Interaction between nitric oxide signaling and gap junctions: Effects on vascular function

Nitric oxide signaling, through eNOS (or possibly nNOS), and gap junction communication are essential for normal vascular function. While each component controls specific aspects of vascular function, there is substantial evidence for cross-talk between nitric oxide signaling and the gap junction proteins (connexins), and more recently, protein protein association between eNOS and connexins. This review will examine the evidence for interaction between these pathways in normal and diseased arteries, highlight the questions that remain about the mechanisms of their interaction, and explore the possible interaction between nitric oxide signaling and the newly discovered pannexin channels. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics. (C) 2011 Elsevier B.V. All rights reserved

MAPK phosphorylation of connexin 43 promotes binding of cyclin E and smooth muscle cell proliferation

<p>Rationale: Dedifferentiation of vascular smooth muscle cells (VSMC) leading to a proliferative cell phenotype significantly contributes to the development of atherosclerosis. Mitogen-activated protein kinase (MAPK) phosphorylation of proteins including connexin 43 (Cx43) has been associated with VSMC proliferation in atherosclerosis.</p> <p>Objective: To investigate whether MAPK phosphorylation of Cx43 is directly involved in VSMC proliferation.</p> <p>Methods and Results: We show in vivo that MAPK-phosphorylated Cx43 forms complexes with the cell cycle control proteins cyclin E and cyclin-dependent kinase 2 (CDK2) in carotids of apolipoprotein-E receptor null (ApoE−/−) mice and in C57Bl/6 mice treated with platelet-derived growth factor–BB (PDGF). We tested the involvement of Cx43 MAPK phosphorylation in vitro using constructs for full-length Cx43 (Cx43) or the Cx43 C-terminus (Cx43CT) and produced null phosphorylation Ser>Ala (Cx43MK4A/Cx43CTMK4A) and phospho-mimetic Ser>Asp (Cx43MK4D/Cx43CTMK4D) mutations. Coimmunoprecipitation studies in primary VSMC isolated from Cx43 wild-type (Cx43+/+) and Cx43 null (Cx43−/−) mice and analytic size exclusion studies of purified proteins identify that interactions between cyclin E and Cx43 requires Cx43 MAPK phosphorylation. We further demonstrate that Cx43 MAPK phosphorylation is required for PDGF-mediated VSMC proliferation. Finally, using a novel knock-in mouse containing Cx43-MK4A mutation, we show in vivo that interactions between Cx43 and cyclin E are lost and VSMC proliferation does not occur after treatment of carotids with PDGF and that neointima formation is significantly reduced in carotids after injury.</p> <p>Conclusions: We identify MAPK-phosphorylated Cx43 as a novel interacting partner of cyclin E in VSMC and show that this interaction is critical for VSMC proliferation. This novel interaction may be important in the development of atherosclerotic lesions.</p&gt

A topos for algebraic quantum theory

The aim of this paper is to relate algebraic quantum mechanics to topos theory, so as to construct new foundations for quantum logic and quantum spaces. Motivated by Bohr's idea that the empirical content of quantum physics is accessible only through classical physics, we show how a C*-algebra of observables A induces a topos T(A) in which the amalgamation of all of its commutative subalgebras comprises a single commutative C*-algebra. According to the constructive Gelfand duality theorem of Banaschewski and Mulvey, the latter has an internal spectrum S(A) in T(A), which in our approach plays the role of a quantum phase space of the system. Thus we associate a locale (which is the topos-theoretical notion of a space and which intrinsically carries the intuitionistic logical structure of a Heyting algebra) to a C*-algebra (which is the noncommutative notion of a space). In this setting, states on A become probability measures (more precisely, valuations) on S(A), and self-adjoint elements of A define continuous functions (more precisely, locale maps) from S(A) to Scott's interval domain. Noting that open subsets of S(A) correspond to propositions about the system, the pairing map that assigns a (generalized) truth value to a state and a proposition assumes an extremely simple categorical form. Formulated in this way, the quantum theory defined by A is essentially turned into a classical theory, internal to the topos T(A).Comment: 52 pages, final version, to appear in Communications in Mathematical Physic

Cold Gas in Cluster Cores

I review the literature's census of the cold gas in clusters of galaxies. Cold gas here is defined as the gas that is cooler than X-ray emitting temperatures (~10^7 K) and is not in stars. I present new Spitzer IRAC and MIPS observations of Abell 2597 (PI: Sparks) that reveal significant amounts of warm dust and star formation at the level of 5 solar masses per year. This rate is inconsistent with the mass cooling rate of 20 +/- 5 solar masses per year inferred from a FUSE [OVI] detection.Comment: 10 pages, conference proceeding

