Mapping of domains on HIV envelope protein mediating association with calnexin and protein-disulfide isomerase.

The cell catalysts calnexin (CNX) and protein-disulfide isomerase (PDI) cooperate in establishing the disulfide bonding of the HIV envelope (Env) glycoprotein. Following HIV binding to lymphocytes, cell-surface PDI also reduces Env to induce the fusogenic conformation. We sought to define the contact points between Env and these catalysts to illustrate their potential as therapeutic targets. In lysates of Env-expressing cells, 15% of the gp160 precursor, but not gp120, coprecipitated with CNX, whereas only 0.25% of gp160 and gp120 coprecipitated with PDI. Under in vitro conditions, which mimic the Env/PDI interaction during virus/cell contact, PDI readily associated with Env. The domains of Env interacting in cellulo with CNX or in vitro with PDI were then determined using anti-Env antibodies whose binding site was occluded by CNX or PDI. Antibodies against domains V1/V2, C2, and the C terminus of V3 did not bind CNX-associated Env, whereas those against C1, V1/V2, and the CD4-binding domain did not react with PDI-associated Env. In addition, a mixture of the latter antibodies interfered with PDI-mediated Env reduction. Thus, Env interacts with intracellular CNX and extracellular PDI via discrete, largely nonoverlapping, regions. The sites of interaction explain the mode of action of compounds that target these two catalysts and may enable the design of further new competitive agents.

Explaining history to children: Otto and Marie Neurath’s work on the ‘Visual history of mankind’

This essay traces the development of Otto Neurath’s ideas that led to the publication of one of the first series of children’s books produced by the Isotype Institute in the late 1940s, the Visual History of Mankind. Described in its publicity material as ‘new in content’ and ‘new in method’, it embodied much of Otto Neurath’s thinking about visual education, and also coincided with other educational ideas in the UK in the 1930s and 1940s. It exemplified the Isotype Institute’s approach: teamwork, thinking about the needs of younger readers, clear explanation, and accessible content. Further, drawing on correspondence, notes and drawings from the Otto and Marie Neurath Isotype Collection at the University of Reading, the essay presents insights to the making of the books and the people involved, the costs of production and the influence of this on design decisions, and how the books were received by teachers and children.

SATgene dietary model to implement diets of differing fat composition in prospectively genotyped groups (apoE) using commercially available foods

esponse to dietary fat manipulation is highly heterogeneous, yet generic population-based recommendations aimed at reducing the burden of CVD are given. The APOE epsilon genotype has been proposed to be an important determinant of this response. The present study reports on the dietary strategy employed in the SATgenɛ (SATurated fat and gene APOE) study, to assess the impact of altered fat content and composition on the blood lipid profile according to the APOE genotype. A flexible dietary exchange model was developed to implement three isoenergetic diets: a low-fat (LF) diet (target composition: 24 % of energy (%E) as fat, 8 %E SFA and 59 %E carbohydrate), a high-saturated fat (HSF) diet (38 %E fat, 18 %E SFA and 45 %E carbohydrate) and a HSF-DHA diet (HSF diet with 3 g DHA/d). Free-living participants (n 88; n 44 E3/E3 and n 44 E3/E4) followed the diets in a sequential design for 8 weeks, each using commercially available spreads, oils and snacks with specific fatty acid profiles. Dietary compositional targets were broadly met with significantly higher total fat (42·8 %E and 41·0 %E v. 25·1 %E, P ≤ 0·0011) and SFA (19·3 %E and 18·6 %E v. 8·33 %E, P ≤ 0·0011) intakes during the HSF and HSF-DHA diets compared with the LF diet, in addition to significantly higher DHA intake during the HSF-DHA diet (P ≤ 0·0011). Plasma phospholipid fatty acid analysis revealed a 2-fold increase in the proportion of DHA after consumption of the HSF-DHA diet for 8 weeks, which was independent of the APOE genotype. In summary, the dietary strategy was successfully implemented in a free-living population resulting in well-tolerated diets which broadly met the dietary targets set.

Dancing in translation: Irina Brook’s mise en scène of 'Danser à Lughnasa', Jean-Marie Besset’s translation of Brian Friel’s 'Dancing at Lughnasa'

This essay contributes to debates about theatre and cross-cultural encounter through an analysis of Irina Brook’s 1999 Swiss / French co-production of Irish playwright Brian Friel’s Dancing at Lughnasa, in a French translation by Jean-Marie Besset. While the translation and Brook’s mise en scène clearly identified the source text and culture as Irish, they avoided cultural stereotypes, and rendered the play accessible to francophone audiences without entirely assimilating it to a specific Swiss or French cultural context. Drawing on discourses of theatre translation, and concepts of cosmopolitanism and conviviality, the essay focuses on the potential of such textual and theatrical translation to acknowledge specific cultural traces but also to estrange the familiar perceptions and boundaries of both the source and target cultures, offering modes of interconnection across diverse cultural affiliations.