Brain activity during automatic semantic priming revealed by event-related functional magnetic resonance imaging

Semantic priming occurs when a subject is faster in recognising a target word when it is preceded by a related word compared to an unrelated word. The effect is attributed to automatic or controlled processing mechanisms elicited by short or long interstimulus intervals (ISIs) between primes and targets. We employed event-related functional magnetic resonance imaging (fMRI) to investigate blood oxygen level dependent (BOLD) responses associated with automatic semantic priming using an experimental design identical to that used in standard behavioural priming tasks. Prime-target semantic strength was manipulated by using lexical ambiguity primes (e.g., bank) and target words related to dominant or subordinate meaning of the ambiguity. Subjects made speeded lexical decisions (word/nonword) on dominant related, subordinate related, and unrelated word pairs presented randomly with a short ISI. The major finding was a pattern of reduced activity in middle temporal and inferior prefrontal regions for dominant versus unrelated and subordinate versus unrelated comparisons, respectively. These findings are consistent with both a dual process model of semantic priming and recent repetition priming data that suggest that reductions in BOLD responses represent neural priming associated with automatic semantic activation and implicate the left middle temporal cortex and inferior prefrontal cortex in more automatic aspects of semantic processing.

Can we get General Practitioners to Promote Physical Activity? Results of the 10,000 Steps Rockhampton Community-Based Physical Activity Promotion Project

Evidence supporting the efficacy of physical activity promotion in primary care settings has evaluated patient-level changes in physical activity, with little focus on the issue of general practitioner (GP) uptake. The 'GP Strategy' of 10,000 Steps Rockhampton provided an opportunity to explore this issue in the context of a multi-strategy, community-based physical activity intervention project. The 'GP Strategy' was developed in partnership with the Capricornia Division of General Practice. It aimed to: 1) increase GP awareness of the 10,000 Steps project, 2) upskill GPs in brief physical activity counselling techniques, and 3) provide GPs with evidencebased physical activity counselling materials and pedometers. The evaluation, which was guided by the RE-AIM evaluation framework, used a pre-post design, including a GP mailed survey, and collection of process data. Survey response rates were 67% (n=44/66; baseline) and 70% (n=37/53; 14-month follow-up). GP awareness of 10,000 Steps Rockhampton increased from 46% to 97%. 21/23 practices were visited by 10,000 Steps staff and accepted 10,000 Steps posters, brochures, and pedometers. At follow-up, 78% had displayed the poster, 81% were using the brochures, and 70% had loaned pedometers to patients. Despite the very high rate of uptake and use of 10,000 Steps materials, there was no change in the percentage of patients counselled, and relatively few pedometers had been loaned to patients. The results of this trial indicate that it will take more effort to change GP physical activity counselling behaviour, and provide only modest support for use of pedometers in the busy general practice setting. Acknowledgement:This project is supported by a grant from Health Promotion Queensland.

10,000 Steps Rockhampton: A Whole Community Approach to Increasing Levels of Physical Activity

10,000 Steps Rockhampton is a multi-strategy health promotion program which aims to develop sustainable community-based strategies to increase physical activity.The central coordinating focus of the project is the use of pedometers to raise awareness of and provide motivation for physical activity, around the theme of '10,000 steps/day - Every step counts.' To date, five key strategies have been implemented: (1) a media-based awareness raising campaign; (2) promotion of physical activity by health professionals; (3) improving social support for physical activity through group-based programs; (4) working with local council to improve environmental support for physical activity; and (5) establishment of a ‘micro-grants’ fund to which community groups could apply for assistance with small, innovative physical activity enhancing projects. Strategies were introduced on a rolling basis beginning in February 2002 with 'layering' of interventions designed to address the multi-level individual social and environmental determinants of physical activity. The project was quasi-experimental in design, involving collection of baseline and two year follow-up data from community based surveys in Rockhampton and in a matched regional Queensland town. In August 2001,the baseline CATI survey (N=1281)found that 47.9% of men and 33.0% of women were meeting the national guidelines for physical activity. In August 2002, a smaller survey (N=400) found an increase in activity levels among women (39.7% active) but not in men (48.5%). Data from the two year follow up survey, to be conducted in August 2003, will be presented, with discussion of the major successes and challenges of this landmark physical activity intervention. Acknowledgement: This project is supported by a grant from Health Promotion Queensland

The contribution model:a school-level funding model

Over a number of years, as the Higher Education Funding Council for England (HEFCE)'s funding models became more transparent, Aston University was able to discover how its funding for teaching and research was calculated. This enabled calculations to be made on the funds earned by each school in the University, and Aston Business School (ABS) in turn to develop models to calculate the funds earned by its programmes and academic groups. These models were a 'load' and a 'contribution' model. The 'load' model records the weighting of activities undertaken by individual members of staff; the 'contribution' model is the means by which funds are allocated to academic units. The 'contribution' model is informed by the 'load' model in determining the volume of activity for which each academic unit is to be funded.

