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Bipolar disorder is a highly heritable polygenic disorder. Recent
enrichment analyses suggest that there may be true risk variants for
bipolar disorder in the expression quantitative trait loci (eQTL) in the
We sought to assess the impact of eQTL variants on bipolar disorder risk
by combining data from both bipolar disorder genome-wide association
studies (GWAS) and brain eQTL.
To detect single nucleotide polymorphisms (SNPs) that influence
expression levels of genes associated with bipolar disorder, we jointly
analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls)
and a genome-wide brain (cortical) eQTL (193 healthy controls) using a
Bayesian statistical method, with independent follow-up replications. The
identified risk SNP was then further tested for association with
hippocampal volume (n = 5775) and cognitive performance
(n = 342) among healthy individuals.
Integrative analysis revealed a significant association between a brain
eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes
factor = 5.48; bipolar disorder P =
5.85×10–5). Follow-up studies across multiple independent
samples confirmed the association of the risk SNP (rs6088662) with gene
expression and bipolar disorder susceptibility (P =
3.54×10–8). Further exploratory analysis revealed that
rs6088662 is also associated with hippocampal volume and cognitive
performance in healthy individuals.
Our findings suggest that 20q11.22 is likely a risk region for bipolar
disorder; they also highlight the informative value of integrating
functional annotation of genetic variants for gene expression in
advancing our understanding of the biological basis underlying complex
disorders, such as bipolar disorder.
During pregnancy, glycine and serine become more important because they are the primary suppliers of methyl groups for the synthesis of fetal DNA, and more glycine is required for fetal collagen synthesis as pregnancy progresses. In an earlier study, we reported that glycine flux decreased by 39 % from the first to the third trimester in pregnant adolescent girls. As serine is a primary precursor for glycine synthesis, the objective of this study was to measure and compare glycine and serine fluxes and inter-conversions in pregnant adolescent girls and adult women in the first and third trimesters. Measurements were made after an overnight fast by continuous intravenous infusions of 2H2-glycine and 15N-serine in eleven adolescent girls (17·4 (se 0·1) years of age) and in ten adult women (25·8 (se 0·5) years of age) for 4 h. Adolescent girls had significantly slower glycine flux and they made less glycine from serine in the third (P<0·05) than in the first trimester. Baby birth length was significantly shorter of adolescent girls (P=0·04) and was significantly associated with third trimester glycine flux. These findings suggest that the pregnant adolescent cannot maintain glycine flux in late pregnancy compared with early pregnancy because of decreased synthesis from serine. It is possible that the inability to maintain glycine synthesis makes her fetus vulnerable to impaired cartilage synthesis, and thus linear growth.
Epidemiological studies have identified increased colorectal cancer (CRC) risk with high red meat (HRM) intakes, whereas dietary fibre intake appears to be protective. In the present study, we examined whether a HRM diet increased rectal O6-methyl-2-deoxyguanosine (O6MeG) adduct levels in healthy human subjects, and whether butyrylated high-amylose maize starch (HAMSB) was protective. A group of twenty-three individuals consumed 300 g/d of cooked red meat without (HRM diet) or with 40 g/d of HAMSB (HRM+HAMSB diet) over 4-week periods separated by a 4-week washout in a randomised cross-over design. Stool and rectal biopsy samples were collected for biochemical, microbial and immunohistochemical analyses at baseline and at the end of each 4-week intervention period. The HRM diet increased rectal O6MeG adducts relative to its baseline by 21 % (P< 0·01), whereas the addition of HAMSB to the HRM diet prevented this increase. Epithelial proliferation increased with both the HRM (P< 0·001) and HRM+HAMSB (P< 0·05) diets when compared with their respective baseline levels, but was lower following the HRM+HAMSB diet compared with the HRM diet (P< 0·05). Relative to its baseline, the HRM+HAMSB diet increased the excretion of SCFA by over 20 % (P< 0·05) and increased the absolute abundances of the Clostridium coccoides group (P< 0·05), the Clostridiumleptum group (P< 0·05), Lactobacillus spp. (P< 0·01), Parabacteroides distasonis (P< 0·001) and Ruminococcus bromii (P< 0·05), but lowered Ruminococcus torques (P< 0·05) and the proportions of Ruminococcus gnavus, Ruminococcus torques and Escherichia coli (P< 0·01). HRM consumption could increase the risk of CRC through increased formation of colorectal epithelial O6MeG adducts. HAMSB consumption prevented red meat-induced adduct formation, which may be associated with increased stool SCFA levels and/or changes in the microbiota composition.
