Phosphorylation of survivin at threonine 34 inhibits its mitotic function and enhances its cytoprotective activity

Survivin is an essential chromosomal passenger protein required for mitotic progression. It is also an inhibitor of apoptosis and can prevent caspase-mediated cell death. In addition, survivin levels are elevated in cancer cells where its presence correlates with increased resistance to chemo- and radio-therapy, which makes it an attractive target for novel anti-cancer strategies. Interestingly, survivin is phosphorylated by the mitotic kinase, cdk1, and a non-phosphorylatable form, survivin(T34A), cannot inhibit apoptosis. Here we rigorously test the ability of survivin(T34A) and its corresponding phosphomimetic, survivin(T34E), to promote cell viability through survivin's dual roles. The effects of these mutations are diametrically opposed: survivin(T34A) accelerates cell proliferation and promotes apoptosis, whereas survivin(T34E) retards growth and promotes survival. Thus the phosphorylation status of survivin at T34 is pivotal to a cell's decision to live or die

The food environment within the primary school fringe

Purpose – The school fringe environment (peripheral 400m buffer) offers an important opportunity for young people to obtain food and drink. There is international evidence to suggest socio-economic influence on food outlet availability and healthfulness within these environments; however the situation in the UK is unclear. The purpose of this paper is to describe food outlet provision (frequency and type) within primary school fringes across the spectrum of deprivation. Design/methodology/approach – Ten primary schools in Newcastle upon Tyne were purposefully selected from a comprehensive list of all schools within the region. Two schools were chosen at random from each quintile of deprivation. A total of 400-metre buffer zones around schools were audited. School fringe food environments were classified using a Food Outlet Classification System. Access (i.e. frequency), and type of food outlets were compared to area level deprivation, obesity prevalence rates and area type. Findings – Food outlet frequency was highest in the most deprived school fringe area. Convenience stores and takeaways represented the greatest proportion of total food outlets across all school fringe environments. More total food outlets were observed in fringes with above national average obesity prevalence rates for children. Research limitations/implications – UK case study approach limits widespread and international applicability. Practical implications – Informs school, health and urban planning disciplines regarding current picture of UK school fringes. Originality/value – Provides evidence in UK context that area deprivation and Census 2001 Supergroup class show significant correlations with school fringe food environment

The Joys and Opportunities of Magazine Publishing

Rachel Barrett: Editor in Chief, Country Living Magazine, Hearst Magazines Jeff Joseph: Publisher & Editorial Director, Luckbox Magazine Jeremy Leslie: Founder & Curator, MagCulture, It\u27s a Mag, Mag World! Jo Packham: Creator/Editor in Chief, & 2018 Magazine Launch of the Year, Where Women Create, Where Women Cook, Where Women Create Work, & What Women Create Magazines Link to Jeff Joseph\u27s presentation Link to Jeremy Leslie\u27s presentation Link to Jo Packham\u27s presentatio

Comparison of biosensor platforms in the evaluation of high affinity antibody-antigen binding kinetics

AbstractThe acquisition of reliable kinetic parameters for the characterization of biomolecular interactions is an important component of the drug discovery and development process. While several benchmark studies have explored the variability of kinetic rate constants obtained from multiple laboratories and biosensors, a direct comparison of these instruments' performance has not been undertaken, and systematic factors contributing to data variability from these systems have not been discussed. To address these questions, a panel of ten high-affinity monoclonal antibodies was simultaneously evaluated for their binding kinetics against the same antigen on four biosensor platforms: GE Healthcare's Biacore T100, Bio-Rad's ProteOn XPR36, ForteBio's Octet RED384, and Wasatch Microfluidics's IBIS MX96. We compared the strengths and weaknesses of these systems and found that despite certain inherent systematic limitations in instrumentation, the rank orders of both the association and dissociation rate constants were highly correlated between these instruments. Our results also revealed a trade-off between data reliability and sample throughput. Biacore T100, followed by ProteOn XPR36, exhibited excellent data quality and consistency, whereas Octet RED384 and IBIS MX96 demonstrated high flexibility and throughput with compromises in data accuracy and reproducibility. Our results support the need for a “fit-for-purpose” approach in instrument selection for biosensor studies

A Statistical Analysis of the Change in Age Distribution of Spawning Hatchery Salmon

Declines in salmon sizes have been reported primarily as a result of younger maturation rates. This change in age distribution poses serious threats to salmon-dependent peoples and ecological systems. We perform a statistical analysis to examine the change in age structure of spawning Alaskan chum salmon Oncorhynchus keta and Chinook salmon O. tshawytscha using 30 years of hatchery data. To highlight the impacts of this change, we investigate the average number of fry/smolt that each age of spawning chum/Chinook salmon produce. Our findings demonstrate an increase in younger hatchery salmon populations returning to spawn, and fewer amounts of fry produced by younger salmon compared to older salmon. These results suggest the potential risks associated with younger spawning salmon and aim to help better understand salmon behavior in order to sustain and protect healthy salmon populations

Non-commutative geometry and the standard model vacuum

The space of Dirac operators for the Connes-Chamseddine spectral action for the standard model of particle physics coupled to gravity is studied. The model is extended by including right-handed neutrino states, and the S0-reality axiom is not assumed. The possibility of allowing more general fluctuations than the inner fluctuations of the vacuum is proposed. The maximal case of all possible fluctuations is studied by considering the equations of motion for the vacuum. Whilst there are interesting non-trivial vacua with Majorana-like mass terms for the leptons, the conclusion is that the equations are too restrictive to allow solutions with the standard model mass matrix.Comment: 21 pages. v2: some comments improve

Personality, Parenting Style, and Academic Cognitions: The Effects of Authoritarian Parenting Style on Personality Traits and Behaviors

Presented is an analysis of self-esteem as a moderator of the effect authoritarian parenting on personality trait and behavior development

Best Practices for Preschool Music Education: Supporting Music‑Making Throughout the Day

Active engagement in music has numerous academic and social benefits for young children and music-making is included in many early childhood standards and preschool curricula. The purpose of this article is to provide quality resources for classroom teachers to use in providing music-making activities for young children, ages 3–5. Although teachers may use music in their classrooms, we provide resources and suggestions for more intentional and extended integration of music-making. Specifically, we identify best practices for preschool music education based on key standards and research as well as with common music pedagogies. We then turn to concrete examples of how teachers can implement these music best practices throughout the entire preschool day. We provide ideas and resources for whole-group activities, focusing on choice-time/center activities and ways to incorporate music activities in other academic areas as these seem to be of greater need for teachers. Finally, we use the stated best practices to review the alignment of a sample of commercially available preschool music curricula as an additional support for teachers