The astacin metalloprotease moulting enzyme NAS-36 is required for normal cuticle ecdysis in free-living and parasitic nematodes

Nematodes represent one of the most abundant and species-rich groups of animals on the planet, with parasitic species causing chronic, debilitating infections in both livestock and humans worldwide. The prevalence and success of the nematodes is a direct consequence of the exceptionally protective properties of their cuticle. The synthesis of this cuticle is a complex multi-step process, which is repeated 4 times from hatchling to adult and has been investigated in detail in the free-living nematode, Caenorhabditis elegans. This process is known as moulting and involves numerous enzymes in the synthesis and degradation of the collagenous matrix. The nas-36 and nas-37 genes in C. elegans encode functionally conserved enzymes of the astacin metalloprotease family which, when mutated, result in a phenotype associated with the late-stage moulting defects, namely the inability to remove the preceding cuticle. Extensive genome searches in the gastrointestinal nematode of sheep, Haemonchus contortus, and in the filarial nematode of humans, Brugia malayi, identified NAS-36 but not NAS-37 homologues. Significantly, the nas-36 gene from B. malayi could successfully complement the moult defects associated with C. elegans nas-36, nas-37 and nas-36/nas-37 double mutants, suggesting a conserved function for NAS-36 between these diverse nematode species. This conservation between species was further indicated when the recombinant enzymes demonstrated a similar range of inhibitable metalloprotease activities

The vertical structure of upper ocean variability at the Porcupine Abyssal Plain during 2012-2013

This study presents the characterization of variability in temperature, salinity and oxygen concentration, including the vertical structure of the variability, in the upper 1000m of the ocean over a full year in the northeast Atlantic. Continuously profiling ocean gliders with vertical resolution between 0.5-1m provide more information on temporal variability throughout the water column than time series from moorings with sensors at a limited number of fixed depths. The heat, salt and dissolved oxygen content are quantified at each depth. While the near surface heat content is consistent with the net surface heat flux, heat content of the deeper layers is driven by gyre-scale water mass changes. Below ~150m, heat and salt content display intraseasonal variability which has not been resolved by previous studies. A mode-1 baroclinic internal tide is detected as a peak in the power spectra of water mass properties. The depth of minimum variability is at ~415m for both temperature and salinity, but this is a depth of high variability for oxygen concentration. The deep variability is dominated by the intermittent appearance of Mediterranean Water, which shows evidence of filamentation. Susceptibility to salt fingering occurs throughout much of the water column for much of the year. Between about 700-900m, the water column is susceptible to diffusive layering, particularly when Mediterranean Water is present. This unique ability to resolve both high vertical and temporal resolution highlights the importance of intraseasonal variability in upper ocean heat and salt content, variations that may be aliased by traditional observing techniques

An investigation of the Eigenvalue Calibration Method (ECM) using GASP for non-imaging and imaging detectors

Polarised light from astronomical targets can yield a wealth of information about their source radiation mechanisms, and about the geometry of the scattered light regions. Optical observations, of both the linear and circular polarisation components, have been impeded due to non-optimised instrumentation. The need for suitable observing conditions and the availability of luminous targets are also limiting factors. GASP uses division of amplitude polarimeter (DOAP) (Compain and Drevillon) to measure the four components of the Stokes vector simultaneously, which eliminates the constraints placed upon the need for moving parts during observation, and offers a real-time complete measurement of polarisation. Results from the GASP calibration are presented in this work for both a 1D detector system, and a pixel-by-pixel analysis on a 2D detector system. Following Compain et al. we use the Eigenvalue Calibration Method (ECM) to measure the polarimetric limitations of the instrument for each of the two systems. Consequently, the ECM is able to compensate for systematic errors introduced by the calibration optics, and it also accounts for all optical elements of the polarimeter in the output. Initial laboratory results of the ECM are presented, using APD detectors, where errors of 0.2% and 0.1{\deg} were measured for the degree of linear polarisation and polarisation angle respectively. Channel-to-channel image registration is an important aspect of 2-D polarimetry. We present our calibration results of the measured Mueller matrix of each sample, used by the ECM. A set of Zenith flat-field images were recorded during an observing campaign at the Palomar 200 inch telescope in November 2012. From these we show the polarimetric errors from the spatial polarimetry indicating both the stability and absolute accuracy of GASP.Comment: Accepted for publication in Experimental Astronom

Policy Implications of a Behavioural Economics Analysis of Land Use Determinants in Rural Scotland

The paper analyses the land use behaviour of Scottish land managers and the factors influencing it in the current context of the EU rural land use policies. The analysis employs a frequently used behavioural economics method, namely structural equation modelling (SEM). Central to the empirical analysis in this paper is a cross-section database containing data collected in May to June 2009 through telephone interviews of 600 land managers in Scotland. The model tests and estimates the relationships between land use behaviour, i.e., behavioural intentions to change the size of business/holding, and several of its a priori determinants found significant in the scientific literature. The results indicate that a stronger propensity to change size of their businesses is exhibited by younger land managers who intend to pass their land on to family, with larger land size and stronger attitudes towards increasing it, with lower percentage of their income made up from Government support, who are less likely to have perceived changes in regulation and input/output prices as having an impact on their business, who discuss and plan changes in size of business with their banks/building societies, and frequently access sources of information to help with their strategic decisions.Land use, rural policies, Scotland, structural equation modelling, Land Economics/Use,

