Systematic genetic array analysis links the Saccharomyces cerevisiae SAGA/SLIK and NuA4 component Tra1 to multiple cellular processes

<p>Abstract</p> <p>Background</p> <p>Tra1 is an essential 437-kDa component of the <it>Saccharomyces cerevisiae </it>SAGA/SLIK and NuA4 histone acetyltransferase complexes. It is a member of a group of key signaling molecules that share a carboxyl-terminal domain related to phosphatidylinositol-3-kinase but unlike many family members, it lacks kinase activity. To identify genetic interactions for <it>TRA1 </it>and provide insight into its function we have performed a systematic genetic array analysis (SGA) on <it>tra1</it>_{<it>SRR</it>3413}, an allele that is defective in transcriptional regulation.</p> <p>Results</p> <p>The SGA analysis revealed 114 synthetic slow growth/lethal (SSL) interactions for <it>tra1</it>_{<it>SRR</it>3413}. The interacting genes are involved in a range of cellular processes including gene expression, mitochondrial function, and membrane sorting/protein trafficking. In addition many of the genes have roles in the cellular response to stress. A hierarchal cluster analysis revealed that the pattern of SSL interactions for <it>tra1</it>_{<it>SRR</it>3413}most closely resembles deletions of a group of regulatory GTPases required for membrane sorting/protein trafficking. Consistent with a role for Tra1 in cellular stress, the <it>tra1</it>_{<it>SRR</it>3413}strain was sensitive to rapamycin. In addition, calcofluor white sensitivity of the strain was enhanced by the protein kinase inhibitor staurosporine, a phenotype shared with the Ada components of the SAGA/SLIK complex. Through analysis of a GFP-Tra1 fusion we show that Tra1 is principally localized to the nucleus.</p> <p>Conclusion</p> <p>We have demonstrated a genetic association of Tra1 with nuclear, mitochondrial and membrane processes. The identity of the SSL genes also connects Tra1 with cellular stress, a result confirmed by the sensitivity of the <it>tra1</it>_{<it>SRR</it>3413}strain to a variety of stress conditions. Based upon the nuclear localization of GFP-Tra1 and the finding that deletion of the Ada components of the SAGA complex result in similar phenotypes as <it>tra1</it>_{<it>SRR</it>3413}, we suggest that the effects of <it>tra1</it>_{<it>SRR</it>3413}are mediated, at least in part, through its role in the SAGA complex.</p

The Angular Correlation Function of K=19.5 Galaxies and the Detection of a Cluster at z=0.775

On five K-band Omega camera images, covering a total of 162.2 sq. arcmin to K=19.5, we investigate (i) the clustering environment of 5 radio galaxies at 0.7<z<0.8 and (ii) the galaxy angular correlation function. We detect a cluster of estimated Abell richness class 1 or 2, centred on the radio galaxy 5C6.75 at z=0.775. Of the other radio galaxies, two appear to be in less rich groups or structures, and two in field environments. The mean clustering environment of all 5 is similar to that of radio galaxies at more moderate redshifts of 0.35<z<0.55. The angular correlation function of the galaxies, at limits K=18.5--20.0, is most consistent with a luminosity evolution model in which E/S0 galaxies are much more clustered than spirals (r_0=8.4 compared to 4.2 1/h Mpc) and clustering is approximately stable (epsilon=0), although the clustering may exceed the stable model at the highest (z>1.5) redshifts. We also find a significant excess of 1.5--5.0 arcsec separation pairs of galaxies compared to the expectation from the inward extrapolation of omega(theta). To K=19.5, we estimate that 11.0\pm 3.4 per cent of galaxies are in close pairs in excess of omega(theta). This can be explained if the local rate of galaxy mergers and interactions increases with redshift as $\sim (1+z)^m$ with $m=1.33_{-0.51}^{+0.36}$.Comment: 14 pages, latex, 8 figures, submitted to MNRA

The driver landscape of sporadic chordoma.

Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the notochordal transcription factor brachyury (T) in up to 27% of cases. These variants recapitulate the rearrangement architecture of the pathogenic germline duplications of T that underlie familial chordoma. In addition, we find potentially clinically actionable PI3K signalling mutations in 16% of cases. Intriguingly, one of the most frequently altered genes, mutated exclusively by inactivating mutation, was LYST (10%), which may represent a novel cancer gene in chordoma.Chordoma is a rare often incurable malignant bone tumour. Here, the authors investigate driver mutations of sporadic chordoma in 104 cases, revealing duplications in notochordal transcription factor brachyury (T), PI3K signalling mutations, and mutations in LYST, a potential novel cancer gene in chordoma

Clustering of galaxies around radio quasars at 0.5 < z < 0.8

We have observed the galaxy environments around a sample of 21 radio-loud, steep-spectrum quasars at 0.5<z<0.82, spanning several orders of magnitude in radio luminosity. The observations also include background control fields used to obtain the excess number of galaxies in each quasar field. The galaxy excess was quantified using the spatial galaxy-quasar correlation amplitude, B_gq, and an Abell-type measurement, N_0.5 (Hill & Lilly 1991). A few quasars are found in relatively rich clusters, but on average, they seem to prefer galaxy groups or clusters of approximately Abell class 0. We have combined our sample with literature samples extending down to z=0.2 and covering the same range in radio luminosity. By using Spearman statistic to disentangle redshift and luminosity dependences, we detect a weak, but significant, positive correlation between the richness of the quasar environment and the quasar's radio luminosity. However, we do not find any epoch dependence in B_gq, as has previously been reported for radio quasars and galaxies. We discuss the radio luminosity-cluster richness link and possible explanations for the weak correlation that is seen.Comment: 18 pages, 9 figures, submitted to MNRA

The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey: measurements of the growth of structure and expansion rate at z=0.57 from anisotropic clustering

We analyze the anisotropic clustering of massive galaxies from the Sloan Digital Sky Survey III Baryon Oscillation Spectroscopic Survey (BOSS) Data Release 9 (DR9) sample, which consists of 264,283 galaxies in the redshift range 0.43 < z < 0.7 spanning 3,275 square degrees. Both peculiar velocities and errors in the assumed redshift-distance relation ("Alcock-Paczynski effect") generate correlations between clustering amplitude and orientation with respect to the line-of-sight. Together with the sharp baryon acoustic oscillation (BAO) standard ruler, our measurements of the broadband shape of the monopole and quadrupole correlation functions simultaneously constrain the comoving angular diameter distance (2190 +/- 61 Mpc) to z=0.57, the Hubble expansion rate at z=0.57 (92.4 +/- 4.5 km/s/Mpc), and the growth rate of structure at that same redshift (d sigma8/d ln a = 0.43 +/- 0.069). Our analysis provides the best current direct determination of both DA and H in galaxy clustering data using this technique. If we further assume a LCDM expansion history, our growth constraint tightens to d sigma8/d ln a = 0.415 +/- 0.034. In combination with the cosmic microwave background, our measurements of DA, H, and growth all separately require dark energy at z > 0.57, and when combined imply \Omega_{\Lambda} = 0.74 +/- 0.016, independent of the Universe's evolution at z<0.57. In our companion paper (Samushia et al. prep), we explore further cosmological implications of these observations.Comment: 19 pages, 11 figures, submitted to MNRAS, comments welcom

CP Violation and Neutrino Oscillations

We review the basic mechanisms of neutrino mass generation and the corresponding structure of the lepton mixing matrix. We summarize the status of three-neutrino oscillation parameters as determined from current observations, using state-of-the-art solar and atmospheric neutrino fluxes, as well as latest experimental data as of September 2007. We also comment on recent attempts to account for these results and to understand flavour from first principles. We discuss extensively the prospects for probing the strength of CP violation in two near term accelerator neutrino oscillation experiments, T2K and NOvA, as well as possible extensions such as T2KK and a second large off-axis detector near the NOvA detector. We also briefly discuss the possibility of probing the effect of Majorana phases in future neutrinoless double beta decay searches and discuss other implications of leptonic CP violation such as leptogenesis. Finally we comment on the issue of robustness of the current oscillation interpretation and possible ways of probing for non-standard neutrino interactions in precision oscillation studies.Comment: 78 pages, 46 figures, minor misprint corrections, a few new references and an acknowledgement to a funding agency. Review to be published in Prog. Part. Nucl. Phy

