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  • 1
    Publication Date: 2012-05-23
    Description: There is an urgent need for new antimalarial drugs with novel mechanisms of action to deliver effective control and eradication programs. Parasite resistance to all existing antimalarial classes, including the artemisinins, has been reported during their clinical use. A failure to generate new antimalarials with novel mechanisms of action that circumvent the current resistance challenges will contribute to a resurgence in the disease which would represent a global health emergency. Here we present a unique generation of quinolone lead antimalarials with a dual mechanism of action against two respiratory enzymes, NADH:ubiquinone oxidoreductase (Plasmodium falciparum NDH2) and cytochrome bc1. Inhibitor specificity for the two enzymes can be controlled subtly by manipulation of the privileged quinolone core at the 2 or 3 position. Inhibitors display potent (nanomolar) activity against both parasite enzymes and against multidrug-resistant P. falciparum parasites as evidenced by rapid and selective depolarization of the parasite mitochondrial membrane potential, leading to a disruption of pyrimidine metabolism and parasite death. Several analogs also display activity against liver-stage parasites (Plasmodium cynomolgi) as well as transmission-blocking properties. Lead optimized molecules also display potent oral antimalarial activity in the Plasmodium berghei mouse malaria model associated with favorable pharmacokinetic features that are aligned with a single-dose treatment. The ease and low cost of synthesis of these inhibitors fulfill the target product profile for the generation of a potent, safe, and inexpensive drug with the potential for eventual clinical deployment in the control and eradication of falciparum malaria.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-10-05
    Description: Insecticide resistance poses a serious threat to current malaria control efforts. The Anopheles gambiae genome will enable identification of new resistance genes and will provide new molecular targets for the design of more effective insecticides.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hemingway, Janet -- Field, Linda -- Vontas, John -- New York, N.Y. -- Science. 2002 Oct 4;298(5591):96-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12364782" target="_blank"〉PubMed〈/a〉
    Keywords: Africa South of the Sahara ; Animals ; Anopheles/*genetics/metabolism/parasitology ; Gene Expression ; Gene Expression Profiling ; *Genes, Insect ; Genes, Regulator ; *Genome ; Genomics ; Host-Parasite Interactions ; Humans ; Insect Proteins/metabolism ; Insect Vectors/genetics/metabolism/parasitology ; *Insecticide Resistance ; Insecticides/metabolism ; Malaria/prevention & control/transmission ; Mutation ; Oxidative Stress ; Parasites/physiology ; Quantitative Trait, Heritable ; Sequence Analysis, DNA
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2002-10-05
    Description: At a recent workshop, experts discussed the benefits, risks, and research priorities associated with using genetically manipulated insects in the control of vector-borne diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alphey, Luke -- Beard, C Ben -- Billingsley, Peter -- Coetzee, Maureen -- Crisanti, Andrea -- Curtis, Chris -- Eggleston, Paul -- Godfray, Charles -- Hemingway, Janet -- Jacobs-Lorena, Marcelo -- James, Anthony A -- Kafatos, Fotis C -- Mukwaya, Louis G -- Paton, Michael -- Powell, Jeffrey R -- Schneider, William -- Scott, Thomas W -- Sina, Barbara -- Sinden, Robert -- Sinkins, Steven -- Spielman, Andrew -- Toure, Yeya -- Collins, Frank H -- New York, N.Y. -- Science. 2002 Oct 4;298(5591):119-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Oxford University, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12364786" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Animals, Genetically Modified ; Anopheles/*genetics/parasitology/physiology ; Clinical Trials as Topic ; Ecology ; Evaluation Studies as Topic ; Genes, Insect ; *Genetic Engineering ; Genetics, Population ; Humans ; Insect Vectors/*genetics/parasitology/physiology ; Malaria/*prevention & control/transmission ; *Pest Control, Biological ; Plasmodium/physiology ; Public Health ; Public Opinion ; Transformation, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2002-10-05
