Physical activity and strength of the femoral neck during the adolescent growth spurt: A longitudinal analysis

Loading of the femoral neck (FN) is dominated by bending and compressive stresses. We hypothesize that adaptation of the FN to physical activity would be manifested in the cross-sectional area (CSA) and section modulus (Z) of bone, indices of axial and bending strength, respectively. We investigated the influence of physical activity on bone strength during adolescence using 7 years of longitudinal data from 109 boys and 121 girls from the Saskatchewan Paediatric Bone and Mineral Accrual Study (PBMAS). Physical activity data (PAC-Q physical activity inventory) and anthropometric measurements were taken every 6 months and DXA bone scans were measured annually (Hologic QDR2000, array mode). We applied hip structural analysis to derive strength and geometric indices of the femoral neck using DXA scans. To control for maturation, we determined a biological maturity age defined as years from age at peak height velocity (APHV). To account for the repeated measures within individual nature of longitudinal data, multilevel random effects regression analyses were used to analyze the data. When biological maturity age and body size (height and weight) were controlled, in both boys and girls, physical activity was a significant positive independent predictor of CSA and Z of the narrow region of the femoral neck (P < 0.05). There was no independent effect of physical activity on the subperiosteal width of the femoral neck. When leg length and leg lean mass were introduced into the random effects models to control for size and muscle mass of the leg (instead of height and weight), all significant effects of physical activity disappeared. Even among adolescents engaged in normal levels of physical activity, the statistically significant relationship between physical activity and indices of bone strength demonstrate that modifiable lifestyle factors like exercise play an important role in optimizing bone strength during the growing years. Physical activity differences were explained by the interdependence between activity and lean mass considerations. Physical activity is important for optimal development of bone strength. (c) 2005 Elsevier Inc. All rights reserved.

Summer dormancy in Dactylis glomerata L.: the influence of season of sowing and a simulated mid-summer storm on two contrasting cultivars

A series of trials to increase understanding of the summer dormancy trait in Dactylis glomerata was conducted. Autumn-sown reproductive and younger, spring-sown plants of 2 drought-resistant cultivars, contrasting for summer dormancy, were established and then tested in summer 2002 under long drought, drought + midsummer storm, or full irrigation. The autumn-sown reproductive plants of cv. Kasbah were summer dormant under all moisture regimes and exhibited the characteristic traits including growth cessation, rapid herbage senescence, and dehydration of surviving organs (-6.7MPa). Cultivar Kasbah used 8% less soil water over the summer and also began to rehydrate its leaf bases from conserved soil water before the drought broke. The non-dormant cv. Medly grew for 10 days longer under drought and whenever moisture was applied; Medly also responded to the storm with a decline in dehydrin expression in leaf bases, whereas no decline occurred in Kasbah, presumably because it remained dormant and therefore much drier. The irrigated, younger, spring-sown swards of cv. Kasbah had restrained growth and produced only about 25% of the herbage of cv. Medly. Drought reduced activity and growth of young plants of both cultivars, but whereas Medly regrew in response to the storm, cv. Kasbah did not, indicating that dormancy, although only partially expressed after spring sowing, was reinforced by summer drought. A longer drought in 2003 caused a 22% loss of the basal cover in cv. Medly, whereas Kasbah fully maintained its sward and therefore produced a higher post-drought autumn yield. This work confirms summer dormancy as a powerful trait for improving persistence over long, dry summers.

Modulation of channel activity and gadolinium block of MscL by static magnetic fields

The magnetic field of the Earth has for long been known to influence the behaviour and orientation of a variety of living organisms. Experimental studies of the magnetic sense have, however, been impaired by the lack of a plausible cellular and/or molecular mechanism providing meaningful explanation for detection of magnetic fields by these organisms. Recently, mechanosensitive (MS) ion channels have been implied to play a role in magnetoreception. In this study we have investigated the effect of static magnetic fields (SMFs) of moderate intensity on the activity and gadolinium block of MscL, the bacterial MS channel of large conductance, which has served as a model channel to study the basic physical principles of mechanosensory transduction in living cells. In addition to showing that direct application of the magnetic field decreased the activity of the MscL channel, our study demonstrates for the first time that SMFs can reverse the effect of gadolinium, a well-known blocker of MS channels. The results of our study are consistent with a notion that (1) the effects of SMFs on the MscL channels may result from changes in physical properties of the lipid bilayer due to diamagnetic anisotropy of phospholipid molecules and consequently (2) cooperative superdiamagnetism of phospholipid molecules under influence of SMFs could cause displacement of Gd3+ stop ions from the membrane bilayer and thus remove the MscL channel block.

