Bisphosphonate-associated osteonecrosis of the jaw is linked to suppressed TGFβ1-signaling and increased Galectin-3 expression: A histological study on biopsies

Background Bisphosphonate associated osteonecrosis of the jaw (BRONJ) implies an impairment in oral hard- and soft tissue repair. An understanding of the signal transduction alterations involved can inform therapeutic strategies. Transforming growth factor β1 (TGFβ1) is a critical regulator of tissue repair; galectin-3 mediates tissue differentiation and specifically modulates periodontopathic bacterial infection. The aim of this study was to compare the expression of TGFβ1-related signaling molecules and Galectin-3 in BRONJ-affected and healthy mucosal tissues. To discriminate between BRONJ-specific impairments in TGFβ1 signaling and secondary inflammatory changes, the results were compared to the expression of TGFβ1 and Galectin-3 in mucosal tissues with osteoradionecrosis. Methods Oral mucosal tissue samples with histologically-confirmed BRONJ (n = 20), osteoradionecrosis (n = 20), and no lesions (normal, n = 20) were processed for immunohistochemistry. Automated staining with an alkaline phosphatase-anti-alkaline phosphatase kit was used to detect TGFβ1, Smad-2/3, Smad-7, and Galectin-3. We semiquantitatively assessed the ratio of stained cells/total number of cells (labeling index, Bonferroni-adjustment). Results TGFβ1 and Smad-2/3 were significantly decreased (p < 0.032 and p(0.028, respectively) in the BRONJ samples and significantly increased (p < 0.04 and p <0.043, respectively) in the osteoradionecrosis samples compared to normal tissue. Smad-7 was significantly increased (p < 0.031) in the BRONJ group and significantly decreased (p < 0.026) in the osteoradionecrosis group. Galectin-3 staining was significantly (p < 0.025) increased in both the BRONJ and the osteoradionecrosis (p < 0.038) groups compared to the normal tissue group. However, Galectin-3 expression was significantly higher in the BRONJ samples than in the osteoradionecrosis samples (p < 0.044). Conclusion Our results showed that disrupted TGFβ1 signaling was associated with delayed periodontal repair in BRONJ samples. The findings also indicated that impairments in TGFβ1-signaling were different in BRONJ compared to osteoradionecrosis. BRONJ appeared to be associated with increased terminal osseous differentiation and decreased soft tissue proliferation. The increase in Galectin-3 reflected the increase in osseous differentiation of mucoperiosteal progenitors, and this might explain the inflammatory anergy observed in BRONJ-affected soft tissues. The results substantiated the clinical success of treating BRONJ with sequestrectomy, followed by strict mucosa closure. BRONJ can be further elucidated by investigating the specific intraoral osteoimmunologic status

Selection and photometric properties of K+A galaxies

Two different simple measurements of galaxy star formation rate with different timescales are compared empirically on $156,395$ fiber spectra of galaxies with $r<17.77$ mag taken from the Sloan Digital Sky Survey in the redshift range $0.05<z<0.20$: a ratio \Aamp / \Kamp found by fitting a linear sum of an average old stellar poplulation spectrum (\Kamp) and average A-star spectrum (\Aamp) to the galaxy spectrum, and the equivalent width (EW) of the \Halpha emission line. The two measures are strongly correlated, but there is a small clearly separated population of outliers from the median correlation that display excess \Aamp /\Kamp relative to \Halpha EW. These ``K+A'' (or ``E+A'') galaxies must have dramatically decreased their star-formation rates over the last $\sim 1$ Gyr. The K+A luminosity distribution is very similar to that of the total galaxy population. The K+A population appears to be bulge-dominated, but bluer and higher surface-brightness than normal bulge-dominated galaxies; it appears that K+A galaxies will fade with time into normal bulge-dominated galaxies. The inferred rate density for K+A galaxy formation is $\sim 10^{-4} h^3 Mpc^{-3} Gyr^{-1}$ at redshift $z\sim 0.1$. These events are taking place in the field; K+A galaxies don't primarily lie in the high-density environments or clusters typical of bulge-dominated populations.Comment: submitted to Ap

