Effects of acute consumption of a fruit and vegetable puree-based drink on vasodilation and oxidative status

Epidemiological studies indicate that diets rich in fruits and vegetables (F&V) are protective against cardiovascular diseases (CVD). Pureed F&V products retain many beneficial components, including flavonoids, carotenoids, vitamin C and dietary fibres. This study aimed to establish the physiological effects of acute ingestion of F&V puree-based drink (FVPD) on vasodilation, antioxidant status, phytochemical bioavailability and other CVD risk factors. 24 Subjects, aged 30-70 years, completed the randomised, single-blind, controlled, crossover test meal study. Subjects consumed 400 ml FVPD, or fruit-flavoured sugar-matched control, after following a low-flavonoid diet for 5 days. Blood and urine samples were collected throughout the study day and vascular reactivity was assessed at 90-minute intervals using laser Doppler iontophoresis (LDI). FVPD significantly increased plasma vitamin C (P=0.002) and total nitrate/nitrite (P=0.001) concentrations. There was a near significant time by treatment effect on ex vivo LDL oxidation (P=0.068), with a longer lag phase after consuming FVPD. During the 6 hours after juice consumption the antioxidant capacity of plasma increased significantly (P=0.003) and there was a simultaneous increase in plasma and urinary phenolic metabolites (P<0.05). There were significantly lower glucose and insulin peaks after ingestion of FVPD compared with control (P=0.019 and P=0.003) and a trend towards increased endothelium-dependent vasodilation following FVPD consumption (P=0.061). Overall, FVPD consumption significantly increased plasma vitamin C and total nitrate/nitrite concentrations, with a trend towards increased endothelium-dependent vasodilation. Pureed F&V products are useful vehicles for increasing micronutrient status, plasma antioxidant capacity and in vivo NO generation, which may contribute to CVD risk reduction.

In vitro antioxidant activity and antigenotoxicity of 5-n-alkylresorcinols

Incubation with 5-n-alkylresorcinols (chain lengths C15:0, C17:0, C19:0, C21:0, and C23:0) increased the self-protection capacity of HT29 human colon cancer cells against DNA damage induced by hydrogen peroxide and genotoxic fecal water samples using comet assay (single-cell gel electrophoresis assay). The alkylresorcinols did not exert potent antioxidant activity in the FRAP (ferric reduction ability of plasma) and DPPH (2,2-diphenyl-1-picrylhydrazyl) radical assays. However they were able to significantly inhibit copper-mediated oxidation of human LDL (low-density lipoprotein) in vitro, and pentadecylresorcinol at 25 micromol/L increased lag time by 65 min. The results show that alkylresorcinols have antigenotoxic and antioxidant activity under in vitro conditions.

The effect of cruciferous and leguminous sprouts on genotoxicity, in vitro and in vivo

Vegetable consumption is associated with a reduced risk of colorectal cancer, which is the second most common cancer after lung/breast cancer within Europe. Some putative protective phytochemicals are found in higher amounts in young sprouts than in mature plants. The effect of an extract of mixed cruciferous and legume sprouts on DNA damage induced by H(2)O(2) was measured in HT29 cells using single cell microgelelectrophoresis (comet). Significant antigenotoxic effect (P < or = 0.05) was observed when HT29 cells were pre-incubated with the extract (100 and 200 microL/mL) for 24 hours and then challenged with H(2)O(2). A parallel design intervention study was carried out on 10 male and 10 female healthy adult volunteers (mean age = 25.5 years) fed 113 g of cruciferous and legume sprouts daily for 14 days. The effect of the supplementation was measured on a range of parameters, including DNA damage in lymphocytes (comet), the activity of various detoxifying enzymes (glutathione S-transferase, glutathione peroxidase, and superoxide dismutase), antioxidant status using the ferric reducing ability of plasma assay, plasma antioxidants (uric acid, ascorbic acid, and alpha-tocopherol), blood lipids, plasma levels of lutein, and lycopene. A significant antigenotoxic effect against H(2)O(2)-induced DNA damage was shown in peripheral blood lymphocytes of volunteers who consumed the supplemented diet when compared with the control diet (P = 0.04). No significant induction of detoxifying enzymes was observed during the study, neither were plasma antioxidant levels or activity altered. The results support the theory that consumption of cruciferous vegetables is linked to a reduced risk of cancer via decreased damage to DNA.

