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  1. AU="Ivens, Al C"
  2. AU="Juan Mucci"
  3. AU="Alejandro Hlavnika"
  4. AU="Makarenko V."

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  1. Article ; Online: Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines.

    Campino, Susana / Benavente, Ernest Diez / Assefa, Samuel / Thompson, Eloise / Drought, Laura G / Taylor, Catherine J / Gorvett, Zaria / Carret, Celine K / Flueck, Christian / Ivens, Al C / Kwiatkowski, Dominic P / Alano, Pietro / Baker, David A / Clark, Taane G

    Malaria journal

    2016  Volume 15, Page(s) 229

    Abstract: Background: Transmission of the malaria parasite Plasmodium falciparum from humans to the mosquito vector requires differentiation of a sub-population of asexual forms replicating within red blood cells into non-dividing male and female gametocytes. The ...

    Abstract Background: Transmission of the malaria parasite Plasmodium falciparum from humans to the mosquito vector requires differentiation of a sub-population of asexual forms replicating within red blood cells into non-dividing male and female gametocytes. The nature of the molecular mechanism underlying this key differentiation event required for malaria transmission is not fully understood.
    Methods: Whole genome sequencing was used to examine the genomic diversity of the gametocyte non-producing 3D7-derived lines F12 and A4. These lines were used in the recent detection of the PF3D7_1222600 locus (encoding PfAP2-G), which acts as a genetic master switch that triggers gametocyte development.
    Results: The evolutionary changes from the 3D7 parental strain through its derivatives F12 (culture-passage derived cloned line) and A4 (transgenic cloned line) were identified. The genetic differences including the formation of chimeric var genes are presented.
    Conclusion: A genomics resource is provided for the further study of gametocytogenesis or other phenotypes using these parasite lines.
    MeSH term(s) Gametogenesis ; Genome, Protozoan ; Plasmodium falciparum/genetics ; Plasmodium falciparum/physiology ; Polymorphism, Genetic ; Sequence Analysis, DNA
    Language English
    Publishing date 2016-04-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2091229-8
    ISSN 1475-2875 ; 1475-2875
    ISSN (online) 1475-2875
    ISSN 1475-2875
    DOI 10.1186/s12936-016-1254-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Secretion of protective antigens by tissue-stage nematode larvae revealed by proteomic analysis and vaccination-induced sterile immunity.

    Hewitson, James P / Ivens, Al C / Harcus, Yvonne / Filbey, Kara J / McSorley, Henry J / Murray, Janice / Bridgett, Stephen / Ashford, David / Dowle, Adam A / Maizels, Rick M

    PLoS pathogens

    2013  Volume 9, Issue 8, Page(s) e1003492

    Abstract: Gastrointestinal nematode parasites infect over 1 billion humans, with little evidence for generation of sterilising immunity. These helminths are highly adapted to their mammalian host, following a developmental program through successive niches, while ... ...

