Novel Soluble Flt-1 Isoforms in Plasma and Cultured Placental Explants from Normotensive Pregnant and Preeclamptic Women

Pregnant women who develop preeclampsia exhibit higher circulating levels of the soluble VEGF receptor-1 (sFlt-1). Recent findings suggest that soluble Flt-1 may contribute to the pathogenesis of preeclampsia by binding and neutralizing vascular endothelial growth factors (VEGF) and placental growth factor (PlGF). Existing literature identifies sFlt-1 as a 100 kDa glycoprotein, a product of an mRNA splice variant. We hypothesized that sFlt-1 expression may be more complex with multiple variants of sFlt-1 as well as multiple sources during normal pregnancy and preeclampsia. Using a combination of affinity purification of sFlt-1 by heparin-agarose and epitope specific antibodies, we performed Western blot analysis with epitope specific antibodies for sFlt-1. Plasma of preeclamptic women exhibits significantly higher amounts of a novel 145 kDa variant of sFlt-1, along with the 100 kDa isoform. We identified sFlt-1 variants in the conditioned medium from placental explant cultures that are hypoxia responsive with varying sizes, including 185, 145,100 and 60 kDa forms, as well as antigenicity. The 145 kDa was similar in antigenicity to the 100 kDa found in plasma whereas the 185 and 60 kDa sFlt-1 demonstrated different epitopes. Deglycosylation studies also confirm that there are multiple sFlt-1 polypeptides. Co-immunoprecipitation with VEGF suggests that these different sFlt isoforms can bind VEGF and therefore, may be of functional importance. Finally, comparison of sFlt-1 in the conditioned medium obtained from cultured cytotrophoblasts, peripheral blood mononuclear cells (PBMCs) and human uterine microvascular cells (HUtMVECs) exhibit mainly the100 kDa sFlt-1. Collectively these data suggest the presence of multiple isoforms of sFlt-1 in the circulation of women with preeclampsia as well as in uncomplicated pregnancies and the possibility of multiple sources. Placental hypoxia may contribute to sFlt-1 over expression but other regulatory mechanisms cannot be ruled out

Fatness and Fable: Regulating the Interactive Body in Video Games

The video game Fable 2 promises new modes of interaction, by which decisions made by the player can shape the game world and the body of their virtual persona. Some decisions affect the good/evil index by which the avatar takes on a diabolical or saintly aspect. Other decisions affect the character's purity/corruption index, which impacts on the relative thinness and upright posture or fatness and hunched posture and of the avatar. This moralisation of fatness, embedded in the ideological code of the game reflects a set of values about consumption, exploitation and the aesthetics of body. These ‘morality systems’ as they are described in video games are connected to the ways in which other characters respond to you, define the life choices and options (in the Fable games this includes marriage and children) and shape the metaphysical powers of your character. As interactive media evolves, and these kinds of complex interactions become more commonplace, we must challenge the design decisions that align meat eating, tenant exploitation, farting on angry people, bigamy, stealing, long periods of sleep and interpersonal meanness with a fat body image. We are increasingly using avatars as a form of virtual embodiment, particularly in social networking and the deployment of avatars in video games provides precedents for their use in other contexts