Attentional changes in pre-stimulus oscillatory activity within early visual cortex are predictive of human visual performance

Physiological and neuroimaging studies provide evidence to suggest that attentional mechanisms operating within the fronto-parietal network may exert top–down control on early visual areas, priming them for forthcoming sensory events. The believed consequence of such priming is enhanced task performance. Using the technique of magnetoencephalography (MEG), we investigated this possibility by examining whether attention-driven changes in cortical activity are correlated with performance on a line-orientation judgment task. We observed that, approximately 200 ms after a covert attentional shift towards the impending visual stimulus, the level of phase-resetting (transient neural coherence) within the calcarine significantly increased for 2–10 Hz activity. This was followed by a suppression of alpha activity (near 10 Hz) which persisted until the onset of the stimulus. The levels of phase-resetting, alpha suppression and subsequent behavioral performance varied between subjects in a systematic fashion. The magnitudes of phase-resetting and alpha-band power were negatively correlated, with high levels of coherence associated with high levels of performance. We propose that top–down attentional control mechanisms exert their initial effects within the calcarine through a phase-resetting within the 2–10 Hz band, which in turn triggers a suppression of alpha activity, priming early visual areas for incoming information and enhancing behavioral performance.

What determines innovation activity in Chinese state-owned enterprises? The role of foreign direct investment

We investigate whether inward foreign direct investment (FDI), either at the firm or industry level, has any impact on product innovation by Chinese state-owned enterprises (SOEs). We use a comprehensive firm-level panel data set of some 20,000 SOEs during 1999-2005. Our results show that foreign capital participation at the firm level is associated with higher innovative activity. Inward FDI in the sector, by contrast, has a negative effect on innovative activity in SOEs on average. However, there is a positive effect of sector-level FDI on SOEs that export, invest in human capital, or undertake R&D. © 2008 Elsevier Ltd. All rights reserved.

Foreign direct investment, access to finance, and innovation activity in Chinese enterprises

A recent, comprehensive database is used to investigate the link between inward foreign direct investment (FDI) and innovation activity in China. The results of the analysis suggest that private and collectively owned firms with foreign capital participation and those with good access to domestic bank loans innovate more than other firms do. Among enterprises not owned by the state, inward FDI at the sectoral level is positively associated with domestic innovative activity only among firms that engage in their own research and development or that have good access to domestic finance. At the sector level the effect of inward FDI into technology transfer is distinguished from the effect on domestic credit opportunities. FDI affecting credit is of little significance for state-owned enterprises and is independent of their access to finance. In contrast, better access to credit is an important channel through which FDI affects the innovation of domestic private and collectively owned enterprises.

Attentional modulation of oscillatory activity in human visual cortex

The effects of attentional modulation on activity within the human visual cortex were investigated using magnetoencephalography. Chromatic sinusoidal stimuli were used to evoke activity from the occipital cortex, with attention directed either toward or away from the stimulus using a bar-orientation judgment task. For five observers, global magnetic field power was plotted as a function of time from stimulus onset. The major peak of each function occurred at about 120 ms latency and was well modeled by a current dipole near the calcarine sulcus. Independent component analysis (ICA) on the non-averaged data for each observer also revealed one component of calcarine origin, the location of which matched that of the dipolar source determined from the averaged data. For two observers, ICA revealed a second component near the parieto-occipital sulcus. Although no effects of attention were evident using standard averaging procedures, time-varying spectral analyses of single trials revealed that the main effect of attention was to alter the level of oscillatory activity. Most notably, a sustained increase in alpha-band (7-12 Hz) activity of both calcarine and parieto-occipital origin was evident. In addition, calcarine activity in the range of 13-21 Hz was enhanced, while calcarine activity in the range of 5-6 Hz was reduced. Our results are consistent with the hypothesis that attentional modulation affects neural processing within the calcarine and parieto-occipital cortex by altering the amplitude of alpha-band activity and other natural brain rhythms. © 2003 Elsevier Inc. All rights reserved.

A study of inputs and their influence on technological innovative activity

Technological innovation has been widely studied: however surprisingly little is known about the experience of managing the process. Most reports tend to be generalistic and/or prescriptive whereas it is argued that multiple sources of variation in the process limit the value of these. A description of the innovation process is given together with a presentation of what is knovrn from existing studies. Gaps identified in this area suggest that a variety of organisational influences are important and an attempt is made to identify some of these at individual, group and organisational level. A simple system model of the innovation management process is developed. Further investigation of the influence of these factors was made possible through an extended on-site case study. Methodology for this based upon participant observation coupled wth a wide and flexible range of techniques is described. Evidence is presented about many aspects of the innovation process from a number of different levels and perspectives: the attempt is to demonstrate the extent to which variation due to contingent influences takes place. It is argued that problems identified all relate to the issue of integration. This theme is also developed from an analytical viewoint and it is suggested that organisational response to increases in complexity in the external environment will be to match them with internal complexity. Differentiation of this kind will require extensive and flexible integration, especially in those inherently uncertain areas associated with innovation. Whilst traditionally a function of management, it is argued that integration needs have increased to the point where a new specialism is required. The concept of integration specialist is developed from this analysis and attempts at simple integrative change during the research are described. Finally a strategy for integration - or rather for building in integrative capability - ln the organisation studied is described.

