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Sample records for receptor m33 occurs

  1. THE DISRUPTION AND FUELING OF M33

    SciTech Connect

    Putman, M. E.; Peek, J. E. G.; Muratov, A.; Gnedin, O. Y.; Hsu, W.; Heiles, C.; Douglas, K. A.; Korpela, E. J.; Stanimirovic, S.; Gibson, S. J.

    2009-10-01

    The disruption of the M33 galaxy is evident from its extended gaseous structure. We present new data from the Galactic Arecibo L-Band Feed Array H I (GALFA-H I) Survey that show the full extent and detailed spatial and kinematic structure of M33's neutral hydrogen. Over 18% of the H I mass of M33 (M{sub HI{sub t{sub o{sub t}}}}=1.4x10{sup 9} M {sub sun}) is found beyond the star-forming disk as traced in the far-ultraviolet (FUV). The most distinct features are extended warps, an arc from the northern warp to the disk, diffuse gas surrounding the galaxy, and a southern cloud with a filament back to the galaxy. The features extend out to 22 kpc from the galaxy center (18 kpc from the edge of the FUV disk), and the gas is directly connected to M33's disk. Only five discrete clouds (i.e., gas not directly connected to M33 in position-velocity space) are cataloged in the vicinity of M33, and these clouds show similar properties to Galactic and M31 halo clouds. M33's gaseous features most likely originate from the tidal disruption of M33 by M31 1-3 Gyr ago as shown by an orbit analysis which results in a tidal radius <15 kpc in the majority of M33's possible orbits. M33 is now beyond the disruptive gravitational influence of M31, and the gas appears to be returning to M33's disk and redistributing its star formation fuel. M33's high mean velocity dispersion in the disk (approx18.5 km s{sup -1}) may also be consistent with the previous interaction and high rate of star formation. M33 will either exhaust its star formation fuel in the next few Gyrs or eventually become star formation fuel for M31. The latter represents the accretion of a large gaseous satellite by a spiral galaxy, similar to the Magellanic Clouds' relationship to the Galaxy.

  2. SQIID Imaging of the M 33 Core

    NASA Astrophysics Data System (ADS)

    Polomski, E.; Gehrz, R. D.; Humphreys, R.; Woodward, C. E.; Jones, T. J.; Lyke, J.; Eicher, K.; Willner, S.; Barmby, P.; Huchra, J.; Strom, S.

    2001-05-01

    We have initiated a program of high spatial resolution infrared mapping of M 33 as part of a study of the stellar populations of nearby spiral galaxies. M 33 is one of the two nearest spiral galaxies, and is oriented nearly face-on, providing a unique opportunity for a comprehensive survey of its population. Large scale surveys in the infrared can penetrate the interstellar obscuration in M 33 and give a more complete assessment of the various stellar components than optical observations. Near-IR colors can also distinguish between different evolutionary classes, such as pre-main sequence stars, red supergiants, Asymptotic Giant Branch stars, and main sequence objects. We present here the first results of this program; near-IR J, H, and K band maps of M 33, obtained with the SQIID imager at KPNO. We focus on the core, ~5x5', region of M 33, and show near-IR colors for the sources in this region, as well as the central engine. Our maps complement those from the 2MASS survey, but go 5 magnitudes deeper (K ~ 20) and achieve better spatial resolution (FWHM < 2" ). These maps will provide the foundation for upcoming SIRTF observations which will involve temporal studies of the same region in the mid and far-IR. The reduced data from our JHK survey will be placed in a publicly available database when the project is complete.

  3. Neon and Oxygen Abundances in M33

    NASA Astrophysics Data System (ADS)

    Crockett, N. R.; Garnett, D. R.; Massey, P.; Jacoby, G.

    2004-05-01

    We present new spectroscopic observations of 13 H II regions in the Local Group spiral galaxy M33. The regions observed range in distance between 1 and 7 kpc from the nucleus. Of the 13 H II regions observed, we were able to detect the [O III] 4363 Å line in six regions, and so were able to determine electron temperatures directly from the spectra using the 5007/4363 line ratio. Based on these temperature measurements we computed abundances for O and Ne for the six regions, and derived radial abundance gradients for both elements. We find that our new measurements lead to a shallower oxygen abundance gradient , --0.03±0.02 dex/kpc, than was derived by earlier studies. We attribute the difference partly to the use of uncertain extrapolations of O/H vs. ([O II] + [O III])/Hβ used in earlier studies to derive abundances for nebulae without measured electron temperatures. The shallower O/H gradient is in much better agreement with the Ne/H gradient derived from ISO spectra by Willner and Nelson-Patel, as expected from predictions of stellar nucleosynthesis. We also identify two new He II-emitting H II regions, the first to be discovered in M33.

  4. BLENDING OF CEPHEIDS IN M33

    SciTech Connect

    Chavez, Joy M.; Macri, Lucas M.; Pellerin, Anne

    2012-10-01

    A precise and accurate determination of the Hubble constant based on Cepheid variables requires proper characterization of many sources of systematic error. One of these is stellar blending, which biases the measured fluxes of Cepheids and the resulting distance estimates. We study the blending of 149 Cepheid variables in M33 by matching archival Hubble Space Telescope data with images obtained at the Wisconsin-Indiana-Yale-NOAO (WIYN) 3.5 m telescope, which differ by a factor of 10 in angular resolution. We find that 55% {+-} 4% of the Cepheids have no detectable nearby companions that could bias the WIYN V-band photometry, while the fraction of Cepheids affected below the 10% level is 73% {+-} 4%. The corresponding values for the I band are 60% {+-} 4% and 72% {+-} 4%, respectively. We find no statistically significant difference in blending statistics as a function of period or surface brightness. Additionally, we report all the detected companions within 2'' of the Cepheids (equivalent to 9 pc at the distance of M33) which may be used to derive empirical blending corrections for Cepheids at larger distances.

  5. No supermassive black hole in M33?

    PubMed

    Merritt, D; Ferrarese, L; Joseph, C L

    2001-08-10

    We observed the nucleus of M33, the third-brightest galaxy in the Local Group, with the Space Telescope Imaging Spectrograph at a resolution at least a factor of 10 higher than previously obtained. Rather than the steep rise expected within the radius of gravitational influence of a supermassive black hole, the random stellar velocities showed a decrease within a parsec of the center of the galaxy. The implied upper limit on the mass of the central black hole is only 3000 solar masses, about three orders of magnitude lower than the dynamically inferred mass of any other supermassive black hole. Detecting black holes of only a few thousand solar masses is observationally challenging, but it is critical to establish how supermassive black holes relate to their host galaxies, and which mechanisms influence the formation and evolution of both. PMID:11463879

  6. Resolved structure in M33 supernova remnants

    NASA Technical Reports Server (NTRS)

    Blair, William P.; Davidsen, Arthur F.

    1993-01-01

    We present WF/PC narrow band forbidden S II 6725-wavelength images of two M33 supernova remnants obtained with the Wide Field/Planetary Camera on the HST. Comparison of these images with ground-based CCD data indicates that HST has resolved the nebular structures into shells or partial shells, permitting improved measurements of the diameters of these objects. Ground-based echelle spectra obtained at Kitt Peak with the 4-m telescope show profiles with half-width zero-intensity velocities of 163 and 275 km/sec for the two objects, indicating rapid bulk motions of the emitting filaments. The morphology of the emission seen in the WF/PC images allows the non-Gaussian shapes of the integrated echelle profiles to be understood. We briefly compare the predicted WF/PC count rates with those actually realized and discuss the reason for the discrepancy.

  7. Unbound molecular complexes in M33

    NASA Astrophysics Data System (ADS)

    Wilson, Christine D.

    1990-07-01

    The HI content of the nearby spiral galaxy M33 (d approx. 0.8 Mpc) has been the subject of many detailed studies (most recently Deul and van der Hulst 1987), but similar data on the molecular gas component has been lacking. This galaxy is currently undergoing vigorous high-mass star formation, as evidenced by the many OB associations and HII regions, and so is expected to possess at least some molecular gas. Interferometric studies have detected molecular clouds similar to Galactic Giant Molecular Clouds (GMCs) (Boulanger et al. 1988; Wilson et al. 1988). Researchers have recently mapped the nuclear region of M33 in the CO J=1-0 line with a 12 m telescope (half power beam width 55 inches approx. 210 pc) out to a radius of 3.5 minutes in order to trace the detailed distribution of the molecular gas. The resulting map reveals six large complexes with diameters of 200 to 400 pc. Interferometer observations of these regions have resolved them into individual molecular clouds similar to Galactic GMCs (Wilson et al. 1988). The complexes shown are much larger than individual Galactic GMCs (Sanders, Scoville, and Solomon 1985), but are somewhat smaller on average than the large associations seen in the grand-design spiral galaxy M51 (Rand and Kulkarni 1989). If we extend the velocity-diameter relation observed for Galactic GMCs to these larger structures, the predicted velocity widths are a factor of 1.5 to 3 times greater than the observed full-width half-maximum velocities (13 to 29 km (s-1). The peak brightness temperatures are approx. 0.2 K, at least a factor of 10 lower than what is observed for Galactic GMCs. If these large structures are made up of objects similar to Galactic GMCs, the area filling factor of the small clouds is roughly 10 percent. These results suggest that these complexes are not very large GMCs, but rather are associations of many individual GMCs or GMCs embedded in a diffuse gas component.

  8. Cool and warm dust emission from M 33 (HerM33es)

    NASA Astrophysics Data System (ADS)

    Xilouris, E. M.; Tabatabaei, F. S.; Boquien, M.; Kramer, C.; Buchbender, C.; Bertoldi, F.; Anderl, S.; Braine, J.; Verley, S.; Relaño, M.; Quintana-Lacaci, G.; Akras, S.; Beck, R.; Calzetti, D.; Combes, F.; Gonzalez, M.; Gratier, P.; Henkel, C.; Israel, F.; Koribalski, B.; Lord, S.; Mookerjea, B.; Rosolowsky, E.; Stacey, G.; Tilanus, R. P. J.; van der Tak, F.; van der Werf, P.

    2012-07-01

    In the framework of the open-time key program "Herschel M 33 extended survey (HerM33es)", we study the far-infrared emission from the nearby spiral galaxy M 33 in order to investigate the physical properties of the dust such as its temperature and luminosity density across the galaxy. Taking advantage of the unique wavelength coverage (100, 160, 250, 350, and 500 μm) of the Herschel Space Observatory and complementing our dataset with Spitzer-IRAC 5.8 and 8 μm and Spitzer-MIPS 24 and 70 μm data, we construct temperature and luminosity density maps by fitting two modified blackbodies of a fixed emissivity index of 1.5. We find that the "cool" dust grains are heated to temperatures of between 11 K and 28 K, with the lowest temperatures being found in the outskirts of the galaxy and the highest ones both at the center and in the bright HII regions. The infrared/submillimeter total luminosity (5-1000 μm) is estimated to be 1.9 × 109 -4.4×108+4.0×108L⊙. Fifty-nine percent of the total infrared/submillimeter luminosity of the galaxy is produced by the "cool" dust grains (~15 K), while the remaining 41% is produced by "warm" dust grains (~55 K). The ratio of the cool-to-warm dust luminosity is close to unity (within the computed uncertainties), throughout the galaxy, with the luminosity of the cool dust being slightly higher at the center than the outer parts of the galaxy. Decomposing the emission of the dust into two components (one emitted by the diffuse disk of the galaxy and one emitted by the spiral arms), we find that the fraction of the emission from the disk in the mid-infrared (24 μm) is 21%, while it gradually rises up to 57% in the submillimeter (500 μm). We find that the bulk of the luminosity comes from the spiral arm network that produces 70% of the total luminosity of the galaxy with the rest coming from the diffuse dust disk. The "cool" dust inside the disk is heated to temperatures in a narrow range between 18 K and 15 K (going from the center

  9. The Spheroid of M33: Bulge or Halo?

    NASA Astrophysics Data System (ADS)

    Regan, Michael W.; Vogel, Stuart N.

    1993-12-01

    Because of its proximity, M33 provides a unique opportunity to investigate a spiral galaxy with a very small bulge. However, the existence of a bulge in M33 remains controversial (van den Bergh 1991). For example, Kent (1987) suggested that the excess light seen near the nucleus is due to spiral structure, while Bothun (1992) stated that the central surface brightness of M33 could not be fit by a single r(1/4) law and may not be a bulge but a large scale diffuse halo. Recently, Minniti, Olszewski, and Rieke (1993) used H-band photometry of individual stars near the center of M33 and concluded that there is a bulge, and that it has undergone recent (<1 Gyr) star formation. We present J, H, and K-band observations of M33 obtained with the SQIID camera on the KPNO 1.3 meter telescope that show that the inner spheriodal light distribution of M33 is better characterized by a halo than a bulge. The total light in the halo is larger than previous estimates for the bulge of M33, leading to an estimate of the ratio of globular clusters to total spheriodal luminosity closer to that measured for other spiral galaxies.

  10. Chandra ACIS Survey of M33: The SNR Population

    NASA Astrophysics Data System (ADS)

    Plucinsky, Paul; Long, Knox S.; Gaetz, Terrance; Tuellmann, Ralph

    The Chandra ACIS Survey of M33 (ChASeM33) is a large program to survey the inner re-gions of the M33 galaxy. The survey consists of 7 different fields observed for 200 ks (each field observed twice for 100 ks), covering 70the key projects of the ChASeM33 project is to characterize the SNR population in M33. We have detected 82 of 137 optically-identified SNRs and SNR candidates with a limiting X-ray luminosity of 2.0e34 ergs/s (0.35-2.0 keV), yielding confirmation of (or at least strongly supporting) their SNR identifications. This represents the largest sample of remnants detected at optical and X-ray wavelengths in any galaxy, including the Milky Way. With the high angular resolution of Chandra, we are able to study the X-ray morphology of the bright remnants for the first time. A spectral analysis of the seven X-ray brightest SNRs reveals that two, G98-31 and G98-35, have spectra that appear to indicate enrichment by ejecta from core-collapse supernova explosions. A comparison of the X-ray lu-minosity function of the SNRs in M33 to the LMC and SMC indicates that the LMC, and to a lesser extent the SMC, have more, high luminosity SNRs than M33. We did not discover any close analogs of Cas A, Kepler's SNR, Tycho's SNR or the Crab Nebula in the regions of M33 surveyed, but we have found an X-ray source with a power law spectrum coincident with a small-diameter radio source that may be the first pulsar-wind nebula recognized in M33.

  11. Dust properties in H II regions in M 33

    NASA Astrophysics Data System (ADS)

    Relaño, M.; Kennicutt, R.; Lisenfeld, U.; Verley, S.; Hermelo, I.; Boquien, M.; Albrecht, M.; Kramer, C.; Braine, J.; Pérez-Montero, E.; De Looze, I.; Xilouris, M.; Kovács, A.; Staguhn, J.

    2016-10-01

    regions can lead to fragmentation of BGs into smaller ones, while the more evolved shell and clear shell objects provide a more quiescent environment where reformation of dust BGs might occur. The gas-to-dust variations found in this analysis might imply that grain coagulation and/or gas-phase metal incorporation into the dust mass is occurring in the interior of the H ii regions in M 33. Full Tables A.1 and A.2 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/595/A43

  12. THE PHOTOMETRIC PROPERTIES OF A VAST STELLAR SUBSTRUCTURE IN THE OUTSKIRTS OF M33

    SciTech Connect

    McConnachie, Alan W.; Ferguson, Annette M. N.; Irwin, Michael J.; Dubinski, John; Widrow, Lawrence M.; Dotter, Aaron; Ibata, Rodrigo; Lewis, Geraint F.

    2010-11-10

    We have surveyed approximately 40 deg{sup 2} surrounding M33 with Canada-France-Hawaii Telescope MegaCam/MegaPrime in the g and i filters out to a maximum projected radius from this galaxy of 50 kpc, as part of the Pan-Andromeda Archaeological Survey (PAndAS). Our observations are deep enough to resolve the top {approx}4 mag of the red giant branch population in this galaxy. We have previously shown that the disk of M33 is surrounded by a large, irregular, low surface brightness substructure. Here, we quantify the stellar populations and structure of this feature using the PAndAS data. We show that the stellar populations of this feature are consistent with an old population with ([Fe/H]) {approx} -1.6 dex and an interquartile range in metallicity of {approx}0.5 dex. We construct a surface brightness map of M33 that traces this feature to {mu}{sub V} {approx_equal} 33 mag arcsec{sup -2}. At these low surface brightness levels, the structure extends to projected radii of {approx}40 kpc from the center of M33 in both the northwest and southeast quadrants of the galaxy. Overall, the structure has an 'S-shaped' appearance that broadly aligns with the orientation of the H I disk warp. We calculate a lower limit to the integrated luminosity of the structure of -12.7 {+-} 0.5 mag, comparable to a bright dwarf galaxy such as Fornax or Andromeda II and slightly less than 1% of the total luminosity of M33. Further, we show that there is tentative evidence for a distortion in the distribution of young stars near the edge of the H I disk that occurs at similar azimuth to the warp in H I. The data also hint at a low-level, extended stellar component at larger radius that may be an M33 halo component. We revisit studies of M33 and its stellar populations in light of these new results and discuss possible formation scenarios for the vast stellar structure. Our favored model is that of the tidal disruption of M33 in its orbit around M31.

  13. The Photometric Properties of a Vast Stellar Substructure in the Outskirts of M33

    NASA Astrophysics Data System (ADS)

    McConnachie, Alan W.; Ferguson, Annette M. N.; Irwin, Michael J.; Dubinski, John; Widrow, Lawrence M.; Dotter, Aaron; Ibata, Rodrigo; Lewis, Geraint F.

    2010-11-01

    We have surveyed approximately 40 deg2 surrounding M33 with Canada-France-Hawaii Telescope MegaCam/MegaPrime in the g and i filters out to a maximum projected radius from this galaxy of 50 kpc, as part of the Pan-Andromeda Archaeological Survey (PAndAS). Our observations are deep enough to resolve the top ~4 mag of the red giant branch population in this galaxy. We have previously shown that the disk of M33 is surrounded by a large, irregular, low surface brightness substructure. Here, we quantify the stellar populations and structure of this feature using the PAndAS data. We show that the stellar populations of this feature are consistent with an old population with lang[Fe/H]rang ~ -1.6 dex and an interquartile range in metallicity of ~0.5 dex. We construct a surface brightness map of M33 that traces this feature to μ V ~= 33 mag arcsec-2. At these low surface brightness levels, the structure extends to projected radii of ~40 kpc from the center of M33 in both the northwest and southeast quadrants of the galaxy. Overall, the structure has an "S-shaped" appearance that broadly aligns with the orientation of the H I disk warp. We calculate a lower limit to the integrated luminosity of the structure of -12.7 ± 0.5 mag, comparable to a bright dwarf galaxy such as Fornax or Andromeda II and slightly less than 1% of the total luminosity of M33. Further, we show that there is tentative evidence for a distortion in the distribution of young stars near the edge of the H I disk that occurs at similar azimuth to the warp in H I. The data also hint at a low-level, extended stellar component at larger radius that may be an M33 halo component. We revisit studies of M33 and its stellar populations in light of these new results and discuss possible formation scenarios for the vast stellar structure. Our favored model is that of the tidal disruption of M33 in its orbit around M31.

  14. NEW UBVRI PHOTOMETRY OF 234 M33 STAR CLUSTERS

    SciTech Connect

    Ma Jun

    2013-04-15

    This is the second paper of our series. In this paper, we present UBVRI photometry for 234 star clusters in the field of M33. For most of these star clusters, there is photometry in only two bands in previous studies. The photometry of these star clusters is performed using archival images from the Local Group Galaxies Survey, which covers 0.8 deg{sup 2} along the major axis of M33. Detailed comparisons show that, in general, our photometry is consistent with previous measurements, and in particular that our photometry is in good agreement with that of Zloczewski and Kaluzny. Combined with star cluster photometry in previous studies, we present some results: none of the M33 youngest clusters ({approx}10{sup 7} yr) have masses approaching 10{sup 5} M{sub Sun }, and comparisons with models of simple stellar populations suggest a large range of ages for M33 star clusters and some as old as the Galactic globular clusters.

  15. Discovery of a Probable Nova in M33

    NASA Astrophysics Data System (ADS)

    Hornoch, K.; Vaduvescu, O.; Tudor, V.

    2014-08-01

    We report the discovery of a probable nova in M33 on co-added 960-s narrow-band H-alpha and 480-s R-band CCD images taken with the 2.5-m Isaac Newton Telescope (INT) + WFC at La Palma under ~1.1" seeing on 2014 July 29.206 and 29.222 UT, respectively.

  16. THE WOLF-RAYET CONTENT OF M33

    SciTech Connect

    Neugent, Kathryn F.; Massey, Philip E-mail: phil.massey@lowell.edu

    2011-06-01

    Wolf-Rayet (WR) stars are evolved massive stars, and the relative number of WC-type and WN-type WRs should vary with metallicity, providing a sensitive test of stellar evolutionary theory. The observed WC/WN ratio is much higher than that predicted by theory in some galaxies but this could be due to observational incompleteness for WN types, which have weaker lines. Previous studies of M33's WR content show a galactocentric gradient in the relative numbers of WCs and WNs, but only small regions have been surveyed with sufficient sensitivity to detect all of the WNs. Here, we present a sensitive survey for WRs covering all of M33, finding 55 new WRs, mostly of WN type. Our spectroscopy also improves the spectral types of many previously known WRs, establishing in one case that the star is actually a background quasar. The total number of spectroscopically confirmed WRs in M33 is 206, a number we argue is complete to {approx}5%, with most WRs residing in OB associations, although {approx}2% are truly isolated. The WC/WN ratio in the central regions (<2 kpc) of M33 is much higher than that predicted by the current Geneva evolutionary models, while the WC/WN ratios in the outer regions are in good accord, as are the values in the Small Magellanic Cloud and Large Magellanic Cloud. The WC/WN ratio and the WC subtype distribution both argue that the oxygen abundance gradient in M33 is significantly larger than that found by some recent studies, but are consistent with the two-component model proposed by Magrini et al.

  17. A mathematical analysis using fractals for binding interactions of nuclear estrogen receptors occurring on biosensor surfaces.

    PubMed

    Ramakrishnan, Anand; Sadana, Ajit

    2002-04-01

    A mathematical approach using fractal concepts is presented for modeling the binding and dissociation interactions between analytes and nuclear estrogen receptors (ER) occurring on surface plasmon resonance biosensor chip surfaces. A kinetic knowledge of the binding interactions mediated by ER would help in better understanding the carcinogenicity of these steroidogenic compounds and assist in modulating these reactions. The fractal approach is applied to analyte-ER interaction data obtained from literature. Numerical values obtained for the binding and dissociation rate coefficients are linked to the degree of roughness or heterogeneity (fractal dimension, D(f)) present on the biosensor surface. For example, a single-fractal analysis is used to describe the binding and dissociation phases for the binding of estradiol and ERalpha in solution to clone 31 protein immobilized on a biosensor chip (C-S. Suen et al., 1998, J. Biol. Chem. 273(42), 27645-27653). The binding and the dissociation rate coefficients are 27.57 and 8.813, respectively, and the corresponding fractal dimensions are 1.986 and 2.268, respectively. In some examples dual-fractal models were employed to obtain a better fit of either the association or the dissociation phases or for both. Predictive relationships are developed for (a) the binding and the dissociation rate coefficients as a function of their respective fractal dimensions and (b) the ratio K(A) (= k/k(d)) as a function of the ratio of the fractal dimensions (D(f)/D(fd)). The analysis should provide further physical insights into the ER-mediated interactions occurring on biosensor and other surfaces.

  18. Naturally-Occurring Marine Brominated Indoles are Aryl Hydrocarbon Receptor Ligands/Agonists

    PubMed Central

    DeGroot, Danica E.; Franks, Diana G.; Higa, Tatsuo; Tanaka, Junichi; Hahn, Mark E.; Denison, Michael S.

    2015-01-01

    The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates the toxic and biological effects of structurally diverse chemicals, including the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). As part of a larger effort to identify the full spectrum of chemicals that can bind to and activate the AhR, we have examined the ability of several naturally-occurring marine-derived brominated indoles and brominated (methylthio)indoles (collectively referred to as “brominated indoles”) to bind to the AhR and stimulate AhR-dependent gene expression. Incubation of mouse, rat and guinea pig recombinant cell lines containing a stably transfected AhR-responsive luciferase reporter gene with eight brominated indoles revealed that all compounds stimulated luciferase reporter gene activity, although some species-specific differences were observed. All compounds induced significantly more luciferase activity when incubated with cells for 4 h as compared to 24 h, demonstrating that these compounds are transient activators of the AhR signaling pathway. Three of the brominated indoles induced CYP1A1 mRNA in human HepG2 cells in vitro and Cyp1a mRNA in zebrafish embryos in vivo. The identification of the brominated indoles as direct ligands and activators/agonists of the AhR was confirmed by their ability to compete with [3H]TCDD for binding to the AhR and to stimulate AhR transformation and DNA binding in vitro. Taken together, these marine-derived brominated indoles are members of a new class of naturally-occurring AhR agonists. PMID:26001051

  19. Molecular cloud formation and the star formation efficiency in M 33. Molecule and star formation in M 33

    NASA Astrophysics Data System (ADS)

    Braine, J.; Gratier, P.; Kramer, C.; Schuster, K. F.; Tabatabaei, F.; Gardan, E.

    2010-09-01

    Does star formation proceed in the same way in large spirals such as the Milky Way and in smaller chemically younger galaxies? Earlier work suggests a more rapid transformation of H2 into stars in these objects but (1) a doubt remains about the validity of the H2 mass estimates and (2) there is currently no explanation for why star formation should be more efficient. M 33, a local group spiral with a mass ~10% and a metallicity half that of the Galaxy, represents a first step towards the metal poor Dwarf Galaxies. We have searched for molecular clouds in the outer disk of M 33 and present here a set of detections of both 12CO and 13CO, including the only detections (for both lines) beyond the R25 radius in a subsolar metallicity galaxy. The spatial resolution enables mass estimates for the clouds and thus a measure of the N(H2)/ICO ratio, which in turn enables a more reliable calculation of the H2 mass. Our estimate for the outer disk of M 33 is N(H2)/ICO(1-0) ~ 5 × 1020 cm-2/(K km s-1) with an estimated uncertainty of a factor ≤2. While the 12/13CO line ratios do not provide a reliable measure of N(H2)/ICO, the values we find are slightly greater than Galactic and corroborate a somewhat higher N(H2)/ICO value. Comparing the CO observations with other tracers of the interstellar medium, no reliable means of predicting where CO would be detected was identified. In particular, CO detections were often not directly on local HI or FIR or Hα peaks, although generally in regions with FIR emission and high HI column density. The results presented here provide support for the quicker transformation of H2 into stars in M 33 than in large local universe spirals.

  20. STRUCTURAL PARAMETERS FOR 10 HALO GLOBULAR CLUSTERS IN M33

    SciTech Connect

    Ma, Jun

    2015-05-15

    In this paper, we present the properties of 10 halo globular clusters (GCs) with luminosities L ≃ 5–7 × 10{sup 5} L{sub ⊙} in the Local Group galaxy M33 using images from the Hubble Space Telescope WFPC2 in the F555W and F814W bands. We obtained the ellipticities, position angles, and surface brightness profiles for each GC. In general, the ellipticities of the M33 sample clusters are similar to those of the M31 clusters. The structural and dynamical parameters are derived by fitting the profiles to three different models combined with mass-to-light ratios (M/L values) from population-synthesis models. The structural parameters include core radii, concentration, half-light radii, and central surface brightness. The dynamical parameters include the integrated cluster mass, integrated binding energy, central surface mass density, and predicted line of sight velocity dispersion at the cluster center. The velocity dispersions of the four clusters predicted here agree well with the observed dispersions by Larsen et al. The results here showed that the majority of the sample halo GCs are better fitted by both the King model and the Wilson model than the Sérsic model. In general, the properties of the clusters in M33, M31, and the Milky Way fall in the same regions of parameter spaces. The tight correlations of cluster properties indicate a “fundamental plane” for clusters, which reflects some universal physical conditions and processes operating at the epoch of cluster formation.

  1. THE WIND OF VARIABLE C IN M33

    SciTech Connect

    Humphreys, Roberta M.; Davidson, Kris; Gordon, Michael S.; Weis, Kerstin; Burggraf, Birgitta; Bomans, D. J.; Martin, John C.

    2014-02-20

    We discuss the spectrum of Var C in M33 obtained just before the onset of its current brightening and its recent spectra during its present ''eruption'' or optically thick wind stage. These spectra illustrate the typical luminous blue variable (LBV) transition in apparent spectral type or temperature that characterizes the classical LBV or S Dor-type variability. LBVs are known to have slow, dense winds during their maximum phase. Interestingly, Var C had a slow wind even during its hot, quiescent stage in comparison with the normal hot supergiants with similar temperatures. Its outflow or wind speeds also show very little change between these two states.

  2. A Study of Structure in M33 Using Adaptive Optics

    NASA Astrophysics Data System (ADS)

    Wittman, David Michael

    1997-08-01

    FASTTRAC (Fast Adaptive Secondary for Tip-Tilt Removal by Automatic Centroiding) is a tip-tilt secondary system which increases the angular resolution of images taken at Steward Observatory's 90' Bok and 61' Bigelow telescopes. K band imagery is gathered with the facility infrared camera and wavefront sensing is done with a small format charge-coupled device (CCD). I examine desirable characteristics of wavefront-sensing CCDs and evaluate the performance of the device used in FASTTRAC according to those criteria. The main drawback of the device is its low quantum efficiency due to frontside illumination. The read noise of the system is adequate, particularly for FASTTRAC which is generally assigned to bright time. The increased angular resolution provided by FASTTRAC is desirable for imaging crowded fields, such as those found in Local Group galaxies. Stellar photometry is a more powerful tool for studying the structure of these galaxies than is surface photometry, in which the light from all types of stars is mixed together. In particular, the distribution of old stars is representative of the underlying mass distribution, so these stars may be used to measure the overdensity in the arms of spiral galaxies. FASTTRAC was used to observe fields in M33, the nearest spiral which is not seen edge-on. These fields were observed in a range of seeing conditions and with guide stars of varying magnitudes and positions relative to the fields of interest. I analyze the performance of FASTTRAC in these varying conditions and offer some advice to future FASTTRAC observers. I also analyze the crowding in the M33 fields and conclude that, to K~16.5, it does not vary significantly with placement in or outside of a spiral arm. Therefore a coarsely-sampled, wide field survey of the populations of M33 will not be systematically biased by crowding. Therefore a survey covering 35' by 25' was conducted in I and K bands, covering all of M33 out to a deprojected radius of 16 prime. The

  3. Variation in the dust emissivity index across M 33 with Herschel and Spitzer (HerM 33es)

    NASA Astrophysics Data System (ADS)

    Tabatabaei, F. S.; Braine, J.; Xilouris, E. M.; Kramer, C.; Boquien, M.; Combes, F.; Henkel, C.; Relano, M.; Verley, S.; Gratier, P.; Israel, F.; Wiedner, M. C.; Röllig, M.; Schuster, K. F.; van der Werf, P.

    2014-01-01

    We study the wavelength dependence of the dust emission as a function of position and environment across the disk of M 33 using Spitzer and Herschel photometric data. M 33 is a Local Group spiral with slightly subsolar metallicity, which makes it an ideal stepping-stone to less regular and lower-metallicity objects such as dwarf galaxies and, probably, young-universe objects. Expressing the emissivity of the dust as a power law, the power-law exponent (β) was estimated from two independent approaches designed to properly treat the degeneracy between β and the dust temperature (T). Both β and T are higher in the inner than in the outer disk, contrary to reported β - T anti-correlations found in other sources. In the cold + warm dust model, the warm component and the ionized gas (Hα) have a very similar distribution across the galaxy, demonstrating that the model separates the components in an appropriate way. Both cold- and warm-dust column densities are high in star-forming regions and reach their maxima toward the giant star-forming complexes NGC 604 and NGC 595. β declines from close to 2 in the center to about 1.3 in the outer disk. β is positively correlated with star formation and with the molecular gas column, as traced by the Hα and CO emission. The lower dust-emissivity index in the outer parts of M 33 is most likely related to the reduced metallicity (different grain composition) and possibly to a different size distribution. It is not due to the decrease in stellar radiation field or temperature in a simple way because the far-infrared-bright regions in the outer disk also have a low β. Like most spirals, M 33 has a (decreasing) radial gradient in star formation and molecular-to-atomic gas ratio such that the regions bright in Hα or CO tend to trace the inner disk, which makes it difficult to distinguish between their effects on the dust. The assumption of a constant emissivity index β is obviously not appropriate.

  4. Selective phthalate activation of naturally occurring human constitutive androstane receptor splice variants and the pregnane X receptor.

    PubMed

    DeKeyser, Joshua G; Laurenzana, Elizabeth M; Peterson, Eric C; Chen, Tao; Omiecinski, Curtis J

    2011-04-01

    Phthalates and other endocrine-disruptive chemicals are manufactured in large quantities for use as plasticizers and other commercial applications, resulting in ubiquitous human exposure and thus, concern regarding their toxicity. Innate defense against small molecule exposures is controlled in large part by the constitutive androstane receptor (CAR) and the pregnane X receptor (PXR). The human CAR gene undergoes multiple alternative splicing events resulting in the CAR2 and CAR3 variant receptors. Recent studies from our laboratory show that CAR2 is potently and specifically activated by di(2-ethylhexyl) phthalate (DEHP). We hypothesized that alternative splicing is a mechanism for increasing CAR's functional diversity, broadening the human receptors' repertoire of response to environmental xenobiotics. In these studies, we examine the interaction of alternatively spliced CARs and PXR with a range of suspected endocrine disruptors, including phthalates, bisphenol A (BPA), and 4-N-nonylphenol (NP). Transactivation and two-hybrid studies in COS-1 cells revealed differential selectivity of endocrine-disrupting chemicals for the variant CAR and PXR. Ex vivo studies showed DEHP and di-isononyl phthalate potently induced CYP2B6 and CYP3A4 expression in human hepatocytes. Mutation analysis of CAR2, in silico modeling, and ligand docking studies suggested that the SPTV amino acid insertion of CAR2 creates a unique ligand-binding pocket. Alternative gene splicing results in variant CAR receptors that selectively recognize phthalates and BPA. The interaction of phthalates with CAR and PXR suggests a xenobiotic response that is complex and biologically redundant.

  5. THE YELLOW AND RED SUPERGIANTS OF M33

    SciTech Connect

    Drout, Maria R.; Massey, Philip; Meynet, Georges E-mail: phil.massey@lowell.edu

    2012-05-10

    Yellow and red supergiants are evolved massive stars whose numbers and locations on the Hertzsprung-Russell (H-R) diagram can provide a stringent test for models of massive star evolution. Previous studies have found large discrepancies between the relative number of yellow supergiants (YSGs) observed as a function of mass and those predicted by evolutionary models, while a disagreement between the predicted and observed locations of red supergiants (RSGs) on the H-R diagram was only recently resolved. Here, we extend these studies by examining the YSG and RSG populations of M33. Unfortunately, identifying these stars is difficult as this portion of the color-magnitude diagram is heavily contaminated by foreground dwarfs. We identify the RSGs through a combination of radial velocities and a two-color surface gravity discriminant, and after re-characterizing the rotation curve of M33 with our newly selected RSGs, we identify the YSGs through a combination of radial velocities and the strength of the O I {lambda}7774 triplet. We examine {approx}1300 spectra in total and identify 121 YSGs (a sample that is unbiased in luminosity above log (L/L{sub Sun }) {approx} 4.8) and 189 RSGs. After placing these objects on the H-R diagram, we find that the latest generation of Geneva evolutionary tracks shows excellent agreement with the observed locations of our RSGs and YSGs, the observed relative number of YSGs with mass, and the observed RSG upper mass limit. These models therefore represent a drastic improvement over previous generations.

  6. Properties of optically selected supernova remnant candidates in M33

    SciTech Connect

    Lee, Jong Hwan; Lee, Myung Gyoon E-mail: mglee@astro.snu.ac.kr

    2014-10-01

    Narrowband images covering strong emission lines are efficient for surveying supernova remnants (SNRs) in nearby galaxies. Using the narrowband images provided by the Local Group Galaxy Survey, we searched for SNRs in M33. Culling the objects with enhanced [S II]/Hα and round morphology in the continuum-subtracted Hα and [S II] images, we produced a list of 199 sources. Among them, 79 are previously unknown. Their progenitor and morphology types were classified. A majority of the sample (170 objects) are likely remnants of core-collapse supernovae (SNe), and 29 are remnants of Type Ia SNe. The cumulative size distribution of these objects is found to be similar to that of the M31 remnants derived in a similar way. We obtain a power-law slope, α = 2.38 ± 0.05. Thus, a majority of the sources are considered to be in the Sedov-Taylor phase, consistent with previous findings. The histogram of the emission-line ratio ([S II]/Hα) of the remnants has two concentrations at [S II]/Hα ∼ 0.55 and ∼0.8, as in M31. Interestingly, L {sub X} (and L {sub 20cm}) of the compact center-bright objects are correlated with their optical luminosity. The remnants with X-ray emission have brighter optical surface brightnesses and smaller diameters than those without X-ray emission.

  7. The Wind of Variable C in M33

    NASA Astrophysics Data System (ADS)

    Humphreys, Roberta M.; Davidson, Kris; Gordon, Michael S.; Weis, Kerstin; Burggraf, Birgitta; Bomans, D. J.; Martin, John C.

    2014-02-01

    We discuss the spectrum of Var C in M33 obtained just before the onset of its current brightening and its recent spectra during its present "eruption" or optically thick wind stage. These spectra illustrate the typical luminous blue variable (LBV) transition in apparent spectral type or temperature that characterizes the classical LBV or S Dor-type variability. LBVs are known to have slow, dense winds during their maximum phase. Interestingly, Var C had a slow wind even during its hot, quiescent stage in comparison with the normal hot supergiants with similar temperatures. Its outflow or wind speeds also show very little change between these two states. Based on observations with the Multiple Mirror Telescope (MMT), a joint facility of the Smithsonian Institution and the University of Arizona and on observations obtained with the Large Binocular Telescope (LBT), an international collaboration among institutions in the United States, Italy, and Germany. LBT Corporation partners are The University of Arizona on behalf of the Arizona University system; Istituto Nazionale di Astrofisica, Italy; LBT Beteiligungsgesellschaft, Germany, representing the Max-Planck Society, the Astrophysical Institute Potsdam, and Heidelberg University; The Ohio State University, and The Research Corporation, on behalf of The University of Notre Dame, University of Minnesota, and University of Virginia.

