Pathogenic Parkinson’s disease mutations across the functional domains of LRRK2 alter the autophagic/lysosomal response to starvation

LRRK2 is one of the most important genetic contributors to Parkinson’s disease (PD). Point mutations in this gene cause an autosomal dominant form of PD, but to date no cellular phenotype has been consis- tently linked with mutations in each of the functional domains (ROC, COR and Kinase) of the protein product of this gene. In this study, primary fibroblasts from individuals carrying pathogenic mutations in the three central domains of LRRK2 were assessed for alterations in the autophagy/lysosomal pathway using a combination of biochemical and cellular approaches. Mutations in all three domains resulted in alterations in markers for autophagy/lysosomal function compared to wild type cells. These data high- light the autophagy and lysosomal pathways as read outs for pathogenic LRRK2 function and as a marker for disease, and provide insight into the mechanisms linking LRRK2 function and mutations.

Any response? How demand response could be enhanced based on early UK experience

Policy makers are in broad agreement that demand response should play a major role in EU electricity systems and provide much needed future system flexibility. Yet, little demand response has been forthcoming in member states to date. This paper identifies some of the technical potential for demand response, based on empirical data from one UK demand aggregator. Half-hourly electricity readings of demand during normal operation and during response events have been analysed for different industry and service sectors. We review these findings in the context of ongoing EU policy developments with particular focus on the role appropriate arrangements to enhance the available resource. We conclude that in some sectors appropriate policy and regulation could triple the available response capacity and thereby lead to stronger commercial uptake of demand response.

Apolipoprotein e genotype has a modest impact on the postprandial plasma response to meals of varying fat composition in healthy men in a randomized controlled trial

BACKGROUND:Apolioprotein E (APOE) genotype is reported to influence a person's fasting lipid profile and potentially the response to dietary fat manipulation. The impact of APOE genotype on the responsiveness to meals of varying fat composition is unknown. OBJECTIVE:We examined the effect of meals containing 50 g of fat rich in saturated fatty acids (SFAs), unsaturated fatty acids (UNSATs), or SFAs with fish oil (SFA-FO) on postprandial lipemia. METHOD:A randomized, controlled, test meal study was performed in men recruited according to the APOE genotype (n = 10 APOE3/3, n = 11 APOE3/E4). RESULTS:For the serum apoE response (meal × genotype interaction P = 0.038), concentrations were on average 8% lower after the UNSAT than the SFA-FO meal in APOE4 carriers (P = 0.015) only. In the genotype groups combined, there was a delay in the time to reach maximum triacylglycerol (TG) concentration (mean ± SEM: 313 ± 25 vs. 266 ± 27 min) and higher maximum nonesterified fatty acid (0.73 ± 0.05 vs. 0.60 ± 0.03 mmol/L) and glucose (7.92 ± 0.22 vs. 7.25 ± 0.22 mmol/L) concentrations after the SFA than the UNSAT meal, respectively (P ≤ 0.05). In the Svedberg flotation rate 60-400 TG-rich lipoprotein fraction, meal × genotype interactions were observed for incremental area under the curve (IAUC) for the TG (P = 0.038) and apoE (P = 0.016) responses with a 58% lower apoE IAUC after the UNSAT than the SFA meal (P = 0.017) in the E4 carriers. CONCLUSIONS:Our data indicate that APOE genotype had a modest impact on the postprandial response to meals of varying fat composition in normolipidemic men. The physiologic importance of greater apoE concentrations after the SFA-rich meals in APOE4 carriers may reflect an impact on TG-rich lipoprotein clearance from the circulation. This trial was registered at clinicaltrials.gov as NCT01522482.

The response of the sea ice edge to atmospheric and oceanic jet formation

The sea ice edge presents a region of many feedback processes between the atmosphere, ocean, and sea ice (Maslowski et al.). Here the authors focus on the impact of on-ice atmospheric and oceanic flows at the sea ice edge. Mesoscale jet formation due to the Coriolis effect is well understood over sharp changes in surface roughness such as coastlines (Hunt et al.). This sharp change in surface roughness is experienced by the atmosphere and ocean encountering a compacted sea ice edge. This paper presents a study of a dynamic sea ice edge responding to prescribed atmospheric and oceanic jet formation. An idealized analytical model of sea ice drift is developed and compared to a sea ice climate model [the Los Alamos Sea Ice Model (CICE)] run on an idealized domain. The response of the CICE model to jet formation is tested at various resolutions. It is found that the formation of atmospheric jets at the sea ice edge increases the wind speed parallel to the sea ice edge and results in the formation of a sea ice drift jet in agreement with an observed sea ice drift jet (Johannessen et al.). The increase in ice drift speed is dependent upon the angle between the ice edge and wind and results in up to a 40% increase in ice transport along the sea ice edge. The possibility of oceanic jet formation and the resultant effect upon the sea ice edge is less conclusive. Observations and climate model data of the polar oceans have been analyzed to show areas of likely atmospheric jet formation, with the Fram Strait being of particular interest.

