A Small Molecule Glycosaminoglycan Mimetic Blocks Plasmodium Invasion of the Mosquito Midgut
Publication Date
November 21, 2013
Journal
PLOS Pathogens
Authors
Derrick K. Mathias, Rebecca Pastrana Mena, Elisabetta Ranucci, Dingyin Tao, et al
Volume
9
Issue
11
Pages
e1003757
DOI
https://dx.plos.org/10.1371/journal.ppat.1003757
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1003757
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/24278017
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836724
Europe PMC
http://europepmc.org/abstract/MED/24278017
Web of Science
000330386900027
Scopus
84888273194
Mendeley
http://www.mendeley.com/research/small-molecule-glycosaminoglycan-mimetic-blocks-plasmodium-invasion-mosquito-midgut
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Mendeley | Further Information

{"title"=>"A Small Molecule Glycosaminoglycan Mimetic Blocks Plasmodium Invasion of the Mosquito Midgut", "type"=>"journal", "authors"=>[{"first_name"=>"Derrick K.", "last_name"=>"Mathias", "scopus_author_id"=>"55212987300"}, {"first_name"=>"Rebecca", "last_name"=>"Pastrana-Mena", "scopus_author_id"=>"26041035900"}, {"first_name"=>"Elisabetta", "last_name"=>"Ranucci", "scopus_author_id"=>"7003897117"}, {"first_name"=>"Dingyin", "last_name"=>"Tao", "scopus_author_id"=>"24529189200"}, {"first_name"=>"Paolo", "last_name"=>"Ferruti", "scopus_author_id"=>"7005363540"}, {"first_name"=>"Corrie", "last_name"=>"Ortega", "scopus_author_id"=>"57198405109"}, {"first_name"=>"Gregory O.", "last_name"=>"Staples", "scopus_author_id"=>"26025797100"}, {"first_name"=>"Joseph", "last_name"=>"Zaia", "scopus_author_id"=>"7005197463"}, {"first_name"=>"Eizo", "last_name"=>"Takashima", "scopus_author_id"=>"10538836100"}, {"first_name"=>"Takafumi", "last_name"=>"Tsuboi", "scopus_author_id"=>"7202976416"}, {"first_name"=>"Natalie A.", "last_name"=>"Borg", "scopus_author_id"=>"6701395118"}, {"first_name"=>"Luisella", "last_name"=>"Verotta", "scopus_author_id"=>"7004493728"}, {"first_name"=>"Rhoel R.", "last_name"=>"Dinglasan", "scopus_author_id"=>"6507528785"}], "year"=>2013, "source"=>"PLoS Pathogens", "identifiers"=>{"doi"=>"10.1371/journal.ppat.1003757", "sgr"=>"84888273194", "issn"=>"15537366", "pui"=>"370341893", "isbn"=>"1553-7374 (Electronic) 1553-7366 (Linking)", "pmid"=>"24278017", "scopus"=>"2-s2.0-84888273194"}, "id"=>"7e53fc1a-522a-35fe-a33d-97d92e696c9d", "abstract"=>"Malaria transmission-blocking (T-B) interventions are essential for malaria elimination. Small molecules that inhibit the Plasmodium ookinete-to-oocyst transition in the midgut of Anopheles mosquitoes, thereby blocking sporogony, represent one approach to achieving this goal. Chondroitin sulfate glycosaminoglycans (CS-GAGs) on the Anopheles gambiae midgut surface are putative ligands for Plasmodium falciparum ookinetes. We hypothesized that our synthetic polysulfonated polymer, VS1, acting as a decoy molecular mimetic of midgut CS-GAGs confers malaria T-B activity. In our study, VS1 repeatedly reduced midgut oocyst development by as much as 99% (P<0.0001) in mosquitoes fed with P. falciparum and Plasmodium berghei. Through direct-binding assays, we observed that VS1 bound to two critical ookinete micronemal proteins, each containing at least one von Willebrand factor A (vWA) domain: (i) circumsporozoite protein and thrombospondin-related anonymous protein-related protein (CTRP) and (ii) vWA domain-related protein (WARP). By immunofluorescence microscopy, we observed that VS1 stains permeabilized P. falciparum and P. berghei ookinetes but does not stain P. berghei CTRP knockouts or transgenic parasites lacking the vWA domains of CTRP while retaining the thrombospondin repeat region. We produced structural homology models of the first vWA domain of CTRP and identified, as expected, putative GAG-binding sites on CTRP that align closely with those predicted for the human vWA A1 domain and the