Polygenic risk for schizophrenia and season of birth within the UK Biobank cohort

Background: There is strong evidence that people born in winter and in spring have a small increased risk of schizophrenia. As this ‘season of birth’ effect underpins some of the most influential hypotheses concerning potentially modifiable risk exposures, it is important to exclude other possible explanations for the phenomenon. Methods: Here we sought to determine whether the season of birth effect reflects gene-environment confounding rather than a pathogenic process indexing environmental exposure. We directly measured, in 136 538 participants from the UK Biobank (UKBB), the burdens of common schizophrenia risk alleles and of copy number variants known to increase the risk for the disorder, and tested whether these were correlated with a season of birth. Results: Neither genetic measure was associated with season or month of birth within the UKBB sample. Conclusions: As our study was highly powered to detect small effects, we conclude that the season of birth effect in schizophrenia reflects a true pathogenic effect of environmental exposure

Why is Africa rifting?

Continental rifting has a fundamental role in the tectonic behaviour of the Earth, shaping the surface we live on. Although there is not yet a consensus about the dominant mechanism for rifting, there is a general agreement that the stresses required to rift the continental lithosphere are not readily available. Here we use a global finite element model of the lithosphere to calculate the stresses acting on Africa. We consider the stresses induced by mantle flow, crustal structure and topography in two types of models: one in which flow is exclusively driven by the subducting slabs and one in which it is derived from a shear wave tomographic model. The latter predicts much larger stresses and a more realistic dynamic topography. It is therefore clear that the mantle structure beneath Africa plays a key part in providing the radial and horizontal tractions, dynamic topography and gravitational potential energy necessary for rifting. Nevertheless, the total available stress (c. 100 MPa) is much less than that needed to break thick, cold continental lithosphere. Instead, we appeal to a model of magma-assisted rifting along pre-existing weaknesses, where the strain is localized in a narrow axial region and the strength of the plate is reduced significantly. Mounting geological and geophysical observations support such a model

The microseismic response at the In Salah Carbon Capture and Storage (CCS) site

AbstractIn 2004, injection of carbon dioxide (CO2) to be stored at depth began at the In Salah Carbon Capture and Storage (CCS) site and a pilot microseismic monitoring array was installed in 2009. The In Salah project presents an unusual dataset since it is the first major non-Enhanced Oil Recovery (EOR) CCS project to be monitored for microseismicity. This paper outlines an extensive seismological study using a range of techniques, relying mainly on data from a single three-component geophone. Important information is derived from the data, such as event locations, event magnitudes and fracture characteristics, that could be used in real-time to regulate the geomechanical response of a site to CO2 injection. The event rate closely follows the CO2 injection rate, with a total of 9506 seismic events detected. The locations for a carefully selected subset of events are estimated to occur at or below the injection interval, thereby ruling out fault or fracture activation caused by CO2 migration at shallow depths. A very small number of events (11) with less well-constrained locations may have occurred above the injection interval. However, there is no microseismic evidence that these events are correlated with CO2 injection and we suggest they are caused by stress transfer rather than CO2 migration into the caprock. The observed maximum moment magnitude, Mw=1.7, is consistent with estimated fracture dimensions at the injection depth. Fracture orientation estimated using shear-wave splitting analysis is approximately NW-SE, in agreement with fracture orientations inferred from logging data. During periods of high injection rates the degree of anisotropy increases slightly and then falls back to original values when injection rates fall. This implies the CO2 is opening pre-existing fractures which then close as pressure decreases.This an important proof-of-concept study that proves the value of microseismic monitoring of CCS projects, even with a limited array. We thus recommend that microseismic monitoring arrays are installed prior to CO2 injection at future CCS sites to enhance our understanding by making baseline and comparative studies possible. This would also provide real-time monitoring of the geomechanical response to injection, allowing operators to modify injection parameters and to help ensure the safe operation of a project

Uveal melanoma cells use ameboid and mesenchymal mechanisms of cell motility crossing the endothelium