Endothelin-converting enzyme-1 regulates trafficking and signalling of the neurokinin 1 receptor in endosomes of myenteric neurones

Neuropeptide signalling at the plasma membrane is terminated by neuropeptide degradation by cell-surface peptidases, and by beta-arrestin-dependent receptor desensitization and endocytosis. However, receptors continue to signal from endosomes by beta-arrestin-dependent processes, and endosomal sorting mediates recycling and resensitization of plasma membrane signalling. The mechanisms that control signalling and trafficking of receptors in endosomes are poorly defined. We report a major role for endothelin-converting enzyme-1 (ECE-1) in controlling substance P (SP) and the neurokinin 1 receptor (NK(1)R) in endosomes of myenteric neurones. ECE-1 mRNA and protein were expressed by myenteric neurones of rat and mouse intestine. SP (10 nM, 10 min) induced interaction of NK(1)R and beta-arrestin at the plasma membrane, and the SP-NK(1)R-beta-arrestin signalosome complex trafficked by a dynamin-mediated mechanism to ECE-1-containing early endosomes, where ECE-1 can degrade SP. After 120 min, NK(1)R recycled from endosomes to the plasma membrane. ECE-1 inhibitors (SM-19712, PD-069185) and the vacuolar H(+)ATPase inhibitor bafilomycin A(1), which prevent endosomal SP degradation, suppressed NK(1)R recycling by >50%. Preincubation of neurones with SP (10 nM, 5 min) desensitized Ca(2+) transients to a second SP challenge after 10 min, and SP signals resensitized after 60 min. SM-19712 inhibited NK(1)R resensitization by >90%. ECE-1 inhibitors also caused sustained SP-induced activation of extracellular signal-regulated kinases, consistent with stabilization of the SP-NK(1)R-beta-arrestin signalosome. By degrading SP and destabilizing endosomal signalosomes, ECE-1 has a dual role in controlling endocytic signalling and trafficking of the NK(1)R: promoting resensitization of G protein-mediated plasma membrane signalling, and terminating beta-arrestin-mediated endosomal signalling.

Constructing the frequency and wave normal distribution of whistler-mode wave power

We introduce a new methodology that allows the construction of wave frequency distributions due to growing incoherent whistler-mode waves in the magnetosphere. The technique combines the equations of geometric optics (i.e. raytracing) with the equation of transfer of radiation in an anisotropic lossy medium to obtain spectral energy density as a function of frequency and wavenormal angle. We describe the method in detail, and then demonstrate how it could be used in an idealised magnetosphere during quiet geomagnetic conditions. For a specific set of plasma conditions, we predict that the wave power peaks off the equator at ~15 degrees magnetic latitude. The new calculations predict that wave power as a function of frequency can be adequately described using a Gaussian function, but as a function of wavenormal angle, it more closely resembles a skew normal distribution. The technique described in this paper is the first known estimate of the parallel and oblique incoherent wave spectrum as a result of growing whistler-mode waves, and provides a means to incorporate self-consistent wave-particle interactions in a kinetic model of the magnetosphere over a large volume.

Using coordinated observations in polarized white light and Faraday rotation to probe the spatial position and magnetic field of an interplanetary sheath

Coronal mass ejections (CMEs) can be continuously tracked through a large portion of the inner heliosphere by direct imaging in visible and radio wavebands. White light (WL) signatures of solar wind transients, such as CMEs, result from Thomson scattering of sunlight by free electrons and therefore depend on both viewing geometry and electron density. The Faraday rotation (FR) of radio waves from extragalactic pulsars and quasars, which arises due to the presence of such solar wind features, depends on the line-of-sight magnetic field component B ∥ and the electron density. To understand coordinated WL and FR observations of CMEs, we perform forward magnetohydrodynamic modeling of an Earth-directed shock and synthesize the signatures that would be remotely sensed at a number of widely distributed vantage points in the inner heliosphere. Removal of the background solar wind contribution reveals the shock-associated enhancements in WL and FR. While the efficiency of Thomson scattering depends on scattering angle, WL radiance I decreases with heliocentric distance r roughly according to the expression Ir –3. The sheath region downstream of the Earth-directed shock is well viewed from the L4 and L5 Lagrangian points, demonstrating the benefits of these points in terms of space weather forecasting. The spatial position of the main scattering site r sheath and the mass of plasma at that position M sheath can be inferred from the polarization of the shock-associated enhancement in WL radiance. From the FR measurements, the local B ∥sheath at r sheath can then be estimated. Simultaneous observations in polarized WL and FR can not only be used to detect CMEs, but also to diagnose their plasma and magnetic field properties.