Toxoplasma gondii MIC2 adhesin. Importantly, the models also identified patches of electropositive residues that may extend CTRP's GAG-binding motif and thus potentiate VS1 binding. Our molecule binds to a critical, conserved ookinete protein, CTRP, and exhibits potent malaria T-B activity. This study lays the framework for a high-throughput screen of existing libraries of safe compounds to identify those with potent T-B activity. We envision that such compounds when used as partner drugs with current antimalarial regimens and with RTS,S vaccine delivery could prevent the transmission of drug-resistant and vaccine-breakthrough strains.", "link"=>"http://www.mendeley.com/research/small-molecule-glycosaminoglycan-mimetic-blocks-plasmodium-invasion-mosquito-midgut", "reader_count"=>42, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>3, "Researcher"=>14, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>1, "Student > Master"=>4, "Other"=>2, "Student > Bachelor"=>2, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>3, "Researcher"=>14, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>1, "Student > Master"=>4, "Other"=>2, "Student > Bachelor"=>2, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>24, "Medicine and Dentistry"=>5, "Veterinary Science and Veterinary Medicine"=>1, "Chemistry"=>1, "Immunology and Microbiology"=>2, "Decision Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Chemistry"=>{"Chemistry"=>1}, "Decision Sciences"=>{"Decision Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>24}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>3}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Colombia"=>1, "Brazil"=>1, "United Kingdom"=>2, "France"=>1}, "group_count"=>3}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1292036"], "description"=>"<p>Immunofluorescence microscopy images of VS1 staining patterns of permeabilized wild type ookinetes from (<b>A</b>) <i>P. falciparum</i> (WT<sub>Pf</sub>) and (<b>B</b>) <i>P. berghei</i> (WT<sub>Pb</sub>). Each row of images depicts brightfield, followed by staining with VS1 (green), P28 (red), and the merged image of VS1, P28, and DAPI nuclear staining (blue). Note that different antibodies were used for each <i>Plasmodium</i> species to stain orthologous surface markers, α-P28 for <i>P. falciparum</i> and α-Pbs21 for <i>P. berghei</i>. Size bar = 10 µm. (<b>C</b>) Binding assays with recombinant <i>P. vivax</i> CTRP and WARP (<a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003757#ppat.1003757.s005\" target=\"_blank\">Figure S5</a>) demonstrate that biotinylated VS1 is recognized by PvWARP and the first vWA domain of PvCTRP. Two representative experiments are shown with assays performed in triplicate. Black bars represent PvWARP (PvW) and gray bars represent PvCTRP (PvC). Each protein, at two concentrations (10 and 5 µg/ml), was allowed to bind with biotinylated VS1 immobilized to a microplate, followed by detection using an anti-HIS MAb (Sigma). In addition, competitive binding assays were performed by incubating the recombinant proteins with heparin (HEP) and chondroitin sulfate A (CS-A) prior to incubation with VS1 and detection of PvWARP and PvCTRP binding to the VS1-coated plate as above. A no-protein control was included in each ELISA assay and used as the background subtraction value. Error bars represent +/−1 standard deviation. (<b>D–F</b>) Immunofluorescence microscopy images demonstrating selective VS1 binding to ookinetes that were generated <i>in vitro</i> from <i>P. berghei</i> (<b>D</b>) CTRP<sub>KO</sub>, (<b>E</b>) ΔTS<sub>7</sub>, and (<b>F</b>) ΔA<sub>6</sub> transgenic lines. VS1 staining of ΔTS<sub>7</sub> but not CTRP<sub>KO</sub> or ΔA<sub>6</sub> ookinetes suggest that the vWA domain of CTRP is the primary binding ligand of VS1, and that staining is specific to the localized expression of CTRP in micronemes. Each row of images depicts brightfield, followed by staining with VS1 (green), P28 (red), and the merged image of VS1, P28, and DAPI nuclear staining (blue). Size bar = 10 µm.