Chronic pain is highly prevalent worldwide and represents a significant socioeconomic and public health burden. Several aspects of chronic pain, for example back pain and a severity-related phenotype ...'chronic pain grade', have been shown previously to be complex heritable traits with a polygenic component. Additional pain-related phenotypes capturing aspects of an individual's overall sensitivity to experiencing and reporting chronic pain have also been suggested as a focus for investigation. We made use of a measure of the number of sites of chronic pain in individuals within the UK general population. This measure, termed Multisite Chronic Pain (MCP), is a complex trait and its genetic architecture has not previously been investigated. To address this, we carried out a large-scale genome-wide association study (GWAS) of MCP in ~380,000 UK Biobank participants. Our findings were consistent with MCP having a significant polygenic component, with a Single Nucleotide Polymorphism (SNP) heritability of 10.2%. In total 76 independent lead SNPs at 39 risk loci were associated with MCP. Additional gene-level association analyses identified neurogenesis, synaptic plasticity, nervous system development, cell-cycle progression and apoptosis genes as enriched for genetic association with MCP. Genetic correlations were observed between MCP and a range of psychiatric, autoimmune and anthropometric traits, including major depressive disorder (MDD), asthma and Body Mass Index (BMI). Furthermore, in Mendelian randomisation (MR) analyses a causal effect of MCP on MDD was observed. Additionally, a polygenic risk score (PRS) for MCP was found to significantly predict chronic widespread pain (pain all over the body), indicating the existence of genetic variants contributing to both of these pain phenotypes. Overall, our findings support the proposition that chronic pain involves a strong nervous system component with implications for our understanding of the physiology of chronic pain. These discoveries may also inform the future development of novel treatment approaches.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Exoplanet detections have revolutionized astronomy, offering new insights into solar system architecture and planet demographics. While nearly 1,900 exoplanets have now been discovered and confirmed, ...none are still in the process of formation. Transition disks, protoplanetary disks with inner clearings best explained by the influence of accreting planets, are natural laboratories for the study of planet formation. Some transition disks show evidence for the presence of young planets in the form of disk asymmetries or infrared sources detected within their clearings, as in the case of LkCa 15 (refs 8, 9). Attempts to observe directly signatures of accretion onto protoplanets have hitherto proven unsuccessful. Here we report adaptive optics observations of LkCa 15 that probe within the disk clearing. With accurate source positions over multiple epochs spanning 2009-2015, we infer the presence of multiple companions on Keplerian orbits. We directly detect Hα emission from the innermost companion, LkCa 15 b, evincing hot (about 10,000 kelvin) gas falling deep into the potential well of an accreting protoplanet.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Unanticipated flooding challenges plant growth and fitness in natural and agricultural ecosystems. Here we describe mechanisms of developmental plasticity and metabolic modulation that underpin ...adaptive traits and acclimation responses to waterlogging of root systems and submergence of aerial tissues. This includes insights into processes that enhance ventilation of submerged organs. At the intersection between metabolism and growth, submergence survival strategies have evolved involving an ethylene-driven and gibberellin-enhanced module that regulates growth of submerged organs. Opposing regulation of this pathway is facilitated by a subgroup of ethylene-response transcription factors (ERFs), which include members that require low O2 or low nitric oxide (NO) conditions for their stabilization. These transcription factors control genes encoding enzymes required for anaerobic metabolism as well as proteins that fine-tune their function in transcription and turnover. Other mechanisms that control metabolism and growth at seed, seedling and mature stages under flooding conditions are reviewed, as well as findings demonstrating that true endurance of submergence includes an ability to restore growth following the deluge. Finally, wehighlight molecular insights obtained from natural variation of domesticated and wild species that occupy different hydrological niches, emphasizing the value of understanding natural flooding survival strategies in efforts to stabilize crop yields in flood-prone environments.
Novel computing technologies that imitate the principles of biological neural systems may offer low power consumption along with distinct cognitive and learning advantages. The development of ...reliable memristive devices capable of storing multiple states of information has opened up new applications such as neuromorphic circuits and adaptive systems. At the same time, the explosive growth of the printed electronics industry has expedited the search for advanced memory materials suitable for manufacturing flexible devices. Here, we demonstrate that solution-processed MoOx/MoS2 and WOx/WS2 heterostructures sandwiched between two printed silver electrodes exhibit an unprecedentedly large and tunable electrical resistance range from 10(2) to 10(8) Ω combined with low programming voltages of 0.1-0.2 V. The bipolar resistive switching, with a concurrent capacitive contribution, is governed by an ultrathin (<3 nm) oxide layer. With strong nonlinearity in switching dynamics, different mechanisms of synaptic plasticity are implemented by applying a sequence of electrical pulses.
