Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis

Background A non-invasive method to grade the severity of steatohepatitis and liver fibrosis is magnetic resonance imaging (MRI) based corrected T1 (cT1). We aimed to identify genetic variants influencing liver cT1 and use genetics to understand mechanisms underlying liver fibroinflammatory disease and its link with other metabolic traits and diseases. Methods First, we performed a genome-wide association study (GWAS) in 14,440 Europeans in UK Biobank with liver cT1 measures. Second, we explored the effects of the cT1 variants on liver blood tests, and a range of metabolic traits and diseases. Third, we used Mendelian randomisation to test the causal effects of 24 predominantly metabolic traits on liver cT1 measures. Results We identified six independent genetic variants associated with liver cT1 that reached GWAS significance threshold (p<5x10-8). Four of the variants (rs75935921 in SLC30A10, rs13107325 in SLC39A8, rs58542926 in TM6SF2, rs738409 in PNPLA3) were also associated with elevated transaminases and had variable effects on liver fat and other metabolic traits. Insulin resistance, type 2 diabetes, non-alcoholic fatty liver and BMI were causally associated with elevated cT1 whilst favourable adiposity (instrumented by variants associated with higher adiposity but lower risk of cardiometabolic disease and lower liver fat) was found to be protective. Conclusion The association between two metal ion transporters and cT1 indicates an important new mechanism in steatohepatitis. Future studies are needed to determine whether interventions targeting the identified transporters might prevent liver disease in at risk individuals

Fragmentation dynamics of the ethyl bromide and ethyl iodide cations: a velocity-map imaging study

The photodissociation dynamics of ethyl bromide and ethyl iodide cations (C2H5Br+ and C2H5I+) have been studied. Ethyl halide cations were formed through vacuum ultraviolet (VUV) photoionization of the respective neutral parent molecules at 118.2 nm, and were photolysed at a number of ultraviolet (UV) photolysis wavelengths, including 355 nm and wavelengths in the range from 236 to 266 nm. Time-of-flight mass spectra and velocity-map images have been acquired for all fragment ions and for ground (Br) and spin–orbit excited (Br*) bromine atom products, allowing multiple fragmentation pathways to be investigated. The experimental studies are complemented by spin–orbit resolved ab initio calculations of cuts through the potential energy surfaces (along the RC–Br/I stretch coordinate) for the ground and first few excited states of the respective cations. Analysis of the velocity-map images indicates that photoexcited C2H5Br+ cations undergo prompt C–Br bond fission to form predominantly C2H5+ + Br* products with a near-limiting ‘parallel’ recoil velocity distribution. The observed C2H3+ + H2 + Br product channel is thought to arise via unimolecular decay of highly internally excited C2H5+ products formed following radiationless transfer from the initial excited state populated by photon absorption. Broadly similar behaviour is observed in the case of C2H5I+, along with an additional energetically accessible C–I bond fission channel to form C2H5 + I+ products. HX (X = Br, I) elimination from the highly internally excited C2H5X+ cation is deemed the most probable route to forming the C2H4+ fragment ions observed from both cations. Finally, both ethyl halide cations also show evidence of a minor C–C bond fission process to form CH2X+ + CH3 products

Lithium alters brain activation in bipolar disorder in a task- and state-dependent manner: an fMRI study

BACKGROUND: It is unknown if medications used to treat bipolar disorder have effects on brain activation, and whether or not any such changes are mood-independent. METHODS: Patients with bipolar disorder who were depressed (n = 5) or euthymic (n = 5) were examined using fMRI before, and 14 days after, being started on lithium (as monotherapy in 6 of these patients). Patients were examined using a word generation task and verbal memory task, both of which have been shown to be sensitive to change in previous fMRI studies. Differences in blood oxygenated level dependent (BOLD) magnitude between the pre- and post-lithium results were determined in previously defined regions of interest. Severity of mood was determined by the Hamilton Depression Scale for Depression (HAM-D) and the Young mania rating scale (YMRS). RESULTS: The mean HAM-D score at baseline in the depressed group was 15.4 ± 0.7, and after 2 weeks of lithium it was 11.0 ± 2.6. In the euthymic group it was 7.6 ± 1.4 and 3.2 ± 1.3 respectively. At baseline mean BOLD signal magnitude in the regions of interest for the euthymic and depressed patients were similar in both the word generation task (1.56 ± 0.10 and 1.49 ± 0.10 respectively) and working memory task (1.02 ± 0.04 and 1.12 ± 0.06 respectively). However, after lithium the mean BOLD signal decreased significantly in the euthymic group in the word generation task only (1.56 ± 0.10 to 1.00 ± 0.07, p < 0.001). Post-hoc analysis showed that these differences were statistically significant in Broca's area, the left pre-central gyrus, and the supplemental motor area. CONCLUSION: This is the first study to examine the effects of lithium on brain activation in bipolar patients. The results suggest that lithium has an effect on euthymic patients very similar to that seen in healthy volunteers. The same effects are not seen in depressed bipolar patients, although it is uncertain if this lack of change is linked to the lack of major improvements in mood in this group of patients. In conclusion, this study suggests that lithium may have effects on brain activation that are task- and state-dependent. Given the small study size and the mildness of the patient's depression these results require replication

The structure and growth of nickel electrodeposits on electropolished copper single-crystal substrates

An exploratory study has been made of the orientation and growth of nickel electrodeposits on copper (110) and (111) substrates. The general nature of the variation of deposit structure with current density and thickness has been elucidated, and the results compared with previous work involving a deposit-substrate pair, where both metals belong to the f.c.c. system

