Ceres' opposition effect observed by the Dawn framing camera

The surface reflectance of planetary regoliths may increase dramatically towards zero phase angle, a phenomenon known as the opposition effect (OE). Two physical processes that are thought to be the dominant contributors to the brightness surge are shadow hiding (SH) and coherent backscatter (CB). The occurrence of shadow hiding in planetary regoliths is self-evident, but it has proved difficult to unambiguously demonstrate CB from remote sensing observations. One prediction of CB theory is the wavelength dependence of the OE angular width. The Dawn spacecraft observed the OE on the surface of dwarf planet Ceres. We characterize the OE over the resolved surface, including the bright Cerealia Facula, and to find evidence for SH and/or CB. We analyze images of the Dawn framing camera by means of photometric modeling of the phase curve. We find that the OE of most of the investigated surface has very similar characteristics, with an enhancement factor of 1.4 and a FWHM of 3{\deg} (broad OE). A notable exception are the fresh ejecta of the Azacca crater, which display a very narrow brightness enhancement that is restricted to phase angles $< 0.5${\deg} (narrow OE); suggestively, this is in the range in which CB is thought to dominate. We do not find a wavelength dependence for the width of the broad OE, and lack the data to investigate the dependence for the narrow OE. The prediction of a wavelength-dependent CB width is rather ambiguous. The zero-phase observations allow us to determine Ceres' visible geometric albedo as $p_V = 0.094 \pm 0.005$. A comparison with other asteroids suggests that Ceres' broad OE is typical for an asteroid of its spectral type, with characteristics that are primarily linked to surface albedo. Our analysis suggests that CB may occur on the dark surface of Ceres in a highly localized fashion.Comment: Credit: Schr\"oder et al, A&A in press, 2018, reproduced with permission, \copyright ES

Assessing the efficacy of a novel galactooligosaccharide to promote fish health and robustness

Aquaculture has been steadily increasing global production; however, there remains a progressively greater demand for sustainable sources of protein, whilst the prevalence of disease represents a major constraint to industry growth. Feed additives are gaining traction as useful tools to help combat disease and promote health, and previous research has documented benefits to the mucosal surfaces and microbial communities within a range of teleost species. Three experimental in vivo feeding trials were undertaken using a range of in-depth analyses, such as growth performance, haematology, immunology, intestinal histology, intestinal gene expression and intestinal bacterial 16S rRNA sequence libraries. Studies were conducted on three important aquaculture species: rainbow trout (Oncorhynchus mykiss), Atlantic salmon (Salmo salar) and Nile tilapia (Oreochromis niloticus). All three experiments revealed that dietary B-GOS® applications modulated the intestinal bacterial communities and intestinal gene expression. Some of these modulations may have potential benefits at the localised level for the hosts. However, no significant improvements of growth performance metrics were observed at the whole organism level, where FCR, SGR, survival, weight gain, condition factor and body composition remained unaffected by treatment. Despite the lack of statistical significance, numerical improvements indicated that GOS at the inclusion rate of 4g kg¯¹ was the optimal concentration. Results from the experimental in vivo trials conducted during this research have provided evidence that a novel GOS tested in three commercially important teleost species had scope to improve localised intestinal health but offered little benefit to growth performance of fish reared with highly nutritious diets and excellent rearing conditions. Further research should prioritise the 4g kg¯¹ B-GOS® inclusion level for further investigation in these fish species whilst under pathogenic or environmental challenge, as this concentration presented the most potential to improve fish health and growth performance

The role of L-type voltage gated calcium channels and psychiatric risk gene CACNA1C in associative learning

CACNA1C codes for the alpha-1 subunit of Cav1.2 L-type voltage gated calcium channels (LVGCCs). Variation in CACNA1C has been reliably implicated in psychiatric illness, including schizophrenia and bipolar disorder. Analyses have indicated a convergence of genetic risk for schizophrenia on abnormalities in the synapse and in behaviours including associative learning. LVGCCs play a role in synaptic plasticity and learning, partly through regulation of gene transcription. Their role in specific aspects of associative learning that are relevant for symptoms of psychiatric illness is yet to be fully elucidated. A hippocampal-dependent fear conditioning paradigm was used to determine the role of Cacna1c and LVGCCs in specific aspects of associative learning in rats. Studies measured the activity-regulated expression of Cacna1c and the effect of inhibition of LVGCCs. A genetic Cacna1c knockdown rat model was used to investigate the effects of reduced expression on behaviour and the expression of brain derived neurotrophic factor (BDNF). This model was additionally tested on reward-based reversal-learning. Analyses were translated to humans, to assess whether disease relevant variation in CACNA1C was associated with similar deficits in reversal learning and expression. Inhibition of LVGCCs affected the consolidation, extinction and latent inhibition of contextual fear memory, whereas reduced expression of Cacan1c had a selective effect on latent inhibition. There were no effects on the acquisition of reward associations, but reversal learning was impaired. Similar deficits in reversal learning were associated with disease relevant variation in CACNA1C in humans. Reduced CACNA1C expression was found to be associated with changes in the expression of BDNF in both rats and humans. Results indicate a role for Cacna1c and LVGCCs in the appropriate formation and update of aversive and reward associations. Impairments in these processes can underlie specific symptoms of disease including emotion dysregulation and delusions. The cross-species effects on BDNF require further investigation