Post-operative atrial fibrillation is influenced by beta-blocker therapy but not by pre-operative atrial cellular electrophysiology

We investigated whether post-cardiac surgery (CS) new-onset atrial fibrillation (AF) is predicted by pre-CS atrial cellular electrophysiology, and whether the antiarrhythmic effect of beta-blocker therapy may involve pre-CS pharmacological remodeling. Atrial myocytes were obtained from consenting patients in sinus rhythm, just prior to CS. Action potentials and ion currents were recorded using whole-cell patch-clamp technique. Post-CS AF occurred in 53 of 212 patients (25%). Those with post-CS AF were older than those without (67 ± 2 vs 62 ± 1 years, P = 0.005). In cells from patients with post-CS AF, the action potential duration at 50% and 90% repolarization, maximum upstroke velocity, and effective refractory period (ERP) were 13 ± 4 ms, 217 ± 16 ms, 185 ± 10 V/s, and 216 ± 14 ms, respectively (n = 30 cells, 11 patients). Peak L-type Ca2+ current, transient outward and inward rectifier K+ currents, and the sustained outward current were −5.0 ± 0.5, 12.9 ± 2.4, −4.1 ± 0.4, and 9.7 ± 1.0 pA/pF, respectively (13-62 cells, 7-19 patients). None of these values were significantly different in cells from patients without post-CS AF (P > 0.05 for each, 60-279 cells, 29-86 patients), confirmed by multiple and logistic regression. In patients treated >7 days with a beta-blocker pre-CS, the incidence of post-CS AF was lower than in non-beta-blocked patients (13% vs 27%, P = 0.038). Pre-CS beta-blockade was associated with a prolonged pre-CS atrial cellular ERP (P = 0.001), by a similar degree (∼20%) in those with and without post-CS AF. Conclusion: Pre-CS human atrial cellular electrophysiology does not predict post-CS AF. Chronic beta-blocker therapy is associated with a reduced incidence of post-CS AF, unrelated to a pre-CS ERP-prolonging effect of this treatment

Circulating emm types of Streptococcus pyogenes in Scotland: 2011-2015

No abstract available

Tissue Inhibitor of Metalloproteinase–3 (TIMP-3) induces FAS dependent apoptosis in human vascular smooth muscle cells

Over expression of Tissue Inhibitor of Metalloproteinases-3 (TIMP-3) in vascular smooth muscle cells (VSMCs) induces apoptosis and reduces neointima formation occurring after saphenous vein interposition grafting or coronary stenting. In studies to address the mechanism of TIMP-3-driven apoptosis in human VSMCs we find that TIMP-3 increased activation of caspase-8 and apoptosis was inhibited by expression of Cytokine response modifier A (CrmA) and dominant negative FAS-Associated protein with Death Domain (FADD). TIMP-3 induced apoptosis did not cause mitochondrial depolarisation, increase activation of caspase-9 and was not inhibited by over-expression of B-cell Lymphoma 2 (Bcl2), indicating a mitochondrial independent/type-I death receptor pathway. TIMP-3 increased levels of the First Apoptosis Signal receptor (FAS) and depletion of FAS with shRNA showed TIMP-3-induced apoptosis was FAS dependent. TIMP-3 induced formation of the Death-Inducing Signalling Complex (DISC), as detected by immunoprecipitation and by immunofluorescence. Cellular-FADD-like IL-1 converting enzyme-Like Inhibitory Protein (c-FLIP) localised with FAS at the cell periphery in the absence of TIMP-3 and this localisation was lost on TIMP-3 expression with c-FLIP adopting a perinuclear localisation. Although TIMP-3 inhibited FAS shedding, this did not increase total surface levels of FAS but instead increased FAS levels within localised regions at the cell surface. A Disintegrin And Metalloproteinase 17 (ADAM17) is inhibited by TIMP-3 and depletion of ADAM17 with shRNA significantly decreased FAS shedding. However ADAM17 depletion did not induce apoptosis or replicate the effects of TIMP-3 by increasing localised clustering of cell surface FAS. ADAM17-depleted cells could activate caspase-3 when expressing levels of TIMP-3 that were otherwise sub-apoptotic, suggesting a partial role for ADAM17 mediated ectodomain shedding in TIMP-3 mediated apoptosis. We conclude that TIMP-3 induced apoptosis in VSMCs is highly dependent on FAS and is associated with changes in FAS and c-FLIP localisation, but is not solely dependent on shedding of the FAS ectodomain