Deubiquitylating Enzymes and DNA Damage Response Pathways

Covalent post-translational modification of proteins by ubiquitin and ubiquitin-like factors has emerged as a general mechanism to regulate myriad intra-cellular processes. The addition and removal of ubiquitin or ubiquitin-like proteins from factors has recently been demonstrated as a key mechanism to modulate DNA damage response (DDR) pathways. It is thus, timely to evaluate the potential for ubiquitin pathway enzymes as DDR drug targets for therapeutic intervention. The synthetic lethal approach provides exciting opportunities for the development of targeted therapies to treat cancer: most tumours have lost critical DDR pathways, and thus rely more heavily on the remaining pathways, while normal tissues are still equipped with all DDR pathways. Here, we review key deubiquitylating enzymes (DUBs) involved in DDR pathways, and describe how targeting DUBs may lead to selective therapies to treat cancer patients

The Bell Laboratories (13)CO Survey: Longitude-Velocity Maps

A survey is presented of the Galactic plane in the J=1-0 transition of (13)CO. About 73,000 spectra were obtained with the 7 m telescope at Bell Laboratories over a ten-year period. The coverage of survey is (l, b) = (-5 to 117, -1 to +1), or 244 square degrees, with a grid spacing of 3' for |b| < 0.5, and a grid spacing of 6' for |b| > 0.5. The data presented here have been resampled onto a 3' grid. For 0.68 km/s channels, the rms noise level of the survey is 0.1 K on the $T_R^*$ scale. The raw data have been transformed into FITS format, and all the reduction processes, such as correcting for emission in the reference positions, baseline removal and interpolation were conducted within IRAF using the FCRAO task package and additional programs. The reduced data are presented here in the form of longitude-velocity color maps at each latitude. These data allow identification and classification of molecular clouds with masses in excess of ~ 1,000 solar masses throughout the first quadrant of the Galaxy. Spiral structure is manifested by the locations of the largest and brightest molecular clouds.Comment: 23 pages, 7 figures, ApJS submitted (out of 41 frames of Figure4, only one is included becaue of size limit

Discovery of Interstellar Hydrogen Fluoride

We report the first detection of interstellar hydrogen fluoride. Using the Long Wavelength Spectrometer (LWS) of the Infrared Space Observatory (ISO), we have detected the 121.6973 micron J = 2 - 1 line of HF in absorption toward the far-infrared continuum source Sagittarius B2. The detection is statistically significant at the 13 sigma level. On the basis of our model for the excitation of HF in Sgr B2, the observed line equivalent width of 1.0 nm implies a hydrogen fluoride abundance of 3E-10 relative to H2. If the elemental abundance of fluorine in Sgr B2 is the same as that in the solar system, then HF accounts for ~ 2% of the total number of fluorine nuclei. We expect hydrogen fluoride to be the dominant reservoir of gas-phase fluorine in Sgr B2, because it is formed rapidly in exothermic reactions of atomic fluorine with either water or molecular hydrogen; thus the measured HF abundance suggests a substantial depletion of fluorine onto dust grains. Similar conclusions regarding depletion have previously been reached for the case of chlorine in dense interstellar clouds. We also find evidence at a lower level of statistical significance (~ 5 sigma) for an emission feature at the expected position of the 4(3,2)-4(2,3) 121.7219 micron line of water. The emission line equivalent width of 0.5 nm for the water feature is consistent with the water abundance of 5E-6 relative to H2 that has been inferred previously from observations of the hot core of Sgr B2.Comment: 11 pages (AASTeX using aaspp4.sty) plus 2 figures; to appear in ApJ Letter

A Neutral Hydrogen Self-Absorption Cloud in the SGPS

Using data from the Southern Galactic Plane Survey (SGPS) we analyze an HI self-absorption cloud centered on l = 318.0 deg, b = -0.5 deg, and velocity, v = -1.1 km/s. The cloud was observed with the Australia Telescope Compact Array (ATCA) and the Parkes Radio Telescope, and is at a near kinematic distance of less than 400 pc with derived dimensions of less than 5 x 11 pc. We apply two different methods to find the optical depth and spin temperature. In both methods we find upper limit spin temperatures ranging from 20 K to 25 K and lower limit optical depths ~ 1. We look into the nature of the HI emission and find that 60-70% originates behind the cloud. We analyze a second cloud at the same velocity centered on l = 319 deg and b = 0.4 deg with an upper limit spin temperature of 20 K and a lower limit optical depth of 1.6. The similarities in spin temperature, optical depth, velocity, and spatial location are evidence the clouds are associated, possibly as one large cloud consisting of smaller clumps of gas. We compare HI emission data with 12CO emission and find a physical association of the HI self-absorption cloud with molecular gas.Comment: 33 pages, 17 figures, 5 tables; Accepted for publication in ApJ. A version with higher quality images availabe at http://www.astro.umn.edu/~dkavars/ms.p

Deuterated Ammonia in Galactic Protostellar Cores

We report on a survey of \nh2d towards protostellar cores in low-mass star formation and quiescent regions in the Galaxy. Twenty-three out of thirty-two observed sources have significant (\gsim 5\sigma) \nh2d emission. Ion-molecule chemistry, which preferentially enhances deuterium in molecules above its cosmological value of \scnot{1.6}{-5} sufficiently explains these abundances. NH2D/NH3 ratios towards Class 0 sources yields information about the ``fossil remnants'' from the era prior to the onset of core collapse and star formation. We compare our observations with predictions of gas-phase chemical networks.Comment: 16 Pages, 7 Figures, Accepted to Ap.J., to appear in the June 20, 2001 editio

