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https://www.readbyqxmd.com/read/28636858/plasmodium-falciparum-mortality-in-africa-between-1990-and-2015
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/28634105/genetic-diversity-in-the-c-terminus-of-merozoite-surface-protein-1-among-plasmodium-knowlesi-isolates-from-selangor-and-sabah-borneo-malaysia
#9
Nan Jiun Yap, Xiang Ting Goh, Anson V Koehler, Timothy William, Tsin Wen Yeo, Indra Vythilingam, Robin B Gasser, Yvonne A L Lim
Plasmodium knowlesi, a malaria parasite of macaques, has emerged as an important parasite of humans. Despite the significance of P. knowlesi malaria in parts of Southeast Asia, very little is known about the genetic variation in this parasite. Our aim here was to explore sequence variation in a molecule called the 42kDa merozoite surface protein-1 (MSP-1), which is found on the surface of blood stages of Plasmodium spp. and plays a key role in erythrocyte invasion. Several studies of P. falciparum have reported that the C-terminus (a 42kDa fragment) of merozoite surface protein-1 (MSP-142; consisting of MSP-119 and MSP-133) is a potential candidate for a malaria vaccine...
June 17, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28630943/parasites-lacking-the-micronemal-protein-mic2-are-deficient-in-surface-attachment-and-host-cell-egress-but-remain-virulent-in-vivo
#10
Simon Gras, Allison Jackson, Stuart Woods, Gurman Pall, Jamie Whitelaw, Jacqueline M Leung, Gary E Ward, Craig W Roberts, Markus Meissner
Background: Micronemal proteins of the thrombospondin-related anonymous protein (TRAP) family are believed to play essential roles during gliding motility and host cell invasion by apicomplexan parasites, and currently represent major vaccine candidates against Plasmodium falciparum, the causative agent of malaria. However, recent evidence suggests that they play multiple and different roles than previously assumed. Here, we analyse a null mutant for MIC2, the TRAP homolog in Toxoplasma gondii. Methods: We performed a careful analysis of parasite motility in a 3D-environment, attachment under shear stress conditions, host cell invasion and in vivo virulence...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28630585/identification-of-the-plasmodium-species-in-clinical-samples-from-children-residing-in-five-epidemiological-strata-of-malaria-in-cameroon
#11
Tebit Emmanuel Kwenti, Tayong Dizzle Bita Kwenti, Longdoh Anna Njunda, Andreas Latz, Kukwah Anthony Tufon, Theresa Nkuo-Akenji
BACKGROUND: Malaria in Cameroon was previously known to be caused solely by Plasmodium falciparum but today, evidence points to other Plasmodium species including P. vivax, P. ovale and P. malariae. The purpose of this study was to identify the Plasmodium species in clinical samples from children residing in five epidemiological strata of malaria in Cameroon, so as to advise control policies. METHODS: One thousand six hundred nine febrile children (≤15 years) were recruited from five epidemiological strata of malaria including the Sudano-sahelian (SS) strata, the High inland plateau (HIP) strata, the South Cameroonian Equatorial forest (SCEF) strata, the High western plateau (HWP) strata and the Coastal (C) strata...
2017: Tropical Medicine and Health
https://www.readbyqxmd.com/read/28630062/the-transcription-factor-nfat1-participates-in-the-induction-of-cd4-t-cell-functional-exhaustion-during-plasmodium-yoelii-infection
#12
Rachel Y Ames, Li-Min Ting, Inessa Gendlina, Kami Kim, Fernando Macian
Repeated stimulation of T cells that occurs in the context of chronic infection results in progressively reduced responsiveness of T cells to pathogen-derived antigens. This phenotype, known as T cell exhaustion, occurs during chronic infections caused by a variety of pathogens, from persistent viruses to parasites. Unlike the memory cells that typically form after successful pathogen clearance following an acute infection, exhausted T cells secrete lower levels of effector cytokines, proliferate less in response to cognate antigen, and up-regulate cell-surface inhibitory molecules such as PD-1 and LAG-3...
June 19, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28628279/acyclic-nucleoside-phosphonates-containing-9-deazahypoxanthine-and-a-5-membered-heterocycle-as-selective-inhibitors-of-plasmodial-6-oxopurine-phosphoribosyltransferases
#13
Martin Maxmilian Kaiser, Ondřej Baszczyňski, Dana Hocková, Lenka Poštová-Slavětínská, Martin Dračínský, Dianne T Keough, Luke W Guddat, Zlatko Janeba
Acyclic nucleoside phosphonates (ANPs) are an important class of therapeutic drugs that act as antiviral agents by inhibiting viral DNA polymerases and reverse transcriptases. ANPs containing a 6-oxopurine instead of 6-aminopurine or pyrimidine bases are inhibitors of the purine salvage enzyme, hypoxanthine-guanine-[xanthine]-phosphoribosyltransferase (HG[X]PRT). Such compounds, and their prodrugs, are able to arrest the growth of Plasmodium falciparum (Pf) in cell culture. A new series of ANPs has been synthesized and tested as inhibitors of human HGPRT, PfHGXPRT and Plasmodium vivax (Pv) HGPRT...
June 19, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28627360/the-plasmodium-falciparum-exported-protein-pf3d7_0402000-binds-to-erythrocyte-ankyrin-and-band-4-1
#14
Bikash Shakya, Wesley D Penn, Ernesto S Nakayasu, Douglas J LaCount
Plasmodium falciparum extensively modifies the infected red blood cell (RBC), resulting in changes in deformability, shape and surface properties. These alterations suggest that the RBC cytoskeleton is a major target for modification during infection. However, the molecular mechanisms leading to these changes are largely unknown. To begin to address this question, we screened for exported P. falciparum proteins that bound to the erythrocyte cytoskeleton proteins ankyrin 1 (ANK1) and band 4.1 (4.1R), which form critical interactions with other cytoskeletal proteins that contribute to the deformability and stability of RBCs...