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Oscillometric central blood pressure and central systolic loading in stroke patients:Short-term reproducibility and effects of posture and fasting state

<div><p>Background</p><p>This study examined the short-term reproducibility of non-invasive estimates of central and peripheral blood pressure and markers of central systolic loading (augmentation index [AIx; a measure of central systolic loading] and AIx75 [AIx standardised to 75 b·min^-1 heart rate]) and the effect of posture and fasting state on these variables in patients with acute stroke.</p><p>Methods</p><p>Twenty-two acute stroke patients (72 ± 10y) had blood pressure measured using the SphygmoCor XCEL in supine and seated postures and whilst fasted and non-fasted.</p><p>Results</p><p>Acceptable short-term reproducibility (ICC >0.75) was reported for all peripheral and central variables in all conditions (ICC = 0.77–0.90) and for AIx and AIx75 in both fasted postures (ICC = 0.78–0.81). Food consumption significantly lowered all blood pressures (<i>p</i> <0.05; η²_p = 0.20–0.55). The seated posture resulted in a significantly greater AIx than supine (<i>p</i> <0.05; η²_p = 0.22). Fasting state had significant main effects on AIx and AIx75 (<i>p</i> <0.05; η²_p = 0.14–0.22).</p><p>Conslusions</p><p>Oscillometric estimates of central blood pressure have high short-term reproducibility in different postures and fasting states but markers of systolic load should be assessed whilst fasted. Fasting state has a large effect on central and peripheral blood pressures and on measures of systolic loading. It is important for clinicians to be aware of optimal assessment conditions without this impacting on patient wellbeing.</p><p>Trial registration</p><p><b>Clinical trial registry name</b>: <a href="https://clinicaltrials.gov/ct2/show/NCT02537652" target="_blank">NCT02537652</a>.</p></div

Oscillometric central blood pressure and central systolic loading in stroke patients:Short-term reproducibility and effects of posture and fasting state

Background This study examined the short-Term reproducibility of non-invasive estimates of central and peripheral blood pressure and markers of central systolic loading (augmentation index [AIx; a measure of central systolic loading] and AIx75 [AIx standardised to 75 b ·min-1 heart rate]) and the effect of posture and fasting state on these variables in patients with acute stroke. Methods Twenty-Two acute stroke patients (72 ± 10y) had blood pressure measured using the SphygmoCor XCEL in supine and seated postures and whilst fasted and non-fasted. Results Acceptable short-Term reproducibility (ICC &gt;0.75) was reported for all peripheral and central variables in all conditions (ICC = 0.77-0.90) and for AIx and AIx75 in both fasted postures (ICC = 0.78-0.81). Food consumption significantly lowered all blood pressures (p &lt;0.05; η2; p = 0.20-0.55). The seated posture resulted in a significantly greater AIx than supine (p &lt;0.05; η2; p = 0.22). Fasting state had significant main effects on AIx and AIx75 (p &lt;0.05; η2; p = 0.14-0.22). Conslusions Oscillometric estimates of central blood pressure have high short-Term reproducibility in different postures and fasting states but markers of systolic load should be assessed whilst fasted. Fasting state has a large effect on central and peripheral blood pressures and on measures of systolic loading. It is important for clinicians to be aware of optimal assessment conditions without this impacting on patient wellbeing. Trial registration Clinical trial registry name: NCT02537652.</p

Genetic variation in the psychiatric risk gene CACNA1C modulates reversal learning across species