Water abundances in high-mass protostellar envelopes: Herschel observations with HIFI

We derive the dense core structure and the water abundance in four massive star-forming regions which may help understand the earliest stages of massive star formation. We present Herschel-HIFI observations of the para-H2O 1_11-0_00 and 2_02-1_11 and the para-H2-18O 1_11-0_00 transitions. The envelope contribution to the line profiles is separated from contributions by outflows and foreground clouds. The envelope contribution is modelled using Monte-Carlo radiative transfer codes for dust and molecular lines (MC3D and RATRAN), with the water abundance and the turbulent velocity width as free parameters. While the outflows are mostly seen in emission in high-J lines, envelopes are seen in absorption in ground-state lines, which are almost saturated. The derived water abundances range from 5E-10 to 4E-8 in the outer envelopes. We detect cold clouds surrounding the protostar envelope, thanks to the very high quality of the Herschel-HIFI data and the unique ability of water to probe them. Several foreground clouds are also detected along the line of sight. The low H2O abundances in massive dense cores are in accordance with the expectation that high densities and low temperatures lead to freeze-out of water on dust grains. The spread in abundance values is not clearly linked to physical properties of the sources.Comment: 8 pages, 5 figures, accepted for publication the 15/07/2010 by Astronomy&Astrophysics as a letter in the Herschel-HIFI special issu

The CHESS chemical Herschel surveys of star forming regions: Peering into the protostellar shock L1157-B1. I. Shock chemical complexity

We present the first results of the unbiased survey of the L1157-B1 bow shock, obtained with HIFI in the framework of the key program Chemical Herschel surveys of star forming regions (CHESS). The L1157 outflow is driven by a low-mass Class 0 protostar and is considered the prototype of the so-called chemically active outflows. The bright blue-shifted bow shock B1 is the ideal laboratory for studying the link between the hot (around 1000-2000 K) component traced by H2 IR-emission and the cold (around 10-20 K) swept-up material. The main aim is to trace the warm gas chemically enriched by the passage of a shock and to infer the excitation conditions in L1157-B1. A total of 27 lines are identified in the 555-636 GHz region, down to an average 3 sigma level of 30 mK. The emission is dominated by CO(5-4) and H2O(110-101) transitions, as discussed by Lefloch et al. (2010). Here we report on the identification of lines from NH3, H2CO, CH3OH, CS, HCN, and HCO+. The comparison between the profiles produced by molecules released from dust mantles (NH3, H2CO, CH3OH) and that of H2O is consistent with a scenario in which water is also formed in the gas-phase in high-temperature regions where sputtering or grain-grain collisions are not efficient. The high excitation range of the observed tracers allows us to infer, for the first time for these species, the existence of a warm (> 200 K) gas component coexisting in the B1 bow structure with the cold and hot gas detected from ground

Nitrogen hydrides in the cold envelope of IRAS16293-2422

Nitrogen is the fifth most abundant element in the Universe, yet the gas-phase chemistry of N-bearing species remains poorly understood. Nitrogen hydrides are key molecules of nitrogen chemistry. Their abundance ratios place strong constraints on the production pathways and reaction rates of nitrogen-bearing molecules. We observed the class 0 protostar IRAS16293-2422 with the heterodyne instrument HIFI, covering most of the frequency range from 0.48 to 1.78~THz at high spectral resolution. The hyperfine structure of the amidogen radical o-NH2 is resolved and seen in absorption against the continuum of the protostar. Several transitions of ammonia from 1.2 to 1.8~THz are also seen in absorption. These lines trace the low-density envelope of the protostar. Column densities and abundances are estimated for each hydride. We find that NH:NH2:NH3=5:1:300. {Dark clouds chemical models predict steady-state abundances of NH2 and NH3 in reasonable agreement with the present observations, whilst that of NH is underpredicted by more than one order of magnitude, even using updated kinetic rates. Additional modelling of the nitrogen gas-phase chemistry in dark-cloud conditions is necessary before having recourse to heterogen processes

Sensitive limits on the abundance of cold water vapor in the DM Tau protoplanetary disk

We performed a sensitive search for the ground-state emission lines of ortho- and para-water vapor in the DM Tau protoplanetary disk using the Herschel/HIFI instrument. No strong lines are detected down to 3sigma levels in 0.5 km/s channels of 4.2 mK for the 1_{10}--1_{01} line and 12.6 mK for the 1_{11}--0_{00} line. We report a very tentative detection, however, of the 1_{10}--1_{01} line in the Wide Band Spectrometer, with a strength of T_{mb}=2.7 mK, a width of 5.6 km/s and an integrated intensity of 16.0 mK km/s. The latter constitutes a 6sigma detection. Regardless of the reality of this tentative detection, model calculations indicate that our sensitive limits on the line strengths preclude efficient desorption of water in the UV illuminated regions of the disk. We hypothesize that more than 95-99% of the water ice is locked up in coagulated grains that have settled to the midplane.Comment: 5 pages, 3 figures. Accepted for publication in the Herschel HIFI special issue of A&