Discovery of ultra-compact dwarfs (UCDs) in the past 15 years blurs the once thought clear division between classic globular clusters (GCs) and early-type galaxies. The intermediate nature of UCDs, which are larger and more massive than typical GCs but more compact than typical dwarf galaxies, has triggered hot debate on whether UCDs should be considered galactic in origin or merely the most extreme GCs. Previous studies of various scaling relations, stellar populations and internal dynamics did not give an unambiguous answer to the primary origin of UCDs. In this contribution, we present the first ever detailed study of global dynamics of 97 UCDs (rh ≳ 10 pc) associated with the central cD galaxy of the Virgo cluster, M87. We found that UCDs follow a different radial number density profile and different rotational properties from GCs. The orbital anisotropies of UCDs are tangentially-biased within ~ 40 kpc of M87 and become radially-biased with radius further out. In contrast, the blue GCs, which have similar median colors to our sample of UCDs, become more tangentially-biased at larger radii beyond ~ 40 kpc. Our analysis suggests that most UCDs in M87 are not consistent with being merely the most luminous and extended examples of otherwise normal GCs. The radially-biased orbital structure of UCDs at large radii is in general agreement with the scenario that most UCDs originated from the tidally threshed dwarf galaxies.
The Dominion Radio Astrophysical Observatory (DRAO) is carrying out a survey as part of an international collaboration to image the northe, at a common resolution, in emission from all major constituents of the interstellar medium; the neutral atomic gas, the molecular gas, the ionised gas, dust and relativistic plasma. For many of these constituents the angular resolution of the images (1 arcmin) will be more than a factor of 10 better than any previous studies. The aim is to produce a publicly-available database of high resolution, high-dynamic range images of the Galaxy for multi-phase studies of the physical states and processes in the interstellar medium. We will sketch the main scientific motivations as well as describe some preliminary results from the Canadian Galactic Plane Survey/Releve Canadien du Plan Galactique (CGPS/RCPG).
The Australian Square Kilometre Array Pathfinder (ASKAP) will give us an unprecedented opportunity to investigate the transient sky at radio wavelengths. In this paper we present VAST, an ASKAP survey for Variables and Slow Transients. VAST will exploit the wide-field survey capabilities of ASKAP to enable the discovery and investigation of variable and transient phenomena from the local to the cosmological, including flare stars, intermittent pulsars, X-ray binaries, magnetars, extreme scattering events, interstellar scintillation, radio supernovae, and orphan afterglows of gamma-ray bursts. In addition, it will allow us to probe unexplored regions of parameter space where new classes of transient sources may be detected. In this paper we review the known radio transient and variable populations and the current results from blind radio surveys. We outline a comprehensive program based on a multi-tiered survey strategy to characterise the radio transient sky through detection and monitoring of transient and variable sources on the ASKAP imaging timescales of 5 s and greater. We also present an analysis of the expected source populations that we will be able to detect with VAST.
We are developing a purely commensal survey experiment for fast (<5 s) transient radio sources. Short-timescale transients are associated with the most energetic and brightest single events in the Universe. Our objective is to cover the enormous volume of transients parameter space made available by ASKAP, with an unprecedented combination of sensitivity and field of view. Fast timescale transients open new vistas on the physics of high brightness temperature emission, extreme states of matter and the physics of strong gravitational fields. In addition, the detection of extragalactic objects affords us an entirely new and extremely sensitive probe on the huge reservoir of baryons present in the IGM. We outline here our approach to the considerable challenge involved in detecting fast transients, particularly the development of hardware fast enough to dedisperse and search the ASKAP data stream at or near real-time rates. Through CRAFT, ASKAP will provide the testbed of many of the key technologies and survey modes proposed for high time resolution science with the SKA.