</p>", "links"=>[], "tags"=>["binds", "micronemal"], "article_id"=>859637, "categories"=>["Biological Sciences"], "users"=>["Derrick K. Mathias", "Rebecca Pastrana-Mena", "Elisabetta Ranucci", "Dingyin Tao", "Paolo Ferruti", "Corrie Ortega", "Gregory O. Staples", "Joseph Zaia", "Eizo Takashima", "Takafumi Tsuboi", "Natalie A. Borg", "Luisella Verotta", "Rhoel R. Dinglasan"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1003757.g004", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/VS1_binds_to_critical_i_Plasmodium_i_micronemal_proteins_/859637", "title"=>"VS1 binds to critical <i>Plasmodium</i> micronemal proteins.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-21 04:00:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/1292031"], "description"=>"<p>(<b>A</b>) Structure of compounds designed to interfere with ionic interactions between <i>Plasmodium</i> ookinetes and midgut apical-surface associated glycosaminoglycans (<a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003757#ppat.1003757.s001\" target=\"_blank\">Figure S1A</a>). The table indicates the average molecular weight (MW) and polydispersity index (PDI) for each species of compound tested in the study. (<b>B–C</b>) <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003757#s3\" target=\"_blank\">Results</a> from representative replicate SMFAs showing <i>P. falciparum</i> midgut-oocyst intensities in <i>An. gambiae</i> plotted by treatment group. Below each graph, experimental details are provided, where N is the number of mosquito midguts dissected and scored for oocysts, prev is the infection prevalence among mosquitoes in a given treatment group, median is the median oocyst number, mean is the mean oocyst number, and % inhibition is calculated as (median<sub>control</sub> – median<sub>treatment</sub>)/median<sub>control</sub>. (<b>D–E</b>) Same as panels B–C except that <i>An. stephensi</i> were used. The level of statistical significance is denoted by asterisks following Bonferroni correction of <i>z-</i>scores, * = p&lt;0.05, ** = p&lt;0.01, *** = p&lt;0.001.</p>", "links"=>[], "tags"=>["exhibits", "marked", "transmission-blocking", "divergent", "anopheline"], "article_id"=>859632, "categories"=>["Biological Sciences"], "users"=>["Derrick K. Mathias", "Rebecca Pastrana-Mena", "Elisabetta Ranucci", "Dingyin Tao", "Paolo Ferruti", "Corrie Ortega", "Gregory O. Staples", "Joseph Zaia", "Eizo Takashima", "Takafumi Tsuboi", "Natalie A. Borg", "Luisella Verotta", "Rhoel R. Dinglasan"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1003757.g001", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/VS1_exhibits_marked_transmission_blocking_activity_against_i_P_falciparum_i_in_two_divergent_anopheline_species_/859632", "title"=>"VS1 exhibits marked transmission-blocking activity against <i>P. falciparum</i> in two divergent anopheline species.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-21 04:00:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/1292040", "https://ndownloader.figshare.com/files/1292041", "https://ndownloader.figshare.com/files/1292042", "https://ndownloader.figshare.com/files/1292043", "https://ndownloader.figshare.com/files/1292044", "https://ndownloader.figshare.com/files/1292045", "https://ndownloader.figshare.com/files/1292046", "https://ndownloader.figshare.com/files/1292047", "https://ndownloader.figshare.com/files/1292048"], "description"=>"<div><p>Malaria transmission-blocking (T-B) interventions are essential for malaria elimination. Small molecules that inhibit the <i>Plasmodium</i> ookinete-to-oocyst transition in the midgut of <i>Anopheles</i> mosquitoes, thereby blocking sporogony, represent one approach to achieving this goal. Chondroitin sulfate glycosaminoglycans (CS-GAGs) on the <i>Anopheles gambiae</i> midgut surface are putative ligands for <i>Plasmodium falciparum</i> ookinetes. We hypothesized that our synthetic polysulfonated polymer, VS1, acting as a decoy molecular mimetic of midgut CS-GAGs confers malaria T-B activity. In our study, VS1 repeatedly reduced midgut oocyst development by as much as 99% (<i>P</i>&lt;0.0001) in mosquitoes fed with <i>P. falciparum</i> and <i>Plasmodium berghei</i>. Through direct-binding assays, we observed that VS1 bound to two critical ookinete micronemal proteins, each containing at least one von Willebrand factor A (vWA) domain: (i) circumsporozoite protein and thrombospondin-related anonymous protein-related protein (CTRP) and (ii) vWA domain-related protein (WARP). By immunofluorescence microscopy, we observed that VS1 stains permeabilized <i>P. falciparum</i> and <i>P. berghei</i> ookinetes but does not stain <i>P. berghei</i> CTRP knockouts or transgenic parasites lacking the vWA domains of CTRP while retaining the thrombospondin repeat region. We produced structural homology models of the first vWA domain of CTRP and identified, as expected, putative GAG-binding sites on CTRP that align closely with those predicted for the human vWA A1 domain and the <i>Toxoplasma gondii</i> MIC2 adhesin. Importantly, the models also identified patches of electropositive residues that may extend CTRP's GAG-binding motif and thus potentiate VS1 binding. Our molecule binds to a critical, conserved ookinete protein, CTRP, and exhibits potent malaria T-B activity. This study lays the framework for a high-throughput screen of existing libraries of safe compounds to identify those with potent T-B activity. We envision that such compounds when used as partner drugs with current antimalarial regimens and with RTS,S vaccine delivery could prevent the transmission of drug-resistant and vaccine-breakthrough strains.</p></div>", "links"=>[], "tags"=>["glycosaminoglycan", "mimetic", "blocks", "mosquito", "midgut"], "article_id"=>859641, "categories"=>["Biological Sciences"], "users"=>["Derrick K. Mathias", "Rebecca Pastrana-Mena", "Elisabetta Ranucci", "Dingyin Tao", "Paolo Ferruti", "Corrie Ortega", "Gregory O. Staples", "Joseph Zaia", "Eizo Takashima", "Takafumi Tsuboi", "Natalie A. Borg", "Luisella Verotta", "Rhoel R. Dinglasan"], "doi"=>[nil, nil, nil, nil, nil, nil, nil, nil, nil], "stats"=>{"downloads"=>12, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/A_Small_Molecule_Glycosaminoglycan_Mimetic_Blocks_i_Plasmodium_i_Invasion_of_the_Mosquito_Midgut/859641", "title"=>"A Small Molecule Glycosaminoglycan Mimetic Blocks <i>Plasmodium</i> Invasion of the Mosquito Midgut", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-11-21 04:00:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/1292038"], "description"=>"<p>For each treatment group, the data are summarized into four columns. In the first two columns, the means of the median number of oocysts per mosquito for 4–5 mice per group are given for pre- and post-injection feedings, respectively, with the standard error for each reported in parentheses below the mean. In the third column, the means of percent Inhibition, calculated as the average of (median<sub>pre</sub> – median<sub>post</sub>)/median<sub>pre</sub> for each mouse, are reported for each treatment group along with standard errors in parentheses. In the fourth column, <i>P-</i>value results of Mann-Whitney U tests are reported for each set of pre- and post-injection feedings. Only <i>P</i>-values that are significant at a Bonferroni-corrected alpha of 0.0028 are given. NS, non-significant.