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      Plasmodium falciparum genetic crosses in a humanized mouse model

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          Abstract

          Genetic crosses of phenotypically distinct strains of the human malaria parasite Plasmodium falciparum are a powerful tool for identifying genes controlling drug resistance and other key phenotypes. Previous studies relied on the isolation of recombinant parasites from splenectomized chimpanzees, a research avenue that is no longer available. Here, we demonstrate that human-liver chimeric mice support recovery of recombinant progeny for the identification of genetic determinants of parasite traits and adaptations.

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          Rapid planetesimal formation in turbulent circumstellar discs

          Anders Johansen, Jeffrey S. Oishi, Mordecai-Mark Mac Low … (2007)
          The initial stages of planet formation in circumstellar gas discs proceed via dust grains that collide and build up larger and larger bodies (Safronov 1969). How this process continues from metre-sized boulders to kilometre-scale planetesimals is a major unsolved problem (Dominik et al. 2007): boulders stick together poorly (Benz 2000), and spiral into the protostar in a few hundred orbits due to a head wind from the slower rotating gas (Weidenschilling 1977). Gravitational collapse of the solid component has been suggested to overcome this barrier (Safronov 1969, Goldreich & Ward 1973, Youdin & Shu 2002). Even low levels of turbulence, however, inhibit sedimentation of solids to a sufficiently dense midplane layer (Weidenschilling & Cuzzi 1993, Dominik et al. 2007), but turbulence must be present to explain observed gas accretion in protostellar discs (Hartmann 1998). Here we report the discovery of efficient gravitational collapse of boulders in locally overdense regions in the midplane. The boulders concentrate initially in transient high pressures in the turbulent gas (Johansen, Klahr, & Henning 2006), and these concentrations are augmented a further order of magnitude by a streaming instability (Youdin & Goodman 2005, Johansen, Henning, & Klahr 2006, Johansen & Youdin 2007) driven by the relative flow of gas and solids. We find that gravitationally bound clusters form with masses comparable to dwarf planets and containing a distribution of boulder sizes. Gravitational collapse happens much faster than radial drift, offering a possible path to planetesimal formation in accreting circumstellar discs.
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            Human malaria parasites in continuous culture.

            W Trager, Jens-Erik B Jensen, Louise Jensen (1976)
            Plasmodium falciparum can now be maintained in continuous culture in human erythrocytes incubated at 38 degrees C in RPMI 1640 medium with human serum under an atmosphere with 7 percent carbon dioxide and low oxygen (1 or 5 percent). The original parasite material, derived from an infected Aotus trivirgatus monkey, was diluted more than 100 million times by the addition of human erythrocytes at 3- or 4-day intervals. The parasites continued to reproduce in their normal asexual cycle of approximately 48 hours but were no longer highly synchronous. The have remained infective to Aotus.
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              Genetic analysis of the human malaria parasite Plasmodium falciparum.

              D Walliker, I Quakyi, T Wellems … (1987)
              Malaria parasites are haploid for most of their life cycle, with zygote formation and meiosis occurring during the mosquito phase of development. The parasites can be analyzed genetically by transmitting mixtures of cloned parasites through mosquitoes to permit cross-fertilization of gametes to occur. A cross was made between two clones of Plasmodium falciparum differing in enzymes, drug sensitivity, antigens, and chromosome patterns. Parasites showing recombination between the parent clone markers were detected at a high frequency. Novel forms of certain chromosomes, detected by pulsed-field gradient gel electrophoresis, were produced readily, showing that extensive rearrangements occur in the parasite genome after cross-fertilization. Since patients are frequently infected with mixtures of genetically distinct parasites, mosquito transmission is likely to provide the principal mechanisms for generating parasites with novel genotypes.
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                Author and article information

                Journal
                Journal ID (nlm-journal-id): 101215604
                Journal ID (pubmed-jr-id): 32338
                Journal ID (nlm-ta): Nat Methods
                Journal ID (iso-abbrev): Nat. Methods
                Title: Nature methods
                ISSN (Print): 1548-7091
                ISSN (Electronic): 1548-7105
                Publication date Nihms-submitted: 20 August 2015
                Publication date (Electronic): 01 June 2015
                Publication date (Print): July 2015
                Publication date PMC-release: 01 January 2016
                Volume: 12
                Issue: 7
                Pages: 631-633
                Affiliations
                [1 ]Seattle Biomedical Research Institute, Seattle, Washington, USA
                [2 ]Eck Institute for Global Health, Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, USA
                [3 ]Texas Biomedical Research Institute, San Antonio, Texas, USA
                [4 ]Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Mae Sot, Thailand
                [5 ]Department of Global Health, University of Washington, Seattle, Washington, USA
                Author notes
                [6 ]To whom correspondence should be sent: SHIK, stefan.kappe@ 123456seattlebiomed.org ; MTF, ferdig.1@ 123456nd.edu
                Article
                Manuscript ID: NIHMS716596
                DOI: 10.1038/nmeth.3432
                PMC ID: 4547688
                PubMed ID: 26030447
                SO-VID: 1ea594f5-caf9-4e6e-9142-5c790b090765
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                ScienceOpen disciplines: Life sciences

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