    Description: The emergence of insecticide resistance in the mosquito poses a serious threat to the efficacy of many malaria control programs. We have searched the Anopheles gambiae genome for members of the three major enzyme families- the carboxylesterases, glutathione transferases, and cytochrome P450s-that are primarily responsible for metabolic resistance to insecticides. A comparative genomic analysis with Drosophila melanogaster reveals that a considerable expansion of these supergene families has occurred in the mosquito. Low gene orthology and little chromosomal synteny paradoxically contrast the easily identified orthologous groups of genes presumably seeded by common ancestors. In A. gambiae, the independent expansion of paralogous genes is mainly a consequence of the formation of clusters among locally duplicated genes. These expansions may reflect the functional diversification of supergene families consistent with major differences in the life history and ecology of these organisms. These data provide a basis for identifying the resistance-associated enzymes within these families. This will enable the resistance status of mosquitoes, flies, and possibly other holometabolous insects to be monitored. The analyses also provide the means for identifying previously unknown molecules involved in fundamental biological processes such as development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ranson, Hilary -- Claudianos, Charles -- Ortelli, Federica -- Abgrall, Christelle -- Hemingway, Janet -- Sharakhova, Maria V -- Unger, Maria F -- Collins, Frank H -- Feyereisen, Rene -- U01 AI48846/AI/NIAID NIH HHS/ -- U01 AI50687/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2002 Oct 4;298(5591):179-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12364796" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anopheles/enzymology/*genetics ; Carboxylic Ester Hydrolases/chemistry/classification/*genetics/metabolism ; Computational Biology ; Conserved Sequence ; Cytochrome P-450 Enzyme System/chemistry/classification/*genetics/metabolism ; Drosophila melanogaster/enzymology/genetics ; *Evolution, Molecular ; Genes, Duplicate ; Genes, Insect ; Genome ; Genomics ; Glutathione Transferase/chemistry/classification/*genetics/metabolism ; Insecticide Resistance/*genetics ; Multigene Family ; Mutation ; Phylogeny ; Physical Chromosome Mapping ; Sequence Analysis, DNA ; Terminology as Topic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2004-03-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hemingway, Janet -- Craig, Alister -- New York, N.Y. -- Science. 2004 Mar 26;303(5666):1984-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK. hemingway@liverpool.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15044794" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anopheles/*genetics/immunology/*parasitology ; Digestive System/parasitology ; Gene Silencing ; Genes, Insect ; Humans ; Insect Proteins/genetics/*physiology ; Insect Vectors/*genetics/immunology/parasitology ; Lectins, C-Type/genetics/*physiology ; Malaria/parasitology/*prevention & control/transmission ; Plasmodium berghei/*growth & development/immunology ; RNA Interference ; RNA, Double-Stranded
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2016-03-16
    Description: Author(s): E. J. Hemingway, M. E. Cates, and S. M. Fielding We consider a continuum model of active viscoelastic matter, whereby an active nematic liquid crystal is coupled to a minimal model of polymer dynamics with a viscoelastic relaxation time τ C . To explore the resulting interplay between active and polymeric dynamics, we first generalize a linear stabi… [Phys. Rev. E 93, 032702] Published Tue Mar 15, 2016
    Keywords: Liquid Crystals
    Print ISSN: 1539-3755
    Electronic ISSN: 1550-2376
    Topics: Physics
