Using sports infrastructure to deliver economic and social change: Lessons for London beyond 2012

Over the last two decades, there has been a new trend emerging within sport, which has seen a shift, from investment for the sake of sport, to investment in sport for good (Sport England, 2008). In the context of the latter approach, there has been an emergence of the use of sport to address regeneration objectives, largely stemming from the belief of government and other sporting and non-sporting organizations, that it can confer a wide range of economic and social benefits to individuals and communities beyond those of a purely physical sporting nature, and can contribute positively to the revitalization of declining urban areas (BURA, 2003). This commentary will examine regeneration legacy in the context of the London Olympic Games. In particular, it will focus on the use of sports stadia as a tool for delivering economic and social change, and by drawing upon previous examples, suggest lessons London can learn to enhance regeneration legacies beyond 2012

Acute effects of exercise on appetite, ad libitum energy intake and appetite-regulatory hormones in lean and overweight/obese men and women

Background: Acute exercise does not elicit compensatory changes in appetite parameters in lean individuals; however, less is known about responses in overweight individuals. This study compared the acute effects of moderate-intensity exercise on appetite, energy intake and appetite-regulatory hormones in lean and overweight/obese individuals. Methods: Forty-seven healthy lean (n=22, 11 females; mean (s.d.) 37.5 (15.2) years; 22.4 (1.5) kg m−2) and overweight/obese (n=25, 11 females; 45.0 (12.4) years, 29.2 (2.9) kg m−2) individuals completed two, 8 h trials (exercise and control). In the exercise trial, participants completed 60 min treadmill exercise (59 (4)% peak oxygen uptake) at 0–1 h and rested thereafter while participants rested throughout the control trial. Appetite ratings and concentrations of acylated ghrelin, peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) were measured at predetermined intervals. Standardised meals were consumed at 1.5 and 4 h and an ad libitum buffet meal was provided at 7 h. Results: Exercise suppressed appetite (95% confidence interval (CI) −3.1 to −0.5 mm, P=0.01), and elevated delta PYY (95% CI 10 to 17 pg ml−1, P<0.001) and GLP-1 (95% CI 7 to 10 pmol l−1, P<0.001) concentrations. Delta acylated ghrelin concentrations (95% CI −5 to 3 pg ml−1, P=0.76) and ad libitum energy intake (95% CI −391 to 346 kJ, P=0.90) were similar between trials. Subjective and hormonal appetite parameters and ad libitum energy intake were similar between lean and overweight/obese individuals (Pgreater than or equal to0.27). The exercise-induced elevation in delta GLP-1 was greater in overweight/obese individuals (trial-by-group interaction P=0.01), whereas lean individuals exhibited a greater exercise-induced increase in delta PYY (trial-by-group interaction P<0.001). Conclusions: Acute moderate-intensity exercise transiently suppressed appetite and increased PYY and GLP-1 in the hours after exercise without stimulating compensatory changes in appetite in lean or overweight/obese individuals. These findings underscore the ability of exercise to induce a short-term energy deficit without any compensatory effects on appetite regardless of weight status

Understanding student satisfaction and dissatisfaction : an interpretive study in the UK higher education context

This article represents a cross-sectional study of undergraduate students across two north-west university business schools in the UK. A purposefully designed questionnaire was collected from 350 students. The student experience was described in the form of hand-written narratives by first and final year students and had been identified by the respondents themselves as being satisfying or dissatisfying with the areas of teaching and learning and the supporting service environment. The study also assessed whether their experiences were likely to influence their loyalty behaviours with respect to remaining on their chosen course of study; recommending the university; and continuing at a higher level of study. The data were captured and analysed using the qualitative critical incident technique to capture the voice of the student and identified the critical determinants of quality within higher education, i.e. those areas that would influence loyalty behaviour, as being Access; Attentiveness; Availability; and Communication. A number of new determinants of quality have been identified out of the research by three independent judges, namely motivation, reward, social inclusion, usefulness, value for money and fellow student behaviour

TGFβ1 rapidly activates Src through a non-canonical redox signaling mechanism.

Transforming growth factor-β1 (TGF-β) is involved in multiple cellular processes through Src activation. In the canonical pathway, Src activation is initiated by pTyr530 dephosphorylation followed by a conformational change allowing Tyr419 auto-phosphorylation. A non-canonical pathway in which oxidation of cysteine allows bypassing of pTyr530 dephosphorylation has been reported. Here, we examined how TGF-β activates Src in H358 cells, a small cell lung carcinoma cell line. TGF-β increased Src Tyr419 phosphorylation, but surprisingly, Tyr530 phosphorylation was increased rather than decreased. Vanadate, a protein tyrosine phosphatase inhibitor, stimulated Src activation itself, but rather than inhibiting Src activation by TGF-β, activation by vanadate was additive with TGF-β showing that pTyr530 dephosphorylation was not required. Thus, the involvement of the non-canonical oxidative activation was suspected. TGF-β increased extracellular H2O2 transiently while GSH-ester and catalase abrogated Src activation by TGF-β. Apocynin, a NADPH oxidase inhibitor, inhibited TGF-β-stimulated H2O2 production. Furthermore, mutation of cysteines to alanine, 248C/A, 277C/A, or 501C/A abrogated, while 490C/A significantly reduced, TGF-β-mediated Src activation. Taken together, the results indicate that TGF-β-mediated Src activation operates largely through a redox dependent mechanism, resulting from enhanced H2O2 production through an NADPH oxidase and that cysteines 248, 277, 490, and 501 are critical for this activation

