Neutron diffraction, NMR and molecular dynamics study of glucose dissolved in the ionic liquid 1-ethyl-3-methylimidazolium acetate

beta-D-glucose dissolved in the ionic liquid 1-ethyl-3-methylimidazolium acetate in a 6 : 1 molar ratio (ionic liquid : glucose) has been studied by neutron scattering, NMR and molecular dynamics simulations. Good agreement was found between simulated neutron scattering profiles generated for isotopically substituted liquid systems and those experimentally determined as well as between simulated and experimental diffusion coefficients obtained by Pulsed Field Gradient NMR spectroscopy. The overriding glucose-ionic liquid interactions in the liquid are hydrogen-bonding between acetate oxygens and sugar hydroxyl groups. The ionic liquid cation was found to play only a minor role in the solvation of the sugar and does not participate in hydrogen-bonding with the sugar to any significant degree. NOESY experiments lend further evidence that there is no direct interaction between sugar hydroxyl groups and acidic hydrogens on the ionic liquid cation.

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10 -5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10 -5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10 -10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression.

Taking pluralism seriously:Embedded moralities in management accounting and control systems

Professor Norman Macintosh has long been a leading, and at times a dissonant, voice in critical accounting studies, exhibiting an intellectual dexterity seldom encountered in the accounting academy. His work ranges from the application of traditional organizational theories within work organizations to poststructural renderings of capital market exigencies. Here, we consider and extend Professor Macintosh's work contemplating the morality embedded within, and propagated by, management accounting and control systems (macs). We begin with Macintosh (1995) employing structuration theory in investigating the ethics of profit manipulation within large, decentralized corporations. The work highlights the fundamental dialectical contradictions within these work organizations, demonstrates the indeterminacy of traditional ethical reasoning, and shows the extent to which macs provide legitimating underpinnings for management action. We propose to extend the conversation using the tools provided in Macintosh's subsequent work: a Levinasian ethic (Macintosh et al., 2009), and heteroglossic accounting (Macintosh, 2002)—both emerging from his poststructuralist predilections. A Levinasian perspective provides an ontologically grounded ethic, and heteroglossic accounting calls for multiple accountings representing alternative moral voices. A critical dialogic framework is proposed as a theoretic for imagining heteroglossic accounting that takes pluralism seriously by recognizing the reality of irresolvable differences and asymmetric power relationships associated with assorted moral perspectives.

Short Isoforms of the Cold Receptor TRPM8 Inhibit Channel Gating by Mimicking Heat Action Rather than Chemical Inhibitors

Transient receptor potential (TRP) channels couple various environmental factors to changes in membrane potential, calcium influx, and cell signaling. They also integrate multiple stimuli through their typically polymodal activation. Thus, although the TRPM8 channel has been extensively investigated as the major neuronal cold sensor, it is also regulated by various chemicals, as well as by several short channel isoforms. Mechanistic understanding of such complex regulation is facilitated by quantitative single-channel analysis. We have recently proposed a single-channel mechanism of TRPM8 regulation by voltage and temperature. Using this gating mechanism, we now investigate TRPM8 inhibition in cell-attached patches using HEK293 cells expressing TRPM8 alone or coexpressed with its short sM8-6 isoform. This is compared with inhibition by the chemicals N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)piperazine-1-carboxamide (BCTC) and clotrimazole or by elevated temperature. We found that within the seven-state single-channel gating mechanism, inhibition of TRPM8 by short sM8-6 isoforms closely resembles inhibition by increased temperature. In contrast, inhibition by BCTC and that by clotrimazole share a different set of common features. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.

THE FORMATION OF OXYGEN-CONTAINING ORGANIC-MOLECULES IN THE ORION COMPACT RIDGE

Following a suggestion of Blake et al., we have attempted to account for the unusually large abundances of selected oxygen-containing organic molecules in the so-called

The synthesis and electronic structure of a novel [NiS4Fe2(CO)(6)] radical cluster: Implications for the active site of the [NiFe] hydrogenases