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  • 7
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    Nature Publishing Group (NPG)
    Publication Date: 2015-10-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hemingway, Janet -- England -- Nature. 2015 Oct 8;526(7572):198-9. doi: 10.1038/526198a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26450051" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2010-10-12
    Description: The mosquito Culex quinquefasciatus poses a substantial threat to human and veterinary health as a primary vector of West Nile virus (WNV), the filarial worm Wuchereria bancrofti, and an avian malaria parasite. Comparative phylogenomics revealed an expanded canonical C. quinquefasciatus immune gene repertoire compared with those of Aedes aegypti and Anopheles gambiae. Transcriptomic analysis of C. quinquefasciatus genes responsive to WNV, W. bancrofti, and non-native bacteria facilitated an unprecedented meta-analysis of 25 vector-pathogen interactions involving arboviruses, filarial worms, bacteria, and malaria parasites, revealing common and distinct responses to these pathogen types in three mosquito genera. Our findings provide support for the hypothesis that mosquito-borne pathogens have evolved to evade innate immune responses in three vector mosquito species of major medical importance.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3104938/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3104938/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bartholomay, Lyric C -- Waterhouse, Robert M -- Mayhew, George F -- Campbell, Corey L -- Michel, Kristin -- Zou, Zhen -- Ramirez, Jose L -- Das, Suchismita -- Alvarez, Kanwal -- Arensburger, Peter -- Bryant, Bart -- Chapman, Sinead B -- Dong, Yuemei -- Erickson, Sara M -- Karunaratne, S H P Parakrama -- Kokoza, Vladimir -- Kodira, Chinnappa D -- Pignatelli, Patricia -- Shin, Sang Woon -- Vanlandingham, Dana L -- Atkinson, Peter W -- Birren, Bruce -- Christophides, George K -- Clem, Rollie J -- Hemingway, Janet -- Higgs, Stephen -- Megy, Karine -- Ranson, Hilary -- Zdobnov, Evgeny M -- Raikhel, Alexander S -- Christensen, Bruce M -- Dimopoulos, George -- Muskavitch, Marc A T -- F31 AI080161/AI/NIAID NIH HHS/ -- F31 AI080161-01A1/AI/NIAID NIH HHS/ -- HHSN266200400001C/AO/NIAID NIH HHS/ -- HHSN266200400001C/PHS HHS/ -- HHSN266200400039C/AI/NIAID NIH HHS/ -- HHSN266200400039C/PHS HHS/ -- P20 RR017686/RR/NCRR NIH HHS/ -- P20 RR017686-01/RR/NCRR NIH HHS/ -- R01 AI019769/AI/NIAID NIH HHS/ -- R01 AI019769-26/AI/NIAID NIH HHS/ -- R01 AI059492/AI/NIAID NIH HHS/ -- R01 AI059492-05/AI/NIAID NIH HHS/ -- R01 AI061576/AI/NIAID NIH HHS/ -- R01 AI061576-08/AI/NIAID NIH HHS/ -- R01 AI067698/AI/NIAID NIH HHS/ -- R01 AI067698-05/AI/NIAID NIH HHS/ -- R01 AI078997/AI/NIAID NIH HHS/ -- R01 AI078997-02/AI/NIAID NIH HHS/ -- R01 AI095842/AI/NIAID NIH HHS/ -- R01 AI19769/AI/NIAID NIH HHS/ -- R01 AI59492/AI/NIAID NIH HHS/ -- R01 AI67698/AI/NIAID NIH HHS/ -- R21 AI067642/AI/NIAID NIH HHS/ -- R21 AI067642-01/AI/NIAID NIH HHS/ -- T01CCT622892/PHS HHS/ -- T32 A107536/PHS HHS/ -- T32 AI007414/AI/NIAID NIH HHS/ -- T32 AI007417/AI/NIAID NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2010 Oct 1;330(6000):88-90. doi: 10.1126/science.1193162.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Entomology, Iowa State University, Ames, IA 50011, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20929811" target="_blank"〉PubMed〈/a〉
    Keywords: Aedes/genetics/immunology/microbiology/parasitology ; Animals ; Anopheles gambiae/genetics/metabolism/microbiology/parasitology ; Arboviruses/immunology/pathogenicity/physiology ; Bacteria/immunology/pathogenicity ; Biological Evolution ; Culex/*genetics/*immunology/microbiology/parasitology ; Ecosystem ; Filarioidea/immunology/pathogenicity/physiology ; Gene Expression Profiling ; Gene Expression Regulation ; *Genes, Insect ; *Host-Pathogen Interactions ; Immunity, Innate/*genetics ; Insect Vectors/*genetics/*immunology/microbiology/parasitology ; Oligonucleotide Array Sequence Analysis ; Phylogeny ; RNA Interference ; Transcription, Genetic ; West Nile virus/immunology/pathogenicity/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2010-10-12
