Evidence for host cells as the major contributor of lipids in the intravacuolar network of Toxoplasma-infected cells

The intracellular parasite Toxoplasma gondii develops inside a parasitophorous vacuole (PV) that derives from the host cell plasma membrane during invasion. Previous electron micrograph images have shown that the membrane of this vacuole undergoes an extraordinary remodeling with an extensive network of thin tubules and vesicles, the intravacuolar network (IVN), which fills the lumen of the PV. While dense granule proteins, secreted during and after invasion, are the main factors for the organization and tubulation of the network, little is known about the source of lipids used for this remodeling. By selectively labeling host cell or parasite membranes, we uncovered evidence that strongly supports the host cell as the primary, if not exclusive, source of lipids for parasite IVN remodeling. Fluorescence recovery after photobleaching (FRAP) microscopy experiments revealed that lipids are surprisingly dynamic within the parasitophorous vacuole and are continuously exchanged or replenished by the host cell. The results presented here suggest a new model for development of the parasitophorous vacuole whereby the host provides a continuous stream of lipids to support the growth and maturation of the PVM and IVN.     

Spread of Academic Success in a High School Social Network

Application of social network analysis to education has revealed how social network positions of K-12 students correlate with their behavior and academic achievements. However, no study has been conducted on how their social network influences their academic progress over time. Here we investigated correlations between high school students’ academic progress over one year and the social environment that surrounds them in their friendship network. We found that students whose friends’ average GPA (Grade Point Average) was greater (or less) than their own had a higher tendency toward increasing (or decreasing) their academic ranking over time, indicating social contagion of academic success taking place in their social network.     

The Toxoplasma Pseudokinase ROP5 Is an Allosteric Inhibitor of the Immunity-related GTPases

The Red Queen hypothesis proposes that there is an evolutionary arms race between host and pathogen. One possible example of such a phenomenon could be the recently discovered interaction between host defense proteins known as immunity-related GTPases (IRGs) and a family of rhoptry pseudokinases (ROP5) expressed by the protozoan parasite, Toxoplasma gondii. Mouse IRGs are encoded by an extensive and rapidly evolving family of over 20 genes. Similarly, the ROP5 family is highly polymorphic and consists of 4–10 genes, depending on the strain of Toxoplasma. IRGs are known to be avidly bound and functionally inactivated by ROP5 proteins, but the molecular basis of this interaction/inactivation has not previously been known. Here we show that ROP5 uses a highly polymorphic surface to bind adjacent to the nucleotide-binding domain of an IRG and that this produces a profound allosteric change in the IRG structure. This has two dramatic effects: 1) it prevents oligomerization of the IRG, and 2) it alters the orientation of two threonine residues that are targeted by the Toxoplasma Ser/Thr kinases, ROP17 and ROP18. ROP5s are highly specific in the IRGs that they will bind, and the fact that it is the most highly polymorphic surface of ROP5 that binds the IRG strongly supports the notion that these two protein families are co-evolving in a way predicted by the Red Queen hypothesis.     

The 'Ice Worm' - the Immature Stages,Phylogeny and Biology of the Glacier Midge Zelandochlus (Diptera: Chironomidae)

The previously unknown female and larva for the New Zealand glacier midge, Zealandochlus latipalpis Brundin are described for the first time, and the pupa described more fully than previously. Unlike the male, which is brachypterous, the female has large wings possessing traces of a vein between R₁ and R₄₊₅ uniquely for the subfamily Podonominae. The larvae, known locally as ice-worms, live in meltwater pools and ice caves of the Franz Joseph and Fox glaciers, New Zealand. Cladistic analysis of this highly autapomorphic species results in an unresolved trichotomy Zelandochlus + Parochlus + Podonomus, which is no advance on the suggestion made by Brundin (1966) concerning the relationships. Information is too scanty on many species of the putative related genera, but additional morphological features indicate that there may be a sister group relationship with part of Parochlus.     

