FAM13A and POM121C are candidate genes for fasting insulin: functional follow-up analysis of a genome-wide association study

Aims/hypothesis: By genome-wide association meta-analysis, 17 genetic loci associated with fasting serum insulin (FSI), a marker of systemic insulin resistance, have been identified. To define potential culprit genes in these loci, in a cross-sectional study we analysed white adipose tissue (WAT) expression of 120 genes in these loci in relation to systemic and adipose tissue variables, and functionally evaluated genes demonstrating genotype-specific expression in WAT (eQTLs). Methods: Abdominal subcutaneous adipose tissue biopsies were obtained from 114 women. Basal lipolytic activity was measured as glycerol release from adipose tissue explants. Adipocytes were isolated and insulin-stimulated incorporation of radiolabelled glucose into lipids was used to quantify adipocyte insulin sensitivity. Small interfering RNA-mediated knockout in human mesenchymal stem cells was used for functional evaluation of genes. Results: Adipose expression of 48 of the studied candidate genes associated significantly with FSI, whereas expression of 24, 17 and 2 genes, respectively, associated with adipocyte insulin sensitivity, lipolysis and/or WAT morphology (i.e. fat cell size relative to total body fat mass). Four genetic loci contained eQTLs. In one chromosome 4 locus (rs3822072), the FSI-increasing allele associated with lower FAM13A expression and FAM13A expression associated with a beneficial metabolic profile including decreased WAT lipolysis (regression coefficient, R = −0.50, p = 5.6 × 10−7). Knockdown of FAM13A increased lipolysis by ~1.5- fold and the expression of LIPE (encoding hormone-sensitive lipase, a rate-limiting enzyme in lipolysis). At the chromosome 7 locus (rs1167800), the FSI-increasing allele associated with lower POM121C expression. Consistent with an insulin-sensitising function, POM121C expression associated with systemic insulin sensitivity (R = −0.22, p = 2.0 × 10−2), adipocyte insulin sensitivity (R = 0.28, p = 3.4 × 10−3) and adipose hyperplasia (R = −0.29, p = 2.6 × 10−2). POM121C knockdown decreased expression of all adipocyte-specific markers by 25–50%, suggesting that POM121C is necessary for adipogenesis. Conclusions/interpretation: Gene expression and adipocyte functional studies support the notion that FAM13A and POM121C control adipocyte lipolysis and adipogenesis, respectively, and might thereby be involved in genetic control of systemic insulin sensitivity

The impact of the dark matter-gas interaction on the collapse behaviour of spherical symmetric systems

If the gas in the evolving cosmic halos is dissipating energy (cooling) then due to the variation of the gravitational potential the dark matter halo also undergoes a compactification. This is well-known as Adiabatic contraction (AC). Complementary to the AC we investigate the resulting dynamical behaviour of the whole system if the backreaction of the AC of DM onto the gas is taken into account. In order to achieve sufficient high resolution also within the central halo region, we use a crude fluid approximation for the DM obeying the adiabatic contraction behaviour. Further, we restrict ourself to spherical symmetry and vanishing angular momentum of the studied matter configurations. The computations are done using a first-order Godunov type scheme. Our results show that the dynamical interaction between gas and DM may lead to significant shorter collapse times. If the gas cools the dynamical behaviour of the whole system depends strongly on the shape of the initial density profile. Our findings indicate that for a certain mass range of halo configurations the dynamical interaction between gas and DM might be important for the halo evolution and must be taken into account.Comment: 9 pages, 13 figures, accepted for publication in A&A, added reference

SPH Simulations of Counterrotating Disk Formation in Spiral Galaxies

We present the results of Smoothed Particle Hydrodynamics (SPH) simulations of the formation of a massive counterrotating disk in a spiral galaxy. The current study revisits and extends (with SPH) previous work carried out with sticky particle gas dynamics, in which adiabatic gas infall and a retrograde gas-rich dwarf merger were tested as the two most likely processes for producing such a counterrotating disk. We report on experiments with a cold primary similar to our Galaxy, as well as a hot, compact primary modeled after NGC 4138. We have also conducted numerical experiments with varying amounts of prograde gas in the primary disk, and an alternative infall model (a spherical shell with retrograde angular momentum). The structure of the resulting counterrotating disks is dramatically different with SPH. The disks we produce are considerably thinner than the primary disks and those produced with sticky particles. The time-scales for counterrotating disk formation are shorter with SPH because the gas loses kinetic energy and angular momentum more rapidly. Spiral structure is evident in most of the disks, but an exponential radial profile is not a natural byproduct of these processes. The infalling gas shells that we tested produce counterrotating bulges and rings rather than disks. The presence of a considerable amount of preexisting prograde gas in the primary causes, at least in the absence of star formation, a rapid inflow of gas to the center and a subsequent hole in the counterrotating disk. In general, our SPH experiments yield stronger evidence to suggest that the accretion of massive counterrotating disks drives the evolution of the host galaxies towards earlier (S0/Sa) Hubble types.Comment: To appear in ApJ. 20 pages LaTex 2-column with 3 tables, 23 figures (GIF) available at this site. Complete gzipped postscript preprint with embedded figures available from http://tarkus.pha.jhu.edu/~thakar/cr3.html (3 Mb