A Lyman-alpha-only AGN from the Sloan Digital Sky Survey

The Sloan Digital Sky Survey has discovered a z=2.4917 radio-loud active galactic nucleus (AGN) with a luminous, variable, low-polarization UV continuum, H I two-photon emission, and a moderately broad Lyman-alpha line (FWHM = 1430 km/s) but without obvious metal-line emission. SDSS J113658.36+024220.1 does have associated metal-line absorption in three distinct, narrow systems spanning a velocity range of 2710 km/s. Despite certain spectral similarities, SDSS J1136+0242 is not a Lyman-break galaxy. Instead, the Ly-alpha and two-photon emission can be attributed to an extended, low-metallicity narrow-line region. The unpolarized continuum argues that we see SDSS J1136+0242 very close to the axis of any ionization cone present. We can conceive of two plausible explanations for why we see a strong UV continuum but no broad-line emission in this `face-on radio galaxy' model for SDSS J1136+0242: the continuum could be relativistically beamed synchrotron emission which swamps the broad-line emission; or, more likely, SDSS J1136+0242 could be similar to PG 1407+265, a quasar in which for some unknown reason the high-ionization emission lines are very broad, very weak, and highly blueshifted.Comment: AJ, in press, 10 pages emulateapj forma

The Spatially Resolved Star Formation Law from Integral Field Spectroscopy: VIRUS-P Observations of NGC 5194

We investigate the relation between the star formation rate surface density (Sigma_SFR) and the mass surface density of gas (Sigma_gas) in NGC 5194. VIRUS-P integral field spectroscopy is used to measure H-alpha, H-beta [NII]6548,6584, and [SII]6717,6731 emission line fluxes for 735 regions ~170 pc in diameter, and derive extinction corrected Sigma_SFRs. HI 21cm and CO maps are used to measure the HI and H_2 gas surface density for each region. We present a new method for fitting the Star Formation Law (SFL), which includes the intrinsic scatter in the relation as a free parameter, allows the inclusion of non-detections, and is free of the systematics involved in performing linear correlations over incomplete data in logarithmic space. We use the [SII]/H-alpha ratio to separate the H-alpha flux contribution from the diffuse ionized gas (DIG). After removing the DIG, we measure a slope N=0.82+/-0.05, and an intrinsic scatter epsilon=0.43+/-0.02 dex for the molecular gas SFL. We also measure a typical depletion timescale tau~2 Gyr, in good agreement with Bigiel et al. (2008). The HI density shows no correlation with the SFR, and the total gas SFL closely follows the molecular gas SFL. We assess the validity of corrections applied in narrow-band H-alpha measurements to overcome issues related to continuum subtraction, underlying photospheric absorption, and contamination by the [NII] doublet. The disagreement with the super-linear molecular SFL measured by Kennicutt et al. (2007) is due to differences in the fitting method. Our results support a low and close to constant star formation efficiency (SFE = 1/tau) in the molecular ISM. The data shows excellent agreement with the model of Krumholz et al (2009). The large intrinsic scatter may imply the existence of other important parameters setting the SFR.Comment: 23 pages, 19 figures, 14 pages of tables. Accepted for publication in ApJ. (Figure 16 has been corrected from the first submitted version.

Two techniques for the preparation of cell-scaffold constructs suitable for sinus augmentation: steps into clinical application.

The objective of this clinical trial was the analysis of 2 methods for engineering of autologous bone grafts for maxillary sinus augmentation with secondary implant placement. Group 1 (8 patients, 12 sinuses): cells of mandibular periosteum were cultured in a good manufacturing practice laboratory (2 weeks) with autologous serum and then transferred onto a collagen matrix. After another week, these composites were transplanted into the sinuses. In group 2A (2 patients, 3 sinuses), cells of maxillary bone were cultivated with autologous serum for 2 weeks, seeded onto natural bone mineral (NBM, diameter [Ø] = 8 mm) blocks, and cultivated for another 1.5 months. These composites were transplanted into the sinuses. Group 2B (control, 3 patients, 5 sinuses) received NBM blocks alone. In the course of implant placement 6 (group 1) and 8 (group 2) months later, core biopsy were taken. Clinical follow-up period was 1 to 2.5 years in group 1 and approximately 7 years in groups 2A and 2B. New vital bone was found in all cases at median densities of 38\% (n = 12) in group 1, 32\% in group 2A (n = 3), and 25\% in group 2B (n = 5). Differences between group 1 and 2B as well as 2A and 2B were statistically significant ( p = 0.025). No adverse effects were seen. All methods described were capable of creating new bone tissue with sufficient stability for successful implant placement