A novel [Ni'S-4'Fe-2(CO)(6)] cluster (1: 'S-4'=(CH3C6H3S2)(2)(CH2)(3)) has been synthesised, structurally characterised and has been shown to undergo a chemically reversible reduction process at -1.31 V versus Fc(+)/Fc to generate the EPR-active monoanion 1(-). Multifrequency Q-, X- and S-band EPR spectra of Ni-61-enriched 1(-) show a well-resolved quartet hyperfine splitting in the low-field region due to the interaction with a single Ni-61 (I = 3/2) nucleus. Simulations of the EPR spectra require the introduction of a single angle of non-coincidence between g, and A(1), and g(3) and A(3) to reproduce all of the features in the S- and X-band spectra. This behaviour provides a rare example of the detection and measurement of non-coincidence effects from frozen-solution EPR spectra without the need for single-crystal measurements, and in which the S-band experiment is sensitive to the non-coincidence. An analysis of the EPR spectra of 1(-) reveals a 24% Ni contribution to the SOMO in 1(-), supporting a delocalisation of the spin-density across the NiFe2 cluster. This observation is supported by IR spectroscopic results which show that the CO stretching frequencies, v(CO), shift to lower frequency by about 70 cm(-1) when 1 is reduced to 1(-). Density functional calculations provide a framework for the interpretation of the spectroscopic properties of 1(-) and suggest that the SOMO is delocalised over the whole cluster, but with little S-centre participation. This electronic structure contrasts with that of the Ni-A, -B, -C and -L forms of [NiFe] hydrogenase in which there is considerable S participation in the SOMO.

Formation of nickel-thiolate aggregates via reaction with CH2Cl2

Reaction of the mononuclear nickel-thiolate complex [Ni(L-1)(dppe)] with CH2Cl2 affords the novel pentanuclear complex Ni5Cl2(L-1)(4)(dppe)(2)], while [Ni(L-1)(dcpe)] reacts with CH2Cl2 to give the binuclear species [Ni2Cl2(L-2)(dcpe)(2)] in which two L-1 units are linked by a methylene group derived from CH2Cl2.

Feedback via Ca²⁺-activated ion channels modulates endothelin 1 signaling in retinal arteriolar smooth muscle

PURPOSE: To investigate the role of feedback by Ca²?-sensitive plasma-membrane ion channels in endothelin 1 (Et1) signaling in vitro and in vivo. Methods. Et1 responses were imaged from Fluo-4-loaded smooth muscle in isolated segments of rat retinal arteriole using two-dimensional (2-D) confocal laser microscopy. Vasoconstrictor responses to intravitreal injections of Et1 were recorded in the absence and presence of appropriate ion channel blockers using fluorescein angiograms imaged using a confocal scanning laser ophthalmoscope. Results. Et1 (10 nM) increased both basal [Ca²?](i) and the amplitude and frequency of Ca²?-waves in retinal arterioles. The Ca²?-activated Cl?-channel blockers DIDS and 9-anthracene carboxylic acid (9AC) blocked Et1-induced increases in wave frequency, and 9AC also inhibited the increase in amplitude. Iberiotoxin, an inhibitor of large conductance (BK) Ca²?-activated K?-channels, increased wave amplitude in the presence of Et1 but had no effect on frequency. None of these drugs affected basal [Ca²?](i). The voltage-operated Ca²?-channel inhibitor nimodipine inhibited wave frequency and amplitude and also lowered basal [Ca²?](i) in the presence of Et1. Intravitreal injection of Et1 caused retinal arteriolar vasoconstriction. This was inhibited by DIDS but not by iberiotoxin or penitrem A, another BK-channel inhibitor. Conclusions. Et1 evokes increases in the frequency of arteriolar Ca²?-waves in vitro, resulting in vasoconstriction in vivo. These responses, initiated by release of stored Ca²?, also require positive feedback via Ca²?-activated Cl?-channels and L-type Ca²?-channels.

Fast Retinal Vessel Detection and Measurement Using Wavelets and Edge Location Refinement

The relationship between changes in retinal vessel morphology and the onset and progression of diseases such as diabetes, hypertension and retinopathy of prematurity (ROP) has been the subject of several large scale clinical studies. However, the difficulty of quantifying changes in retinal vessels in a sufficiently fast, accurate and repeatable manner has restricted the application of the insights gleaned from these studies to clinical practice. This paper presents a novel algorithm for the efficient detection and measurement of retinal vessels, which is general enough that it can be applied to both low and high resolution fundus photographs and fluorescein angiograms upon the adjustment of only a few intuitive parameters. Firstly, we describe the simple vessel segmentation strategy, formulated in the language of wavelets, that is used for fast vessel detection. When validated using a publicly available database of retinal images, this segmentation achieves a true positive rate of 70.27%, false positive rate of 2.83%, and accuracy score of 0.9371. Vessel edges are then more precisely localised using image profiles computed perpendicularly across a spline fit of each detected vessel centreline, so that both local and global changes in vessel diameter can be readily quantified. Using a second image database, we show that the diameters output by our algorithm display good agreement with the manual measurements made by three independent observers. We conclude that the improved speed and generality offered by our algorithm are achieved without sacrificing accuracy. The algorithm is implemented in MATLAB along with a graphical user interface, and we have made the source code freely available. 

