Minimum recovery time between reactive hyperemia stimulus in the repeated measurement of brachial flow-mediated dilatation.

The ability to undertake repeat measurements of flow-mediated dilatation (FMD) within a short time of a previous measurement would be useful to improve accuracy or to repeat a failed initial procedure. Although standard methods report that a minimum of 10 min is required between measurements, there is no published data to support this. Thirty healthy volunteers had five FMD measurements performed within a 2-h period, separated by various time intervals (5, 15 and 30 min). In 19 volunteers, FMD was also performed as soon as the vessel had returned to its baseline diameter. There was no significant difference between any of the FMD measurements or parameters across the visits indicating that repeat measurements may be taken after a minimum of 5 min or as soon as the vessel has returned to its baseline diameter, which in some subjects may be less than 5 min.

View-based modelling of human visual navigation errors

View-based and Cartesian representations provide rival accounts of visual navigation in humans, and here we explore possible models for the view-based case. A visual “homing” experiment was undertaken by human participants in immersive virtual reality. The distributions of end-point errors on the ground plane differed significantly in shape and extent depending on visual landmark configuration and relative goal location. A model based on simple visual cues captures important characteristics of these distributions. Augmenting visual features to include 3D elements such as stereo and motion parallax result in a set of models that describe the data accurately, demonstrating the effectiveness of a view-based approach.

Riluzole neuroprotection in a parkinson’s disease model involves suppression of reactive astrocytosis but not GLT-1 regulation

Background Riluzole is a neuroprotective drug used in the treatment of motor neurone disease. Recent evidence suggests that riluzole can up-regulate the expression and activity of the astrocyte glutamate transporter, GLT-1. Given that regulation of glutamate transport is predicted to be neuroprotective in Parkinson's disease, we tested the effect of riluzole in parkinsonian rats which had received a unilateral 6-hydroxydopamine injection into the median forebrain bundle. Results Rats were treated with intraperitoneal riluzole (4 mg/kg or 8 mg/kg), 1 hour before the lesion then once daily for seven days. Riluzole produced a modest but significant attenuation of dopamine neurone degeneration, assessed by suppression of amphetamine-induced rotations, preservation of tyrosine hydroxylase positive neuronal cell bodies in the substantia nigra pars compacta and attenuation of striatal tyrosine hydroxylase protein loss. Seven days after 6-hydroxydopamine lesion, reactive astrocytosis was observed in the striatum, as determined by increases in expression of glial fibrillary acidic protein, however the glutamate transporter, GLT-1, which is also expressed in astrocytes was not regulated by the lesion. Conclusions The results confirm that riluzole is a neuroprotective agent in a rodent model of parkinson’s disease. Riluzole administration did not regulate GLT-1 levels but significantly reduced GFAP levels, in the lesioned striatum. Riluzole suppression of reactive astrocytosis is an intriguing finding which might contribute to the neuroprotective effects of this drug.

APOE genotype influences triglyceride and C-reactive protein responses to altered dietary fat intake in UK adults

Background: The response of plasma lipids to dietary fat manipulation is highly heterogeneous, with some indications that APOE genotype may be important. Objective: The objective was to use a prospective recruitment approach to determine the effect of dietary fat quantity and composition on both lipid and nonlipid cardiovascular disease biomarkers according to APOE genotype. Design: Participants had a mean (±SD) age of 51 ± 9 y and a BMI (in kg/m2) of 26.0 ± 3.8 (n = 44 E3/E3, n = 44 E3/E4) and followed a sequential dietary intervention (the SATgenϵ study) in which they were assigned to a low-fat diet, a high-fat high-SFA (HSF) diet, and the HSF diet with 3.45 g DHA/d (HSF-DHA), each for 8 wk. Fasting blood samples were collected at the end of each intervention arm. Results: An overall diet effect was evident for all cholesterol fractions (P < 0.01), with no significant genotype × diet interactions observed. A genotype × diet interaction (P = 0.033) was evident for plasma triglycerides, with 17% and 30% decreases in APOE3/E3 and APOE3/E4 individuals after the HSF-DHA diet relative to the low-fat diet. A significant genotype × diet interaction (P = 0.009) was also observed for C-reactive protein (CRP), with only significant increases in concentrations after the HSF and HSF-DHA diets relative to the low-fat diet in the APOE3/E4 group (P < 0.015). Conclusions: Relative to the wild-type APOE3/E3 group, our results indicate a greater sensitivity of fasting triglycerides and CRP to dietary fat manipulation in those with an APOE3/E4 genotype (25% population), with no effect of this allelic profile on cholesterol concentrations. The SATgenϵ study was registered at clinicaltrials.gov as NCT01384032.