The influence of diet on protein oxidation

Protein oxidation can be perceived as essential for the control of intracellular signalling and gene expression on the one hand, but in contrast, a potentially cytotoxic hazard of aerobic life. Reduction and oxidation of thiol groups on specific cysteine residues can act as critical molecular switches, in modulating response to growth factors, apoptotic and inflammatory stimuli to name a few. Such oxidative reactions are likely to be transient and represent low levels of oxidative modification to a protein. Sustained oxidative stress conditions through absence of essential dietary antioxidant or low activity of endogenous enzyme scavengers can cause irreversible damage and loss of function. Such modifications are believed to be important in many diseases associated with ageing. Therefore, it has been postulated that diet may exert an influence on the steady state of protein oxidation and thus offer potential health benefits through preservation of normal protein function. In the present paper, the current evidence from in vivo studies on the effects of dietary antioxidants and oxidants on protein oxidation will be evaluated, and needs for future research will be highlighted.

Attentional shifts towards an expected visual target alter the level of alpha-band oscillatory activity in the human calcarine cortex

Neuronal operations associated with the top-down control process of shifting attention from one locus to another involve a network of cortical regions, and their influence is deemed fundamental to visual perception. However, the extent and nature of these operations within primary visual areas are unknown. In this paper, we used magnetoencephalography (MEG) in combination with magnetic resonance imaging (MRI) to determine whether, prior to the onset of a visual stimulus, neuronal activity within early visual cortex is affected by covert attentional shifts. Time/frequency analyses were used to identify the nature of this activity. Our results show that shifting attention towards an expected visual target results in a late-onset (600 ms postcue onset) depression of alpha activity which persists until the appearance of the target. Independent component analysis (ICA) and dipolar source modeling confirmed that the neuronal changes we observed originated from within the calcarine cortex. Our results further show that the amplitude changes in alpha activity were induced not evoked (i.e., not phase-locked to the cued attentional task). We argue that the decrease in alpha prior to the onset of the target may serve to prime the early visual cortex for incoming sensory information. We conclude that attentional shifts affect activity within the human calcarine cortex by altering the amplitude of spontaneous alpha rhythms and that subsequent modulation of visual input with attentional engagement follows as a consequence of these localized changes in oscillatory activity. © 2005 Elsevier B.V. All rights reserved.

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.

The activity of pH membrane disruptive pseudopeptides and their subcellular fate in mammalian cells cultured in-vitro

This thesis describes investigations upon pseudopeptides which were conducted to improve our understanding of the fate of synthetic macromolecules in cells and to develop approaches to influence that fate. The low uptake of molecules across the external cellular membrane is the principal barrier against effective delivery of therapeutic products to within the cell structure. In nature, disruption of this membrane by amphiphilic peptides plays a central role in the pathogenesis by bacterial and toxin infections. These amphiphilic peptides contain both hydrophobic and weakly charged hydrophilic amino acid residues and upon activation they become integrated into the lipid bilayers of the extracellular or endosomal membranes. The architectures of the pseudopeptides described here were designed to display similar pH dependent membrane rupturing activity to that of peptides derived from the influenza virus hemagglutinin HA-2. This HA protein promotes fusion of the influenza virus envelope with the cell endosome membrane due to a change in conformation in response to the acidic pH of the endosome lumen (pH 5.0-6.0). The pseudopeptides were obtained by the copolymerisation of L-lysine and L-lysine ethyl-ester with various dicarboxylic acid moieties. In this way a linear polyamide comprising of alternating pendant carboxylic acids and pendant hydrophobic moieties was made. At physiological pH (pH 7.4), electrostatic repulsion of pendant anionic carboxyl groups along the polymer backbone is sufficient to overcome the intramolecular association of the hydrophobic groups resulting in an extended conformation. At low pH (typically pH 4.8) loss of charge results in increased intramolecular hydrophobic association and the polymer chain collapses to a compact conformation, leading to precipitation of the polymer. Consequently, a conformation dependent functional property could be made to respond to small changes in the environmental pH. Pseudopepides were investigated for their cytoxicity towards a well known cell line, namely C26 (colorectal adenocarcinoma) and were shown through the use of a cell viability assay, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide) to be well tolerated by C26 cells over a range of concentrations (2-500,μg/ml) at physiological pH (pH 7.4). A modified version of a shorter 30-minute coupled enzymatic assay, the LDH (lactate dehydrogenase) assay was used to evaluate the ability of the pseudopeptides to disrupt the membrane of two different cell lines (COS-1; African green monkey, kidney and A2780; human ovarian carcinoma) at low pH (pH 5.5). The cell membrane disruption property of the pseudopeptides was successfully demonstrated for COS-I and A2780 cell lines at this pH (pH 5.5). A variety of cell lines were chosen owing to limited availability and to compare the cytotoxic action of these pH responsive psudopeptides towards normal and tumorogenic cell lines. To investigate the intracellular delivery of one of the pseudopeptides, poly (L-lysine iso-phthalamide) and its subcellular location, a Cy3 bisamine fluorophore was conjugated into its backbone, at ratios of dye:lysine of 1:20, 1:30, 1:40, 1:60 and 1:80. Native polyacrylacrylamide gel electrophoresis (PAGE) and high voltage paper electrophoresis (HVPE) studies of the polydyes were conducted and provided evidence that that the Cy3 bisamine fluorophore was conjugated into the backbone of the polymer, poly (L-lysine iso-phthalamide). The subcellular fate of the fluorescentlylabelled "polydye" (hereafter PD20) was monitored by laser scanning confocal microscopy (LSCM) in CHO (Chinese hamster ovary) cells cultured in-vitro at various pH values (pH 7.4 and 5.0). LSCM images depicting time-dependent internalisation of PD20 indicated that PD20 traversed the extracellular membrane of CHO cells cultured in-vitro within ten minutes and migrated towards the endosomal regions where the pH is in the region of 5.0 to 6.0. Nuclear localisation of PD20 was demonstrated in a subpopulation of CHO cells. A further study was completed in CHO and HepG2 (hepatocellular carcinoma) cells cultured in-vitro using a lower molecular weight polymer to demonstrate that the molecular weight of "polydye" could be tailored to attain nuclear trafficking in cells. Prospective use of this technology encompasses a method of delivering a payload into a living cell based upon the hypercoiling nature of the pseudopeptides studied in this thesis and has led to a patent application (GB0228525.2; 20(2).

