The citrus flavanone naringenin inhibits inflammatory signalling in glial cells and protects against neuroinflammatory injury

Neuroinflammation plays an integral role in the progression of neurodegeneration. In this study we investigated the anti-inflammatory effects of different classes of flavonoids (flavanones, flavanols and anthocyanidins) in primary mixed glial cells. We found that the flavanones naringenin and hesperetin and the flavols (+)-catechin and (-)-epicatechin, but not the anthocyanidins cyanidin and pelargonidin, attenuated LPS/IFN-gamma-induced TNF-alpha production in glial cells. Naringenin also inhibited LPS/IFN-gamma-induced iNOS expression and nitric oxide production in glial cells, thus showing the strongest antiinflammatory activity among all flavonoids tested. Moreover, naringenin protected against inflammatory-induced neuronal death in a primary neuronal-glial co-culture system. Naringenin also inhibited LPS/IFN-gamma-induced p38 mitogen-activated protein kinase (MAPK) phosphorylation and downstream signal transducer and activator of transcription-1 (STAT-1) in LPS/IFN-gamma stimulated primary mixed glial cells. Taken together, our results suggest that naringenin may produce an anti-inflammatory effect in LPS/IFN-gamma stimulated glial cells that may be due to its interaction with p38 signalling cascades and the STAT-I trascription factor. (C) 2009 Elseiver Inc. All rights reserved.

Relationship between sublethal injury and microbial inactivation by the combination of high hydrostatic pressure and citral or tert-butyl hydroquinone

The aim was to investigate (i) the occurrence of sublethal injury in Listeria monocytogenes, Escherichia coli, and Saccharomyces cerevisiae after high hydrostatic pressure (HHP) treatment as a function of the treatment medium pH and composition and (ii) the relationship between the occurrence of sublethal injury and the inactivating effect of a combination of HHP and two antimicrobial compounds, tert-butyl hydroquinone (TBHQ) and citral. The three microorganisms showed a high proportion of sublethally injured cells (up to 99.99% of the surviving population) after HHP. In E. coli and L. monocytogenes, the extent of inactivation and sublethal injury depended on the pH and the composition of the treatment medium, whereas in S. cerevisiae, inactivation and sublethal injury were independent of medium pH or composition under the conditions tested. TBHQ alone was not lethal to E. coli or L. monocytogenes but acted synergistically with HHP and 24-h refrigeration, resulting in a viability decrease of >5 log(10) cycles of both organisms. The antimicrobial effect of citral depended on the microorganism and the treatment medium pH. Acting alone for 24 h under refrigeration, 1,000 ppm of citral caused a reduction of 5 log(10) cycles of E. coli at pH 7.0 and almost 3 log(10) cycles of L. monocytogenes at pH 4.0. The combination of citral and HHP also showed a synergistic effect. Our results have confirmed that the detection of sublethal injury after HHP may contribute to the identification of those treatment conditions under which HHP may act synergistically with other preserving processes.

Modulation of peroxynitrite-induced fibroblast injury by hesperetin: a role for intracellular scavenging and modulation of ERK signalling

Peroxynitrite is thought to contribute to the progression of many diseases including cardiovascular disease, cancer, and neurodegenerative disorders. We report that pre-treatment of fibroblasts with the citrus flavanone, hesperetin, prior to peroxynitrite exposure protects against peroxynitrite-mediated cytotoxicity. This protection was partially mediated by the intracellular scavenging of peroxynitrite by hesperctin as exposure of fibroblasts to peroxynitrite following hesperetin loading led to the formation of two intracellular nitrohesperetin derivatives. In addition, protection appeared to be mediated by hesperetin-induced changes in MAP kinase signalling. Exposure of fibroblasts to hesperetin led to concentration-dependent increases in the phosphorylation of ERK1/2 and was observed to restore peroxynitrite-mediated decreases in ERK1/2 phosphorylation. We propose that the protective potential of hesperetin in fibroblasts may be mediated both by intracellular scavenging of peroxynitrite and by modulation of fibroblast signalling. (c) 2006 Elsevier Inc. All rights reserved.

Activation of glutathione peroxidase via Nrf1 mediates genistein's protection against oxidative endothelial cell injury

Cellular actions of isoflavones may mediate the beneficial health effects associated with high soy consumption. We have investigated protection by genistein and daidzein against oxidative stress-induced endothelial injury. Genistein but not daidzein protected endothelial cells from damage induced by oxidative stress. This protection was accompanied by decreases in intracellular glutathione levels that could be explained by the generation of glutathionyl conjugates of the oxidised genistein metabolite, 5,7,3',4'-tetrahydroxyisoflavone. Both isoflavones evoked increased protein expression of gamma-glutamylcysteine synthetase-heavy subunit (gamma-GCS-HS) and increased cytosolic accumulation and nuclear translocation of Nrf2. However, only genistein led to increases in the cytosolic accumulation and nuclear translocation of Nrf1 and the increased expression of and activity of glutathione peroxidase. These results suggest that genistein-induced protective effects depend primarily on the activation of glutathione peroxidase mediated by Nrf1 activation, and not on Nrf2 activation or increases in glutathione synthesis. (c) 2006 Elsevier Inc. All rights reserved.

