Endothelin-converting enzyme 1 promotes re-sensitization of neurokinin 1 receptor-dependent neurogenic inflammation

BACKGROUND AND PURPOSE: The metalloendopeptidase endothelin-converting enzyme 1 (ECE-1) is prominently expressed in the endothelium where it converts big endothelin to endothelin-1, a vasoconstrictor peptide. Although ECE-1 is found in endosomes in endothelial cells, the role of endosomal ECE-1 is unclear. ECE-1 degrades the pro-inflammatory neuropeptide substance P (SP) in endosomes to promote recycling and re-sensitization of its neurokinin 1 (NK(1)) receptor. We investigated whether ECE-1 regulates NK(1) receptor re-sensitization and the pro-inflammatory effects of SP in the endothelium. EXPERIMENTAL APPROACH: We examined ECE-1 expression, SP trafficking and NK(1) receptor re-sensitization in human microvascular endothelial cells (HMEC-1), and investigated re-sensitization of SP-induced plasma extravasation in rats. KEY RESULTS: HMEC-1 expressed all four ECE-1 isoforms (a-d), and fluorescent SP trafficked to early endosomes containing ECE-1b/d. The ECE-1 inhibitor SM-19712 prevented re-sensitization of SP-induced Ca2+ signals in HMEC-1 cells. Immunoreactive ECE-1 and NK(1) receptors co-localized in microvascular endothelial cells in the rat. SP-induced extravasation of Evans blue in the urinary bladder, skin and ears of the rat desensitized when the interval between two SP injections was 10 min, and re-sensitized after 480 min. SM-19712 inhibited this re-sensitization. CONCLUSIONS AND IMPLICATIONS: By degrading endocytosed SP, ECE-1 promotes the recycling and re-sensitization of NK(1) receptors in endothelial cells, and thereby induces re-sensitization of the pro-inflammatory effects of SP. Thus, ECE-1 inhibitors may ameliorate the pro-inflammatory actions of SP.

Briefing: re-engineering the city 2020–2050 – urban foresight and transition management

Cities may be responsible for up to 70% of global carbon emissions and 75% of global energy consumption and by 2050 it is estimated that 70% of the world's population could live in cities. The critical challenge for contemporary urbanism, therefore, is to understand how to develop the knowledge, capacity and capability for public agencies, the private sector and multiple users in city regions systemically to re-engineer their built environment and urban infrastructure in response to climate change and resource constraints. Re-Engineering the City 2020–2050: Urban Foresight and Transition Management (Retrofit 2050) is a major new interdisciplinary project funded under the Engineering and Physical Science Research Council's (EPSRC) Sustainable Urban Environments Programme which seeks to address this challenge. This briefing describes the background and conceptual framing of Retrofit 2050 project, its aims and objectives and research approach.

Eye candy for the blind: re-introducing Lyotard's Acinema into discourses on excess, motion and spectacle in contemporary Hollywood

Jean-François Lyotard's 1973 essay ‘Acinema’ is explicitly concerned with the cinematic medium, but has received scant critical attention. Lyotard's acinema conceives of an experimental, excessive form of film-making that uses stillness and movement to shift away from the orderly process of meaning-making within mainstream cinema. What motivates this present paper is a striking link between Lyotard's writing and contemporary Hollywood production; both are concerned with a sense of excess, especially within moments of motion. Using Charlie's Angels (McG, 2000) as a case study – a film that has been critically dismissed as ‘eye candy for the blind’ – my methodology brings together two different discourses, high culture theory and mainstream film-making, to test out and propose the value of Lyotard's ideas for the study of contemporary film. Combining close textual analysis and engagement with key scholarship on film spectacle, I reflexively engage with the process of film analysis and re-direct attention to a neglected essay by a major theorist, in order to stimulate further engagement with his work.

