Nutrient stress alters the glycosylation status of LGR5 resulting in reduced protein stability and membrane localisation in colorectal tumour cells: implications for targeting cancer stem cells

BACKGROUND LGR5 is an important marker of intestinal stem cells and performs its vital functions at the cell membrane. Despite the importance of LGR5 to both normal and cancer stem cell biology, it is not known how microenvironmental stress affects the expression and subcellular distribution of the protein. METHODS Nutrient stress was induced through glucose starvation. Glycosylation status was assessed using endoglycosidase or tunicamycin treatment. Flow cytometry and confocal microscopy were used to assess subcellular distribution of LGR5. RESULTS Glucose deprivation altered the glycosylation status of LGR5 resulting in reduced protein stability and cell surface expression. Furthermore, inhibiting LGR5 glycosylation resulted in depleted surface expression and reduced localisation in the cis-Golgi network. CONCLUSIONS Nutrient stress within a tumour microenvironment has the capacity to alter LGR5 protein stability and membrane localisation through modulation of LGR5 glycosylation status. As LGR5 surface localisation is required for enhanced Wnt signalling, this is the first report to show a mechanism by which the microenvironment could affect LGR5 function

Who are these youths? Language in the service of policy

In the 1990s policy relating to children and young people who offend developed as a result of the interplay of political imperatives and populist demands. The ‘responsibilisation’ of young offenders and the ‘no excuses’ culture of youth justice have been ‘marketed’ through a discourse which evidences linguistic changes. This article focuses on one particular area of policy change, that relating to the prosecutorial decision, to show how particular images of children were both reflected and constructed through a changing selection of words to describe the non-adult suspect and offender. In such minutiae of discourse can be found not only the signifiers of public attitudinal and policy change but also the means by which undesirable policy developments can be challenged

Preliminary diagnostic reference levels for endoscopic retrograde cholangio-pancreatography in Greece

The main objective of this study was to determine the preliminary Diagnostic Reference Levels (DRLs) in terms of Kerma Area Product (KAP) and fluoroscopy time (Tf) during Endoscopic Retrograde Cholangio-Pancreatography (ERCP) procedures. Additionally, an investigation was conducted to explore the statistical relation between KAP and Tf. Data from a set of 200 randomly selected patients treated in 4 large hospitals in Greece (50 patients per hospital) were analyzed in order to obtain preliminary DRLs for KAP and Tf during therapeutic ERCP procedures. Non-parametric statistic tests were performed in order to determine a statistically significant relation between KAP and Tf. The resulting third quartiles for KAP and Tf for hospitals (A, B, C and D) were found as followed: KAPA = 10.7 Gy cm^2, TfA = 4.9 min; KAPB = 7.5 Gy cm^2, TfB = 5.0 min; KAPC = 19.0 Gy cm^2, TfC = 7.3 min; KAPD = 52.4 Gy cm^2, TfD = 15.8 min. The third quartiles, calculated for the total 200 cases sample, are: KAP = 18.8 Gy cm^2 and Tf = 8.2 min. For 3 out of 4 hospitals and for the total sample, p-values of statistical indices (correlation of KAP and Tf) are less than 0.001, while for the Hospital A p-values are ranging from 0.07 to 0.08. Using curve fitting, we finally determine that the relation of Tf and KAP is deriving from a power equation (KAP = Tf^1.282) with R^2 = 0.85. The suggested Preliminary DRLs (deriving from the third quartiles of the total sample) for Greece are: KAP = 19 Gy cm^2 and Tf = 8 min, while the relation between KAP and Tf is efficiently described by a power equatio

Consumer opinion on social policy approaches to promoting positive body image: Airbrushed media images and disclaimer labels

© The Author(s) 2015. Disclaimer labels on airbrushed media images have generated political attention and advocacy as a social policy approach to promoting positive body image. Experimental research suggests that labelling is ineffective and consumers' viewpoints have been overlooked. A mixed-method study explored British consumers' (N = 1555, aged 11-78 years) opinions on body image and social policy approaches. Thematic analysis indicated scepticism about the effectiveness of labelling images. Quantitatively, adults, although not adolescents, reported that labelling was unlikely to improve body image. Appearance diversity in media and reorienting social norms from appearance to function and health were perceived as effective strategies. Social policy and research implications are discussed

Performance-Based Seismic Design and Assessment of Bridges

Current trends in the seismic design and assessment of bridges are discussed, with emphasis on two procedures that merit some particular attention, displacement-based procedures and deformation-based procedures. The available performance-based methods for bridges are critically reviewed and a number of critical issues are identified, which arise in all procedures. Then two recently proposed methods are presented in some detail, one based on the direct displacement-based design approach, using equivalent elastic analysis and properly reduced displacement spectra, and one based on the deformation-based approach, which involves a type of partially inelastic response-history analysis for a set of ground motions and wherein pier ductility is included as a design parameter, along with displacement criteria. The current trends in seismic assessment of bridges are then summarised and the more rigorous assessment procedure, i.e. nonlinear dynamic response-history analysis, is used to assess the performance of bridges designed to the previously described procedures. Finally some comments are offered on the feasibility of including such methods in the new generation of bridge codes