Cytosine methylation is required for mammalian development and is often perturbed in human cancer. To determine how this epigenetic modification is distributed in the genomes of primary and transformed cells, we used an immunocapturing approach followed by DNA microarray analysis to generate methylation profiles of all human chromosomes at 80-kb resolution and for a large set of CpG islands. In primary cells we identified broad genomic regions of differential methylation with higher levels in gene-rich neighborhoods. Female and male cells had indistinguishable profiles for autosomes but differences on the X chromosome. The inactive X chromosome (Xi) was hypermethylated at only a subset of gene-rich regions and, unexpectedly, overall hypomethylated relative to its active counterpart. The chromosomal methylation profile of transformed cells was similar to that of primary cells. Nevertheless, we detected large genomic segments with hypomethylation in the transformed cell residing in gene-poor areas. Furthermore, analysis of 6,000 CpG islands showed that only a small set of promoters was methylated differentially, suggesting that aberrant methylation of CpG island promoters in malignancy might be less frequent than previously hypothesized.
Aims. The purpose of this work is the characterization of the radial distribution of dust, stars, gas, and star-formation rate (SFR) in a sub-sample of 18 face-on spiral galaxies extracted from the DustPedia sample. Methods. This study is performed by exploiting the multi-wavelength, from ultraviolet (UV) to sub-millimeter bands, DustPedia database, in addition to molecular ( 12 CO) and atomic (Hi) gas maps and metallicity abundance information available in the literature. We fitted the surface brightness profiles of the tracers of dust and stars, the mass surface density profiles of dust, stars, molecular gas, and total gas, and the SFR surface density profiles with an exponential curve and derived their scale-lengths. We also developed a method to solve for the CO-to-H 2 conversion factor (α CO ) per galaxy by using dust and gas mass profiles. Results. Although each galaxy has its own peculiar behaviour, we identified a common trend of the exponential scale-lengths vs. wavelength. On average, the scale-lengths normalized to the B-band 25 mag/arcsec 2 radius decrease from UV to 70 µm, from 0.4 to 0.2, and then increase back up to ∼0.3 at 500 microns. The main result is that, on average, the dust mass surface density scale-length is about 1.8 times the stellar one derived from IRAC data and the 3.6 µm surface brightness, and close to that in the UV. We found a mild dependence of the scale-lengths on the Hubble stage T: the scale-lengths of the Herschel bands and the 3.6 µm scale-length tend to increase from earlier to later types, the scale-length at 70 µm tends to be smaller than that at longer sub-mm wavelength with ratios between longer sub-mm wavelengths and 70 µm that decrease with increasing T. The scale-length ratio of SFR and stars shows a weak increasing trend towards later types. Our α CO determinations are in the range (0.3 − 9) M pc −2 (K km s −1 ) −1 , almost invariant by using a fixed dust-to-gas ratio mass (DGR) or a DGR depending on metallicity gradient.
We examine the connection between the properties of the circumgalactic medium (CGM) and the quenching and morphological evolution of central galaxies in the EAGLE and Illus-trisTNG simulations. The simulations yield very different median CGM mass fractions, f CGM , as a function of halo mass, M 200 , with low-mass haloes being significantly more gas-rich in IllustrisTNG than in EAGLE. Nonetheless, in both cases scatter in f CGM at fixed M 200 is strongly correlated with the specific star formation rate and the kinematic morphology of central galaxies. The correlations are strongest for ∼ L galaxies, corresponding to the mass scale at which expulsive AGN feedback becomes efficient. This feedback elevates the CGM cooling time, preventing gas from accreting onto the galaxy to fuel star formation, and thus establishing a preference for quenched, spheroidal galaxies to be hosted by haloes with low f CGM for their mass. In both simulations, f CGM correlates negatively with the host halo's intrinsic concentration, and hence with its binding energy and formation redshift, primarily because early halo formation fosters the rapid early growth of the central black hole (BH). This leads to a lower f CGM at fixed M 200 in EAGLE because the BH reaches high accretion rates sooner, whilst in IllustrisTNG it occurs because the central BH reaches the mass threshold at which AGN feedback is assumed to switch from thermal to kinetic injection earlier. Despite these differences, there is consensus from these state-of-the-art simulations that the expulsion of efficiently-cooling gas from the CGM is a crucial step in the quenching and morphological evolution of central galaxies.
We examine the origin of scatter in the relationship between the gas fraction and mass of dark matter haloes hosting present-day ∼ L central galaxies in the EAGLE simulations. The scatter is uncorrelated with the accretion rate of the central galaxy's black hole (BH), but correlates strongly and negatively with the BH's mass, implicating differences in the expulsion of gas by active galactic nucleus feedback, throughout the assembly of the halo, as the main cause of scatter. Haloes whose central galaxies host undermassive BHs also tend to retain a higher gas fraction, and exhibit elevated star formation rates (SFRs). Diversity in the mass of central BHs stems primarily from diversity in the dark matter halo binding energy, as these quantities are strongly and positively correlated at fixed halo mass, such that ∼ L galaxies hosted by haloes that are more (less) tightly-bound develop central BHs that are more (less) massive than is typical for their halo mass. Variations in the halo gas fraction at fixed halo mass are reflected in both the soft X-ray luminosity and thermal Sunyaev-Zel'dovich flux, suggesting that the prediction of a strong coupling between the properties of galaxies and their halo gas fractions can be tested with measurements of these diagnostics for galaxies with diverse SFRs but similar halo masses.
Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin's lymphoma with median patient survival times of approximately 3 years. Although the characteristic t(11;14)(q13;q32) is found in virtually all cases, experimental evidence suggests that this event alone is insufficient to result in lymphoma and secondary genomic alterations are required. Using a newly developed DNA microarray of 32 433 overlapping genomic segments spanning the entire human genome, we can for the first time move beyond marker based analysis and comprehensively search for secondary genomic alterations concomitant with the t(11;14) in eight commonly used cell models of MCL (Granta-519, HBL-2, NCEB-1, Rec-1, SP49, UPN-1, Z138C and JVM-2). Examining these genomes at tiling resolution identified an unexpected average of 35 genetic alterations per cell line, with equal numbers of amplifications and deletions. Recurrent high-level amplifications were identified at 18q21 containing BCL2, and at 13q31 containing GPC5. In addition, a recurrent homozygous deletion was identified at 9p21 containing p15 and p16. Alignment of these profiles revealed 14 recurrent losses and 21 recurrent gains as small as 130 kb. Remarkably, even the intra immunoglobulin gene deletions at 2p11 and 22q11 were detected, demonstrating the power of combining the detection sensitivity of array comparative genomic hybridization (CGH) with the resolution of an overlapping whole genome tiling-set. These alterations not only coincided with previously described aberrations in MCL, but also defined 13 novel regions. Further characterization of such minimally altered genomic regions identified using whole genome array CGH will define novel dominant oncogenes and tumor suppressor genes that play important roles in the pathogenesis of MCL.
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