Induced Anisotropies in NiCo Obliquely Deposited Films and Their effect on Magnetic Domains

English Article: Oblique and in-plane anisotropies in obliquely evaporated NiCo thin films were investigated in order to understand their origin. All the compositions studied clearly show the effect of columnar grain morphology coupled with some intrinsic factors such as magnetostriction and crystallinity. Energy calculations are undertaken to explain the effect of

Measurement of liver iron by magnetic resonance imaging in the UK Biobank population

The burden of liver disease continues to increase in the UK, with liver cirrhosis reported to be the third most common cause of premature death. Iron overload, a condition that impacts liver health, was traditionally associated with genetic disorders such as hereditary haemochromatosis, however, it is now increasingly associated with obesity, type-2 diabetes and non-alcoholic fatty liver disease. The aim of this study was to assess the prevalence of elevated levels of liver iron within the UK Biobank imaging study in a cohort of 9108 individuals. Magnetic resonance imaging (MRI) was undertaken at the UK Biobank imaging centre, acquiring a multi-echo spoiled gradient-echo single-breath-hold MRI sequence from the liver. All images were analysed for liver iron and fat (expressed as proton density fat fraction or PDFF) content using LiverMultiScan™. Liver iron was measured in 97.3% of the cohort. The mean liver iron content was 1.32 ± 0.32 mg/g while the median was 1.25 mg/g (min: 0.85 max: 6.44 mg/g). Overall 4.82% of the population were defined as having elevated liver iron, above commonly accepted 1.8 mg/g threshold based on biochemical iron measurements in liver specimens obtained by biopsy. Further analysis using univariate models showed elevated liver iron to be related to male sex (p5.6% PDFF) was associated with a slight increase in prevalence of elevated liver iron (4.4% vs 6.3%, p=0.0007). This study shows that population studies including measurement of liver iron concentration are feasible, which may in future be used to better inform patient stratification and treatment

Simulated SKA maps from Galactic 3D-emission models

(Abridged) We present maps for various Galactic longitudes and latitudes at 1.4 GHz, which is the frequency where deep SKA surveys are proposed. The maps are about 1.5 deg in size and have an angular resolution of about 1.6 arcsec. We analyse the maps in terms of their probability density functions (PDFs) and structure functions. Total intensity emission is more smooth in the plane than at high latitudes due to the different contributions from the regular and random magnetic field. The high latitude fields show more extended polarized emission and RM structures than those in the plane, where patchy emission structures on very small scales dominate. The RM PDFs in the plane are close to Gaussians, but clearly deviate from that at high latitudes. The RM structure functions show smaller amplitudes and steeper slopes towards high latitudes. These results emerge from the fact that much more turbulent cells are passed through by the line-of-sights in the plane. Although the simulated random magnetic field components distribute in 3D, the magnetic field spectrum extracted from the structure functions of RMs conforms to 2D in the plane and approaches 3D at high latitudes. This is partly related to the outer scale of the turbulent magnetic field, but mainly to the different lengths of the line-of-sights.Comment: 19 pages, 15 figures, accepted for publication in Astronomy and Astrophysics. The sizes of figures have been significantly reduced. For the version with full resolution, see ftp://ftp.mpifr-bonn.mpg.de/outgoing/p098wre/sun-reich.pd

Riding the wake of a merging galaxy cluster

Using WHT OASIS integral field unit observations, we report the discovery of a thin plume of ionised gas extending from the brightest cluster galaxy in Abell 2146 to the sub-cluster X-ray cool core which is offset from the BCG by ~37 kpc. The plume is greater than 15 kpc long and less than 3 kpc wide. This plume is unique in that the cluster it is situated in is currently undergoing a major galaxy cluster merger. The brightest cluster galaxy is unusually located behind the X-ray shock front and in the wake of the ram pressure stripped X-ray cool core and evidence for recent disruption to the BCG is observed. We examine the gas and stellar morphology, the gas kinematics of the BCG and their relation to the X-ray gas. We propose that a causal link between the ionised gas plume and the offset X-ray cool core provides the simplest explanation for the formation of the plume. An interaction or merger between the BCG and another cluster galaxy is probably the cause of the offset.Comment: 14 pages, 18 figures, accepted for publication in MNRA

The obscured growth of massive black holes

The mass density of massive black holes observed locally is consistent with the hard X-ray Background provided that most of the radiation produced during their growth was absorbed by surrounding gas. A simple model is proposed here for the formation of galaxy bulges and central black holes in which young spheroidal galaxies have a significant distributed component of cold dusty clouds which accounts for the absorption. The central accreting black hole is assumed to emit both a quasar-like spectrum, which is absorbed by the surrounding gas, and a slow wind. The power in both is less than the Eddington limit for the black hole. The wind however exerts the most force on the gas and, as earlier suggested by Silk & Rees, when the black hole reaches a critical mass, it is powerful enough to eject the cold gas from the galaxy, so terminating the growth of both black hole and galaxy. In the present model this point occurs when the Thomson depth in the surrounding gas has dropped to about unity and results in the mass of the black hole being proportional to the mass of the spheroid, with the normalization agreeing with that found for local galaxies by Magorrian et al. for reasonable wind parameters. The model predicts a new population of hard X-ray and sub-mm sources at redshifts above one which are powered by black holes in their main growth phase.Comment: 5 pages, no figures, MN LATEX style, accepted for publication in the MNRA