  8. Properties of Optically Selected Supernova Remnant Candidates in M33

    NASA Astrophysics Data System (ADS)

    Lee, Jong Hwan; Lee, Myung Gyoon

    2014-10-01

    Narrowband images covering strong emission lines are efficient for surveying supernova remnants (SNRs) in nearby galaxies. Using the narrowband images provided by the Local Group Galaxy Survey, we searched for SNRs in M33. Culling the objects with enhanced [S II]/Hα and round morphology in the continuum-subtracted Hα and [S II] images, we produced a list of 199 sources. Among them, 79 are previously unknown. Their progenitor and morphology types were classified. A majority of the sample (170 objects) are likely remnants of core-collapse supernovae (SNe), and 29 are remnants of Type Ia SNe. The cumulative size distribution of these objects is found to be similar to that of the M31 remnants derived in a similar way. We obtain a power-law slope, α = 2.38 ± 0.05. Thus, a majority of the sources are considered to be in the Sedov-Taylor phase, consistent with previous findings. The histogram of the emission-line ratio ([S II]/Hα) of the remnants has two concentrations at [S II]/Hα ~ 0.55 and ~0.8, as in M31. Interestingly, L X (and L 20 cm) of the compact center-bright objects are correlated with their optical luminosity. The remnants with X-ray emission have brighter optical surface brightnesses and smaller diameters than those without X-ray emission.

  9. Three supernova shells around a young M33 star cluster

    NASA Astrophysics Data System (ADS)

    Camps-Fariña, A.; Beckman, J. E.; Font, J.; Borlaff, A.; Zaragoza-Cardiel, J.; Amram, P.

    2016-09-01

    Using a specialized technique sensitive to the presence of expanding ionized gas, we have detected a set of three concentric expanding shells in an H II region in the nearby spiral galaxy M33. After mapping the kinematics in Hα with Fabry-Perot spectroscopy, we used slit spectra to measure the intensities of the [S II] doublet at λλ671.9, 673.1 nm and the [N II] doublet at λλ645.8, 658.3 nm to corroborate the kinematics and apply diagnostic tests using line ratios. These showed that the expanding shells are shock dominated as would be the case if they had originated with supernova explosions. Estimating their kinetic energies, we find fairly low values, indicating a fairly advanced stage of evolution. We obtain density, mass and parent star mass estimates, which, along with the kinetic energies, are inconsistent with the simplest models of shock-interstellar medium interaction. We propose that the presence and properties of an inhomogeneous medium offer a scenario which can account for these observations, and discuss the implications. Comparing our results with data from the literature supports the combined presence of an H II region and supernova remnant material at the observed position.

  10. Spectroscopy of Of/WN Star in M33

    NASA Astrophysics Data System (ADS)

    Conti, Peter S.

    In a recent study of optical spectra of Wolf-Rayet stars in M33 we have discovered an object, MCA-1b, whose optical spectrum closely resembles that of the Of/WN9 star R84 in the LMC (Willis, Schild & Smith, 1991). We propose to secure a SWP+LWP ultraviolet spectrum of MCA-lb to complement our optical data, which will be analysed together using the state-of-the art, non- LTE moving atmosphere models now available at University College London. We will determine the physical and chemical properties of MCA-Ib from a detailed analysis similar to that carried out for R84 by Schmutz et al. (1991). The UV data will allow us to model the observed continuum energy distribution from 11509000 A, allowing an accurate determination of Teff, L*, Mbol, and R*, through model atmosphere fitting. The UV region is crucial in this respect, since the optical range alone is not sufficient to constrain models for objects with Teff >15000 K.

  11. Improved optical spectrophotometry of supernova remnants in M33

    NASA Technical Reports Server (NTRS)

    Blair, W. P.; Kirshner, R. P.

    1985-01-01

    Optical spectra of SNRs in M33 have been used to investigate abundance gradients and SNR evolution in this galaxy. Abundances of O, N, and S are derived from the spectra using new shock models by Dopita et al. (1984). The results for N and S show abundance gradients similar to those in NGC 300 and the Galaxy. The O abundances may be affected by possible contamination from H II regions and low-velocity shocks. Electron densities derived from the forbidden S II 6717 A/6731 A line ratio are used with a pressure equilibrium argument to estimate the initial explosion energy for each SNR. Evolutionary models for the remnants are investigated, and the distribution of the number of remnants with diameter is found to be consistent with free expansion of the SNRs to diameters of about 26 pc. The results may also be consistent with Sedov evolution if the ranges of initial supernova energies and surrounding interstellar medium densities are large enough.

  12. α7 Nicotinic Acetylcholine Receptors Occur at Postsynaptic Densities of AMPA Receptor-Positive and -Negative Excitatory Synapses in Rat Sensory Cortex

    PubMed Central

    Levy, Robert B.; Aoki, Chiye

    2010-01-01

    NMDA receptor (NMDAR) activation requires concurrent membrane depolarization, and glutamatergic synapses lacking AMPA receptors (AMPARs) are often considered “silent” in the absence of another source of membrane depolarization. During the second postnatal week, NMDA currents can be enhanced in rat auditory cortex through activation of the α7 nicotinic acetylcholine receptor (α7nAChR). Electrophysiological results support a mainly presynaptic role for α7nAChR at these synapses. However, immunocytochemical evidence that α7nAChR is prevalent at postsynaptic sites of glutamatergic synapses in hippocampus and neocortex, along with emerging electrophysiological evidence for postsynaptic nicotinic currents in neocortex and hippocampus, has prompted speculation that α7nAChR allows for activation of NMDAR postsynaptically at synapses lacking AMPAR. Here we used dual immunolabeling and electron microscopy to examine the distribution of α7nAChR relative to AMPAR (GluR1, GluR2, and GluR3 subunits combined) at excitatory synapses in somatosensory cortex of adult and 1-week-old rats. α7nAChR occurred discretely over most of the thick postsynaptic densities in all cortical layers of both age groups. AMPAR immunoreactivity was also detectable at most synapses; its distribution was independent of that of α7nAChR. In both age groups, approximately one-quarter of asymmetrical synapses were α7nAChR positive and AMPAR negative. The variability of postsynaptic α7nAChR labeling density was greater at postnatal day (PD) 7 than in adulthood, and PD 7 neuropil contained a subset of small AMPA receptor-negative synapses with a high density of α7nAChR immunoreactivity. These observations support the idea that acetylcholine receptors can aid in activating glutamatergic synapses and work together with AMPA receptors to mediate postsynaptic excitation throughout life. PMID:12077196

  13. CHANDRA ACIS SURVEY OF M33 (ChASeM33): THE ENIGMATIC X-RAY EMISSION FROM IC131

    SciTech Connect

    Tuellmann, Ralph; Plucinsky, Paul P.; Gaetz, Terrance J.; Smith, Randall K.; Long, Knox S.; Pannuti, Thomas G.; Winkler, P. Frank; Williams, Ben; Kuntz, Kip D.; Blair, William P.; Pietsch, Wolfgang; Haberl, Frank

    2009-12-20

    We present the first X-ray analysis of the diffuse hot ionized gas and the point sources in IC131, after NGC604 the second most X-ray luminous giant H II region (GHR) in M33. The X-ray emission is detected only in the south eastern part of IC131 (named IC131-se) and is limited to an elliptical region of approx200 pc in extent. This region appears to be confined toward the west by a hemispherical shell of warm ionized gas and only fills about half that volume. Although the corresponding X-ray spectrum has 1215 counts, it cannot conclusively be told whether the extended X-ray emission is thermal, non-thermal, or a combination of both. A thermal plasma model of kT{sub e} = 4.3 keV or a single power law of GAMMA approx = 2.1 fit the spectrum equally well. If the spectrum is purely thermal (non-thermal), the total unabsorbed X-ray luminosity in the 0.35-8 keV energy band amounts to L{sub X} = 6.8(8.7) x 10{sup 35} erg s{sup -1}. Among other known H II regions IC131-se seems to be extreme regarding the combination of its large extent of the X-ray plasma, the lack of massive O stars, its unusually high electron temperature (if thermal), and the large fraction of L{sub X} emitted above 2 keV (approx40%-53%). A thermal plasma of approx4 keV poses serious challenges to theoretical models, as it is not clear how high electron temperatures can be produced in H II regions in view of mass-proportional and collisionless heating. If the gas is non-thermal or has non-thermal contributions, synchrotron emission would clearly dominate over inverse Compton emission. It is not clear if the same mechanisms which create non-thermal X-rays or accelerate cosmic rays in supernova remnants can be applied to much larger scales of 200 pc. In both cases the existing theoretical models for GHRs and superbubbles do not explain the hardness and extent of the X-ray emission in IC131-se. We also detect a variable source candidate in IC131. It seems that this object (CXO J013315.10+304453.0) is a

  14. Chandra ACIS Survey of M33 (ChASeM33): The Enigmatic X-Ray Emission from IC131

    NASA Astrophysics Data System (ADS)

    Tüllmann, Ralph; Long, Knox S.; Pannuti, Thomas G.; Winkler, P. Frank; Plucinsky, Paul P.; Gaetz, Terrance J.; Williams, Ben; Kuntz, Kip D.; Pietsch, Wolfgang; Blair, William P.; Haberl, Frank; Smith, Randall K.

    2009-12-01

    We present the first X-ray analysis of the diffuse hot ionized gas and the point sources in IC131, after NGC604 the second most X-ray luminous giant H II region (GHR) in M33. The X-ray emission is detected only in the south eastern part of IC131 (named IC131-se) and is limited to an elliptical region of ~200 pc in extent. This region appears to be confined toward the west by a hemispherical shell of warm ionized gas and only fills about half that volume. Although the corresponding X-ray spectrum has 1215 counts, it cannot conclusively be told whether the extended X-ray emission is thermal, non-thermal, or a combination of both. A thermal plasma model of kTe = 4.3 keV or a single power law of Γ sime 2.1 fit the spectrum equally well. If the spectrum is purely thermal (non-thermal), the total unabsorbed X-ray luminosity in the 0.35-8 keV energy band amounts to LX = 6.8(8.7) × 1035 erg s-1. Among other known H II regions IC131-se seems to be extreme regarding the combination of its large extent of the X-ray plasma, the lack of massive O stars, its unusually high electron temperature (if thermal), and the large fraction of LX emitted above 2 keV (~40%-53%). A thermal plasma of ~4 keV poses serious challenges to theoretical models, as it is not clear how high electron temperatures can be produced in H II regions in view of mass-proportional and collisionless heating. If the gas is non-thermal or has non-thermal contributions, synchrotron emission would clearly dominate over inverse Compton emission. It is not clear if the same mechanisms which create non-thermal X-rays or accelerate cosmic rays in supernova remnants can be applied to much larger scales of 200 pc. In both cases the existing theoretical models for GHRs and superbubbles do not explain the hardness and extent of the X-ray emission in IC131-se. We also detect a variable source candidate in IC131. It seems that this object (CXO J013315.10+304453.0) is a high mass X-ray binary whose optical counterpart is a

  15. A role for naturally occurring variation of the murine coronavirus spike protein in stabilizing association with the cellular receptor.

    PubMed

    Gallagher, T M

    1997-04-01

    Murine hepatitis virus (MHV), a coronavirus, initiates infection by binding to its cellular receptor (MHVR) via spike (S) proteins projecting from the virion membrane. The structures of these S proteins vary considerably among MHV strains, and this variation is generally considered to be important in determining the strain-specific pathologies of MHV infection, perhaps by affecting the interaction between MHV and the MHVR. To address the relationships between S variation and receptor binding, assays capable of measuring interactions between MHV and MHVR were developed. The assays made use of a novel soluble form of the MHVR, sMHVR-Ig, which comprised the virus-binding immunoglobulin-like domain of MHVR fused to the Fc portion of human immunoglobulin G1. sMHVR-Ig was stably expressed as a disulfide-linked dimer in human 293 EBNA cells and was immobilized to Sepharose-protein G via the Fc domain. The resulting Sepharose beads were used to adsorb radiolabelled MHV particles. At 4 degrees C, the beads specifically adsorbed two prototype MHV strains, MHV JHM (strain 4) and a tissue culture-adapted mutant of MHV JHM, the JHMX strain. A shift to 37 degrees C resulted in elution of JHM but not JHMX. This in vitro observation of JHM (but not JHMX) elution from its receptor at 37 degrees C was paralleled by a corresponding 37 degrees C elution of receptor-associated JHM (but not JHMX) from tissue culture cells. The basis for this difference in maintenance of receptor association was correlated with a large deletion mutation present within the JHMX S protein, as sMHVR-Ig exhibited relatively thermostable binding to vaccinia virus-expressed S proteins containing the deletion. These results indicate that naturally occurring mutations in the coronavirus S protein affect the stability of the initial interaction with the host cell and thus contribute to the likelihood of successful infection by incoming virions. These changes in virus entry features may result in coronaviruses

  16. Expression of a naturally occurring angiotensin AT1 receptor cleavage fragment elicits caspase-activation and apoptosis

    PubMed Central

    Singh, Akannsha; deHaro, Dawn; Alam, Jawed; Re, Richard N.

    2011-01-01

    Several transmembrane receptors are documented to accumulate in nuclei, some as holoreceptors and others as cleaved receptor products. Our prior studies indicate that a population of the 7-transmembrane angiotensin type-1 receptor (AT1R) is cleaved in a ligand-augmented manner after which the cytoplasmic, carboxy-terminal cleavage fragment (CF) traffics to the nucleus. In the present report, we determine the precise cleavage site within the AT1R by mass spectrometry and Edman sequencing. Cleavage occurs between Leu(305) and Gly(306) at the junction of the seventh transmembrane domain and the intracellular cytoplasmic carboxy-terminal domain. To evaluate the function of the CF distinct from the holoreceptor, we generated a construct encoding the CF as an in-frame yellow fluorescent protein fusion. The CF accumulates in nuclei and induces apoptosis in CHO-K1 cells, rat aortic smooth muscle cells (RASMCs), MCF-7 human breast adenocarcinoma cells, and H9c2 rat cardiomyoblasts. All cell types show nuclear fragmentation and disintegration, as well as evidence for phosphotidylserine displacement in the plasma membrane and activated caspases. RASMCs specifically showed a 5.2-fold increase (P < 0.001) in CF-induced active caspases compared with control and a 7.2-fold increase (P < 0.001) in cleaved caspase-3 (Asp174). Poly(ADP-ribose)polymerase was upregulated 4.8-fold (P < 0.001) in CF expressing cardiomyoblasts and colocalized with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). CF expression also induces DNA laddering, the gold-standard for apoptosis in all cell types studied. CF-induced apoptosis, therefore, appears to be a general phenomenon as it is observed in multiple cell types including smooth muscle cells and cardiomyoblasts. PMID:21813711

  17. Expression of a naturally occurring angiotensin AT(1) receptor cleavage fragment elicits caspase-activation and apoptosis.

    PubMed

    Cook, Julia L; Singh, Akannsha; DeHaro, Dawn; Alam, Jawed; Re, Richard N

    2011-11-01

    Several transmembrane receptors are documented to accumulate in nuclei, some as holoreceptors and others as cleaved receptor products. Our prior studies indicate that a population of the 7-transmembrane angiotensin type-1 receptor (AT(1)R) is cleaved in a ligand-augmented manner after which the cytoplasmic, carboxy-terminal cleavage fragment (CF) traffics to the nucleus. In the present report, we determine the precise cleavage site within the AT(1)R by mass spectrometry and Edman sequencing. Cleavage occurs between Leu(305) and Gly(306) at the junction of the seventh transmembrane domain and the intracellular cytoplasmic carboxy-terminal domain. To evaluate the function of the CF distinct from the holoreceptor, we generated a construct encoding the CF as an in-frame yellow fluorescent protein fusion. The CF accumulates in nuclei and induces apoptosis in CHO-K1 cells, rat aortic smooth muscle cells (RASMCs), MCF-7 human breast adenocarcinoma cells, and H9c2 rat cardiomyoblasts. All cell types show nuclear fragmentation and disintegration, as well as evidence for phosphotidylserine displacement in the plasma membrane and activated caspases. RASMCs specifically showed a 5.2-fold increase (P < 0.001) in CF-induced active caspases compared with control and a 7.2-fold increase (P < 0.001) in cleaved caspase-3 (Asp174). Poly(ADP-ribose)polymerase was upregulated 4.8-fold (P < 0.001) in CF expressing cardiomyoblasts and colocalized with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). CF expression also induces DNA laddering, the gold-standard for apoptosis in all cell types studied. CF-induced apoptosis, therefore, appears to be a general phenomenon as it is observed in multiple cell types including smooth muscle cells and cardiomyoblasts.

  18. A 15.65-solar-mass black hole in an eclipsing binary in the nearby spiral galaxy M 33.

    PubMed

    Orosz, Jerome A; McClintock, Jeffrey E; Narayan, Ramesh; Bailyn, Charles D; Hartman, Joel D; Macri, Lucas; Liu, Jiefeng; Pietsch, Wolfgang; Remillard, Ronald A; Shporer, Avi; Mazeh, Tsevi

    2007-10-18

    Stellar-mass black holes are found in X-ray-emitting binary systems, where their mass can be determined from the dynamics of their companion stars. Models of stellar evolution have difficulty producing black holes in close binaries with masses more than ten times that of the Sun (>10; ref. 4), which is consistent with the fact that the most massive stellar black holes known so far all have masses within one standard deviation of 10. Here we report a mass of (15.65 +/- 1.45) for the black hole in the recently discovered system M 33 X-7, which is located in the nearby galaxy Messier 33 (M 33) and is the only known black hole that is in an eclipsing binary. To produce such a massive black hole, the progenitor star must have retained much of its outer envelope until after helium fusion in the core was completed. On the other hand, in order for the black hole to be in its present 3.45-day orbit about its (70.0 +/- 6.9) companion, there must have been a 'common envelope' phase of evolution in which a significant amount of mass was lost from the system. We find that the common envelope phase could not have occurred in M 33 X-7 unless the amount of mass lost from the progenitor during its evolution was an order of magnitude less than what is usually assumed in evolutionary models of massive stars. PMID:17943124

  19. A 15.65-solar-mass black hole in an eclipsing binary in the nearby spiral galaxy M 33.

    PubMed

    Orosz, Jerome A; McClintock, Jeffrey E; Narayan, Ramesh; Bailyn, Charles D; Hartman, Joel D; Macri, Lucas; Liu, Jiefeng; Pietsch, Wolfgang; Remillard, Ronald A; Shporer, Avi; Mazeh, Tsevi

    2007-10-18

    Stellar-mass black holes are found in X-ray-emitting binary systems, where their mass can be determined from the dynamics of their companion stars. Models of stellar evolution have difficulty producing black holes in close binaries with masses more than ten times that of the Sun (>10; ref. 4), which is consistent with the fact that the most massive stellar black holes known so far all have masses within one standard deviation of 10. Here we report a mass of (15.65 +/- 1.45) for the black hole in the recently discovered system M 33 X-7, which is located in the nearby galaxy Messier 33 (M 33) and is the only known black hole that is in an eclipsing binary. To produce such a massive black hole, the progenitor star must have retained much of its outer envelope until after helium fusion in the core was completed. On the other hand, in order for the black hole to be in its present 3.45-day orbit about its (70.0 +/- 6.9) companion, there must have been a 'common envelope' phase of evolution in which a significant amount of mass was lost from the system. We find that the common envelope phase could not have occurred in M 33 X-7 unless the amount of mass lost from the progenitor during its evolution was an order of magnitude less than what is usually assumed in evolutionary models of massive stars.

  20. Tyrosine phosphorylation of the BRI1 receptor kinase occurs via a posttranslational modification and is activated by the juxtamembrane domain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In metazoans, receptor kinases control many essential processes related to growth and development and response to the environment. The receptor kinases in plants and animals are structurally similar but evolutionarily distinct from one another, and thus while most animal receptor kinases are tyrosin...

  1. The geometric distance and proper motion of the Triangulum Galaxy (M33).

    PubMed

    Brunthaler, Andreas; Reid, Mark J; Falcke, Heino; Greenhill, Lincoln J; Henkel, Christian

    2005-03-01

    We measured the angular rotation and proper motion of the Triangulum Galaxy (M33) with the Very Long Baseline Array by observing two H2O masers on opposite sides of the galaxy. By comparing the angular rotation rate with the inclination and rotation speed, we obtained a distance of 730 +/- 168 kiloparsecs. This distance is consistent with the most recent Cepheid distance measurement. M33 is moving with a velocity of 190 +/- 59 kilometers per second relative to the Milky Way. These measurements promise a method to determine dynamical models for the Local Group and the mass and dark-matter halos of M31, M33, and the Milky Way.

  2. VizieR Online Data Catalog: M33 HII regions SED (Relano+, 2013)

    NASA Astrophysics Data System (ADS)

    Relano, M.; Verley, S.; Perez, I.; Kramer, C.; Calzetti, D.; Xilouris, E. M.; Boquien, M.; Abreu-Vicente, J.; Combes, F.; Israel, F.; Tabatabaei, F. S.; Braine, J.; Buchbender, C.; Gonzalez, M.; Gratier, P.; Lord, S.; Mookerjea, B.; Quintana-Lacaci, G.; van der Werf, P.

    2013-09-01

    To investigate the continuum UV emission of M 33, we used the data from GALEX, in particular the data distributed by de Paz et al. (2007, Cat. J/ApJS/173/185). To trace the ionised gas, we used the narrow-line Hα image of M 33 obtained by Greenawalt (1998, Ph.D. Thesis, New Mexico state University). Dust emission can be investigated through the mid-IR (MIR) and FIR data of M 33 obtained with the Spitzer Infrared Array Camera (IRAC) and Multiband Imaging Photometer (MIPS). (3 data files).

  3. Chandra ACIS Survey of M33 (ChASeM33): A Deep X-ray Survey of the Nearest Face-on Spiral Galaxy

    NASA Astrophysics Data System (ADS)

    Gaetz, Terrance J.; Tuellmann, R.; Plucinsky, P. P.; Kuntz, K.; Long, K. S.; Williams, B.; Blair, W. P.; Edgar, R. J.; Ghavamian, P.; Haberl, F.; Helfand, D.; Hughes, J. P.; Kirshner, R.; Mazeh, T.; Pannuti, T.; Pietsch, W.; Shporer, A.; Smith, R. K.; Winkler, P. F.; ChASeM33 Team

    2009-01-01

    The Chandra ACIS Survey of M33 (ChASeM33) is a deep survey of the nearest face-on Spiral Galaxy. The 1.4 Ms survey covers the galaxy out to R 18 arcmin ( 4 kpc at 790 kpc), providing the most extensive high spatial resolution assessment of the X-ray source populations available for M33. Mosaic images of the ChASeM33 observations show several hundred individual X-ray sources as well as soft diffuse emission from the hot interstellar medium. Bright extended emission surrounds the nucleus and is also detected from the giant HII regions NGC604 and IC131. Fainter extended emission and numerous individual sources appear to trace the inner spiral structure. An initial source catalog based on 2/3 of the survey data has been published, and published papers based on the survey include: the discovery of the first eclipsing black hole binary system, an analysis of the brightest supernova remnant in M33, an analysis of the giant HII region NGC604, and an analysis of a number of transient sources. A catalog for the whole survey has now been prepared. We will discuss the improvements made in reducing the data and the approach for detecting and characterizing sources. Adjacent poster presentations include analyses of the new catalog, the X-ray emitting giant HII region (IC131), the supernova remnant population, a preliminary analysis of the diffuse emission, and initial results of a new radio survey complementing the X-ray survey. Support for this work was provided by NASA through Chandra Award Number G06-7073A and contract NAS8-03060.

  4. CHARACTERIZATION OF THE MOST LUMINOUS STAR IN M33: A SUPER SYMBIOTIC BINARY

    SciTech Connect

    Mikołajewska, Joanna; Iłkiewicz, Krystian; Caldwell, Nelson; Shara, Michael M.

    2015-01-30

    We present the first spectrum of the most luminous infrared star in M33, and use it to demonstrate that the object is almost certainly a binary composed of a massive O star and a dust-enshrouded red hypergiant. This is the most luminous symbiotic binary ever discovered. Its radial velocity is an excellent match to that of the hydrogen gas in the disk of M33, supporting our interpretation that it is a very young and massive binary star.

  5. Background Quasars in the Vicinity of M31/M33 with LAMOST

    NASA Astrophysics Data System (ADS)

    Huo, Zhiying

    2015-08-01

    We present quasars discovered in the vicinity of the Andromeda (M31) and Triangulum (M33) galaxies withthe LAMOST (Large Sky Area Multi-Object Fiber Spectroscopic Telescope, also named Guoshoujing Telescope) during the 2013 observational season, the second year of regular survey. In total 1330 new quasars are discovered in an area of ~133 square degree nearby M31 and M33. The 1330 new quasars have i-band magnitudes ranging from 14.79 to 20.0, redshifts from 0.08 to 4.85, and represent a significant increase of the number of identified quasars in the vicinity of M31 and M33. Until now, there are in total 1870 quasars discovered by LAMOST in the vicinity of M31and M33 (see also Huo et al. 2010, 2013). The much enlarged sample of known quasars in the vicinity of M31 and M33 can potentially be utilized to construct a perfect astrometric reference frame to measurement the minute proper motion of M31, M33 and the associated substructures. We know that those proper motions are some of the most fundamental properties for understanding the formation and evolution of M31, M33 and the Local Group galaxies. Meanwhile, there are in total 45, 98 and 225 quasars with i-band magnitudes brighter than 17.0, 17.5 and 18.0 respectively, in this area. In the aforementioned brightness bins, 15, 35 and 84 quasars are report here for the first time, 6, 21 and 81 are reported in Huo et al. (2010, 2013), while 0, 1 and 6 are from the Sloan Digital Sky Survey, and 24, 41 and 54 are from the NED database. These bright quasars provide an invaluable sample to probe the kinematics and chemistry of the interstellar/intergalactic medium in M31 and M33, the associated substructures, and the Local Group of galaxies.

  6. VizieR Online Data Catalog: Deep XMM-Newton survey of M33 (Williams+, 2015)

    NASA Astrophysics Data System (ADS)

    Williams, B. F.; Wold, B.; Haberl, F.; Garofali, K.; Blair, W. P.; Gaetz, T. J.; Kuntz, K. D.; Long, K. S.; Pannuti, T. G.; Pietsch, W.; Plucinsky, P. P.; Winkler, P. F.

    2015-07-01

    To produce an M33 catalog, we have used data of several newly observed XMM-Newton fields in M33 and archival observations of an eighth field (PI: Pietsch; from 2010-01-07 to 2010-02-24). The observation dates for the seven new data fields ranged from 2010 July 09 to August 15 and from 2012 January 10 to January 12. (2 data files).

  7. AN UPDATED CATALOG OF M33 CLUSTERS AND CANDIDATES: UBVRI PHOTOMETRY AND SOME STATISTICAL RESULTS

    SciTech Connect

    Ma Jun

    2012-08-15

    We present UBVRI photometry for 392 star clusters and candidates in the field of M33, which are selected from the most recent star cluster catalog. In this catalog, the authors listed star clusters' parameters such as cluster positions, magnitudes, colors in the UBVRIJHK{sub s} filters, and so on. However, a large fraction of objects in this catalog do not have previously published photometry. Photometry is performed using archival images from the Local Group Galaxies Survey, which covers 0.8 deg{sup 2} along the major axis of M33. Detailed comparisons show that, in general, our photometry is consistent with previous measurements. Positions (right ascension and declination) for some clusters are corrected here. Combined with previous literature, ours constitute a large sample of M33 star clusters. Based on this cluster sample, we present some statistical results: none of the youngest M33 clusters ({approx}10{sup 7} yr) have masses approaching 10{sup 5} M{sub Sun} ; roughly half the star clusters are consistent with the 10{sup 4}-10{sup 5} M{sub Sun} mass models; the continuous distribution of star clusters along the model line indicates that M33 star clusters have been formed continuously from the epoch of the first star cluster formation until recent times; and there are {approx}50 star clusters which are overlapped with the Galactic globular clusters on the color-color diagram, and these clusters are old globular cluster candidates in M33.

  8. Naturally-Occurring Glucosinolates, Glucoraphanin and Glucoerucin, are Antagonists to Aryl Hydrocarbon Receptor as Their Chemopreventive Potency.

    PubMed

    Abdull Razis, Ahmad Faizal; Noor, Noramaliza Mohd

    2015-01-01

    As a cytosolic transcription factor, the aryl hydrocarbon (Ah) receptor is involved in several patho- physiological events leading to immunosuppression and cancer; hence antagonists of the Ah receptor may possess chemoprevention properties. It is known to modulate carcinogen-metabolising enzymes, for instance the CYP1 family of cytochromes P450 and quinone reductase, both important in the biotransformation of many chemical carcinogens via regulating phase I and phase II enzyme systems. Utilising chemically-activated luciferase expression (CALUX) assay it was revealed that intact glucosinolates, glucoraphanin and glucoerucin, isolated from Brassica oleracea L. var. acephala sabellica and Eruca sativa ripe seeds, respectively, are such antagonists. Both glucosinolates were poor ligands for the Ah receptor; however, they effectively antagonised activation of the receptor by the avid ligand benzo[a]pyrene. Indeed, intact glucosinolate glucoraphanin was a more potent antagonist to the receptor than glucoerucin. It can be concluded that both glucosinolates effectively act as antagonists for the Ah receptor, and this may contribute to their established chemoprevention potency. PMID:26320454

  9. THE M33 GLOBULAR CLUSTER SYSTEM WITH PAndAS DATA: THE LAST OUTER HALO CLUSTER?

    SciTech Connect

    Cockcroft, Robert; Harris, William E.; Ferguson, Annette M. N. E-mail: harris@physics.mcmaster.ca

    2011-04-01

    We use CFHT/MegaCam data to search for outer halo star clusters in M33 as part of the Pan-Andromeda Archaeological Survey. This work extends previous studies out to a projected radius of 50 kpc and covers over 40 deg{sup 2}. We find only one new unambiguous star cluster in addition to the five previously known in the M33 outer halo (10 kpc {<=} r {<=} 50 kpc). Although we identify 2440 cluster candidates of various degrees of confidence from our objective image search procedure, almost all of these are likely background contaminants, mostly faint unresolved galaxies. We measure the luminosity, color, and structural parameters of the new cluster in addition to the five previously known outer halo clusters. At a projected radius of 22 kpc, the new cluster is slightly smaller, fainter, and redder than all but one of the other outer halo clusters, and has g' {approx} 19.9, (g' - i') {approx} 0.6, concentration parameter c {approx} 1.0, a core radius r{sub c} {approx} 3.5 pc, and a half-light radius r{sub h} {approx} 5.5 pc. For M33 to have so few outer halo clusters compared to M31 suggests either tidal stripping of M33's outer halo clusters by M31, or a very different, much calmer accretion history of M33.

  10. The M33 Globular Cluster System with PAndAS Data: the Last Outer Halo Cluster?

    NASA Astrophysics Data System (ADS)

    Cockcroft, Robert; Harris, William E.; Ferguson, Annette M. N.; Huxor, Avon; Ibata, Rodrigo; Irwin, Mike J.; McConnachie, Alan W.; Woodley, Kristin A.; Chapman, Scott C.; Lewis, Geraint F.; Puzia, Thomas H.

    2011-04-01

    We use CFHT/MegaCam data to search for outer halo star clusters in M33 as part of the Pan-Andromeda Archaeological Survey. This work extends previous studies out to a projected radius of 50 kpc and covers over 40 deg2. We find only one new unambiguous star cluster in addition to the five previously known in the M33 outer halo (10 kpc <= r <= 50 kpc). Although we identify 2440 cluster candidates of various degrees of confidence from our objective image search procedure, almost all of these are likely background contaminants, mostly faint unresolved galaxies. We measure the luminosity, color, and structural parameters of the new cluster in addition to the five previously known outer halo clusters. At a projected radius of 22 kpc, the new cluster is slightly smaller, fainter, and redder than all but one of the other outer halo clusters, and has g' ≈ 19.9, (g' - i') ≈ 0.6, concentration parameter c ≈ 1.0, a core radius rc ≈ 3.5 pc, and a half-light radius rh ≈ 5.5 pc. For M33 to have so few outer halo clusters compared to M31 suggests either tidal stripping of M33's outer halo clusters by M31, or a very different, much calmer accretion history of M33.

  11. Stellar content of nearby galaxies. III - The local group spiral galaxy M33

    NASA Technical Reports Server (NTRS)

    Wilson, Christine D.; Madore, Barry F.; Freedman, Wendy L.

    1990-01-01

    BVRI CCD photometry is presented for stars brighter than V = 21 mag in four fields in the nearby spiral galaxy M33. V vs (B - V) and I vs (V - I) color-magnitude diagrams clearly show both a young stellar population (as indicated by the blue main sequence and red supergiant plumes) as well as an intermediate-age population of asymptotic giant branch stars. Deep photometry in the outer field (where crowding is less severe) reveals a population consistent in color and magnitude with the tip of the first red giant branch. The M33 distance modulus, 24.6 + or - 0.3 mag, derived from this Population II component is consistent with a recent redetermination of the distance modulus found from Population I Cepheid variables. Finally, some evidence is presented for a radial gradient in the average internal reddening for the fields in M33 reported here.

  12. M33: A Close Neighbor Reveals its True Size and Splendor (3-color composite)

    NASA Technical Reports Server (NTRS)

    2009-01-01

    One of our closest galactic neighbors shows its awesome beauty in this new image from NASA's Spitzer Space Telescope. M33, also known as the Triangulum Galaxy, is a member of what's known as our Local Group of galaxies. Along with our own Milky Way, this group travels together in the universe, as they are gravitationally bound. In fact, M33 is one of the few galaxies that is moving toward the Milky Way despite the fact that space itself is expanding, causing most galaxies in the universe to grow farther and farther apart.

    When viewed with Spitzer's infrared eyes, this elegant spiral galaxy sparkles with color and detail. Stars appear as glistening blue gems (several of which are actually foreground stars in our own galaxy), while dust rich in organic molecules glows green. The diffuse orange-red glowing areas indicate star-forming regions, while small red flecks outside the spiral disk of M33 are most likely distant background galaxies. But not only is this new image beautiful, it also shows M33 to be surprising large bigger than its visible-light appearance would suggest. With its ability to detect cold, dark dust, Spitzer can see emission from cooler material well beyond the visible range of M33's disk. Exactly how this cold material moved outward from the galaxy is still a mystery, but winds from giant stars or supernovas may be responsible.

    M33 is located about 2.9 million light-years away in the constellation Triangulum. This is a three-color composite image showing infrared observations from two of Spitzer instruments. Blue represents combined 3.6- and 4.5-micron light and green shows light of 8 microns, both captured by Spitzer's infrared array camera. Red is 24-micron light detected by Spitzer's multiband imaging photometer.

  13. ASASSN-15th (M33N 2015-12a): Additional Spectroscopic Observations

    NASA Astrophysics Data System (ADS)

    Darnley, M. J.; Williams, S. C.

    2015-12-01

    We report additional spectroscopic observations of the developing M33 nova eruption ASASSN-15th (M33N 2015-12a; see ATel #8349, #8352). The low resolution, high throughput, SPRAT instrument on the 2m fully-robotic Liverpool Telescope obtained three 600s spectra of ASASSN-15th at 2015 Dec. 10.9 UT. These spectra show significant evolution from that reported in ATel #8352, in that the deep P Cygni profiles seen in the few days after discovery have now almost completely disappeared, with the emission component of these lines growing in strength.

  14. Activation and desensitization of peripheral muscle and neuronal nicotinic acetylcholine receptors by selected, naturally-occurring pyridine alkaloids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Teratogenic alkaloids can cause developmental defects due to inhibition of fetal movement that results from desensitization of fetal muscletype nicotinic acetylcholine receptors (nAChRs). We investigated the ability of two known teratogens, the piperidinyl-pyridine anabasine and its 1,2-dehydropiper...

  15. A soluble class II cytokine receptor, IL-22RA2, is a naturally occurring IL-22 antagonist

    PubMed Central

    Xu, Wenfeng; Presnell, Scott R.; Parrish-Novak, Julia; Kindsvogel, Wayne; Jaspers, Steve; Chen, Zhi; Dillon, Stacey R.; Gao, Zeren; Gilbert, Teresa; Madden, Karen; Schlutsmeyer, Stacy; Yao, Lena; Whitmore, Theodore E.; Chandrasekher, Yasmin; Grant, Francis J.; Maurer, Mark; Jelinek, Laura; Storey, Harold; Brender, Ty; Hammond, Angie; Topouzis, Stavros; Clegg, Christopher H.; Foster, Donald C.

    2001-01-01

    IL-22 is an IL-10 homologue that binds to and signals through the class II cytokine receptor heterodimer IL-22RA1/CRF2–4. IL-22 is produced by T cells and induces the production of acute-phase reactants in vitro and in vivo, suggesting its involvement in inflammation. Here we report the identification of a class II cytokine receptor designated IL-22RA2 (IL-22 receptor-α 2) that appears to be a naturally expressed soluble receptor. IL-22RA2 shares amino acid sequence homology with IL-22RA1 (also known as IL-22R, zcytor11, and CRF2–9) and is physically adjacent to IL-20Rα and IFN-γR1 on chromosome 6q23.3–24.2. We demonstrate that IL-22RA2 binds specifically to IL-22 and neutralizes IL-22-induced proliferation of BaF3 cells expressing IL-22 receptor subunits. IL-22RA2 mRNA is highly expressed in placenta and spleen by Northern blotting. PCR analysis using RNA from various tissues and cell lines showed that IL-22RA2 was expressed in a range of tissues, including those in the digestive, female reproductive, and immune systems. In situ hybridization revealed the dominant cell types expressing IL-22RA2 were mononuclear cells and epithelium. Because IL-22 induces the expression of acute phase reactants, IL-22RA2 may play an important role as an IL-22 antagonist in the regulation of inflammatory responses. PMID:11481447

  16. Receptor-Mediated Endocytosis of Two-Dimensional Nanomaterials Undergoes Flat Vesiculation and Occurs by Revolution and Self-Rotation.

