The Par polarity complex creates mutually exclusive cortical domains in diverse animal cells. Activity of the atypical protein kinase C (aPKC) is a key output of the Par complex as phosphorylation removes substrates from the Par domain. Here we investigate how diverse, apparently unrelated Par substrates, couple phosphorylation to cortical displacement. Each protein contains a basic and hydrophobic (BH) motif that interacts directly with phospholipids and also overlaps with aPKC phosphorylation sites. Phosphorylation alters the electrostatic character of the sequence, inhibiting interaction with phospholipids and the cell cortex. We searched for overlapping BH and aPKC phosphorylation site motifs (i.e. putative PhosphoRegulated BH motifs) in several animal proteomes. Candidate proteins with strong PRBH signals associated with the cell cortex but were displaced into the cytoplasm by aPKC. These findings demonstrate a potentially general mechanism for exclusion of proteins from the Par cortical domain in polarized cells.

We report the results of a systematic investigation to quantify the losses of protein during a well-established two-dimensional polyacrylamide gel electrophoresis (2-DE) procedure. Radioactively labelled proteins ([(14)C]bovine serum albumin and a homogenate prepared from the liver of a rat that had been injected with [(35)S]methionine) were used, and recovery was quantified by digesting pieces of gel in H(2)O(2) and subjecting the digests to liquid scintillation counting. When samples were loaded onto the first dimension immobilised pH gradient strips by in-gel rehydration, recovery of protein from the strips was 44-80% of the amount of protein loaded, depending on the amount of protein in the sample. Most of the unrecovered protein appeared to have adhered to the reswelling tray. Losses during isoelectric focusing (IEF) were much smaller (7-14%), although approximately 2% of the protein appeared to migrate from sample strips to adjacent blank strips in the focussing apparatus. A further 17-24% of the proteins were lost into the buffers during equilibration prior to running in the second dimension. Losses during the second dimension run and subsequent staining with SYPRO Ruby amounted to less than 10%. The overall loss during 2-DE was reduced by approximately 25% when proteins were loaded onto the IEF strips using sample cups instead of by in-gel rehydration. These extensive and variable losses during the 2-DE procedure mean that spot intensities on 2-DE gels cannot be used to derive reliable, quantitative information on the amounts of proteins present in the original sample.

This article analyses the nature of the support given to the candidates in the 1975 Conservative leadership contest, in which Margaret Thatcher replaced Edward Heath. In contrast to the orthodox account of the contest -which interprets it as largely non-ideological -the article argues that there were clear ideological forces at work. The right strongly supported Thatcher in both rounds; the left strongly backed Heath and then Whitelaw. Region, experience and education also influenced the voting. The traditional accounts, which explain those voting for Thatcher as doing so simply because she was not Heath, have, therefore, to explain why only certain types of MPs felt this way. Margaret Thatcher may have won because she was not Ted Heath; but she did not win solely because she was not Ted Heath.One trembles to think what would have happened to our country had we not chosen that remarkable woman to lead us.(Conservative Member of Parliament) 1Margaret Thatcher ceased to be the British prime minister in November 1990, having dominated British politics for more than a decade. She won three consecutive general elections, something achieved by no other party leader since the beginning of the nineteenth century. The effect of her premiership was profound, producing dramatic and significant changes in many aspects of British life, and in the case of some of those changes -such as privatization -even exporting them overseas. She was the first prime minister to generate an 'ism', and this eponymous ideology -'Thatcherism' -did not depart with her, living

