Atherosclerosis and calcium signalling in endothelial cells

The link between atherosclerosis and regions of disturbed flow and low wall shear stress is now firmly established, but the causal mechanisms underlying the link are not yet understood. It is now recognised that the endothelium is not simply a passive barrier between the blood and the vessel wall, but plays an active role in maintaining vascular homeostasis and participates in the onset of atherosclerosis. Calcium signalling is one of the principal intracellular signalling mechanisms by which endothelial cells (EC) respond to external stimuli, such as fluid shear stress and ligand binding. Previous studies have separately modelled mass transport of chemical species in the bloodstream and calcium dynamics in EC via the inositol triphosphate (IP₃) signalling pathway. In this study, we integrate these two important components to provide an inclusive model for the calcium response of the endothelium in an arbitrary vessel geometry. This enables the combined effects of fluid flow and biochemical stimulation on EC to be investigated. Model results show that low endothelial calcium levels in the area of disturbed flow at an arterial widening may be one contributing factor to the onset of vascular disease

Rich Cluster and Non-Cluster Radio Galaxies & the (P,D) Diagram for a Large Number of FR I and FR II Sources

We present a comparison of the optical and radio properties of radio sources inside and outside the cores of rich clusters from combined samples of more than 380 radio sources. We also examine the nature of FR I and FR II host galaxies, and in particular, we illustrate the importance of selection effects in propagating the misconception that FR I's and FR II's are found in hosts of very different optical luminosity. Given the large sample size, we also discuss the power-size (P,D) distributions as a function of optical luminosity.Comment: to appear in Life Cycles of Radio Galaxies, ed. J. Biretta et al., New Astronomy Reviews; 6 pages, including 2 figure

Revealed Competition for Greenfield Investments between European Regions

In the modern economy, cities are assumed to be in fierce competition over attracting foreign investments in leading sectors of the world economy. Despite the rich theoretical discourse on these 'wars', it remains unclear which territories are competing with each other over which types of investments Combining insights from international economics, international business, and urban systems literature, we develop an indicator to measure revealed competition between territories for investments based on the overlap of investment portfolios of regions. Taking competition for greenfield investments between European regions as a test subject, we identify competitive market segments, derive the competitive threat a region faces from other regions, the competitive threat regions pose to other regions, and the most important market segments in which regions compete. We show that European regions with similar locational endowments pose a fiercer competitive thre at to one another. In addition, regions that are sufficiently large and distinctive, face the smallest average competitive threat from all other regions

The MK2 cascade regulates mGluR-dependent synaptic plasticity and reversal learning

YesThe ability to either erase or update the memories of a previously learned spatial task is an essential process that is required to modify behaviour in a changing environment. Current evidence suggests that the neural representation of such cognitive flexibility involves the balancing of synaptic potentiation (acquisition of memories) with synaptic depression (modulation and updating previously acquired memories). Here we demonstrate that the p38 MAPK/MAPK-activated protein kinase 2 (MK2) cascade is required to maintain the precise tuning of long-term potentiation and long-term depression at CA1 synapses of the hippocampus which is correlated with efficient reversal learning. Using the MK2 knockout (KO) mouse, we show that mGluR-LTD, but not NMDAR-LTD, is markedly impaired in mice aged between 4 and 5 weeks (juvenile) to 7 months (mature adult). Although the amplitude of LTP was the same as in wildtype mice, priming of LTP by the activation of group I metabotropic receptors was impaired in MK2 KO mice. Consistent with unaltered LTP amplitude and compromised mGluR-LTD, MK2 KO mice had intact spatial learning when performing the Barnes maze task, but showed specific deficits in selecting the most efficient combination of search strategies to perform the task reversal. Findings from this study suggest that the mGluR-p38-MK2 cascade is important for cognitive flexibility by regulating LTD amplitude and the priming of LTP.Professor Richard Greene at the University of Bradford - startup fund to setup electrophysiological facility and Wellcome Trust 200646/Z/16/Z to S.A.L.C

Single electron magneto-conductivity of a nondegenerate 2D electron system in a quantizing magnetic field

We study transport properties of a non-degenerate two-dimensional system of non-interacting electrons in the presence of a quantizing magnetic field and a short-range disorder potential. We show that the low-frequency magnetoconductivity displays a strongly asymmetric peak at a nonzero frequency. The shape of the peak is restored from the calculated 14 spectral moments, the asymptotic form of its high-frequency tail, and the scaling behavior of the conductivity for omega -> 0. We also calculate 10 spectral moments of the cyclotron resonance absorption peak and restore the corresponding (non-singular) frequency dependence using the continuous fraction expansion. Both expansions converge rapidly with increasing number of included moments, and give numerically accurate results throughout the region of interest. We discuss the possibility of experimental observation of the predicted effects for electrons on helium.Comment: RevTeX 3.0, 14 pages, 8 eps figures included with eps

The temporal dynamics of Arc expression regulate cognitive flexibility

YesNeuronal activity regulates the transcription and translation of the immediate-early gene Arc/Arg3.1, a key mediator of synaptic plasticity. Proteasomedependent degradation of Arc tightly limits its temporal expression, yet the significance of this regulation remains unknown. We disrupted the temporal control of Arc degradation by creating an Arc knockin mouse (ArcKR) where the predominant Arc ubiquitination sites were mutated. ArcKR mice had intact spatial learning but showed specific deficits in selecting an optimal strategy during reversal learning. This cognitive inflexibility was coupled to changes in Arc mRNA and protein expression resulting in a reduced threshold to induce mGluR-LTD and enhanced mGluR-LTD amplitude. These findings show that the abnormal persistence of Arc protein limits the dynamic range of Arc signaling pathways specifically during reversal learning. Our work illuminates how the precise temporal control of activity-dependent molecules, such as Arc, regulates synaptic plasticity and is crucial for cognition.Open access funded by Biotechnology and Biological Sciences Research Counci

Different value of coronary calcium score to predict obstructive coronary artery disease in patients with and without moderate chronic kidney disease.

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Dynamic Critical Behavior of an Extended Reptation Dynamics for Self-Avoiding Walks

We consider lattice self-avoiding walks and discuss the dynamic critical behavior of two dynamics that use local and bilocal moves and generalize the usual reptation dynamics. We determine the integrated and exponential autocorrelation times for several observables, perform a dynamic finite-size scaling study of the autocorrelation functions, and compute the associated dynamic critical exponents $z$. For the variables that describe the size of the walks, in the absence of interactions we find $z \approx 2.2$ in two dimensions and $z\approx 2.1$ in three dimensions. At the $\theta$-point in two dimensions we have $z\approx 2.3$.Comment: laTeX2e, 32 pages, 11 eps figure