A numerical model of the ionospheric signatures of time-varying magnetic reconnection: II. Measuring expansions in the ionospheric flow response

A numerical model embodying the concepts of the Cowley-Lockwood (Cowley and Lockwood, 1992, 1997) paradigm has been used to produce a simple Cowley– Lockwood type expanding flow pattern and to calculate the resulting change in ion temperature. Cross-correlation, fixed threshold analysis and threshold relative to peak are used to determine the phase speed of the change in convection pattern, in response to a change in applied reconnection. Each of these methods fails to fully recover the expansion of the onset of the convection response that is inherent in the simulations. The results of this study indicate that any expansion of the convection pattern will be best observed in time-series data using a threshold which is a fixed fraction of the peak response. We show that these methods used to determine the expansion velocity can be used to discriminate between the two main models for the convection response to a change in reconnection.

Long term changes in EUV and X-ray emissions from the solar corona and chromosphere as measured by the response of the Earth’s ionosphere during total solar eclipses from 1932 to 1999

Measurements of the ionospheric E region during total solar eclipses in the period 1932-1999 have been used to investigate the fraction of Extreme Ultra Violet and soft X-ray radiation, phi, that is emitted from the limb corona and chromosphere. The relative apparent sizes of the Moon and the Sun are different for each eclipse, and techniques are presented which correct the measurements and, therefore, allow direct comparisons between different eclipses. The results show that the fraction of ionising radiation emitted by the limb corona has a clear solar cycle variation and that the underlying trend shows this fraction has been increasing since 1932. Data from the SOHO spacecraft are used to study the effects of short-term variability and it is shown that the observed long-term rise in phi has a negligible probability of being a chance occurrence.

ESR and EISCAT observations of the response of the cusp and cleft to IMF orientation changes

We report observations of the cusp/cleft ionosphere made on December 16th 1998 by the EISCAT (European incoherent scatter) VHF radar at Tromso and the EISCAT Svalbard radar (ESR). We compare them with observations of the dayside auroral luminosity, as seen by meridian scanning photometers at Ny Alesund and of HF radar backscatter, as observed by the CUTLASS radar. We study the response to an interval of about one hour when the interplanetary magnetic field (IMF), monitored by the WIND and ACE spacecraft, was southward. The cusp/cleft aurora is shown to correspond to a spatially extended region of elevated electron temperatures in the VHF radar data. Initial conditions were characterised by a northward-directed IMF and cusp/cleft aurora poleward of the ESR. A strong southward turning then occurred, causing an equatorward motion of the cusp/cleft aurora. Within the equatorward expanding, southward-IMF cusp/cleft, the ESR observed structured and elevated plasma densities and ion and electron temperatures. Cleft ion fountain upflows were seen in association with elevated ion temperatures and rapid eastward convection, consistent with the magnetic curvature force on newly opened held lines for the observed negative IMF B-y. Subsequently, the ESR beam remained immediately poleward of the main cusp/cleft and a sequence of poleward-moving auroral transients passed over it. After the last of these, the ESR was in the polar cap and the radar observations were characterised by extremely low ionospheric densities and downward field-aligned flows. The IMF then turned northward again and the auroral oval contracted such that the ESR moved back into the cusp/cleft region. For the poleward-retreating northward-IMF cusp/cleft, the convection flows were slower, upflows were weaker and the electron density and temperature enhancements were less structured. Following the northward turning, the bands of high electron temperature and cusp/cleft aurora bifurcated, consistent with both subsolar and lobe reconnection taking place simultaneously. The present paper describes the large-scale behaviour of the ionosphere during this interval, as observed by a powerful combination of instruments. Two companion papers, by Lockwood et al. (2000) and Thorolfsson et al. (2000), both in this issue, describe the detailed behaviour of the poleward-moving transients observed during the interval of southward B-z, and explain their morphology in the context of previous theoretical work.

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.

