A latent green fluorescent styrylcoumarin probe for the selective growth and detection of Gram negative bacteria

A novel, green fluorescent β-alanylstyrylcoumarin derivative was synthesized and evaluated for its performance as a fluorogenic enzyme substrate on a range of clinically relevant microorganisms. The substrate was selectively hydrolysed by β-alanyl aminopeptidase producing P. aeruginosa resulting in an on-to-off fluorescent signal. Growth inhibitory effect of the substrate was observed on Gram positive bacteria and yeasts. Meanwhile, Gram negative species, despite their extremely protective cell envelope, showed ready uptake and accumulation of the substrate within their healthy growing colonies displaying intense green fluorescence.NHMR

Gifted and talented education: The English policy highway at a crossroads?

Copyright © 2013 by Sage Publications. This is the author's accepted manuscript. The final published article is available from the link below.In 1999, the British government launched an education program for gifted and talented pupils as part of its Excellence in Cities initiative (EiC) that was initially designed to raise the educational achievement of very able pupils in state-maintained secondary schools in inner-city areas. Although some activities targeting gifted children had already been initiated by various voluntary organizations over several previous decades, this was the first time that the topic of improved provision for these pupils had been placed firmly within the national agenda. This article provides the background to the English gifted and talented policy “highway” and an overview of what was expected of schools. How practitioners responded to the policy, their beliefs and attitudes toward identifying gifted and talented pupils, and the opportunities and challenges that arose along the way to the current crossroads are explored. The need to empower teachers to feel more confident in classroom provisions for gifted and talented pupils is identified along with the potentially pivotal role of action research and “pupil voice” in the process of continued professional development and support

Modulation of adipocyte G-protein expression in cancer cachexia by a lipid-mobilizing factor (LMF)

Adipocytes isolated from cachectic mice bearing the MAC 16 tumour showed over a 3-fold increase in lipolytic response to both low concentrations of isoprenaline and a tumour-derived lipid mobilizing factor (LMF). This was reflected by an enhanced stimulation of adenylate cyclase in plasma membrane fractions of adipocytes in the presence of both factors. There was no up-regulation of adenylate cyclase in response to forskolin, suggesting that the effect arose from a change in receptor number or G-protein expression. Immunoblotting of adipocyte membranes from mice bearing the MAC16 tumour showed an increased expression of Gαs up to 10% weight loss and a reciprocal decrease in Gα. There was also an increased expression of Gαs and a decrease in Gα in adipose tissue from a patient with cancer-associated weight loss compared with a non-cachectic cancer patient. The changes in G-protein expression were also seen in adipose tissue of normal mice administered pure LMF as well as in 3T3L1 adipocytes in vitro. The changes in G-protein expression induced by LMF were attenuated by the polyunsaturated fatty acid, eicosapentaenoic acid (EPA). This suggests that this tumour-derived lipolytic factor acts to sensitize adipose tissue to lipolytic stimuli, and that this effect is attenuated by EPA, which is known to preserve adipose tissue in cancer cachexia. © 2001 Cancer Research Campaig

Expression of uncoupling proteins-1,-2 and-3 mRNA is induced by an adenocarcinoma-derived lipid-mobilizing factor

The abnormalities of lipid metabolism observed in cancer cachexia may be induced by a lipid-mobilizing factor produced by adenocarcinomas. The specific molecules and metabolic pathways that mediate the actions of lipid-mobilizing factor are not known. The mitochondrial uncoupling proteins-1, -2 and -3 are suggested to play essential roles in energy dissipation and disposal of excess lipid. Here, we studied the effects of lipid-mobilizing factor on the expression of uncoupling proteins-1, -2 and -3 in normal mice. Lipid-mobilizing factor isolated from the urine of cancer patients was injected intravenously into mice over a 52-h period, while vehicle was similarly given to controls. Lipid-mobilizing factor caused significant reductions in body weight (-10%, P=0.03) and fat mass (-20%, P<0.01) accompanied by a marked decrease in plasma leptin (-59%, P<0.01) and heavy lipid deposition in the liver. In brown adipose tissue, uncoupling protein-1 mRNA levels were elevated in lipid-mobilizing factor-treated mice (+96%, P<0.01), as were uncoupling proteins-2 and -3 (+57% and +37%, both P<0.05). Lipid-mobilizing factor increased uncoupling protein-2 mRNA in both skeletal muscle (+146%, P<0.05) and liver (+142%, P=0.03). The protein levels of uncoupling protein-1 in brown adipose tissue and uncoupling protein-2 in liver were also increased with lipid-mobilizing factor administration (+49% and +67%, both P=0.02). Upregulation by lipid-mobilizing factor of uncoupling proteins-1, -2 and -3 in brown adipose tissue, and of uncoupling protein-2 in skeletal muscle and liver, suggests that these uncoupling proteins may serve to utilize excess lipid mobilized during fat catabolism in cancer cachexia

Role of β3-adrenergic receptors in the action of a tumour lipid mobilizing factor

Induction of lipolysis in murine white adipocytes, and stimulation of adenylate cyclase in adipocyte plasma membranes, by a tumour-produced lipid mobilizing factor, was attenuated by low concentrations (10−7–10−5 M) of the specific β3-adrenoceptor antagonist SR59230A. Lipid mobilizing factor (250 nM) produced comparable increases in intracellular cyclic AMP in CHOK1 cells transfected with the human β3-adrenoceptor to that obtained with isoprenaline (1 nM). In both cases cyclic AMP production was attenuated by SR59230A confirming that the effect is mediated through a β3-adrenoceptor. A non-linear regression analysis of binding of lipid mobilizing factor to the β3-adrenoceptor showed a high affinity binding site with a Kd value 78±45 nM and a Bmax value (282±1 fmole mg protein−1) comparable with that of other β3-adrenoceptor agonists. These results suggest that lipid mobilizing factor induces lipolysis through binding to a β3-adrenoceptor

Theorising variation in engagement in professional and curriculum development: performativity, capital, systems and purpose

Increasingly, policymakers seek to improve the quality of teaching through curriculum innovations and continuing professional development (CPD) programmes. However, engagement by schools and teachers varies due to mediating influences of neoliberal policies. In this article, we contribute to understanding how these tendencies affect participation. Problematising the notion of context, we examine ways in which systemic influences interacted with participation in a government-funded mathematics professional and curriculum development programme and also with participants’ purposes. A 3-level clustered Randomised Controlled Trial (RCT) and an implementation and process evaluation were augmented by in-depth case studies, cross-case analysis and the application of theoretical constructs to interpret findings. Theories of capital, figured worlds and systemic coupling are utilised to theorise context. Different levels of engagement are partly explainable by: the interaction of schools' relative systemic advantage and disadvantage; their orientation and coupling to performativity regimes; and the alignment or dissonance between continuing professional development or change programmes and the pedagogical and CPD cultures and purposes of the ‘actors’ (schools, departments and teachers). Performativity concerns restricted what were considered legitimate outcomes in some case study schools. This depended on teachers and schools' positioning in terms of relative degrees of systemic privilege or disadvantage - understood as economic, cultural, social and symbolic capital - and also in terms of figured worlds and system coupling. The case studies provide insights into how collaborative professional learning can be fostered more productively. Methodologically, we demonstrate the power of combining methodologies and applying explanatory social theory to augment quasi-experimental paradigms