Transcriptomic Analysis of Toxoplasma Development Reveals Many Novel Functions and Structures Specific to Sporozoites and Oocysts

Sexual reproduction of Toxoplasma gondii occurs exclusively within enterocytes of the definitive felid host. The resulting immature oocysts are excreted into the environment during defecation, where in the days following, they undergo a complex developmental process. Within each oocyst, this culminates in the generation of two sporocysts, each containing 4 sporozoites. A single felid host is capable of shedding millions of oocysts, which can survive for years in the environment, are resistant to most methods of microbial inactivation during water-treatment and are capable of producing infection in warm-blooded hosts at doses as low as 1–10 ingested oocysts. Despite its extremely interesting developmental biology and crucial role in initiating an infection, almost nothing is known about the oocyst stage beyond morphological descriptions. Here, we present a complete transcriptomic analysis of the oocyst from beginning to end of its development. In addition, and to identify genes whose expression is unique to this developmental form, we compared the transcriptomes of developing oocysts with those of in vitro-derived tachyzoites and in vivo-derived bradyzoites. Our results reveal many genes whose expression is specifically up- or down-regulated in different developmental stages, including many genes that are likely critical to oocyst development, wall formation, resistance to environmental destruction and sporozoite infectivity. Of special note is the up-regulation of genes that appear “off” in tachyzoites and bradyzoites but that encode homologues of proteins known to serve key functions in those asexual stages, including a novel pairing of sporozoite-specific paralogues of AMA1 and RON2, two proteins that have recently been shown to form a crucial bridge during tachyzoite invasion of host cells. This work provides the first in-depth insight into the development and functioning of one of the most important but least studied stages in the Toxoplasma life cycle

Mirror Neurons, Prediction and Hemispheric Coordination; The Prioritizing of Intersubjectivity over 'Intrasubjectivity'

We observe that approaches to intersubjectivity, involving mirror neurons and involving emulation and prediction, have eclipsed discussion of those same mechanisms for achieving coordination between the two hemispheres of the human brain. We explore some of the implications of the suggestion that the mutual modelling of the two situated hemispheres (each hemisphere ‘second guessing’ the other) is a productive place to start in understanding the phylogenetic and ontogenetic development of cognition and of intersubjectivity

Atomic resolution insight into host cell recognition by Toxoplasma gondii

The obligate intracellular parasite Toxoplasma gondii, a member of the phylum Apicomplexa that includes Plasmodium spp., is one of the most widespread parasites and the causative agent of toxoplasmosis. Micronemal proteins (MICs) are released onto the parasite surface just before invasion of host cells and play important roles in host cell recognition, attachment and penetration. Here, we report the atomic structure for a key MIC, TgMIC1, and reveal a novel cell-binding motif called the microneme adhesive repeat (MAR). Using glycoarray analyses, we identified a novel interaction with sialylated oligosaccharides that resolves several prevailing misconceptions concerning TgMIC1. Structural studies of various complexes between TgMIC1 and sialylated oligosaccharides provide high-resolution insights into the recognition of sialylated oligosaccharides by a parasite surface protein. We observe that MAR domains exist in tandem repeats, which provide a highly specialized structure for glycan discrimination. Our work uncovers new features of parasite–receptor interactions at the early stages of host cell invasion, which will assist the design of new therapeutic strategies

Scattering of wave packets with phases

A general problem of 2→Nf scattering is addressed with all the states being wave packets with arbitrary phases. Depending on these phases, one deals with coherent states in (3+1) D, vortex particles with orbital angular momentum, the Airy beams, and their generalizations. A method is developed in which a number of events represents a functional of the Wigner functions of such states. Using width of a packet σp/⟨p⟩ as a small parameter, the Wigner functions, the number of events, and a cross section are represented as power series in this parameter, the first non-vanishing corrections to their plane-wave expressions are derived, and generalizations for beams are made. Although in this regime the Wigner functions turn out to be everywhere positive, the cross section develops new specifically quantum features, inaccessible in the plane-wave approximation. Among them is dependence on an impact parameter between the beams, on phases of the incoming states, and on a phase of the scattering amplitude. A model-independent analysis of these effects is made. Two ways of measuring how a Coulomb phase and a hadronic one change with a transferred momentum t are discussed