Exogenous alpha-Synuclein decreases raft partitioning of Cav2.2 channels inducing dopamine release

alpha-Synuclein is thought to regulate neurotransmitter release through multiple interactions with presynaptic proteins, cytoskeletal elements, ion channels, and synaptic vesicles membrane. alpha-Synuclein is abundant in the presynaptic compartment, and its release from neurons and glia has been described as responsible for spreading of alpha-synuclein-derived pathology. alpha-Synuclein-dependent dysregulation of neurotransmitter release might occur via its action on surface-exposed calcium channels. Here, we provide electrophysiological and biochemical evidence to show that alpha-synuclein, applied to rat neurons in culture or striatal slices, selectively activates Cav2.2 channels, and said activation correlates with increased neurotransmitter release. Furthermore, in vivo perfusion of alpha-synuclein into the striatum also leads to acute dopamine release. We further demonstrate that alpha-synuclein reduces the amount of plasma membrane cholesterol and alters the partitioning of Cav2.2 channels, which move from raft to cholesterol-poor areas of the plasma membrane. We provide evidence for a novel mechanism through which alpha-synuclein acts from the extracellular milieu to modulate neurotransmitter release and propose a unifying hypothesis for the mechanism of alpha-synuclein action on multiple targets: the reorganization of plasma membrane microdomains.

Comparison of interplanetary signatures of streamers and pseudostreamers

If the source of the slow solar wind is a web comprising pseudostreamer belts connected to the streamer belt, then one expects the properties of interplanetary pseudostreamer flows to be similar to those of streamer flows. That expectation is tested with data from the slow wind preceding stream interfaces in stream interaction regions at 1 AU, where the interfaces separate what was originally slow and fast wind. Pseudostreamer cases were separated from streamer cases with the aid of the streamer identification tool developed by Owens et al. (2013), and superposed epoch analysis was performed to compare the patterns of a number of plasma and composition parameters. The results reveal that pseudostreamer flows have all of the slow-wind characteristics of streamer flows except that they are slightly less pronounced than streamer characteristics when compared to fast wind. The results are consistent with the concept that the solar wind displays a continuum of dynamic states rather than only slow and fast states.

Dominant components of the Thoroughbred metabolome characterised by 1H‐NMR spectroscopy: a metabolite atlas of common biofluids

Summary Reasons for performing study: Metabonomics is emerging as a powerful tool for disease screening and investigating mammalian metabolism. This study aims to create a metabolic framework by producing a preliminary reference guide for the normal equine metabolic milieu. Objectives: To metabolically profile plasma, urine and faecal water from healthy racehorses using high resolution 1H-NMR spectroscopy and to provide a list of dominant metabolites present in each biofluid for the benefit of future research in this area. Study design: This study was performed using seven Thoroughbreds in race training at a single time-point. Urine and faecal samples were collected non-invasively and plasma was obtained from samples taken for routine clinical chemistry purposes. Methods: Biofluids were analysed using 1H-NMR spectroscopy. Metabolite assignment was achieved via a range of 1D and 2D experiments. Results: A total of 102 metabolites were assigned across the three biological matrices. A core metabonome of 14 metabolites was ubiquitous across all biofluids. All biological matrices provided a unique window on different aspects of systematic metabolism. Urine was the most populated metabolite matrix with 65 identified metabolites, 39 of which were unique to this biological compartment. A number of these were related to gut microbial host co-metabolism. Faecal samples were the most metabolically variable between animals; acetate was responsible for the majority (28%) of this variation. Short chain fatty acids were the predominant features identified within this biofluid by 1H-NMR spectroscopy. Conclusions: Metabonomics provides a platform for investigating complex and dynamic interactions between the host and its consortium of gut microbes and has the potential to uncover markers for health and disease in a variety of biofluids. Inherent variation in faecal extracts along with the relative abundance of microbial-mammalian metabolites in urine and invasive nature of plasma sampling, infers that urine is the most appropriate biofluid for the purposes of metabonomic analysis.

