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.
Determining the mechanisms by which genes are switched on and off during development is a key aim of current biomedical research. Gene transcription has been widely observed to occur in a ...discontinuous fashion, with short bursts of activity interspersed with periods of inactivity. It is currently not known if or how this dynamic behaviour changes as mammalian cells differentiate. To investigate this, using an on-microscope analysis, we monitored mouse α-globin transcription in live cells throughout erythropoiesis. We find that changes in the overall levels of α-globin transcription are most closely associated with changes in the fraction of time a gene spends in the active transcriptional state. We identify differences in the patterns of transcriptional bursting throughout differentiation, with maximal transcriptional activity occurring in the mid-phase of differentiation. Early in differentiation, we observe increased fluctuation in transcriptional activity whereas at the peak of gene expression, in early erythroblasts, transcription is relatively stable. Later during differentiation as α-globin expression declines, we again observe more variability in transcription within individual cells. We propose that the observed changes in transcriptional behaviour may reflect changes in the stability of active transcriptional compartments as gene expression is regulated during differentiation.
Three inherited autosomal dominant conditions-BRCA-related hereditary breast and ovarian cancer (HBOC), Lynch syndrome (LS) and familial hypercholesterolemia (FH)-have been termed the Centers for ...Disease Control and Prevention Tier 1 (CDCT1) genetic conditions, for which early identification and intervention have a meaningful potential for clinical actionability and a positive impact on public health
. In typical medical practice, genetic testing for these conditions is based on personal or family history, ethnic background or other demographic characteristics
. In this study of a cohort of 26,906 participants in the Healthy Nevada Project (HNP), we first evaluated whether population screening could efficiently identify carriers of these genetic conditions and, second, we evaluated the impact of genetic risk on health outcomes for these participants. We found a 1.33% combined carrier rate for pathogenic and likely pathogenic (P/LP) genetic variants for HBOC, LS and FH. Of these carriers, 21.9% of participants had clinically relevant disease, among whom 70% had been diagnosed with relevant disease before age 65. Moreover, 90% of the risk carriers had not been previously identified, and less than 19.8% of these had documentation in their medical records of inherited genetic disease risk, including family history. In a direct follow-up survey with all carriers, only 25.2% of individuals reported a family history of relevant disease. Our experience with the HNP suggests that genetic screening in patients could identify at-risk carriers, who would not be otherwise identified in routine care.
Optically luminous quasars at
z
> 5 are important probes of super-massive black hole (SMBH) formation. With new and future radio facilities, the discovery of the brightest low-frequency radio ...sources in this epoch would be an important new probe of cosmic reionization through 21-cm absorption experiments. In this work, we systematically study the low-frequency radio properties of a sample of 115 known spectroscopically confirmed
z
> 5 quasars using the second data release of the Low Frequency Array (LOFAR) Two Metre Sky survey (LoTSS-DR2), reaching noise levels of ∼80 μJy beam
−1
(at 144 MHz) over an area of ∼5720 deg
2
. We find that 41 sources (36%) are detected in LoTSS-DR2 at > 2
σ
significance and we explore the evolution of their radio properties (power, spectral index, and radio loudness) as a function of redshift and rest-frame ultra-violet properties. We obtain a median spectral index of −0.29
−0.09
+0.10
by stacking 93 quasars using LoTSS-DR2 and Faint Images of the Radio Sky at Twenty Centimetres (FIRST) data at 1.4 GHz, in line with observations of quasars at
z
< 3. We compare the radio loudness of the high-
z
quasar sample to a lower-
z
quasar sample at
z
∼ 2 and find that the two radio loudness distributions are consistent with no evolution, although the low number of high-
z
quasars means that we cannot rule out weak evolution. Furthermore, we make a first order empirical estimate of the
z
= 6 quasar radio luminosity function, which is used to derive the expected number of high-
z
sources that will be detected in the completed LoTSS survey. This work highlights the fact that new deep radio observations can be a valuable tool in selecting high-
z
quasar candidates for follow-up spectroscopic observations by decreasing contamination of stellar dwarfs and reducing possible selection biases introduced by strict colour cuts.
We report the first plausible optical electromagnetic counterpart to a (candidate) binary black hole merger. Detected by the Zwicky Transient Facility, the electromagnetic flare is consistent with ...expectations for a kicked binary black hole merger in the accretion disk of an active galactic nucleus B. McKernan, K. E. S. Ford, I. Bartoset al., Astrophys. J. Lett.884, L50 (2019) and is unlikely <O(0.01%)) due to intrinsic variability of this source. The lack of color evolution implies that it is not a supernova and instead is strongly suggestive of a constant temperature shock. Other false-positive events, such as microlensing ora tidal disruption event, are ruled out or constrained to be <O(0.1%). If the flare is associated withS190521g, we find plausible values of total mass M(BBH) ∼ 100 Mꙩ, kick velocity v(k) ∼ 200 km/s at θ ∼ 60° in a disk with aspect ratio H/a ∼ 0.01(i.e., disk height H at radius a) and gas density ρ ∼ 10^(−10)g/cu.cm. The merger could have occurred at a disk migration trap (a ∼ 700 r(g); r(g) ≡ GM(SMBH)/sq.c, where M(SMBH) is the mass of the active galactic nucleus supermassive black hole). The combination of parameters implies a significant spin for at least one of the black holes in S190521g. The timing of our spectroscopy prevents useful constraints on broad-line asymmetry due to an off-center flare. We predict a repeat flare in this source due to a reencountering with the disk in ∼ 1.6 yr(M(SMBH)/10^(8) Mꙩ)(a/10^(3)r(g))^(3/2).
