Role of the endothelium and COX-1 in prostacyclin generation by whole vessels stimulated with different agonists

Prostacyclin is an important cardioprotective hormone produced by the vascular wall, whose synthesis is dependent on cyclo-oxygenase (COX) enzymes. In healthy vessels the endothelium is thought to be the main site of prostacyclin release (Moncada et al 1977). Two isoforms of COX exist, and we have recently published data demonstrating that it is COX-1 rather than COX-2 that drives the production of prostacyclin in mouse aorta (Kirkby et al 2012). In this study we aimed to extend these observations by investigating what proportion of the COX-1 driven aortic prostacyclin production that comes from the endothelium versus the rest of the vessel wall (smooth muscle layers and adventitia). To do this, we explored how removal of the endothelium would influence the ability of aortic tissue to release prostacyclin in response to a range of agonists that are known to activate the endothelium and the vessel wallNon peer reviewe

Role of shear stress in endothelial cell morphology and expression of cyclooxygenase isoforms

MEDLINE® is the source for the MeSH terms of this document.Objective-: The goal of this study was to examine the effect of chronic heterogeneous shear stress, applied using an orbital shaker, on endothelial cell morphology and the expression of cyclooxygenases 1 and 2. Methods and results-: Porcine aortic endothelial cells were plated on fibronectin-coated Transwell plates. Cells were cultured for up to 7 days either under static conditions or on an orbital shaker that generated a wave of medium inducing shear stress over the cells. Cells were fixed and stained for the endothelial surface marker CD31 or cyclooxygenases 1 and 2. En face confocal microscopy and scanning ion conductance microscopy were used to show that endothelial cells were randomly oriented at the center of the well, aligned with shear stress nearer the periphery, and expressed cyclooxygenase-1 under all conditions. Lipopolysaccharide induced cyclooxygenase-2 and the production of 6-keto-prostaglandin F1α in all cells. Conclusion-: Cyclooxygenase-1 is expressed in endothelial cells cultured under chronic shear stress of high or low directionality.Peer reviewedSubmitted Versio

Symmetries and Elasticity of Nematic Gels

A nematic liquid-crystal gel is a macroscopically homogeneous elastic medium with the rotational symmetry of a nematic liquid crystal. In this paper, we develop a general approach to the study of these gels that incorporates all underlying symmetries. After reviewing traditional elasticity and clarifying the role of broken rotational symmetries in both the reference space of points in the undistorted medium and the target space into which these points are mapped, we explore the unusual properties of nematic gels from a number of perspectives. We show how symmetries of nematic gels formed via spontaneous symmetry breaking from an isotropic gel enforce soft elastic response characterized by the vanishing of a shear modulus and the vanishing of stress up to a critical value of strain along certain directions. We also study the phase transition from isotropic to nematic gels. In addition to being fully consistent with approaches to nematic gels based on rubber elasticity, our description has the important advantages of being independent of a microscopic model, of emphasizing and clarifying the role of broken symmetries in determining elastic response, and of permitting easy incorporation of spatial variations, thermal fluctuations, and gel heterogeneity, thereby allowing a full statistical-mechanical treatment of these novel materials.Comment: 21 pages, 4 eps figure

Instanton Expansions for Mass Deformed N=4 Super Yang-Mills Theories

We derive modular anomaly equations from the Seiberg-Witten-Donagi curves for softly broken N=4 SU(n) gauge theories. From these equations we can derive recursion relations for the pre-potential in powers of m^2, where m is the mass of the adjoint hypermultiplet. Given the perturbative contribution of the pre-potential and the presence of ``gaps'' we can easily generate the m^2 expansion in terms of polynomials of Eisenstein series, at least for relatively low rank groups. This enables us to determine efficiently the instanton expansion up to fairly high order for these gauge groups, e. g. eighth order for SU(3). We find that after taking a derivative, the instanton expansion of the pre-potential has integer coefficients. We also postulate the form of the modular anomaly equations, the recursion relations and the form of the instanton expansions for the SO(2n) and E_n gauge groups, even though the corresponding Seiberg-Witten-Donagi curves are unknown at this time.Comment: harvmac(b) 28 page