June 13, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28626547/structure-guided-optimization-of-quinoline-inhibitors-of-plasmodium-n-myristoyltransferase
#15
Victor Goncalves, James A Brannigan, Alice Laporte, Andrew S Bell, Shirley M Roberts, Anthony J Wilkinson, Robin J Leatherbarrow, Edward W Tate
The parasite Plasmodium vivax is the most widely distributed cause of recurring malaria. N-Myristoyltransferase (NMT), an enzyme that catalyses the covalent attachment of myristate to the N-terminal glycine of substrate proteins, has been described as a potential target for the treatment of this disease. Herein, we report the synthesis and the structure-guided optimization of a series of quinolines with balanced activity against both Plasmodium vivax and Plasmodium falciparum N-myristoyltransferase (NMT).
January 1, 2017: MedChemComm
https://www.readbyqxmd.com/read/28626211/once-malaria-is-eliminated-more-attention-should-be-paid-to-imported-malaria-data-from-five-years-of-surveillance-in-the-city-of-yiwu-in-eastern-china
#16
Xuanjun Dong, Jie Yang, Lianqin Lou, Liebo Zhu, Xiayan Feng, Linong Yao
This study reviewed and analyzed data on malaria cases in Yiwu from 2012 to 2016 via a webbased system for managing and reporting information on infectious diseases. A total of 161 cases were diagnosed (77.02% due to Plasmodium falciparum, 18.01% due to P. vivax, 4.35% due to P. ovale, and 0.62% due to P. malariae). One case was imported from Yunnan Province in China and the others were imported from overseas. The ratio of male to female patients was 7.47:1. The average age was 36.34 years (SD: 9.63). Most cases (87...
June 18, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/28623926/perennial-transmission-of-malaria-in-the-low-altitude-areas-of-baringo-county-kenya
#17
Collince J Omondi, Daniel Onguru, Lucy Kamau, Mark Nanyingi, George Ong'amo, Benson Estambale
BACKGROUND: Malaria causes the greatest public health burden in sub-Saharan Africa where high mortality occurs mainly in children under 5 years of age. Traditionally, malaria has been reported mainly in the lowlands endemic regions of western Kenya, while the highlands of the Rift Valley have been relatively free except for the sporadic epidemics in some areas. Baringo County is located in the Kenyan highlands. The county generally experiences seasonal transmission of malaria. A few hotspots which experience continuous malaria transmission in the county do however exist...
June 17, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28622791/prevalence-and-associated-risk-factors-of-haemoparasites-and-their-effects-on-hematological-profile-in-domesticated-chickens-in-district-layyah-punjab-pakistan
#18
Muhammad Ali-Ul-Husnain Naqvi, Muhammad Kasib Khan, Zafar Iqbal, Hafiz Muhammad Rizwan, Muhammad Nisar Khan, Sana Zahra Naqvi, Arsalan Zafar, Zia Ud Din Sindhu, Rao Zahid Abbas, Asghar Abbas
Several haemoparasites commonly infect avian species, including chicken that significantly decline productivity and ultimately lead to high mortality rate. The current study was designed to assess the prevalence and associated risk factors of haemoparasites in domesticated chickens in and around District Layyah, Punjab Province, Pakistan. For this purpose, blood samples from a total of 384 backyard chickens were collected from wing vein using sterile insulin syringe. The parasites were identified from Giemsa stained thin blood smears based on morphological features using standard keys...
August 1, 2017: Preventive Veterinary Medicine
https://www.readbyqxmd.com/read/28621040/bioactive-neolignans-and-other-compounds-from-magnolia-grandiflora-l-isolation-and-antiplasmodial-activity
#19
Abdul Latif, Yongle Du, Seema R Dalal, Emilio F Merino, Maria B Cassera, Michael Goetz, David G I Kingston
Bioassay-guided fractionation of a methanol extract of Magnolia grandiflora against Plasmodium falciparum yielded two new (1 and 2) and six known (3 - 8) bioactive compounds. The structures of the new compounds were assigned by mass spectrometric and 1D and 2D NMR data. Known compounds were identified by comparison of (1) H NMR and MS data with literature data. The two known neolignans 3 and 4 showed moderate antiplasmodial activity with IC50 values of 2.8 ± 0.1 and 3.4 ± 0.1 μM, respectively. Weak antiplasmodial activity was recorded for compounds 1, 2, 5, 6, 7 and 8, with IC50 values of 38 ± 2, 23 ± 2, 16...
June 16, 2017: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/28620583/engineering-of-genetically-arrested-parasites-gaps-for-a-precision-malaria-vaccine
#20
REVIEW
Oriana Kreutzfeld, Katja Müller, Kai Matuschewski
Continuous stage conversion and swift changes in the antigenic repertoire in response to acquired immunity are hallmarks of complex eukaryotic pathogens, including Plasmodium species, the causative agents of malaria. Efficient elimination of Plasmodium liver stages prior to blood infection is one of the most promising malaria vaccine strategies. Here, we describe different genetically arrested parasites (GAPs) that have been engineered in Plasmodium berghei, P. yoelii and P. falciparum and compare their vaccine potential...
2017: Frontiers in Cellular and Infection Microbiology
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