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Ebola virus (EBOV) glycoprotein (GP) can be recognized by neutralizing antibodies (NAbs) and is the main target for vaccine design. Here, we first investigate the contribution of the stalk and heptad repeat 1-C (HR1C) regions to GP metastability. Specific stalk and HR1C modifications in a mucin-deleted form (GPΔmuc) increase trimer yield, whereas alterations of HR1C exert a more complex effect on thermostability. Crystal structures are determined to validate two rationally designed GPΔmuc trimers in their unliganded state. We then display a modified GPΔmuc trimer on reengineered protein nanoparticles that encapsulate a layer of locking domains (LD) and a cluster of helper T-cell epitopes. In mice and rabbits, GP trimers and nanoparticles elicit cross-ebolavirus NAbs, as well as non-NAbs that enhance pseudovirus infection. Repertoire sequencing reveals quantitative profiles of vaccine-induced B-cell responses. This study demonstrates a promising vaccine strategy for filoviruses, such as EBOV, based on GP stabilization and nanoparticle display. Ebola virus glycoprotein (GP) is a major target for vaccine design. Here, the authors identify mutations to improve GP stability and yield, design two multilayered nanoparticle carriers, and demonstrate good immunogenicity of the modified GP on nanoparticles in mice and rabbits.

Contact: A Journal for Contemporary Music (1971-1988), No 34 (1989): Contact: A Journal for Contemporary Music

The aim of this investigation was to compare the effects of three different degrees of expectancy on the perception of relative length. It was assumed that expectancy would be (a) maximal when erroneous information about the relative length of two equal lines was deduced fallaciously by the subjects, (b) intermediate when the same information was presented by the experimenter, and (c) zero when no such information was presented. It was predicted that the subsequent perception of length would vary in accordance with the degree of expectancy induced, i.e. (a) > (b) > (c). The prediction was confirmed at a high confidence level for the frequency of perceptual judgements, but the amount of perceptual distortion did not differ significantly although the means were in the predicted order. The results are discussed in relation to theories of perception and cognition.

An intensive study of heroin use in an English provincial town was conducted by field survey. Data were collected, largely by interview, from 37 heroin users living there. The approach adopted enabled insight into the social factors surrounding heroin use to be gained. Details are given of the users' family and social backgrounds, of their past and present social functioning, their use of drugs and their general medical and psychiatric history. 54% of the users came from families in the higher social classes, 37% were in fulltime employment and 19% were students. There was a high rate of " dropping out " of school or college courses before heroin use began. The 37 users were found to differ from other samples studied and differences within the sample were equally marked. It is concluded that any notion of a " typical " heroin user must finally be abandoned and instead typologies of heroin users must be sought.

Summary Three hundred and five students with experience of cannabis from 2 university colleges in Southern England were classified according to their degree of experience of the drug. Approximately half the sample had used it 10 times or less (‘novices’) and half more than 10 times (‘experienced users’). Forty per cent considered they had now stopped using (63 per cent of novices, 18 per cent of experienced users), and 25 per cent were using once a week or more (‘regular users’), this latter figure including 7 per cent using at least 4 times per week (‘heavy users’). More experienced users were differentiated from less experienced users on a number of other characteristics of their drug use. They differed in the nature of their first experience (with more experienced users being more likely to have it earlier, at school, enjoy it and want it for drug effect rather than curiosity), the attributed importance of the drug in their lives (the heavier the use the more attributed importance), the social role of the drug (with it playing a greater part in the lives of more experienced), the preferred level of intoxication (heavy users tending to aim for higher levels), the effects experienced (greater range with greater experience) the reasons given for using, the reservations about using, and experience with other drugs. Discussion focusses on what the drug may offer individuals by looking at differences between those who decide to stop (and when) and those who continue using, and amongst those who continue, different patterns of use and the costs and benefits associated with them. Questions raised for future analyses include whether use patterns may be predicted by non-drug variables.