Down-regulation of human topoisomerase IIα expression correlates with relative amounts of specificity factors Sp1 and Sp3 bound at proximal and distal promoter regions

<p>Abstract</p> <p>Background</p> <p>Topoisomerase IIα has been shown to be down-regulated in doxorubicin-resistant cell lines. The specificity proteins Sp1 and Sp3 have been implicated in regulation of topoisomerase IIα transcription, although the mechanism by which they regulate expression is not fully understood. Sp1 has been shown to bind specifically to both proximal and distal GC elements of the human topoisomerase IIα promoter <it>in vitro</it>, while Sp3 binds only to the distal GC element unless additional flanking sequences are included. While Sp1 is thought to be an activator of human topoisomerase IIα, the functional significance of Sp3 binding is not known. Therefore, we sought to determine the functional relationship between Sp1 and Sp3 binding to the topoisomerase IIα promoter <it>in vivo</it>. We investigated endogenous levels of Sp1, Sp3 and topoisomerase IIα as well as binding of both Sp1 and Sp3 to the GC boxes of the topoisomerase IIα promoter in breast cancer cell lines <it>in vivo </it>after short term doxorubicin exposure.</p> <p>Results</p> <p>Functional effects of Sp1 and Sp3 were studied using transient cotransfection assays using a topoisomerase IIα promoter reporter construct. The <it>in vivo </it>interactions of Sp1 and Sp3 with the GC elements of the topoisomerase IIα promoter were studied in doxorubicin-treated breast cancer cell lines using chromatin immunoprecipitation assays. Relative amounts of endogenous proteins were measured using immunoblotting. <it>In vivo </it>DNA looping mediated by proteins bound at the GC1 and GC2 elements was studied using the chromatin conformation capture assay. Both Sp1 and Sp3 bound to the GC1 and GC2 regions. Sp1 and Sp3 were transcriptional activators and repressors respectively, with Sp3 repression being dominant over Sp1-mediated activation. The GC1 and GC2 elements are linked <it>in vivo </it>to form a loop, thus bringing distal regulatory elements and their cognate transcription factors into close proximity with the transcription start site.</p> <p>Conclusion</p> <p>These observations provide a mechanistic explanation for the modulation of topoisomerase IIα and concomitant down-regulation that can be mediated by topoisomerase II poisons. Competition between Sp1 and Sp3 for the same cognate DNA would result in activation or repression depending on absolute amounts of each transcription factor in cells treated with doxorubicin.</p

MASSIV: Mass Assembly Survey with SINFONI in VVDS. IV. Fundamental relations of star-forming galaxies at 1<z< 1.6

How mass assembly occurs in galaxies and which process(es) contribute to this activity are among the most highly debated questions in galaxy formation theories. This has motivated our survey MASSIV of 0.9<z<1.9 star-forming galaxies selected from the purely flux-limited VVDS redshift survey. For the first time, we derive the relations between galaxy size, mass, and internal velocity, and the baryonic Tully-Fisher relation, from a statistically representative sample of star-forming galaxies. We find a dynamical mass that agrees with those of rotating galaxies containing a gas fraction of ~20%, perfectly consistent with the content derived using the Kennicutt-Schmidt formulation and the expected evolution. Non-rotating galaxies have more compact sizes for their stellar component, and are less massive than rotators, but do not have statistically different sizes for their gas-component. We measure a marginal evolution in the size-stellar mass and size-velocity relations in which discs become evenly smaller with cosmic time at fixed stellar mass or velocity, and are less massive at a given velocity than in the local Universe. The scatter in the Tully-Fisher relation is smaller when we introduce the S05 index, which we interpret as evidence of an increase in the contribution to galactic kinematics of turbulent motions with cosmic time. We report a persistently large scatter for rotators in our relations, that we suggest is intrinsic, and possibly caused by complex physical mechanism(s) at work in our stellar mass/luminosity regime and redshift range. Our results consistently point towards a mild, net evolution of these relations, comparable to those predicted by cosmological simulations of disc formation for at least 8Gyr and a dark halo strongly coupled with galactic spectrophotometric properties

MASSIV: Mass Assembly Survey with SINFONI in VVDS. V. The major merger rate of star-forming galaxies at 0.9 < z < 1.8 from IFS-based close pairs

We aim to measure the major merger rate of star-forming galaxies at 0.9 < z <1.8, using close pairs identified from integral field spectroscopy (IFS). We use the velocity field maps obtained with SINFONI/VLT on the MASSIV sample, selected from the star-forming population in the VVDS. We identify physical pairs of galaxies from the measurement of the relative velocity and the projected separation (r_p) of the galaxies in the pair. Using the well constrained selection function of the MASSIV sample we derive the gas-rich major merger fraction (luminosity ratio mu = L_2/L_1 >= 1/4), and, using merger time scales from cosmological simulations, the gas-rich major merger rate at a mean redshift up to z = 1.54. We find a high gas-rich major merger fraction of 20.8+15.2-6.8 %, 20.1+8.0-5.1 % and 22.0+13.7-7.3 % for close pairs with r_p <= 20h^-1 kpc in redshift ranges z = [0.94, 1.06], [1.2, 1.5) and [1.5, 1.8), respectively. This translates into a gas-rich major merger rate of 0.116+0.084-0.038 Gyr^-1, 0.147+0.058-0.037 Gyr^-1 and 0.127+0.079-0.042 Gyr^-1 at z = 1.03, 1.32 and 1.54, respectively. Combining our results with previous studies at z < 1, the gas-rich major merger rate evolves as (1+z)^n, with n = 3.95 +- 0.12, up to z = 1.5. From these results we infer that ~35% of the star-forming galaxies with stellar masses M = 10^10 - 10^10.5 M_Sun have undergone a major merger since z ~ 1.5. We develop a simple model which shows that, assuming that all gas-rich major mergers lead to early-type galaxies, the combined effect of gas-rich and dry mergers is able to explain most of the evolution in the number density of massive early-type galaxies since z ~ 1.5, with our measured gas-rich merger rate accounting for about two-thirds of this evolution.Comment: Published in Astronomy and Astrophysics, 24 pages, 30 figures, 2 tables. Appendix with the residual images from GALFIT added. Minor changes with respect to the initial versio