    Abstract Gastrointestinal nematode parasites infect over 1 billion humans, with little evidence for generation of sterilising immunity. These helminths are highly adapted to their mammalian host, following a developmental program through successive niches, while effectively down-modulating host immune responsiveness. Larvae of Heligmosomoides polygyrus, for example, encyst in the intestinal submucosa, before emerging as adult worms into the duodenal lumen. Adults release immunomodulatory excretory-secretory (ES) products, but mice immunised with adult H. polygyrus ES become fully immune to challenge infection. ES products of the intestinal wall 4th stage (L4) larvae are similarly important in host-parasite interactions, as they readily generate sterile immunity against infection, while released material from the egg stage is ineffective. Proteomic analyses of L4 ES identifies protective antigen targets as well as potential tissue-phase immunomodulatory molecules, using as comparators the adult ES proteome and a profile of H. polygyrus egg-released material. While 135 proteins are shared between L4 and adult ES, 72 are L4 ES-specific; L4-specific proteins correspond to those whose transcription is restricted to larval stages, while shared proteins are generally transcribed by all life cycle forms. Two protein families are more heavily represented in the L4 secretome, the Sushi domain, associated with complement regulation, and the ShK/SXC domain related to a toxin interfering with T cell signalling. Both adult and L4 ES contain extensive but distinct arrays of Venom allergen/Ancylostoma secreted protein-Like (VAL) members, with acetylcholinesterases (ACEs) and apyrase APY-3 particularly abundant in L4 ES. Serum antibodies from mice vaccinated with L4 and adult ES react strongly to the VAL-1 protein and to ACE-1, indicating that these two antigens represent major vaccine targets for this intestinal nematode. We have thus defined an extensive and novel repertoire of H. polygyrus proteins closely implicated in immune modulation and protective immunity.
    MeSH term(s) Animals ; Antibodies, Helminth/analysis ; Antibodies, Helminth/immunology ; Antigens, Helminth/immunology ; Antigens, Helminth/metabolism ; Blotting, Western ; Chromatography, Liquid ; Computational Biology ; Electrophoresis, Gel, Two-Dimensional ; Enzyme-Linked Immunosorbent Assay ; Female ; Gene Expression Profiling ; Helminth Proteins/immunology ; Helminth Proteins/metabolism ; Host-Parasite Interactions ; Immunization ; Immunoprecipitation ; Larva/immunology ; Larva/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Nematode Infections/immunology ; Nematode Infections/parasitology ; Nematospiroides dubius/growth & development ; Nematospiroides dubius/immunology ; Proteomics ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Vaccination
    Chemical Substances Antibodies, Helminth ; Antigens, Helminth ; Helminth Proteins
    Language English
    Publishing date 2013-08-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1003492
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Analysis of ESTs from Lutzomyia longipalpis sand flies and their contribution toward understanding the insect-parasite relationship.

    Dillon, Rod J / Ivens, Al C / Churcher, Carol / Holroyd, Nancy / Quail, Michael A / Rogers, Matthew E / Soares, M Bento / Bonaldo, Maria F / Casavant, Thomas L / Lehane, Mike J / Bates, Paul A

    Genomics

    2006  Volume 88, Issue 6, Page(s) 831–840

    Abstract: An expressed sequence tag library has been generated from a sand fly vector of visceral leishmaniasis, Lutzomyia longipalpis. A normalized cDNA library was constructed from whole adults and 16,608 clones were sequenced from both ends and assembled into ... ...

    Abstract An expressed sequence tag library has been generated from a sand fly vector of visceral leishmaniasis, Lutzomyia longipalpis. A normalized cDNA library was constructed from whole adults and 16,608 clones were sequenced from both ends and assembled into 10,203 contigs and singlets. Of these 58% showed significant similarity to known genes from other organisms, <4% were identical to described sand fly genes, and 42% had no match to any database sequence. Our analyses revealed putative proteins involved in the barrier function of the gut (peritrophins, microvillar proteins, glutamine synthase), digestive physiology (secreted and membrane-anchored hydrolytic enzymes), and the immune response (gram-negative binding proteins, thioester proteins, scavenger receptors, galectins, signaling pathway factors, caspases, serpins, and peroxidases). Sequence analysis of this transcriptome dataset has provided new insights into genes that might be associated with the response of the vector to the development of Leishmania.
    MeSH term(s) Animals ; Computational Biology ; Expressed Sequence Tags ; Host-Parasite Interactions ; Insect Proteins/genetics ; Insect Proteins/metabolism ; Leishmania/physiology ; Molecular Sequence Data ; Psychodidae/genetics ; Psychodidae/parasitology ; Sequence Analysis, DNA
    Chemical Substances Insect Proteins
    Language English
    Publishing date 2006-08-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 356334-0
    ISSN 1089-8646 ; 0888-7543
    ISSN (online) 1089-8646
    ISSN 0888-7543
    DOI 10.1016/j.ygeno.2006.06.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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