Five separate data sets on the mean velocity distributions in the Princeton University/ONR Superpipe are used to establish the best estimate for the value of von Kármán’s constant for the flow in a ...fully developed, hydraulically smooth pipe. The profiles were taken using Pitot tubes, conventional hot wires and nanoscale thermal anemometry probes. The value of the constant was found to vary significantly due to measurement uncertainties in the mean velocity, friction velocity and the wall distance, and the number of data points included in the analysis. The best estimate for the von Kármán constant in turbulent pipe flow is found to be
$0.40 \pm 0.02$
. A more precise estimate will require improved instrumentation.
CADM2 has been associated with a range of behavioural and metabolic traits, including physical activity, risk-taking, educational attainment, alcohol and cannabis use and obesity. Here, we set out to ...determine whether CADM2 contributes to mechanisms shared between mental and physical health disorders. We assessed genetic variants in the CADM2 locus for association with phenotypes in the UK Biobank, IMPROVE, PROCARDIS and SCARFSHEEP studies, before performing meta-analyses. A wide range of metabolic phenotypes were meta-analysed. Psychological phenotypes analysed in UK Biobank only were major depressive disorder, generalised anxiety disorder, bipolar disorder, neuroticism, mood instability and risk-taking behaviour. In UK Biobank, four, 88 and 172 genetic variants were significantly (p < 1 × 10
) associated with neuroticism, mood instability and risk-taking respectively. In meta-analyses of 4 cohorts, we identified 362, 63 and 11 genetic variants significantly (p < 1 × 10
) associated with BMI, SBP and CRP respectively. Genetic effects on BMI, CRP and risk-taking were all positively correlated, and were consistently inversely correlated with genetic effects on SBP, mood instability and neuroticism. Conditional analyses suggested an overlap in the signals for physical and psychological traits. Many significant variants had genotype-specific effects on CADM2 expression levels in adult brain and adipose tissues. CADM2 variants influence a wide range of both psychological and metabolic traits, suggesting common biological mechanisms across phenotypes via regulation of CADM2 expression levels in adipose tissue. Functional studies of CADM2 are required to fully understand mechanisms connecting mental and physical health conditions.
Well-resolved streamwise velocity spectra are reported for smooth- and rough-wall turbulent pipe flow over a large range of Reynolds numbers. The turbulence structure far from the wall is seen to be ...unaffected by the roughness, in accordance with Townsend’s Reynolds number similarity hypothesis. Moreover, the energy spectra within the turbulent wall region follow the classical inner and outer scaling behaviour. While an overlap region between the two scalings and the associated
${ k}_{x}^{- 1} $
law are observed near
${R}^{+ } \approx 3000$
, the
${ k}_{x}^{- 1} $
behaviour is obfuscated at higher Reynolds numbers due to the evolving energy content of the large scales (the very-large-scale motions, or VLSMs). We apply a semi-empirical correction (del Álamo & Jiménez, J. Fluid Mech., vol. 640, 2009, pp. 5–26) to the experimental data to estimate how Taylor’s frozen field hypothesis distorts the pseudo-spatial spectra inferred from time-resolved measurements. While the correction tends to suppress the long wavelength peak in the logarithmic layer spectrum, the peak nonetheless appears to be a robust feature of pipe flow at high Reynolds number. The inertial subrange develops around
${R}^{+ } \gt 2000$
where the characteristic
${ k}_{x}^{- 5/ 3} $
region is evident, which, for high Reynolds numbers, persists in the wake and logarithmic regions. In the logarithmic region, the streamwise wavelength of the VLSM peak scales with distance from the wall, which is in contrast to boundary layers, where the superstructures have been shown to scale with boundary layer thickness throughout the entire shear layer. Moreover, the similarity in the streamwise wavelength scaling of the large- and very-large-scale motions supports the notion that the two are physically interdependent.