Chandra X-ray observations of the 3C295 cluster core

We examine the properties of the X-ray gas in the central regions of the distant (z=0.46), X-ray luminous cluster of galaxies surrounding the powerful radio source 3C 295, using observations made with the Chandra Observatory. Between radii of 50-500 kpc, the cluster gas is approximately isothermal with an emission-weighted temperature, kT ~5 keV. Within the central 50 kpc radius this value drops to kT ~3.7 keV. The spectral and imaging Chandra data indicate the presence of a cooling flow within the central 50 kpc radius of the cluster, with a mass deposition rate of approximately 280 solar masses per year. We estimate an age for the cooling flow of 1-2 Gyr, which is approximately one thousand times older than the central radio source. We find no evidence in the X-ray spectra or images for significant heating of the X-ray gas by the radio source. We report the detection of an edge-like absorption feature in the spectrum for the central 50 kpc region, which may be due to oxygen-enriched dust grains. The implied mass in metals seen in absorption could have been accumulated by the cooling flow over its lifetime. Combining the results on the X-ray gas density profile with radio measurements of the Faraday rotation measure in 3C295, we estimate the magnetic field strength in the region of the cluster core to be B ~12 \muG.Comment: 27 pages, 16 figs, 5 tables. Accepted for publication in MNRA

'Education, education, education' : legal, moral and clinical

This article brings together Professor Donald Nicolson's intellectual interest in professional legal ethics and his long-standing involvement with law clinics both as an advisor at the University of Cape Town and Director of the University of Bristol Law Clinic and the University of Strathclyde Law Clinic. In this article he looks at how legal education may help start this process of character development, arguing that the best means is through student involvement in voluntary law clinics. And here he builds upon his recent article which argues for voluntary, community service oriented law clinics over those which emphasise the education of students

X-ray Spectroscopy of Cooling Clusters

We review the X-ray spectra of the cores of clusters of galaxies. Recent high resolution X-ray spectroscopic observations have demonstrated a severe deficit of emission at the lowest X-ray temperatures as compared to that expected from simple radiative cooling models. The same observations have provided compelling evidence that the gas in the cores is cooling below half the maximum temperature. We review these results, discuss physical models of cooling clusters, and describe the X-ray instrumentation and analysis techniques used to make these observations. We discuss several viable mechanisms designed to cancel or distort the expected process of X-ray cluster cooling.Comment: To appear in Physics Reports, 71 pages, 20 figure

HST imaging of the dusty filaments and nucleus swirl in NGC4696 at the centre of the Centaurus Cluster

Narrow-band HST imaging has resolved the detailed internal structure of the 10 kpc diameter H α+[N II] emission line nebulosity in NGC4696, the central galaxy in the nearby Centaurus cluster, showing that the dusty, molecular, filaments have a width of about 60 pc. Optical morphology and velocity measurements indicate that the filaments are dragged out by the bubbling action of the radio source as part of the active galactic nucleus feedback cycle. Using the drag force we find that the magnetic field in the filaments is in approximate pressure equipartition with the hot gas. The filamentary nature of the cold gas continues inwards, swirling around and within the Bondi accretion radius of the central black hole, revealing the magnetic nature of the gas flows in massive elliptical galaxies. HST imaging resolves the magnetic, dusty, molecular filaments at the centre of the Centaurus cluster to a swirl around and within the Bondi radius

`What is a Thing?': Topos Theory in the Foundations of Physics

The goal of this paper is to summarise the first steps in developing a fundamentally new way of constructing theories of physics. The motivation comes from a desire to address certain deep issues that arise when contemplating quantum theories of space and time. In doing so we provide a new answer to Heidegger's timeless question ``What is a thing?''. Our basic contention is that constructing a theory of physics is equivalent to finding a representation in a topos of a certain formal language that is attached to the system. Classical physics uses the topos of sets. Other theories involve a different topos. For the types of theory discussed in this paper, a key goal is to represent any physical quantity $A$ with an arrow \breve{A}_\phi:\Si_\phi\map\R_\phi where \Si_\phi and $\R_\phi$ are two special objects (the `state-object' and `quantity-value object') in the appropriate topos, $\tau_\phi$. We discuss two different types of language that can be attached to a system, $S$. The first, \PL{S}, is a propositional language; the second, \L{S}, is a higher-order, typed language. Both languages provide deductive systems with an intuitionistic logic. With the aid of \PL{S} we expand and develop some of the earlier work (By CJI and collaborators.) on topos theory and quantum physics. A key step is a process we term `daseinisation' by which a projection operator is mapped to a sub-object of the spectral presheaf \Sig--the topos quantum analogue of a classical state space. The topos concerned is \SetH{}: the category of contravariant set-valued functors on the category (partially ordered set) \V{} of commutative sub-algebras of the algebra of bounded operators on the quantum Hilbert space \Hi.Comment: To appear in ``New Structures in Physics'' ed R. Coeck