Ionospheric convection response to slow, strong variations in a northward interplanetary magnetic field: A case study for January 14, 1988

We analyze ionospheric convection patterns over the polar regions during the passage of an interplanetary magnetic cloud on January 14, 1988, when the interplanetary magnetic field (IMF) rotated slowly in direction and had a large amplitude. Using the assimilative mapping of ionospheric electrodynamics (AMIE) procedure, we combine simultaneous observations of ionospheric drifts and magnetic perturbations from many different instruments into consistent patterns of high-latitude electrodynamics, focusing on the period of northward IMF. By combining satellite data with ground-based observations, we have generated one of the most comprehensive data sets yet assembled and used it to produce convection maps for both hemispheres. We present evidence that a lobe convection cell was embedded within normal merging convection during a period when the IMF By and Bz components were large and positive. As the IMF became predominantly northward, a strong reversed convection pattern (afternoon-to-morning potential drop of around 100 kV) appeared in the southern (summer) polar cap, while convection in the northern (winter) hemisphere became weak and disordered with a dawn-to-dusk potential drop of the order of 30 kV. These patterns persisted for about 3 hours, until the IMF rotated significantly toward the west. We interpret this behavior in terms of a recently proposed merging model for northward IMF under solstice conditions, for which lobe field lines from the hemisphere tilted toward the Sun (summer hemisphere) drape over the dayside magnetosphere, producing reverse convection in the summer hemisphere and impeding direct contact between the solar wind and field lines connected to the winter polar cap. The positive IMF Bx component present at this time could have contributed to the observed hemispheric asymmetry. Reverse convection in the summer hemisphere broke down rapidly after the ratio |By/Bz| exceeded unity, while convection in the winter hemisphere strengthened. A dominant dawn-to-dusk potential drop was established in both hemispheres when the magnitude of By exceeded that of Bz, with potential drops of the order of 100 kV, even while Bz remained northward. The later transition to southward Bz produced a gradual intensification of the convection, but a greater qualitative change occurred at the transition through |By/Bz| = 1 than at the transition through Bz = 0. The various convection patterns we derive under northward IMF conditions illustrate all possibilities previously discussed in the literature: nearly single-cell and multicell, distorted and symmetric, ordered and unordered, and sunward and antisunward.

Dayside ionospheric convection changes in response to long-period interplanetary Magnetic field oscillations: Determination of the ionospheric phase velocity

Ground magnetic field perturbations recorded by the CANOPUS magnetometer network in the 7 to 13 MLT sector are used to examine how reconfigurations of the dayside polar ionospheric flow take place in response to north-south changes of the IMF. During the 6-hour interval in question IMF Bz oscillates between ±7 nT with about a 1-hour period. Corresponding variations in the ground magnetic disturbance are observed which we infer are due to changes in ionospheric flow. Cross correlation of the data obtained from two ground stations at 73.5° magnetic latitude, but separated by ∼2 hours in MLT, shows that changes in the flow are initiated in the prenoon sector (∼10 MLT) and then spread outward toward dawn and dusk with a phase speed of ∼5 km s−1 over the longitude range ∼8 to 12 MLT, slowing to ∼2 km s−1 outside this range. Cross correlating the data from these ground stations with IMP 8 IMF Bz records produces a MLT variation in the ground response delay relative to the IMF which is compatible with these deduced phase speeds. We interpret these observations in terms of the ionospheric response to the onset, expansion and decay of magnetic reconnection at the dayside magnetopause.

Pressure-driven magnetopause motions and attendant response on the ground

The terrestrial magnetopause suffered considerable sudden changes in its location on 9–10 September 1978. These magnetopause motions were accompanied by disturbances of the geomagnetic field on the ground. We present a study of the magnetopause motions and the ground magnetic signatures using, for the latter, 10 s averaged data from 14 high latitude ground magnetometer stations. Observations in the solar wind (from IMP 8) are employed and the motions of the magnetopause are monitored directly by the spacecraft ISEE 1 and 2. With these coordinated observations we are able to show that it is the sudden changes in the solar wind dynamic pressure that are responsible for the disturbances seen on the ground. At some ground stations we see evidence of a “ringing” of the magnetospheric cavity, while at others only the initial impulse is evident. We note that at some stations field perturbations closely match the hypothesized ground signatures of flux transfer events. In accordance with more recent work in the area (e.g. Potemra et al., 1989, J. geophys. Res., in press), we argue that causes other than impulsive reeonnection may produce the twin ionospheric flow vortex originally proposed as a flux transfer even signature.