Inhibition of transglutaminase 2 enzymatic activity ameliorates the anti-angiogenic effects of coeliac disease autoantibodies

Objective. Earlier work has demonstrated that serum autoantibodies from coeliac patients targeted against transglutaminase 2 (TG2) inhibit in vitro angiogenesis. The aim of this study was to establish whether coeliac patient-derived monoclonal TG2-targeted antibodies produced by recombination technology exert similar anti-angiogenic effects to serum-derived coeliac autoantibodies. In addition, we studied whether the monoclonal patient autoantibodies modulate endothelial cell TG2 activity and whether such modulation is related to the anti-angiogenic effects. Material and methods. The influence of coeliac patient-derived monoclonal TG2-targeted antibodies on endothelial cell tubule formation was studied using a three-dimensional angiogenic cell culture model. Endothelial cell TG2 enzymatic activity was determined by means of a live-cell enzyme-linked immunosorbent assay. Results. Coeliac patient-derived monoclonal TG2-targeted antibodies produced by recombination technology inhibited endothelial tubule formation and enhanced the crosslinking activity of TG2. When this enzymatic activity was inhibited using site-directed irreversible TG2 inhibitors in the presence of autoantibodies, in vitro angiogenesis reverted to the control level. Conclusions. Since we found a significant negative correlation between endothelial cell angiogenesis and TG2 activity, we suggest that the anti-angiogenic effects of coeliac patient-derived TG2-targeted autoantibodies are exerted by enhanced enzymatic activity of TG2.

Do changes in transglutaminase activity alter latent transforming growth factor beta activation in experimental diabetic nephropathy?

Background. Diabetic nephropathy is the leading cause of end-stage kidney failure worldwide. It is characterized by excessive extracellular matrix accumulation. Transforming growth factor beta 1 (TGF-ß1) is a fibrogenic cytokine playing a major role in the healing process and scarring by regulating extracellular matrix turnover, cell proliferation and epithelial mesanchymal transdifferentiation. Newly synthesized TGF-ß is released as a latent, biologically inactive complex. The cross-linking of the large latent TGF-ß to the extracellular matrix by transglutaminase 2 (TG2) is one of the key mechanisms of recruitment and activation of this cytokine. TG2 is an enzyme catalyzing an acyl transfer reaction leading to the formation of a stable e(?-glutamyl)-lysine cross-link between peptides.Methods. To investigate if changes in TG activity can modulate TGF-ß1 activation, we used the mink lung cell bioassay to assess TGF-ß activity in the streptozotocin model of diabetic nephropathy treated with TG inhibitor NTU281 and in TG2 overexpressing opossum kidney (OK) proximal tubular epithelial cells.Results. Application of the site-directed TG inhibitor NTU281 caused a 25% reduction in kidney levels of active TGF-ß1. Specific upregulation of TG2 in OK proximal tubular epithelial cells increased latent TGF-ß recruitment and activation by 20.7% and 19.7%, respectively, in co-cultures with latent TGF-ß binding protein producing fibroblasts.Conclusions. Regulation of TG2 directly influences the level of active TGF-ß1, and thus, TG inhibition may exert a renoprotective effect by targeting not only a direct extracellular matrix deposition but also TGF-ß1 activation and recruitment.

Modulation of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase activity and oxidative modification during the development of adjuvant arthritis

Adjuvant arthritis (AA) was induced by intradermal administration of Mycobacterium butyricum to the tail of Lewis rats. In sarcoplasmic reticulum (SR) of skeletal muscles, we investigated the development of AA. SR Ca(2+)-ATPase (SERCA) activity decreased on day 21, suggesting possible conformational changes in the transmembrane part of the enzyme, especially at the site of the calcium binding transmembrane part. These events were associated with an increased level of protein carbonyls, a decrease in cysteine SH groups, and alterations in SR membrane fluidity. There was no alteration in the nucleotide binding site at any time point of AA, as detected by a FITC fluorescence marker. Some changes observed on day 21 appeared to be reversible, as indicated by SERCA activity, cysteine SH groups, SR membrane fluidity, protein carbonyl content and fluorescence of an NCD-4 marker specific for the calcium binding site. The reversibility may represent adaptive mechanisms of AA, induced by higher relative expression of SERCA, oxidation of cysteine, nitration of tyrosine and presence of acidic phospholipids such as phosphatidic acid. Nitric oxide may regulate cytoplasmic Ca(2+) level through conformational alterations of SERCA, and decreasing levels of calsequestrin in SR may also play regulatory role in SERCA activity and expression.