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

Gemini/GMOS Imaging of Globular Cluster Systems in Five Early-type Galaxies

This paper presents deep high quality photometry of globular cluster (GC) systems belonging to five early-type galaxies covering a range of mass and environment. Photometric data were obtained with the Gemini North and Gemini South telescopes in the filter passbands g', r', and i'. The combination of these filters with good seeing conditions allows an excellent separation between GC candidates and unresolved field objects. Bimodal GC colour distributions are found in all five galaxies. Most of the GC systems appear bimodal even in the (g' -r') vs (r' -i') plane. A population of resolved/marginally resolved GC and Ultra Compact Dwarf candidates was found in all the galaxies. A search for the so-called "blue tilt" in the colour-magnitude diagrams reveals that NGC 4649 clearly shows that phenomenon although no conclusive evidence was found for the other galaxies in the sample. This "blue tilt" translates into a mass-metallicity relation given by Z \propto M^0.28\pm0.03 . This dependence was found using a new empirical (g' -i') vs [Z/H] relation which relies on an homogeneous sample of GC colours and metallicities. This paper also explores the radial trends in both colour and surface density for the blue (metal-poor) and red (metal-rich) GC subpopulations. As usual, the red GCs show a steeper radial distribution than the blue ones. Evidence of galactocentric colour gradients is found in some of the GC systems, being more significant for the two S0 galaxies in the sample. Red GC subpopulations show similar colours and gradients to the galaxy halo stars in their inner region. A GC mean colour-galaxy luminosity relation, consistent with [Z/H] \propto L_B ^0.26\pm0.08, is present for the red GCs. An estimate of the total GC populations and specific frequency SN values is presented for NGC 3115, NGC 3379, NGC 3923 and NGC 4649.Comment: 23 pages, 13 figures and 9 tables. Tables A1 and A2 will be published in full online only. Accepted for publication in 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 Canine Papillomavirus and Gamma HPV E7 Proteins Use an Alternative Domain to Bind and Destabilize the Retinoblastoma Protein

The high-risk HPV E6 and E7 proteins cooperate to immortalize primary human cervical cells and the E7 protein can independently transform fibroblasts in vitro, primarily due to its ability to associate with and degrade the retinoblastoma tumor suppressor protein, pRb. The binding of E7 to pRb is mediated by a conserved Leu-X-Cys-X-Glu (LXCXE) motif in the conserved region 2 (CR2) of E7 and this domain is both necessary and sufficient for E7/pRb association. In the current study, we report that the E7 protein of the malignancy-associated canine papillomavirus type 2 encodes an E7 protein that has serine substituted for cysteine in the LXCXE motif. In HPV, this substitution in E7 abrogates pRb binding and degradation. However, despite variation at this critical site, the canine papillomavirus E7 protein still bound and degraded pRb. Even complete deletion of the LXSXE domain of canine E7 failed to interfere with binding to pRb in vitro and in vivo. Rather, the dominant binding site for pRb mapped to the C-terminal domain of canine E7. Finally, while the CR1 and CR2 domains of HPV E7 are sufficient for degradation of pRb, the C-terminal region of canine E7 was also required for pRb degradation. Screening of HPV genome sequences revealed that the LXSXE motif of the canine E7 protein was also present in the gamma HPVs and we demonstrate that the gamma HPV-4 E7 protein also binds pRb in a similar way. It appears, therefore, that the type 2 canine PV and gamma-type HPVs not only share similar properties with respect to tissue specificity and association with immunosuppression, but also the mechanism by which their E7 proteins interact with pRb

PTF10fqs: A Luminous Red Nova in the Spiral Galaxy Messier 99

The Palomar Transient Factory (PTF) is systematically charting the optical transient and variable sky. A primary science driver of PTF is building a complete inventory of transients in the local Universe (distance less than 200 Mpc). Here, we report the discovery of PTF10fqs, a transient in the luminosity "gap" between novae and supernovae. Located on a spiral arm of Messier 99, PTF 10fqs has a peak luminosity of Mr = -12.3, red color (g-r = 1.0) and is slowly evolving (decayed by 1 mag in 68 days). It has a spectrum dominated by intermediate-width H (930 km/s) and narrow calcium emission lines. The explosion signature (the light curve and spectra) is overall similar to thatof M85OT2006-1, SN2008S, and NGC300OT. The origin of these events is shrouded in mystery and controversy (and in some cases, in dust). PTF10fqs shows some evidence of a broad feature (around 8600A) that may suggest very large velocities (10,000 km/s) in this explosion. Ongoing surveys can be expected to find a few such events per year. Sensitive spectroscopy, infrared monitoring and statistics (e.g. disk versus bulge) will eventually make it possible for astronomers to unravel the nature of these mysterious explosions.Comment: 12 pages, 12 figures, Replaced with published versio