Multi-site phosphorylation controls the neurogenic and myogenic activity of E47.

The superfamily of basic-Helix-Loop-Helix (bHLH) transcription factors influence cell fate in all three embryonic germ layers, and the tissue-specific class II factors have received prominent attention for their potent ability to direct differentiation during development and in cellular reprogramming. The activity of many class II bHLH proteins driving differentiation, and the inhibitory class VI bHLH factor Hes1, is controlled by phosphorylation on multiple sites by Cyclin-dependent kinases (Cdks). As class II proteins are generally thought to be active through hetero-dimerisation with the ubiquitously expressed class I E proteins, regulation of class I transcription factors such as E47 may influence the activity of multiple tissue-specific bHLH proteins. Using differentiation of nerve and muscle in Xenopus frog embryos as a model system, we set out to explore whether with the ubiquitously expressed class I E protein E47 that hetero-dimerises with Class II bHLHs to control their activity, is also regulated by multi-site phosphorylation. We demonstrate that E47 can be readily phosphorylated by Cdks on multiple sites in vitro, while ectopically-expressed E47 exists in multiple phosphorylated forms in Xenopus embryos. Preventing multi-site phosphorylation using a phospho-mutant version of E47 enhances the neurogenic and myogenic activity of three different class II bHLH reprogramming factors, and also when E47 acts in hetero-dimerisation with endogenous proteins. Mechanistically, unlike phospho-regulation of class II bHLH factors, we find that preventing phosphorylation of E47 increases the amount of chromatin-bound E47 protein but without affecting its overall protein stability. Thus, multi-site phosphorylation is a conserved regulatory mechanism across the bHLH superfamily that can be manipulated to enhance cellular differentiation.This work was supported by Medical Research Council Research Grants MR/L021129/1 and MR/K018329 and AP receives core funding from Wellcome and MRC at the Wellcome-MRC Cambridge Stem Cell Institute. LH is supported by a Peterhouse Research Fellowship

Oxidative stress response and Nrf2 signaling in aging.

Increasing oxidative stress, a major characteristic of aging, has been implicated in a variety of age-related pathologies. In aging, oxidant production from several sources is increased, whereas antioxidant enzymes, the primary lines of defense, are decreased. Repair systems, including the proteasomal degradation of damaged proteins, also decline. Importantly, the adaptive response to oxidative stress declines with aging. Nrf2/EpRE signaling regulates the basal and inducible expression of many antioxidant enzymes and the proteasome. Nrf2/EpRE activity is regulated at several levels, including transcription, posttranslation, and interactions with other proteins. This review summarizes current studies on age-related impairment of Nrf2/EpRE function and discusses the changes in Nrf2 regulatory mechanisms with aging

How do nutritional antioxidants really work: nucleophilic tone and para-hormesis versus free radical scavenging in vivo.

We present arguments for an evolution in our understanding of how antioxidants in fruits and vegetables exert their health-protective effects. There is much epidemiological evidence for disease prevention by dietary antioxidants and chemical evidence that such compounds react in one-electron reactions with free radicals in vitro. Nonetheless, kinetic constraints indicate that in vivo scavenging of radicals is ineffective in antioxidant defense. Instead, enzymatic removal of nonradical electrophiles, such as hydroperoxides, in two-electron redox reactions is the major antioxidant mechanism. Furthermore, we propose that a major mechanism of action for nutritional antioxidants is the paradoxical oxidative activation of the Nrf2 (NF-E2-related factor 2) signaling pathway, which maintains protective oxidoreductases and their nucleophilic substrates. This maintenance of "nucleophilic tone," by a mechanism that can be called "para-hormesis," provides a means for regulating physiological nontoxic concentrations of the nonradical oxidant electrophiles that boost antioxidant enzymes, and damage removal and repair systems (for proteins, lipids, and DNA), at the optimal levels consistent with good health

Contrasting impacts of land use change on phylogenetic and functional diversity of tropical forest birds

