Rapid incorporation of carbon from ectomycorrhizal mycelial necromass into soil fungal communities

Peer reviewedPublisher PD

High level of telomerase RNA gene expression is associated with chromatin modification, the ALT phenotype and poor prognosis in liposarcoma

Telomere length is maintained by two known mechanisms, activation of telomerase or alternative lengthening of telomeres (ALT). The ALT pathway is more commonly activated in tumours of mesenchymal origin, although the mechanisms involved in the decision of a cell to activate either telomerase or ALT are unknown at present and no molecular markers exist to define the ALT phenotype. We have previously shown an association between chromatin remodelling, telomerase gene expression and ALT in cell line models. Here, we evaluate these findings and investigate their prognostic significance in a panel of liposarcoma tissue samples to understand the biology underlying the ALT phenotype. Liposarcoma samples were split into three groups: telomerase positive (Tel+); ALT positive; ALT−/Tel−. Differences in telomerase gene expression were evident between the groups with increased expression of hTR in ALT and Tel+ compared to ALT−/Tel− samples and increased hTERT in Tel+ samples only. Investigation of a small panel of chromatin modifications revealed significantly increased binding of acetyl H3 in association with hTR expression. We confirm that the presence of the ALT phenotype is associated with poor prognosis and in addition, for the first time, we show a direct association between hTR expression and poor prognosis in liposarcoma patients

Fracture toughness testing using photogrammetry and digital image correlation

Digital image correlation (DIC) is an optical technique commonly used for measuring displacement fields by tracking artificially applied random speckle patterns, which can sometimes be a problem for tracking small-scale displacements. DIC is particularly useful for tracking the crack mouth opening displacement (CMOD) of a notched metallic specimen subjected to three-point bending for fracture toughness determination because the edges of the notch provide the required textural features for DIC without the need for speckle patterns. This simplifies the set-up process as the specimen and stage geometries do not need to account for the placement of a strain gauge. To enhance the accuracy of DIC, this study then successfully downscaled a photogrammetry technique commonly used to track crack propagation in large scale concrete tests so that the pixel coordinates of the captured images can be automatically related to their real-world coordinates, allowing for small scale displacements to be accurately tracked.ARC Linkage Project LP130100111, ARC DECRA DE15010170

The New British Policy Style: From a British to a Scottish Political Tradition?

The new context of coalition government and the ‘Big Society' suggests that the UK government is moving towards a style of politics followed successfully in Scotland, extending a partnership approach from national to local forms of government. Yet the two arenas have never been as far apart as is commonly imagined. The majoritarian (UK) and consensus (Scottish) labels are misleading. British politics is not as exceptional as it is often made out to be, while Scottish politics retains many elements of its British counterpart. This article assesses the state of British politics in this light. It sets out a counter-exceptionalism thesis based on the theory and evidence from public policy. It then summarises the post-devolution evidence, producing insights on the British policy style when compared to the ‘new politics' in Scotland

Has Devolution Changed the 'British Policy Style'?

The term ‘policy style' simply means the way that governments make and implement policy. Yet, the term ‘British policy style' may be confusing since it has the potential to relate to British exceptionalism or European convergence. Lijphart's important contribution identifies the former. It sets up a simple distinction between policy styles in majoritarian and consensual democracies and portrays British policy-making as top down and different from a consensual European approach. In contrast, Richardson identifies a common ‘European policy style'. This suggests that although the political structures of each country vary, they share a ‘standard operating procedure' based on two factors - an incremental approach to policy and an attempt to reach a consensus with interest groups rather than impose decisions. This article extends these arguments to British politics since devolution. It questions the assumption that policy styles are diverging within Britain. Although consultation in the devolved territories may appear to be more consensual, they are often contrasted with a caricature of the UK process based on atypical examples of top-down policy-making. While there may be a different ‘feel' to participation in Scotland and Wales, a similar logic of consultation and bureaucratic accommodation exists in the UK. This suggests that, although devolution has made a difference, a British (or European) policy style can still be identified

Quercetin elevates p27Kip1 and arrests both primary and HPV16 E6/E7 transformed human keratinocytes in G1

Our previous work with primary bovine fibroblasts demonstrated that quercetin, a potent mutagen found in high levels in bracken fern (Pteridium aquilinum), arrested cells in G1 and G2/M, in correlation with p53 activation. The expression of bovine papillomavirus type 4 (BPV-4) E7 overcame this arrest and lead to the development of tumorigenic cells lines (Beniston et al., 2001). Given the possible link between papillomavirus infection, bracken fern in the diet and cancer of the upper gastrointestinal (GI) tract in humans, we investigated whether a similar situation would occur in human cells transformed by human papillomavirus type 16 (HPV-16) oncoproteins. Quercetin arrested primary human foreskin keratinocytes in G1. Arrest was linked to an elevation of the cyclin-dependent kinase inhibitor (cdki) p27Kip1. Expression of the HPV16 E6 and E7 oncoproteins in transformed cells failed to abrogate cell cycle arrest. G1 arrest in the transformed cells was also linked to an increase of p27Kip1 with a concomitant reduction of cyclin E-associated kinase activity. This elevation of p27Kip1 was due not only to increased protein half-life, but also to increased mRNA transcription

Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms

Cancer cells depend on transcription of telomerase reverse transcriptase (TERT). Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3′-oxime (BIO) predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several aspects of TERT regulation including previously unknown mechanisms. An extrapolation suggests that a dominant stimulatory system may programme TERT for transcriptional stability