We present first results of the H2O Southern Galactic Plane Survey (HOPS), using the Mopra Radio Telescope with a broad-band backend and a beam size of about 2 arcmin. We have observed 100 deg2 of ...the southern Galactic plane at 12 mm (19.5-27.5 GHz), including spectral line emission from H2O masers, multiple metastable transitions of ammonia, cyanoacetylene, methanol and radio recombination lines. In this paper, we report on the characteristics of the survey and H2O maser emission. We find 540 H2O masers, of which 334 are new detections. The strongest maser is 3933 Jy and the weakest is 0.7 Jy, with 62 masers over 100 Jy. In 14 maser sites, the spread in the velocity of the H2O maser emission exceeds 100 km s−1. In one region, the H2O maser velocities are separated by 351.3 km s−1. The rms noise levels are typically between 1 and 2 Jy, with 95 per cent of the survey under 2 Jy. We estimate completeness limits of 98 per cent at around 8.4 Jy and 50 per cent at around 5.5 Jy. We estimate that there are between 800 and 1500 H2O masers in the Galaxy that are detectable in a survey with similar completeness limits to HOPS. We report possible masers in NH3 (11,9) and (8,6) emission towards G19.61−0.23 and in the NH3 (3,3) line towards G23.33−0.30.
Abstract
Radio emission is a key indicator of star formation activity in galaxies, but the radio luminosity–star formation relation has to date been studied almost exclusively at frequencies of ...1.4 GHz or above. At lower radio frequencies, the effects of thermal radio emission are greatly reduced, and so we would expect the radio emission observed to be completely dominated by synchrotron radiation from supernova-generated cosmic rays. As part of the LOFAR Surveys Key Science project, the Herschel-ATLAS NGP field has been surveyed with LOFAR at an effective frequency of 150 MHz. We select a sample from the MPA-JHU catalogue of Sloan Digital Sky Survey galaxies in this area: the combination of Herschel, optical and mid-infrared data enable us to derive star formation rates (SFRs) for our sources using spectral energy distribution fitting, allowing a detailed study of the low-frequency radio luminosity–star formation relation in the nearby Universe. For those objects selected as star-forming galaxies (SFGs) using optical emission line diagnostics, we find a tight relationship between the 150 MHz radio luminosity (L150) and SFR. Interestingly, we find that a single power-law relationship between L150 and SFR is not a good description of all SFGs: a broken power-law model provides a better fit. This may indicate an additional mechanism for the generation of radio-emitting cosmic rays. Also, at given SFR, the radio luminosity depends on the stellar mass of the galaxy. Objects that were not classified as SFGs have higher 150-MHz radio luminosity than would be expected given their SFR, implying an important role for low-level active galactic nucleus activity.
We present Low-Frequency Array (LOFAR) High-Band Array observations of the Herschel-ATLAS North Galactic Pole survey area. The survey we have carried out, consisting of four pointings covering around ...142 deg2 of sky in the frequency range 126–173 MHz, does not provide uniform noise coverage but otherwise is representative of the quality of data to be expected in the planned LOFAR wide-area surveys, and has been reduced using recently developed ‘facet calibration’ methods at a resolution approaching the full resolution of the data sets (∼10 × 6 arcsec) and an rms off-source noise that ranges from 100 μJy beam−1 in the centre of the best fields to around 2 mJy beam−1 at the furthest extent of our imaging. We describe the imaging, cataloguing and source identification processes, and present some initial science results based on a 5σ source catalogue. These include (i) an initial look at the radio/far-infrared correlation at 150 MHz, showing that many Herschel sources are not yet detected by LOFAR; (ii) number counts at 150 MHz, including, for the first time, observational constraints on the numbers of star-forming galaxies; (iii) the 150-MHz luminosity functions for active and star-forming galaxies, which agree well with determinations at higher frequencies at low redshift, and show strong redshift evolution of the star-forming population; and (iv) some discussion of the implications of our observations for studies of radio galaxy life cycles.
The West Antarctic Ice Sheet is one of the largest potential sources of rising sea levels. Over the past 40 years, glaciers flowing into the Amundsen Sea sector of the ice sheet have thinned at an ...accelerating rate, and several numerical models suggest that unstable and irreversible retreat of the grounding line-which marks the boundary between grounded ice and floating ice shelf-is underway. Understanding this recent retreat requires a detailed knowledge of grounding-line history, but the locations of the grounding line before the advent of satellite monitoring in the 1990s are poorly dated. In particular, a history of grounding-line retreat is required to understand the relative roles of contemporaneous ocean-forced change and of ongoing glacier response to an earlier perturbation in driving ice-sheet loss. Here we show that the present thinning and retreat of Pine Island Glacier in West Antarctica is part of a climatically forced trend that was triggered in the 1940s. Our conclusions arise from analysis of sediment cores recovered beneath the floating Pine Island Glacier ice shelf, and constrain the date at which the grounding line retreated from a prominent seafloor ridge. We find that incursion of marine water beyond the crest of this ridge, forming an ocean cavity beneath the ice shelf, occurred in 1945 (±12 years); final ungrounding of the ice shelf from the ridge occurred in 1970 (±4 years). The initial opening of this ocean cavity followed a period of strong warming of West Antarctica, associated with El Niño activity. Thus our results suggest that, even when climate forcing weakened, ice-sheet retreat continued.
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