The response of ionospheric convection in the polar cap to substorm activity

We report multi-instrument observations during an isolated substorm on 17 October 1989. The EISCAT radar operated in the SP-UK-POLI mode measuring ionospheric convection at latitudes 71°-78°. SAMNET and the EISCAT Magnetometer Cross provide information on the timing of substorm expansion phase onset and subsequent intensifications, as well as the location of the field aligned and ionospheric currents associated with the substorm current wedge. IMP-8 magnetic field data are also included. Evidence of a substorm growth phase is provided by the equatorward motion of a flow reversal boundary across the EISCAT radar field of view at 2130 MLT, following a southward turning of the interplanetary magnetic field (IMF). We infer that the polar cap expanded as a result of the addition of open magnetic flux to the tail lobes during this interval. The flow reversal boundary, which is a lower limit to the polar cap boundary, reached an invariant latitude equatorward of 71° by the time of the expansion phase onset. A westward electrojet, centred at 65.4°, occurred at the onset of the expansion phase. This electrojet subsequently moved poleward to a maximum of 68.1° at 2000 UT and also widened. During the expansion phase, there is evidence of bursts of plasma flow which are spatially localised at longitudes within the substorm current wedge and which occurred well poleward of the westward electrojet. We conclude that the substorm onset region in the ionosphere, defined by the westward electrojet, mapped to a part of the tail radially earthward of the boundary between open and closed magnetic flux, the “distant” neutral line. Thus the substorm was not initiated at the distant neutral line, although there is evidence that it remained active during the expansion phase. It is not obvious whether the electrojet mapped to a near-Earth neutral line, but at its most poleward, the expanded electrojet does not reach the estimated latitude of the polar cap boundary.

EISCAT observations of unusual flows in the morning sector associated with weak substorm activity

A discussion is given of plasma flows in the dawn and nightside high-latitude ionospheric regions during substorms occurring on a contracted auroral oval, as observed using the EISCAT CP-4-A experiment. Supporting data from the PACE radar, Greenland magnetometer chain, SAMNET magnetometers and geostationary satellites are compared to the EISCAT observations. On 4 October 1989 a weak substorm with initial expansion phase onset signatures at 0030 UT, resulted in the convection reversal boundary observed by EISCAT (at \sim0415 MLT) contracting rapidly poleward, causing a band of elevated ionospheric ion temperatures and a localised plasma density depletion. This polar cap contraction event is shown to be associated with various substorm signatures; Pi2 pulsations at mid-latitudes, magnetic bays in the midnight sector and particle injections at geosynchronous orbit. A similar event was observed on the following day around 0230 UT (\sim0515 MLT) with the unusual and significant difference that two convection reversals were observed, both contracting poleward. We show that this feature is not an ionospheric signature of two active reconnection neutral lines as predicted by the near-Earth neutral model before the plasmoid is “pinched off”, and present two alternative explanations in terms of (1) viscous and lobe circulation cells and (2) polar cap contraction during northward IMF. The voltage associated with the anti-sunward flow between the reversals reaches a maximum of 13 kV during the substorm expansion phase. This suggests it to be associated with the polar cap contraction and caused by the reconnection of open flux in the geomagnetic tail which has mimicked “viscous-like” momentum transfer across the magnetopause.

Ionospheric Signatures of Pulsed Magnetopause Reconnection

The concept of zero-flow equilibria of the magnetosphere-ionosphere system leads to a large number of predictions concerning the ionospheric signatures of pulsed magnetopause reconnection. These include: poleward-moving F-region electron temperature enhancements and associated transient 630nm emission; associated poleward plasma flow which, compared to the pulsed variation of the reconnection rate, is highly smoothed by induction effects; oscillatory latitudinal motion of the open/closed field line boundary; phase lag of plasma flow enhancements after equatorward motions of the boundary; azimuthal plasma flow bursts, coincident in time and space with the 630nm-dominant auroral transients, only when the magnitude of the By component of the interplanetary magnetic field (IMF) is large; azimuthal-then-poleward motion of 630nm-dominant transients at a velocity which at all times equals the internal plasma flow velocity; 557.7nm-dominant transients on one edge of the 630nm-dominant transient (initially, and for large |By|, on the poleward or equatorward edge depending on the polarity of IMF By); tailward expansion of the flow response at several km s-1; and discrete steps in the cusp ion dispersion signature between the polewardmoving structures. This paper discusses these predictions and how all have recently been confirmed by combinations of observations by optical instruments on the Svalbard Islands, the EISCAT radars and the DMSP and DE satellites.

