetich, Sandra Chishimba, Max Gerdsen, Audrey Lorthiois, Marga van de Vegte, Dominique Mazier, Else M Bijker, Jaap J van Hellemond, Perry J J van Genderen, Robert W Sauerwein
Malaria sporozoites must first undergo intrahepatic development before a pathogenic blood-stage infection is established. The success of infection depends on host and parasite factors. In healthy human volunteers undergoing controlled human malaria infection (CHMI), we directly compared three clinical Plasmodium falciparum isolates for their ability to infect primary human hepatocytes in vitro and to drive the production of blood-stage parasites in vivo. Our data show a correlation between the efficiency of strain-specific sporozoite invasion of human hepatocytes and the dynamics of patent parasitemia in study subjects, highlighting intrinsic differences in infectivity among P...
June 21, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28637467/imported-plasmodium-falciparum-and-locally-transmitted-plasmodium-vivax-cross-border-malaria-transmission-scenario-in-northwestern-thailand
#11
Patchara Sriwichai, Stephan Karl, Yudthana Samung, Kirakorn Kiattibutr, Jeeraphat Sirichaisinthop, Ivo Mueller, Liwang Cui, Jetsumon Sattabongkot
BACKGROUND: Cross-border malaria transmission is an important problem for national malaria control programmes. The epidemiology of cross-border malaria is further complicated in areas where Plasmodium falciparum and Plasmodium vivax are both endemic. By combining passive case detection data with entomological data, a transmission scenario on the northwestern Thai-Myanmar border where P. falciparum is likely driven by importation was described, whereas P. vivax is also locally transmitted...
June 21, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28637390/isolation-structural-elucidation-and-antiplasmodial-activity-of-fucosterol-compound-from-brown-seaweed-sargassum%C3%A2-linearifolium-against-malarial-parasite-plasmodium-falciparum
#12
Pachiappan Perumal, Rajamani Sowmiya, Sundaram Prasanna Kumar, Sundaram Ravikumar, Paramasivam Deepak, Govindasamy Balasubramani
The brown seaweed, Sargassum linearifolium (Turner) C. Agardh, 1820 is commonly available along the south-east coast of India. Its compound fucosterol was isolated and confirmed through spectral characterisation and chemical transformation methods. The antiplasmodial effect of the isolated fucosterol was investigated against the 3D7 chloroquine sensitive Plasmodium falciparum strain, parasitaemia percentage was determined at 48 h and morphological change was studied through microscopic examination after Giemsa staining...
June 21, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28636858/plasmodium-falciparum-mortality-in-africa-between-1990-and-2015
#13
LETTER
Peter W Gething, Simon I Hay, Stephen S Lim
No abstract text is available yet for this article.
June 22, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28636857/plasmodium-falciparum-mortality-in-africa-between-1990-and-2015
#14
LETTER
Melissa A Penny, Thomas A Smith
New England Journal of Medicine, Volume 376, Issue 25, Page 2493-2494, June 2017.
June 22, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28636461/genice-a-novel-framework-for-gene-network-inference-by-clustering-exhaustive-search-and-multivariate-analysis
#15
Ricardo de Souza Jacomini, David Correa Martins-Jr, Felipe Leno da Silva, Anna Helena Reali Costa
Gene network (GN) inference from temporal gene expression data is a crucial and challenging problem in systems biology. Expression data sets usually consist of dozens of temporal samples, while networks consist of thousands of genes, thus rendering many inference methods unfeasible in practice. To improve the scalability of GN inference methods, we propose a novel framework called GeNICE, based on probabilistic GNs; the main novelty is the introduction of a clustering procedure to group genes with related expression profiles and to provide an approximate solution with reduced computational complexity...