Substance P released by TRPV1-expressing neurons produces reactive oxygen species that mediate ethanol-induced gastric injury

Although neurokinin 1 receptor antagonists prevent ethanol (EtOH)-induced gastric lesions, the mechanisms by which EtOH releases substance P (SP) and SP damages the mucosa are unknown. We hypothesized that EtOH activates transient receptor potential vanilloid 1 (TRPV1) on sensory nerves to release SP, which stimulates epithelial neurokinin 1 receptors to generate damaging reactive oxygen species (ROS). SP release was assayed in the mouse stomach, ROS were detected using dichlorofluorescein diacetate, and neurokinin 1 receptors were localized by immunofluorescence. EtOH-induced SP release was prevented by TRPV1 antagonism. High dose EtOH caused lesions, and TRPV1 or neurokinin 1 receptor antagonism and neurokinin 1 receptor deletion inhibited lesion formation. Coadministration of low, innocuous doses of EtOH and SP caused lesions by a TRPV1-independent but neurokinin 1 receptor-dependent process. EtOH, capsaicin, and SP stimulated generation of ROS by superficial gastric epithelial cells expressing neurokinin 1 receptors by a neurokinin 1 receptor-dependent mechanism. ROS scavengers prevented lesions induced by a high EtOH dose or a low EtOH dose plus SP. Gastric lesions are caused by an initial detrimental effect of EtOH, which is damaging only if associated with TRPV1 activation, SP release from sensory nerves, stimulation of neurokinin 1 receptors on epithelial cells, and ROS generation.

Carbon monoxide inhibits L-type Ca2+ channels via redox modulation of key cysteine residues by mitochondrial reactive oxygen species

Conditions of stress, such as myocardial infarction, stimulate up-regulation of heme oxygenase (HO-1) to provide cardioprotection. Here, we show that CO, a product of heme catabolism by HO-1, directly inhibits native rat cardiomyocyte L-type Ca2+ currents and the recombinant alpha1C subunit of the human cardiac L-type Ca2+ channel. CO (applied via a recognized CO donor molecule or as the dissolved gas) caused reversible, voltage-independent channel inhibition, which was dependent on the presence of a spliced insert in the cytoplasmic C-terminal region of the channel. Sequential molecular dissection and point mutagenesis identified three key cysteine residues within the proximal 31 amino acids of the splice insert required for CO sensitivity. CO-mediated inhibition was independent of nitric oxide and protein kinase G but was prevented by antioxidants and the reducing agent, dithiothreitol. Inhibition of NADPH oxidase and xanthine oxidase did not affect the inhibitory actions of CO. Instead, inhibitors of complex III (but not complex I) of the mitochondrial electron transport chain and a mitochondrially targeted antioxidant (Mito Q) fully prevented the effects of CO. Our data indicate that the cardioprotective effects of HO-1 activity may be attributable to an inhibitory action of CO on cardiac L-type Ca2+ channels. Inhibition arises from the ability of CO to promote generation of reactive oxygen species from complex III of mitochondria. This in turn leads to redox modulation of any or all of three critical cysteine residues in the channel's cytoplasmic C-terminal tail, resulting in channel inhibition.

Networks, agency and (de)stabilisation: the issue of navigation on the River Wye, UK

This paper assesses the way in which an actor network presiding over the management of the River Wye has stabilized through accepting a particular view on the issue of navigation. The paper provides an account of how the network was challenged by a dissonant actor who, through reviving an old company, developed a counter network. It is argued that network stabilization is a form of consensus-building and it is contended that the way in which an issue is defined is crucial in terms of the successful enrolment of actors. The paper illustrates some of the conflicts and complexities encountered in resource planning, suggesting that research of this nature should trace actors back through time as well as through space if dynamics between actors involved in rural planning and management are to be effectively understood.