Problems in the coupling of eye and hand in the sequential movements of children with developmental coordination disorder

Background: Shifting gaze and attention ahead of the hand is a natural component in the performance of skilled manual actions. Very few studies have examined the precise co-ordination between the eye and hand in children with Developmental Coordination Disorder (DCD). Methods This study directly assessed the maturity of eye-hand co-ordination in children with DCD. A double-step pointing task was used to investigate the coupling of the eye and hand in 7-year-old children with and without DCD. Sequential targets were presented on a computer screen, and eye and hand movements were recorded simultaneously. Results There were no differences between typically developing (TD) and DCD groups when completing fast single-target tasks. There were very few differences in the completion of the first movement in the double-step tasks, but differences did occur during the second sequential movement. One factor appeared to be the propensity for the DCD children to delay their hand movement until some period after the eye had landed on the target. This resulted in a marked increase in eye-hand lead during the second movement, disrupting the close coupling and leading to a slower and less accurate hand movement among children with DCD. Conclusions In contrast to skilled adults, both groups of children preferred to foveate the target prior to initiating a hand movement if time allowed. The TD children, however, were more able to reduce this foveation period and shift towards a feedforward mode of control for hand movements. The children with DCD persevered with a look-then-move strategy, which led to an increase in error. For the group of DCD children in this study, there was no evidence of a problem in speed or accuracy of simple movements, but there was a difficulty in concatenating the sequential shifts of gaze and hand required for the completion of everyday tasks or typical assessment items.

Eye-movements aid the control of locomotion

Eye-movements have long been considered a problem when trying to understand the visual control of locomotion. They transform the retinal image from a simple expanding pattern of moving texture elements (pure optic flow), into a complex combination of translation and rotation components (retinal flow). In this article we investigate whether there are measurable advantages to having an active free gaze, over a static gaze or tracking gaze, when steering along a winding path. We also examine patterns of free gaze behavior to determine preferred gaze strategies during active locomotion. Participants were asked to steer along a computer-simulated textured roadway with free gaze, fixed gaze, or gaze tracking the center of the roadway. Deviation of position from the center of the road was recorded along with their point of gaze. It was found that visually tracking the middle of the road produced smaller steering errors than for fixed gaze. Participants performed best at the steering task when allowed to sample naturally from the road ahead with free gaze. There was some variation in the gaze strategies used, but sampling was predominantly of areas proximal to the center of the road. These results diverge from traditional models of flow analysis.

Theory of mind in children with traumatic brain injury

Objective: This study was designed to examine the existence of deficits in mentalizing or theory of mind (ToM) in children with traumatic brain injury (TBI). Research design: ToM functioning was assessed in 12 children aged 6-12 years with TBI and documented frontal lobe damage and compared to 12 controls matched for age, sex and verbal ability. Brief measures of attention and memory were also included. Main outcome and results: The TBI group was significantly impaired relative to controls on the advanced ToM measure and a measure of basic emotion recognition. No difference was found in a basic measure of ToM. Conclusion: Traumatic brain damage in childhood may disrupt the developmental acquisition of emotion recognition and advanced ToM skills. The clinical and theoretical importance of these findings is discussed and the implications for the assessment and treatment of children who have experienced TBI are outlined.

The integration of figurative language and static depictions: an eye movement study of fictive motion

Do we view the world differently if it is described to us in figurative rather than literal terms? An answer to this question would reveal something about both the conceptual representation of figurative language and the scope of top-down influences oil scene perception. Previous work has shown that participants will look longer at a path region of a picture when it is described with a type of figurative language called fictive motion (The road goes through the desert) rather than without (The road is in the desert). The current experiment provided evidence that such fictive motion descriptions affect eye movements by evoking mental representations of motion. If participants heard contextual information that would hinder actual motion, it influenced how they viewed a picture when it was described with fictive motion. Inspection times and eye movements scanning along the path increased during fictive motion descriptions when the terrain was first described as difficult (The desert is hilly) as compared to easy (The desert is flat); there were no such effects for descriptions without fictive motion. It is argued that fictive motion evokes a mental simulation of motion that is immediately integrated with visual processing, and hence figurative language can have a distinct effect on perception. (c) 2005 Elsevier B.V. All rights reserved.

