Sequence Context Influences the Structure and Aggregation Behavior of a PolyQ Tract

Expansions of polyglutamine (polyQ) tracts in nine different proteins cause a family of neurodegenerative disorders called polyQ diseases. Because polyQ tracts are potential therapeutic targets for these pathologies there is great interest in characterizing the conformations that they adopt and in understanding how their aggregation behavior is influenced by the sequences flanking them. We used solution NMR to study at single-residue resolution a 156-residue proteolytic fragment of the androgen receptor that contains a polyQ tract associated with the disease spinobulbar muscular atrophy, also known as Kennedy disease. Our findings indicate that a Leu-rich region preceding the polyQ tract causes it to become α-helical and appears to protect the protein against aggregation, which represents a new, to our knowledge, mechanism by which sequence context can minimize the deleterious properties of these repetitive regions. Our results have implications for drug discovery for polyQ diseases because they suggest that the residues flanking these repetitive sequences may represent viable therapeutic targets

The free energy landscape of the oncogene protein E7 of human papillomavirus type 16 reveals a complex interplay between ordered and disordered regions.

When present, structural disorder makes it very challenging to characterise the conformational properties of proteins. This is particularly the case of proteins, such as the oncogene protein E7 of human papillomavirus type 16, which contain both ordered and disordered domains, and that can populate monomeric and oligomeric states under physiological conditions. Nuclear magnetic resonance (NMR) spectroscopy is emerging as a powerful method to study these complex systems, most notably in combination with molecular dynamics simulations. Here we use NMR chemical shifts and residual dipolar couplings as structural restraints in replica-averaged molecular dynamics simulations to determine the free energy landscape of E7. This landscape reveals a complex interplay between a folded but highly dynamical C-terminal domain and a disordered N-terminal domain that forms transient secondary and tertiary structures, as well as an equilibrium between a high-populated (98%) dimeric state and a low-populated (2%) monomeric state. These results provide compelling evidence of the complex conformational heterogeneity associated with the behaviour and interactions of this disordered protein associated with disease.University of Florence (Italy) “Science without borders” of the Brazilian Ministry of Science and Technology (CNPq

Chandra Study of the Cepheus B Star Forming Region: Stellar Populations and the Initial Mass Function

Cepheus B (Cep B) molecular cloud and a portion of the nearby Cep OB3b OB association, one of the most active regions of star formation within 1 kpc, has been observed with the ACIS detector on board the Chandra X-ray Observatory. We detect 431 X-ray sources, of which 89% are confidently identified as clustered pre-main sequence stars. Two main results are obtained. First, we provide the best census to date for the stellar population of the region. We identify many members of two rich stellar clusters: the lightly obscured Cep OB3b association, and the deeply embedded cluster in Cep B whose existence was previously traced only by a handful of radio sources and T Tauri stars. Second, we find a discrepancy between the X-ray Luminosity Functions of the Cep OB3b and the Orion Nebula Cluster. This may be due to different Initial Mass Functions of two regions (excess of ~0.3 solar mass stars), or different age distributions. Several other results are obtained. A diffuse X-ray component seen in the field is attributed to the integrated emission of unresolved low mass PMS stars. The X-ray emission from HD 217086 (O7n), the principle ionizing source of the region, follows the standard model involving many small shocks in an unmagnetized radiatively accelerated wind. The X-ray source #294 joins a number of similar superflare PMS stars where long magnetic structures may connect the protoplanetary disk to the stellar surface.Comment: 72 pages, 31 figures, 8 tables. Accepted for publication in Ap