Climate-induced evolution will determine population persistence in a changing world. However, finding natural systems in which to study these responses has been a barrier to estimating the impact of ...global change on a broad scale. We propose that isolated sky islands (SI) and adjacent mountain chains (MC) are natural laboratories for studying long-term and contemporary climatic pressures on natural populations. We used greenhouse common garden trees to test whether populations on SI exposed to hot and dry climates since the end of the Pleistocene have phenotypically diverged from populations on MC, and if SI populations have converged in these traits. We show: (1) populations of Populus angustifolia from SI have diverged from MC, and converged across SI, in reproductive and productivity traits, (2) these traits (cloning and aboveground biomass, respectively) are significantly correlated, suggesting a genetic linkage between them, and (3) the trait variation is driven by both natural selection and genetic drift. These shifts represent potentially beneficial phenotypes for population persistence in a changing world. These results suggest that the SI-MC comparison is a natural laboratory, as well as a predictive framework, for studying long-term responses to climate change across the globe.
Context.
On 2020 April 19 a coronal mass ejection (CME) was detected in situ by Solar Orbiter at a heliocentric distance of about 0.8 AU. The CME was later observed in situ on April 20 by the Wind ...and BepiColombo spacecraft whilst BepiColombo was located very close to Earth. This CME presents a good opportunity for a triple radial alignment study, as the spacecraft were separated by less than 5° in longitude. The source of the CME, which was launched on April 15, was an almost entirely isolated streamer blowout. The Solar Terrestrial Relations Observatory (STEREO)-A spacecraft observed the event remotely from −75.1° longitude, which is an exceptionally well suited viewpoint for heliospheric imaging of an Earth directed CME.
Aims.
The configuration of the four spacecraft has provided an exceptionally clean link between remote imaging and in situ observations of the CME. We have used the in situ observations of the CME at Solar Orbiter, Wind, and BepiColombo and the remote observations of the CME at STEREO-A to determine the global shape of the CME and its evolution as it propagated through the inner heliosphere.
Methods.
We used three magnetic flux rope models that are based on different assumptions about the flux rope morphology to interpret the large-scale structure of the interplanetary CME (ICME). The 3DCORE model assumes an elliptical cross-section with a fixed aspect-ratio calculated by using the STEREO Heliospheric Imager (HI) observations as a constraint. The other two models are variants of the kinematically-distorted flux rope (KFR) technique, where two flux rope cross-sections are considered: one in a uniform solar wind and another in a solar-minimum-like structured solar wind. Analysis of CME evolution has been complemented by the use of (1) the ELEvoHI model to compare predicted CME arrival times and confirm the connection between the imaging and in situ observations, and (2) the PREDSTORM model, which provides an estimate of the
Dst
index at Earth using Solar Orbiter magnetometer data as if it were a real–time upstream solar wind monitor.
Results.
A clear flattening of the CME cross-section has been observed by STEREO-A, and further confirmed by comparing profiles of the flux rope models to the in situ data, where the distorted flux rope cross-section qualitatively agrees most with in situ observations of the magnetic field at Solar Orbiter. Comparing in situ observations of the magnetic field between spacecraft, we find that the dependence of the maximum (mean) magnetic field strength decreases with heliocentric distance as
r
−1.24 ± 0.50
(
r
−1.12 ± 0.14
), which is in disagreement with previous studies. Further assessment of the axial and poloidal magnetic field strength dependencies suggests that the expansion of the CME is likely neither self-similar nor cylindrically symmetric.
Measurements of the streamwise component of the turbulent fluctuations in fully developed smooth and rough pipe flow are presented over an unprecedented Reynolds number range. For Reynolds numbers
...$R{e}_{\tau } \gt 20\hspace{0.167em} 000$
, the streamwise Reynolds stress closely follows the scaling of the mean velocity profile, independent of the roughness, and over the same spatial extent. This observation extends the findings of a logarithmic law in the turbulence fluctuations as reported by Hultmark, Vallikivi & Smits (Phys. Rev. Lett., vol. 108, 2012) to include rough flows. The onset of the logarithmic region is found at a location where the wall distance is equal to ∼100 times the Kolmogorov length scale, which then marks sufficient scale separation for inertial scaling. Furthermore, in the logarithmic region the square root of the fourth-order moment also displays logarithmic behaviour, in accordance with the observation that the underlying probability density function is close to Gaussian in this region.
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