Optical activity in photorefractive Bi12TiO20

The influence of optical activity on two-wave mixing (TWM) in photorefractive BTO and BSO crystals in the absence of an applied field is studied both theoretically and experimentally. For the conventinal orientations of the grating vector, K [001] and K[001], the piezoelectric and photoelastic effects are either zero or negligible. This makes an analytical treatment of the TWM problem possible. We obtain an analytical solution for the coupled wave equations of TWM valid for arbitrary optical activity. This result is of special importance for BTO crystals. In these crystals under the condition of maximum energy transfer (|K|rD=1, where rD is the Debye radius) neither the approximation of small optical activity nor the one of dominating optical activity is applicable and our analytical solution becomes essential. Our experimental setup uses beams with a trapezoidal overlap that allows us to study the thickness-dependence of the gain in a single measurement. Experimental and theoretical results for a BTO crystal are compared with those for a BSO crystal and are explained in the framework of the model used.

The effects of negative affectivity on self-reported activity limitations in stroke patients:testing the symptom perception, disability and psychosomatic hypotheses

This study investigated whether Negative Affectivity (NA) causes bias in self-report measures of activity limitations or whether NA has a real, non-artifactual association with activity limitations. The Symptom Perception Hypothesis (NA negatively biases self-reporting), Disability Hypothesis (activity limitations cause NA) and Psychosomatic Hypothesis (NA causes activity limitations) were examined longitudinally using both self-report and objective activity limitations measures. Participants were 101 stroke patients and their caregivers interviewed within two weeks of discharge, six weeks later and six months post-discharge. NA and self-report, proxy-report and observed performance activity (walking) limitations were assessed at each interview. NA was associated with activity limitations across measures. Both the Disability and Psychosomatic Hypotheses were supported: initial NA predicted objective activity limitations at six weeks but, additionally, activity limitations at six weeks predicted NA at six months. These results suggest that NA both affects and is affected by activity limitations and does not simply influence reporting.

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.

Influence of ethical beliefs, national culture and institutions on preferences for HRM in Oman

Purpose – The paper seeks to investigate the association between ethical beliefs, aspects of national culture and national institutions, and preferences for specific human resource management practices in the Sultanate of Oman. Design/methodology/approach – A total of 712 individuals working in six organisations (both private and public sectors) responded to a self-administered questionnaire in the Sultanate of Oman. To test the raised research questions of the proposed framework, the methodology of structural equation models was used. Findings – The results highlight significant differences in the belief systems on the basis of different demographic characteristics. The findings also confirm impact of ethical beliefs, and aspects of national culture and national institutions on preferences for human resource management (HRM) practices. Research limitations/implications – Although the goodness-of-fit indexes confirmed the validity of the proposed operational model, some indices were attained at rather flexible levels. Practical implications – Studies on managerial beliefs and values can offer important insights into the extent that work is viewed as an integral life activity. Such information can help differentiate among managerial styles in various cultures, and in predicting managerial behaviour such as ethical decision-making. Based on such understanding, the findings can be used to educate government officials and outside consultants interested in Oman. Originality/value – The study contributes to the accumulation of knowledge about under-researched developing countries such as Oman, as limited data are available on HRM, value orientations and ethical beliefs' issues in this region.