Comparative growth rates and internal banding periodicity of maerl species (Corallinales, Rhodophyta) from northern Europe

Maerl is a type of rhodolith, found in ecologically important beds of high conservation value; a major conservation objective is to establish growth rates. Maerl shows internal banding of controversial periodicity that may contain a high-resolution record of palaeoceanographic-palaeoclimatic data. To investigate growth rates and banding periodicity, we used the vital stain Alizarin Red in combination with scanning electron microscopy (SEM). Three maerl species, Phymatolithon calcareum, Lithothamnion corallioides and L. glaciale, were collected from maerl beds in Ireland. Following staining, maerl was grown in three controlled temperature treatments and at two depths in the field (P. calcareum only), with Corallina officinalis as a control for the stain. Alizarin Red was shown to be a suitable marker for growth in European maerl species and for C. officinalis. The average tip growth rate of P. calcareum from Northern Ireland at 10 m depth and under constant laboratory conditions was c. 0.9 mm yr(-1), double the rates observed at 5 m depth and in L. corallioides. Our measurements and re-examination of reported data allow us to conclude that the three most abundant maerl species in Europe grow about 1 (0.5-1.5) mm per tip per year under a wide range of field and artificial conditions. Internal banding in temperate European maerl revealed by SEM is a result of regular changes in wall thickness; the approximately monthly periodicity of bands in field-grown specimens is consistent with previous suggestions that they may be lunar. The potential for maerl banding to be a high-resolution record of palaeoclimatic and palaeoenvironmental change could be realized with this vital stain in conjunction with isotopic or microgeochemical analyses.

Effect of glucose on endothelin-1-induced calcium transients in cultured bovine retinal pericytes

Published work has shown that endothelin-l-induced contractility of bovine retinal pericytes is reduced after culture in high concentrations of glucose. The purpose of the present study was to establish the profile of endothelin-l-induced calcium transients in pericytes and to identify changes occurring after culture in high concentrations of glucose. Glucose had no effect on basal levels of cytosolic calcium or on endothelin-l-induced calcium release from intracellular stores. However, influx of calcium from the extracellular medium after endothelin-l stimulation was reduced in pericytes that had been cultured in 25 mM D-glucose. L-type Ca2+ currents were identified by patch clamping. The L-type Ca2+ channel agonist, (-)-Bay K8644, caused less influx of calcium from the extracellular medium in pericytes that had been cultured in 25 mM D-glucose than in those cultured with 5 mM D-glucose. However, 3-O-methylglucose, a nonmetabolizable analogue of glucose which can cause glycation, had similar effects to those of high concentrations of glucose. The results suggest that reduced function of the L-type Ca2+ channel that occurs in bovine retinal pericytes after culture in high concentrations of D-glucose is probably due to glycation of a channel protein.

Acculturation and religion in schools: the views of young people from minority belief backgrounds

This paper aims to explore the relationship between religious identity, acculturation strategies and perceptions of acculturation orientation in the school context amongst young people from minority
belief backgrounds. Based on a qualitative study including interviews with 26 young people from religious minority belief backgrounds in Northern Ireland, it is argued that acculturation theory provides a useful lens for understanding how young people from religious minority belief backgrounds navigate majority religious school contexts. Using a qualitative approach to explore acculturation theory enables an in-depth understanding of the inter-relationship between minority belief youth’s acculturation strategies and their respective school contexts. Similar to previous research, integrationist attitudes generally prevailed amongst minority belief young people in this study. The findings highlight how young people negotiate their religious identities in a complex web of inter-relationships between their minority religious belief community and the mainstream school culture as represented through peer and staff attitudes, school ethos and practices and religious education. Young people demonstrated differentiated understandings of acculturation orientations within the school context, which they evaluated on the basis of complex perceptions of educational policy, interpersonal relationships and individuals’ motivations. Findings are discussed in view of acculturation tensions, which arose particularly in relation to the religious education curriculum and their implications for opt-out provision as stipulated by human rights law.