1. Biodiversity conservation strategies increasingly target maintaining evolutionary history and the resilience of ecosystem function, not just species richness (SR). This has led to the emergence of two metrics commonly proposed as tools for decision making: phylogenetic diversity (PD) and functional diversity (FD). Yet the extent to which they are interchangeable remains poorly understood. 2. We explore shifts in and relationships between FD and PD of bird communities across a disturbance gradient in Borneo, from old-growth tropical forest to oil palm plantation. 3. We show a marked decline in PD, and an increase in phylogenetic mean nearest taxon distance (MNTD) from forest to oil palm, in line with declining SR across the gradient. However, phylogenetic mean pairwise distance (MPD) is constrained by forest logging more than by conversion to oil palm, taking account of SR. 4. The decline in FD across the gradient is less severe than in PD, with all metrics indicating relatively high trait diversity in oil palm despite low SR, although functional redundancy is much reduced. Accounting for SR, levels of functional over- or under-dispersion of bird communities are strongly coupled to habitat disturbance level rather than to any equivalent phylogenetic metric. 5. Policy Implications. We suggest that while phylogenetic diversity (PD) is an improvement on species richness as a proxy for functional diversity (FD), conservation decisions based on PD alone cannot reliably safeguard maximal FD. Thus, PD and FD are related but still complementary. Priority setting exercises should use these metrics in combination to identify conservation targets

Investigating the Impact of Cerium Oxide Nanoparticles Upon the Ecologically Significant Marine Cyanobacterium Prochlorococcus

Cerium oxide nanoparticles (nCeO_{2}) are used at an ever-increasing rate, however, their impact within the aquatic environment remains uncertain. Here, we expose the ecologically significant marine cyanobacterium Prochlorococcus sp. MED4 to nCeO_{2} at a wide range of concentrations (1 μg L^{–1} to 100 mg L^{–1}) under simulated natural and nutrient rich growth conditions. Flow cytometric analysis of cyanobacterial populations displays the potential of nCeO_{2} (100 μg L^{–1}) to significantly reduce Prochlorococcus cell density in the short-term (72 h) by up to 68.8% under environmentally relevant conditions. However, following longer exposure (240 h) cyanobacterial populations are observed to recover under simulated natural conditions. In contrast, cell-dense cultures grown under optimal conditions appear more sensitive to exposure during extended incubation, likely as a result of increased rate of encounter between cyanobacteria and nanoparticles at high cell densities. Exposure to supra-environmental nCeO_{2} concentrations (i.e., 100 mg L^{–1}) resulted in significant declines in cell density up to 95.7 and 82.7% in natural oligotrophic seawater and nutrient enriched media, respectively. Observed cell decline is associated with extensive aggregation behaviour of nCeO_{2} upon entry into natural seawater, as observed by dynamic light scattering (DLS), and hetero-aggregation with cyanobacteria, confirmed by fluorescent microscopy. Hence, the reduction of planktonic cells is believed to result from physical removal due to co-aggregation and co-sedimentation with nCeO_{2} rather than by a toxicological and cell death effect. The observed recovery of the cyanobacterial population under simulated natural conditions, and likely reduction in nCeO_{2} bioavailability as nanoparticles aggregate and undergo sedimentation in saline media, means that the likely environmental risk of nCeO_{2} in the marine environment appears low

Transplanted astrocytes derived from BMP- or CNTF-treated glial-restricted precursors have opposite effects on recovery and allodynia after spinal cord injury

<p>Abstract</p> <p>Background</p> <p>Two critical challenges in developing cell-transplantation therapies for injured or diseased tissues are to identify optimal cells and harmful side effects. This is of particular concern in the case of spinal cord injury, where recent studies have shown that transplanted neuroepithelial stem cells can generate pain syndromes.</p> <p>Results</p> <p>We have previously shown that astrocytes derived from glial-restricted precursor cells (GRPs) treated with bone morphogenetic protein-4 (BMP-4) can promote robust axon regeneration and functional recovery when transplanted into rat spinal cord injuries. In contrast, we now show that transplantation of GRP-derived astrocytes (GDAs) generated by exposure to the gp130 agonist ciliary neurotrophic factor (GDAs^CNTF), the other major signaling pathway involved in astrogenesis, results in failure of axon regeneration and functional recovery. Moreover, transplantation of GDA^CNTFcells promoted the onset of mechanical allodynia and thermal hyperalgesia at 2 weeks after injury, an effect that persisted through 5 weeks post-injury. Delayed onset of similar neuropathic pain was also caused by transplantation of undifferentiated GRPs. In contrast, rats transplanted with GDAs^BMP did not exhibit pain syndromes.</p> <p>Conclusion</p> <p>Our results show that not all astrocytes derived from embryonic precursors are equally beneficial for spinal cord repair and they provide the first identification of a differentiated neural cell type that can cause pain syndromes on transplantation into the damaged spinal cord, emphasizing the importance of evaluating the capacity of candidate cells to cause allodynia before initiating clinical trials. They also confirm the particular promise of GDAs treated with bone morphogenetic protein for spinal cord injury repair.</p