Correlated preferences for facial masculinity and ideal or actual partner's masculinity

Studies of women's preferences for male faces have variously reported preferences for masculine faces, preferences for feminine faces and no effect of masculinity-femininity on male facial attractiveness. It has been suggested that these apparently inconsistent findings are, at least partly, due to differences in the methods used to manipulate the masculinity of face images or individual differences in attraction to facial cues associated with youth. Here, however, we show that women's preferences for masculinity manipulated in male faces using techniques similar to the three most widely used methods are positively inter-related. We also show that women's preferences for masculine male faces are positively related to ratings of the masculinity of their actual partner and their ideal partner. Correlations with partner masculinity were independent of real and ideal partner age, which were not associated with facial masculinity preference. Collectively, these findings suggest that variability among studies in their findings for women's masculinity preferences reflects individual differences in attraction to masculinity rather than differences in the methods used to manufacture stimuli, and are important for the interpretation of previous and future studies of facial masculinity.     

Facial and bodily correlates of family background

It has been suggested that absence of the father during early childhood has long-reaching effects on reproductive strategy and development of offspring. This paper reports two studies designed to investigate the physical characteristics of daughters associated with father absence. Study 1 used a facial averaging method to produce composite images of faces of women whose parents separated during their childhood (who were 'father absent'), women whose parents remained together, but had poor quality relationships and women whose parents were together and had good quality relationships. Images were then rated by male and female judges. Father absence and poor parental relationships were associated with apparent facial masculinity and reduced attractiveness in daughters. Poor parental relationships were also associated with reduced apparent health. Study 2 compared family background with body measurements and found that father absence or a poor quality relationship between parents were associated with body masculinity (high waist-to-hip ratio) and increased weight-for-height and adiposity. These results highlight the possibility of physical masculinization being associated with purported father absence 'effects'.     

A Helical Membrane-Binding Domain Targets the Toxoplasma ROP2 Family to the Parasitophorous Vacuole

During invasion, the obligate intracellular pathogen, Toxoplasma gondii , secretes into its host cell a variety of effector molecules, several of which have been implicated in strain-specific variation in disease. The largest family of these effectors, defined by the canonical member ROP2, quickly associates with the nascent parasitophorous vacuole membrane (PVM) after secretion. Here we demonstrate that the NH₂-terminal domain of the ROP2 family contains a series of amphipathic helices that are necessary and sufficient for membrane association. While each of the amphipathic helices is individually competent to bind cellular membranes, together they act to bind the PVM preferentially, possibly through sensing its strong negative curvature. This previously uncharacterized helical domain is an evolutionarily robust and energetically efficient design for membrane association.     

Toxoplasma gondii sequesters lysosomes from mammalian hosts in the vacuolar space

The intracellular compartment harboring Toxoplasma gondii satisfies the parasite's nutritional needs for rapid growth in mammalian cells. We demonstrate that the parasitophorous vacuole (PV) of T. gondii accumulates material coming from the host mammalian cell via the exploitation of the host endo-lysosomal system. The parasite actively recruits host microtubules, resulting in selective attraction of endo-lysosomes to the PV. Microtubule-based invaginations of the PV membrane serve as conduits for the delivery of host endo-lysosomes within the PV. These tubular conduits are decorated by a parasite coat, including the tubulogenic protein GRA7, which acts like a garrote that sequesters host endocytic organelles in the vacuolar space. These data define an unanticipated process allowing the parasite intimate and concentrated access to a diverse range of low molecular weight components produced by the endo-lysosomal system. More generally, they identify a unique mechanism for unidirectional transport and sequestration of host organelles.     

A highly sensitive FRET-based approach reveals secretion of the actin-binding protein toxofilin during Toxoplasma gondii infection

We have utilized a highly sensitive approach based on fluorescence resonance energy transfer (FRET) and β-lactamase (BLA), which we adapted for the detection of Toxoplasma gondii secreted proteins. This assay revealed that the actin-binding protein toxofilin appears to be secreted into host cells during invasion. To determine the function of toxofilin during infection, we engineered a type I (RH strain) parasite with a targeted deletion of the toxofilin gene and compared the phenotypes of control and toxofilin knockout (Δ txf ) parasites in several in vitro assays, including invasion, growth, gliding motility, and egress of the Δ txf parasites, as well as F-actin staining, phagocytosis and migration of cells infected with Δ txf parasites or wild-type controls. Despite its apparent secretion into host cells and its ability to bind to and modulate host actin, we observed that toxofilin does not appear to play a role in these processes, under the conditions we examined, and we report these findings here.