Modelling human visual navigation using multi-view scene reconstruction

It is often assumed that humans generate a 3D reconstruction of the environment, either in egocentric or world-based coordinates, but the steps involved are unknown. Here, we propose two reconstruction-based models, evaluated using data from two tasks in immersive virtual reality. We model the observer’s prediction of landmark location based on standard photogrammetric methods and then combine location predictions to compute likelihood maps of navigation behaviour. In one model, each scene point is treated independently in the reconstruction; in the other, the pertinent variable is the spatial relationship between pairs of points. Participants viewed a simple environment from one location, were transported (virtually) to another part of the scene and were asked to navigate back. Error distributions varied substantially with changes in scene layout; we compared these directly with the likelihood maps to quantify the success of the models. We also measured error distributions when participants manipulated the location of a landmark to match the preceding interval, providing a direct test of the landmark-location stage of the navigation models. Models such as this, which start with scenes and end with a probabilistic prediction of behaviour, are likely to be increasingly useful for understanding 3D vision.

Changes in reactive stratospheric gases due to a change in Brewer–Dobson circulation: results from a simple model

Amounts of source gases with stratospheric sinks (CFCs, N2O, CH4) are affected by changes in Brewer–Dobson circulation. Source gases and their degradation products are important for atmospheric chemistry and climate. With a simple model, we examine how amounts and lifetimes of source gases and products depend on speed of the circulation. Transient results differ from steady-state and stratospheric results differ from those for stratosphere plus troposphere. Increases in speed increase the stratospheric burden of source gases, but reduce products and reduce total burdens and lifetimes of source gases

Estimation of visual motion parameters used for bio-inspired navigation

Visual motion cues play an important role in animal and humans locomotion without the need to extract actual ego-motion information. This paper demonstrates a method for estimating the visual motion parameters, namely the Time-To-Contact (TTC), Focus of Expansion (FOE), and image angular velocities, from a sparse optical flow estimation registered from a downward looking camera. The presented method is capable of estimating the visual motion parameters in a complicated 6 degrees of freedom motion and in real time with suitable accuracy for mobile robots visual navigation.

Predicting solar disturbance effects on navigation systems

A variety of operational systems are vulnerable to disruption by solar disturbances brought to the Earth by the solar wind. Of particular importance to navigation systems are energetic charged particles which can generate temporary malfunctions and permanent damage in satellites. Modern spacecraft technology may prove to be particularly at risk during the next maximum of the solar cycle. In addition, the associated ionospheric disturbances cause phase shifts of transionospheric and ionosphere-reflected signals, giving positioning errors and loss of signal for GPS and Loran-C positioning systems and for over-the-horizon radars. We now have sufficient understanding of the solar wind, and how it interacts with the Earth's magnetic field, to predict statistically the likely effects on operational systems over the next solar cycle. We also have a number of advanced ways of detecting and tracking these disturbances through space but we cannot, as yet, provide accurate forecasts of individual disturbances that could be used to protect satellites and to correct errors. In addition, we have recently discovered long-term changes in the Sun, which mean that the number and severity of the disturbances to operational systems are increasing.

Evaluation of methods of detecting cell reactive oxygen species production for drug screening and cell cycle studies

Intracellular reactive oxygen species (ROS) production is essential to normal cell function. However, excessive ROS production causes oxidative damage and cell death. Many pharmacological compounds exert their effects on cell cycle progression by changing intracellular redox state and in many cases cause oxidative damage leading to drug cytotoxicity. Appropriate measurement of intracellular ROS levels during cell cycle progression is therefore crucial in understanding redox-regulation of cell function and drug toxicity and for the development of new drugs. However, due to the extremely short half-life of ROS, measuring the changes in intracellular ROS levels during a particular phase of cell cycle for drug intervention can be challenging. In this article, we have provided updated information on the rationale, the applications, the advantages and limitations of common methods for screening drug effects on intracellular ROS production linked to cell cycle study. Our aim is to facilitate biomedical scientists and researchers in the pharmaceutical industry in choosing or developing specific experimental regimens to suit their research needs.