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

Minimum clinically important difference of the Social Functioning in Dementia Scale (SF-DEM)

Objectives: Good social functioning is important for people living with dementia and their families. The Social Functioning in Dementia Scale (SF-DEM) is a valid and reliable instrument measuring social functioning in dementia. However the minimum clinically important difference (MCID) has not yet been derived for SF-DEM. This study aims to define the MCID for the SF-DEM. // Design: We used triangulation, incorporating data from a cross-sectional study to calculate the MCID using distribution-based and anchor-based methods, and a Delphi survey. // Setting and participants: The cross-sectional survey comprised 299 family carers of people with dementia. Twenty dementia experts (researchers, clinicians, family carers) rated whether changes on clinical vignettes represented a meaningful change in the Delphi survey. // Primary outcome measures: We calculated the distribution-based MCID as 0.5 of an SD for each of the three SF-DEM domains (1—spending time with others, 2—communicating with others, 3—sensitivity to others). We used the carers’ rating of social functioning to calculate the anchor-based MCID. For the Delphi survey, we defined consensus as ≥75% agreement. Where there was lack of consensus, experts were asked to complete a further survey round. // Results: We found that 0.5 SD of SF-DEM was 1.9 points, 2.2 and 1.4 points in domains 1, 2 and 3, respectively. Using the anchoring analysis, the MCIDs were 1.7 points, 1.7 points, and 0.9 points in domains 1, 2 and 3, respectively. The Delphi method required two rounds. In the second round, a consensus was reached that a 2-point change was considered significant in all three domains, but no consensus was reached on a 1-point change. // Conclusions: By triangulating all three methods, the SF-DEM’s MCIDs were 1.9, 2.0 and 1.4 points for domains 1, 2 and 3, respectively. For individuals, these values should be rounded to a 2-point change for each domain

Fortnight

Fortnight is a two-week long, fully immersive, experience based in the interactions and communications of daily life. Up to 200 participants sign up to receive messages that are sent to their mobile phones, email, and home address; these messages contain a series of poetic nudges that encourage those participating to question their sense of place. Participants also receive daily invitations to visit locations throughout their city where they can pause to reflect on what it means to be here now. Fortnight enables the experience of “theatre” to penetrate beneath a seemingly brittle aesthetic surface of performance, deep into the consciousnesses of our participants as they begin to interact with and perceive world around us as the performance itself; the place where we act out our own daily lives. In Fortnight, the spectator becomes participant; the journey becomes narrative. Fortnight therefore subverts the notion of an audience, in which each spectator’s perspective is forced to examine not the situation and setting of performers on a stage, but rather the situation and setting of our own sense of place and the meaning we apportion to our everyday lives. Fortnight uses various forms of ubiquitous technology such as: Radio Frequency Identification (aka, RFID tags of the type contained in key fobs), which are used in badges sent to each participant that allow them to interact with real-world “portals” to trigger certain effects in their surroundings; QR technology (in the form of barcodes on posters that reveal additional hidden messages, should the participant choose to delve further; SMS messages; email; and, Twitter. Alongside this, older modes of communication such as handwritten letters, give Fortnight a decidedly low-fi aesthetic. Throughout Fortnight, participants are encouraged to explore the creative possibilities of pervasive and communicative media without reverting to mere technological fetishism. In Fortnight, each mode of communication is used not only for its functionality but also as symbols that bind the project and the participant together, rooting them to the here and now with the everyday tools of modern society. The mediated messages within Fortnight lead participants down a living, breathing rabbit hole where the familiar becomes unfamiliar and reality distorts. The project becomes an experience for the participant that is as immersive as their own life; creating an alternative reality, that not only co-exists alongside their own everyday realities, but also merges with them.This is a performance with shared responsibilities, reflecting the actions and consequences of our daily lives: what we put in, we get out

Exploration of barriers and enablers for evidence-based interventions for upper limb rehabilitation following a stroke : use of Constraint Induced Movement Therapy and Robot Assisted Therapy in NHS Scotland

The routine use of evidence-based upper limb rehabilitation interventions after stroke has the potential to improve function and increase independence. Two such interventions are Constraint Induced Movement Therapy and Robot Assisted Therapy. Despite evidence to support both interventions, their use within the National Health Service appears, anecdotally, to be low. We sought to understand user perceptions in order to explain low uptake in clinical practice. Methods A combination of a cross-sectional online survey with therapists and semi-structured interviews with stroke patients was used to explore uptake and user opinions on the benefits, enablers and barriers to each intervention. Findings The therapists surveyed reported low use of Constraint Induced Movement Therapy and Robot Assisted Therapy in clinical practice within the Scottish National Health Service. Barriers identified by therapists were inadequate staffing, and a lack of training and resources. Interviews with stroke patients identified themes that may help us to understand the acceptability of each intervention, such as the impact of motivation. Conclusion Barriers to the uptake of Constraint Induced Movement Therapy and Robot Assisted Therapy within the clinical setting were found to be similar. Further qualitative research should be completed in order to help us understand the role patient motivation plays in uptake

Mechanisms of HIV Transcriptional Regulation and Their Contribution to Latency

Long-lived latent HIV-infected cells lead to the rebound of virus replication following antiretroviral treatment interruption and present a major barrier to eliminating HIV infection. These latent reservoirs, which include quiescent memory T cells and tissue-resident macrophages, represent a subset of cells with decreased or inactive proviral transcription. HIV proviral transcription is regulated at multiple levels including transcription initiation, polymerase recruitment, transcription elongation, and chromatin organization. How these biochemical processes are coordinated and their potential role in repressing HIV transcription along with establishing and maintaining latency are reviewed