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The physiological environment which hosts the conformational conversion of the cellular prion protein (PrP C ) to diseaseassociated isoforms has remained enigmatic. A quantitative investigation of the PrP C interactome was conducted in a cell culture model permissive to prion replication. To facilitate recognition of relevant interactors, the study was extended to Doppel (Prnd) and Shadoo (Sprn), two mammalian PrP C paralogs. Interestingly, this work not only established a similar physiological environment for the three prion protein family members in neuroblastoma cells, but also suggested direct interactions amongst them. Furthermore, multiple interactions between PrP C and the neural cell adhesion molecule, the laminin receptor precursor, Na/K ATPases and protein disulfide isomerases (PDI) were confirmed, thereby reconciling previously separate findings. Subsequent validation experiments established that interactions of PrP C with PDIs may extend beyond the endoplasmic reticulum and may play a hitherto unrecognized role in the accumulation of PrP Sc . A simple hypothesis is presented which accounts for the majority of interactions observed in uninfected cells and suggests that PrP C organizes its molecular environment on account of its ability to bind to adhesion molecules harboring immunoglobulin-like domains, which in turn recognize oligomannose-bearing membrane proteins.

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Background:Training in obstetric anal sphincter injuries (OASIS) in Australia and New Zealand relies upon consultant teaching and has not previously been assessed. Aims:The aims of this study are to establish if training in OASIS is consistent and optimal in Australia and New Zealand and to evaluate trainee perspectives on supervision and teaching, along with confidence in repairing OASIS. Materials and Methods: A descriptive cross-sectional study was performed. Royal Australian and New Zealand College of Obstetricians and Gynaecologists trainees were sent a 21-question survey. The survey was distributed to 725 trainees, and 132 trainees provided complete responses (18.2%). The main outcome measures were (i) comparison of confidence in performing a caesarean section versus OASIS repair and (ii) descriptive analysis of views towards training and suggestions for improvement.Results: Trainees were significantly more confident in performing a caesarean section independently compared to OASIS repair (P < 0.05). This was the case for all year groups. Confidence increased with each year of training. Only 62% reported credentialing at their site. Whereas 50% reported training at the time of first unsupervised repair as good or excellent, 22.7% felt it was suboptimal and 2.3% unsatisfactory; 75.8% had attended a workshop; 38.6% requested mandatory workshops.Requests included that workshops be yearly, include video training and be required at consultant level. Trainees asked for supervision despite credentialing and for separate credentialing for 3A/B-and 3C/4th-degree tears. Conclusions:Trainees have increasing confidence in their ability to independently perform OASIS repairs throughout training. They requested that improvements be made to training and that there be an increase in structured teaching.