</p>", "links"=>[], "tags"=>["replicate", "feeding", "assays", "vs1", "fed", "anka", "-infected", "mice", "pre-", "post-injection", "pbs", "pvp", "polymer"], "article_id"=>859639, "categories"=>["Biological Sciences"], "users"=>["Derrick K. Mathias", "Rebecca Pastrana-Mena", "Elisabetta Ranucci", "Dingyin Tao", "Paolo Ferruti", "Corrie Ortega", "Gregory O. Staples", "Joseph Zaia", "Eizo Takashima", "Takafumi Tsuboi", "Natalie A. Borg", "Luisella Verotta", "Rhoel R. Dinglasan"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1003757.t001", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Summary_of_the_results_from_two_replicate_direct_feeding_assays_DFA_for_each_VS1_compound_using_i_Anopheles_stephensi_i_that_fed_on_i_Plasmodium_berghei_i_ANKA_2_34_infected_mice_pre_and_post_injection_with_either_PBS_carrier_only_control_PVP_non_sulfated/859639", "title"=>"Summary of the results from two replicate direct feeding assays (DFA) for each VS1 compound using <i>Anopheles stephensi</i> that fed on <i>Plasmodium berghei</i> ANKA 2.34 -infected mice pre- and post-injection with either PBS (carrier-only control), PVP", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-11-21 04:00:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/1292037"], "description"=>"<p>(<b>A</b>) Amino acid alignment of CTRP vWA domain 1 from <i>P. falciparum</i> (PfCTRP 1), <i>P. berghei</i> (PbCTRP 1), and <i>P. vivax</i> (PvCTRP 1) with vWA domains from <i>P. falciparum</i> thrombospondin-related anonymous protein (PfTRAP), <i>T. gondii</i> micronemal protein 2 (TgMIC2), and human von Willebrand Factor (Hs vWF A1). Arginine and Lysine residues are highlighted in red and motifs involved in heparin-binding in Hs vWF A1 are boxed. Secondary structural elements for Hs vWFA1 are provided above each row of amino acids as described <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003757#ppat.1003757-Emsley1\" target=\"_blank\">[32]</a>. Arrows represent beta strands (labeled A–F), closed rectangles represent alpha helices (labeled 1–7; α2 intentionally missing due to lack of equivalent helix relative to other human vWA domains), and open rectangles represent 3–10 helices. (<b>B–C</b>) Homology model (light gray) of <i>P. falciparum</i> CTRP (Model 1) based on the crystal structure of the human vWF A1 domain (PDB: 1AUQ) and the same Model rotated 180°. In (B) the homology model is presented as a ribbon diagram, while a space-filling model is shown in (C). (<b>D–E</b>) Homology model (steel gray) of <i>P. falciparum</i> CTRP based on the <i>Toxoplasma</i> MIC2 structure (PDB: 2XGG) and the same model rotated 180°. In (D) the homology model is presented as a ribbon diagram, while a space-filling model is shown in (E). In (B–E) yellow residues indicate the predicted heparin-binding domains for Models 1 and 2 that have been described for the vWF A1 domain and indicated as boxed areas in the sequence alignment in panel (A). Red residues indicate the positively charged Arg and Lys moieties present outside of the predicted heparin-binding domains (in yellow) for Models 1 and 2. Blue residues correspond to the putative MIDAS metal-ion binding motif [DXSXR in vWF A1, DXSXS in the apicomplexan vWA domains included in panel (A)].</p>", "links"=>[], "tags"=>["homology", "ctrp", "provides", "vs1", "binding"], "article_id"=>859638, "categories"=>["Biological Sciences"], "users"=>["Derrick K. Mathias", "Rebecca Pastrana-Mena", "Elisabetta Ranucci", "Dingyin Tao", "Paolo Ferruti", "Corrie Ortega", "Gregory O. Staples", "Joseph Zaia", "Eizo Takashima", "Takafumi Tsuboi", "Natalie A. Borg", "Luisella Verotta", "Rhoel R. Dinglasan"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1003757.g005", "stats"=>{"downloads"=>0, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/A_Homology_model_of_i_Plasmodium_falciparum_i_CTRP_provides_insight_into_the_potential_VS1_binding_motifs_/859638", "title"=>"A Homology model of <i>Plasmodium falciparum</i> CTRP provides insight into the potential VS1 binding motifs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-21 04:00:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/1292034"], "description"=>"<p>(<b>A</b>) <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003757#s3\" target=\"_blank\">Results</a> from