The art of conversation is coordination: common ground and the coupling of eye movements during dialogue

When two people discuss something they can see in front of them, what is the relationship between their eye movements? We recorded the gaze of pairs of subjects engaged in live, spontaneous dialogue. Cross-recurrence analysis revealed a coupling between the eye movements of the two conversants. In the first study, we found their eye movements were coupled across several seconds. In the second, we found that this coupling increased if they both heard the same background information prior to their conversation. These results provide a direct quantification of joint attention during unscripted conversation and show that it is influenced by knowledge in the common ground.

Saccadic eye movements as an index of perceptual decision-making

One of the most common decisions we make is the one about where to move our eyes next. Here we examine the impact that processing the evidence supporting competing options has on saccade programming. Participants were asked to saccade to one of two possible visual targets indicated by a cloud of moving dots. We varied the evidence which supported saccade target choice by manipulating the proportion of dots moving towards one target or the other. The task was found to become easier as the evidence supporting target choice increased. This was reflected in an increase in percent correct and a decrease in saccade latency. The trajectory and landing position of saccades were found to deviate away from the non-selected target reflecting the choice of the target and the inhibition of the non-target. The extent of the deviation was found to increase with amount of sensory evidence supporting target choice. This shows that decision-making processes involved in saccade target choice have an impact on the spatial control of a saccade. This would seem to extend the notion of the processes involved in the control of saccade metrics beyond a competition between visual stimuli to one also reflecting a competition between options.

The effect of a perceptual cognitive task on exercise performance: the dual-task condition after brain injury

Objective: To examine the effect of additional cognitive demand on cycling performance in individuals with acquired brain injury (ABI). Design: Prospective observational study. Setting: Rivermead Rehabilitation Centre. Participants: Ten individuals with ABI ( 7 men, 3 women) ( traumatic brain injury 7, tumour 1, stroke 2) and 10 healthy controls ( 6 men, 4 women). Intervention: Individuals were asked to maintain a set cadence during a three-stage incremental cycling test in both single-task ( no additional task) and dual-task ( whilst performing an additional cognitive task) conditions. Results: The ABI group showed a slight slowing in cadence in stages 1 and 3 of the graded exercise test from the single-to the dual-task condition, although this was not significant ( p less than or equal to 0.05). The control group showed no slowing of cadence at any incremental stage. When directly comparing the ABI with the control group, the change in cadence observed in dual-task conditions was only significantly different in stage 3 ( p less than or equal to 0.05). Conclusions: Clinicians should be aware of the possibility that giving additional cognitive tasks ( such as monitoring exercise intensity) while individuals with acquired brain injury are performing exercises may detrimentally affect performance. The effect may be more marked when the individuals are performing exercise at higher intensities.

Eye-tracking for avatar eye-gaze and interactional analysis in immersive collaborative virtual environments

Participants' eye-gaze is generally not captured or represented in immersive collaborative virtual environment (ICVE) systems. We present EyeCVE. which uses mobile eye-trackers to drive the gaze of each participant's virtual avatar, thus supporting remote mutual eye-contact and awareness of others' gaze in a perceptually unfragmented shared virtual workspace. We detail trials in which participants took part in three-way conferences between remote CAVE (TM) systems linked via EyeCVE. Eye-tracking data was recorded and used to evaluate interaction, confirming; the system's support for the use of gaze as a communicational and management resource in multiparty conversational scenarios. We point toward subsequent investigation of eye-tracking in ICVEs for enhanced remote social-interaction and analysis.

Communicating eye gaze across a distance without rooting participants to the spot

Eye gaze is an important conversational resource that until now could only be supported across a distance if people were rooted to the spot. We introduce EyeCVE, the worldpsilas first tele-presence system that allows people in different physical locations to not only see what each other are doing but follow each otherpsilas eyes, even when walking about. Projected into each space are avatar representations of remote participants, that reproduce not only body, head and hand movements, but also those of the eyes. Spatial and temporal alignment of remote spaces allows the focus of gaze as well as activity and gesture to be used as a resource for non-verbal communication. The temporal challenge met was to reproduce eye movements quick enough and often enough to interpret their focus during a multi-way interaction, along with communicating other verbal and non-verbal language. The spatial challenge met was to maintain communicational eye gaze while allowing free movement of participants within a virtually shared common frame of reference. This paper reports on the technical and especially temporal characteristics of the system.

Visual eye disease simulator

Visually impaired people have a very different view of the world such that seemingly simple environments as viewed by a ‘normally’ sighted people can be difficult for people with visual impairments to access and move around. This is a problem that can be hard to fully comprehend by people with ‘normal vision’ even when guidelines for inclusive design are available. This paper investigates ways in which image processing techniques can be used to simulate the characteristics of a number of common visual impairments in order to provide, planners, designers and architects, with a visual representation of how people with visual impairments view their environment, thereby promoting greater understanding of the issues, the creation of more accessible buildings and public spaces and increased accessibility for visually impaired people in everyday situations.