A solar cycle of spacecraft anomalies due to internal charging

International audienceIt is important to appreciate how the morphology of internal charging of spacecraft systems, due to penetrating electrons, differs from that of the more common surface charging, due to electrons with lower energy. A specific and recurrent anomaly on a geostationary communication satellite has been tracked for ten years so that solar cycle and seasonal dependencies can be clearly established. Concurrent measurements of sunspot number, solar wind speed and 2-day >2 MeV electron fluence are presented to highlight pertinent space weather relationships, and the importance of understanding the complex particle interaction processes involved

The Ellipticity of the Disks of Spiral Galaxies

The disks of spiral galaxies are generally elliptical rather than circular. The distribution of ellipticities can be fit with a log-normal distribution. For a sample of 12,764 galaxies from the Sloan Digital Sky Survey Data Release 1 (SDSS DR1), the distribution of apparent axis ratios in the i band is best fit by a log-normal distribution of intrinsic ellipticities with ln epsilon = -1.85 +/- 0.89. For a sample of nearly face-on spiral galaxies, analyzed by Andersen and Bershady using both photometric and spectroscopic data, the best fitting distribution of ellipticities has ln epsilon = -2.29 +/- 1.04. Given the small size of the Andersen-Bershady sample, the two distribution are not necessarily inconsistent. If the ellipticity of the potential were equal to that of the light distribution of the SDSS DR1 galaxies, it would produce 1.0 magnitudes of scatter in the Tully-Fisher relation, greater than is observed. The Andersen-Bershady results, however, are consistent with a scatter as small as 0.25 magnitudes in the Tully-Fisher relation.Comment: 19 pages, 5 figures; ApJ, accepte

NGC 4138 - A Case Study in Counterrotating Disk Formation

The Sa(r) galaxy NGC 4138 has been recently found to contain an extensive counterrotating disk which appears to be still forming. Up to a third of the stars in the disk system may be on retrograde orbits. A counterrotating ring of H II regions, along with extended counterrotating H I gas, suggests that the retrograde material has been recently acquired in the gas phase and is still trickling in. Using numerical simulations, we have attempted to model the process by which the counterrotating mass has been accreted by this galaxy. We investigate two possibilities: continuous retrograde infall of gas, and a retrograde merger with a gas-rich dwarf galaxy. Both processes are successful in producing a counterrotating disk of the observed mass and dimensions without heating up the primary significantly. Contrary to our experience with a fiducial cold, thin primary disk, the gas-rich merger works well for the massive, compact primary disk of NGC 4138 even though the mass of the dwarf galaxy is a significant fraction of the mass of the primary disk. Although we have restricted ourselves mainly to coplanar infall and mergers, we report on one inclined infall simulation as well. We also explore the possibility that the H-alpha ring seen in the inner half of the disk is a consequence of counterrotating gas clouds colliding with corotating gas already present in the disk and forming stars in the process.Comment: To appear in ApJ, 21 pages, LaTeX (aaspp4) format, 17 figs (gzipped tar file) also available at ftp://bessel.mps.ohio-state.edu/pub/thakar/cr2/ or at http://www-astronomy.mps.ohio-state.edu/~thakar

Robust, data-driven inference in non-linear cosmostatistics

We discuss two projects in non-linear cosmostatistics applicable to very large surveys of galaxies. The first is a Bayesian reconstruction of galaxy redshifts and their number density distribution from approximate, photometric redshift data. The second focuses on cosmic voids and uses them to construct cosmic spheres that allow reconstructing the expansion history of the Universe using the Alcock-Paczynski test. In both cases we find that non-linearities enable the methods or enhance the results: non-linear gravitational evolution creates voids and our photo-z reconstruction works best in the highest density (and hence most non-linear) portions of our simulations.Comment: 14 pages, 10 figures. Talk given at "Statistical Challenges in Modern Astronomy V," held at Penn Stat