    PubMed

    Mao, Jian; Chen, Pengyu; Liang, Junshi; Guo, Ruohai; Yan, Li-Tang

    2016-01-26

    Two-dimensional nanomaterials, such as graphene and transitional metal dichalcogenide nanosheets, are promising materials for the development of antimicrobial surfaces and the nanocarriers for intracellular therapy. Understanding cell interaction with these emerging materials is an urgently important issue to promoting their wide applications. Experimental studies suggest that two-dimensional nanomaterials enter cells mainly through receptor-mediated endocytosis. However, the detailed molecular mechanisms and kinetic pathways of such processes remain unknown. Here, we combine computer simulations and theoretical derivation of the energy within the system to show that the receptor-mediated transport of two-dimensional nanomaterials, such as graphene nanosheet across model lipid membrane, experiences a flat vesiculation event governed by the receptor density and membrane tension. The graphene nanosheet is found to undergo revolution relative to the membrane and, particularly, unique self-rotation around its normal during membrane wrapping. We derive explicit expressions for the formation of the flat vesiculation, which reveals that the flat vesiculation event can be fundamentally dominated by a dimensionless parameter and a defined relationship determined by complicated energy contributions. The mechanism offers an essential understanding on the cellular internalization and cytotoxicity of the emerging two-dimensional nanomaterials.

  17. Discrete clouds of neutral gas between the galaxies M31 and M33.

    PubMed

    Wolfe, Spencer A; Pisano, D J; Lockman, Felix J; McGaugh, Stacy S; Shaya, Edward J

    2013-05-01

    Spiral galaxies must acquire gas to maintain their observed level of star formation beyond the next few billion years. A source of this material may be the gas that resides between galaxies, but our understanding of the state and distribution of this gas is incomplete. Radio observations of the Local Group of galaxies have revealed hydrogen gas extending from the disk of the galaxy M31 at least halfway to M33. This feature has been interpreted to be the neutral component of a condensing intergalactic filament, which would be able to fuel star formation in M31 and M33, but simulations suggest that such a feature could also result from an interaction between both galaxies within the past few billion years (ref. 5). Here we report radio observations showing that about 50 per cent of this gas is composed of clouds, with the rest distributed in an extended, diffuse component. The clouds have velocities comparable to those of M31 and M33, and have properties suggesting that they are unrelated to other Local Group objects. We conclude that the clouds are likely to be transient condensations of gas embedded in an intergalactic filament and are therefore a potential source of fuel for future star formation in M31 and M33.

  18. M33: A Close Neighbor Reveals its True Size and Splendor

    NASA Technical Reports Server (NTRS)

    2009-01-01

    One of our closest galactic neighbors shows its awesome beauty in this new image from NASA's Spitzer Space Telescope. M33, also known as the Triangulum Galaxy, is a member of what's known as our Local Group of galaxies. Along with our own Milky Way, this group travels together in the universe, as they are gravitationally bound. In fact, M33 is one of the few galaxies that is moving toward the Milky Way despite the fact that space itself is expanding, causing most galaxies in the universe to grow farther and farther apart.

    When viewed with Spitzer's infrared eyes, this elegant spiral galaxy sparkles with color and detail. Stars appear as glistening blue gems (many of which are actually foreground stars in our own galaxy), while dust in the spiral disk of the galaxy glows pink and red. But not only is this new image beautiful, it also shows M33 to be surprising large bigger than its visible-light appearance would suggest. With its ability to detect cold, dark dust, Spitzer can see emission from cooler material well beyond the visible range of M33's disk. Exactly how this cold material moved outward from the galaxy is still a mystery, but winds from giant stars or supernovas may be responsible.

    M33 is located about 2.9 million light-years away in the constellation Triangulum. This composite image was taken by Spitzer's infrared array camera. The color blue indicates infrared light of 3.6 microns, green shows 4.5-micron light, and red 8.0 microns.

  19. The Herschel M 33 extended survey (HerM33es): PACS spectroscopy of the star-forming region BCLMP 302

    NASA Astrophysics Data System (ADS)

    Mookerjea, B.; Kramer, C.; Buchbender, C.; Boquien, M.; Verley, S.; Relaño, M.; Quintana-Lacaci, G.; Aalto, S.; Braine, J.; Calzetti, D.; Combes, F.; Garcia-Burillo, S.; Gratier, P.; Henkel, C.; Israel, F.; Lord, , S.; Nikola, T.; Röllig, M.; Stacey, G.; Tabatabaei, F. S.; van der Tak, F.; van der Werf, P.

    2011-08-01

    Context. The emission line of [C ii] at 158 μm is one of the strongest cooling lines of the interstellar medium (ISM) in galaxies. Aims: Distinguishing the relative contributions of the different ISM phases to [C ii] emission is a major objective of the HerM33es program, a Herschel key project to study the ISM in the nearby spiral galaxy M 33. Methods: Using PACS, we have mapped the emission of [C ii] 158 μm, [O i] 63 μm, and other FIR lines in a 2' × 2' region of the northern spiral arm of M 33, centered on the H ii region BCLMP 302. At the peak of Hα emission, we observed in addition a velocity-resolved [C ii] spectrum using HIFI. We use scatterplots to compare these data with PACS 160 μm continuum maps, and with maps of CO and H i data, at a common resolution of 12″ or 50 pc. Maps of Hα and 24 μm emission observed with Spitzer are used to estimate the SFR. We created maps of the [C ii] and [O i] 63 μm emission and detected [N ii] 122 μm and [N iii] 57 μm at individual positions. Results: The [C ii] line observed with HIFI is significantly broader than that of CO, and slightly blue-shifted. In addition, there is little spatial correlation between [C ii] observed with PACS and CO over the mapped region. There is even less spatial correlation between [C ii] and the atomic gas traced by H i. Detailed comparison of the observed intensities towards the H ii region with models of photo-ionization and photon-dominated regions, confirms that a significant fraction, 20-30%, of the observed [C ii] emission stems from the ionized gas and not from the molecular cloud. The gas heating efficiency, using the ratio of [C ii] to the TIR as a proxy, varies between 0.07 and 1.5%, with the largest variations found outside the H ii region. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.

  20. Discovery of naturally occurring splice variants of the rat histamine H3 receptor that act as dominant-negative isoforms.

    PubMed

    Bakker, Remko A; Lozada, Adrian Flores; van Marle, André; Shenton, Fiona C; Drutel, Guillaume; Karlstedt, Kaj; Hoffmann, Marcel; Lintunen, Minnamaija; Yamamoto, Yumiko; van Rijn, Richard M; Chazot, Paul L; Panula, Pertti; Leurs, Rob

    2006-04-01

    We described previously the cDNA cloning of three functional rat histamine H3 receptor (rH3R) isoforms as well as the differential brain expression patterns of their corresponding mRNAs and signaling properties of the resulting rH3A, rH3B, and rH3C receptor isoforms (Mol Pharmacol 59:1-8). In the current report, we describe the cDNA cloning, mRNA localization in the rat central nervous system, and pharmacological characterization of three additional rH3R splice variants (rH3D, rH3E, and rH3F) that differ from the previously published isoforms in that they result from an additional alternative-splicing event. These new H3R isoforms lack the seventh transmembrane (TM) helix and contain an alternative, putatively extracellular, C terminus (6TM-rH3 isoforms). After heterologous expression in COS-7 cells, radioligand binding or functional responses upon the application of various H3R ligands could not be detected for the 6TM-rH3 isoforms. In contrast to the rH3A receptor (rH3AR), detection of the rH3D isoform using hemagglutinin antibodies revealed that the rH3D isoform remains mainly intracellular. The expression of the rH3D-F splice variants, however, modulates the cell surface expression-levels and subsequent functional responses of the 7TM H3R isoforms. Coexpression of the rH3AR and the rH3D isoforms resulted in the intracellular retention of the rH3AR and reduced rH3AR functionality. Finally, we show that in rat brain, the H3R mRNA expression levels are modulated upon treatment with the convulsant pentylenetetrazole, suggesting that the rH3R isoforms described herein thus represent a novel physiological mechanism for controlling the activity of the histaminergic system.

  1. Identification and pharmacological analyses of eight naturally occurring caprine melanocortin-1 receptor mutations in three different goat breeds.

    PubMed

    Xiong, Qi; Chai, Jin; Chen, Mingxin; Tao, Ya-Xiong

    2016-09-01

    The melanocortin-1 receptor (MC1R) belongs to the family of seven transmembrane G protein-coupled receptors and plays a central role in animal coat color. We have sequenced the full coding region of 954bp of the MC1R gene in 72 goats of three breeds with different coat colors and identified five missense mutations (K226E, F250V, G255D, V265I, and C267W) and one silent mutation (A61A), among which two haplotypes with complete linkage disequilibrium (A61A and F250V, G255D and V265I) were found. We performed detailed functional studies on the six single and two double mutations in transiently transfected HEK293T cells. We found that none of the mutants had decreased cell surface expression. However, all the mutants except A61A had decreased constitutive activities in the cAMP pathway. Five mutations (F250V, G255D, G267W, A61A/F250V, G255D/V265I) exhibited significant defects in ligand binding and consequent agonist-induced cAMP signaling and ERK1/2 activation. Additionally, K226E, with normal ligand binding affinity and cAMP signaling, showed a significant defect in ERK1/2 activation, exhibiting biased signaling. Co-expression studies showed that the five defective mutants did not affect wild-type MC1R signaling, hence they were not dominant negative. In summary, we provided detailed data of these goat MC1R mutations leading to a better understanding of the role of MC1R mutation and coat color in goats. PMID:27229376

  2. The conjugated linoleic acid isomer trans-9,trans-11 is a dietary occurring agonist of liver X receptor {alpha}

    SciTech Connect

    Ecker, Josef; Liebisch, Gerhard; Patsch, Wolfgang; Schmitz, Gerd

    2009-10-30

    Conjugated linoleic acid (CLA) isomers are dietary fatty acids that modulate gene expression in many cell types. We have previously reported that specifically trans-9,trans-11 (t9,t11)-CLA induces expression of genes involved in lipid metabolism of human macrophages. To elucidate the molecular mechanism underlying this transcriptional activation, we asked whether t9,t11-CLA affects activity of liver X receptor (LXR) {alpha}, a major regulator of macrophage lipid metabolism. Here we show that t9,t11-CLA is a regulator of LXR{alpha}. We further demonstrate that the CLA isomer induces expression of direct LXR{alpha} target genes in human primary macrophages. Knockdown of LXR{alpha} with RNA interference in THP-1 cells inhibited t9,t11-CLA mediated activation of LXR{alpha} including its target genes. To evaluate the effective concentration range of t9,t11-CLA, human primary macrophages were treated with various doses of CLA and well known natural and synthetic LXR agonists and mRNA expression of ABCA1 and ABCG1 was analyzed. Incubation of human macrophages with 10 {mu}M t9,t11-CLA led to a significant modulation of ABCA1 and ABCG1 transcription and caused enhanced cholesterol efflux to high density lipoproteins and apolipoprotein AI. In summary, these data show that t9,t11-CLA is an agonist of LXR{alpha} in human macrophages and that its effects on macrophage lipid metabolism can be attributed to transcriptional regulations associated with this nuclear receptor.

  3. The alignment of molecular cloud magnetic fields with the spiral arms in M33.

    PubMed

    Li, Hua-bai; Henning, Thomas

    2011-11-24

    The formation of molecular clouds, which serve as stellar nurseries in galaxies, is poorly understood. A class of cloud formation models suggests that a large-scale galactic magnetic field is irrelevant at the scale of individual clouds, because the turbulence and rotation of a cloud may randomize the orientation of its magnetic field. Alternatively, galactic fields could be strong enough to impose their direction upon individual clouds, thereby regulating cloud accumulation and fragmentation, and affecting the rate and efficiency of star formation. Our location in the disk of the Galaxy makes an assessment of the situation difficult. Here we report observations of the magnetic field orientation of six giant molecular cloud complexes in the nearby, almost face-on, galaxy M33. The fields are aligned with the spiral arms, suggesting that the large-scale field in M33 anchors the clouds.

  4. The alignment of molecular cloud magnetic fields with the spiral arms in M33

    NASA Astrophysics Data System (ADS)

    Li, Hua-Bai; Henning, Thomas

    2011-11-01

    The formation of molecular clouds, which serve as stellar nurseries in galaxies, is poorly understood. A class of cloud formation models suggests that a large-scale galactic magnetic field is irrelevant at the scale of individual clouds, because the turbulence and rotation of a cloud may randomize the orientation of its magnetic field. Alternatively, galactic fields could be strong enough to impose their direction upon individual clouds, thereby regulating cloud accumulation and fragmentation, and affecting the rate and efficiency of star formation. Our location in the disk of the Galaxy makes an assessment of the situation difficult. Here we report observations of the magnetic field orientation of six giant molecular cloud complexes in the nearby, almost face-on, galaxy M33. The fields are aligned with the spiral arms, suggesting that the large-scale field in M33 anchors the clouds.

  5. The Early Spectral Evolution of the Classical Nova ASASSN-15th in M33

    NASA Astrophysics Data System (ADS)

    Wagner, R. Mark; Neric, Marko; Darnley, Matt J.; Williams, Steven; Starrfield, Sumner; Woodward, Charles E.; Prieto, Jose Luis

    2016-06-01

    During the course of the All Sky Automated Survey for SuperNovae (ASAS-SN) a new transient source designated ASASSN-15th was identified on images of the nearby galaxy M33 obtained with the 14 cm Brutus telescope in Haleakala, Hawaii on 2015 Dec 1.4 UT at V ~ 16.5 mag. Given the location of the transient in M33 and its apparent V magnitude at discovery, the implied absolute visual magnitude was about -8.5 mag suggesting that the transient was a new classical nova outburst in M33. Optical spectroscopy obtained by us on 2015 Dec 2.3 showed broad emission lines of Balmer, Fe II, and Na I D with P Cygni-type line profiles superposed on a blue continuum. The spectrum was consistent with a Fe II-type classical nova in M33 discovered early in the outburst. Subsequent spectra obtained by us on 2015 Dec 10.9 UT showed significant evolution since our first spectrum in that the deep P Cygni-type line profiles seen earlier were now extremely shallow or had almost completely disappeared with the emission component growing in strength. Additional emission lines from O I, Si II, and possibly He I were also present. We obtained optical spectroscopy of ASASSN-15th on 17 epochs between 2015 Dec 1 and 2016 Feb 11 UT with the 2.4 m Hiltner telescope (+OSMOS) of the MDM Observatory, the 2 m fully robotic Liverpool Telescope (+SPRAT), and the 2 x 8.4 m Large Binocular Telescope (+MODS). We will present our spectroscopy and discuss the early evolution of ASASSN-15th in the context of Galactic Fe II-class novae.

  6. STAR CLUSTERS IN M33: UPDATED UBVRI PHOTOMETRY, AGES, METALLICITIES, AND MASSES

    SciTech Connect

    Fan, Zhou; De Grijs, Richard E-mail: grijs@pku.edu.cn

    2014-04-01

    The photometric characterization of M33 star clusters is far from complete. In this paper, we present homogeneous UBVRI photometry of 708 star clusters and cluster candidates in M33 based on archival images from the Local Group Galaxies Survey, which covers 0.8 deg{sup 2} along the galaxy's major axis. Our photometry includes 387, 563, 616, 580, and 478 objects in the UBVRI bands, respectively, of which 276, 405, 430, 457, and 363 do not have previously published UBVRI photometry. Our photometry is consistent with previous measurements (where available) in all filters. We adopted Sloan Digital Sky Survey ugriz photometry for complementary purposes, as well as Two Micron All Sky Survey near-infrared JHK photometry where available. We fitted the spectral-energy distributions of 671 star clusters and candidates to derive their ages, metallicities, and masses based on the updated PARSEC simple stellar populations synthesis models. The results of our χ{sup 2} minimization routines show that only 205 of the 671 clusters (31%) are older than 2 Gyr, which represents a much smaller fraction of the cluster population than that in M31 (56%), suggesting that M33 is dominated by young star clusters (<1 Gyr). We investigate the mass distributions of the star clusters—both open and globular clusters—in M33, M31, the Milky Way, and the Large Magellanic Cloud. Their mean values are log (M {sub cl}/M {sub ☉}) = 4.25, 5.43, 2.72, and 4.18, respectively. The fraction of open to globular clusters is highest in the Milky Way and lowest in M31. Our comparisons of the cluster ages, masses, and metallicities show that our results are basically in agreement with previous studies (where objects in common are available); differences can be traced back to differences in the models adopted, the fitting methods used, and stochastic sampling effects.

  7. A NEW DISTANCE TO M33 USING BLUE SUPERGIANTS AND THE FGLR METHOD

    SciTech Connect

    U, Vivian; Urbaneja, Miguel A.; Kudritzki, Rolf-Peter; Jacobs, Bradley A.; Bresolin, Fabio; Przybilla, Norbert E-mail: urbaneja@ifa.hawaii.ed E-mail: bjacobs@ifa.hawaii.ed E-mail: przybilla@sternwarte.uni-erlangen.d

    2009-10-20

    The quantitative spectral analysis of medium resolution optical spectra of A and B supergiants obtained with DEIMOS and ESI at the Keck Telescopes is used to determine a distance modulus of 24.93 +- 0.11 mag (968 +- 50 kpc) for the Triangulum Galaxy M33. The analysis yields stellar effective temperatures, gravities, interstellar reddening, and extinction, the combination of which provides a distance estimate via the flux-weighted gravity-luminosity relationship (FGLR). This result is based on an FGLR calibration that is continually being polished. An average reddening of (E(B - V)) approx 0.08 mag is found, with a large variation ranging from 0.01 to 0.16 mag, however, demonstrating the importance of accurate individual reddening measurements for stellar distance indicators in galaxies with evident signatures of interstellar absorption. The large-distance modulus found is in good agreement with recent work on eclipsing binaries, planetary nebulae, long-period variables, RR Lyrae stars, and also with Hubble Space Telescope (HST) observations of Cepheids, if reasonable reddening assumptions are made for the Cepheids. Since distances based on the tip of the red giant branch (TRGB) method found in the literature give conflicting results, we have used HST Advanced Camera for Surveys V- and I-band images of outer regions of M33 to determine a TRGB distance of 24.84 +- 0.10 mag, in basic agreement with the FGLR result. We have also determined stellar metallicities and discussed the metallicity gradient in the disk of M33. We find metallicity of Z {sub sun} at the center and 0.3 Z {sub sun} in the outskirts at a distance of one isophotal radius. The average logarithmic metallicity gradient is -0.07 +- 0.01 dex kpc{sup -1}. However, there is a large scatter around this average value, very similar to what has been found for the H II regions in M33.

  8. Activation and Desensitization of Peripheral Muscle and Neuronal Nicotinic Acetylcholine Receptors by Selected, Naturally-Occurring Pyridine Alkaloids.

    PubMed

    Green, Benedict T; Lee, Stephen T; Welch, Kevin D; Cook, Daniel; Kem, William R

    2016-07-04

    Teratogenic alkaloids can cause developmental defects due to the inhibition of fetal movement that results from desensitization of fetal muscle-type nicotinic acetylcholine receptors (nAChRs). We investigated the ability of two known teratogens, the piperidinyl-pyridine anabasine and its 1,2-dehydropiperidinyl analog anabaseine, to activate and desensitize peripheral nAChRs expressed in TE-671 and SH-SY5Y cells. Activation-concentration response curves for each alkaloid were obtained in the same multi-well plate. To measure rapid desensitization, cells were first exposed to five potentially-desensitizing concentrations of each alkaloid in log10 molar increments from 10 nM to 100 µM and then to a fixed concentration of acetylcholine (ACh), which alone produces near-maximal activation. The fifty percent desensitization concentration (DC50) was calculated from the alkaloid concentration-ACh response curve. Agonist fast desensitization potency was predicted by the agonist potency measured in the initial response. Anabaseine was a more potent desensitizer than anabasine. Relative to anabaseine, nicotine was more potent to autonomic nAChRs, but less potent to the fetal neuromuscular nAChRs. Our experiments have demonstrated that anabaseine is more effective at desensitizing fetal muscle-type nAChRs than anabasine or nicotine and, thus, it is predicted to be more teratogenic.

  9. Activation and Desensitization of Peripheral Muscle and Neuronal Nicotinic Acetylcholine Receptors by Selected, Naturally-Occurring Pyridine Alkaloids

    PubMed Central

    Green, Benedict T.; Lee, Stephen T.; Welch, Kevin D.; Cook, Daniel; Kem, William R.

    2016-01-01

    Teratogenic alkaloids can cause developmental defects due to the inhibition of fetal movement that results from desensitization of fetal muscle-type nicotinic acetylcholine receptors (nAChRs). We investigated the ability of two known teratogens, the piperidinyl-pyridine anabasine and its 1,2-dehydropiperidinyl analog anabaseine, to activate and desensitize peripheral nAChRs expressed in TE-671 and SH-SY5Y cells. Activation-concentration response curves for each alkaloid were obtained in the same multi-well plate. To measure rapid desensitization, cells were first exposed to five potentially-desensitizing concentrations of each alkaloid in log10 molar increments from 10 nM to 100 µM and then to a fixed concentration of acetylcholine (ACh), which alone produces near-maximal activation. The fifty percent desensitization concentration (DC50) was calculated from the alkaloid concentration-ACh response curve. Agonist fast desensitization potency was predicted by the agonist potency measured in the initial response. Anabaseine was a more potent desensitizer than anabasine. Relative to anabaseine, nicotine was more potent to autonomic nAChRs, but less potent to the fetal neuromuscular nAChRs. Our experiments have demonstrated that anabaseine is more effective at desensitizing fetal muscle-type nAChRs than anabasine or nicotine and, thus, it is predicted to be more teratogenic. PMID:27384586

  10. Activation and Inhibition of the Receptor Histidine Kinase AgrC Occurs Through Opposite Helical Transduction Motions

    PubMed Central

    Wang, Boyuan; Zhao, Aishan; Novick, Richard; Muir, Tom W.

    2014-01-01

    Summary Staphylococcus aureus virulence is regulated when secreted autoinducing peptides (AIPs) are recognized by a membrane-bound receptor histidine kinase (RHK), AgrC. Some AIPs are agonists of virulence gene expression, while others are antagonists. It is unclear how AIP binding regulates AgrC activity. Here, we reconstitute an AgrC family member, AgrC-I, using nanometer-scale lipid bilayer discs. We show that AgrC-I requires membranes rich in anionic lipids to function. The agonist, AIP-I, binds AgrC-I non-cooperatively in a 2:2 stoichiometry, while an antagonist ligand, AIP-II, functions as an inverse agonist of the kinase activity. We also demonstrate the kinase and sensor domains in AgrC are connected by a helical linker whose conformational state exercises rheostat-like control over the kinase activity. Binding of agonist or inverse-agonist peptides results in twisting of the linker in different directions. These two observations provide a view of the molecular motions triggered by ligand binding in an intact membrane-bound RHK. PMID:24656130

  11. Activation and Desensitization of Peripheral Muscle and Neuronal Nicotinic Acetylcholine Receptors by Selected, Naturally-Occurring Pyridine Alkaloids.

    PubMed

    Green, Benedict T; Lee, Stephen T; Welch, Kevin D; Cook, Daniel; Kem, William R

    2016-01-01

    Teratogenic alkaloids can cause developmental defects due to the inhibition of fetal movement that results from desensitization of fetal muscle-type nicotinic acetylcholine receptors (nAChRs). We investigated the ability of two known teratogens, the piperidinyl-pyridine anabasine and its 1,2-dehydropiperidinyl analog anabaseine, to activate and desensitize peripheral nAChRs expressed in TE-671 and SH-SY5Y cells. Activation-concentration response curves for each alkaloid were obtained in the same multi-well plate. To measure rapid desensitization, cells were first exposed to five potentially-desensitizing concentrations of each alkaloid in log10 molar increments from 10 nM to 100 µM and then to a fixed concentration of acetylcholine (ACh), which alone produces near-maximal activation. The fifty percent desensitization concentration (DC50) was calculated from the alkaloid concentration-ACh response curve. Agonist fast desensitization potency was predicted by the agonist potency measured in the initial response. Anabaseine was a more potent desensitizer than anabasine. Relative to anabaseine, nicotine was more potent to autonomic nAChRs, but less potent to the fetal neuromuscular nAChRs. Our experiments have demonstrated that anabaseine is more effective at desensitizing fetal muscle-type nAChRs than anabasine or nicotine and, thus, it is predicted to be more teratogenic. PMID:27384586

  12. Radio properties of M33 supernova remnants: results from a new deep JVLA Survey

    NASA Astrophysics Data System (ADS)

    Long, Knox S.; White, Richard L.; Becker, Robert H.; Helfand, David J.; Blair, William P.; Winkler, P. Frank

    2016-06-01

    We have carried out new 6 and 20 cm observations of M33 with the Jansky Very Large Array, primarily to study the properties of supernova remnants in the galaxy. Our scaled array observations have a limiting sensitivity of about 25 μJy (5σ) and a resolution of 5`` (FWHM), corresponding to a spatial resolution of 20 pc at the distance of M33. We detect about 85 of the SNRs contained in the list of 137 optically identified SNRs described by Long et al. (2010), and a few additional objects from the survey of Lee & Lee (2014). A substantial fraction of the optical SNRs not detected are in regions where emission from H II recombination makes identification of non-thermal emission from the SNR difficult. We also discuss a blind search for SNRs based on the radio emission alone. Of the SNRs we detect in this search at radio wavelengths, 53 have also been detected at X-ray wavelengths. Thus we are able make a direct comparison of the X-ray, optical, and radio properties of the SNRs in M33, the first time that has been possible to a significant extent in an external spiral galaxy.

  13. THE DEGENERACY OF M33 MASS MODELING AND ITS PHYSICAL IMPLICATIONS

    SciTech Connect

    Hague, P. R.; Wilkinson, M. I. E-mail: miw6@le.ac.uk

    2015-02-10

    The Local Group galaxy M33 exhibits a regular spiral structure and is close enough to permit high resolution analysis of its kinematics, making it an ideal candidate for rotation curve studies of its inner regions. Previous studies have claimed the galaxy has a dark matter halo with an Navarro-Frenk-White profile, based on statistical comparisons with a small number of other profiles. We apply a Bayesian method from our previous paper to place the dark matter density profile in the context of a continuous, and more general, parameter space. For a wide range of initial assumptions we find that models with inner log slope γ{sub in} < 0.9 are strongly excluded by the kinematics of the galaxy unless the mass-to-light ratio of the stellar components in the 3.6 μm band satisfies Y{sub 3.6} ≥ 2. Such a high Y{sub 3.6} is inconsistent with current modeling of the stellar population of M33. This suggests that M33 is a galaxy whose dark matter halo has not been significantly modified by feedback. We discuss possible explanations of this result, including ram pressure stripping during earlier interactions with M31.

  14. On the Neutral Hydrogen Filament Between M31 and M33

    NASA Astrophysics Data System (ADS)

    Lockman, Felix J.; Free, N.; Shields, J. C.

    2012-01-01

    In 2004, Braun & Thilker (B&T) reported the detection of extremely faint 21cm HI emission at the level log10(NH)=17.0 that formed a partial bridge about 200 kpc in extent between M31 and M33. This has been interpreted as the neutral component of a WHIM filament, or the remnant of a past encounter between the two galaxies. B&T used data from the Westerbork Synthesis Radio Telescope, operated as an array of single dishes, to obtain the necessary sensitivity, but at the expense of angular resolution ( 45'). Subsequently, Putman et al (2009) have questioned the existence of this filament, noting its absence from the immediate vicinity of M33 at the level log10(NH) 18 in data from Arecibo. We have reobserved much of the region between M31 and M33 using the Green Bank Telescope (GBT) at 9' resolution, with a 5-sigma sensitivity limit of log10(NHI) 18.0 and a few much deeper pointings. We detect HI lines consistent with the B&T results. In two locations the emission appears at log(NHI)>18.3, suggesting clumping in the otherwise diffuse gas. We estimate the mass of HI in the bridge, and show examples of the GBT's freedom from instrumental effects down to detection levels of log(NHI) 17.0. The National Radio Astronomy Observatory is a facility of the National Science Foundation, operated under a cooperative agreement by Associated Universities, Inc.

  15. Spectroscopic study of formation, evolution and interaction of M31 and M33 with star clusters

    NASA Astrophysics Data System (ADS)

    Fan, Zhou; Yang, Yanbin

    2016-02-01

    The recent studies show that the formation and evolution process of the nearby galaxies are still unclear. By using the Canada France Hawaii Telescope (CFHT) 3.6m telescope, the PanDAS shows complicated substructures (dwarf satellite galaxies, halo globular clusters, extended clusters, star streams, etc.) in the halo of M31 to ~150 kpc from the center of galaxy and M31-M33 interaction has been studied. In our work, we would like to investigate formation, evolution and interaction of M31 and M33, which are the nearest two spiral galaxies in Local Group. The star cluster systems of the two galaxies are good tracers to study the dynamics of the substructures and the interaction. Since 2010, the Xinglong 2.16m, Lijiang 2.4m and MMT 6.5m telescopes have been used for our spectroscopic observations. The radial velocities and Lick absorption-line indices can thus be measured with the spectroscopy and then ages, metallicities and masses of the star clusters can be fitted with the simple stellar population models. These parameters could be used as the input physical parameters for numerical simulations of M31-M33 interaction.

  16. Radial Velocity and Metallicity Determinations for Remote Globular Clusters in M31 and M33

    NASA Astrophysics Data System (ADS)

    Ferguson, Annette; Barmby, Pauline; Cote, Pat; Harris, Bill; Huxor, Avon; Mackey, Dougal; Puzia, Thomas

    2009-08-01

    We propose to determine radial velocities and metallicities for a sample of ~ 20 remote globular clusters (GCs) which we have discovered in the outer halos of the Local Group galaxies M31 and M33. Most of these objects have been uncovered in the course of the PAndAs survey, an international collaboration which is using CFHT/MegaPrime to map more than 300 square degrees in the g and i bands around M31 and M33. The target clusters, all of which have been identified from high- quality imaging (typically ≲ 0.8'' seeing), lie at projected radii of up to 130 kpc from M31 and 30 kpc from M33 and thus lie significantly beyond all previously-known GCs in these systems. Rather intriguingly, many of the new discoveries exhibit either possible associations with halo tidal streams, or show unusual spatial anisotropies with respect to their host galaxy. Velocity and metallicity data for these objects will provide a detailed characterization of the ensemble properties of the outer halo GC populations, and, through the search for kinematic and metallicity correlations within groups of GCs, help determine what fraction of these objects can be attributed to either late or ongoing accretion events. Ultimately, these data will also provide a basis for improved dynamical mass estimates of both galaxies.

  17. Millimeter and submillimeter excess emission in M 33 revealed by Planck and LABOCA

    NASA Astrophysics Data System (ADS)

    Hermelo, I.; Relaño, M.; Lisenfeld, U.; Verley, S.; Kramer, C.; Ruiz-Lara, T.; Boquien, M.; Xilouris, E. M.; Albrecht, M.

    2016-05-01

    Context. Previous studies have shown the existence of an excess of emission at submillimeter (submm) and millimeter (mm) wavelengths in the spectral energy distribution (SED) of many low-metallicity galaxies. The so-called "submm excess", whose origin remains unknown, challenges our understanding of the dust properties in low-metallicity environments. Aims: The goal of the present study is to model separately the emission from the star forming (SF) component and the emission from the diffuse interstellar medium (ISM) in the nearby spiral galaxy M 33 in order to determine whether both components can be well fitted using radiation transfer models or whether there is an excess of submm emission associated with one or both of them. Methods: We decomposed the observed SED of M 33 into its SF and diffuse components. Mid-infrared (MIR) and far-infrared (FIR) fluxes were extracted from Spitzer and Herschel data. At submm and mm wavelengths, we used ground-based observations from APEX to measure the emission from the SF component and data from the Planck space telescope to estimate the diffuse emission. Both components were separately fitted using radiation transfer models based on standard dust properties (i.e., emissivity index β = 2) and a realistic geometry. The large number of previous studies helped us to estimate the thermal radio emission and to constrain an important part of the input parameters of the models. Both modeled SEDs were combined to build the global SED of M 33. In addition, the radiation field necessary to power the dust emission in our modeling was compared with observations from GALEX, Sloan, and Spitzer. Results: Our modeling is able to reproduce the observations at MIR and FIR wavelengths, but we found a strong excess of emission at submm and mm wavelengths where the model expectations severely underestimate the LABOCA and Planck fluxes. We also found that the ultraviolet (UV) radiation escaping the galaxy is 70% higher than the model predictions

  18. The naturally occurring luteinizing hormone surge is diminished in mice lacking estrogen receptor Beta in the ovary.

    PubMed

    Jayes, Friederike L; Burns, Katherine A; Rodriguez, Karina F; Kissling, Grace E; Korach, Kenneth S

    2014-02-01

    Female ESR2-null mice (betaERKO) display defects in ovarian function and are subfertile. Follicular maturation is impaired and explains smaller litters, but betaERKO also produce fewer litters, which may be partially due to inadequate ovulatory signals. To test this, the amplitude and timing of the naturally occurring luteinizing hormone (LH) surge was measured in individual intact betaERKO and wild-type (WT) mice. Vaginal cytology was evaluated daily, and blood samples were taken from mice in proestrus. The amplitude of the LH surge was severely blunted in betaERKO mice compared to WT, but pituitary LH levels revealed no differences. The betaERKO mice did not produce a preovulatory estradiol surge. To determine if the smaller LH surges and the reduced number of litters in betaERKO were due to the lack of ESR2 in the hypothalamic-pituitary axis or due to the absence of ESR2 in the ovary, ovaries were transplanted from WT into betaERKO mice and vice versa. The size of the LH surge was reduced only in mice lacking ESR2 within the ovary, and these mice had fewer litters. Fertility and size of the LH surge were rescued in betaERKO mice receiving a WT ovary. These data provide the first experimental evidence that the LH surge is impaired in betaERKO females and may contribute to their reduced fertility. ESR2 is not necessary within the pituitary and hypothalamus for the generation of a normal LH surge and for normal fertility, but ESR2 is essential within the ovary to provide proper signals.

  19. Evidence for temporal evolution in the M33 disc as traced by its star clusters

    NASA Astrophysics Data System (ADS)

    Beasley, Michael A.; San Roman, Izaskun; Gallart, Carme; Sarajedini, Ata; Aparicio, Antonio

    2015-08-01

    We present precision radial velocities and stellar population parameters for 77 star clusters in the Local Group galaxy M33. Our Gran Telescopio de Canarias and William Herschel Telescope observations sample both young, massive clusters and known/candidate globular clusters (GCs), spanning ages ˜106-1010 yr, and metallicities, [M/H] ˜ -1.7 to solar. The cluster system exhibits an age-metallicity relation; the youngest clusters are the most metal rich. When compared to H I data, clusters with [M/H] ˜ -1.0 and younger than ˜4 Gyr are clearly identified as a disc population. The clusters show evidence for strong time evolution in the disc radial metallicity gradient (d[M/H]dt/dR = 0.03 dex kpc-1 Gyr-1). The oldest clusters have stronger, more negative gradients than the youngest clusters in M33. The clusters also show a clear age-velocity dispersion relation. The line-of-sight velocity dispersions of the clusters increases with age similar to Milky Way open clusters and stars. The general shape of the relation is reproduced by disc heating simulations, and the similarity between the relations in M33 and the Milky Way suggests that heating by substructure and cooling of the interstellar medium both play a role in shaping this relation. We identify 12 `classical' GCs, six of which are newly identified GC candidates. The GCs are more metal rich than Milky Way halo clusters, and show weak rotation. The inner (R < 4.5 kpc) GCs exhibit a steep radial metallicity gradient (d[M/H]/dR = -0.29 ± 0.11 dex kpc-1) and an exponential-like surface density profile. We argue that these inner GCs are thick disc rather than halo objects.

  20. Planetary nebulae search in the outskirts of M33: looking for the farthest candidates

    NASA Astrophysics Data System (ADS)

    Galera Rosillo, Rebeca; Corradi, Romano L. M.; Mampaso Recio, Antonio

    2015-08-01

    The nearby disc galaxy M33 is one of the best laboratories for testing chemical evolution models in galaxies and for understanding disc formation mechanisms. In this galaxy, planetary nebulae (PNe) were previously extensively studied only within a galactocentric radius of 8 kpc.In the framework of a broad study of the population of PNe in Local Group disc galaxies, we present the results of a deep narrow-band imaging of the outer regions of M33, performed using the Wide Field Camera at the 2.5 m Isaac Newton Telescope (INT).The INT images were obtained in the narrow-band filters selecting the [OIII] 5007 Å and Hα 6563 Å lines, plus broad-band filters SDSS g and i. A photometric catalog of around 150000 sources covering a total area of 5 square degrees, and extending out to 2 deg (30 kpc at the adopted distance of 840 kpc) from the centre of the galaxy is presented.PNe candidates are selected in the [OIII]-g vs Hα-r colour-colour diagram as bright emitters in the narrowband filters. A number of candidates with similar colours to those of known PNe, and with an apparent [OIII] magnitude > 21 have been selected for future follow-up. Three of these have been already spectroscopically confirmed at the William Herschel Telescope (WHT).Our survey will improve the knowledge of the PNe population in the outskirts of M33, constraining the properties of its metal-poor halo and of the extended disc substructures that have been proposed to be related to a relatively recent interaction with M31.

  1. Halpha Emission Line Stars in M31, M33 and Seven Local Group Dwarfs

    NASA Astrophysics Data System (ADS)

    McNeill, Reagin T.; Massey, P.; Olsen, K. A.; Hodge, P. W.; Jacoby, G. H.; Blaha, C.; Smith, R. C.; Holmes, S. B.

    2006-12-01

    While there are many ideas as to how differing galactic environments affect the formation and evolution of massive stars, the numbers of stars with known physical properties outside the Milky Way are too scarce to provide much insight. For instance, we have a very poor idea as to the actual number of Luminous Blue Variables (LBVs) in nearby galaxies, since these have mostly been found on the basis of strong photometric variability over a span of a few decades. But, we know that the Galactic LBVs P Cygni and Eta Car had their last major photometric upsets centuries ago. Were these stars located in a nearby galaxy, we might well be unaware of them. In order to help rectify this situation, we have used the recent UBVRI catalogs of M31 and M33 (Massey et al. 2006) and seven dwarf galaxies in the Local Group (Massey et al. 2007) in conjunction with data from narrowband filters centered on Halpha, [SII] and [OIII] to select Halpha emission sources with similar characteristics to the known LBVs. This search uncovered over 300 potential Halpha emission sources in M31 and M33, and 41 potential Halpha emission sources in the dwarf galaxies. Many of the most promising objects in M31 and M33 were observed spectroscopically at WIYN in September, revealing a wealth of new LBVs and Wolf-Rayet stars. In our poster we will outline our selection method and show some of the newly found emission-lined stars. Funding provided by the NSF through grant number AST-0453611.

