Sodium-dependent uptake of inorganic phosphate by the intracellular malaria parasite

As the malaria parasite, Plasmodium falciparum, grows within its host erythrocyte it induces an increase in the permeability of the erythrocyte membrane to a range of low-molecular-mass solutes, including Na+ and K+ (ref. 1). This results in a progressive increase in the concentration of Na+ in the erythrocyte cytosol. The parasite cytosol has a relatively low Na+ concentration and there is therefore a large inward Na+ gradient across the parasite plasma membrane. Here we show that the parasite exploits the Na+ electrochemical gradient to energize the uptake of inorganic phosphate (P(i)), an essential nutrient. P(i) was taken up into the intracellular parasite by a Na+-dependent transporter, with a stoichiometry of 2Na+:1P(i) and with an apparent preference for the monovalent over the divalent form of P(i). A P(i) transporter (PfPiT) belonging to the PiT family was cloned from the parasite and localized to the parasite surface. Expression of PfPiT in Xenopus oocytes resulted in Na+-dependent P(i) uptake with characteristics similar to those observed for P(i) uptake in the parasite. This study provides new insight into the significance of the malaria-parasite-induced alteration of the ionic composition of its host cell.     

Graphene-based composite materials

Graphene sheets--one-atom-thick two-dimensional layers of sp2-bonded carbon--are predicted to have a range of unusual properties. Their thermal conductivity and mechanical stiffness may rival the remarkable in-plane values for graphite (approximately 3,000 W m(-1) K(-1) and 1,060 GPa, respectively); their fracture strength should be comparable to that of carbon nanotubes for similar types of defects; and recent studies have shown that individual graphene sheets have extraordinary electronic transport properties. One possible route to harnessing these properties for applications would be to incorporate graphene sheets in a composite material. The manufacturing of such composites requires not only that graphene sheets be produced on a sufficient scale but that they also be incorporated, and homogeneously distributed, into various matrices. Graphite, inexpensive and available in large quantity, unfortunately does not readily exfoliate to yield individual graphene sheets. Here we present a general approach for the preparation of graphene-polymer composites via complete exfoliation of graphite and molecular-level dispersion of individual, chemically modified graphene sheets within polymer hosts. A polystyrene-graphene composite formed by this route exhibits a percolation threshold of approximately 0.1 volume per cent for room-temperature electrical conductivity, the lowest reported value for any carbon-based composite except for those involving carbon nanotubes; at only 1 volume per cent, this composite has a conductivity of approximately 0.1 S m(-1), sufficient for many electrical applications. Our bottom-up chemical approach of tuning the graphene sheet properties provides a path to a broad new class of graphene-based materials and their use in a variety of applications.     

A dynamic role for the mushroom bodies in promoting sleep in Drosophila

The fruitfly, Drosophila melanogaster, exhibits many of the cardinal features of sleep, yet little is known about the neural circuits governing its sleep. Here we have performed a screen of GAL4 lines expressing a temperature-sensitive synaptic blocker shibire(ts1) (ref. 2) in a range of discrete neural circuits, and assayed the amount of sleep at different temperatures. We identified three short-sleep lines at the restrictive temperature with shared expression in the mushroom bodies, a neural locus central to learning and memory. Chemical ablation of the mushroom bodies also resulted in reduced sleep. These studies highlight a central role for the mushroom bodies in sleep regulation.     

Parthenogenesis in Komodo dragons

Parthenogenesis, the production of offspring without fertilization by a male, is rare in vertebrate species, which usually reproduce after fusion of male and female gametes. Here we use genetic fingerprinting to identify parthenogenetic offspring produced by two female Komodo dragons (Varanus komodoensis) that had been kept at separate institutions and isolated from males; one of these females subsequently produced additional offspring sexually. This reproductive plasticity indicates that female Komodo dragons may switch between asexual and sexual reproduction, depending on the availability of a mate--a finding that has implications for the breeding of this threatened species in captivity. Most zoos keep only females, with males being moved between zoos for mating, but perhaps they should be kept together to avoid triggering parthenogenesis and thereby decreasing genetic diversity.     