Genetic variation in CACNA1C, which encodes the alpha-1 subunit of Cav1.2 L-type voltage-gated calcium channels (VGCCs), has been strongly linked to risk for psychiatric disorders including schizophrenia and bipolar disorder. How genetic variation in CACNA1C contributes to risk for these disorders is however not fully known. Both schizophrenia and bipolar disorder are associated with impairments in reversal learning (RL), which may contribute to symptoms seen in these conditions. We used a translational RL paradigm to investigate whether genetic variation in CACNA1C affects RL in both humans and transgenic rats. Associated changes in gene expression were explored using in situ hybridization and quantitative PCR in rats and the BRAINEAC online human database. Risk-associated genetic variation in CACNA1C in healthy human participants was associated with impairments in RL. Consistent with this finding, rats bearing a heterozygous deletion of Cacna1c were impaired in an analogous touchscreen RL task. We investigated the possible molecular mechanism underlying this impairment and found that Cacna1c +/- rats show decreased expression of Bdnf in prefrontal cortex. Examination of BRAINEAC data showed that human risk-associated genetic variation in CACNA1C is also associated with altered expression of brain-derived neurotrophic factor (BDNF) in the prefrontal cortex in humans. These results indicate that genetic variation in CACNA1C may contribute to risk for schizophrenia and bipolar disorder by impacting behavioral flexibility, potentially through altered regulation of BDNF expression in the prefrontal cortex. Tests of RL may be useful for translational studies and in the development of therapies targeting VGCC

Can wave coupling improve operational regional ocean forecasts for the north-west European Shelf?

Operational ocean forecasts are typically produced by modelling systems run using a forced mode approach. The evolution of the ocean state is not directly influenced by surface waves, and the ocean dynamics are driven by an external source of meteorological data which are independent of the ocean state. Model coupling provides one approach to increase the extent to which ocean forecast systems can represent the interactions and feedbacks between ocean, waves, and the atmosphere seen in nature. This paper demonstrates the impact of improving how the effect of waves on the momentum exchange across the ocean–atmosphere interface is represented through ocean–wave coupling on the performance of an operational regional ocean prediction system. This study focuses on the eddy-resolving (1.5 km resolution) Atlantic Margin Model (AMM15) ocean model configuration for the north-west European Shelf (NWS) region. A series of 2-year duration forecast trials of the Copernicus Marine Environment Monitoring Service (CMEMS) north-west European Shelf regional ocean prediction system are analysed. The impact of including ocean–wave feedbacks via dynamic coupling on the simulated ocean is discussed. The main interactions included are the modification of surface stress by wave growth and dissipation, Stokes–Coriolis forcing, and wave-height-dependent ocean surface roughness. Given the relevance to operational forecasting, trials with and without ocean data assimilation are considered. Summary forecast metrics demonstrate that the ocean–wave coupled system is a viable evolution for future operational implementation. When results are considered in more depth, wave coupling was found to result in an annual cycle of relatively warmer winter and cooler summer sea surface temperatures for seasonally stratified regions of the NWS. This is driven by enhanced mixing due to waves, and a deepening of the ocean mixed layer during summer. The impact of wave coupling is shown to be reduced within the mixed layer with assimilation of ocean observations. Evaluation of salinity and ocean currents against profile measurements in the German Bight demonstrates improved simulation with wave coupling relative to control simulations. Further, evidence is provided of improvement to simulation of extremes of sea surface height anomalies relative to coastal tide gauges

Somatic mutation and selection at population scale

As we age, many tissues become colonized by microscopic clones carrying somatic driver mutations1, 2, 3, 4, 5, 6–7. Some of these clones represent a first step towards cancer whereas others may contribute to ageing and other diseases. However, our understanding of this phenomenon remains limited due to the challenge of detecting mutations in small clones. Here we introduce a new version of nanorate sequencing (NanoSeq)8, a duplex sequencing method with an error rate lower than five errors per billion base pairs, which is compatible with whole-exome and targeted capture. Deep sequencing of polyclonal samples with single-molecule sensitivity simultaneously profiles large numbers of clones, providing accurate mutation rates, signatures and driver frequencies in any tissue. Applying targeted NanoSeq to 1,042 non-invasive samples of oral epithelium and 371 blood samples from a twin cohort, we report an extremely rich selection landscape, with 46 genes under positive selection in oral epithelium, more than 62,000 driver mutations and evidence of negative selection in essential genes. High-resolution maps of selection across coding and non-coding sites are obtained for many genes: a form of in vivo saturation mutagenesis. Multivariate regression models enable mutational epidemiology studies on how exposures and cancer risk factors, such as age, tobacco or alcohol, alter the acquisition or selection of somatic mutations. Accurate single-molecule sequencing provides a powerful tool to study early carcinogenesis, cancer prevention and the role of somatic mutations in ageing and disease.</p