  2. OBJECT X: THE BRIGHTEST MID-INFRARED POINT SOURCE IN M33

    SciTech Connect

    Khan, Rubab; Stanek, K. Z.; Kochanek, C. S.; Bonanos, A. Z. E-mail: kstanek@astronomy.ohio-state.edu E-mail: bonanos@astro.noa.gr

    2011-05-01

    We discuss the nature of the brightest mid-IR point source (which we dub Object X) in the nearby galaxy M33. Although multi-wavelength data on this object have existed in the literature for some time, it had not previously been recognized as the most luminous mid-IR object in M33 because it is entirely unremarkable in both optical and near-IR light. In the Local Group Galaxies Survey, Object X is a faint red source visible in VRI and H{alpha} but not U or B. It was easily seen at JHK{sub s} in the Two Micron All Sky Survey. It is the brightest point source in all four Spitzer IRAC bands and is also visible in the MIPS 24 {mu}m band. Its bolometric luminosity is {approx}5 x 10{sup 5} L{sub sun}. The source is optically variable on short timescales (tens of days) and is also slightly variable in the mid-IR, indicating that it is a star. Archival photographic plates (from 1949 and 1991) show no optical source, so the star has been obscured for at least half a century. Its properties are similar to those of the Galactic OH/IR star IRC+10420, which has a complex dusty circumstellar structure resulting from episodic low-velocity mass ejections. We propose that Object X is an M {approx}> 30 M{sub sun} evolved star obscured in its own dust ejected during episodic mass-loss events over at least {approx}half a century. It may emerge from its current ultra-short evolutionary phase as a hotter post-red-supergiant star analogous to M33 Var A. The existence and rarity of such objects can be an important probe of a very brief yet eventful stellar evolutionary phase.

  3. The Massive Stellar Population in the Diffuse Ionized Gas of M33

    NASA Technical Reports Server (NTRS)

    Hoopes, Charles G.; Walterbos, Rene A. M.

    1995-01-01

    We compare Far-UV, H alpha, and optical broadband images of the nearby spiral galaxy M33, to investigate the massive stars associated with the diffuse ionized gas. The H-alpha/FUV ratio is higher in HII regions than in the DIG, possibly indicating that an older population ionizes the DIG. The broad-band colors support this conclusion. The HII region population is consistent with a young burst, while the DIG colors resemble an older population with constant star formation. Our results indicate that there may be enough massive field stars to ionize the DIG, without the need for photon leakage from HII regions.

  4. Carbon and oxygen abundance gradients in NGC 300 and M33 from optical recombination lines

    NASA Astrophysics Data System (ADS)

    Toribio San Cipriano, L.; García-Rojas, J.; Esteban, C.; Bresolin, F.; Peimbert, M.

    2016-05-01

    We present deep spectrophotometry of several H II regions in the nearby low-mass spiral galaxies NGC 300 and M33. The data have been taken with Ultraviolet-Visual Echelle Spectrograph and Optical System for Imaging and low-Intermediate-Resolution Integrated Spectroscopy spectrographs attached to the 8-m Very Large Telescope and 10.4-m Gran Telescopio Canarias telescopes, respectively. We have derived precise values of the physical conditions for each object making use of several emission line-intensity ratios. In particular, we have obtained direct determinations of the electron temperature in all the observed objects. We detect pure recombination lines (RLs) of C II and O II in several of the H II regions, permitting to derive their C/H and C/O ratios. We have derived the radial abundance gradient of O for each galaxy making use of collisionally excited lines (CELs) and RLs, as well as the C and N gradients using RLs and CELs, respectively. We obtain the first determination of the C/H gradient of NGC 300 and improve its determination in the case of M33. In both galaxies, the C/H gradients are steeper than those of O/H, leading to negative C/O gradients. Comparing with similar results for other spiral galaxies, we find a strong correlation between the slope of the C/H gradient and MV. We find that some H II regions located close to the isophotal radius (R25) of NGC 300 and M33 show C/O ratios more similar to those typical of dwarf galaxies than those of H II regions in the discs of more massive spirals. This may be related to the absence of flattening of the gradients in the external parts of NGC 300 and M33. Finally, we find very similar N/H gradients in both galaxies and a fair correlation between the slope of the N/H gradient and MV comparing with similar data for a sample of spiral galaxies.

  5. VizieR Online Data Catalog: Star clusters in M33 (Beasley+, 2015)

    NASA Astrophysics Data System (ADS)

    Beasley, M. A.; San, Roman I.; Gallart, G.; Sarajedini, A.; Aparicio, A.

    2015-08-01

    Basic and derived data for M33 cluster sample. This is the full table 2 corresponding to the abbreviated one in the online journal article. Previously confirmed candidates (identified by radial velocities or high-resolution imaging) were observed using OSIRIS on the GTC in long-slit mode during semesters 2010B-2012A. Previously identified star clusters and star cluster candidates identified by San Roman et al. (2010ApJ...720.1674S, Cat. J/ApJ/720/1674) were observed using the WYFFOS/AF2 multifibre instrument on the WHT in La Palma. (1 data file).

  6. Massive Young Star Clusters in M33: Stochastic Star Formation Ruled Out

    NASA Astrophysics Data System (ADS)

    González-Lópezlira, R. A.; Pflamm-Altenburg, J.; Kroupa, P.

    2014-09-01

    It is widely accepted that the distribution function of the masses of young star clusters is universal and can be purely interpreted as a probability density distribution function with a constant upper mass limit. As a result of this picture, the masses of the most massive objects would be exclusively determined by the size of the sample. Conversely we show, with very high confidence, that the masses of the most massive young (< 10 Myr) star clusters in the flocculent galaxy M33 decrease with increasing galactocentric radius, in contradiction with a constant shape and upper mass limit of the cluster mass function. Moreover, by comparing the radial distributions of gas surface densities and highest cluster masses, we find that M_{max} ∝ Σ_{gas, total}^{3.8 ± 0.3}, M_{max} ∝ Σ_{H_2}^{1.2± 0.1} and M_{max} ∝ Σ_{SFR}^{0.9 ± 0.1}. Hence, in M33 we can rule out stochastic star formation. The change of the maximum cluster mass there must be due to physical causes, i.e., very massive star clusters may require special physical conditions, like high gas surface densities, in order to form.

  7. The Herschel view of HII regions in M 33 (HERM33ES)

    NASA Astrophysics Data System (ADS)

    Verley, S.; Relaño, M.; Kramer, C.; Xilouris, E. M.; Boquien, M.; Calzetti, D.; Combes, F.; Buchbender, C.; Braine, J.; Quintana-Lacaci, G.; Tabatabaei, F. S.; Lord, S.; Israel, F.; Stacey, G.; van der Werf, P.

    2010-12-01

    Within the framework of the HERM33ES Key Project (Kramer et al. 2010), using the high resolution and sensitivity of the Herschel photometric data, we study the compact emission in the Local Group spiral galaxy M 33. We present a catalogue of 159 compact emission sources in M 33 identified by SExtractor in the 250 μm SPIRE band which is the one that provides the best spatial resolution. We measure fluxes at 24 μm and Hα for those 159 extracted sources. We find a very strong Pearson correlation coefficient with the MIPS 24 μm emission (r24 = 0.94) and a rather strong correlation with the Hα emission, although with more scatter (rHα = 0.83). Due to the very strong link between the 250 μm compact emission and the 24 μm and Hα emissions, by recovering the star formation rate from standard recipes for H II regions, we are able to provide star formation rate calibrations based on the 250 μm compact emission alone. Finally, the morphological study of a set of three Hα shells shows that there is a displacement between far-ultraviolet and the SPIRE bands, while the Hα structure is in general much more coincident with the cool dust.

  8. Spectral Analyses of the Nearest Persistent Ultraluminous X-Ray Source M 33 X-8

    NASA Astrophysics Data System (ADS)

    Weng, Shan-Shan; Wang, Jun-Xian; Gu, Wei-Min; Lu, Ju-Fu

    2009-12-01

    We provide a detailed analysis of 12 XMM observations of the nearest persistent extragalactic ultraluminous X-ray source (ULX), M 33 X-8. No significant spectral evolution has been detected for the period of the observations, and therefore we combine the individual observations to increase the signal-to-noise ratio for a spectral fitting. The combined spectra are best fitted by a self-consistent p-free disk plus power-law component model with p = 0.571+0.032-0.030, kTin (inner disk temperature) = 1.38+0.09-0.08 keV, and the flux ratio of the p-free disk component to the power-law component being 0.63 : 0.37 in the 0.3-10 keV band. The fitting indicates that the black hole in M 33 X-8 is of ˜10odot, and accretes at a super-Eddington rate (˜1.5LEdd); also, the phase of the accretion disk is close to that of a slim disk (p = 0.5). We report, for the first time, that an extra power-law component is required in addition to the p-free disk model for ULXs. In super-Eddington cases, the power-law component may possibly result from an optically thin inner region of the disk or a Comptonized corona, similar to that of a standard thin disk.

  9. A Spectroscopic Survey of Massive Stars in M31 and M33

    NASA Astrophysics Data System (ADS)

    Massey, Philip; Neugent, Kathryn F.; Smart, Brianna M.

    2016-09-01

    We describe our spectroscopic follow-up to the Local Group Galaxy Survey (LGGS) photometry of M31 and M33. We have obtained new spectroscopy of 1895 stars, allowing us to classify 1496 of them for the first time. Our study has identified many foreground stars, and established membership for hundreds of early- and mid-type supergiants. We have also found nine new candidate luminous blue variables and a previously unrecognized Wolf-Rayet star. We republish the LGGS M31 and M33 catalogs with improved coordinates, and including spectroscopy from the literature and our new results. The spectroscopy in this paper is responsible for the vast majority of the stellar classifications in these two nearby spiral neighbors. The most luminous (and hence massive) of the stars in our sample are early-type B supergiants, as expected; the more massive O stars are more rare and fainter visually, and thus mostly remain unobserved so far. The majority of the unevolved stars in our sample are in the 20-40 M ⊙ range. The spectroscopic observations reported here were obtained at the MMT Observatory, a joint facility of the University of Arizona and the Smithsonian Institution. MMT telescope time was granted by NOAO, through the Telescope System Instrumentation Program (TSIP). TSIP is funded by the National Science Foundation. This paper uses data products produced by the OIR Telescope Data Center, supported by the Smithsonian Astrophysical Observatory.

  10. A Spectroscopic Survey of Massive Stars in M31 and M33

    NASA Astrophysics Data System (ADS)

    Massey, Philip; Neugent, Kathryn F.; Smart, Brianna M.

    2016-09-01

    We describe our spectroscopic follow-up to the Local Group Galaxy Survey (LGGS) photometry of M31 and M33. We have obtained new spectroscopy of 1895 stars, allowing us to classify 1496 of them for the first time. Our study has identified many foreground stars, and established membership for hundreds of early- and mid-type supergiants. We have also found nine new candidate luminous blue variables and a previously unrecognized Wolf–Rayet star. We republish the LGGS M31 and M33 catalogs with improved coordinates, and including spectroscopy from the literature and our new results. The spectroscopy in this paper is responsible for the vast majority of the stellar classifications in these two nearby spiral neighbors. The most luminous (and hence massive) of the stars in our sample are early-type B supergiants, as expected; the more massive O stars are more rare and fainter visually, and thus mostly remain unobserved so far. The majority of the unevolved stars in our sample are in the 20–40 M ⊙ range. The spectroscopic observations reported here were obtained at the MMT Observatory, a joint facility of the University of Arizona and the Smithsonian Institution. MMT telescope time was granted by NOAO, through the Telescope System Instrumentation Program (TSIP). TSIP is funded by the National Science Foundation. This paper uses data products produced by the OIR Telescope Data Center, supported by the Smithsonian Astrophysical Observatory.

  11. The molecular gas content of the nuclear region of M33

    NASA Astrophysics Data System (ADS)

    Wilson, Christine D.; Scoville, Nick

    1989-12-01

    The nearby Sc galaxy M33 has been mapped at half-beamwidth spacing out to a 3.5 arcmin radius in the CO J = 1-0 line using the NRAO 12 m telescope. The map reveals seven large-scale features with sizes of 200-400 pc, and in several cases they are associated with spiral arms. The masses of these structures are insufficient to gravitationally or tidally bind them given their measured sizes and velocity dispersions, and distances from the center of M33. The total mass of molecular hydrogen in the region mapped is 3.4 x 10 to the 7th solar, roughly twice the mass in atomic hydrogen. Within a radius of 800 pc, no evidence is seen for an exponential decrease in the azimuthally averaged molecular hydrogen column density. The rotation curve obtained from the molecular gas agrees well with previous observations, yielding a disk mass of 5 x 10 to the 8th solar, out to a radius of 800 pc and a molecular gas mass total mass ratio of 4 percent.

  12. THE FRACTAL DIMENSION OF STAR-FORMING REGIONS AT DIFFERENT SPATIAL SCALES IN M33

    SciTech Connect

    Sanchez, Nestor; Alfaro, Emilio J.; Anez, Neyda; Odekon, Mary Crone

    2010-09-01

    We study the distribution of stars, H II regions, molecular gas, and individual giant molecular clouds in M33 over a wide range of spatial scales. The clustering strength of these components is systematically estimated through the fractal dimension. We find scale-free behavior at small spatial scales and a transition to a larger correlation dimension (consistent with a nearly uniform distribution) at larger scales. The transition region lies in the range {approx}500-1000 pc. This transition defines a characteristic size that separates the regime of small-scale turbulent motion from that of large-scale galactic dynamics. At small spatial scales, bright young stars and molecular gas are distributed with nearly the same three-dimensional fractal dimension (D {sub f,3D} {approx}< 1.9), whereas fainter stars and H II regions exhibit higher values, D {sub f,3D} {approx_equal} 2.2-2.5. Our results indicate that the interstellar medium in M33 is on average more fragmented and irregular than in the Milky Way.

  13. Dust and gas power spectrum in M 33 (HERM33ES)

    NASA Astrophysics Data System (ADS)

    Combes, F.; Boquien, M.; Kramer, C.; Xilouris, E. M.; Bertoldi, F.; Braine, J.; Buchbender, C.; Calzetti, D.; Gratier, P.; Israel, F.; Koribalski, B.; Lord, S.; Quintana-Lacaci, G.; Relaño, M.; Röllig, M.; Stacey, G.; Tabatabaei, F. S.; Tilanus, R. P. J.; van der Tak, F.; van der Werf, P.; Verley, S.

    2012-03-01

    Power spectra of deprojected images of late-type galaxies in gas or dust emission are very useful diagnostics of the dynamics and stability of their interstellar medium. Previous studies have shown that the power spectra can be approximated as two power laws, a shallow one on large scales (larger than 500 pc) and a steeper one on small scales, with the break between the two corresponding to the line-of-sight thickness of the galaxy disk. The break separates the 3D behavior of the interstellar medium on small scales, controlled by star formation and feedback, from the 2D behavior on large scales, driven by density waves in the disk. The break between these two regimes depends on the thickness of the plane, which is determined by the natural self-gravitating scale of the interstellar medium. We present a thorough analysis of the power spectra of the dust and gas emission at several wavelengths in the nearby galaxy M 33. In particular, we use the recently obtained images at five wavelengths by PACS and SPIRE onboard Herschel. The wide dynamical range (2-3 dex in scale) of most images allows us to clearly determine the change in slopes from -1.5 to -4, with some variations with wavelength. The break scale increases with wavelength from 100 pc at 24 and 100 μm to 350 pc at 500 μm, suggesting that the cool dust lies in a thicker disk than the warm dust, perhaps because of star formation that is more confined to the plane. The slope on small scales tends to be steeper at longer wavelength, meaning that the warmer dust is more concentrated in clumps. Numerical simulations of an isolated late-type galaxy, rich in gas and with no bulge, such as M 33, are carried out to better interpret these observed results. Varying the star formation and feedback parameters, it is possible to obtain a range of power spectra, with two power-law slopes and breaks, that nicelybracket the data. The small-scale power-law does indeed reflect the 3D behavior of the gas layer, steepening

  14. On the nature of candidate luminous blue variables in M 33

    NASA Astrophysics Data System (ADS)

    Clark, J. S.; Castro, N.; Garcia, M.; Herrero, A.; Najarro, F.; Negueruela, I.; Ritchie, B. W.; Smith, K. T.

    2012-05-01

    Context. Luminous blue variables (LBVs) are a class of highly unstable stars that have been proposed to play a critical role in massive stellar evolution as well as being the progenitors of some of the most luminous supernovae known. However the physical processes underlying their characteristic instabilities are currently unknown. Aims: In order to provide observational constraints on this behaviour we have initiated a pilot study of the population of (candidate) LBVs in the Local Group galaxy M 33. Methods: To accomplish this we have obtained new spectra of 18 examples within M 33. These provide a baseline of ≥ 4 yr with respect to previous observations, which is well suited to identifying LBV outbursts. We also employed existing multi-epoch optical and mid-IR surveys of M 33 to further constrain the variability of the sample and search for the presence of dusty ejecta. Results: Combining the datasets reveals that spectroscopic and photometric variability appears common, although in the majority of cases further observations will be needed to distinguish between an origin for this behavour in short lived stochastic wind structure and low level photospheric pulsations or coherent long term LBV excursions. Of the known LBVs we report a hitherto unidentified excursion of M 33 Var C between 2001-5, while the transition of the WNLh star B517 to a cooler B supergiant phase between 1993-2010 implies an LBV classification. Proof-of-concept quantitative model atmosphere analysis is provided for Romano's star; the resultant stellar parameters being consistent with the finding that the LBV excursions of this star are accompanied by changes in bolometric luminosity. The combination of temperature and luminosity of two stars, the BHG [HS80] 110A and the cool hypergiant B324, appear to be in violation of the empirical Humphreys-Davidson limit. Mid-IR observations demonstrate that a number of candidates appear associated with hot circumstellar dust, although no objects as

  15. Velocity resolved [C ii] spectroscopy of the center and the BCLMP 302 region of M 33 (HerM 33es)

    NASA Astrophysics Data System (ADS)

    Mookerjea, B.; Israel, F.; Kramer, C.; Nikola, T.; Braine, J.; Ossenkopf, V.; Röllig, M.; Henkel, C.; van der Werf, P.; van der Tak, F.; Wiedner, M. C.

    2016-02-01

    Context. The forbidden fine structure transition of C+ at 158 μm is one of the major cooling lines of the interstellar medium (ISM). Aims: We aim to understand the contribution of the ionized, atomic, and molecular phases of the ISM to the [C ii] emission from clouds near the dynamical center and the BCLMP302 H ii region in the north of the nearby galaxy M 33 at a spatial resolution of 50 pc. Methods: We combine high-resolution [C ii] spectra taken with the HIFI spectrometer onboard the Herschel satellite with [C ii] Herschel-PACS maps and ground-based observations of CO(2-1) and H i. All data are at a common spatial resolution of 50 pc. Correlation coefficients between the integrated intensities of [C ii], CO(2-1) and H i are estimated from the velocity-integrated PACS data and from the HIFI data. We decomposed the [C ii] spectra in terms of contribution from molecular and atomic gas detected in CO(2-1) and H i, respectively. At a few positions, we estimated the contribution of ionized gas to [C ii] from the emission measure observed at radio wavelengths. Results: In both regions, the center and BCLMP302, the correlation seen in the [C ii], CO(2-1) and H i intensities from structures of all sizes is significantly higher than the highest correlation in intensity obtained when comparing only structures of the same size. The correlations between the intensities of tracers corresponding to the same velocity range as [C ii], differ from the correlation derived from PACS data. Typically, the [C ii] lines have widths intermediate between the narrower CO(2-1) and broader H i line profiles. A comparison of the spectra shows that the relative contribution of molecular and atomic gas traced by CO(2-1) and H i varies substantially between positions and depends mostly on the local physical conditions and geometry. At the positions of the H ii regions, the ionized gas contributes between 10-25% of the observed [C ii] intensity. We estimate that 11-60% and 5-34% of the [C ii

  16. Contributions of the GABAA Receptor α6 Subunit to Phasic and Tonic Inhibition Revealed by a Naturally Occurring Polymorphism in the α6 Gene

    PubMed Central

    Santhakumar, Vijayalakshmi; Hanchar, H. Jacob; Wallner, Martin; Olsen, Richard W.; Otis, Thomas S.

    2007-01-01

    GABAA receptors (GABARs) are heteromultimeric proteins composed of five subunits. The specific subunit composition determines critical properties of a GABAR such as pharmacological sensitivities and whether the receptor contributes to synaptic or extrasynaptic forms of inhibition. Classically, synaptic but not extrasynaptic GABARs are thought to respond to benzodiazepines, whereas the reverse has been suggested for ethanol. To examine the effects of subunit composition on GABAR function in situ, we took advantage of two naturally occurring alleles of the rat gene for GABAR subunit α6 (Gabra6100R and Gabra6100Q). Depending on their subunit partners, these two variants of α6 can lead to differential sensitivities to benzodiazepines and ethanol. An examination of synaptic and extrasynaptic GABA-mediated currents in cerebellar granule cells from Gabra6100R/100R and Gabra6100Q/100Q rats uncovered marked allele-dependent differences in benzodiazepine sensitivity. Unexpectedly, we found that the benzodiazepines flunitrazepam and diazepam enhanced extrasynaptic inhibition mediated by δ subunit-containing GABARs in Gabra6100Q/100Q rats. Complementary experiments on recombinant GABARs confirmed that, at subsaturating [GABA], flunitrazepam potentiates α6/δ subunit-containing GABARs. Based on data and a simple theoretical analysis, we estimate that the average extrasynaptic [GABA] is ∼160 nm in perfused slices. These results (1) demonstrate contributions of α6 subunits to both synaptic and extrasynaptic GABA responses, (2) establish that δ subunit-containing GABARs are benzodiazepine sensitive at subsaturating [GABA] and, (3) provide an empirical estimate of extrasynaptic [GABA] in slices. PMID:16554486

  17. VizieR Online Data Catalog: Multi-resolution images of M33 (Boquien+, 2015)

    NASA Astrophysics Data System (ADS)

    Boquien, M.; Calzetti, D.; Aalto, S.; Boselli, A.; Braine, J.; Buat, V.; Combes, F.; Israel, F.; Kramer, C.; Lord, S.; Relano, M.; Rosolowsky, E.; Stacey, G.; Tabatabaei, F.; van der Tak, F.; van der Werf, P.; Verley, S.; Xilouris, M.

    2015-02-01

    The FITS file contains maps of the flux in star formation tracing bands, maps of the SFR, maps of the attenuation in star formation tracing bands, and a map of the stellar mass of M33, each from a resolution of 8"/pixel to 512"/pixel. The FUV GALEX data from NGS were obtained directly from the GALEX website through GALEXVIEW. The observation was carried out on 25 November 2003 for a total exposure time of 3334s. Hα+[NII] observations were carried out in November 1995 on the Burrel Schmidt telescope at Kitt Peak National Observatory. The observations and the data processing are analysed in detail in Hoopes & Walterbos (2000ApJ...541..597H). The Spitzer IRAC 8um image sensitive to the emission of Polycyclic Aromatic Hydrocarbons (PAH) and the MIPS 24um image sensitive to the emission of Very Small Grains (VSG) were obtained from the NASA Extragalactic Database and have been analysed by Hinz et al. (2004ApJS..154..259H) and Verley et al. (2007A&A...476.1161V, Cat. J/A+A/476/1161). The PACS data at 70um and 100um, which are sensitive to the warm dust heated by massive stars, come from two different programmes. The 100um image was obtained in the context of the Herschel HerM33es open time key project (Kramer et al., 2010A&A...518L..67K, observation ID 1342189079 and 1342189080). The observation was carried out in parallel mode on 7 January 2010 for a duration of 6.3h. It consisted in 2 orthogonal scans at a speed of 20"/s, with a leg length of 7'. The 70um image was obtained as a follow-up open time cycle 2 programme (OT2mboquien4, observation ID 1342247408 and 1342247409). M33 was scanned on 25 June 2012 at a speed of 20"/s in 2 orthogonal directions over 50' with 5 repetitions of this scheme in order to match the depth of the 100um image. The total duration of the observation was 9.9h. The cube, cube.fits files, contains 16 extensions: * FUV * HALPHA * 8 * 24 * 70 * 100 * SFR_FUV * SFR_HALPHA * SFR_24 * SFR_70 * SFR_100 * SFRFUV24 * SFRHALPHA24 * A_FUV * A

  18. A search for globular clusters in more remote areas around M31 and M33 II

    SciTech Connect

    Di Tullio Zinn, Graziella; Zinn, Robert

    2014-04-01

    Using the Sloan Digital Sky Survey (SDSS), ∼900 deg{sup 2} of the sky surrounding M31 and M33 have been searched for globular clusters (GCs) that through galaxy interaction have become unbound from their parent systems and M31 (hence, intergalactic globular clusters, IGCs). This search reached a maximum of ∼500 kpc in projected galactocentric distance (R {sub gc}) from M31. Visual examination of 283,871 SDSS cutout images and of 1143 fits images yielded 320 candidates. This sample was reduced to six GCs and one likely candidate by excluding galaxies on the basis of combinations of their optical, ultraviolet, and infrared colors from the SDSS, the Galaxy Evolution Explorer satellite, and the Wide-field Infrared Survey Explorer satellite, as well as their photometric redshifts from the SDSS. Since these seven objects have 14 kpc ≤ R {sub gc} ≤ 137 kpc, they are more likely to be GCs in the halo of M31 than IGCs. They are all 'classical' as opposed to 'extended' GCs, and they provide further evidence that the remote halo of M31 (R {sub gc} ≥ 50 kpc) contains more GCs of all types and, in particular, far more 'classical' ones than the remote halo of the Milky Way.

  19. A Naturally Occurring Mutation of the Opsin Gene (T4R) in Dogs Affects Glycosylation and Stability of the G Protein-coupled Receptor*

    PubMed Central

    Zhu, Li; Jang, Geeng-Fu; Jastrzebska, Beata; Filipek, Sławomir; Pearce-Kelling, Susan E.; Aguirre, Gustavo D.; Stenkamp, Ronald E.; Acland, Gregory M.; Palczewski, Krzysztof

    2005-01-01

    Rho (rhodopsin; opsin plus 11-cis-retinal) is a prototypical G protein-coupled receptor responsible for the capture of a photon in retinal photoreceptor cells. A large number of mutations in the opsin gene associated with autosomal dominant retinitis pigmentosa have been identified. The naturally occurring T4R opsin mutation in the English mastiff dog leads to a progressive retinal degeneration that closely resembles human retinitis pigmentosa caused by the T4K mutation in the opsin gene. Using genetic approaches and biochemical assays, we explored the properties of the T4R mutant protein. Employing immunoaffinity-purified Rho from affected RHOT4R/T4R dog retina, we found that the mutation abolished glycosylation at Asn2, whereas glycosylation at Asn15 was unaffected, and the mutant opsin localized normally to the rod outer segments. Moreover, we found that T4R Rho* lost its chromophore faster as measured by the decay of meta-rhodopsin II and that it was less resistant to heat denaturation. Detergent-solubilized T4R opsin regenerated poorly and interacted abnormally with the G protein transducin (Gt). Structurally, the mutation affected mainly the “plug” at the intradiscal (extracellular) side of Rho, which is possibly responsible for protecting the chromophore from the access of bulk water. The T4R mutation may represent a novel molecular mechanism of degeneration where the unliganded form of the mutant opsin exerts a detrimental effect by losing its structural integrity. PMID:15459196

  20. A Naturally Occurring Null Variant of the NMDA Type Glutamate Receptor NR3B Subunit Is a Risk Factor of Schizophrenia

    PubMed Central

    Hashimoto, Ryota; Yamamori, Hidenaga; Yasuda, Yuka; Fujimoto, Michiko; Yano-Umeda, Satomi; Saneyoshi, Takeo; Takeda, Masatoshi; Hayashi, Yasunori

    2015-01-01

    Hypofunction of the N-methyl-D-aspartate type glutamate receptor (NMDAR) has been implicated in the pathogenesis of schizophrenia. Here, we investigated the significance of a common human genetic variation of the NMDAR NR3B subunit that inserts 4 bases within the coding region (insCGTT) in the pathogenesis of schizophrenia. The cDNA carrying this polymorphism generates a truncated protein, which is electrophysiologically non-functional in heterologous expression systems. Among 586 schizophrenia patients and 754 healthy controls, insCGTT was significantly overrepresented in patients compared to controls (odds ratio = 1.37, p = 0.035). Among 121 schizophrenia patients and 372 healthy controls, genetic analyses of normal individuals revealed that those carrying insCGTT have a predisposition to schizotypal personality traits (F1,356 = 4.69, p = 0.031). Furthermore, pre-pulse inhibition, a neurobiological trait disturbed in patients with schizophrenia, was significantly impaired in patients carrying insCGTT compared with those with the major allele (F1,116 = 5.72, p = 0.018, F1,238 = 4.46, p = 0.036, respectively). These results indicate that a naturally occurring null variant in NR3B could be a risk factor of schizophrenia. PMID:25768306

  1. THE CHANDRA ACIS SURVEY OF M33: X-RAY, OPTICAL, AND RADIO PROPERTIES OF THE SUPERNOVA REMNANTS

    SciTech Connect

    Long, Knox S.; Ghavamian, Parviz; Blair, William P.; Kuntz, Kip D.; Winkler, P. Frank; McNeil, Emily K.; Becker, Robert H.; Gaetz, Terrance J.; Kirshner, Robert P.; Plucinsky, Paul P.; Tuellmann, Ralph; Helfand, David J.; Saul, Destry; Hughes, John P.; Pannuti, Thomas G.; Williams, Benjamin E-mail: wpb@pha.jhu.edu

    2010-04-01

    M33 contains a large number of emission nebulae identified as supernova remnants (SNRs) based on the high [S II]:H{alpha} ratios characteristic of shocked gas. Using Chandra data from the ChASeM33 survey with a 0.35-2 keV sensitivity of {approx}2 x 10{sup 34} erg s{sup -1}, we have detected 82 of 137 SNR candidates, yielding confirmation of (or at least strongly support for) their SNR identifications. This provides the largest sample of remnants detected at optical and X-ray wavelengths in any galaxy, including the Milky Way. A spectral analysis of the seven X-ray brightest SNRs reveals that two, G98-31 and G98-35, have spectra that appear to indicate enrichment by ejecta from core-collapse supernova explosions. In general, the X-ray-detected SNRs have soft X-ray spectra compared to the vast majority of sources detected along the line of sight to M33. It is unlikely that there are any other undiscovered thermally dominated X-ray SNRs with luminosities in excess of {approx}4 x 10{sup 35} erg s{sup -1} in the portions of M33 covered by the ChASeM33 survey. We have used a combination of new and archival optical and radio observations to attempt to better understand why some objects are detected as X-ray sources and others are not. We have also developed a morphological classification scheme for the optically identified SNRs and discussed the efficacy of this scheme as a predictor of X-ray detectability. Finally, we have compared the SNRs found in M33 to those that have been observed in the Galaxy and the Magellanic Clouds. There are no close analogs of Cas A, Kepler's SNR, Tycho's SNR, or the Crab Nebula in the regions of M33 surveyed, but we have found an X-ray source with a power-law spectrum coincident with a small-diameter radio source that may be the first pulsar-wind nebula recognized in M33.

  2. The Chandra ACIS Survey of M33: X-ray, Optical, and Radio Properties of the Supernova Remnants

    NASA Astrophysics Data System (ADS)

    Long, Knox S.; Blair, William P.; Winkler, P. Frank; Becker, Robert H.; Gaetz, Terrance J.; Ghavamian, Parviz; Helfand, David J.; Hughes, John P.; Kirshner, Robert P.; Kuntz, Kip D.; McNeil, Emily K.; Pannuti, Thomas G.; Plucinsky, Paul P.; Saul, Destry; Tüllmann, Ralph; Williams, Benjamin

    2010-04-01

    M33 contains a large number of emission nebulae identified as supernova remnants (SNRs) based on the high [S II]:Hα ratios characteristic of shocked gas. Using Chandra data from the ChASeM33 survey with a 0.35-2 keV sensitivity of ~2 × 1034 erg s-1, we have detected 82 of 137 SNR candidates, yielding confirmation of (or at least strongly support for) their SNR identifications. This provides the largest sample of remnants detected at optical and X-ray wavelengths in any galaxy, including the Milky Way. A spectral analysis of the seven X-ray brightest SNRs reveals that two, G98-31 and G98-35, have spectra that appear to indicate enrichment by ejecta from core-collapse supernova explosions. In general, the X-ray-detected SNRs have soft X-ray spectra compared to the vast majority of sources detected along the line of sight to M33. It is unlikely that there are any other undiscovered thermally dominated X-ray SNRs with luminosities in excess of ~4 × 1035 erg s-1 in the portions of M33 covered by the ChASeM33 survey. We have used a combination of new and archival optical and radio observations to attempt to better understand why some objects are detected as X-ray sources and others are not. We have also developed a morphological classification scheme for the optically identified SNRs and discussed the efficacy of this scheme as a predictor of X-ray detectability. Finally, we have compared the SNRs found in M33 to those that have been observed in the Galaxy and the Magellanic Clouds. There are no close analogs of Cas A, Kepler's SNR, Tycho's SNR, or the Crab Nebula in the regions of M33 surveyed, but we have found an X-ray source with a power-law spectrum coincident with a small-diameter radio source that may be the first pulsar-wind nebula recognized in M33.

  3. ISO Mid-Infrared Observations of Giant HII Regions in M33

    NASA Technical Reports Server (NTRS)

    Skelton, B. P.; Waller, W. H.; Hodge, P. W.; Boulanger, F.; Cornett, R. H.; Fanelli, M. N.; Lequeux, J.; Stecher, T. P.; Viallefond, F.; Hui, Y.

    1999-01-01

    We present Infrared Space Observatory Camera (ISOCAM) Circular Variable Filter scans of three giant HII regions in M33. IC 133, NGC 595, and CC 93 span a wide range of metallicity, luminosity, nebular excitation, and infrared excess; three other emission regions (CC 43, CC 99, and a region to the northeast of the core of NGC 595) are luminous enough in the mid-infrared to be detected in the observed fields. ISOCAM CVF observations provide spatially resolved observations (5'') of 151 wavelengths between 5.1 and 16.5 microns with a spectral resolution R = 35 to 50. We observe atomic emission lines ([Ne II], [Ne III], and [S IV]), several "unidentified infrared bands" (UIBs; 6.2, 7.7, 8.6, 11.3, 12.0, and 12.7 microns), and in some cases a continuum which rises steeply at longer wavelengths. We conclude that the spectra of these three GHRs are well explained by combinations of ionized gas, PAHs, and very small grains in various proportions and with different spatial distributions. Comparisons between observed ratios of the various UIBs with model ratios indicate that the PAHs in all three of the GHRs are dehydrogenated and that the small PAHs have been destroyed in IC 133 but have survived in NGC 595 and CC 93. The [Ne III]/[Ne II] ratios observed in IC 133 and NGC 595 are consistent with their ages of 5 and 4.5 Myr, respectively; the deduced ionization parameter is higher in IC 133, consistent with its more compact region of emission.

  4. GIANT MOLECULAR CLOUD EVOLUTIONS IN THE NEARBY SPIRAL GALAXY M33

    SciTech Connect

    Miura, Rie E.; Espada, Daniel; Hwang, Narae; Okumura, Sachiko K.; Komugi, Shinya; Nakanishi, Kouichiro; Sawada, Tsuyoshi; Kohno, Kotaro; Tosaki, Tomoka; Kuno, Nario; Hirota, Akihiko; Onodera, Sachiko; Kaneko, Hiroyuki; Kawabe, Ryohei; Muraoka, Kazuyuki; Minamidani, Tetsuhiro

    2012-12-10

    We present a giant molecular cloud (GMC) catalog of M33, containing 71 GMCs in total, based on wide-field and high-sensitivity CO(J = 3-2) observations with a spatial resolution of 100 pc using the ASTE 10 m telescope. Employing archival optical data, we identify 75 young stellar groups (YSGs) from the excess of the surface stellar density, and estimate their ages by comparing with stellar evolution models. A spatial comparison among the GMCs, YSGs, and H II regions enable us to classify GMCs into four categories: Type A, showing no sign of massive star formation (SF); Type B, being associated only with H II regions; Type C, with both H II regions and <10 Myr old YSGs; and Type D, with both H II regions and 10-30 Myr YSGs. Out of 65 GMCs (discarding those at the edges of the observed fields), 1 (1%), 13 (20%), 29 (45%), and 22 (34%) are Types A, B, C, and D, respectively. We interpret these categories as stages in a GMC evolutionary sequence. Assuming that the timescale for each evolutionary stage is proportional to the number of GMCs, the lifetime of a GMC with a mass >10{sup 5} M{sub Sun} is estimated to be 20-40 Myr. In addition, we find that the dense gas fraction as traced by the CO(J = 3-2)/CO(J = 1-0) ratio is enhanced around SF regions. This confirms a scenario where dense gas is preferentially formed around previously generated stars, and will be the fuel for the next stellar generation. In this way, massive SF gradually propagates in a GMC until gas is exhausted.

  5. BREAKDOWN OF KENNICUTT-SCHMIDT LAW AT GIANT MOLECULAR CLOUD SCALES IN M33

    SciTech Connect

    Onodera, Sachiko; Kuno, Nario; Tosaki, Tomoka; Hirota, Akihiko; Kawabe, Ryohei; Kohno, Kotaro; Nakanishi, Kouichiro; Kaneko, Hiroyuki; Sawada, Tsuyoshi; Muraoka, Kazuyuki; Komugi, Shinya; Miura, Rie

    2010-10-20

    We have mapped the northern area (30' x 20') of a Local Group spiral galaxy M33 in {sup 12}CO(J = 1-0) line with the 45 m telescope at the Nobeyama Radio Observatory. Along with H{alpha} and Spitzer 24 {mu}m data, we have investigated the relationship between the surface density of molecular gas mass and that of star formation rate (SFR) in an external galaxy (Kennicutt-Schmidt law) with the highest spatial resolution ({approx}80 pc) to date, which is comparable to scales of giant molecular clouds (GMCs). At positions where CO is significantly detected, the SFR surface density exhibits a wide range of over four orders of magnitude, from {Sigma}{sub SFR} {approx_lt} 10{sup -10} to {approx}10{sup -6} M {sub sun} yr{sup -1} pc{sup -2}, whereas the {Sigma}{sub H{sub 2}} values are mostly within 10-40 M {sub sun} pc{sup -2}. The surface density of gas and that of SFR correlate well at an {approx}1 kpc resolution, but the correlation becomes looser with higher resolution and breaks down at GMC scales. The scatter of the {Sigma}{sub SFR}-{Sigma}{sub H{sub 2}} relationship in the {approx}80 pc resolution results from the variety of star-forming activity among GMCs, which is attributed to the various evolutionary stages of GMCs and to the drift of young clusters from their parent GMCs. This result shows that the Kennicutt-Schmidt law is valid only in scales larger than that of GMCs, when we average the spatial offset between GMCs and star-forming regions, and their various evolutionary stages.