Pleiotropy as a mechanism to stabilize cooperation

Most genes affect many traits. This phenomenon, known as pleiotropy, is a major constraint on evolution because adaptive change in one trait may be prevented because it would compromise other traits affected by the same genes. Here we show that pleiotropy can have an unexpected effect and benefit one of the most enigmatic of adaptations--cooperation. A spectacular act of cooperation occurs in the social amoeba Dictyostelium discoideum, in which some cells die to form a stalk that holds the other cells aloft as reproductive spores. We have identified a gene, dimA, in D. discoideum that has two contrasting effects. It is required to receive the signalling molecule DIF-1 that causes differentiation into prestalk cells. Ignoring DIF-1 and not becoming prestalk should allow cells to cheat by avoiding the stalk. However, we find that in aggregations containing the wild-type cells, lack of the dimA gene results in exclusion from spores. This pleiotropic linkage of stalk and spore formation limits the potential for cheating in D. discoideum because defecting on prestalk cell production results in an even greater reduction in spores. We propose that the evolution of pleiotropic links between cheating and personal costs can stabilize cooperative adaptations.     

Transient cross-reactive immune responses can orchestrate antigenic variation in malaria

The malaria parasite Plasmodium falciparum has evolved to prolong its duration of infection by antigenic variation of a major immune target on the surface of the infected red blood cell. This immune evasion strategy depends on the sequential, rather than simultaneous, appearance of immunologically distinct variants. Although the molecular mechanisms by which a single organism switches between variants are known in part, it remains unclear how an entire population of parasites within the host can synchronize expression to avoid rapidly exhausting the variant repertoire. Here we show that short-lived, partially cross-reactive immune responses to parasite-infected erythrocyte surface antigens can produce a cascade of sequentially dominant antigenic variants, each of which is the most immunologically distinct from its preceding types. This model reconciles several previously unexplained and apparently conflicting epidemiological observations by demonstrating that individuals with stronger cross-reactive immune responses can, paradoxically, be more likely to sustain chronic infections. Antigenic variation has always been seen as an adaptation of the parasite to evade host defence: we show that the coordination necessary for the success of this strategy might be provided by the host.     

Systematic generation of high-resolution deletion coverage of the Drosophila melanogaster genome

In fruit fly research, chromosomal deletions are indispensable tools for mapping mutations, characterizing alleles and identifying interacting loci. Most widely used deletions were generated by irradiation or chemical mutagenesis. These methods are labor-intensive, generate random breakpoints and result in unwanted secondary mutations that can confound phenotypic analyses. Most of the existing deletions are large, have molecularly undefined endpoints and are maintained in genetically complex stocks. Furthermore, the existence of haplolethal or haplosterile loci makes the recovery of deletions of certain regions exceedingly difficult by traditional methods, resulting in gaps in coverage. Here we describe two methods that address these problems by providing for the systematic isolation of targeted deletions in the D. melanogaster genome. The first strategy used a P element-based technique to generate deletions that closely flank haploinsufficient genes and minimize undeleted regions. This deletion set has increased overall genomic coverage by 5-7%. The second strategy used FLP recombinase and the large array of FRT-bearing insertions described in the accompanying paper to generate 519 isogenic deletions with molecularly defined endpoints. This second deletion collection provides 56% genome coverage so far. The latter methodology enables the generation of small custom deletions with predictable endpoints throughout the genome and should make their isolation a simple and routine task.     

Cell fusion-independent differentiation of neural stem cells to the endothelial lineage

Somatic stem cells have been claimed to possess an unexpectedly broad differentiation potential (referred to here as plasticity) that could be induced by exposing stem cells to the extracellular developmental signals of other lineages in mixed-cell cultures. Recently, this and other experimental evidence supporting the existence of stem-cell plasticity have been refuted because stem cells have been shown to adopt the functional features of other lineages by means of cell-fusion-mediated acquisition of lineage-specific determinants (chromosomal DNA) rather than by signal-mediated differentiation. In this study we co-cultured mouse neural stem cells (NSCs), which are committed to become neurons and glial cells, with human endothelial cells, which form the lining of blood vessels. We show that in the presence of endothelial cells six per cent of the NSC population converted to cells that did not express neuronal or glial markers, but instead showed the stable expression of multiple endothelial markers and the capacity to form capillary networks. This was surprising because NSCs and endothelial cells are believed to develop from the ectoderm and mesoderm, respectively. Experiments in which endothelial cells were killed by fixation before co-culture with live NSCs (to prevent cell fusion) and karyotyping analyses, revealed that NSCs had differentiated into endothelial-like cells independently of cell fusion. We conclude that stem-cell plasticity is a true characteristic of NSCs and that the conversion of NSCs to unanticipated cell types can be accomplished without cell fusion.