a gametocyte-dilution SMFA showing the relationship between percent gametocytemia and midgut infection with (X% + VS1) and without (X% + PBS) VS1-3,000. The dashed box denotes the data highlighted in panel C. (<b>B</b>) <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003757#s3\" target=\"_blank\">Results</a> from a representative dose-ranging SMFA with <i>An. gambiae</i> (replicate 2 in panel D) where mosquitoes were fed <i>P. falciparum</i> gametocytes in combination with VS1-3,000 in concentrations ranging from 12.5–400 µg/ml in 2-fold increments. The column headings in the table below are as in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003757#ppat-1003757-g001\" target=\"_blank\">Figure 1</a>. (<b>C</b>) <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003757#s3\" target=\"_blank\">Results</a> of SMFA experimental treatments in panel A from 0.1% gametocytemia and lower. The data are displayed at a scale that better shows the range of oocyst intensities at lower gametocyte concentrations. (<b>D</b>) Relationship between percent inhibition and VS1 concentration from four independent experiments. Each data point represents the percent inhibition of <i>P. falciparum</i> infection for a specific concentration of VS1-3,000. <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003757#s3\" target=\"_blank\">Results</a> are shown for two experiments using <i>An. gambiae</i> and two using <i>An. stephensi</i>. The dashed line approximates the IC<sub>50</sub>.</p>", "links"=>[], "tags"=>["experiments", "dose-response", "relationships", "percent", "inhibition"], "article_id"=>859635, "categories"=>["Biological Sciences"], "users"=>["Derrick K. Mathias", "Rebecca Pastrana-Mena", "Elisabetta Ranucci", "Dingyin Tao", "Paolo Ferruti", "Corrie Ortega", "Gregory O. Staples", "Joseph Zaia", "Eizo Takashima", "Takafumi Tsuboi", "Natalie A. Borg", "Luisella Verotta", "Rhoel R. Dinglasan"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1003757.g003", "stats"=>{"downloads"=>0, "page_views"=>25, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Dose_ranging_experiments_demonstrate_consistent_dose_response_relationships_between_gametocytemia_VS1_and_percent_inhibition_of_i_Plasmodium_i_infection_/859635", "title"=>"Dose-ranging experiments demonstrate consistent dose-response relationships between gametocytemia, VS1, and percent inhibition of <i>Plasmodium</i> infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-21 04:00:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/1292033"], "description"=>"<p>Panels (<b>A–C</b>) show midgut oocyst intensities from a representative experiment in which <i>An. stephensi</i> mosquitoes were fed on mice infected with <i>Plasmodium berghei</i> pre- and post-injection with VS1-3,000. Each panel represents a different treatment group (A, PBS; B, PVP; C, VS1-3,000) and the X-axis of each is arranged by parasitized mouse (labeled 1–5) pre- and post-injection with VS1.</p>", "links"=>[], "tags"=>["exhibits", "malaria", "transmission-blocking"], "article_id"=>859634, "categories"=>["Biological Sciences"], "users"=>["Derrick K. Mathias", "Rebecca Pastrana-Mena", "Elisabetta Ranucci", "Dingyin Tao", "Paolo Ferruti", "Corrie Ortega", "Gregory O. Staples", "Joseph Zaia", "Eizo Takashima", "Takafumi Tsuboi", "Natalie A. Borg", "Luisella Verotta", "Rhoel R. Dinglasan"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1003757.g002", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/VS1_exhibits_malaria_transmission_blocking_activity_in_an_i_in_vivo_i_system_/859634", "title"=>"VS1 exhibits malaria transmission-blocking activity in an <i>in vivo</i> system.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-21 04:00:51"}

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Relative Metric

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