  6. Strong H-alpha Emission Detected in the M33 Nova Candidate PNV J01340288+3035111

    NASA Astrophysics Data System (ADS)

    Hornoch, K.; Vaduvescu, O.; Tudor, V.

    2014-07-01

    We obtained four 240-s narrow-band H-alpha and four 120-s R-band CCD frames of M33 on 2014 July 29.206 and 29.222 UT, respectively, with the 2.5-m Isaac Newton Telescope (INT) + WFC at La Palma under ~1.1" seeing.

  7. Measuring star formation with resolved observations: the test case of M 33

    NASA Astrophysics Data System (ADS)

    Boquien, M.; Calzetti, D.; Aalto, S.; Boselli, A.; Braine, J.; Buat, V.; Combes, F.; Israel, F.; Kramer, C.; Lord, S.; Relaño, M.; Rosolowsky, E.; Stacey, G.; Tabatabaei, F.; van der Tak, F.; van der Werf, P.; Verley, S.; Xilouris, M.

    2015-06-01

    Context. Measuring star formation on a local scale is important to constrain star formation laws. It is not clear yet, however, whether and how the measure of star formation is affected by the spatial scale at which a galaxy is observed. Aims: We wish to understand the impact of the resolution on the determination of the spatially resolved star formation rate (SFR) and other directly associated physical parameters such as the attenuation. Methods: We carried out a multi-scale, pixel-by-pixel study of the nearby galaxy M 33. Assembling FUV, Hα, 8 μm, 24 μm, 70 μm, and 100 μm maps, we have systematically compared the emission in individual bands with various SFR estimators from a resolution of 33 pc to 2084 pc. Results: There are strong, scale-dependent, discrepancies of up to a factor 3 between monochromatic SFR estimators and Hα+24 μm. The scaling factors between individual IR bands and the SFR show a strong dependence on the spatial scale and on the intensity of star formation. Finally, strong variations of the differential reddening between the nebular emission and the stellar continuum are seen, depending on the specific SFR (sSFR) and on the resolution. At the finest spatial scales, there is little differential reddening at high sSFR. The differential reddening increases with decreasing sSFR. At the coarsest spatial scales the differential reddening is compatible with the canonical value found for starburst galaxies. Conclusions: Our results confirm that monochromatic estimators of the SFR are unreliable at scales smaller than 1 kpc. Furthermore, the extension of local calibrations to high-redshift galaxies presents non-trivial challenges because the properties of these systems may be poorly known. The maps (FITS files) and the data cube used in this article are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/578/A8

  8. Chemical evolution models for spiral disks: the Milky Way, M 31, and M 33

    NASA Astrophysics Data System (ADS)

    Marcon-Uchida, M. M.; Matteucci, F.; Costa, R. D. D.

    2010-09-01

    Context. The distribution of chemical abundances and their variation with time are important tools for understanding the chemical evolution of galaxies. In particular, the study of chemical evolution models can improve our understanding of the basic assumptions made when modelling our Galaxy and other spirals. Aims: We test a standard chemical evolution model for spiral disks in the Local Universe and study the influence of a threshold gas density and different efficiencies in the star formation rate (SFR) law on radial gradients of abundance, gas, and SFR. The model is then applied to specific galaxies. Methods: We adopt a one-infall chemical evolution model where the Galactic disk forms inside-out by means of infall of gas, and we test different thresholds and efficiencies in the SFR. The model is scaled to the disk properties of three Local Group galaxies (the Milky Way, M 31 and M 33) by varying its dependence on the star formation efficiency and the timescale for the infall of gas onto the disk. Results: Using this simple model, we are able to reproduce most of the observed constraints available in the literature for the studied galaxies. The radial oxygen abundance gradients and their time evolution are studied in detail. The present day abundance gradients are more sensitive to the threshold than to other parameters, while their temporal evolutions are more dependent on the chosen SFR efficiency. A variable efficiency along the galaxy radius can reproduce the present day gas distribution in the disk of spirals with prominent arms. The steepness in the distribution of stellar surface density differs from massive to lower mass disks, owing to the different star formation histories. Conclusions: The most massive disks seem to have evolved faster (i.e., with more efficient star formation) than the less massive ones, thus suggesting a downsizing in star formation for spirals. The threshold and the efficiency of star formation play a very important role in the

  9. Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors

    PubMed Central

    Lanfumey, Laurence; Cordomí, Arnau; Pastor, Antoni; de La Torre, Rafael; Gasperini, Paola; Navarro, Gemma; Howell, Lesley A.; Pardo, Leonardo; Lluís, Carmen; Canela, Enric I.; McCormick, Peter J.; Maldonado, Rafael; Robledo, Patricia

    2015-01-01

    Activation of cannabinoid CB1 receptors (CB1R) by delta9-tetrahydrocannabinol (THC) produces a variety of negative effects with major consequences in cannabis users that constitute important drawbacks for the use of cannabinoids as therapeutic agents. For this reason, there is a tremendous medical interest in harnessing the beneficial effects of THC. Behavioral studies carried out in mice lacking 5-HT2A receptors (5-HT2AR) revealed a remarkable 5-HT2AR-dependent dissociation in the beneficial antinociceptive effects of THC and its detrimental amnesic properties. We found that specific effects of THC such as memory deficits, anxiolytic-like effects, and social interaction are under the control of 5-HT2AR, but its acute hypolocomotor, hypothermic, anxiogenic, and antinociceptive effects are not. In biochemical studies, we show that CB1R and 5-HT2AR form heteromers that are expressed and functionally active in specific brain regions involved in memory impairment. Remarkably, our functional data shows that costimulation of both receptors by agonists reduces cell signaling, antagonist binding to one receptor blocks signaling of the interacting receptor, and heteromer formation leads to a switch in G-protein coupling for 5-HT2AR from Gq to Gi proteins. Synthetic peptides with the sequence of transmembrane helices 5 and 6 of CB1R, fused to a cell-penetrating peptide, were able to disrupt receptor heteromerization in vivo, leading to a selective abrogation of memory impairments caused by exposure to THC. These data reveal a novel molecular mechanism for the functional interaction between CB1R and 5-HT2AR mediating cognitive impairment. CB1R-5-HT2AR heteromers are thus good targets to dissociate the cognitive deficits induced by THC from its beneficial antinociceptive properties. PMID:26158621

  10. An atlas of H-alpha-emitting regions in M33: A systematic search for SS433 star candidates

    NASA Technical Reports Server (NTRS)

    Calzetti, Daniela; Kinney, Anne L.; Ford, Holland; Doggett, Jesse; Long, Knox S.

    1995-01-01

    We report finding charts and accurate positions for 432 compact H-alpha emitting regions in the Local Group galaxy M 33 (NGC 598), in an effort to isolate candidates for an SS433-like stellar system. The objects were extracted from narrow band images, centered in the rest-frame H-alpha (lambda 6563 A) and in the red continuum at 6100 A. The atlas is complete down to V approximately equal to 20 and includes 279 compact HII regions and 153 line emitting point-like sources. The point-like sources undoubtedly include a variety of objects: very small HII regions, early type stars with intense stellar winds, and Wolf-Rayet stars, but should also contain objects with the characteristics of SS433. This extensive survey of compact H-alpha regions in M 33 is a first step towards the identification of peculiar stellar systems like SS433 in external galaxies.

  11. Spectroscopic Classification of M33N 2015-12b (PNV J01335420+3026108) as a Classical Nova

    NASA Astrophysics Data System (ADS)

    Williams, S. C.; Darnley, M. J.

    2016-01-01

    We obtained a spectrum of nova candidate M33N 2015-12b (PNV J01335420+3026108; see CBAT TOCP) with the SPRAT spectrograph on the 2m Liverpool Telescope (Steele et al. 2004) on 2016 January 4.81 UT. The spectrum shows strong Balmer emission and numerous Fe II lines (including multiplets 27, 28 and 42). Na I (D) and O I (7773 & Aring;) emission lines are also present.

  12. A comparative study of giant molecular clouds in M51, M33, and the Large Magellanic Cloud

    SciTech Connect

    Hughes, Annie; Meidt, Sharon E.; Colombo, Dario; Schinnerer, Eva; Pety, Jerôme; Dumas, Gaëlle; Schuster, Karl F.; Leroy, Adam K.; Dobbs, Clare L.; García-Burillo, Santiago; Thompson, Todd A.; Kramer, Carsten

    2013-12-10

    We compare the properties of giant molecular clouds (GMCs) in M51 identified by the Plateau de Bure Interferometer Whirlpool Arcsecond Survey with GMCs identified in wide-field, high-resolution surveys of CO emission in M33 and the Large Magellanic Cloud (LMC). We find that GMCs in M51 are larger, brighter, and have higher velocity dispersions relative to their sizes than equivalent structures in M33 and the LMC. These differences imply that there are genuine variations in the average mass surface density 〈Σ{sub H{sub 2}}〉 of the different GMC populations. To explain this, we propose that the pressure in the interstellar medium surrounding the GMCs plays a role in regulating their density and velocity dispersion. We find no evidence for a correlation between size and linewidth in M51, M33, or the LMC when the CO emission is decomposed into GMCs, although moderately robust correlations are apparent when regions of contiguous CO emission (with no size limitation) are used. Our work demonstrates that observational bias remains an important obstacle to the identification and study of extragalactic GMC populations using CO emission, especially in molecule-rich galactic environments.

  13. The LOFAR search for radio pulsars and fast transients in M 33, M 81, and M 82

    NASA Astrophysics Data System (ADS)

    Mikhailov, K.; van Leeuwen, J.

    2016-08-01

    Context. The radio pulsar and rotating radio transient populations are only known in and near the Milky Way. Investigating such populations in other galaxies requires deep pulsar and transient searches. We performed 4-h radio observations of nearby galaxies M 33, M 81 and M 82 with LOFAR. Aims: Our main purpose was to characterise the bright end of the pulsar population in other galaxies, and compare it to that of the Milky Way. Methods: We searched for extragalactic radio pulsars through a periodic-pulse search, and for sporadic fast radio transients through a single-pulse search. We coherently combined at most 23 LOFAR Core High-Band Antenna (HBA) stations and covered M 33, M 81, and M 82 in their entirety using multiple tied-array beams. Results: No pulsating sources or single pulses were found. We have, therefore established stricter limits on the extragalactic pulsar flux density at lower frequencies than those obtained in previous Arecibo, GBT, and WSRT searches. Conclusions: We conclude that in nearby galaxies M 33, M 81, and M 82 there are no pulsars shining toward Earth with pseudo luminosities greater than a few times that of the brightest pulsars in our Milky Way.

  14. VizieR Online Data Catalog: Revised LGGS UBVRI photometry of M31 and M33 stars (Massey+, 2016)

    NASA Astrophysics Data System (ADS)

    Massey, P.; Neugent, K. F.; Smart, B. M.

    2016-09-01

    The Local Group Galaxy Survey (LGGS) provides UBVRI plus interference-image photometry of luminous stars in the spiral galaxies M31 and M33, along with those found in seven dwarf systems currently forming massive stars (IC 10, NGC 6822, WLM, Sextans A and B, Pegasus, and Phoenix) with the intent of serving as a starting point for systematic exploration of the stellar content of our nearest neighbors beyond the Magellanic Clouds (MCs; Massey et al. 2006, Cat. J/AJ/131/2478; Massey ey al. 2007, Cat. J/AJ/134/2474; Massey et al. 2007, Cat. J/AJ/133/2393; Massey et al. 2011AJ....141...28M). All of the observations on which our new spectroscopy is based come from the 6.5m MMT telescope used with the 300 fiber positioner Hectospec. This instrument provides a 1° field-of-view, with a choice of two gratings: (1) a 270 line/mm blazed at 5000Å, which covers the entire visible region (3650-9200Å) at once with a resolution of ~5Å, and (2) a 600 line/mm grating blazed 6000Å, which covers 2300Å at one time at a resolution of ~2Å. The fibers have a diameter of 1.5''. The majority of the new observations reported here were obtained with the higher dispersion grating nominally centered at 4800Å but actually covering 3700-6000Å. Some additional new spectral types are those of the Wolf-Rayet stars (non-WRs) found by Neugent & Massey 2011 (Cat. J/ApJ/733/123) and Neugent et al. 2012 (Cat. J/ApJ/759/11); these data were obtained with the lower-dispersion grating, with details reported in that paper. The first year of observations were obtained during the Fall of 2009, with nominally three nights assigned (2009B-0149), but poor weather during the semester meant we obtained only four fields in M31 and one field in M33. Each observation consisted of 3*45 minute exposures. The second year (Fall 2010), two nights were nominally assigned (NOAO 2010B-0260), allowing us to observe three additional fields in M33, two with 3*45 minute exposures and one with 3*40 minute exposures. We

  15. Synergistic activity between the delta-opioid agonist SNC80 and amphetamine occurs via a glutamatergic NMDA-receptor dependent mechanism

    PubMed Central

    Bosse, Kelly E.; Jutkiewicz, Emily M.; Schultz, Kristin N.; Mabrouk, Omar S.; Kennedy, Robert T.; Gnegy, Margaret E.; Traynor, John R.

    2014-01-01

    Glutamate is known to cause the release of dopamine through a Ca2+-sensitive mechanism that involves activation of NMDA ionotropic glutamate receptors. In the current study, we tested the hypothesis that the delta opioid agonist SNC80 acts indirectly, via the glutamatergic system, to enhance both amphetamine-stimulated dopamine efflux from striatal preparations and amphetamine-stimulated locomotor activity. SNC80 increased extracellular glutamate content, which was accompanied by a concurrent decrease in GABA levels. Inhibition of NMDA signaling with the selective antagonist MK801 blocked the enhancement of both amphetamine-induced dopamine efflux and hyperlocomotion observed with SNC80 pretreatment. Addition of exogenous glutamate also potentiated amphetamine-stimulated dopamine efflux in a Mg2+- and MK801-sensitive manner. After removal of Mg2+ to relieve the ion conductance inhibition of NMDA receptors, SNC80 both elicited dopamine release alone and produced a greater enhancement of amphetamine-evoked dopamine efflux. The action of SNC80 to enhance amphetamine-evoked dopamine efflux was mimicked by the GABAB antagonist 2-hydroxysaclofen. These cumulative findings suggest SNC80 modulates amphetamine-stimulated dopamine efflux through an intra-striatal mechanism involving inhibition of GABA transmission leading to the local release of glutamate followed by subsequent activation of NMDA receptors. PMID:24035916

  16. Effects of the xenoestrogen bisphenol A in diencephalic regions of the teleost fish Coris julis occur preferentially via distinct somatostatin receptor subtypes.

    PubMed

    Alo', Raffaella; Facciolo, Rosa Maria; Madeo, Maria; Giusi, Giuseppina; Carelli, Antonio; Canonaco, Marcello

    2005-04-15

    The xenoestrogen bisphenol A, a contaminant used in the manufacturing of polymers for many consumer products, has been shown to mimic estrogenic actions. This xenoestrogen regulates secretion and expression of pituitary lactotrophs plus morphological and structural features of estrogen target tissues in rodents. Recently, ecological hazards produced by bisphenol A have drawn interests towards the effects of this environmental chemical on neurobiological functions of aquatic vertebrates of which little is known. In this study, the effects of bisphenol A on the distribution of the biologically more active somatostatin receptor subtypes in diencephalic regions of the teleost fish Coris julis were assessed using nonpeptide agonists (L-779, 976 and L-817, 818) that are highly selective for subtype(2) and subtype(5), respectively. Bisphenol A proved to be responsible for highly significant increased binding levels of subtype(2) in hypothalamic areas, while markedly decreased levels of subtype(5) were found in these diencephalic areas, as well as in the medial preglomerular nucleus. The extensive distribution of somatostatin receptor subtype(2) and subtype(5) in the teleost diencephalic areas suggests that, like in mammals, this receptor system may not only be involved in enhanced hypophysiotropic neurohormonal functions but might also promote neuroplasticity events.

  17. The metabotropic glutamate receptor, mGlu5, is required for extinction learning that occurs in the absence of a context change.

    PubMed

    André, Marion Agnes Emma; Güntürkün, Onur; Manahan-Vaughan, Denise

    2015-02-01

    The metabotropic glutamate (mGlu) receptors and, in particular, mGlu5 are crucially involved in multiple forms of synaptic plasticity that are believed to underlie explicit memory. MGlu5 is also required for information transfer through neuronal oscillations and for spatial memory. Furthermore, mGlu5 is involved in extinction of implicit forms of learning. This places this receptor in a unique position with regard to information encoding. Here, we explored the role of this receptor in context-dependent extinction learning under constant, or changed, contextual conditions. Animals were trained over 3 days to take a left turn under 25% reward probability in a T-maze with a distinct floor pattern (Context A). On Day 4, they experienced either a floor pattern change (Context B) or the same floor pattern (Context A) in the absence of reward. After acquisition of the task, the animals were returned to the maze once more on Day 5 (Context A, no reward). Treatment with the mGlu5 antagonist, 2-methyl-6-(phenylethynyl) pyridine, before maze exposure on Day 4 completely inhibited extinction learning in the AAA paradigm but had no effect in the ABA paradigm. A subsequent return to the original context (A, on Day 5) revealed successful extinction in the AAA paradigm, but impairment of extinction in the ABA paradigm. These data support that although extinction learning in a new context is unaffected by mGlu5 antagonism, extinction of the consolidated context is impaired. This suggests that mGlu5 is intrinsically involved in enabling learning that once-relevant information is no longer valid.

  18. The LAMOST spectroscopic survey of globular clusters in M31 and M33. I. catalog and new identifications

    NASA Astrophysics Data System (ADS)

    Chen, Bing-Qiu; Liu, Xiao-Wei; Xiang, Mao-Sheng; Yuan, Hai-Bo; Huang, Yang; Huo, Zhi-Ying; Sun, Ning-Chen; Wang, Chun; Ren, Juan-Juan; Zhang, Hua-Wei; Rebassa-Mansergas, Alberto; Yang, Ming; Zhang, Yong; Hou, Yong-Hui; Wang, Yue-Fei

    2015-08-01

    We present a catalog of 908 objects observed with the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) in fields in the vicinity of M31 and M33, targeted as globular clusters (GCs) and candidates. The targets include known GCs and candidates selected from the literature, as well as new candidates selected from the Sloan Digital Sky Survey (SDSS). Analysis shows that 356 of them are likely GCs with various confidence levels, while the remaining ones turn out to be background galaxies and quasars, stars and H ii regions in M31 or foreground Galactic stars. The 356 likely GCs include 298 bona fide GCs and 26 candidates known in the literature. Three candidates, selected from the Revised Bologna Catalog of M31 GCs and candidates (RBC) and one possible cluster from Johnson et al., are confirmed to be bona fide clusters. We search for new GCs in the halo of the M31 among the new candidates selected from the SDSS photometry. Based on radial velocities yielded by LAMOST spectra and visual examination of the SDSS images, we find 28 objects, 5 bona fide and 23 likely GCs. Among the five bona fide GCs, three have been recently discovered independently by others, and the remaining 25 are our new identifications, including two bona fide ones. The newly identified objects fall at projected distances ranging from 13 to 265kpc from M31. Of the two newly discovered bona fide GCs, one is located near M33, probably a GC belonging to M33. The other bona fide GC falls on the Giant Stream with a projected distance of 78 kpc from M31. Of the 23 newly identified likely GCs, one has a projected distance of about 265 kpc from M31 and could be an intergalactic cluster.

  19. The supernova progenitor mass distributions of M31 and M33: further evidence for an upper mass limit

    SciTech Connect

    Jennings, Zachary G.; Weisz, Daniel R.; Williams, Benjamin F.; Dalcanton, Julianne J.; Gilbert, Karoline M.; Fouesneau, Morgan; Murphy, Jeremiah W.; Dolphin, Andrew E. E-mail: adolphin@raytheon.com

    2014-11-10

    Using Hubble Space Telescope photometry to measure star formation histories, we age-date the stellar populations surrounding supernova remnants (SNRs) in M31 and M33. We then apply stellar evolution models to the ages to infer the corresponding masses for their supernova progenitor stars. We analyze 33 M33 SNR progenitors and 29 M31 SNR progenitors in this work. We then combine these measurements with 53 previously published M31 SNR progenitor measurements to bring our total number of progenitor mass estimates to 115. To quantify the mass distributions, we fit power laws of the form dN/dM∝M {sup –α}. Our new larger sample of M31 progenitors follows a distribution with α=4.4{sub −0.4}{sup +0.4}, and the M33 sample follows a distribution with α=3.8{sub −0.5}{sup +0.4}. Thus both samples are consistent within the uncertainties, and the full sample across both galaxies gives α=4.2{sub −0.3}{sup +0.3}. Both the individual and full distributions display a paucity of massive stars when compared to a Salpeter initial mass function, which we would expect to observe if all massive stars exploded as SN that leave behind observable SNR. If we instead fix α = 2.35 and treat the maximum mass as a free parameter, we find M {sub max} ∼ 35-45 M {sub ☉}, indicative of a potential maximum cutoff mass for SN production. Our results suggest that either SNR surveys are biased against finding objects in the youngest (<10 Myr old) regions, or the highest mass stars do not produce SNe.

  20. The Abundance Scatter in M33 from H II Regions: Is There Any Evidence for Azimuthal Metallicity Variations?

    NASA Astrophysics Data System (ADS)

    Bresolin, Fabio

    2011-04-01

    Optical spectra of 25 H II regions in the inner 2 kpc of the M33 disk have been obtained with the Gemini Multi-Object Spectrograph at the Gemini North telescope. The oxygen abundance gradient measured from the detection of the [O III] λ4363 auroral line displays a scatter of approximately 0.06 dex, a much smaller value than recently reported by Rosolowsky & Simon in this galaxy. The analysis of the abundances for a large sample of H II regions derived from the R 23 strong-line indicator confirms that the scatter is small over the full disk of M33, consistent with the measuring uncertainties, and comparable to what is observed in other spiral galaxies. No evidence is therefore found for significant azimuthal variations in the present-day metallicity of the interstellar medium in this galaxy on spatial scales from ~100 pc to a few kpc. A considerable fraction of M33 H II regions with auroral line detections show spectral features revealing sources of hard ionizing radiation (such as He II emission and large [Ne III], [O III] line fluxes). Since R 23 is shown to severely underestimate the oxygen abundances in such cases, care must be taken in chemical abundance studies of extragalactic H II regions based on this strong-line indicator. Based on observations obtained at the Gemini Observatory, which is operated by the Association of Universities for Research in Astronomy, Inc., under a cooperative agreement with the NSF on behalf of the Gemini partnership: the National Science Foundation (United States), the Science and Technology Facilities Council (United Kingdom), the National Research Council (Canada), CONICYT (Chile), the Australian Research Council (Australia), Ministério da Ciência e Tecnologia (Brazil) and Ministerio de Ciencia, Tecnología e Innovación Productiva (Argentina).

  1. Phosphorylation of arylsulphatase A occurs through multiple interactions with the UDP-N-acetylglucosamine-1-phosphotransferase proximal and distal to its retrieval site by the KDEL receptor.

    PubMed Central

    Dittmer, F; von Figura, K

    1999-01-01

    Phosphorylation of oligosaccharides of the lysosomal enzyme arylsulphatase A (ASA), which accumulate in the secretions of cells that mis-sort most of the newly synthesized lysosomal enzymes due to a deficiency of mannose 6-phosphate receptors, was found to be site specific. ASA residing within the secretory route of these cells contains about one third of the incorporated [2-3H]mannose in phosphorylated oligosaccharides. Oligosaccharides carrying two phosphate groups are almost 2-fold less frequent than those with one phosphate group and only a few of the phosphate groups are uncovered. Addition of a KDEL (Lys-Asp-Glu-Leu) retention signal prolongs the residence time of ASA within the secretory route 6-fold, but does not result in more efficient phosphorylation. In contrast, more than 90% of the [2-3H]mannose incorporated into secreted ASA (with or without a KDEL retention signal) is present in phosphorylated oligosaccharides. Those with two phosphate groups are almost twice as frequent as those with one phosphate group and most of the phosphate groups are uncovered. Thus, ASA receives N-acetylglucosamine 1-phosphate groups in a sequential manner at two or more sites located within the secretory route proximal and distal to the site where ASA is retrieved by the KDEL receptor, i.e. proximal to the trans-Golgi. At each of these sites up to two N-acetylglucosamine 1-phosphate groups can be added to a single oligosaccharide. Of several drugs known to inhibit transit of ASA through the secretory route only the ionophore monensin had a major inhibitory effect on phosphorylation, uncovering and sialylation. PMID:10359658

  2. Direct Toll-like receptor-mediated stimulation of hematopoietic stem and progenitor cells occurs in vivo and promotes differentiation toward macrophages.

    PubMed

    Megías, Javier; Yáñez, Alberto; Moriano, Silvia; O'Connor, José-Enrique; Gozalbo, Daniel; Gil, María-Luisa

    2012-07-01

    As Toll-like receptors (TLRs) are expressed by hematopoietic stem and progenitor cells (HSPCs), they may play a role in hematopoiesis in response to pathogens during infection. We show here that TLR2, TLR4, and TLR9 agonists (tripalmitoyl-S-glyceryl-L-Cys-Ser-(Lys)4 [Pam3CSK4], lipopolysaccharide [LPS], and CpG oligodeoxynucleotide [ODN]) induce the in vitro differentiation of purified murine lineage negative cells (Lin(-) ) as well as HSPCs (identified as Lin(-) c-Kit(+) Sca-1(+) IL-7Rα(-) [LKS] cells) toward macrophages (Mph), through a myeloid differentiation factor 88 (MyD88)-dependent pathway. In order to investigate the possible direct interaction of soluble microorganism-associated molecular patterns and TLRs on HSPCs in vivo, we designed a new experimental approach: purified Lin(-) and LKS cells from bone marrow of B6Ly5.1 mice (CD45.1 alloantigen) were transplanted into TLR2(-/-) , TLR4(-/-) , or MyD88(-/-) mice (CD45.2 alloantigen), which were then injected with soluble TLR ligands (Pam3CSK4, LPS, or ODN, respectively). As recipient mouse cells do not recognize the TLR ligands injected, interference by soluble mediators secreted by recipient cells is negligible. Transplanted cells were detected in the spleen and bone marrow of recipient mice, and in response to soluble TLR ligands, cells differentiated preferentially to Mph. These results show, for the first time, that HSPCs may be directly stimulated by TLR agonists in vivo, and that the engagement of these receptors induces differentiation toward Mph. Therefore, HSPCs may sense pathogen or pathogen-derived products directly during infection, inducing a rapid generation of cells of the innate immune system.

  3. The close binary frequency of Wolf-Rayet stars as a function of metallicity in M31 and M33

    SciTech Connect

    Neugent, Kathryn F.; Massey, Philip E-mail: phil.massey@lowell.edu

    2014-07-01

    Massive star evolutionary models generally predict the correct ratio of WC-type and WN-type Wolf-Rayet stars at low metallicities, but underestimate the ratio at higher (solar and above) metallicities. One possible explanation for this failure is perhaps single-star models are not sufficient and Roche-lobe overflow in close binaries is necessary to produce the 'extra' WC stars at higher metallicities. However, this would require the frequency of close massive binaries to be metallicity dependent. Here we test this hypothesis by searching for close Wolf-Rayet binaries in the high metallicity environments of M31 and the center of M33 as well as in the lower metallicity environments of the middle and outer regions of M33. After identifying ∼100 Wolf-Rayet binaries based on radial velocity variations, we conclude that the close binary frequency of Wolf-Rayets is not metallicity dependent and thus other factors must be responsible for the overabundance of WC stars at high metallicities. However, our initial identifications and observations of these close binaries have already been put to good use as we are currently observing additional epochs for eventual orbit and mass determinations.

  4. VizieR Online Data Catalog: Variable stars in M31 & M33. II. LBVs (Humphreys+, 2014)

    NASA Astrophysics Data System (ADS)

    Humphreys, R. M.; Weis, K.; Davidson, K.; Bomans, D. J.; Burggraf, B.

    2016-08-01

    In Paper I (Humphreys et al. 2013ApJ...773...46H), we discussed a small group of intermediate temperature supergiants, the warm hypergiants, and suggested that they were likely post-red supergiants. In this second paper, we review the spectral characteristics, spectral energy distributions (SEDs), circumstellar ejecta, and mass loss of the LBVs, candidate LBVs, emission line stars, and other luminous and variable stars in M31 and M33. The observations (described in paper I) were made in 2010 October with the Hectospec Multi-Object Spectrograph on the 6.5m MMT on Mount Hopkins. A few stars of special interest (5 in M31 and 8 in M33) were also observed with the MODS1 spectrograph on the Large Binocular Telescope (LBT) during commissioning in 2011 September, and in 2012 October and November, and 2013 January. All of the stars for which we have spectra are listed in Table 1 in order of right ascension. (2 data files).

  5. PAndAS IN THE MIST: THE STELLAR AND GASEOUS MASS WITHIN THE HALOS OF M31 AND M33

    SciTech Connect

    Lewis, Geraint F.; Braun, Robert; McConnachie, Alan W.; Irwin, Michael J.; Chapman, Scott C.; Ibata, Rodrigo A.; Martin, Nicolas F.; Ferguson, Annette M. N.; Fardal, Mark; Dubinski, John; Widrow, Larry; Mackey, A. Dougal; Babul, Arif; Tanvir, Nial R.; Rich, Michael

    2013-01-20

    Large-scale surveys of the prominent members of the Local Group have provided compelling evidence for the hierarchical formation of massive galaxies, revealing a wealth of substructure that is thought to be the debris from ancient and ongoing accretion events. In this paper, we compare two extant surveys of the M31-M33 subgroup of galaxies: the Pan-Andromeda Archaeological Survey of the stellar structure, and a combination of observations of the H I gaseous content, detected at 21 cm. Our key finding is a marked lack of spatial correlation between these two components on all scales, with only a few potential overlaps between stars and gas. The paucity of spatial correlation significantly restricts the analysis of kinematic correlations, although there does appear to be H I kinematically associated with the Giant Stellar Stream where it passes the disk of M31. These results demonstrate that different processes must significantly influence the dynamical evolution of the stellar and H I components of substructures, such as ram pressure driving gas away from a purely gravitational path. Detailed modeling of the offset between the stellar and gaseous substructures will provide a determination of the properties of the gaseous halos of M31 and M33.

  6. Growth, photosynthetic efficiency, and biochemical composition of Tetraselmis suecica F&M-M33 grown with LEDs of different colors.

    PubMed

    Abiusi, Fabian; Sampietro, Giacomo; Marturano, Giovanni; Biondi, Natascia; Rodolfi, Liliana; D'Ottavio, Massimo; Tredici, Mario R

    2014-05-01

    The effect of light quality on cell size and cell cycle, growth rate, productivity, photosynthetic efficiency and biomass composition of the marine prasinophyte Tetraselmis suecica F&M-M33 grown in 2-L flat panel photobioreactors illuminated with light emitting diodes (LEDs) of different colors was investigated. Biomass productivity and photosynthetic efficiency were comparable between white and red light, while under blue and green light productivity decreased to less than half and photosynthetic efficiency to about one third. Differences in cell size and number correlated with the cell cycle phase. Under red light cells were smaller and more motile. Chlorophyll content was strongly reduced with red and enhanced with blue light, while carotenoids and gross biomass composition were not affected by light quality. The eicosapentaenoic acid content increased under red light. Red light can substitute white light without affecting productivity of T. suecica F&M-M33, leading to smaller and more motile cells and increased eicosapentaenoic acid content. Red LEDs can thus be profitably used for the production of this microalga for aquaculture.

  7. PAndAS in the Mist: The Stellar and Gaseous Mass within the Halos of M31 and M33

    NASA Astrophysics Data System (ADS)

    Lewis, Geraint F.; Braun, Robert; McConnachie, Alan W.; Irwin, Michael J.; Ibata, Rodrigo A.; Chapman, Scott C.; Ferguson, Annette M. N.; Martin, Nicolas F.; Fardal, Mark; Dubinski, John; Widrow, Larry; Mackey, A. Dougal; Babul, Arif; Tanvir, Nial R.; Rich, Michael

    2013-01-01

    Large-scale surveys of the prominent members of the Local Group have provided compelling evidence for the hierarchical formation of massive galaxies, revealing a wealth of substructure that is thought to be the debris from ancient and ongoing accretion events. In this paper, we compare two extant surveys of the M31-M33 subgroup of galaxies: the Pan-Andromeda Archaeological Survey of the stellar structure, and a combination of observations of the H I gaseous content, detected at 21 cm. Our key finding is a marked lack of spatial correlation between these two components on all scales, with only a few potential overlaps between stars and gas. The paucity of spatial correlation significantly restricts the analysis of kinematic correlations, although there does appear to be H I kinematically associated with the Giant Stellar Stream where it passes the disk of M31. These results demonstrate that different processes must significantly influence the dynamical evolution of the stellar and H I components of substructures, such as ram pressure driving gas away from a purely gravitational path. Detailed modeling of the offset between the stellar and gaseous substructures will provide a determination of the properties of the gaseous halos of M31 and M33.

  8. Internalization of RGD peptide conjugates of near-infrared fluorescent probes in different cell lines occurs via different integrin receptor subtypes

    NASA Astrophysics Data System (ADS)

    Bloch, S.; Xu, B.; Ye, Y.; Liang, K.; Achilefu, S.

    2006-02-01

    Expression of integrin α vβ 3 is upregulated in a number of cancers including colon, pancreas, lung and breast. Previous studies demonstrated that near infrared (NIR) fluorescent probes designed to target α vβ 3 accumulated both in vitro and in vivo in α vβ 3-positive tumor cells. To evaluate the selectivity of some NIR-labeled RGD peptides for α vβ 3, the molecular probes were incubated in different cells, including the α vβ 3-positive U87 and A549 cells, and α vβ 3-negative HT29 cells. Whereas the RGD compounds tested internalized in the A549 cells, their uptake by the HT29 cell line, which is positive for α vβ 5 and α vβ 6, was low. The uptake of these probes in U87 depended on the structural features of the compounds. Further studies with functional blocking antibodies showed that the internalization in the α vβ 3-positive cells may be mediated by different integrin receptor subtypes. The preliminary results suggest that the internalization of linear RGD peptides is mediated by the α vβ 3 heterodimer but rearrangement of the peptide sequence could alter the selectivity of the molecular probes for different integrin subunits in the dimeric α and β proteins. Thus, a careful choice of RGD peptides can be used to monitor the functional status of different integrins in cells and tissues.

  9. Suzaku Investigation into the Nature of the Nearest Ultraluminous X-Ray Source, M33 X-8

    NASA Astrophysics Data System (ADS)

    Isobe, Naoki; Kubota, Aya; Sato, Hiroshi; Mizuno, Tsunefumi

    2012-12-01

    The X-ray spectrum of the nearest ultraluminous X-ray source, M 33 X-8, obtained by Suzaku during 2010 January 11-13, was closely analyzed in order to examine its nature. It is, by far, the only data with the highest signal statistic in the 0.4-10 keV range. Despite being able to reproduce the X-ray spectrum, Comptonization of the disk photons failed to give a physically meaningful solution. A modified version of the multi-color disk model, in which the dependence of the disk temperature on the radius is described as r-p, with p being a free parameter, can also approximate the spectrum. From this model, the innermost disk temperature and bolometric luminosity were obtained as Tin = 2.00+0.06-0.05 keV and Ldisk = 1.36 × 1039 (cos i )-1 erg s-1, respectively, where i is the disk inclination. A small temperature gradient of p = 0.535-0.004-0.005, together with the high disk temperature, is regarded as signatures of the slim accretion disk model, suggesting that M 33 X-8 was accreting at a high mass-accretion rate. With a correction factor for the slim-disk taken into account, the innermost disk radius, Rin = 81.9+5.9-6.5 (cos i )-0.5 km, corresponds to a black-hole mass of M˜ 10⊙ (cos i )-0.5. Accordingly, the bolometric disk luminosity is estimated to be about 80(cos i )-0.5% of the Eddington limit. A numerically calculated slim-disk spectrum was found to reach a similar result. Thus, the extremely super-Eddington luminosity is not required to explain the nature of M 33 X-8. This conclusion is utilized to argue for the existence of intermediate-mass black holes with M gtrsim 100⊙ radiating at the sub/trans-Eddington luminosity, among ultraluminous X-ray sources with Ldisc gtrsim 1040 erg s-1.

  10. Formation of the black-hole binary M33 X-7 through mass exchange in a tight massive system.

    PubMed

    Valsecchi, Francesca; Glebbeek, Evert; Farr, Will M; Fragos, Tassos; Willems, Bart; Orosz, Jerome A; Liu, Jifeng; Kalogera, Vassiliki

    2010-11-01

    The X-ray source M33 X-7 in the nearby galaxy Messier 33 is among the most massive X-ray binary stellar systems known, hosting a rapidly spinning, 15.65M(⊙) black hole orbiting an underluminous, 70M(⊙) main-sequence companion in a slightly eccentric 3.45-day orbit (M(⊙), solar mass). Although post-main-sequence mass transfer explains the masses and tight orbit, it leaves unexplained the observed X-ray luminosity, the star's underluminosity, the black hole's spin and the orbital eccentricity. A common envelope phase, or rotational mixing, could explain the orbit, but the former would lead to a merger and the latter to an overluminous companion. A merger would also ensue if mass transfer to the black hole were invoked for its spin-up. Here we report simulations of evolutionary tracks which reveal that if M33 X-7 started as a primary body of 85M(⊙)-99M(⊙) and a secondary body of 28M(⊙)-32M(⊙), in a 2.8-3.1-d orbit, its observed properties can be consistently explained. In this model, the main-sequence primary transfers part of its envelope to the secondary and loses the rest in a wind; it ends its life as a ∼16M(⊙) helium star with an iron-nickel core that collapses to a black hole (with or without an accompanying supernova). The release of binding energy, and possibly collapse asymmetries, 'kick' the nascent black hole into an eccentric orbit. Wind accretion explains the X-ray luminosity, and the black-hole spin can be natal.