Estimates of aerosol radiative forcing from the MACC re-analysis

The European Centre for Medium-range Weather Forecast (ECMWF) provides an aerosol re-analysis starting from year 2003 for the Monitoring Atmospheric Composition and Climate (MACC) project. The re-analysis assimilates total aerosol optical depth retrieved by the Moderate Resolution Imaging Spectroradiometer (MODIS) to correct for model departures from observed aerosols. The reanalysis therefore combines satellite retrievals with the full spatial coverage of a numerical model. Re-analysed products are used here to estimate the shortwave direct and first indirect radiative forcing of anthropogenic aerosols over the period 2003–2010, using methods previously applied to satellite retrievals of aerosols and clouds. The best estimate of globally-averaged, all-sky direct radiative forcing is −0.7±0.3Wm−2. The standard deviation is obtained by a Monte-Carlo analysis of uncertainties, which accounts for uncertainties in the aerosol anthropogenic fraction, aerosol absorption, and cloudy-sky effects. Further accounting for differences between the present-day natural and pre-industrial aerosols provides a direct radiative forcing estimate of −0.4±0.3Wm−2. The best estimate of globally-averaged, all-sky first indirect radiative forcing is −0.6±0.4Wm−2. Its standard deviation accounts for uncertainties in the aerosol anthropogenic fraction, and in cloud albedo and cloud droplet number concentration susceptibilities to aerosol changes. The distribution of first indirect radiative forcing is asymmetric and is bounded by −0.1 and −2.0Wm−2. In order to decrease uncertainty ranges, better observational constraints on aerosol absorption and sensitivity of cloud droplet number concentrations to aerosol changes are required.

Terrorism and electoral accountability: one strike, you're out!

We examine the relationship between terrorism and electoral accountability. We find that terror has a robust positive effect on the probability that the incumbent government is replaced. The magnitude of the effect increases with the severity of the terrorist attack.

Temperature-dependent reduction pathways of complexes fac-[Re(CO)3(N-R-imidazole)(1,10-phenanthroline)]+ (R = H, CH3)

Peculiar reduction pathways of the complexes fac-[Re(imH)(CO)3(phen)]+ and fac-[Re(imCH3)(CO)3(phen)]+ (imH = imidazole, imCH3 = N-methylimidazole and phen = 1,10-phenanthroline) have been unravelled by performing combined cyclic voltammetric and in situ IR spectroelectrochemical experiments. In the temperature range of 293–233 K, the initial reduction of the phen ligand in [Re(imH)(CO)3(phen)]+ results in irreversible conversion of the imidazole ligand to 3-imidazolate by a rapid phen•−→ imH intramolecular electron transfer coupled with N H bond cleavage. This process is followed by second phen-localized 1e− reduction producing [ReI(3-im−)(CO)3(phen•−)]−, similar to the analogous 2,2'-bipyridine complex. In contrast to the bpy analogue, the stability of the phen•−-containing complexes is significantly affected by lowering the temperature. At 233 K, a secondary reaction occurs in both [Re(3-im−)(CO)3(phen•−)]− and [Re(imCH3)(CO)3(phen•−)]. The resulting products exhibit v(CO) wavenumbers indistinguishable from those of the parent phen•− complexes; however, their oxidation occurs at a considerably more positive electrode potential. It is proposed that these species are produced by a new C C bond formation between the C(2) site of 3-im− or imCH3 and the C(2) site of the phen•−ligand.

Structure and stress of Re(11%21); chiral terraces at a racemic surface

The surface structure and morphology of the clean Re(11%21) surface has been investigated through combined low energy electron diffraction intensity analysis of data taken at multiple angles of incidence, scanning tunneling microscopy, and first-principles density functional calculations. The results show how this globally racemic surface terminates in two chirally distinct terraces, which show largescale out-of-plane atomic relaxations and in-plane lateral movement of the uppermost atoms. We further identify and discuss the initial stages of step bunching upon adsorption of oxygen that leads ultimately to the large-scale faceting of the surface. Finally, we present calculations of surface stress and the response to applied surface strain, which suggest routes to the exertion of control over the expression of chirality at the surface.

Emotions and the habitus: Young people with socio-emotional differences (re)producing social, emotional and cultural capital in family and leisure space-times

In this paper we explore the importance of emotionally inter-dependent relationships to the functioning of embodied social capital and habitus. Drawing upon the experiences of young people with socio-emotional differences, we demonstrate how emotionally inter-dependent and relatively nurturing relationships are integral to the acquisition of social capital and to the co-construction and embodiment of habitus. The young people presented in this paper often had difficulties in forging social relationships and in acquiring symbolic and cultural capital in school spaces. However, we outline how these young people (re)produce and embody alternative kinds of habitus, based on emotionally reciprocal relationships forged through formal and informal leisure activities and familial and fraternal social relationships. These alternative forms of habitus provide sites of subjection, scope for acquiring social and cultural capital and a positive sense of identity in the face of problematic relations and experiences in school spaces.