    Description: Culex quinquefasciatus (the southern house mosquito) is an important mosquito vector of viruses such as West Nile virus and St. Louis encephalitis virus, as well as of nematodes that cause lymphatic filariasis. C. quinquefasciatus is one species within the Culex pipiens species complex and can be found throughout tropical and temperate climates of the world. The ability of C. quinquefasciatus to take blood meals from birds, livestock, and humans contributes to its ability to vector pathogens between species. Here, we describe the genomic sequence of C. quinquefasciatus: Its repertoire of 18,883 protein-coding genes is 22% larger than that of Aedes aegypti and 52% larger than that of Anopheles gambiae with multiple gene-family expansions, including olfactory and gustatory receptors, salivary gland genes, and genes associated with xenobiotic detoxification.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3740384/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3740384/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arensburger, Peter -- Megy, Karine -- Waterhouse, Robert M -- Abrudan, Jenica -- Amedeo, Paolo -- Antelo, Beatriz -- Bartholomay, Lyric -- Bidwell, Shelby -- Caler, Elisabet -- Camara, Francisco -- Campbell, Corey L -- Campbell, Kathryn S -- Casola, Claudio -- Castro, Marta T -- Chandramouliswaran, Ishwar -- Chapman, Sinead B -- Christley, Scott -- Costas, Javier -- Eisenstadt, Eric -- Feschotte, Cedric -- Fraser-Liggett, Claire -- Guigo, Roderic -- Haas, Brian -- Hammond, Martin -- Hansson, Bill S -- Hemingway, Janet -- Hill, Sharon R -- Howarth, Clint -- Ignell, Rickard -- Kennedy, Ryan C -- Kodira, Chinnappa D -- Lobo, Neil F -- Mao, Chunhong -- Mayhew, George -- Michel, Kristin -- Mori, Akio -- Liu, Nannan -- Naveira, Horacio -- Nene, Vishvanath -- Nguyen, Nam -- Pearson, Matthew D -- Pritham, Ellen J -- Puiu, Daniela -- Qi, Yumin -- Ranson, Hilary -- Ribeiro, Jose M C -- Roberston, Hugh M -- Severson, David W -- Shumway, Martin -- Stanke, Mario -- Strausberg, Robert L -- Sun, Cheng -- Sutton, Granger -- Tu, Zhijian Jake -- Tubio, Jose Manuel C -- Unger, Maria F -- Vanlandingham, Dana L -- Vilella, Albert J -- White, Owen -- White, Jared R -- Wondji, Charles S -- Wortman, Jennifer -- Zdobnov, Evgeny M -- Birren, Bruce -- Christensen, Bruce M -- Collins, Frank H -- Cornel, Anthony -- Dimopoulos, George -- Hannick, Linda I -- Higgs, Stephen -- Lanzaro, Gregory C -- Lawson, Daniel -- Lee, Norman H -- Muskavitch, Marc A T -- Raikhel, Alexander S -- Atkinson, Peter W -- HHSN266200400001C/PHS HHS/ -- HHSN266200400039C/AI/NIAID NIH HHS/ -- HHSN266200400039C/PHS HHS/ -- N01-AI-30071/AI/NIAID NIH HHS/ -- N01AI30071/AI/NIAID NIH HHS/ -- ZIA AI000810-13/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2010 Oct 1;330(6000):86-8. doi: 10.1126/science.1191864.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Disease Vector Research, University of California Riverside, Riverside, CA 92521, USA. arensburger@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20929810" target="_blank"〉PubMed〈/a〉
    Keywords: Aedes/genetics ; Animals ; Anopheles gambiae/genetics ; Chromosome Mapping ; Chromosomes/*genetics ; Culex/classification/*genetics/physiology ; DNA Transposable Elements ; *Genes, Insect ; *Genome ; Insect Proteins/genetics/physiology ; Insect Vectors/genetics ; Molecular Sequence Data ; Multigene Family ; Phylogeny ; Receptors, Odorant/genetics ; Retroelements ; *Sequence Analysis, DNA
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2018-03-31
    Description: Author(s): Ewan J. Hemingway and Suzanne M. Fielding Small disturbances at the air-fluid interface of entangled polymeric fluids can produce strong apparent banding that invades deep into the bulk. [Phys. Rev. Lett. 120, 138002] Published Fri Mar 30, 2018
    Keywords: Polymer, Soft Matter, Biological, Climate, and Interdisciplinary Physics
    Print ISSN: 0031-9007
    Electronic ISSN: 1079-7114
    Topics: Physics
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