Corporate political activity in less developed countries:The Volta River Project in Ghana, 1958-66

The article expands existing categorisations of political and economic governance by including literature on less developed countries (LDCs). In four consecutive negotiations between the US multinational Kaisers and the US and Ghana governments in the early 1960s, it is argued that the company reached levels of influence that are at odds with existing explanations. In order to understand corporate political activities in LDCs, analysis needs to go beyond static factors (political risk) and include dynamic factors such as diplomatic relations and 'arenas of power', and consider the role of the investor's home country relative to the host economy.

Optical activity in photorefractive Bi12TiO20

The influence of optical activity on two-wave mixing (TWM) in photorefractive BTO and BSO crystals in the absence of an applied field is studied both theoretically and experimentally. For the conventinal orientations of the grating vector, K [001] and K[001], the piezoelectric and photoelastic effects are either zero or negligible. This makes an analytical treatment of the TWM problem possible. We obtain an analytical solution for the coupled wave equations of TWM valid for arbitrary optical activity. This result is of special importance for BTO crystals. In these crystals under the condition of maximum energy transfer (|K|rD=1, where rD is the Debye radius) neither the approximation of small optical activity nor the one of dominating optical activity is applicable and our analytical solution becomes essential. Our experimental setup uses beams with a trapezoidal overlap that allows us to study the thickness-dependence of the gain in a single measurement. Experimental and theoretical results for a BTO crystal are compared with those for a BSO crystal and are explained in the framework of the model used.

The influence of pH and fluid dynamics on the antibacterial efficacy of 45S5 Bioglass

In recent years, there has been considerable interest in the potential antibacterial properties that bioactive glasses may possess. However, there have been several conflicting reports on the antibacterial efficacy of 45S5 Bioglass®. Various mechanisms regarding its mode of action have been proposed, such as changes in the environmental pH, increased osmotic pressure, and ‘needle like’ sharp glass debris which could potentially damage prokaryotic cell walls and thus inactivate bacteria. In this current study, a systematic investigation was undertaken on the antibacterial efficacy of 45S5 Bioglass® on Escherichia coli NCTC 10538 and Staphylococcus aureus ATCO 6538 under a range of clinically relevant scenarios including varying Bioglass® concentration, direct and indirect contact between Bioglass® and microorganisms, static and shaking incubation conditions, elevated and neutralised pH environments. The results demonstrated that under elevated pH conditions, Bioglass® particles has no antibacterial effect on S. aureus whilst, a concentration dependent antibacterial effect against E. coli was observed. However, the antibacterial activity ceased when the pH of the media was neutralised. The results of this current study therefore suggest that the mechanism of antibacterial activity of Bioglass® is associated with changes in the environmental pH; an environment that is less likely to occur in vivo due to buffering of the system.

Examining the influence of fame in the presence of beauty:an electrodermal 'neuromarketing' study

The use of famous and/or attractive models in brand marketing is ubiquitous yet little work, if any, has been carried out examining differences in their efficiency in driving subsequent consumer behaviour. Such brand platforms have an emotional selling proposition (ESP) that refers to the unique personality and image attributes that a particular endorsement generates. However, celebrity endorsers are also more than likely to be considered attractive and thus differences in the ESP (if any) would be very small. Such differences in an emotional response could be measured by a participant's electrodermal activity (EDA). This is a psychophysiological response, measurement of which is sensitive enough to detect differences engendered by a particular brand platform's ESP. In the present study, EDA measurements were recorded from participants who were shown advertisements containing a target product within four different types of endorsement platforms depicting models who were either famous/non-famous or attractive/average looking. The results showed that average looking celebrity endorsers produced a greater EDA response than any of the other conditions including the attractive looking celebrity endorsers. Furthermore, this effect was only revealed from recordings taken from the left hand side of the participants. Given that the right side of the brain would orchestrate any EDA responses recorded from the subjects' left side, the current results suggest a dedicated neural response for celebrity endorsed brand platforms. Future work examining the relationship between the specific EDA signature and consumer preferences is discussed.