an overview of the MHONGOOSE survey: Observing nearby galaxies with MeerKAT

© Copyright owned by the author(s). MHONGOOSE is a deep survey of the neutral hydrogen distribution in a representative sample of 30 nearby disk and dwarf galaxies with H I masses from ∼ 106 to ∼ 1011 M, and luminosities from MR ∼ 12 to MR ∼ −22. The sample is selected to uniformly cover the available range in log(MHI). Our extremely deep observations, down to H I column density limits of well below 1018 cm−2 — or a few hundred times fainter than the typical H I disks in galaxies — will directly detect the effects of cold accretion from the intergalactic medium and the links with the cosmic web. These observations will be the first ever to probe the very low-column density neutral gas in galaxies at these high resolutions. Combination with data at other wavelengths, most of it already available, will enable accurate modeling of the properties and evolution of the mass components in these galaxies and link these with the effects of environment, dark matter distribution, and other fundamental properties such as halo mass and angular momentum. MHONGOOSE can already start addressing some of the SKA-1 science goals and will provide a comprehensive inventory of the processes driving the transformation and evolution of galaxies in the nearby universe at high resolution and over 5 orders of magnitude in column density. It will be a Nearby Galaxies Legacy Survey that will be unsurpassed until the advent of the SKA, and can serve as a highly visible, lasting statement of MeerKAT’s capabilities

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations

Measurement of the production of a W boson in association with a charm quark in pp collisions at √s = 7 TeV with the ATLAS detector

The production of a W boson in association with a single charm quark is studied using 4.6 fb−1 of pp collision data at s√ = 7 TeV collected with the ATLAS detector at the Large Hadron Collider. In events in which a W boson decays to an electron or muon, the charm quark is tagged either by its semileptonic decay to a muon or by the presence of a charmed meson. The integrated and differential cross sections as a function of the pseudorapidity of the lepton from the W-boson decay are measured. Results are compared to the predictions of next-to-leading-order QCD calculations obtained from various parton distribution function parameterisations. The ratio of the strange-to-down sea-quark distributions is determined to be 0.96+0.26−0.30 at Q 2 = 1.9 GeV2, which supports the hypothesis of an SU(3)-symmetric composition of the light-quark sea. Additionally, the cross-section ratio σ(W + +c¯¯)/σ(W − + c) is compared to the predictions obtained using parton distribution function parameterisations with different assumptions about the s−s¯¯¯ quark asymmetry

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured

Evidence for the Higgs-boson Yukawa coupling to tau leptons with the ATLAS detector

Results of a search for H → τ τ decays are presented, based on the full set of proton-proton collision data recorded by the ATLAS experiment at the LHC during 2011 and 2012. The data correspond to integrated luminosities of 4.5 fb−1 and 20.3 fb−1 at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV respectively. All combinations of leptonic (τ → `νν¯ with ` = e, µ) and hadronic (τ → hadrons ν) tau decays are considered. An excess of events over the expected background from other Standard Model processes is found with an observed (expected) significance of 4.5 (3.4) standard deviations. This excess provides evidence for the direct coupling of the recently discovered Higgs boson to fermions. The measured signal strength, normalised to the Standard Model expectation, of µ = 1.43 +0.43 −0.37 is consistent with the predicted Yukawa coupling strength in the Standard Model

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30

Search for squarks and gluinos with the ATLAS detector in final states with jets and missing transverse momentum using √s=8 TeV proton-proton collision data

A search for squarks and gluinos in final states containing high-p T jets, missing transverse momentum and no electrons or muons is presented. The data were recorded in 2012 by the ATLAS experiment in s√=8 TeV proton-proton collisions at the Large Hadron Collider, with a total integrated luminosity of 20.3 fb−1. Results are interpreted in a variety of simplified and specific supersymmetry-breaking models assuming that R-parity is conserved and that the lightest neutralino is the lightest supersymmetric particle. An exclusion limit at the 95% confidence level on the mass of the gluino is set at 1330 GeV for a simplified model incorporating only a gluino and the lightest neutralino. For a simplified model involving the strong production of first- and second-generation squarks, squark masses below 850 GeV (440 GeV) are excluded for a massless lightest neutralino, assuming mass degenerate (single light-flavour) squarks. In mSUGRA/CMSSM models with tan β = 30, A 0 = −2m 0 and μ > 0, squarks and gluinos of equal mass are excluded for masses below 1700 GeV. Additional limits are set for non-universal Higgs mass models with gaugino mediation and for simplified models involving the pair production of gluinos, each decaying to a top squark and a top quark, with the top squark decaying to a charm quark and a neutralino. These limits extend the region of supersymmetric parameter space excluded by previous searches with the ATLAS detector