  11. The heating of mid-infrared dust in the nearby galaxy M33: A testbed for tracing galaxy evolution

    SciTech Connect

    Calapa, Marie D.; Calzetti, Daniela; Draine, Bruce T. E-mail: calzetti@astro.umass.edu; and others

    2014-04-01

    Infrared emission is an invaluable tool for quantifying star formation in galaxies. Because the 8 μm polycyclic aromatic hydrocarbon (PAH) emission has been found to correlate with other well-known star formation tracers, it has widely been used as a star formation rate (SFR) tracer. There are, however, studies that challenge the accuracy and reliability of the 8 μm emission as a SFR tracer. Our study, part of the Herschel (Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA) M33 Extended Survey (HERM33ES) open time key program, aims at addressing this issue by analyzing the infrared emission from the nearby spiral galaxy M33 at the high spatial scale of ∼75 pc. Combining data from the Herschel Space Observatory and the Spitzer Space Telescope, we find that the 8 μm emission is better correlated with the 250 μm emission, which traces cold interstellar gas, than with the 24 μm emission. Furthermore, the L(8)/L(250) ratio is more tightly correlated with the 3.6 μm emission, a tracer of evolved stellar populations and stellar mass, than with a combination of Hα and 24 μm emission, a tracer of SFR. The L(8)/L(24) ratio is highly depressed in 24 μm luminous regions, which correlate with known H II regions. We also compare our results with the dust emission models by Draine and Li. We confirm that the depression of 8 μm PAH emission near star-forming regions is higher than what is predicted by models; this is possibly an effect of increased stellar radiation from young stars destroying the dust grains responsible for the 8 μm emission as already suggested by other authors. We find that the majority of the 8 μm emission is fully consistent with heating by the diffuse interstellar medium, similar to what recently determined for the dust emission in M31 by Draine et al. We also find that the fraction of 8 μm emission associated with the diffuse

  12. THE ARAUCARIA PROJECT. A DISTANCE DETERMINATION TO THE LOCAL GROUP SPIRAL M33 FROM NEAR-INFRARED PHOTOMETRY OF CEPHEID VARIABLES

    SciTech Connect

    Gieren, Wolfgang; Pietrzynski, Grzegorz; Graczyk, Dariusz E-mail: pietrzyn@hubble.cfm.udec.cl; and others

    2013-08-10

    Motivated by an amazing range of reported distances to the nearby Local Group spiral galaxy M33, we have obtained deep near-infrared photometry for 26 long-period Cepheids in this galaxy with the ESO Very Large Telescope. From the data, we constructed period-luminosity relations in the J and K bands which together with previous optical VI photometry for the Cepheids by Macri et al. were used to determine the true distance modulus of M33, and the mean reddening affecting the Cepheid sample with the multiwavelength fit method developed in the Araucaria Project. We find a true distance modulus of 24.62 for M33, with a total uncertainty of {+-}0.07 mag which is dominated by the uncertainty on the photometric zero points in our photometry. The reddening is determined as E(B - V) = 0.19 {+-} 0.02, in agreement with the value used by the Hubble Space Telescope Key Project of Freedman et al. but in some discrepancy with other recent determinations based on blue supergiant spectroscopy and an O-type eclipsing binary which yielded lower reddening values. Our derived M33 distance modulus is extremely insensitive to the adopted reddening law. We show that the possible effects of metallicity and crowding on our present distance determination are both at the 1%-2% level and therefore minor contributors to the total uncertainty of our distance result for M33.

  13. Swift-XRT six-year monitoring of the ultraluminous X-ray source M33 X-8

    NASA Astrophysics Data System (ADS)

    La Parola, V.; D'Aí, A.; Cusumano, G.; Mineo, T.

    2015-08-01

    Context. The long-term evolution of ultraluminous X-ray sources (ULX) with their spectral and luminosity variations in time give important clues on the nature of ULX and on the accretion process that powers them. Aims: We report here the results of a Swift-XRT six-year monitoring campaign of the closest example of a persistent ULX, M33 X-8, that extends the monitoring of this source in the soft X-rays to 16 years. The luminosity of this source is a few 1039 erg s-1, marking the faint end of the ULX luminosity function. Methods: We analyzed the set of 15 observations collected during the Swift monitoring. We searched for differences in the spectral parameters at different observing epochs, adopting several models commonly used to fit the X-ray spectra of ULX. Results: The source exhibits flux variations of about 30%. No significant spectral variations are observed during the monitoring. The average 0.5-10 keV spectrum can be well described by a thermal model, either in the form of a slim disk, or as a combination of a Comptonized corona and a standard accretion disk.

  14. The Wolf-Rayet star population in the most massive giant H II regions of M33

    NASA Technical Reports Server (NTRS)

    Drissen, Laurent; Moffat, Anthony F. J.; Shara, Michael M.

    1990-01-01

    Narrow-band images of NGC 604, NGC 595, and NGC 592, the most massive giant H II regions (GHRs) in M33 have been obtained, in order to study their Wolf-Rayet content. These images reveal the presence of nine candidates in NGC 604 (seven WN, two WC), 10 in NGC 595 (nine WN, one WC), and two in NGC 592 (two WN). Precise positions and estimated magnitudes are given for the candidates, half of which have so far been confirmed spectroscopically as genuine W-R stars. The flux in the emission lines of all candidates is comparable to that of normal Galactic W-R stars of similar subtype. A few of the putative superluminous W-R stars are shown to be close visual double or multiple stars; their newly estimated luminosities are now more compatible with those of normal W-R stars. NGC 595 seems to be overabundant in W-R stars for its mass compared to other GHRs, while NGC 604 is normal. Factors influencing the W-R/O number ratio in GHRs are discussed: metallicity and age appear to be the most important.

  15. Evolved Massive Stars in the Local Group. I. Identification of Red Supergiants in NGC 6822, M31, and M33

    NASA Astrophysics Data System (ADS)

    Massey, Philip

    1998-07-01

    Knowledge of the red supergiant (RSG) population of nearby galaxies allows us to probe massive star evolution as a function of metallicity; however, contamination by foreground Galactic dwarfs dominates surveys for red stars in Local Group galaxies beyond the Magellanic Clouds. Model atmospheres predict that low-gravity supergiants will have B-V values that are redder by several tenths of a magnitude than foreground dwarfs at a given V-R color, a result that is largely independent of reddening. We conduct a BVR survey of several fields in the Local Group galaxies NGC 6822, M33, and M31 as well as neighboring control fields and identify RSG candidates from CCD photometry. The survey is complete to V = 20.5, corresponding to MV = -4.5 or an Mbol of -6.3 for the reddest stars. Follow-up spectroscopy at the Ca II triplet of 130 stars is used to demonstrate that our photometric criterion for identifying RSGs is highly successful (96% for stars brighter than V = 19.5; 82% for V = 19.5-20.5). Classification spectra are also obtained for a number of stars in order to calibrate color with spectral type empirically. We find that there is a marked progression in the average (B-V)0 and (V-R)0 colors of RSGs in these three galaxies, with the higher metallicity systems having a later average spectral type, which is consistent with previous findings by Elias, Frogel, & Humphreys for the Milky Way and Magellanic Clouds. More significantly, we find that there is a clear progression with metallicity in the relative number of the highest luminosity RSGs, a trend that is apparent both in absolute visual magnitude and in bolometric luminosity. Thus any use of RSGs as distance indicators requires correction for the metallicity of the parent galaxy. Our findings are in accord with the predictions of the ``Conti scenario'' in which higher metallicities result in higher mass-loss rates, resulting in a star of a given luminosity spending an increasing fraction of its He-burning lifetime as

  16. The LAMOST survey of background quasars in the vicinity of M31 and M33 - III. results from the 2013 regular survey

    NASA Astrophysics Data System (ADS)

    Huo, Zhi-Ying; Liu, Xiao-Wei; Xiang, Mao-Sheng; Shi, Jian-Rong; Yuan, Hai-Bo; Huang, Yang; Zhang, Yong; Hou, Yong-Hui; Wang, Yue-Fei; Yang, Ming

    2015-08-01

    In this work, we report new quasars discovered in fields in the vicinity of the Andromeda (M31) and Triangulum (M33) galaxies with the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST, also called the Guo Shou Jing Telescope) during the 2013 observational season, the second year of the regular survey. In total, 1330 new quasars are discovered in an area of ˜133 deg2 around M31 and M33. With i magnitudes ranging from 14.79 to 20.0 and redshifts from 0.08 to 4.85, the 1330 new quasars represent a significant increase in the number of identified quasars in fields in the vicinity of M31 and M33. Up to now, there have been a total of 1870 quasars discovered by LAMOST in this area. The much enlarged sample of known quasars in this area can potentially be utilized to construct a precise astrometric reference frame for the measurement of minute proper motions of M31, M33 and their associated substructures, which are vital for understanding the formation and evolution of M31, M33 and the Local Group of galaxies. Moreover, in the sample, there are a total of 45, 98 and 225 quasars with i magnitudes brighter than 17.0, 17.5 and 18.0 respectively. In the aforementioned brightness bins, 15, 35 and 84 quasars are reported here for the first time, and 6, 21 and 81 are reported in our pervious work. In addition, 0, 1 and 6 are from the Sloan Digital Sky Survey and 24, 41 and 54 are from the NED database. These bright quasars provide an invaluable sample to study the kinematics and chemistry of the interstellar/intergalactic medium of the Local Group.

  17. OPTICAL SPECTROPHOTOMETRIC MONITORING OF THE EXTREME LUMINOUS BLUE VARIABLE STAR GR 290 (ROMANO's STAR) IN M 33

    SciTech Connect

    Polcaro, V. F.; Viotti, R. F.; Rossi, C.; Galleti, S.; Gualandi, R.; Norci, L.

    2011-01-15

    We study the long-term, S Dor-type variability and the present hot phase of the luminous blue variable (LBV) star GR 290 (Romano's Star) in M 33 in order to investigate possible links between the LBV and the late, nitrogen sequence Wolf-Rayet Stars (WNL) stages of very massive stars. We use intermediate-resolution spectra, obtained with the William Herschel Telescope (WHT) in 2008 December, when GR 290 was at minimum (V = {approx}18.6), as well as new low-resolution spectra and BVRI photometry obtained with the Loiano and Cima Ekar telescopes during 2007-2010. We identify more than 80 emission lines in the 3100-10000 A range covered by the WHT spectra, belonging to different species: the hydrogen Balmer and Paschen series, neutral and ionized helium, C III, N II-III, S IV, Si III-IV, and many forbidden lines of [N II], [O III], [S III], [A III], [Ne III], and [Fe III]. Many lines, especially the He I triplets, show a P Cygni profile with an a-e radial velocity difference of -300 to -500 km s{sup -1}. The shape of the 4630-4713 A emission blend and of other emission lines resembles that of WN9 stars; the blend deconvolution shows that the He II 4686 A has a strong broad component with FWHM {approx_equal} 1700 km s{sup -1}. During 2003-2010 the star underwent large spectral variations, best seen in the 4630-4686 A emission feature. Using the late-WN spectral types of Crowther and Smith, GR 290 apparently varied between the WN11 and WN8-9 spectral types; the hotter the star was the fainter its visual magnitude was. This spectrum-visual luminosity anticorrelation of GR 290 is reminiscent of the behavior of the best-studied LBVs, such as S Dor and AG Car. During the 2008 minimum, we found a significant decrease in bolometric luminosity, which could be attributed to absorption by newly formed circumstellar matter. We suggest that the broad 4686 A line and the optical continuum formed in a central Wolf-Rayet region, while the narrow emission line spectrum originated in an

  18. Luminous and Variable Stars in M31 and M33. I. The Warm Hypergiants and Post-red Supergiant Evolution

    NASA Astrophysics Data System (ADS)

    Humphreys, Roberta M.; Davidson, Kris; Grammer, Skyler; Kneeland, Nathan; Martin, John C.; Weis, Kerstin; Burggraf, Birgitta

    2013-08-01

    The progenitors of Type IIP supernovae (SNe) have an apparent upper limit to their initial masses of about 20 M ⊙, suggesting that the most massive red supergiants evolve to warmer temperatures before their terminal explosion. But very few post-red supergiants are known. We have identified a small group of luminous stars in M31 and M33 that are candidates for post-red supergiant evolution. These stars have A-F-type supergiant absorption line spectra and strong hydrogen emission. Their spectra are also distinguished by the Ca II triplet and [Ca II] doublet in emission formed in a low-density circumstellar environment. They all have significant near- and mid-infrared excess radiation due to free-free emission and thermal emission from dust. We estimate the amount of mass they have shed and discuss their wind parameters and mass loss rates, which range from a few × 10-6 to 10-4 M ⊙ yr-1. On an H-R diagram, these stars will overlap the region of the luminous blue variables (LBVs) at maximum light; however, the warm hypergiants are not LBVs. Their non-spherical winds are not optically thick, and they have not exhibited any significant variability. We suggest, however, that the warm hypergiants may be the progenitors of the "less luminous" LBVs such as R71 and even SN1987A. Based on observations with the Multiple Mirror Telescope, a joint facility of the Smithsonian Institution and the University of Arizona and on observations obtained with the Large Binocular Telescope (LBT), an international collaboration among institutions in the United States, Italy, and Germany. LBT Corporation partners are: The University of Arizona on behalf of the Arizona University system; Istituto Nazionale di Astrofisica, Italy; LBT Beteiligungsgesellschaft, Germany, representing the Max-Planck Society, the Astrophysical Institute Potsdam, and Heidelberg University; The Ohio State University, and The Research Corporation, on behalf of The University of Notre Dame, University of Minnesota

  19. Var C: Long-term photometric and spectral variability of a luminous blue variable in M 33

    NASA Astrophysics Data System (ADS)

    Burggraf, B.; Weis, K.; Bomans, D. J.; Henze, M.; Meusinger, H.; Sholukhova, O.; Zharova, A.; Pellerin, A.; Becker, A.

    2015-09-01

    Aims: So far the highly unstable phase of luminous blue variables (LBVs) has not been understood well. It is still uncertain why and which massive stars enter this phase. Investigating the variabilities by looking for a possible regular or even (semi-)periodic behaviour could give a hint at the underlying mechanism for these variations and might answer the question of where these variabilities originate. Finding out more about the LBV phase also means understanding massive stars better in general, which have (e.g. by enriching the ISM with heavy elements, providing ionising radiation and kinetic energy) a strong and significant influence on the ISM, hence also on their host galaxy. Methods: Photometric and spectroscopic data were taken for the LBV Var C in M 33 to investigate its recent status. In addition, scanned historic plates, archival data, and data from the literature were gathered to trace Var C's behaviour in the past. Its long-term variability and periodicity was investigated. Results: Our investigation of the variability indicates possible (semi-)periodic behaviour with a period of 42.3 years for Var C. That Var C's light curve covers a time span of more than 100 years means that more than two full periods of the cycle are visible. The critical historic maximum around 1905 is less strong but discernible even with the currently rare historic data. The semi-periodic and secular structure of the light curve is similar to the one of LMC R71. Both light curves hint at a new aspect in the evolution of LBVs. Based on observations collected at the Thüringer Landessternwarte (TLS) Tautenburg.Based on observations collected at the Centro Astronómico Hispano Alemán (CAHA) at Calar Alto, operated jointly by the Max-Planck Institut für Astronomie and the Instituto de Astrofísica de Andalucía (CSIC).Tables 2-4, and 6 are available in electronic form at http://www.aanda.org

  20. Luminous and variable stars in M31 and M33. II. Luminous blue variables, candidate LBVs, Fe II emission line stars, and other supergiants

    SciTech Connect

    Humphreys, Roberta M.; Davidson, Kris; Weis, Kerstin; Bomans, D. J.; Burggraf, Birgitta E-mail: kweis@astro.rub.de

    2014-07-20

    An increasing number of non-terminal eruptions are being found in the numerous surveys for optical transients. Very little is known about these giant eruptions, their progenitors and their evolutionary state. A greatly improved census of the likely progenitor class, including the most luminous evolved stars, the luminous blue variables (LBVs), and the warm and cool hypergiants is now needed for a complete picture of the final pre-supernova stages of very massive stars. We have begun a survey of the evolved and unstable luminous star populations in several nearby resolved galaxies. In this second paper on M31 and M33, we review the spectral characteristics, spectral energy distributions, circumstellar ejecta, and evidence for mass loss for 82 luminous and variable stars. We show that many of these stars have warm circumstellar dust including several of the Fe II emission line stars, but conclude that the confirmed LBVs in M31 and M33 do not. The confirmed LBVs have relatively low wind speeds even in their hot, quiescent or visual minimum state compared to the B-type supergiants and Of/WN stars which they spectroscopically resemble. The nature of the Fe II emission line stars and their relation to the LBV state remains uncertain, but some have properties in common with the warm hypergiants and the sgB[e] stars. Several individual stars are discussed in detail. We identify three possible candidate LBVs and three additional post-red supergiant candidates. We suggest that M33-013406.63 (UIT301,B416) is not an LBV/S Dor variable, but is a very luminous late O-type supergiant and one of the most luminous stars or pair of stars in M33.

  1. IgG-Mediated Immune Suppression to Erythrocytes by Polyclonal Antibodies Can Occur in the Absence of Activating or Inhibitory Fcγ Receptors in a Full Mouse Model.

    PubMed

    Bernardo, Lidice; Yu, Honghui; Amash, Alaa; Zimring, James C; Lazarus, Alan H

    2015-09-01

    Polyclonal anti-D has been used to prevent RhD-negative mothers from becoming immunized against RhD positive fetal erythrocytes, and this mechanism has been referred as Ab or IgG-mediated immune suppression (AMIS). Although anti-D has been highly successful, the inhibitory mechanisms remain poorly understood. Two major theories behind AMIS involve the binding of IgG to activating or inhibitory FcγR, which can induce either erythrocyte clearance or immune inhibition, respectively. In this work, we explored the absolute role of activating and inhibitory FcγR in the AMIS mechanism using the HOD mouse model of RBC immunization. HOD mice contain a RBC-specific recombinant protein composed of hen egg lysozyme (HEL), OVA and human transmembrane Duffy Ag, and erythrocytes from HOD mice can stimulate an immune response to HEL. To assess the contribution of activating and inhibitory FcγR to AMIS, C57BL/6 versus FcRγ-chain(-/-) or FcγRIIB(-/-) mice were used as recipients of HOD-RBC alone or together with anti-HEL Abs (i.e., AMIS) and the resulting immune response to HEL evaluated. We show that anti-HEL polyclonal Abs induce the same degree of AMIS effect in mice lacking these IgG binding receptors as compared with wild-type mice. In agreement with this, F(ab')2 fragments of the AMIS Ab also significantly reduced the Ab response to the HOD cells. In conclusion, successful inhibition of in vivo Ab responses to HOD-RBC by polyclonal IgG can occur independently of activating or inhibitory FcγR involvement. These results may have implications for the understanding of RhD prophylaxis.

  2. IgG-Mediated Immune Suppression to Erythrocytes by Polyclonal Antibodies Can Occur in the Absence of Activating or Inhibitory Fcγ Receptors in a Full Mouse Model.

    PubMed

    Bernardo, Lidice; Yu, Honghui; Amash, Alaa; Zimring, James C; Lazarus, Alan H

    2015-09-01

    Polyclonal anti-D has been used to prevent RhD-negative mothers from becoming immunized against RhD positive fetal erythrocytes, and this mechanism has been referred as Ab or IgG-mediated immune suppression (AMIS). Although anti-D has been highly successful, the inhibitory mechanisms remain poorly understood. Two major theories behind AMIS involve the binding of IgG to activating or inhibitory FcγR, which can induce either erythrocyte clearance or immune inhibition, respectively. In this work, we explored the absolute role of activating and inhibitory FcγR in the AMIS mechanism using the HOD mouse model of RBC immunization. HOD mice contain a RBC-specific recombinant protein composed of hen egg lysozyme (HEL), OVA and human transmembrane Duffy Ag, and erythrocytes from HOD mice can stimulate an immune response to HEL. To assess the contribution of activating and inhibitory FcγR to AMIS, C57BL/6 versus FcRγ-chain(-/-) or FcγRIIB(-/-) mice were used as recipients of HOD-RBC alone or together with anti-HEL Abs (i.e., AMIS) and the resulting immune response to HEL evaluated. We show that anti-HEL polyclonal Abs induce the same degree of AMIS effect in mice lacking these IgG binding receptors as compared with wild-type mice. In agreement with this, F(ab')2 fragments of the AMIS Ab also significantly reduced the Ab response to the HOD cells. In conclusion, successful inhibition of in vivo Ab responses to HOD-RBC by polyclonal IgG can occur independently of activating or inhibitory FcγR involvement. These results may have implications for the understanding of RhD prophylaxis. PMID:26188060

  3. Co-Occurring Disorders

    MedlinePlus

    ... Care of You Top Ten Freshman Year Issues Alcohol, Substance Abuse and Depression Winter Break Survival Tips for College Students Implementing ... supporters and consumers in the mental health field. Alcohol and Drug Abuse, Addiction and Co-occurring Disorders: Co-occurring ... In Crisis? Call ...

  4. The identification of extreme asymptotic giant branch stars and red supergiants in M33 with 24 μm variability

    SciTech Connect

    Montiel, Edward J.; Clayton, Geoffrey C.; Johnson, Christopher B.; Srinivasan, Sundar; Engelbracht, Charles W.

    2015-02-01

    We present the first detection of 24 μm variability in 24 sources in the Local Group galaxy M33. These results are based on 4 epochs of Multiband Imaging Photometer for Spitzer observations, which are irregularly spaced over ∼750 days. We find that these sources are constrained exclusively to the Holmberg radius of the galaxy, which increases their chances of being members of M33. We have constructed spectral energy distributions (SEDs) ranging from the optical to the submillimeter to investigate the nature of these objects. We find that 23 of our objects are most likely heavily self-obscured, evolved stars, while the remaining source is the Giant H ii region, NGC 604. We believe that the observed variability is the intrinsic variability of the central star reprocessed through their circumstellar dust shells. Radiative transfer modeling was carried out to determine their likely chemical composition, luminosity, and dust production rate (DPR). As a sample, our modeling has determined an average luminosity of (3.8±0.9)×10{sup 4} L{sub ⊙} and a total DPR of (2.3±0.1)×10{sup −5} M{sub ⊙} yr{sup −1}. Most of the sources, given the high DPRs and short wavelength obscuration, are likely extreme asymptotic giant branch (XAGB) stars. Five of the sources are found to have luminosities above the classical AGB limit (M{sub bol} <−7.1 mag, L > 54,000 L{sub ⊙}), which classifies them as probable red supergiants (RSGs). Almost all of the sources are classified as oxygen-rich. As also seen in the LMC, a significant fraction of the dust in M33 is produced by a handful of XAGB and RSG stars.

  5. Luminous and Variable Stars in M31 and M33. II. Luminous Blue Variables, Candidate LBVs, Fe II Emission Line Stars, and Other Supergiants

    NASA Astrophysics Data System (ADS)

    Humphreys, Roberta M.; Weis, Kerstin; Davidson, Kris; Bomans, D. J.; Burggraf, Birgitta

    2014-07-01

    An increasing number of non-terminal eruptions are being found in the numerous surveys for optical transients. Very little is known about these giant eruptions, their progenitors and their evolutionary state. A greatly improved census of the likely progenitor class, including the most luminous evolved stars, the luminous blue variables (LBVs), and the warm and cool hypergiants is now needed for a complete picture of the final pre-supernova stages of very massive stars. We have begun a survey of the evolved and unstable luminous star populations in several nearby resolved galaxies. In this second paper on M31 and M33, we review the spectral characteristics, spectral energy distributions, circumstellar ejecta, and evidence for mass loss for 82 luminous and variable stars. We show that many of these stars have warm circumstellar dust including several of the Fe II emission line stars, but conclude that the confirmed LBVs in M31 and M33 do not. The confirmed LBVs have relatively low wind speeds even in their hot, quiescent or visual minimum state compared to the B-type supergiants and Of/WN stars which they spectroscopically resemble. The nature of the Fe II emission line stars and their relation to the LBV state remains uncertain, but some have properties in common with the warm hypergiants and the sgB[e] stars. Several individual stars are discussed in detail. We identify three possible candidate LBVs and three additional post-red supergiant candidates. We suggest that M33-013406.63 (UIT301,B416) is not an LBV/S Dor variable, but is a very luminous late O-type supergiant and one of the most luminous stars or pair of stars in M33. Based on observations with the Multiple Mirror Telescope, a joint facility of the Smithsonian Institution and the University of Arizona and on observations obtained with the Large Binocular Telescope (LBT), an international collaboration among institutions in the United States, Italy and Germany. LBT Corporation partners are: The University

  6. "Naturally occurring asbestos

    NASA Astrophysics Data System (ADS)

    Cagnard, F.; Lahondère, D.; Blein, O.; Lahfid, A.; Wille, G.

    2012-04-01

    The term asbestos refers to six silicate minerals from amphibole and serpentine groups. By definition, it consists in bundles of thin and flexible long fibers, with high-tensile strength, and chemical and heat resistance. In contrast to asbestos found within commercial products and mining, the specific term ''naturally occurring asbestos'' (NOA) refers to asbestiform minerals occurring within rocks or soils that can be released by human activities or weathering processes. The fact that the exposure to asbestos is related to lung pathologies is now widely demonstrated (e.g. asbestosis, mesothelioma and lung cancer). However, if health risks associated with exposure to NOA exist, they are not yet well documented. The crystallization of natural asbestos occurs in specific Mg-rich lithologies associated with peculiar structural and metamorphic conditions. By recognizing and combining such specific geologic criteria, the presence or the absence of asbestos in bedrock terrains can be reasonably predicted and maps of NOA hazard can be drawn. We present here new results of geological mapping and petrological study concerning the evaluation of the NOA hazard in the Alps and Corsica, in France. The three folds approach consists in (1) a determination of lithologies with potential NOA from a bibliographic compilation and extraction of target zones from a geological geodatabase (2) a geological mapping of the target zones followed by a petrological characterization of sampled asbestiform minerals in the laboratory (optical microscopy, TEM, SEM, and Raman spectroscopy technics), and (3) the drawing of the final map of NOA hazard, at regional-scale. Occurrence criteria can be retained as follows: 1. NOA are abundant in the internal zones of the Alps and Corsica, especially within ophiolitic complexes. Natural asbestos are mostly concentrated within ultramafic rocks but can also occur within basic lithologies such as Mg-metagabbros, metabasalts and meta-pillow-lavas, 2. Asbestos

  7. The Strange Case of Hubble's V19 in M33: Monitoring the Remarkable Changes and Possible Real-Time Evolution of a Classical Cepheid

    NASA Astrophysics Data System (ADS)

    Engle, Scott G.; Guinan, E.; Macri, L.; Pellerin, A.

    2011-01-01

    In the influential work "A Spiral Nebula as a Stellar System: Messier 33” (Hubble 1926) Edwin Hubble determined the distance to M33 by using 35 Cepheids he discovered. One of those Cepheids was designated V19. Observations revealed V19 to have a 54.7-day period and B-band (converted from photographic magnitudes) light amplitude of 1.1-mag. Its mean B-magnitude was 19.59+/-0.23. Its properties were consistent with the Period-Luminosity Law for M33 derived by Hubble at that time. Follow up observations in 1996-1997 as part of the DIRECT Program (Macri et al. 2001), however, revealed large and surprising changes in the properties of V19. Its mean B-magnitude had risen to 19.05+/-0.05 and its amplitude had fallen to < 0.1-mag. The DIRECT study thoroughly checked for possible misclassifications of the variable or contamination by nearby objects, and found none. For all intents and purposes, V19 was no longer a Classical Cepheid, or at least varying below the detectable levels of the photometry. The only other well-documented instance of Cepheid pulsations declining over time is in the case of Polaris - whose V-band amplitude fell from just over 0.1-mag to below 0.03-mag over the course of a century (Engle et al 2004). Also, a study of Polaris’ visual magnitudes over the past two millennia has shown a possible increase in brightness of 1-mag over the past 1000 years. The changes present in V19 are obviously on a much more dramatic scale. We report on our continuing efforts to monitor the behavior and properties of Hubble's V19 in M33. Photometry has been carried out with the WIYN 3.5-m telescope and the 1.3-m RCT (Robotically Controlled Telescope) at KPNO. It is our hope that these observations will help solve the mystery of V19 and its unprecedented evolutionary behavior. We gratefully acknowledge NASA/HST grant and NSF/RUI grant AST1009903.

  8. Naturally occurring insecticides.

    PubMed Central

    Soloway, S B

    1976-01-01

    Naturally occurring insecticides are abundant and varied in their effects, though but a few are articles of commerce. Even for these, pyrethrum, nicotine, rotenone, hellebore, ryania, and sabadilla, there is a paucity of information on mammalian toxicology and environmental effects. In general, these materials are characterized favorably by low acute toxicity and ready dissipation in nature. Unfavorable aspects of natural insecticides are the contained mixture of active and inactive components and the low active ingredient content on a crop yield basis pointing to a high unit cost. Natural insecticides can serve additionally as leads to unnatural mimics, of which the commercially successful synthetic pyrethroids are prime examples. The chemical nature, relationship of insecticidal activity to chemical structure, occurrence, production, and utilization, registered uses, metabolism, and insect and mammalian toxicity are reviewed. PMID:789058

  9. GAS SURFACE DENSITY, STAR FORMATION RATE SURFACE DENSITY, AND THE MAXIMUM MASS OF YOUNG STAR CLUSTERS IN A DISK GALAXY. I. THE FLOCCULENT GALAXY M 33

    SciTech Connect

    Gonzalez-Lopezlira, Rosa A.; Pflamm-Altenburg, Jan; Kroupa, Pavel

    2012-12-20

    We analyze the relationship between maximum cluster mass M{sub max} and surface densities of total gas ({Sigma}{sub gas}), molecular gas ({Sigma}{sub H{sub 2}}), and star formation rate ({Sigma}{sub SFR}) in the flocculent galaxy M 33, using published gas data and a catalog of more than 600 young star clusters in its disk. By comparing the radial distributions of gas and most massive cluster masses, we find that M{sub max}{proportional_to}{Sigma}{sup 4.7{+-}0.4}{sub gas}, M{sub max}{proportional_to}{Sigma}{sup 1.3{+-}0.1}{sub H{sub 2}}, and M{sub max}{proportional_to}{Sigma}{sup 1.0{+-}0.1}{sub SFR}. We rule out that these correlations result from the size of the sample; hence, the change of the maximum cluster mass must be due to physical causes.

  10. Luminous and Variable Stars in M31 and M33. III. The Yellow and Red Supergiants and Post-red Supergiant Evolution

    NASA Astrophysics Data System (ADS)

    Gordon, Michael S.; Humphreys, Roberta M.; Jones, Terry J.

    2016-07-01

    Recent supernova (SN) and transient surveys have revealed an increasing number of non-terminal stellar eruptions. Though the progenitor class of these eruptions includes the most luminous stars, little is known of the pre-SN mechanics of massive stars in their most evolved state, thus motivating a census of possible progenitors. From surveys of evolved and unstable luminous star populations in nearby galaxies, we select a sample of yellow and red supergiant (RSG) candidates in M31 and M33 for review of their spectral characteristics and spectral energy distributions (SEDs). Since the position of intermediate- and late-type supergiants on the color–magnitude diagram can be heavily contaminated by foreground dwarfs, we employ spectral classification and multi-band photometry from optical and near-infrared surveys to confirm membership. Based on spectroscopic evidence for mass loss and the presence of circumstellar (CS) dust in their SEDs, we find that 30%–40% of the yellow supergiants are likely in a post-RSG state. Comparison with evolutionary tracks shows that these mass-losing, post-RSGs have initial masses between 20 and 40 M ⊙. More than half of the observed RSGs in M31 and M33 are producing dusty CS ejecta. We also identify two new warm hypergiants in M31, J004621.05+421308.06 and J004051.59+403303.00, both of which are likely in a post-RSG state. Based on observations obtained with the Large Binocular Telescope (LBT), an international collaboration among institutions in the United States, Italy, and Germany. LBT Corporation partners are: The University of Arizona on behalf of the Arizona university system; Istituto Nazionale di Astrofisica, Italy; LBT Beteiligungsgesellschaft, Germany, representing the Max-Planck Society, the Astrophysical Institute Potsdam, and Heidelberg University; The Ohio State University, and The Research Corporation, on behalf of The University of Notre Dame, University of Minnesota, and University of Virginia.

  11. Luminous and Variable Stars in M31 and M33. III. The Yellow and Red Supergiants and Post-red Supergiant Evolution

    NASA Astrophysics Data System (ADS)

    Gordon, Michael S.; Humphreys, Roberta M.; Jones, Terry J.

    2016-07-01

    Recent supernova (SN) and transient surveys have revealed an increasing number of non-terminal stellar eruptions. Though the progenitor class of these eruptions includes the most luminous stars, little is known of the pre-SN mechanics of massive stars in their most evolved state, thus motivating a census of possible progenitors. From surveys of evolved and unstable luminous star populations in nearby galaxies, we select a sample of yellow and red supergiant (RSG) candidates in M31 and M33 for review of their spectral characteristics and spectral energy distributions (SEDs). Since the position of intermediate- and late-type supergiants on the color-magnitude diagram can be heavily contaminated by foreground dwarfs, we employ spectral classification and multi-band photometry from optical and near-infrared surveys to confirm membership. Based on spectroscopic evidence for mass loss and the presence of circumstellar (CS) dust in their SEDs, we find that 30%-40% of the yellow supergiants are likely in a post-RSG state. Comparison with evolutionary tracks shows that these mass-losing, post-RSGs have initial masses between 20 and 40 M ⊙. More than half of the observed RSGs in M31 and M33 are producing dusty CS ejecta. We also identify two new warm hypergiants in M31, J004621.05+421308.06 and J004051.59+403303.00, both of which are likely in a post-RSG state. Based on observations obtained with the Large Binocular Telescope (LBT), an international collaboration among institutions in the United States, Italy, and Germany. LBT Corporation partners are: The University of Arizona on behalf of the Arizona university system; Istituto Nazionale di Astrofisica, Italy; LBT Beteiligungsgesellschaft, Germany, representing the Max-Planck Society, the Astrophysical Institute Potsdam, and Heidelberg University; The Ohio State University, and The Research Corporation, on behalf of The University of Notre Dame, University of Minnesota, and University of Virginia.

  12. Role of polycomb group protein cbx2/m33 in meiosis onset and maintenance of chromosome stability in the Mammalian germline.

    PubMed

    Baumann, Claudia; De La Fuente, Rabindranath

    2011-01-01

    Polycomb group proteins (PcG) are major epigenetic regulators, essential for establishing heritable expression patterns of developmental control genes. The mouse PcG family member M33/Cbx2 (Chromobox homolog protein 2) is a component of the Polycomb-Repressive Complex 1 (PRC1). Targeted deletion of Cbx2/M33 in mice results in homeotic transformations of the axial skeleton, growth retardation and male-to-female sex reversal. In this study, we tested whether Cbx2 is involved in the control of chromatin remodeling processes during meiosis. Our analysis revealed sex reversal in 28.6% of XY(-/-) embryos, in which a hypoplastic testis and a contralateral ovary were observed in close proximity to the kidney, while the remaining male mutant fetuses exhibited bilateral testicular hypoplasia. Notably, germ cells recovered from Cbx2((XY-/-)) testes on day 18.5 of fetal development exhibited premature meiosis onset with synaptonemal complex formation suggesting a role for Cbx2 in the control of meiotic entry in male germ cells. Mutant females exhibited small ovaries with significant germ cell loss and a high proportion of oocytes with abnormal synapsis and non-homologous interactions at the pachytene stage as well as formation of univalents at diplotene. These defects were associated with failure to resolve DNA double strand breaks marked by persistent γH2AX and Rad51 foci at the late pachytene stage. Importantly, two factors required for meiotic silencing of asynapsed chromatin, ubiquitinated histone H2A (ubH2A) and the chromatin remodeling protein BRCA1, co-localized with fully synapsed chromosome axes in the majority of Cbx2((-/-)) oocytes. These results provide novel evidence that Cbx2 plays a critical and previously unrecognized role in germ cell viability, meiosis onset and homologous chromosome synapsis in the mammalian germline. PMID:22200029

  13. Naturally Occurring Food Toxins

    PubMed Central

    Dolan, Laurie C.; Matulka, Ray A.; Burdock, George A.

    2010-01-01

    Although many foods contain toxins as a naturally-occurring constituent or, are formed as the result of handling or processing, the incidence of adverse reactions to food is relatively low. The low incidence of adverse effects is the result of some pragmatic solutions by the US Food and Drug Administration (FDA) and other regulatory agencies through the creative use of specifications, action levels, tolerances, warning labels and prohibitions. Manufacturers have also played a role by setting limits on certain substances and developing mitigation procedures for process-induced toxins. Regardless of measures taken by regulators and food producers to protect consumers from natural food toxins, consumption of small levels of these materials is unavoidable. Although the risk for toxicity due to consumption of food toxins is fairly low, there is always the possibility of toxicity due to contamination, overconsumption, allergy or an unpredictable idiosyncratic response. The purpose of this review is to provide a toxicological and regulatory overview of some of the toxins present in some commonly consumed foods, and where possible, discuss the steps that have been taken to reduce consumer exposure, many of which are possible because of the unique process of food regulation in the United States. PMID:22069686

  14. Serotonin 5-HT3 Receptor-Mediated Vomiting Occurs via the Activation of Ca2+/CaMKII-Dependent ERK1/2 Signaling in the Least Shrew (Cryptotis parva)

    PubMed Central

    Zhong, Weixia; Hutchinson, Tarun E.; Chebolu, Seetha; Darmani, Nissar A.