Modelling the high-latitude ionosphere for time-varying plasma convection

The paper discusses how variations in the pattern of convective plasma flows should beincluded in self-consistent time-dependent models of the coupled ionosphere-thermosphere system. The author shows how these variations depend upon the mechanism by which the solar wind flow excites the convection. The modelling of these effects is not just of relevance to the polar ionosphere. This is because the influence of convection is not confined to high latitudes: the resultant heating and composition changes in the thermosphere are communicated to lower latitudes by the winds which are also greatly modified by the plasma convection. These thermospheric changes alter the global distribution of plasma by modulatingthe rates of the chemical reactions which areresponsible for the loss of plasma. Hence the modelling of these high-latitude processes is of relevanceto the design and operation of HF communication, radar and navigation systems worldwide.

EISCAT observations of ion composition and temperature anisotropy in the high-latitude F-region

The papers by Winser et al. [(1990) J. atmos. terr. Phys.52, 501] and Häggström and Collis [(1990) J. atmos. terr. Phys.52, 519] used plasma flows and ion temperatures, as measured by the EISCAT tristatic incoherent scatter radar, to investigate changes in the ion composition of the ionospheric F-layer at high latitudes, in response to increases in the speed of plasma convection. These studies reported that the ion composition rapidly changed from mainly O+ to almost completely (>90%) molecular ions, following rapid increases in ion drift speed by >1 km s−1. These changes appeared inconsisent with theoretical considerations of the ion chemistry, which could not account for the large fractions of molecular ions inferred from the obsevations. In this paper, we discuss two causes of this discrepancy. First, we reevaluate the theoretical calculations for chemical equilibrium and show that, if we correct the derived temperatures for the effect of the molecular ions, and if we employ more realistic dependences of the reaction rates on the ion temperature, the composition changes derived for the faster convection speeds can be explained. For the Winser et al. observations with the radar beam at an aspect angle of ϕ = 54.7° to the geomagnetic field, we now compute a change to 89% molecular ions in < 2 min, in response to the 3 km s−1 drift. This is broadly consistent with the observations. But for the two cases considered by Häggström and Collis, looking along the field line (ϕ = 0°), we compute the proportion of molecular ions to be only 4 and 16% for the observed plasma drifts of 1.2 and 1.6 km s−1, respectively. These computed proportions are much smaller than those derived experimentally (70 and 90%). We attribute the differences to the effects of non-Maxwellian, anisotropic ion velocity distribution functions. We also discuss the effect of ion composition changes on the various radar observations that report anisotropies of ion temperature.

Comparisons between EISCAT observations and model calculations of the high latitude ionosphere

Calculations using a numerical model of the convection dominated high latitude ionosphere are compared with observations made by EISCAT as part of the UK-POLAR Special Programme. The data used were for 24–25 October 1984, which was characterized by an unusually steady IMF, with Bz < 0 and By > 0; in the calculations it was assumed that a steady IMF implies steady convection conditions. Using the electric field models of Heppner and Maynard (1983) appropriate to By > 0 and precipitation data taken from Spiroet al. (1982), we calculated the velocities and electron densities appropriate to the EISCAT observations. Many of the general features of the velocity data were reproduced by the model. In particular, the phasing of the change from eastward to westward flow in the vicinity of the Harang discontinuity, flows near the dayside throat and a region of slow flow at higher latitudes near dusk were well reproduced. In the afternoon sector modelled velocity values were significantly less than those observed. Electron density calculations showed good agreement with EISCAT observations near the F-peak, but compared poorly with observations near 211 km. In both cases, the greatest disagreement occurred in the early part of the observations, where the convection pattern was poorly known and showed some evidence of long term temporal change. Possible causes for the disagreement between observations and calculations are discussed and shown to raise interesting and, as yet, unresolved questions concerning the interpretation of the data. For the data set used, the late afternoon dip in electron density observed near the F-peak and interpreted as the signature of the mid-latitude trough is well reproduced by the calculations. Calculations indicate that it does not arise from long residence times of plasma on the nightside, but is the signature of a gap between two major ionization sources, viz. photoionization and particle precipitation.