Microtubule dynamics drive enhanced chromatin motion and mobilize telomeres in response to DNA damage

Chromatin exhibits increased mobility on DNA damage, but the biophysical basis for this behavior remains unknown. To explore the mechanisms that drive DNA damage–induced chromosome mobility, we use single-particle tracking of tagged chromosomal loci during interphase in live yeast cells together with polymer models of chromatin chains. Telomeres become mobilized from sites on the nuclear envelope and the pericentromere expands after exposure to DNA-damaging agents. The magnitude of chromatin mobility induced by a single double-strand break requires active microtubule function. These findings reveal how relaxation of external tethers to the nuclear envelope and internal chromatin–chromatin tethers, together with microtubule dynamics, can mobilize the genome in response to DNA damage

Overview on Patient Centricity in Cancer Care

Successful implementation of treatment in cancer care partially depends on how patients’ perspectives are taken into account, as preferences of health care professionals and patients may differ. Objectives of this exploratory research were I) to identify patient preferences and values (PPVs) in cancer care as indicated by patient organizations (POs), II) to determine how these PPVs are captured in cancer care guidelines and III) to review how guidelines take into account these PPVs. Based on a survey developed and completed by 19 POs, a literature review was conducted to analyse how patient perspectives are incorporated in oncology treatment guidelines. Based on survey results traditional health technology assessment value propositions of oncology care, such as extended life, treatment-free remission and pain reduction, were also highly rated by POs. However, the heterogeneity of cancer PPVs were clearly reflected in the survey results. PPVs in cancer care guidelines were mostly limited to those micro-level aspects that are strictly related to health care provision, such as side-effects and comorbidities. Patient experience, emotional support and convenience of care were relatively neglected fields in the reviewed guidelines. Patient engagement was rarely presented in the guideline development phase. POs believe that patients should be encouraged to take an active role in their own care due to the heterogeneity of cancer patients and PPVs. Even if patient-centricity is a leading paradigm in cancer policy, based on our research it is not yet standard practice to include patients or POs at all appropriate levels of decision-making processes that are related to their health and well-being. Patient engagement should be an integral part of cancer care decision-making. This complexity must be reflected throughout policy making, avoiding a population level ‘one-size-fits-all’ solution

The UV-Optical Color Dependence of Galaxy Clustering in the Local Universe

We measure the UV-optical color dependence of galaxy clustering in the local universe. Using the clean separation of the red and blue sequences made possible by the NUV - r color-magnitude diagram, we segregate the galaxies into red, blue and intermediate "green" classes. We explore the clustering as a function of this segregation by removing the dependence on luminosity and by excluding edge-on galaxies as a means of a non-model dependent veto of highly extincted galaxies. We find that \xi (r_p, \pi) for both red and green galaxies shows strong redshift space distortion on small scales -- the "finger-of-God" effect, with green galaxies having a lower amplitude than is seen for the red sequence, and the blue sequence showing almost no distortion. On large scales, \xi (r_p, \pi) for all three samples show the effect of large-scale streaming from coherent infall. On scales 1 Mpc/h < r_p < 10 Mpc/h, the projected auto-correlation function w_p(r_p) for red and green galaxies fits a power-law with slope \gamma ~ 1.93 and amplitude r_0 ~ 7.5 and 5.3, compared with \gamma ~ 1.75 and r_0 ~ 3.9 Mpc/h for blue sequence galaxies. Compared to the clustering of a fiducial L* galaxy, the red, green, and blue have a relative bias of 1.5, 1.1, and 0.9 respectively. The w_p(r_p) for blue galaxies display an increase in convexity at ~ 1 Mpc/h, with an excess of large scale clustering. Our results suggest that the majority of blue galaxies are likely central galaxies in less massive halos, while red and green galaxies have larger satellite fractions, and preferentially reside in virialized structures. If blue sequence galaxies migrate to the red sequence via processes like mergers or quenching that take them through the green valley, such a transformation may be accompanied by a change in environment in addition to any change in luminosity and color.Comment: accepted by MNRA

The Extreme Hosts of Extreme Supernovae

We use GALEX ultraviolet (UV) and optical integrated photometry of the hosts of seventeen luminous supernovae (LSNe, having peak M_V < -21) and compare them to a sample of 26,000 galaxies from a cross-match between the SDSS DR4 spectral catalog and GALEX interim release 1.1. We place the LSNe hosts on the galaxy NUV-r versus M_r color magnitude diagram (CMD) with the larger sample to illustrate how extreme they are. The LSN hosts appear to favor low-density regions of the galaxy CMD falling on the blue edge of the blue cloud toward the low luminosity end. From the UV-optical photometry, we estimate the star formation history of the LSN hosts. The hosts have moderately low star formation rates (SFRs) and low stellar masses (M_*) resulting in high specific star formation rates (sSFR). Compared with the larger sample, the LSN hosts occupy low-density regions of a diagram plotting sSFR versus M_* in the area having higher sSFR and lower M_*. This preference for low M_*, high sSFR hosts implies the LSNe are produced by an effect having to do with their local environment. The correlation of mass with metallicity suggests that perhaps wind-driven mass loss is the factor that prevents LSNe from arising in higher-mass, higher-metallicity hosts. The massive progenitors of the LSNe (>100 M_sun), by appearing in low-SFR hosts, are potential tests for theories of the initial mass function that limit the maximum mass of a star based on the SFR.Comment: 8 pages, 3 figures, 2 tables, accepted to ApJ, amended references and updated SN designation