High Mass Star Formation. II. The Mass Function of Submillimeter Clumps in M17

We have mapped an approximately 5.5 by 5.5 pc portion of the M17 massive star-forming region in both 850 and 450 micron dust continuum emission using the Submillimeter Common-User Bolometer Array (SCUBA) on the James Clerk Maxwell Telescope (JCMT). The maps reveal more than 100 dusty clumps with deconvolved linear sizes of 0.05--0.2 pc and masses of 0.8--120 solar masses, most of which are not associated with known mid-infrared point sources. Fitting the clump mass function with a double power law gives a mean power law exponent of alpha_high = -2.4 +/- 0.3 for the high-mass power law, consistent with the exponent of the Salpeter stellar mass function. We show that a lognormal clump mass distribution with a peak at about 4 solar masses produces as good a fit to the clump mass function as does a double power law. This 4 solar mass peak mass is well above the peak masses of both the stellar initial mass function and the mass function of clumps in low-mass star-forming regions. Despite the difference in intrinsic mass scale, the shape of the M17 clump mass function appears to be consistent with the shape of the core mass function in low-mass star-forming regions. Thus, we suggest that the clump mass function in high-mass star-forming regions may be a scaled-up version of that in low-mass regions, instead of its extension to higher masses.Comment: 33 pages, 6 figures, 3 tables. Accepted for publication in the Astrophysical Journa

Gas Analysis and Monitoring Systems for the RPC Detector of CMS at LHC

The Resistive Plate Chambers (RPC) detector of the CMS experiment at the LHC proton collider (CERN, Switzerland) will employ an online gas analysis and monitoring system of the freon-based gas mixture used. We give an overview of the CMS RPC gas system, describe the project parameters and first results on gas-chromatograph analysis. Finally, we report on preliminary results for a set of monitor RPC.Comment: 9 pages, 8 figures. Presented by Stefano Bianco (Laboratori Nazionali di Frascati dell'INFN) at the IEEE NSS, San Diego (USA), October 200

ISOGAL: A deep survey of the obscured inner Milky Way with ISO at 7 and 15 micron and with DENIS in the near-infrared

The ISOGAL project is an infrared survey of specific regions sampling the Galactic Plane selected to provide information on Galactic structure,stellar populations,stellar mass-loss and the recent star formation history of the inner disk and Bulge of the Galaxy. ISOGAL combines 7 and 15 micron ISOCAM observations - with a resolution of 6'' at worst - with DENIS IJKs data to determine the nature of the sources and theinterstellar extinction. We have observed about 16 square degrees with a sensitivity approaching 10-20mJy, detecting ~10^5 sources,mostly AGB stars,red giants and young stars. The main features of the ISOGAL survey and the observations are summarized in this paper,together with a brief discussion of data processing and quality. The primary ISOGAL products are described briefly (a full description is given in Schuller et al. 2003, astro-ph/0304309): viz. the images and theISOGAL-DENIS five-wavelength point source catalogue. The main scientific results already derived or in progress are summarized. These include astrometrically calibrated 7 and 15um images,determining structures of resolved sources; identification and properties of interstellar dark clouds; quantification of the infrared extinction law and source dereddening; analysis of red giant and (especially) AGB stellar populations in the central Bulge,determining luminosity,presence of circumstellar dust and mass--loss rate,and source classification,supplemented in some cases by ISO/CVF spectroscopy; detection of young stellar objects of diverse types,especially in the inner Bulge with information about the present and recent star formation rate; identification of foreground sources with mid-IR excess. These results are the subject of about 25 refereed papers published or in preparation.Comment: A&A in press. 19 pages,10 Ps figures; problems with figures fixe