Fluctuating Nematic Elastomer Membranes: a New Universality Class

We study the flat phase of nematic elastomer membranes with rotational symmetry spontaneously broken by in-plane nematic order. Such state is characterized by a vanishing elastic modulus for simple shear and soft transverse phonons. At harmonic level, in-plane orientational (nematic) order is stable to thermal fluctuations, that lead to short-range in-plane translational (phonon) correlations. To treat thermal fluctuations and relevant elastic nonlinearities, we introduce two generalizations of two-dimensional membranes in a three dimensional space to arbitrary D-dimensional membranes embedded in a d-dimensional space, and analyze their anomalous elasticities in an expansion about D=4. We find a new stable fixed point, that controls long-scale properties of nematic elastomer membranes. It is characterized by singular in-plane elastic moduli that vanish as a power-law eta_lambda=4-D of a relevant inverse length scale (e.g., wavevector) and a finite bending rigidity. Our predictions are asymptotically exact near 4 dimensions.Comment: 18 pages, 4 eps figures. submitted to PR

Hypoxia modulates platelet purinergic signalling pathways.

BACKGROUND:  Hypoxia resulting from ascent to high-altitude or pathological states at sea level is known to increase platelet reactivity. Previous work from our group has suggested that this may be adenosine diphosphate (ADP)-specific. Given the clinical importance of drugs targeting ADP pathways, research into the impact of hypoxia on platelet ADP pathways is highly important. METHODS:  Optimul aggregometry was performed on plasma from 29 lowland residents ascending to 4,700 m, allowing systematic assessment of platelet reactivity in response to several platelet agonists. Aggregometry was also performed in response to ADP in the presence of inhibitors of the two main ADP receptors, P2Y1 and P2Y12 (MRS2500 and cangrelor, respectively). Phosphorylation of vasodilator-stimulated phosphoprotein (VASP), a key determinant of platelet aggregation, was analysed using the VASPFix assay. RESULTS:  Hypobaric hypoxia significantly reduced the ability of a fixed concentration of cangrelor to inhibit ADP-induced aggregation and increased basal VASP phosphorylation. However, in the absence of P2Y receptor inhibitors, we did not find evidence of increased platelet sensitivity to any of the agonists tested and found reduced sensitivity to thrombin receptor-activating peptide-6 amide. CONCLUSION:  Our results provide evidence of increased P2Y1 receptor activity at high altitude and suggest down-regulation of the P2Y12 pathway through increased VASP phosphorylation. These changes in ADP pathway activity are of potential therapeutic significance to high-altitude sojourners and hypoxic sea level patients prescribed platelet inhibitors and warrant further investigation

Pharmacological assessment of ibuprofen arginate on platelet aggregation and colon cancer cell killing

This work was funded in part by grants from the Wellcome Trust (0852551Z108/Z, to J.A.M.) and British Heart Foundation (FS/16/1/31699, to NSK). SM is a recipient of a PhD award from the King of Saud University, AT is a recipient of a MRC PhD studentship

High-resolution spectroscopy of the R Coronae Borealis and Other Hydrogen Deficient Stars

High-resolution spectroscopy is a very important tool for studying stellar physics, perhaps, particularly so for such enigmatic objects like the R Coronae Borealis and related Hydrogen deficient stars that produce carbon dust in addition to their peculiar abundances. Examples of how high-resolution spectroscopy is used in the study of these stars to address the two major puzzles are presented: (i) How are such rare H-deficient stars created? and (ii) How and where are the obscuring soot clouds produced around the R Coronae Borealis stars?Comment: 16 pages, 9 figures, Astrophysics and Space Science Proceedings, Springer-Verlag, Berlin, 201

Spectroscopy of the N=Z-2 nucleus Cr46 and mirror energy differences

Excited states in Cr46 were sought using the C12(Ar36,2n) reaction. Gamma rays were detected with the Gammasphere array, and the Z value of the reaction products was determined with an ionization chamber located at the focal plane of the Fragment Mass Analyzer. In addition to the ground-state band observed up to IÏ€=10+ (tentatively 12+), five states are proposed to belong to the 3- band. The mirror energy differences with the analog states in Ti46 present a pronounced staggering effect between the odd and even spin members that is reproduced well by shell-model calculations incorporating the different Coulomb contributions, monopole, multipole, and single-particle effects together with an isospin-nonconserving interaction that accounts for the so-called J=2 anomaly. Dramatically different E1 decay patterns for members of the 3- band between the Cr46 and Ti46 mirrors are also observed