The GALEX Arecibo SDSS Survey. I. Gas Fraction Scaling Relations of Massive Galaxies and First Data Release

We introduce the GALEX Arecibo SDSS Survey (GASS), an on-going large program that is gathering high quality HI-line spectra using the Arecibo radio telescope for an unbiased sample of ~1000 galaxies with stellar masses greater than 10^10 Msun and redshifts 0.025<z<0.05, selected from the SDSS spectroscopic and GALEX imaging surveys. The galaxies are observed until detected or until a low gas mass fraction limit (1.5-5%) is reached. This paper presents the first Data Release, consisting of ~20% of the final GASS sample. We use this data set to explore the main scaling relations of HI gas fraction with galaxy structure and NUV-r colour. A large fraction (~60%) of the galaxies in our sample are detected in HI. We find that the atomic gas fraction decreases strongly with stellar mass, stellar surface mass density and NUV-r colour, but is only weakly correlated with galaxy bulge-to-disk ratio (as measured by the concentration index of the r-band light). We also find that the fraction of galaxies with significant (more than a few percent) HI decreases sharply above a characteristic stellar surface mass density of 10^8.5 Msun kpc^-2. The fraction of gas-rich galaxies decreases much more smoothly with stellar mass. One of the key goals of GASS is to identify and quantify the incidence of galaxies that are transitioning between the blue, star-forming cloud and the red sequence of passively-evolving galaxies. Likely transition candidates can be identified as outliers from the mean scaling relations between gas fraction and other galaxy properties. [abridged]Comment: 25 pages, 12 figures. Accepted for publication in MNRAS. Version with high resolution figures available at http://www.mpa-garching.mpg.de/GASS/pubs.ph

The WiggleZ Dark Energy Survey: the selection function and z=0.6 galaxy power spectrum

We report one of the most accurate measurements of the three-dimensional large-scale galaxy power spectrum achieved to date, using 56,159 redshifts of bright emission-line galaxies at effective redshift z=0.6 from the WiggleZ Dark Energy Survey at the Anglo-Australian Telescope. We describe in detail how we construct the survey selection function allowing for the varying target completeness and redshift completeness. We measure the total power with an accuracy of approximately 5% in wavenumber bands of dk=0.01 h/Mpc. A model power spectrum including non-linear corrections, combined with a linear galaxy bias factor and a simple model for redshift-space distortions, provides a good fit to our data for scales k < 0.4 h/Mpc. The large-scale shape of the power spectrum is consistent with the best-fitting matter and baryon densities determined by observations of the Cosmic Microwave Background radiation. By splitting the power spectrum measurement as a function of tangential and radial wavenumbers we delineate the characteristic imprint of peculiar velocities. We use these to determine the growth rate of structure as a function of redshift in the range 0.4 < z < 0.8, including a data point at z=0.78 with an accuracy of 20%. Our growth rate measurements are a close match to the self-consistent prediction of the LCDM model. The WiggleZ Survey data will allow a wide range of investigations into the cosmological model, cosmic expansion and growth history, topology of cosmic structure, and Gaussianity of the initial conditions. Our calculation of the survey selection function will be released at a future date via our website wigglez.swin.edu.au.Comment: 21 pages, 22 figures, accepted for publication in MNRA

The WiggleZ Dark Energy Survey: measuring the cosmic expansion history using the Alcock-Paczynski test and distant supernovae

Astronomical observations suggest that today's Universe is dominated by a dark energy of unknown physical origin. One of the most notable consequences in many models is that dark energy should cause the expansion of the Universe to accelerate: but the expansion rate as a function of time has proven very difficult to measure directly. We present a new determination of the cosmic expansion history by combining distant supernovae observations with a geometrical analysis of large-scale galaxy clustering within the WiggleZ Dark Energy Survey, using the Alcock-Paczynski test to measure the distortion of standard spheres. Our result constitutes a robust and non-parametric measurement of the Hubble expansion rate as a function of time, which we measure with 10-15% precision in four bins within the redshift range 0.1 < z < 0.9. We demonstrate that the cosmic expansion is accelerating, in a manner independent of the parameterization of the cosmological model (although assuming cosmic homogeneity in our data analysis). Furthermore, we find that this expansion history is consistent with a cosmological-constant dark energy.Comment: 13 pages, 7 figures, accepted for publication by MNRA