    2014-01-01

    Stimulation of 5-HT3 receptors (5-HT3Rs) by 2-methylserotonin (2-Me-5-HT), a selective 5-HT3 receptor agonist, can induce vomiting. However, downstream signaling pathways for the induced emesis remain unknown. The 5-HT3R channel has high permeability to extracellular calcium (Ca2+) and upon stimulation allows increased Ca2+ influx. We examined the contribution of Ca2+/calmodulin-dependent protein kinase IIα (Ca2+/CaMKIIα), interaction of 5-HT3R with calmodulin, and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling to 2-Me-5-HT-induced emesis in the least shrew. Using fluo-4 AM dye, we found that 2-Me-5-HT augments intracellular Ca2+ levels in brainstem slices and that the selective 5-HT3R antagonist palonosetron, can abolish the induced Ca2+ signaling. Pre-treatment of shrews with either: i) amlodipine, an antagonist of L-type Ca2+ channels present on the cell membrane; ii) dantrolene, an inhibitor of ryanodine receptors (RyRs) Ca2+-release channels located on the endoplasmic reticulum (ER); iii) a combination of their less-effective doses; or iv) inhibitors of CaMKII (KN93) and ERK1/2 (PD98059); dose-dependently suppressed emesis caused by 2-Me-5-HT. Administration of 2-Me-5-HT also significantly: i) enhanced the interaction of 5-HT3R with calmodulin in the brainstem as revealed by immunoprecipitation, as well as their colocalization in the area postrema (brainstem) and small intestine by immunohistochemistry; and ii) activated CaMKIIα in brainstem and in isolated enterochromaffin cells of the small intestine as shown by Western blot and immunocytochemistry. These effects were suppressed by palonosetron. 2-Me-5-HT also activated ERK1/2 in brainstem, which was abrogated by palonosetron, KN93, PD98059, amlodipine, dantrolene, or a combination of amlodipine plus dantrolene. However, blockade of ER inositol-1, 4, 5-triphosphate receptors by 2-APB, had no significant effect on the discussed behavioral and biochemical parameters. This study demonstrates

  15. RCT photometry of the Hubble Classical Cepheid V19 in M33: Evidence for the Cessation of Pulsations - A Case of Stellar Evolution in Real Time

    NASA Astrophysics Data System (ADS)

    Engle, Scott G.; Guinan, Edward F.; Macri, Lucas; Pellerin, Ann

    2011-03-01

    We report on our continuing efforts to monitor the photometric behavior of Hubble's Variable Star V19 in the Triangulum Spiral Galaxy M33. B,V photometry has been carried out of this unusual 18th mag (previous) Cepheid with the 1.3-m RCT (Robotically Controlled Telescope) at KPNO. With time-series photometry, with a dedicated robotic telescope, we can hope to solve the mystery of V19 and its unprecedented evolutionary behavior. In the influential work "A Spiral Nebula as a Stellar System: Messier 33" (Hubble 1926) Edwin Hubble determined the distance to M33 by using 35 Cepheids he discovered. One of those Cepheids was designated V19. At that time observations revealed V19 to have a 54.7-day period and B-band (converted from photographic magnitudes) light amplitude of 1.1-mag. Its mean B-magnitude was 19.6 /-0.2. V19 properties were consistent with the Period-Luminosity Law for M33 derived by Hubble at that time. Follow-up observations in 1996-1997 as part of the DIRECT Program (Macri et al. 2001), however, revealed large and surprising changes in the properties of V19. Its mean B-magnitude had risen to 19.05 /-0.05 and its amplitude had decreased to less than 0.1-mag. The DIRECT study thoroughly checked for possible misclassifications of the variable or contamination by nearby objects, and found none. For all intents and purposes, V19 is no longer a Classical Cepheid, or at least varying below the detectable levels of the photometry. The only other well-documented instance of Cepheid pulsations declining over time is in the case of Polaris - whose V-band amplitude decreased from just over 0.1-mag to below 0.03-mag over the course of a century (Engle et al 2004). Also, a study of the visual magnitudes of Polaris over the past two millennia has shown a possible increase in brightness of 1-mag over the past 1000 years. The changes observed for V19 are obviously on a much more dramatic scale. We discuss the properties of this unusual (former) Cepheid and discuss

  16. CONSTRAINTS ON THE COMPACT OBJECT MASS IN THE ECLIPSING HIGH-MASS X-RAY BINARY XMMU J013236.7+303228 IN M 33

    SciTech Connect

    Bhalerao, Varun B.; Harrison, Fiona A.; Van Kerkwijk, Marten H.

    2012-09-20

    We present optical spectroscopic measurements of the eclipsing high-mass X-ray binary (HMXB) XMMU J013236.7+303228 in M 33. Based on spectra taken at multiple epochs of the 1.73 day binary orbital period we determine physical as well as orbital parameters for the donor star. We find the donor to be a B1.5IV subgiant with effective temperature T = 22, 000-23, 000 K. From the luminosity, temperature, and known distance to M 33 we derive a radius of R 8.9 {+-} 0.5 R{sub Sun }. From the radial-velocity measurements, we determine a velocity semi-amplitude of K{sub opt} = 63 {+-} 12 km s{sup -1}. Using the physical properties of the B star determined from the optical spectrum, we estimate the star's mass to be M{sub opt} = 11 {+-} 1 M{sub Sun }. Based on the X-ray spectrum, the compact companion is likely a neutron star, although no pulsations have yet been detected. Using the spectroscopically derived B star mass we find the neutron star companion mass to be M{sub X} = 2.0 {+-} 0.4 M{sub Sun }, consistent with the neutron star mass in the HMXB Vela X-1, but heavier than the canonical value of 1.4 M{sub Sun} found for many millisecond pulsars. We attempt to use as an additional constraint that the B star radius inferred from temperature, flux, and distance should equate to the Roche radius, since the system accretes by Roche lobe overflow. This leads to substantially larger masses, but by trying to apply the technique to known systems, we find that the masses are consistently overestimated. Attempting to account for that in our uncertainties, we derive M{sub X} = 2.2{sup +0.8}{sub -0.6} M{sub Sun} and M{sub opt} = 13 {+-} 4 M{sub Sun }. We conclude that precise constraints require detailed modeling of the shape of the Roche surface.

  17. Circumstantial Starbirth in Starbursts: Systematic Variations in the Stellar and Nebular Content of Giant HII Regions in the Local Group Galaxy M33

    NASA Astrophysics Data System (ADS)

    Waller, W. H.; Murphy, E. J.; Gherz, R. D.; Polomski, E.; Woodward, C. E.; Fazio, G. G.; Rieke, G. H.; Spitzer/M33 Research Team

    2005-12-01

    From the Orion Nebula to the Hubble Deep Field, starburst activity can be seen transforming galaxian clouds of gas into populous clusters of stars. The pyrotechnics and chemical enrichment associated with this activity have led to outcomes as ubiquitous as interstellar dust and as exquisite as life on Earth. In this talk, I will focus on the circumstances of star formation in the environmental context of ongoing starburst activity. I begin with the premises that (1) the formation of a single star takes time, (2) the formation of a populous cluster takes even more time, and (3) ''stuff'' happens in the interim. Hubble images of the Orion Nebula and Eagle Nebula show how hot stars can excavate neighboring clouds of gas and photoevaporate the star-forming cores that are exposed. Hubble observations of giant HII regions in M33 reveal a significant variation in the stellar populations, such that the most metal-rich HII regions contain the greatest proportions of the most massive stars. ISO and Spitzer observations of these same HII regions reveal corresponding variations in the nebular content. These multi-wavelength diagnostics of the stellar-nebular feedback in galaxian starbursts suggest a star-forming mechanism which is subject to photo-evaporative ablation -- an erosive process that is systematically mediated by the metal abundance and corresponding amounts of protective dust in the starbursting environment.

  18. Numerical computation of gravitational field of infinitely thin axisymmetric disc with arbitrary surface mass density profile and its application to preliminary study of rotation curve of M33

    NASA Astrophysics Data System (ADS)

    Fukushima, Toshio

    2016-03-01

    We developed a numerical method to compute the gravitational field of an infinitely thin axisymmetric disc with an arbitrary surface mass density profile. We evaluate the gravitational potential by a split quadrature using the double exponential rule and obtain the acceleration vector by numerically differentiating the potential by Ridder's algorithm. The new method is of around 12 digit accuracy and sufficiently fast because requiring only one-dimensional integration. By using the new method, we show the rotation curves of some non-trivial discs: (i) truncated power-law discs, (ii) discs with a non-negligible centre hole, (iii) truncated Mestel discs with edge softening, (iv) double power-law discs, (v) exponentially damped power-law discs, and (vi) an exponential disc with a sinusoidal modulation of the density profile. Also, we present a couple of model fittings to the observed rotation curve of M33: (i) the standard deconvolution by assuming a spherical distribution of the dark matter and (ii) a direct fit of infinitely thin disc mass with a double power-law distribution of the surface mass density. Although the number of free parameters is a little larger, the latter model provides a significantly better fit. The FORTRAN 90 programs of the new method are electronically available.

  19. Hepatocellular hypertrophy and cell proliferation in Sprague-Dawley rats following dietary exposure to ammonium perfluorooctanoate occurs through increased activation of the xenosensor nuclear receptors PPARα and CAR/PXR.

    PubMed

    Elcombe, Clifford R; Elcombe, Barbara M; Foster, John R; Farrar, David G; Jung, Reinhard; Chang, Shu-Ching; Kennedy, Gerald L; Butenhoff, John L

    2010-10-01

    Ammonium perfluorooctanoate (APFO), a processing aid used in the production of fluoropolymers, produces hepatomegaly and hepatocellular hypertrophy in rodents. In mice, APFO-induced hepatomegaly is associated with increased activation of the xenosensor nuclear receptors, PPARα and CAR/PXR. Although non-genotoxic, chronic dietary treatment of Sprague-Dawley (S-D) rats with APFO produced an increase in benign tumours of the liver, acinar pancreas, and testicular Leydig cells. Most of the criteria for establishing a PPARα-mediated mode of action for the observed hepatocellular tumours have been previously established with the exception of the demonstration of increased hepatocellular proliferation. The present study evaluates the potential roles for APFO-induced activation of PPARα and CAR/PXR with respect to liver tumour production in the S-D rat and when compared to the specific PPARα agonist, 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid (Wy 14,643). Male S-D rats were fed APFO (300 ppm in diet) or Wy 14,643 (50 ppm in diet) for either 1, 7, or 28 days. Effects of treatment with APFO included: decreased body weight; hepatomegaly, hepatocellular hypertrophy, hepatocellular hyperplasia (microscopically and by BrdU labelling index), and hepatocellular glycogen loss; increased activation of PPARα (peroxisomal β-oxidation and microsomal CYP4A1 protein); decreased plasma triglycerides, cholesterol, and glucose; increased activation of CAR (CYP2B1/2 protein) and CAR/PXR (CYP3A1 protein). Responses to treatment with Wy 14,643 were consistent with increased activation of PPARα, specifically: increased CYP4A1 and peroxisomal β-oxidation; increased hepatocellular hypertrophy and cell proliferation; decreased apoptosis; and hypolipidaemia. With the exception of decreased apoptosis, the effects observed with Wy 14,643 were noted with APFO, and APFO was less potent. These data clearly demonstrate an early hepatocellular proliferative response to APFO

  20. APERTURE SYNTHESIS OBSERVATIONS OF CO, HCN, AND 89 GHz CONTINUUM EMISSION TOWARD NGC 604 IN M33: SEQUENTIAL STAR FORMATION INDUCED BY A SUPERGIANT H II REGION

    SciTech Connect

    Miura, Rie; Okumura, Sachiko K.; Kurono, Yasutaka; Nakanishi, Kouichiro; Tosaki, Tomoka; Tamura, Yoichi; Kuno, Nario; Kawabe, Ryohei; Sakamoto, Seiichi; Hasegawa, Takashi

    2010-12-01

    We present the results from new Nobeyama Millimeter Array observations of CO(1-0), HCN(1-0), and 89 GHz continuum emission toward NGC 604, known as the supergiant H II region in the nearby galaxy M33. Our high spatial resolution images (4.''2 x 2.''6, corresponding to 17 pc x 11 pc physical size) of CO emission allowed us to uncover 10 individual molecular clouds that have masses of (0.8-7.4) x10{sup 5} M{sub sun} and sizes of 5-29 pc, comparable to those of typical Galactic giant molecular clouds. Moreover, we detected for the first time HCN emission in the two most massive clouds and 89 GHz continuum emission at the rims of the 'H{alpha} shells'. The HCN and 89 GHz continuum emission are offset from the CO peak and are distributed in the direction of the central cluster. Three out of ten CO clouds are well correlated with the H{alpha} shells both in spatial and velocity domains, implying an interaction between molecular gas and the expanding H II region. The CO clouds show varieties in star formation efficiencies (SFEs), which are estimated from the 89 GHz emission and combination of H{alpha} and Spitzer 24 {mu}m data. Furthermore, we found that the SFEs decrease with increasing projected distance measured from the heart of the central OB star cluster in NGC 604, suggesting radial changes in the evolutionary stages of the molecular clouds in the course of stellar cluster formation. Our results provide further support to the picture of sequential star formation in NGC 604 initially proposed by Tosaki et al. with the higher spatially resolved molecular clouds, in which an isotropic expansion of the H II region pushes gases outward, which accumulates to form dense molecular clouds, and then induces massive star formations.

  1. Nipah virus entry can occur by macropinocytosis

    SciTech Connect

    Pernet, Olivier; Pohl, Christine; Ainouze, Michelle; Kweder, Hasan; Buckland, Robin

    2009-12-20

    Nipah virus (NiV) is a zoonotic biosafety level 4 paramyxovirus that emerged recently in Asia with high mortality in man. NiV is a member, with Hendra virus (HeV), of the Henipavirus genus in the Paramyxoviridae family. Although NiV entry, like that of other paramyxoviruses, is believed to occur via pH-independent fusion with the host cell's plasma membrane we present evidence that entry can occur by an endocytic pathway. The NiV receptor ephrinB2 has receptor kinase activity and we find that ephrinB2's cytoplasmic domain is required for entry but is dispensable for post-entry viral spread. The mutation of a single tyrosine residue (Y304F) in ephrinB2's cytoplasmic tail abrogates NiV entry. Moreover, our results show that NiV entry is inhibited by constructions and drugs specific for the endocytic pathway of macropinocytosis. Our findings could potentially permit the rapid development of novel low-cost antiviral treatments not only for NiV but also HeV.

  2. Naturally Occurring Radioactive Materials (NORM)

    SciTech Connect

    Gray, P.

    1997-02-01

    This paper discusses the broad problems presented by Naturally Occuring Radioactive Materials (NORM). Technologically Enhanced naturally occuring radioactive material includes any radionuclides whose physical, chemical, radiological properties or radionuclide concentration have been altered from their natural state. With regard to NORM in particular, radioactive contamination is radioactive material in an undesired location. This is a concern in a range of industries: petroleum; uranium mining; phosphorus and phosphates; fertilizers; fossil fuels; forestry products; water treatment; metal mining and processing; geothermal energy. The author discusses in more detail the problem in the petroleum industry, including the isotopes of concern, the hazards they present, the contamination which they cause, ways to dispose of contaminated materials, and regulatory issues. He points out there are three key programs to reduce legal exposure and problems due to these contaminants: waste minimization; NORM assesment (surveys); NORM compliance (training).

  3. Foliicolous microfungi occurring on Encephalartos.

    PubMed

    Crous, P W; Wood, A R; Okada, G; Groenewald, J Z

    2008-12-01

    Species of Encephalartos, commonly known as bread trees, bread palms or cycads are native to Africa; the genus encompasses more than 60 species and represents an important component of the indigenous African flora. Recently, a leaf blight disease was noted on several E. altensteinii plants growing at the foot of Table Mountain in the Kirstenbosch Botanical Gardens of South Africa. Preliminary isolations from dead and dying leaves of E. alten-steinii, E. lebomboensis and E. princeps, collected from South Africa, revealed the presence of several novel microfungi on this host. Novelties include Phaeomoniella capensis, Saccharata kirstenboschensis, Teratosphaeria altensteinii and T. encephalarti. New host records of species previously only known to occur on Proteaceae include Cladophialophora proteae and Catenulostroma microsporum, as well as a hyperparasite, Dactylaria leptosphaeriicola, occurring on ascomata of T. encephalarti. PMID:20396583

  4. Caffeine, a naturally occurring acaricide.

    PubMed

    Russell, D W; Fernández-Caldas, E; Swanson, M C; Seleznick, M J; Trudeau, W L; Lockey, R F

    1991-01-01

    Since caffeine is a plant alkaloid that has been described as a naturally occurring insecticide, its acaricidal effect on Dermatophagoides pteronyssinus (Dp) was investigated. Twelve cultures were established by adding 30 Dp to 200 mg of Tetramin fish food and brewer's yeast (8:2 ratio); six cultures were treated with 20 mg of finely ground caffeine. All 12 cultures were incubated at 75% relative humidity, 25 degrees C, and observed during 8 weeks. Live mites were then counted under a stereoscope, cultures were extracted, and supernatants were analyzed for Der p I and Der f I allergen content with a two-site monoclonal RIA. Live mite counts in untreated cultures varied from 146 to 274 (215 +/- 47.1), and in caffeine-treated cultures from 0 to 3 (1 +/- 1.2; p less than or equal to 0.0001). Der p I concentrations in untreated cultures varied from 588 to 9000 ng/gm (3138.3 +/- 2990.8 ng/gm), and in caffeine-treated cultures from 52 to 117 ng/gm (78 +/- 23.8 ng/gm; p less than or equal to 0.01). Der p I was not detected in the food media or caffeine; Der f I was not detected in any of the cultures. Results demonstrate that caffeine inhibits mite growth and allergen production.

  5. Elevation of Alanine Aminotransferase Activity Occurs after Activation of the Cell-Death Signaling Initiated by Pattern-Recognition Receptors ‎but before Activation of Cytolytic Effectors in NK or CD8+ T Cells in the Liver During Acute HCV Infection

    PubMed Central

    Choi, Youkyung H.; Jin, Nancy; Kelly, Fiona; Sakthivel, SenthilKumar K.; Yu, Tianwei

    2016-01-01

    Pattern-recognition receptors (PRRs) promote host defenses against HCV infection by binding to their corresponding adapter molecules leading to the initiation of innate immune responses including cell death. We investigated the expression of PRR genes, biomarkers of liver cell-death, and T cell and NK cell activation/inhibition-related genes in liver and serum obtained from three experimentally infected chimpanzees with acute HCV infection, and analyzed the correlation between gene expression levels and clinical profiles. Our results showed that expression of hepatic RIG-I, TLR3, TLR7, 2OAS1, and CXCL10 mRNAs was upregulated as early as 7 days post-inoculation and peaked 12 to 83 days post-inoculation. All of the three HCV infected chimpanzees exhibited significant elevations of serum alanine aminotransferase (ALT) activity between 70 and 95 days after inoculation. Elevated levels of serum cytokeratin 18 (CK-18) and caspases 3 and 7 activity coincided closely with the rise of ALT activity, and were preceded by significant increases in levels of caspase 3 and caspase 7 mRNAs in the liver. Particularly we found that significant positive auto-correlations were observed between RIG-I, TLR3, CXCL10, 2OAS1, and PD-L1 mRNA and ALT activity at 3 to 12 days before the peak of ALT activity. However, we observed substantial negative auto-correlations between T cell and NK cell activation/inhibition-related genes and ALT activity at 5 to 32 days after the peak of ALT activity. Our results indicated cell death signaling is preceded by early induction of RIG-I, TLR3, 2OAS1, and CXCL10 mRNAs which leads to elevation of ALT activity and this signaling pathway occurs before the activation of NK and T cells during acute HCV infection. Our study suggests that PRRs and type I IFN response may play a critical role in development of liver cell injury related to viral clearance during acute HCV infection. PMID:27788241

  6. Breast carcinomas occurring in young women (< 35 years) are different.

    PubMed Central

    Walker, R. A.; Lees, E.; Webb, M. B.; Dearing, S. J.

    1996-01-01

    One hundred and sixty-three breast carcinomas occurring in women aged between 26 and 44 years were examined for pathological features, oestrogen and progesterone receptor status, proliferation as determined by Ki-67 labelling and the presence of c-erbB-2 and p53 protein, and were compared with a control group of carcinomas from women in the 50-67 years age group. Carcinomas occurring in women aged under 35 years had a significantly high incidence of being poorly differentiated and of having high proliferation rates. This group also had a significantly high incidence of p53 protein staining. Carcinomas in the under 30 years age group had a lower incidence of oestrogen and progesterone receptor positivity. No differences were found in c-erbB-2-positive staining between the groups. Infiltrating lobular carcinomas were only identified in women aged 40 years and over. There was a higher incidence of a family history in the 35-44 years age group (18%) than in the under 35 years age group (11%). Breast carcinomas occurring in women aged under 35 years are more aggressive. An important finding is the high incidence of p53 positivity, which may indicate genetic instability. Images Figure 1 PMID:8956795

  7. Signals and Receptors.

    PubMed

    Heldin, Carl-Henrik; Lu, Benson; Evans, Ron; Gutkind, J Silvio

    2016-04-01

    Communication between cells in a multicellular organism occurs by the production of ligands (proteins, peptides, fatty acids, steroids, gases, and other low-molecular-weight compounds) that are either secreted by cells or presented on their surface, and act on receptors on, or in, other target cells. Such signals control cell growth, migration, survival, and differentiation. Signaling receptors can be single-span plasma membrane receptors associated with tyrosine or serine/threonine kinase activities, proteins with seven transmembrane domains, or intracellular receptors. Ligand-activated receptors convey signals into the cell by activating signaling pathways that ultimately affect cytosolic machineries or nuclear transcriptional programs or by directly translocating to the nucleus to regulate transcription. PMID:27037414

  8. Estrogenic activity of naturally occurring anthocyanidins.

    PubMed

    Schmitt, E; Stopper, H

    2001-01-01

    Anthocyanins, which are natural plant pigments from the flavonoid family, represent substantial constituents of the human diet. Because some other bioflavonoids are known to have estrogenic activity, the aim of this study was to determine the estrogenic activity of the anthocyanine aglycones. Binding affinity to the estrogen receptor-alpha was 10,000- to 20,000-fold lower than that of the endogenous estrogen estradiol. In the estrogen receptor-positive cell line MCF-7, the anthocyanidins induced expression of a reporter gene. The tested anthocyanidins showed estrogen-inducible cell proliferation in two cell lines (MCF-7 and BG-1), but not in the receptor-negative human breast cancer cell line MDA-MB-231. The phytoestrogen-induced cell proliferation could be blocked by addition of the receptor antagonist 4-hydroxytamoxifen. Combination treatments with the endogenous estrogen estradiol resulted in a reduction of estradiol-induced cell proliferation. Overall, the tested anthocyanidins exert estrogenic activity, which might play a role in altering the development of hormone-dependent adverse effects.

  9. Dopamine Receptors and Neurodegeneration

    PubMed Central

    Rangel-Barajas, Claudia; Coronel, Israel; Florán, Benjamín

    2015-01-01

    Dopamine (DA) is one of the major neurotransmitters and participates in a number of functions such as motor coordination, emotions, memory, reward mechanism, neuroendocrine regulation etc. DA exerts its effects through five DA receptors that are subdivided in 2 families: D1-like DA receptors (D1 and D5) and the D2-like (D2, D3 and D4). All DA receptors are widely expressed in the central nervous system (CNS) and play an important role in not only in physiological conditions but also pathological scenarios. Abnormalities in the DAergic system and its receptors in the basal ganglia structures are the basis Parkinson’s disease (PD), however DA also participates in other neurodegenerative disorders such as Huntington disease (HD) and multiple sclerosis (MS). Under pathological conditions reorganization of DAergic system has been observed and most of the times, those changes occur as a mechanism of compensation, but in some cases contributes to worsening the alterations. Here we review the changes that occur on DA transmission and DA receptors (DARs) at both levels expression and signals transduction pathways as a result of neurotoxicity, inflammation and in neurodegenerative processes. The better understanding of the role of DA receptors in neuropathological conditions is crucial for development of novel therapeutic approaches to treat alterations related to neurodegenerative diseases. PMID:26425390

  10. Adverse events occurring after smallpox vaccination.

    PubMed

    Lane, J Michael; Goldstein, Joel

    2003-07-01

    We reviewed the literature on adverse events reported to occur after smallpox vaccination. Nearly one-half of the United States population is vaccinia-naïve and may be at risk for development of serious adverse events. We describe the clinical features of postvaccinial central nervous system disease, progressive vaccinia, eczema vaccinatum, accidental implantations, "generalized vaccinia," and the common erythematous and/or urticarial rashes. In the 1960s, death occurred approximately once in every million primary vaccinations, with fatalities resulting from progressive vaccinia, postvaccinial encephalitis, and eczema vaccinatum. Death in revaccinees occurred less commonly and almost entirely from progressive vaccinia. In today's population, death rates might be higher because of the increased prevalence of immune deficiency and atopic dermatitis.

  11. Young Children's Reports of when Learning Occurred

    ERIC Educational Resources Information Center

    Tang, Connie M.; Bartsch, Karen; Nunez, Narina

    2007-01-01

    This study investigated young children's reports of when learning occurred. A total of 96 4-, 5-, and 6-year-olds were recruited from suburban preschools and elementary schools. The children learned an animal fact and a body movement. A week later, children learned another animal fact and another body movement and then answered questions about…

  12. Naturally occurring iridoids. A review, part 1.

    PubMed

    Dinda, Biswanath; Debnath, Sudhan; Harigaya, Yoshihiro

    2007-02-01

    A compilation of new naturally occurring iridoid glycosides, iridoid aglycones, iridoid derivatives and bis-iridoids reported during 1994-2005 is provided with available physical and spectral data: mp, [alpha]D, UV, IR, 1H- and 13C-NMR as well as natural source with family and references. 418 compounds with 202 references are cited.

  13. Phonetic Recalibration Only Occurs in Speech Mode

    ERIC Educational Resources Information Center

    Vroomen, Jean; Baart, Martijn

    2009-01-01

    Upon hearing an ambiguous speech sound dubbed onto lipread speech, listeners adjust their phonetic categories in accordance with the lipread information (recalibration) that tells what the phoneme should be. Here we used sine wave speech (SWS) to show that this tuning effect occurs if the SWS sounds are perceived as speech, but not if the sounds…

  14. Preferential flow occurs in unsaturated conditions

    USGS Publications Warehouse

    Nimmo, John R.

    2012-01-01

    Because it commonly generates high-speed, high-volume flow with minimal exposure to solid earth materials, preferential flow in the unsaturated zone is a dominant influence in many problems of infiltration, recharge, contaminant transport, and ecohydrology. By definition, preferential flow occurs in a portion of a medium – that is, a preferred part, whether a pathway, pore, or macroscopic subvolume. There are many possible classification schemes, but usual consideration of preferential flow includes macropore or fracture flow, funneled flow determined by macroscale heterogeneities, and fingered flow determined by hydraulic instability rather than intrinsic heterogeneity. That preferential flow is spatially concentrated associates it with other characteristics that are typical, although not defining: it tends to be unusually fast, to transport high fluxes, and to occur with hydraulic disequilibrium within the medium. It also has a tendency to occur in association with large conduits and high water content, although these are less universal than is commonly assumed. Predictive unsaturated-zone flow models in common use employ several different criteria for when and where preferential flow occurs, almost always requiring a nearly saturated medium. A threshold to be exceeded may be specified in terms of the following (i) water content; (ii) matric potential, typically a value high enough to cause capillary filling in a macropore of minimum size; (iii) infiltration capacity or other indication of incipient surface ponding; or (iv) other conditions related to total filling of certain pores. Yet preferential flow does occur without meeting these criteria. My purpose in this commentary is to point out important exceptions and implications of ignoring them. Some of these pertain mainly to macropore flow, others to fingered or funneled flow, and others to combined or undifferentiated flow modes.

  15. Can Burkitt's Lymphoma and Hodgkin's Lymphoma occur in siblings simultaneously?

    PubMed

    Kaymak Cihan, Meriç; Kandemir, Olcay; Dalva, Klara; Sarı, Neriman; Kurucu, Nilgün; Ergürhan İlhan, İnci

    2015-01-01

    Familial clustering of Hodgkin lymphoma (HL) and increased risk of developing disease among the siblings has been reported earlier. Usually familial lymphoma in sibling pairs occurs in the pairs of either non-Hodgkin lymphoma or HL. In the familial HL, same type of human leukocyte antigens (HLA) is responsible in the affected family members. There are also some studies stating "Killer cell immunoglobulin like receptor (KIR)" genotypes can be important in the etiology of familial HL. Here we report two siblings; one with Non-Hodgkin and the other with Hodgkin lymphoma which showed Epstein-Barr virus encoded small RNAs positivity in the tumor tissues. We have also found that their HLA genotypes are same with each other. In addition, we have discussed familial lymphoma pathogenesis and HLA haplotypes. PMID:27411427

  16. Could a megaquake occur in the Himalayas?

    NASA Astrophysics Data System (ADS)

    Balcerak, Ernie

    2011-12-01

    GPS measurements of crustal deformation are showing that a magnitude 9 earthquake could occur in the Himalayas. Roger Bilham of the University of Colorado at Boulder reported at the AGU Fall Meeting that the region, known to be seismically active, could produce a much larger earthquake than previously thought. Bilham and colleagues used GPS to monitor rates of crustal deformation in the Himalayas. They found that the potential rupture zone is larger than scientists had believed—the region where strain is building is twice as wide as expected. Previous estimates, which were based on the historical earthquake record, suggested that the largest earthquake that would occur in the region would have a magnitude in the low 8s. Such an earthquake could be devastating—the Kashmir valley region alone is home to 6 million people.

  17. Young children's reports of when learning occurred.

    PubMed

    Tang, Connie M; Bartsch, Karen; Nunez, Narina

    2007-06-01

    This study investigated young children's reports of when learning occurred. A total of 96 4-, 5-, and 6-year-olds were recruited from suburban preschools and elementary schools. The children learned an animal fact and a body movement. A week later, children learned another animal fact and another body movement and then answered questions about when the different learning events occurred. Responses of children who responded correctly to control questions about time supported the hypothesis that temporal distance questions would elicit more correct responses than would temporal location questions. Partial support was also found for the hypothesis that behavior learning would generate more correct reports than would fact learning. Implications for characterizations of children's developing understanding of knowledge and for applications of those characterizations in education and eyewitness testimony are discussed. PMID:17346740

  18. Synthesis of Naturally Occurring Tropones and Tropolones

    PubMed Central

    Liu, Na; Song, Wangze; Schienebeck, Casi M.; Zhang, Min; Tang, Weiping

    2014-01-01

    Tropones and tropolones are an important class of seven-membered non-benzenoid aromatic compounds. They can be prepared directly by oxidation of seven-membered rings. They can also be derived from cyclization or cycloaddition of appropriate precursors followed by elimination or rearrangement. This review discusses the types of naturally occurring tropones and tropolones and outlines important methods developed for the synthesis of tropone and tropolone natural products. PMID:25400298

  19. Radiodefluorination of 3-Fluoro-5-(2-(2-[18F](fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile ([18F]SP203), a Radioligand for Imaging Brain Metabotropic Glutamate Subtype-5 Receptors with Positron Emission Tomography, Occurs by Glutathionylation in Rat Brain

    PubMed Central

    Zoghbi, Sami S.; Siméon, Fabrice G.; Liow, Jeih-San; Brown, Amira K.; Kannan, Pavitra; Innis, Robert B.; Pike, Victor W.

    2008-01-01

    Metabotropic glutamate subtype-5-receptors (mGluR5) are implicated in several neuropsychiatric disorders. Positron emission tomography (PET) with a suitable radioligand may enable monitoring of regional brain mGluR5 density before and during treatments. We have developed a new radioligand, 3-fluoro-5-(2-(2-[18F](fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile ([18F]SP203), for imaging brain mGluR5 in monkey and human. In monkey, radioactivity was observed in bone, showing release of [18F]fluoride ion from [18F]SP203. This defluorination was not inhibited by disulfiram, a potent inhibitor of CYP2E1. PET confirmed bone uptake of radioactivity and therefore defluorination of [18F]SP203 in rats. To understand the biochemical basis for defluorination, we administered [18F]SP203 plus SP203 in rats for ex vivo analysis of metabolites. Radio-HPLC detected [18F]fluoride ion as a major radiometabolite in both brain extract and urine. Incubation of [18F]SP203 with brain homogenate also generated this radiometabolite, whereas no metabolism was detected in whole blood in vitro. LC-MS analysis of the brain extract detected m/z 548 and m/z 404 ions, assignable to the [M+H]+ of S-glutathione (SP203Glu) and N-acetyl-S-L-cysteine (SP203Nac) conjugates of SP203, respectively. In urine, only the [M+H]+ of SP203Nac was detected. MS-MS and MS3 analyses of each metabolite yielded product ions consistent with its proposed structure, including the former fluoromethyl group as the site of conjugation. Metabolite structures were confirmed by similar analyses of SP203Glu and SP203Nac, prepared by glutathione S-transferase reaction and chemical synthesis, respectively. Thus, glutathionylation at the 2-fluoromethyl group is responsible for the radiodefluorination of [18F]SP203 in rat. This study provides the first demonstration of glutathione-promoted radiodefluorination of a PET radioligand. PMID:18806125

  20. spin pumping occurred under nonlinear spin precession

    NASA Astrophysics Data System (ADS)

    Zhou, Hengan; Fan, Xiaolong; Ma, Li; Zhou, Shiming; Xue, Desheng

    Spin pumping occurs when a pure-spin current is injected into a normal metal thin layer by an adjacent ferromagnetic metal layer undergoing ferromagnetic resonance, which can be understood as the inverse effect of spin torque, and gives access to the physics of magnetization dynamics and damping. An interesting question is that whether spin pumping occurring under nonlinear spin dynamics would differ from linear case. It is known that nonlinear spin dynamics differ distinctly from linear response, a variety of amplitude dependent nonlinear effect would present. It has been found that for spin precession angle above a few degrees, nonlinear damping term would present and dominated the dynamic energy/spin-moment dissipation. Since spin pumping are closely related to the damping process, it is interesting to ask whether the nonlinear damping term could be involved in spin pumping process. We studied the spin pumping effect occurring under nonlinear spin precession. A device which is a Pt/YIG microstrip coupled with coplanar waveguide was used. High power excitation resulted in spin precession entering in a nonlinear regime. Foldover resonance lineshape and nonlinear damping have been observed. Based on those nonlinear effects, we determined the values of the precession cone angles, and the maximum cone angle can reach a values as high as 21.5 degrees. We found that even in nonlinear regime, spin pumping is still linear, which means the nonlinear damping and foldover would not affect spin pumping process.

  1. Melatonin Receptor Genes in Vertebrates

    PubMed Central

    Li, Di Yan; Smith, David Glenn; Hardeland, Rüdiger; Yang, Ming Yao; Xu, Huai Liang; Zhang, Long; Yin, Hua Dong; Zhu, Qing

    2013-01-01

    Melatonin receptors are members of the G protein-coupled receptor (GPCR) family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A) and MT2 (or Mel1b or MTNR1B) receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C), has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor. PMID:23712359

  2. Naturally occurring products in cancer therapy

    PubMed Central

    Rajesh, E.; Sankari, Leena S.; Malathi, L.; Krupaa, Jayasri R.

    2015-01-01

    Natural products have been used for the treatment of various diseases and are becoming an important research area for drug discovery. These products, especially phytochemicals have been extensively studies and have exhibited anti-carcinogenic activities by interfering with the initiation, development and progression of cancer through the modulation of various mechanisms including cellular proliferation, differentiation, apoptosis, angiogenesis, and metastasis. This concept is gaining attention because it is a cost-effective alternative to cancer treatment. In this article, we have discussed some of the naturally occurring products used in cancer treatment. PMID:26015704

  3. Naturally occurring antimicrobials for minimally processed foods.

    PubMed

    Davidson, P Michael; Critzer, Faith J; Taylor, T Matthew

    2013-01-01

    Natural antimicrobials are gaining increased interest from researchers and food manufacturers alike seeking to discover label-friendly alternatives to the widely implemented synthetic compounds. Naturally occurring antimicrobials can be applied directly to food to protect food quality, extend food shelf life by inhibiting or inactivating spoilage microorganisms, and improve food safety by inhibiting or inactivating food-borne pathogens. There are a great number of natural antimicrobials derived from animal, plant, and microbial sources. This manuscript reviews their efficacy against spoilage and pathogenic organisms, their methods of evaluation, and their application in various foods as well as the development of novel delivery systems and incorporation with other hurdles.

  4. Atypical Mycobacterium furunculosis occurring after pedicures.

    PubMed

    Redbord, Kelley Pagliai; Shearer, David A; Gloster, Hugh; Younger, Bruce; Connelly, Beverly L; Kindel, Susan E; Lucky, Anne W

    2006-03-01

    Mycobacterium fortuitum complex are rapidly-growing nontuberculous mycobacteria found ubiquitously in the environment including, water, soil, dust, and biofilms. M fortuitum has been reported to cause skin and soft-tissue infections in association with nail salon footbath use during pedicures. Four cases of M fortuitum complex furunculosis are reported that occurred after pedicures in the Cincinnati, Ohio/Northern Kentucky area. Dermatologists and clinicians should consider mycobacterial infections from the M fortuitum complex when patients present with nonhealing furuncles on the lower legs and should inquire about recent pedicures. Early recognition and institution of appropriate therapy are critical. Public health measures should be explored to protect against such infections, given the recent popularity of the nail care industry.

  5. Introduction to naturally occurring radioactive material

    SciTech Connect

    Egidi, P.