Response time of the high-latitude dayside ionosphere to sudden changes in the north-south component of the IMF

The time scale of the response of the high-latitude dayside ionospheric flow to changes in the North-South component of the interplanetary magnetic field (IMF) has been investigated by examining the time delays between corresponding sudden changes. Approximately 40 h of simultaneous IMF and ionospheric flow data have been examined, obtained by the AMPTE-UKS and -IRM spacecraft and the EISCAT “Polar” experiment, respectively, in which 20 corresponding sudden changes have been identified. Ten of these changes were associated with southward turnings of the IMF, and 10 with northward turnings. It has been found that the corresponding flow changes occurred simultaneously over the whole of the “Polar” field-of-view, extending more than 2° in invariant latitude, and that the ionospheric response delay following northward turnings is the same as that following southward turnings, though the form of the response is different in the two cases. The shortest response time, 5.5 ± 3.2 min, is found in the early- to mid-afternoon sector, increasing to 9.5 ± 3.0 min in the mid-morning sector, and to 9.5 ± 3.1 min near to dusk. These times represent the delays in the appearance of perturbed flows in the “Polar” field-of-view following the arrival of IMF changes at the subsolar magnetopause. Overall, the results agree very well with those derived by Etemadi et al. (1988, Planet. Space Sci.36, 471) from a general cross-correlation analysis of the IMF Bz and “Polar” beam-swinging vector flow data.

The dependence of high-latitude dayside ionospheric flows on the North-South component of the IMF: A high time resolution correlation analysis using EISCAT “Polar” and AMPTE UKS and IRM data

In 1984 and 1985 a series of experiments was undertaken in which dayside ionospheric flows were measured by the EISCAT “Polar” experiment, while observations of the solar wind and interplanetary magnetic field (IMF) were made by the AMPTE UKS and IRM spacecraft upstream from the Earth's bow shock. As a result, 40 h of simultaneous data were acquired, which are analysed in this paper to investigate the relationship between the ionospheric flow and the North-South (Bz) component of the IMF. The ionospheric flow data have 2.5 min resolution, and cover the dayside local time sector from ∼ 09:30 to ∼ 18:30 M.L.T. and the latitude range from 70.8° to 74.3°. Using cross-correlation analysis it is shown that clear relationships do exist between the ionospheric flow and IMF Bz, but that the form of the relations depends strongly on latitude and local time. These dependencies are readily interpreted in terms of a twinvortex flow pattern in which the magnitude and latitudinal extent of the flows become successively larger as Bz becomes successively more negative. Detailed maps of the flow are derived for a range of Bz values (between ± 4 nT) which clearly demonstrate the presence of these effects in the data. The data also suggest that the morning reversal in the East-West component of flow moves to earlier local times as Bz, declines in value and becomes negative. The correlation analysis also provides information on the ionospheric response time to changes in IMF Bz, it being found that the response is very rapid indeed. The most rapid response occurs in the noon to mid-afternoon sector, where the westward flows of the dusk cell respond with a delay of 3.9 ± 2.2 min to changes in the North-South field at the subsolar magnetopause. The flows appear to evolve in form over the subsequent ~ 5 min interval, however, as indicated by the longer response times found for the northward component of flow in this sector (6.7 ±2.2 min), and in data from earlier and later local times. No evidence is found for a latitudinal gradient in response time; changes in flow take place coherently in time across the entire radar field-of-view.

A lagged response to the 11 year solar cycle in observed winter Atlantic/European weather patterns

The surface response to 11 year solar cycle variations is investigated by analyzing the long-term mean sea level pressure and sea surface temperature observations for the period 1870–2010. The analysis reveals a statistically significant 11 year solar signal over Europe, and the North Atlantic provided that the data are lagged by a few years. The delayed signal resembles the positive phase of the North Atlantic Oscillation (NAO) following a solar maximum. The corresponding sea surface temperature response is consistent with this. A similar analysis is performed on long-term climate simulations from a coupled ocean-atmosphere version of the Hadley Centre model that has an extended upper lid so that influences of solar variability via the stratosphere are well resolved. The model reproduces the positive NAO signal over the Atlantic/European sector, but the lag of the surface response is not well reproduced. Possible mechanisms for the lagged nature of the observed response are discussed.

Unrestricted Skyrme-tensor time-dependent Hartree-Fock model and its application to the nuclear response from spherical to triaxial nuclei

The nuclear time-dependent Hartree-Fock model formulated in three-dimensional space, based on the full standard Skyrme energy density functional complemented with the tensor force, is presented. Full self-consistency is achieved by the model. The application to the isovector giant dipole resonance is discussed in the linear limit, ranging from spherical nuclei (16O and 120Sn) to systems displaying axial or triaxial deformation (24Mg, 28Si, 178Os, 190W and 238U). Particular attention is paid to the spin-dependent terms from the central sector of the functional, recently included together with the tensor. They turn out to be capable of producing a qualitative change on the strength distribution in this channel. The effect on the deformation properties is also discussed. The quantitative effects on the linear response are small and, overall, the giant dipole energy remains unaffected. Calculations are compared to predictions from the (quasi)-particle random-phase approximation and experimental data where available, finding good agreement