June 21, 2017: Journal of Computational Biology: a Journal of Computational Molecular Cell Biology
https://www.readbyqxmd.com/read/28636311/insights-into-integrated-lead-generation-and-target-identification-in-malaria-and-tuberculosis-drug-discovery
#16
John Okombo, Kelly Chibale
New, safe and effective drugs are urgently needed to treat and control malaria and tuberculosis, which affect millions of people annually. However, financial return on investment in the poor settings where these diseases are mostly prevalent is very minimal to support market-driven drug discovery and development. Moreover, the imminent loss of therapeutic lifespan of existing therapies due to evolution and spread of drug resistance further compounds the urgency to identify novel effective drugs. However, the advent of new public-private partnerships focused on tropical diseases and the recent release of large data sets by pharmaceutical companies on antimalarial and antituberculosis compounds derived from phenotypic whole cell high throughput screening have spurred renewed interest and opened new frontiers in malaria and tuberculosis drug discovery...
June 21, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28635296/benzoxaborole-antimalarial-agents-part-5-lead-optimization-of-novel-amide-pyrazinyloxy-benzoxaboroles-and-identification-of-a-preclinical-candidate
#17
Yong-Kang Zhang, Jacob J Plattner, Eric E Easom, Robert Toms Jacobs, Denghui Guo, Yvonne R Freund, Pamela Berry, Vic Ciaravino, John C L Erve, Philip J Rosenthal, Brice Campo, Francisco-Javier Gamo, Laura M Sanz, Jianxin Cao
Carboxamide pyrazinyloxy benzoxaboroles were investigated with the goal to identify a molecule with satisfactory antimalarial activity, physicochemical properties, pharmacokinetic profile, in vivo efficacy, and safety profile. This optimization effort discovered 46, which met our target candidate profile. Compound 46 had excellent activity against cultured Plasmodium falciparum, and in vivo against P. falciparum and P. berghei in infected mice. It exhibited good PK properties in mouse, rat and dog. It was highly active against other eleven P...
June 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28634831/malaria-2017-update-on-the-clinical-literature-and-management
#18
REVIEW
Johanna P Daily
PURPOSE OF REVIEW: Malaria is a prevalent disease in travelers to and residents of malaria-endemic regions. Health care workers in both endemic and non-endemic settings should be familiar with the latest evidence for the diagnosis, management and prevention of malaria. This article will discuss the recent malaria epidemiologic and medical literature to review the progress, challenges, and optimal management of malaria. RECENT FINDINGS: There has been a marked decrease in malaria-related global morbidity and mortality secondary to malaria control programs over the last few decades...
June 20, 2017: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/28634346/generating-conditional-gene-knockouts-in-plasmodium-a-toolkit-to-produce-stable-dicre-recombinase-expressing-parasite-lines-using-crispr-cas9
#19
Ellen Knuepfer, Marta Napiorkowska, Christiaan van Ooij, Anthony A Holder
Successful establishment of CRISPR/Cas9 genome editing technology in Plasmodium spp. has provided a powerful tool to transform Plasmodium falciparum into a genetically more tractable organism. Conditional gene regulation approaches are required to study the function of gene products critical for growth and erythrocyte invasion of blood stage parasites. Here we employ CRISPR/Cas9 to facilitate use of the dimerisable Cre-recombinase (DiCre) that is frequently used to mediate the excision and loss of loxP-flanked DNA sequences in a rapamycin controlled manner...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634183/syk-inhibitors-interfere-with-erythrocyte-membrane-modification-during-p-falciparum-growth-and-suppress-parasite-egress
#20
Antonella Pantaleo, Kristina R Kesely, Maria Carmina Pau, Ioannis Tsamesidis, Evelin Schwarzer, Oleksii A Skorokhod, Huynh D Chien, Marta Ponzi, Lucia Bertuccini, Philip S Low, Francesco M Turrini
Band 3 (a.k.a. the anion exchanger, SLCA1, AE1) constitutes the major attachment site of the spectrin-based cytoskeleton to the erythrocyte's lipid bilayer and thereby contributes critically to the stability of the red cell membrane. During the intra-erythrocytic stage of Plasmodium falciparum's life cycle, band 3 becomes tyrosine phosphorylated in response to oxidative stress, leading to a decrease in its affinity for the spectrin/actin cytoskeleton and causing global membrane destabilization. Because this membrane weakening is hypothesized to facilitate parasite egress and the consequent dissemination of released merozoites throughout the bloodstream, we decided to explore which tyrosine kinase inhibitors might block the kinase-induced membrane destabilization...
June 20, 2017: Blood
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