Uveal melanomas (UMs) are malignant cancers arising from the pigmented layers of the eye. UM cells spread through the bloodstream, and circulating UM cells are detectable in patients before metastases appear. Extravasation of UM cells is necessary for formation of metastases, and transendothelial migration (TEM) is a key step in extravasation. UM cells execute TEM via a stepwise process involving the actin-based processes of ameboid blebbing and mesenchymal lamellipodial protrusion. UM cancers are driven by oncogenic mutations that activate Gαq/11, and this activates TRIO, a guanine nucleotide exchange factor for RhoA and Rac1. We found that pharmacologic inhibition of Gαq/11 in UM cells reduced TEM. Inhibition of the RhoA pathway blocked amoeboid motility but led to enhanced TEM; in contrast, inhibition of the Rac1 pathway decreased mesenchymal motility and reduced TEM. Inhibition of Arp2/3 complex allowed cells to transmigrate without intercalation, a direct mechanism similar to the one often displayed by immune cells. BAP1-deficient (+/-) UM subclones displayed motility behavior and increased levels of TEM, similar to the effects of RhoA inhibitors. We conclude that RhoA and Rac1 signaling pathways, downstream of oncogenic Gαq/11, combine with pathways regulated by BAP1 to control the motility and transmigration of UM cells

Differences in peripheral noradrenergic function among actively drinking and abstinent alcohol-dependent individuals.

We examined whether excessive alcohol consumption was related to changes in plasma levels of noradrenaline (NA) and whether these changes recover following abstinence. We also explored whether there were differences in NA levels between Type I and Type II alcoholics and controls during active drinking and abstinence. Plasma concentrations of NA were determined in (1) 27 Caucasian men with alcohol dependence who were regularly drinking (active drinkers) within 24 hours of hospitalization, (2) 29 Caucasian alcohol-dependent men who were in remission (abstinent for a minimum of three months), and (3) 28 race- and gender-matched healthy controls. NA concentrations were significantly higher in actively drinking alcohol-dependent subjects compared to those in remission and controls. While Type I and Type II alcoholic individuals differed across clinical measures, NA levels were similar in the two subtypes. Both subtypes showed an elevation in NA levels during active drinking compared to controls, but NA levels did not differ between the two subtypes and controls during remission. The findings indicate that chronic exposure to alcohol may lead to disturbances in NA activity that may manifest in early abstinence. However, the changes in NA activity appears to normalize after a longer period of abstinence. Alterations in NA activity do not seem to be specific for Type I or Type II subtypes of alcoholism

Transtensional deformation of Montserrat revealed by shear wave splitting

Here we investigate seismic anisotropy of the upper crust in the vicinity of Soufrière Hills volcano using shear wave splitting (SWS) analysis from volcano-tectonic (VT) events. Soufrière Hills, which is located on the island of Montserrat in the Lesser Antilles, became active in 1995 and has been erupting ever since with five major phases of extrusive activity. We use data recorded on a network of seismometers between 1996 and 2007 partially spanning three extrusive phases. Shear-wave splitting in the crust is often assumed to be controlled either by structural features, or by stress aligned cracks. In such a case the polarization of the fast shear wave (ϕ) would align parallel to the strike of the structure, or to the maximum compressive stress direction. Previous studies analyzing SWS in the region using regional earthquakes observed temporal variations in ϕ which were interpreted as being caused by stress perturbations associated with pressurization of a dyke. Our analysis, which uses much shallower sources and thus only samples the anisotropy of the upper few kilometres of the crust, shows no clear temporal variation. However, temporal effects cannot be ruled out, as large fluctuations in the rate of VT events over the course of the study period as well as changes in the seismic network configuration make it difficult to assess. Average delay times of approximately 0.2 s, similar in magnitude to those reported for much deeper slab events, suggest that the bulk of the anisotropy is in the shallow crust. We observe clear spatial variations in anisotropy which we believe are consistent with structurally controlled anisotropy resulting from a left-lateral transtensional array of faults which crosses the volcanic complex

Low-frequency earthquakes beneath Tullu Moye volcano, Ethiopia, reveal fluid pulses from shallow magma chamber