Mass-Losing Semiregular Variable Stars in Baade's Windows

By cross-correlating the results of two recent large-scale surveys, the general properties of a well defined sample of semi-regular variable stars have been determined. ISOGAL mid-infrared photometry and MACHO lightcurves are assembled for approximately 300 stars in the Baade's Windows of low extinction towards the Galactic bulge. These stars are mainly giants of late M spectral type, evolving along the asymptotic giant branch (AGB). They are found to possess a wide and continuous distribution of pulsation periods and to obey an approximate log~period -- bolometric magnitude relation or set of such relations. Approximate mass-loss rates in the range of 1e-8 to 5e-7 M_sun per year are derived from ISOGAL mid-infrared photometry and models of stellar spectra adjusted for the presence of optically-thin circumstellar silicate dust. Mass-loss rates depend on luminosity and pulsation period. Some stars lose mass as rapidly as short-period Miras but do not show Mira-like amplitudes. A period of 70 days or longer is a necessary but not a sufficient condition for mass loss to occur. For AGB stars in the mass-loss ranges that we observe, the functional dependence of mass-loss rate on temperature and luminosity is found to be in agreement with recent theoretical predictions. If we include our mass-loss rates with a sample of extreme mass-losing AGB stars in the Large Magellanic Cloud, we get the general result for AGB stars that mass-loss rate is proportional to luminosity^{2.7}, valid for AGB stars with 10^{-8} to 10^{-4} M_sun per year (Abridged).Comment: to appear in The Astrophysical Journal, 51 pages, 9 figures, 3 tables; table 1 will be available in machine-readable format at the electronic Ap

Ten Million Degree Gas in M 17 and the Rosette Nebula: X-ray Flows in Galactic H II Regions

We present the first high-spatial-resolution X-ray images of two high-mass star forming regions, the Omega Nebula (M 17) and the Rosette Nebula (NGC 2237--2246), obtained with the Chandra X-ray Observatory Advanced CCD Imaging Spectrometer (ACIS) instrument. The massive clusters powering these H II regions are resolved at the arcsecond level into >900 (M 17) and >300 (Rosette) stellar sources similar to those seen in closer young stellar clusters. However, we also detect soft diffuse X-ray emission on parsec scales that is spatially and spectrally distinct from the point source population. The diffuse emission has luminosity L_x ~ 3.4e33 ergs/s in M~17 with plasma energy components at kT ~0.13 and ~0.6 keV (1.5 and 7 MK), while in Rosette it has L_x \~6e32 ergs/s with plasma energy components at kT ~0.06 and ~0.8 keV (0.7 and 9 MK). This extended emission most likely arises from the fast O-star winds thermalized either by wind-wind collisions or by a termination shock against the surrounding media. We establish that only a small portion of the wind energy and mass appears in the observed diffuse X-ray plasma; in these blister H II regions, we suspect that most of it flows without cooling into the low-density interstellar medium. These data provide compelling observational evidence that strong wind shocks are present in H II regions.Comment: 35 pages, including 11 figures; to appear in ApJ, August 20, 2003. A version with high-resolution figures is available at ftp://ftp.astro.psu.edu/pub/townsley/diffuse.ps.g

The Detection of Magnetic Fields Toward M17 through the HI Zeeman Effect

We have carried out VLA Zeeman observations of HI absorption lines toward the HII region in the M17 giant molecular cloud complex. The HI absorption lines toward M17 show between 5 and 8 distinct velocity components which vary spatially in a complex manner across the source. We explore possible physical connections between these components and the M17 region based on calculations of HI column densities, line of sight magnetic field strengths, as well as comparisons with a wide array of previous optical, infrared, and radio observations. In particular, an HI component at the same velocity as the southwestern molecular cloud (M17 SW) ~20 km/s seems to originate from the edge-on interface between the HII region and M17 SW, in un-shocked PDR gas. We have detected a steep enhancement in the 20 km/s HI column density and line of sight magnetic field strengths (Blos) toward this boundary. A lower limit for the peak 20 km/s HI column density is N_{HI}/T_s > 5.6 x 10^{19} cm^{-2}/K while the peak Blos is ~ -450 muG. In addition, blended components at velocities of 11-17 km/s appear to originate from shocked gas in the PDR between the HII region and an extension of M17 SW, which partially obscures the southern bar of the HII region. The peak N_{HI}/T_s and Blos for this component are > 4.4 x 10^{19} cm^{-2}/K and +550 muG, respectively. Comparison of the peak magnetic fields detected toward M17 with virial equilibrium calculations suggest that ~1/3 of M17 SW's total support comes from its static magnetic field and the other 2/3 from its turbulent kinetic energy which includes support from Alfven waves.Comment: Contains 29 pages, 14 figures (Latex). Text and figures can be downloaded separately at http://www.pa.uky.edu/~brogan, submitted to Ap