Principles for the post-GWAS functional characterisation of risk loci

Several challenges lie ahead in assigning functionality to susceptibility SNPs. For example, most effect sizes are small relative to effects seen in monogenic diseases, with per allele odds ratios usually ranging from 1.15 to 1.3. It is unclear whether current molecular biology methods have enough resolution to differentiate such small effects. Our objective here is therefore to provide a set of recommendations to optimize the allocation of effort and resources in order maximize the chances of elucidating the functional contribution of specific loci to the disease phenotype. It has been estimated that 88% of currently identified disease-associated SNP are intronic or intergenic. Thus, in this paper we will focus our attention on the analysis of non-coding variants and outline a hierarchical approach for post-GWAS functional studies

Developing pre-service teacher professional capabilities through action research

There is a growing interest in pre-service teacher education programs on how to maximise the learning benefits of professional experience. This study attempts to discover how action research can be used as a vehicle to bridge the divide between theory and practice and to support pre-service teachers in the development of authentic professional knowledge. In this paper, we share the experiences of four pre-service teachers who undertook an action research study whilst on a ten-week professional experience placement in an Australian High School. The findings of the study indicate that preservice teachers see the benefit of being able to conduct an authentic study not only in terms of developing research skills, but also in order to reflect upon their strengths and areas of development in their own teaching. We argue that with a growing attentiveness to raising accountability across the sector, this approach prepares pre-service teachers for the Teacher Performance Assessment and the classroom

Inhibition of PI3K by PX-866 Prevents Transforming Growth Factor-α–Induced Pulmonary Fibrosis

Transforming growth factor-α (TGFα) is a ligand for the epidermal growth factor receptor (EGFR). EGFR activation is associated with fibroproliferative processes in human lung disease and animal models of pulmonary fibrosis. EGFR signaling activates several intracellular signaling pathways including phosphatidylinositol 3′-kinase (PI3K). We previously showed that induction of lung-specific TGFα expression in transgenic mice caused progressive pulmonary fibrosis over a 4-week period. The increase in levels of phosphorylated Akt, detected after 1 day of doxycycline-induced TGFα expression, was blocked by treatment with the PI3K inhibitor, PX-866. Daily administration of PX-866 during TGFα induction prevented increases in lung collagen and airway resistance as well as decreases in lung compliance. Treatment of mice with oral PX-866 4 weeks after the induction of TGFα prevented additional weight loss and further increases in total collagen, and attenuated changes in pulmonary mechanics. These data show that PI3K is activated in TGFα/EGFR-mediated pulmonary fibrosis and support further studies to determine the role of PI3K activation in human lung fibrotic disease, which could be amenable to targeted therapy

BEDMAP: A new ice thickness and subglacial topographic model of Antarctica

Measurements of ice thickness on the Antarctic ice sheet collected during surveys undertaken over the past 50 years have been brought together into a single database. From these data, a seamless suite of digital topographic models have been compiled for Antarctica and its surrounding ocean. This includes grids of ice sheet thickness over the grounded ice sheet and ice shelves, water column thickness beneath the floating ice shelves, bed elevation beneath the grounded ice sheet, and bathymetry to 60°S, including the sub-ice-shelf cavities. These grids are consistent with a recent high-resolution surface elevation model of Antarctica. While the digital models have a nominal spatial resolution of 5 km, such high resolution is justified by the original data density only over a few parts of the ice sheet. The suite does, however, provide an unparalleled vision of the geosphere beneath the ice sheet and a more reliable basis for ice sheet modeling than earlier maps. The total volume of the Antarctic ice sheet calculated from the BEDMAP grid is 25.4 million km3, and the total sea level equivalent, derived from the amount of ice contained within the grounded ice sheet, is 57 m, comprising 52 m from the East Antarctic ice sheet and 5 m from the West Antarctic ice sheet, slightly less than earlier estimates. The gridded data sets can be obtained from the authors