The active magmatic processes beneath volcanoes in continental rifts is poorly understood. For example, until recently in the East African rift (EAR), the majority of the young volcanoes were thought to be inactive. More recent studies have shown that numerous volcanoes in the EAR are seismically active and deforming rapidly. However, an unambiguous sign of actively degassing magma hosted in shallow magma bodies has eluded most investigators. Here we present detailed analysis of the first low-frequency (LF) earthquake swarms to be observed in the Main Ethiopian Rift. The earthquakes locate to beneath Tullu Moye volcano and are directly related to the presence of a shallow magma body with a high fluid content. Using spectral modelling we show that the LF earthquakes appear to have low stress-drops (1�50 kPa) which we interpret in terms of low rupture velocities and high pore-fluid pressure. Careful relocation of the LF earthquakes place them approximately 4 km below the surface within one of two possible clusters. However, analysis of the correlation between earthquake waveforms show that each swarm contains a range of earthquake families and as such a diversity of earthquake source mechanisms. To explain these observations, we propose the seismicity is induced by H2O/CO2 fluid pulses from the shallow magma body into a highly fractured region. Fluid pulses cause high pore fluid pressures, which also cause the low rupture velocities

Local seismicity near the actively deforming Corbetti volcano in the Main Ethiopian Rift

Corbetti is currently one of the fastest uplifting volcanoes globally, with strong evidence from geodetic and gravity data for a subsurface inflating magma body. A dense network of 18 stations has been deployed around Corbetti and Hawassa calderas between February 2016 and October 2017, to place seismic constraints on the magmatic, hydrothermal and tectonic processes in the region. We locate 122 events of magnitudes between 0.4 and 4.2 using a new local velocity model. The seismicity is focused in two areas: directly beneath Corbetti caldera and beneath the city of Hawassa. The shallower 0–5 km depth below sea level (b.s.l.) earthquakes beneath Corbetti are mainly focused in EW- to NS-elongated clusters at Urji and Chabbi volcanic centres. This distribution is interpreted to be mainly controlled by a northward propagation of hydrothermal fluids away from a cross-rift pre-existing fault. Source mechanisms are predominantly strike-slip and different to the normal faulting away from the volcano, suggesting a local rotation of the stress-field. These observations, along with a low Vp/Vs ratio, are consistent with the inflation of a gas-rich sill, likely of silicic composition, beneath Corbetti. In contrast, the seismicity beneath Hawassa extends to greater depth (16 km b.s.l.). These earthquakes are focused on 8–10 km long segmented faults, which are active in seismic swarms. One of these swarms, in August 2016, is focused between 5 and 16 km depth b.s.l. along a steep normal fault beneath the city of Hawassa, highlighting the earthquake hazard for the local population

Seismic anisotropy in deforming halite:Evidence from the Mahogany salt body

We present unambiguous evidence that the Mahogany salt body, located in the Northern part of the Gulf of Mexico, is seismically anisotropic. Evidence of anisotropy comes from shear wave splitting data obtained from a vertical seismic profile VSP. The data set consists of 48 vertically aligned receivers in a borehole drilled through the salt body. Splitting analysis is performed on shear wave phases that are converted from compressional waves at the top and bottom of the salt body. The phase converted at the top of the salt layer shows a clear signature of seismic anisotropy, while the phase at the base of the salt layer shows negligible splitting. We investigate the possibility of rock salt halite LPO as a cause of the observed anisotropy. A finite element geomechanical salt deformation model of the Mahogany salt body is developed, where deformation history is used as an input to the texture plasticity simulation program VPSC. Assuming a halite salt body, a full elasticity model is then calculated and used to create a synthetic VSP splitting data set. The comparison between the synthetic and real VSP data set shows that LPO of rock salt can explain the observed anisotropy remarkably well. This is the strongest evidence to date of seismic anisotropy in a deforming salt structure. Furthermore, for the first time, we are able to demonstrate clear evidence that deforming halite is the most likely cause of this anisotropy, combining data set analysis and synthetic full wave form modelling based on calculated rock salt elasticities. Neglecting anisotropy in seismic processing in salt settings could lead to potential imaging errors, for example the deformation models show an averaged delta parameter of δ=-0.06, which would lead in a zero offset reflection setting to a depth mismatch of 6.2 per cent. Our work also show how observations of salt anisotropy can be used to probe characteristics of salt deformation