The WiggleZ Dark Energy Survey: Survey Design and First Data Release

The WiggleZ Dark Energy Survey is a survey of 240,000 emission line galaxies in the distant universe, measured with the AAOmega spectrograph on the 3.9-m Anglo-Australian Telescope (AAT). The target galaxies are selected using ultraviolet photometry from the GALEX satellite, with a flux limit of NUV<22.8 mag. The redshift range containing 90% of the galaxies is 0.2<z<1.0. The primary aim of the survey is to precisely measure the scale of baryon acoustic oscillations (BAO) imprinted on the spatial distribution of these galaxies at look-back times of 4-8 Gyrs. Detailed forecasts indicate the survey will measure the BAO scale to better than 2% and the tangential and radial acoustic wave scales to approximately 3% and 5%, respectively. This paper provides a detailed description of the survey and its design, as well as the spectroscopic observations, data reduction, and redshift measurement techniques employed. It also presents an analysis of the properties of the target galaxies, including emission line diagnostics which show that they are mostly extreme starburst galaxies, and Hubble Space Telescope images, which show they contain a high fraction of interacting or distorted systems. In conjunction with this paper, we make a public data release of data for the first 100,000 galaxies measured for the project.Comment: Accepted by MNRAS; this has some figures in low resolution format. Full resolution PDF version (7MB) available at http://www.physics.uq.edu.au/people/mjd/pub/wigglez1.pdf The WiggleZ home page is at http://wigglez.swin.edu.au

Human Genome-Wide RNAi Screen Identifies an Essential Role for Inositol Pyrophosphates in Type-I Interferon Response

The pattern recognition receptor RIG-I is critical for Type-I interferon production. However, the global regulation of RIG-I signaling is only partially understood. Using a human genome-wide RNAi-screen, we identified 226 novel regulatory proteins of RIG-I mediated interferon-β production. Furthermore, the screen identified a metabolic pathway that synthesizes the inositol pyrophosphate 1-IP7 as a previously unrecognized positive regulator of interferon production. Detailed genetic and biochemical experiments demonstrated that the kinase activities of IPPK, PPIP5K1 and PPIP5K2 (which convert IP5 to1-IP7) were critical for both interferon induction, and the control of cellular infection by Sendai and influenza A viruses. Conversely, ectopically expressed inositol pyrophosphate-hydrolases DIPPs attenuated interferon transcription. Mechanistic experiments in intact cells revealed that the expression of IPPK, PPIP5K1 and PPIP5K2 was needed for the phosphorylation and activation of IRF3, a transcription factor for interferon. The addition of purified individual inositol pyrophosphates to a cell free reconstituted RIG-I signaling assay further identified 1-IP7 as an essential component required for IRF3 activation. The inositol pyrophosphate may act by β-phosphoryl transfer, since its action was not recapitulated by a synthetic phosphonoacetate analogue of 1-IP7. This study thus identified several novel regulators of RIG-I, and a new role for inositol pyrophosphates in augmenting innate immune responses to viral infection that may have therapeutic applications

The WiggleZ Dark Energy Survey: Direct constraints on blue galaxy intrinsic alignments at intermediate redshifts

Correlations between the intrinsic shapes of galaxy pairs, and between the intrinsic shapes of galaxies and the large-scale density field, may be induced by tidal fields. These correlations, which have been detected at low redshifts (z<0.35) for bright red galaxies in the Sloan Digital Sky Survey (SDSS), and for which upper limits exist for blue galaxies at z~0.1, provide a window into galaxy formation and evolution, and are also an important contaminant for current and future weak lensing surveys. Measurements of these alignments at intermediate redshifts (z~0.6) that are more relevant for cosmic shear observations are very important for understanding the origin and redshift evolution of these alignments, and for minimising their impact on weak lensing measurements. We present the first such intermediate-redshift measurement for blue galaxies, using galaxy shape measurements from SDSS and spectroscopic redshifts from the WiggleZ Dark Energy Survey. Our null detection allows us to place upper limits on the contamination of weak lensing measurements by blue galaxy intrinsic alignments that, for the first time, do not require significant model-dependent extrapolation from the z~0.1 SDSS observations. Also, combining the SDSS and WiggleZ constraints gives us a long redshift baseline with which to constrain intrinsic alignment models and contamination of the cosmic shear power spectrum. Assuming that the alignments can be explained by linear alignment with the smoothed local density field, we find that a measurement of \sigma_8 in a blue-galaxy dominated, CFHTLS-like survey would be contaminated by at most +/-0.02 (95% confidence level, SDSS and WiggleZ) or +/-0.03 (WiggleZ alone) due to intrinsic alignments. [Abridged]Comment: 18 pages, 12 figures, accepted to MNRAS; v2 has correction to one author's name, NO other changes; v3 has minor changes in explanation and calculations, no significant difference in results or conclusions; v4 has an additional footnote about model interpretation, no changes to data/calculations/result