Modulation of network oscillatory activity and GABAergic synaptic transmission by CB1 cannabinoid receptors in the rat medial entorhinal cortex

Cannabinoids modulate inhibitory GABAergic neurotransmission in many brain regions. Within the temporal lobe, cannabinoid receptors are highly expressed, and are located presynaptically at inhibitory terminals. Here, we have explored the role of type-1 cannabinoid receptors (CB1Rs) at the level of inhibitory synaptic currents and field-recorded network oscillations. We report that arachidonylcyclopropylamide, an agonist at CB1R, inhibits GABAergic synaptic transmission onto both superficial and deep medial entorhinal (mEC) neurones, but this has little effect on network oscillations in beta/gamma frequency bands. By contrast, the CB1R antagonist/inverse agonist LY320135 (500?nM), increased GABAergic synaptic activity and beta/gamma oscillatory activity in superficial mEC, was suppressed, whilst that in deep mEC was enhanced. These data indicate that cannabinoid-mediated effects on inhibitory synaptic activity may be constitutively active in vitro, and that modulation of CB1R activation using inverse agonists unmasks complex effects of CBR function on network activity.

Peptidoglycan derived from Staphylococcus epidermidis induces Connexin43 hemichannel activity with consequences on the innate immune response in endothelial cells

Gram-positive bacterial cell wall components including PGN (peptidoglycan) elicit a potent pro-inflammatory response in diverse cell types, including endothelial cells, by activating TLR2 (Toll-like receptor 2) signalling. The functional integrity of the endothelium is under the influence of a network of gap junction intercellular communication channels composed of Cxs (connexins) that also form hemichannels, signalling conduits that are implicated in ATP release and purinergic signalling. PGN modulates Cx expression in a variety of cell types, yet effects in endothelial cells remain unresolved. Using the endothelial cell line b.End5, a 6 h challenge with PGN induced IL-6 (interleukin 6), TLR2 and Cx43 mRNA expression that was associated with enhanced Cx43 protein expression and gap junction coupling. Cx43 hemichannel activity, measured by ATP release from the cells, was induced following 15 min of exposure to PGN. Inhibition of hemichannel activity with carbenoxolone or apyrase prevented induction of IL-6 and TLR2 mRNA expression by PGN, but had no effect on Cx43 mRNA expression levels. In contrast, knockdown of TLR2 expression had no effect on PGN-induced hemichannel activity, but reduced the level of TLR2 and Cx43 mRNA expression following 6 h of PGN challenge. PGN also acutely induced hemichannel activity in HeLa cells transfected to express Cx43, but had no effect in Cx43-deficient HeLa OHIO cells. All ATP responses were blocked with Cx-specific channel blockers. We conclude that acute Cx43 hemichannel signalling plays a role in the initiation of early innate immune responses in the endothelium.

Decreased NADPH oxidase expression and antioxidant activity in cachectic skeletal muscle

Background - Cancer cachexia is the progressive loss of skeletal muscle protein that contributes significantly to cancer morbidity and mortality. Evidence of antioxidant attenuation and the presence of oxidised proteins in patients with cancer cachexia indicate a role for oxidative stress. The level of oxidative stress in tissues is determined by an imbalance between reactive oxygen species production and antioxidant activity. This study aimed to investigate the superoxide generating NADPH oxidase (NOX) enzyme and antioxidant enzyme systems in murine adenocarcinoma tumour-bearing cachectic mice. Methods - Superoxide levels, mRNA levels of NOX enzyme subunits and the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidise (GPx) and catalase was measured in the skeletal muscle of mice with cancer and cancer cachexia. Protein expression levels of NOX enzyme subunits and antioxidant enzyme activity was also measured in the same muscle samples. Results - Superoxide levels increased 1.4-fold in the muscle of mice with cancer cachexia, and this was associated with a decrease in mRNA of NOX enzyme subunits, NOX2, p40phox and p67phox along with the antioxidant enzymes SOD1, SOD2 and GPx. Cancer cachexia was also associated with a 1.3-fold decrease in SOD1 and 2.0-fold decrease in GPx enzyme activity. Conclusion - Despite increased superoxide levels in cachectic skeletal muscle, NOX enzyme subunits, NOX2, p40phox and p67phox, were downregulated along with the expression and activity of the antioxidant enzymes. Therefore, the increased superoxide levels in cachectic skeletal muscle may be attributed to the reduction in the activity of endogenous antioxidant enzymes.