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Objectives To design and evaluate the effectiveness of a pre-notification leaflet about research to increase recruitment to a randomized controlled trial (RCT). Methods A methodological, two-arm, RCT was conducted, embedded within an existing cohort RCT (REFORM). Participants were randomized for the embedded trial, using a 1:2 ratio (intervention : control) before being randomized for REFORM. Controls received a trial recruitment pack. The intervention group received an additional pre-notification leaflet 2-3 weeks before the recruitment pack. Primary and secondary analyses were conducted using relative risk, the Cox proportional hazards model and incremental cost-effectiveness ratios.Results Of the 1436 intervention group participants, 73 (5.1%) were randomized into the REFORM trial compared with 126 (4.4%) of the 2878 control group participants. The associated relative risk (1.16) was not statistically significant [95% confidence interval (CI) 0.88-1.56]. Return rate was not significantly increased (relative risk 1.10, 95% CI 0.92-1.28) nor time to return decreased (hazard ratio: 1.11, 95% CI 0.93-1.33). Incremental cost-effectiveness ratios indicated the intervention may be cost-effective if the true estimate of effect was close to the upper bound of the associated 95% CI. Conclusion Pre-notification for potential trial participants demonstrated a small difference to randomization (0.7% difference) and return rates (1.1% difference) in favour of the intervention. Results should however be interpreted with caution as CIs for these estimates cross the point of no effect. Nevertheless, this research enhances existing evidence for pre-notification to increase recruitment rates, with further development and assessment of this potentially cost-effective intervention being recommended.

Objective: To examine the association of objectively measured, self-paced physical and cognitive activities across the first week postconcussion with symptom resolution in youth. Setting: Emergency department or concussion clinics. Participants: Youth aged 11 to 17 years with physician-confirmed concussion. Design: Prospective cohort with repeated measures. Main Measure(s): Days from injury to symptom resolution, based on daily ratings by youth on the Post-Concussive Symptom Scale. Physical and cognitive activities were assessed using an ActiGraph and a Narrative Clip, respectively. Results: A total of 83 youth participants were included (n = 54 [65%] males; mean age = 14.2 years, SD = 1.9). While self-paced daily physical and cognitive activities increased across the first week postinjury, daily postconcussion symptoms decreased. Increased daily step count was associated with an increased likelihood of early symptom resolution (hazard ratio [HR] = 1.17; 95% confidence interval [CI], 1.02-1.34). However, this association was not statistically significant after adjusting for acute postconcussion symptoms and other covariates. Greater school attendance time was associated with earlier symptom resolution (adjusted HR = 1.14; 95% CI, 1.02-1.27). Conclusion: Self-paced physical and cognitive activities across the first week postinjury alone neither hastened nor prolonged concussion recovery. Youth with concussion may have some latitude to determine their activity levels.

The biomimetic route to inorganic synthesis presents an opportunity to produce complex materials with superior properties under ambient conditions and from nontoxic precursors. While there has been significant progress in using solid-binding peptides (SBPs), proteins, and organisms to produce a variety of inorganic and hybrid structures, it has been more challenging to understand the interplay of solution conditions and solid-binding peptide (SBP) sequence, structure, and self-association on synthetic outcomes. Here, we show that fusing the Car9 silica-binding peptidebut not the silaffin-derived R5 peptideto superfolder green fluorescent protein (sfGFP) enhances the ability of micromolar concentrations of protein to induce rapid titania (TiO2) precipitation from acidified solutions of tetrakis­(di-lactato)-oxo-titanate (TiBALDH). TiO2 is produced stoichiometrically and although predominantly amorphous, contains nanosized anatase and monoclinic TiO2(B) inclusions. Remarkably, the phase of these nanocrystallites can be tuned from about 80% TiO2(B) to about 65% anatase by using Car9 mutants impaired in their ability to drive the formation of higher-order sfGFP-Car9 oligomers. Our results suggest that the presentation of multiple basic side chains in an extended plane formed by SBP self-association is critical to template the formation of monoclinic crystallites and underscore the subtle influence that single or dual substitutions in dodecameric SBPs can exert on the yield and crystallinity of biomineralized inorganics.

This article examines the choices students make when deciding the mode of study they will enrol in for university. It expands on previous work in the field by surveying 744 Faculty of Arts students at an Australian university who had the choice of enrolling in one of three study modes: on-campus, distance or purely online. Influences on enrolment mode were categorised into six factors: personal, logistics, teaching and learning, learning support, environment, and advice and marketing. Significant differences in influence were found between the three cohorts of students, while the teaching and learning and logistics factors were found to be the most influential for all cohorts. The findings of this research offer administrators, learning and teaching support staff, and academics important information that can be used to tailor the delivery of teaching and services to the varying needs of different cohorts.