Effectiveness of in planta control measures for Xylella fastidiosa

This opinion updates the information included in the previous EFSA Scientific Opinion concerning the in planta control measures for Xylella fastidiosa, with a systematic review and critical analysis of the potential treatment solutions that have been published against this pest so far. The output of this opinion focuses on the application of chemical or biological treatments on living plants. In vitro studies, hot water treatments, use of resistant varieties and vector control are excluded from the review. The use of antibiotics is not considered due to the risk of antimicrobial resistance development. The use of weakly virulent or avirulent strains of X. fastidiosa is covered in this review, although this organism is an EU quarantine plant pest and its introduction in the EU territory is banned. Experiments were recently conducted to assess the effect of application of zinc, copper, and citric acid biocomplex, of N-acetylcysteine, and of ‘diffusible signal factor’ (and of its homologs). Their results showed that these control measures were sometimes able to reduce symptoms caused by X. fastidiosa. Recent experiments also showed that several species of endophytic microorganisms, some bacteriophages and inoculation of weakly virulent/avirulent strains of X. fastidiosa could offer some protection against the Pierce’s disease. However, based on the reviewed results, the Panel concludes that, although several published experiments show some effects in reducing symptoms development, the tested control measures are not able to completely eliminate X. fastidiosa from diseased plants. The Panel confirms as previously stated that there is currently no control measure available to eliminate the bacteria from a diseased plant in open field conditions

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors.

Messenger RNA encodes cellular function and phenotype. In the context of human cancer, it defines the identities of malignant cells and the diversity of tumor tissue. We studied 72,501 single-cell transcriptomes of human renal tumors and normal tissue from fetal, pediatric, and adult kidneys. We matched childhood Wilms tumor with specific fetal cell types, thus providing evidence for the hypothesis that Wilms tumor cells are aberrant fetal cells. In adult renal cell carcinoma, we identified a canonical cancer transcriptome that matched a little-known subtype of proximal convoluted tubular cell. Analyses of the tumor composition defined cancer-associated normal cells and delineated a complex vascular endothelial growth factor (VEGF) signaling circuit. Our findings reveal the precise cellular identities and compositions of human kidney tumors

The MassiveBlack-II simulation: the evolution of haloes and galaxies to z 0

(Abridged for arXiv)We investigate the properties of halos, galaxies and blackholes to z=0 in the high resolution hydrodynamical simulation MassiveBlack-II (MBII) which evolves a LCDM cosmology in a comoving volume Vbox=100(Mpc/h)^3. MBII is the highest resolution simulation of this size which includes a self-consistent model for star formation, black hole accretion and associated feedback. We provide a simulation browser web application which enables interactive search and tagging of halos, subhalos and their properties and publicly release our galaxy catalogs. Our analysis of the halo mass function (MF) in MBII reveals that baryons have strong effects, with changes in the halo abundance of 20-35% below the knee of the MF (Mhalo < 10^13.2 Msun/h at z=0) when compared to fits based on dark matter only simulations. We provide a fitting function for the halo MF out to redshift z=11 and discuss how the onset of non-universality in the MF limits the accuracy of our fit. We study the halo occupation distribution and clustering of galaxies, in particular the evolution and scale dependence of stochasticity and bias finding reasonable agreement with observational data. The shape of the cosmic spectral energy distribution predicted by MBII is consistent with observations, but lower in amplitude. The Galaxy Stellar Mass Function (GSMF) function is broadly consistent with observations at z>=2. At z<2, the population of passive low mass (for M*<10^9 Msun) galaxies in MBII makes the GSMF too steep compared to observations whereas at the high mass end (M*>10^11 Msun) galaxies hosting bright AGNs make significant contributions to the GSMF. The quasar bolometric luminosity function is also largely consistent with observations. We note however that more efficient AGN feedback (beyond simple thermal coupling used here) is likely necessary for the largest, rarest objects/clusters at low redshifts.Comment: 26 pages, 25 figures. Submitted to MNRAS. High-resolution version and MBII galaxy catalogs can be found at http://mbii.phys.cmu.edu/data