    1997-08-01

    Naturally occurring radioactive material (NORM) is everywhere; we are exposed to it every day. It is found in our bodies, the food we eat, the places where we live and work, and in products we use. We are also bathed in a sea of natural radiation coming from the sun and deep space. Living systems have adapted to these levels of radiation and radioactivity. But some industrial practices involving natural resources concentrate these radionuclides to a degree that they may pose risk to humans and the environment if they are not controlled. Other activities, such as flying at high altitudes, expose us to elevated levels of NORM. This session will concentrate on diffuse sources of technologically-enhanced (TE) NORM, which are generally large-volume, low-activity waste streams produced by industries such as mineral mining, ore benefication, production of phosphate Fertilizers, water treatment and purification, and oil and gas production. The majority of radionuclides in TENORM are found in the uranium and thorium decay chains. Radium and its subsequent decay products (radon) are the principal radionuclides used in characterizing the redistribution of TENORM in the environment by human activity. We will briefly review other radionuclides occurring in nature (potassium and rubidium) that contribute primarily to background doses. TENORM is found in many waste streams; for example, scrap metal, sludges, slags, fluids, and is being discovered in industries traditionally not thought of as affected by radionuclide contamination. Not only the forms and volumes, but the levels of radioactivity in TENORM vary. Current discussions about the validity of the linear no dose threshold theory are central to the TENORM issue. TENORM is not regulated by the Atomic Energy Act or other Federal regulations. Control and regulation of TENORM is not consistent from industry to industry nor from state to state. Proposed regulations are moving from concentration-based standards to dose

  6. Epigenetic Mechanisms in Commonly Occurring Cancers

    PubMed Central

    2012-01-01

    Cancer is a collection of very complex diseases that share many traits while differing in many ways as well. This makes a universal cure difficult to attain, and it highlights the importance of understanding each type of cancer at a molecular level. Although many strides have been made in identifying the genetic causes for some cancers, we now understand that simple changes in the primary DNA sequence cannot explain the many steps that are necessary to turn a normal cell into a rouge cancer cell. In recent years, some research has shifted to focusing on detailing epigenetic contributions to the development and progression of cancer. These changes occur apart from primary genomic sequences and include DNA methylation, histone modifications, and miRNA expression. Since these epigenetic modifications are reversible, drugs targeting epigenetic changes are becoming more common in clinical settings. Daily discoveries elucidating these complex epigenetic processes are leading to advances in the field of cancer research. These advances, however, come at a rapid and often overwhelming pace. This review specifically summarizes the main epigenetic mechanisms currently documented in solid tumors common in the United States and Europe. PMID:22519822

  7. Naturally occurring contamination in the Mancos Shale.

    PubMed

    Morrison, Stan J; Goodknight, Craig S; Tigar, Aaron D; Bush, Richard P; Gil, April

    2012-02-01

    Some uranium mill tailings disposal cells were constructed on dark-gray shale of the Upper Cretaceous Mancos Shale. Shale of this formation contains contaminants similar to those in mill tailings. To establish the contributions derived from the Mancos, we sampled 51 locations in Colorado, New Mexico, and Utah. Many of the groundwater samples were saline with nitrate, selenium, and uranium concentrations commonly exceeding 250, 000, 1000, and 200 μg/L, respectively. Higher concentrations were limited to groundwater associated with shale beds, but were not correlated with geographic area, stratigraphic position, or source of water. The elevated concentrations suggest that naturally occurring contamination should be considered when evaluating groundwater cleanup levels. At several locations, seep water was yellow or red, caused in part by dissolved organic carbon concentrations up to 280 mg/L. Most seeps had (234)U to (238)U activity ratios greater than 2, indicating preferential leaching of (234)U. Seeps were slightly enriched in (18)O relative to the meteoric water line, indicating limited evaporation. Conceptually, major ion chemical reactions are dominated by calcite dissolution following proton release from pyrite oxidation and subsequent exchange by calcium for sodium residing on clay mineral exchange sites. Contaminants are likely released from organic matter and mineral surfaces during weathering.

  8. Somatostatin receptors.

    PubMed

    Srikant, C B; Patel, Y C

    1985-01-01

    It is now well established that the biological actions of tetradecapeptide somatostatin (somatostatin-14, S-14) are receptor-mediated. These receptors were first quantified in GH4C pituitary tumor cells using [125I-Tyr1] S-14 as radioligand which was found to exhibit high non-specific binding to membrane receptor preparations from normal tissues. Our studies have shown that [125I-Tyr11] S-14 in which the radiolabel is situated away from the N-terminus exhibits significantly lower non-specific binding and therefore is more suitable for S-14 receptor studies. In the CNS, highest concentration of S-14 receptors was found in the cerebral cortex, followed by thalamus, hypothalamus, striatum, amygdala and hippocampus while medulla-pons, cerebellum and spinal cord exhibited negligible binding. Outside the CNS membrane receptors for S-14 have been characterized in pituitary, adrenal cortex and pancreatic acini. In all these tissues a single class of high affinity binding sites for S-14 were present, the receptors in pancreatic acinar cells exhibiting significantly greater affinity for binding S-14 than in other tissues.

  9. Naturally occurring secoiridoids and bioactivity of naturally occurring iridoids and secoiridoids. A review, part 2.

    PubMed

    Dinda, Biswanath; Debnath, Sudhan; Harigaya, Yoshihiro

    2007-05-01

    Naturally occurring new secoiridoids published during 1994-2005 are reviewed with available physical and spectral data: mp, [alpha](D), UV, IR, (1)H- and (13)C-NMR and plant source. The works on biological and pharmacological activity of naturally occurring iridoids and secoiridoids reported during 1998-2005 are also reviewed. Bioactivities like antiallergic, antiarthritis, antibacterial, anticancer, anticoagulant, anticomplement, antifungal, antiinflammatory, antioxidative, antiprotozoal, antispasmodic, antiviral, immunomodulatory, neuroprotective, nerve growth factor potentiating and wound healing activities are highlighted.

  10. Differential dormancy of co-occurring copepods

    NASA Astrophysics Data System (ADS)

    Ohman, Mark D.; Drits, Aleksandr V.; Elizabeth Clarke, M.; Plourde, Stéphane

    1998-08-01

    Four species of planktonic calanoid copepods that co-occur in the California Current System ( Eucalanus californicus Johnson, Rhincalanus nasutus Giesbrecht, Calanus pacificus californicus Brodsky, and Metridia pacifica Brodsky) were investigated for evidence of seasonal dormancy in the San Diego Trough. Indices used to differentiate actively growing from dormant animals included developmental stage structure and vertical distribution; activity of aerobic metabolic enzymes (Citrate Synthase and the Electron Transfer System complex); investment in depot lipids (wax esters and triacylglycerols); in situ grazing activity from gut fluorescence; and egg production rates in simulated in situ conditions. None of the 4 species exhibited a canonical calanoid pattern of winter dormancy - i.e., synchronous developmental arrest as copepodid stage V, descent into deep waters, reduced metabolism, and lack of winter reproduction. Instead, Calanus pacificus californicus has a biphasic life history in this region, with an actively reproducing segment of the population in surface waters overlying a deep dormant segment in winter. Eucalanus californicus is dormant as both adult females and copepodid V's, although winter females respond relatively rapidly to elevated food and temperature conditions; they begin feeding and producing eggs within 2-3 days. Rhincalanus nasutus appears to enter dormancy as adult females, although the evidence is equivocal. Metridia pacifica shows no evidence of dormancy, with sustained active feeding, diel vertical migration behavior, and elevated activity of metabolic enzymes in December as well as in June. The four species also differ markedly in water content, classes of storage lipids, and specific activity of Citrate Synthase. These results suggest that copepod dormancy traits and structural composition reflect diverse adaptations to regional environmental conditions rather than a uniform, canonical series of traits that remain invariant among taxa

  11. Sundew adhesive: a naturally occurring hydrogel

    PubMed Central

    Huang, Yujian; Wang, Yongzhong; Sun, Leming; Agrawal, Richa; Zhang, Mingjun

    2015-01-01

    Bioadhesives have drawn increasing interest in recent years, owing to their eco-friendly, biocompatible and biodegradable nature. As a typical bioadhesive, sticky exudate observed on the stalked glands of sundew plants aids in the capture of insects and this viscoelastic adhesive has triggered extensive interests in revealing the implied adhesion mechanisms. Despite the significant progress that has been made, the structural traits of the sundew adhesive, especially the morphological characteristics in nanoscale, which may give rise to the viscous and elastic properties of this mucilage, remain unclear. Here, we show that the sundew adhesive is a naturally occurring hydrogel, consisting of nano-network architectures assembled with polysaccharides. The assembly process of the polysaccharides in this hydrogel is proposed to be driven by electrostatic interactions mediated with divalent cations. Negatively charged nanoparticles, with an average diameter of 231.9 ± 14.8 nm, are also obtained from this hydrogel and these nanoparticles are presumed to exert vital roles in the assembly of the nano-networks. Further characterization via atomic force microscopy indicates that the stretching deformation of the sundew adhesive is associated with the flexibility of its fibrous architectures. It is also observed that the adhesion strength of the sundew adhesive is susceptible to low temperatures. Both elasticity and adhesion strength of the sundew adhesive reduce in response to lowering the ambient temperature. The feasibility of applying sundew adhesive for tissue engineering is subsequently explored in this study. Results show that the fibrous scaffolds obtained from sundew adhesive are capable of increasing the adhesion of multiple types of cells, including fibroblast cells and smooth muscle cells, a property that results from the enhanced adsorption of serum proteins. In addition, in light of the weak cytotoxic activity exhibited by these scaffolds towards a variety of

  12. Assessment of receptor internalization and recycling.

    PubMed

    Koenig, Jennifer A

    2004-01-01

    Internalization of G-protein-coupled receptors (GPCRs) occurs in response to agonist activation of the receptors and causes a redistribution of receptors away from the plasma membrane toward endosomes. Internalization of lower-affinity small molecule GPCRs such as muscarinic acetylcholine and adrenergic receptors has been measured using hydrophilic antagonist radioligands that are membrane impermeant. In contrast, internalization of peptide hormone receptors is assessed by measuring the internalization of a radiolabeled- or fluorescently labeled peptide hormone. More recently, the use of epitope-tagged receptors has allowed the measurement of changes in receptor subcellular distribution by the use of immunoassay and immunofluorescence confocal microscopy. This chapter describes each of these approaches to the measurement of receptor internalization and describes the advantages and disadvantages of each method.

  13. Information Needs While A Disaster Is Occurring

    NASA Astrophysics Data System (ADS)

    Perry, S. C.

    2010-12-01

    that rainfall intensity at their homes might be less than the intensity up in the mountains where the debris flows would start. Nor did they know that debris flows travel too quickly to be outrun. These and many other examples indicate need for social and natural scientists to increase awareness of what to expect when the disaster strikes. This information must be solidly understood before the event occurs - while a disaster is unfolding there are no teachable moments. Case studies indicate that even those who come into a disaster well educated about the phenomenon can struggle to apply what they know when the real situation is at hand. In addition, psychological studies confirm diminished ability to comprehend information at times of stress.

  14. Somatostatin receptors.

    PubMed

    Patel, Y C; Srikant, C B

    1997-12-01

    The diverse biological effects of somatostatin (SRIF) are mediated by a family of G protein-coupled receptors (termed sst) that are encoded by five nonallelic genes located on separate chromosomes. The receptors can be further divided into two subfamilies: sst(2,3,5) react with octapeptide and hexapeptide SRIF analogues and belong to one subclass; sst(1,4) react poorly with these compounds and fall into another subclass. This review focuses on the molecular pharmacology and function of these receptors, with particular emphasis on the ligand-binding domain, subtype-selective analogues, agonist-dependent receptor regulation and desensitization responses, subtype-specific effector coupling, and signal transduction pathways responsible for inhibiting cell secretion and cell growth or induction of apoptosis.

  15. GABAB receptors modulate NMDA receptor calcium signals in dendritic spines.

    PubMed

    Chalifoux, Jason R; Carter, Adam G

    2010-04-15

    Metabotropic GABA(B) receptors play a fundamental role in modulating the excitability of neurons and circuits throughout the brain. These receptors influence synaptic transmission by inhibiting presynaptic release or activating postsynaptic potassium channels. However, their ability to directly influence different types of postsynaptic glutamate receptors remains unresolved. Here we examine GABA(B) receptor modulation in layer 2/3 pyramidal neurons from the mouse prefrontal cortex. We use two-photon laser-scanning microscopy to study synaptic modulation at individual dendritic spines. Using two-photon optical quantal analysis, we first demonstrate robust presynaptic modulation of multivesicular release at single synapses. Using two-photon glutamate uncaging, we then reveal that GABA(B) receptors strongly inhibit NMDA receptor calcium signals. This postsynaptic modulation occurs via the PKA pathway and does not affect synaptic currents mediated by AMPA or NMDA receptors. This form of GABA(B) receptor modulation has widespread implications for the control of calcium-dependent neuronal function.

  16. Lipoxin receptors.

    PubMed

    Romano, Mario; Recchia, Irene; Recchiuti, Antonio

    2007-01-01

    Lipoxins (LXs) represent a class of arachidonic acid (AA) metabolites that carry potent immunoregulatory and anti-inflammatory properties, LXA4 and LXB4 being the main components of this series. LXs are generated by cooperation between 5-lipoxygenase (LO) and 12- or 15-LO during cell-cell interactions or by single cell types. LX epimers at carbon 15, the 15-epi-LXs, are formed by aspirin-acetylated cyclooxygenase-2 (COX-2) in cooperation with 5-LO. 15-epi-LXA4 is also termed aspirin-triggered LX (ATL). In vivo studies with stable LX and ATL analogs have established that these eicosanoids possess potent anti-inflammatory activities. A LXA4 receptor has been cloned. It belongs to the family of chemotactic receptors and clusters with formyl peptide receptors on chromosome 19. Therefore, it was initially denominated formyl peptide receptor like 1 (FPRL1). This receptor binds with high affinity and stereoselectivity LXA4 and ATL. It also recognizes a variety of peptides, synthetic, endogenously generated, or disease associated, but with lower affinity compared to LXA4. For this reason, this receptor has been renamed ALX. This review summarizes the current knowledge on ALX expression, signaling, and potential pathophysiological role. The involvement of additional recognition sites in LX bioactions is also discussed. PMID:17767357

  17. Neurodegeneration in Lurcher mice occurs via multiple cell death pathways.

    PubMed

    Doughty, M L; De Jager, P L; Korsmeyer, S J; Heintz, N

    2000-05-15

    Lurcher (Lc) is a gain-of-function mutation in the delta2 glutamate receptor (GRID2) that results in the cell-autonomous death of cerebellar Purkinje cells in heterozygous lurcher (+/Lc) mice. This in turn triggers the massive loss of afferent granule cells during the first few postnatal weeks. Evidence suggests that the death of Purkinje cells as a direct consequence of GRID2(Lc) activation and the secondary death of granule cells because of target deprivation occur by apoptosis. We have used mice carrying null mutations of both the Bax and p53 genes to examine the roles of these genes in cell loss in lurcher animals. The absence of Bax delayed Purkinje cell death in response to the GRID2(Lc) mutation and permanently rescued the secondary death of granule cells. In contrast, the p53 deletion had no effect on either cell death pathway. Our results demonstrate that target deprivation induces a Bax-dependent, p53-independent cell death response in cerebellar granule cells in vivo. In contrast, Bax plays a minor role in GRID2(Lc)-mediated Purkinje cell death.

  18. Memory impairment due to fipronil pesticide exposure occurs at the GABAA receptor level, in rats.

    PubMed

    Godinho, Antonio Francisco; de Oliveira Souza, Ana Carolina; Carvalho, Caio Cristóvão; Horta, Daniel França; De Fraia, Daniel; Anselmo, Fabio; Chaguri, João Leandro; Faria, Caique Aparecido

    2016-10-15

    Fipronil (F) a pesticide considered of second generation cause various toxic effects in target and non-target organisms including humans in which provoke neurotoxicity, having the antagonism of gamma-amino butyric acid (GABA) as their main mechanism for toxic action. GABAergic system has been involved in processes related to the memory formation and consolidation. The present work studied the importance of GABA to the mechanisms involved in the very early development of fipronil-induced memory impairment in rats. Memory behavior was assessed using new object recognition task (ORT) and eight radial arm maze task (8-RAM) to study effects on cognitive and spatial memory. Locomotor behavior was assessed using open field task (OF). The dose of fipronil utilized was studied through a pilot experiment. The GABA antagonist picrotoxin (P) was used to enhance fipronil effects on GABAergic system. Fipronil or picrotoxin decrease memory studied in ORT and 8-RAM tasks. Additionally, F and P co-exposure enhanced effects on memory compared to controls, F, and P, suggesting strongly a GABAergic effect. Weight gain modulation and fipronil in blood were utilized as animal's intoxication indicators. In conclusion, here we report that second-generation pesticides, such as fipronil, can have toxic interactions with the CNS of mammals and lead to memory impairment by modulating the GABAergic system. PMID:27374426

  19. Memory impairment due to fipronil pesticide exposure occurs at the GABAA receptor level, in rats.

    PubMed

    Godinho, Antonio Francisco; de Oliveira Souza, Ana Carolina; Carvalho, Caio Cristóvão; Horta, Daniel França; De Fraia, Daniel; Anselmo, Fabio; Chaguri, João Leandro; Faria, Caique Aparecido

    2016-10-15

    Fipronil (F) a pesticide considered of second generation cause various toxic effects in target and non-target organisms including humans in which provoke neurotoxicity, having the antagonism of gamma-amino butyric acid (GABA) as their main mechanism for toxic action. GABAergic system has been involved in processes related to the memory formation and consolidation. The present work studied the importance of GABA to the mechanisms involved in the very early development of fipronil-induced memory impairment in rats. Memory behavior was assessed using new object recognition task (ORT) and eight radial arm maze task (8-RAM) to study effects on cognitive and spatial memory. Locomotor behavior was assessed using open field task (OF). The dose of fipronil utilized was studied through a pilot experiment. The GABA antagonist picrotoxin (P) was used to enhance fipronil effects on GABAergic system. Fipronil or picrotoxin decrease memory studied in ORT and 8-RAM tasks. Additionally, F and P co-exposure enhanced effects on memory compared to controls, F, and P, suggesting strongly a GABAergic effect. Weight gain modulation and fipronil in blood were utilized as animal's intoxication indicators. In conclusion, here we report that second-generation pesticides, such as fipronil, can have toxic interactions with the CNS of mammals and lead to memory impairment by modulating the GABAergic system.

  20. Direct imaging of lateral movements of AMPA receptors inside synapses.

    PubMed

    Tardin, Catherine; Cognet, Laurent; Bats, Cécile; Lounis, Brahim; Choquet, Daniel

    2003-09-15

    Trafficking of AMPA receptors in and out of synapses is crucial for synaptic plasticity. Previous studies have focused on the role of endo/exocytosis processes or that of lateral diffusion of extra-synaptic receptors. We have now directly imaged AMPAR movements inside and outside synapses of live neurons using single-molecule fluorescence microscopy. Inside individual synapses, we found immobile and mobile receptors, which display restricted diffusion. Extra-synaptic receptors display free diffusion. Receptors could also exchange between these membrane compartments through lateral diffusion. Glutamate application increased both receptor mobility inside synapses and the fraction of mobile receptors present in a juxtasynaptic region. Block of inhibitory transmission to favor excitatory synaptic activity induced a transient increase in the fraction of mobile receptors and a decrease in the proportion of juxtasynaptic receptors. Altogether, our data show that rapid exchange of receptors between a synaptic and extra-synaptic localization occurs through regulation of receptor diffusion inside synapses. PMID:12970178

  1. Naturally occurring HCA1 missense mutations result in loss of function: potential impact on lipid deposition

    PubMed Central

    Doyle, Jamie R.; Lane, Jacqueline M.; Beinborn, Martin; Kopin, Alan S.

    2013-01-01

    The hydroxy-carboxylic acid receptor (HCA1) is a G protein-coupled receptor that is highly expressed on adipocytes and considered a potential target for the treatment of dyslipidemia. In the current study, we investigated the pharmacological properties of naturally occurring variants in this receptor (H43Q, A110V, S172L, and D253H). After transient expression of these receptors into human embryonic kidney 293 cells, basal and ligand-induced signaling were assessed using luciferase reporter gene assays. The A110V, S172L, and D253 variants showed reduced basal activity; the S172L mutant displayed a decrease in potency to the endogenous ligand l-lactate. Both the S172L and D253H variants also showed impaired cell surface expression, which may in part explain the reduced activity of these receptors. The impact of a loss in HCA1 function on lipid accumulation was investigated in the adipocyte cell line, OP9. In these cells, endogenous HCA1 transcript levels rapidly increased and reached maximal levels 3 days after the addition of differentiation media. Knockdown of HCA1 using siRNA resulted in an increase in lipid accumulation as assessed by quantification of Nile Red staining and TLC analysis. Our data suggest that lipid homeostasis may be altered in carriers of selected HCA1 missense variants. PMID:23268337

  2. Evolution of vertebrate opioid receptors

    PubMed Central

    Dreborg, Susanne; Sundström, Görel; Larsson, Tomas A.; Larhammar, Dan

    2008-01-01

    The opioid peptides and receptors have prominent roles in pain transmission and reward mechanisms in mammals. The evolution of the opioid receptors has so far been little studied, with only a few reports on species other than tetrapods. We have investigated species representing a broader range of vertebrates and found that the four opioid receptor types (delta, kappa, mu, and NOP) are present in most of the species. The gene relationships were deduced by using both phylogenetic analyses and chromosomal location relative to 20 neighboring gene families in databases of assembled genomes. The combined results show that the vertebrate opioid receptor gene family arose by quadruplication of a large chromosomal block containing at least 14 other gene families. The quadruplication seems to coincide with, and, therefore, probably resulted from, the two proposed genome duplications in early vertebrate evolution. We conclude that the quartet of opioid receptors was already present at the origin of jawed vertebrates ≈450 million years ago. A few additional opioid receptor gene duplications have occurred in bony fishes. Interestingly, the ancestral receptor gene duplications coincide with the origin of the four opioid peptide precursor genes. Thus, the complete vertebrate opioid system was already established in the first jawed vertebrates. PMID:18832151

  3. Angiotensin II receptor signalling.

    PubMed

    Daniels, Derek; Yee, Daniel K; Fluharty, Steven J

    2007-05-01

    Angiotensin II plays a key role in the regulation of body fluid homeostasis. To correct body fluid deficits that occur during hypovolaemia, an animal needs to ingest both water and electrolytes. Thus, it is not surprising that angiotensin II, which is synthesized in response to hypovolaemia, acts centrally to increase both water and NaCl intake. Here, we review findings relating to the properties of angiotensin II receptors that give rise to changes in behaviour. Data are described to suggest that divergent signal transduction pathways are responsible for separable behavioural responses to angiotensin II, and a hypothesis is proposed to explain how this divergence may map onto neural circuits in the brain.

  4. Signal transduction activated by cannabinoid receptors.

    PubMed

    Díaz-Laviada, Inés; Ruiz-Llorente, Lidia

    2005-07-01

    Since the discovery that cannabinoids exert biological actions through binding to specific receptors, signal mechanisms triggered by these receptors have been focus of extensive study. This review summarizes the current knowledge of the signalling events produced by cannabinoids from membrane receptors to downstream regulators. Two types of cannabinoid receptors have been identified to date: CB(1) and CB(2) both belonging to the heptahelichoidal receptor family but with different tissue distribution and signalling mechanisms. Coupling to inhibitory guanine nucleotide-binding protein and thus inhibition of adenylyl cyclase has been observed in both receptors but other signal transduction pathways that are regulated or not by these G proteins are differently activated upon ligand-receptor binding including ion channels, sphingomyelin hydrolysis, ceramide generation, phospholipases activation and downstream targets as MAP kinase cascade, PI3K, FAK or NOS regulation. Cannabinoids may also act independently of CB(1)or CB(2) receptors. The existence of new unidentified putative cannabinoid receptors has been claimed by many investigators. Endocannabinoids activate vanilloid TRPV1 receptors that may mediate some of the cannabinoid effects. Other actions of cannabinoids can occur through non-receptor-mediated mechanisms.

  5. Structural determinants of sigma receptor affinity

    SciTech Connect

    Largent, B.L.; Wikstroem, H.G.; Gundlach, A.L.; Snyder, S.H.

    1987-12-01

    The structural determinants of sigma receptor affinity have been evaluated by examining a wide range of compounds related to opioids, neuroleptics, and phenylpiperidine dopaminergic structures for affinity at sigma receptor-binding sites labeled with (+)-(/sup 3/H)3-PPP. Among opioid compounds, requirements for sigma receptor affinity differ strikingly from the determinants of affinity for conventional opiate receptors. Sigma sites display reverse stereoselectivity to classical opiate receptors. Multi-ringed opiate-related compounds such as morphine and naloxone have negligible affinity for sigma sites, with the highest sigma receptor affinity apparent for benzomorphans which lack the C ring of opioids. Highest affinity among opioids and other compounds occurs with more lipophilic N-substituents. This feature is particularly striking among the 3-PPP derivatives as well as the opioids. The butyrophenone haloperidol is the most potent drug at sigma receptors we have detected. Among the series of butyrophenones, receptor affinity is primarily associated with the 4-phenylpiperidine moiety. Conformational calculations for various compounds indicate a fairly wide range of tolerance for distances between the aromatic ring and the amine nitrogen, which may account for the potency at sigma receptors of structures of considerable diversity. Among the wide range of structures that bind to sigma receptor-binding sites, the common pharmacophore associated with high receptor affinity is a phenylpiperidine with a lipophilic N-substituent.

  6. Human Parechovirus 1 Infection Occurs via αVβ1 Integrin.

    PubMed

    Merilahti, Pirjo; Tauriainen, Sisko; Susi, Petri

    2016-01-01

    Human parechovirus 1 (HPeV-1) (family Picornaviridae) is a global cause of pediatric respiratory and CNS infections for which there is no treatment. Although biochemical and in vitro studies have suggested that HPeV-1 binds to αVβ1, αVβ3 and αVβ6 integrin receptor(s), the actual cellular receptors required for infectious entry of HPeV-1 remain unknown. In this paper we analyzed the expression profiles of αVβ1, αVβ3, αVβ6 and α5β1 in susceptible cell lines (A549, HeLa and SW480) to identify which integrin receptors support HPeV-1 internalization and/or replication cycle. We demonstrate by antibody blocking assay, immunofluorescence microscopy and RT-qPCR that HPeV-1 internalizes and replicates in cell lines that express αVβ1 integrin but not αVβ3 or αVβ6 integrins. To further study the role of β1 integrin, we used a mouse cell line, GE11-KO, which is deficient in β1 expression, and its derivate GE11-β1 in which human integrin β1 subunit is overexpressed. HPeV-1 (Harris strain) and three clinical HPeV-1 isolates did not internalize into GE11-KO whereas GE11-β1 supported the internalization process. An integrin β1-activating antibody, TS2/16, enhanced HPeV-1 infectivity, but infection occurred in the absence of visible receptor clustering. HPeV-1 also co-localized with β1 integrin on the cell surface, and HPeV-1 and β1 integrin co-endocytosed into the cells. In conclusion, our results demonstrate that in some cell lines the cellular entry of HPeV-1 is primarily mediated by the active form of αVβ1 integrin without visible receptor clustering.

  7. Human Parechovirus 1 Infection Occurs via αVβ1 Integrin

    PubMed Central

    Merilahti, Pirjo; Tauriainen, Sisko

    2016-01-01

    Human parechovirus 1 (HPeV-1) (family Picornaviridae) is a global cause of pediatric respiratory and CNS infections for which there is no treatment. Although biochemical and in vitro studies have suggested that HPeV-1 binds to αVβ1, αVβ3 and αVβ6 integrin receptor(s), the actual cellular receptors required for infectious entry of HPeV-1 remain unknown. In this paper we analyzed the expression profiles of αVβ1, αVβ3, αVβ6 and α5β1 in susceptible cell lines (A549, HeLa and SW480) to identify which integrin receptors support HPeV-1 internalization and/or replication cycle. We demonstrate by antibody blocking assay, immunofluorescence microscopy and RT-qPCR that HPeV-1 internalizes and replicates in cell lines that express αVβ1 integrin but not αVβ3 or αVβ6 integrins. To further study the role of β1 integrin, we used a mouse cell line, GE11-KO, which is deficient in β1 expression, and its derivate GE11-β1 in which human integrin β1 subunit is overexpressed. HPeV-1 (Harris strain) and three clinical HPeV-1 isolates did not internalize into GE11-KO whereas GE11-β1 supported the internalization process. An integrin β1-activating antibody, TS2/16, enhanced HPeV-1 infectivity, but infection occurred in the absence of visible receptor clustering. HPeV-1 also co-localized with β1 integrin on the cell surface, and HPeV-1 and β1 integrin co-endocytosed into the cells. In conclusion, our results demonstrate that in some cell lines the cellular entry of HPeV-1 is primarily mediated by the active form of αVβ1 integrin without visible receptor clustering. PMID:27128974

  8. Naturally occurring dominant drug resistance mutations occur infrequently in the setting of recently acquired hepatitis C

    PubMed Central

    Applegate, Tanya L; Gaudieri, Silvana; Plauzolles, Anne; Chopra, Abha; Grebely, Jason; Lucas, Michaela; Hellard, Margaret; Luciani, Fabio; Dore, Gregory J; Matthews, Gail V

    2014-01-01

    Background Directly Acting Antivirals (DAAs) are predicted to transform hepatitis C (HCV) therapy, yet little is known about the prevalence of naturally occurring resistance mutations in recently acquired HCV. This study aimed to determine the prevalence and frequency of drug resistance mutations in the viral quasispecies among HIV positive and negative individuals with recent HCV. Methods The NS3 protease, NS5A and NS5B polymerase genes were amplified from fifty genotype 1a participants of the Australian Trial in Acute Hepatitis C. Amino acid variations at sites known to be associated with possible drug resistance were analysed by ultra-deep pyrosequencing. Results Twelve percent of individuals harboured dominant resistance mutations, while 36% demonstrated non dominant resistant variants below that detectable by bulk sequencing (ie < 20%) but above a threshold of 1%. Resistance variants (< 1%) were observed at most sites associated with DAA resistance from all classes, with the exception of sofosbuvir. Conclusions Dominant resistant mutations were uncommonly observed in the setting of recent HCV. However, low level mutations to all DAA classes were observed by deep sequencing at the majority of sites, and in most individuals. The significance of these variants and impact on future treatment options remains to be determined. PMID:25105742

  9. Chemotactic peptide receptor modulation in polymorphonuclear leukocytes

    PubMed Central

    1980-01-01

    The binding of the chemotactic peptide N- formylnorleucylleucylphenylalanine (FNLLP) to its receptor on rabbit polymorphonuclear leukocytes (PMNs) modulates the number of available peptide receptors. Incubation with FNLLP decreases subsequent binding capacity, a phenomenon that has been termed receptor down regulation. Down regulation of the chemotactic peptide receptor is concentration dependent in both the rate and extent of receptor loss. The dose response parallels that of FNLLP binding to the recptor. The time- course is rapid; even at concentrations of FNLLP as low as 3 x 10(-9) M, the new equilibrium concentration of receptors is reached within 15 min. Down regulation is temperature dependent, but does occur even at 4 degrees C. Concomitant with down regulation, some of the peptide becomes irreversibly cell associated. At 4 degrees C, there is a small accumulation of nondissociable peptide that rapidly reaches a plateau. At higher temperatures, accumulation of nondissociable peptide continues after the rceptor number has reached equilibrium, and the amount accumulated can exceed the initial number of receptors by as much as 300%. The dose response of peptide uptake at 37 degrees C reflects that of binding, suggesting that it is receptor mediated. This uptake may occur via a pinocytosis mechanism. Although PMNs have not been considered to be pinocytic, the addition of FNLLP causes a fourfold stimulation of the rate of pinocytosis as measured by the uptake of [3H]sucrose. PMID:7391138

  10. Causes and Outcomes of Pediatric Injuries Occurring at School.

    ERIC Educational Resources Information Center

    Di Scala, Carla; Gallagher, Susan Scavo; Schneps, Sue E.

    1997-01-01

    Used the National Pediatric Trauma Registry, which collects data on child injuries requiring hospitalization, to examine causes and outcomes of injuries occurring at school. Analysis of 1,558 cases indicated that most injuries were unintentional and occurred among students age 10-14 years. Nearly half occurred in recreational areas. Falls and…

  11. The LDL receptor.

    PubMed

    Goldstein, Joseph L; Brown, Michael S

    2009-04-01

    In this article, the history of the LDL receptor is recounted by its codiscoverers. Their early work on the LDL receptor explained a genetic cause of heart attacks and led to new ways of thinking about cholesterol metabolism. The LDL receptor discovery also introduced three general concepts to cell biology: receptor-mediated endocytosis, receptor recycling, and feedback regulation of receptors. The latter concept provides the mechanism by which statins selectively lower plasma LDL, reducing heart attacks and prolonging life. PMID:19299327

  12. Ghrelin Receptor Mutations and Human Obesity.

    PubMed

    Wang, W; Tao, Y-X

    2016-01-01

    Growth hormone secretagogue receptor (GHSR) was originally identified as an orphan receptor in porcine and rat anterior pituitary membranes. In 1999, GHSR was deorphanized and shown to be a receptor for ghrelin, a peptide hormone secreted from the stomach. Therefore, GHSR is also called ghrelin receptor. In addition to regulating growth hormone secretion, ghrelin receptor regulates various physiological processes, including food intake and energy expenditure, glucose metabolism, cardiovascular functions, gastric acid secretion and motility, and immune function. Several human genetic studies conducted in populations originated from Europe, Africa, South America, and East Asia identified rare mutations and single nucleotide polymorphisms that might be associated with human obesity and short stature. Functional analyses of mutant GHSRs reveal multiple defects, including cell surface expression, ligand binding, and basal and stimulated signaling. With growing understanding in the functionality of naturally occurring GHSR mutations, potential therapeutic strategies including pharmacological chaperones and novel ligands could be used to correct the GHSR mutants. PMID:27288828

  13. Rubemamine and Rubescenamine, Two Naturally Occurring N-Cinnamoyl Phenethylamines with Umami-Taste-Modulating Properties.

    PubMed

    Backes, Michael; Obst, Katja; Bojahr, Juliane; Thorhauer, Anika; Roudnitzky, Natacha; Paetz, Susanne; Reichelt, Katharina V; Krammer, Gerhard E; Meyerhof, Wolfgang; Ley, Jakob P

    2015-10-01

    Sensory screening of a series of naturally occurring N-cinnamoyl derivatives of substituted phenethylamines revealed that rubemamine (9, from Chenopodium album) and rubescenamine (10, from Zanthoxylum rubsecens) elicit strong intrinsic umami taste in water at 50 and 10 ppm, respectively. Sensory tests in glutamate- and nucleotide-containing bases showed that the compounds influence the whole flavor profile of savory formulations. Both rubemamine (9) and rubescenamine (10) at 10-100 ppm dose-dependently positively modulated the umami taste of MSG (0.17-0.22%) up to threefold. Among the investigated amides, only rubemamine (9) and rubescenamine (10) are able to directly activate the TAS1R1-TAS1R3 umami taste receptor. Moreover, both compounds also synergistically modulated the activation of TAS1R1-TAS1R3 by MSG. Most remarkably, rubemamine (9) was able to further positively modulate the IMP-enhanced TAS1R1-TAS1R3 response to MSG ∼ 1.8-fold. Finally, armatamide (11), zanthosinamide (13), and dioxamine (14), which lack intrinsic umami taste in vivo and direct receptor response in vitro, also positively modulated receptor activation by MSG about twofold and the IMP-enhanced MSG-induced TAS1R1-TAS1R3 responses approximately by 50%. In sensory experiments, dioxamine (14) at 25 ppm in combination with 0.17% MSG exhibited a sensory equivalent to 0.37% MSG. PMID:26375852

  14. 32 CFR 716.6 - Death occurring after active service.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 5 2014-07-01 2014-07-01 false Death occurring after active service. 716.6 Section 716.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after...

  15. 32 CFR 716.6 - Death occurring after active service.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 5 2011-07-01 2011-07-01 false Death occurring after active service. 716.6 Section 716.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after...

  16. 32 CFR 716.6 - Death occurring after active service.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 5 2012-07-01 2012-07-01 false Death occurring after active service. 716.6 Section 716.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after...

  17. 32 CFR 716.6 - Death occurring after active service.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 5 2013-07-01 2013-07-01 false Death occurring after active service. 716.6 Section 716.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after...

  18. 32 CFR 716.6 - Death occurring after active service.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 5 2010-07-01 2010-07-01 false Death occurring after active service. 716.6 Section 716.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after...

  19. Drosophila TRPA1 channel is required to avoid the naturally occurring insect repellent citronellal

    PubMed Central

    Kwon, Young; Kim, Sang Hoon; Ronderos, David S.; Lee, Youngseok; Akitake, Bradley; Woodward, Owen M.; Guggino, William B.; Smith, Dean P.; Montell, Craig

    2010-01-01

    Summary Plants produce naturally occurring insect repellents, such as citronellal, which is the main component of citronellal oil and is among the most widely-used-naturally-occurring insect repellents. However, the molecular pathways through which insects sense botanical repellents are unknown. Here, we showed that Drosophila used two pathways for direct avoidance of citronellal. The olfactory co-receptor, Or83b, which is required for the response to the synthetic repellent DEET, contributed to citronellal repulsion, and was essential for citronellal-evoked action potentials. Mutations affecting the Ca2+-permeable cation channel, TRPA1 resulted in a comparable defect in avoiding citronellal vapor. The TRPA1-dependent aversion to citronellal relied on a G protein/phospholipase C (PLC) signaling cascade, rather than direct detection of citronellal by TRPA1. Loss of TRPA1, Gq or PLC caused an increase in the frequency of citronellal-evoked action potentials in olfactory receptor neurons. Absence of the Ca2+-activated K+ channel, Slowpoke, resulted in a similar impairment in citronellal avoidance, and an increase in the frequency of action potentials. These results suggest that TRPA1 is required for activation of a BK channel to modulate citronellal-evoked action potentials, and for aversion to citronellal. In contrast to Drosophila TRPA1, Anopheles gambiae TRPA1 was directly and potently activated by citronellal, thereby raising the possibility that mosquito TRPA1 may be a target for developing improved repellents to reduce insect-borne diseases such as malaria. PMID:20797863

  20. Cocaine Disrupts Histamine H3 Receptor Modulation of Dopamine D1 Receptor Signaling: σ1-D1-H3 Receptor Complexes as Key Targets for Reducing Cocaine's Effects

    PubMed Central

    Moreno, Estefanía; Moreno-Delgado, David; Navarro, Gemma; Hoffmann, Hanne M.; Fuentes, Silvia; Rosell-Vilar, Santi; Gasperini, Paola; Rodríguez-Ruiz, Mar; Medrano, Mireia; Mallol, Josefa; Cortés, Antoni; Casadó, Vicent; Lluís, Carme; Ferré, Sergi; Ortiz, Jordi; Canela, Enric

    2014-01-01

    The general effects of cocaine are not well understood at the molecular level. What is known is that the dopamine D1 receptor plays an important role. Here we show that a key mechanism may be cocaine's blockade of the histamine H3 receptor-mediated inhibition of D1 receptor function. This blockade requires the σ1 receptor and occurs upon cocaine binding to σ1-D1-H3 receptor complexes. The cocaine-mediated disruption leaves an uninhibited D1 receptor that activates Gs, freely recruits β-arrestin, increases p-ERK 1/2 levels, and induces cell death when over activated. Using in vitro assays with transfected cells and in ex vivo experiments using both rats acutely treated or self-administered with cocaine along with mice depleted of σ1 receptor, we show that blockade of σ1 receptor by an antagonist restores the protective H3 receptor-mediated brake on D1 receptor signaling and prevents the cell death from elevated D1 receptor signaling. These findings suggest that a combination therapy of σ1R antagonists with H3 receptor agonists could serve to reduce some effects of cocaine. PMID:24599455

  1. Dual pathways of internalization of the cholecystokinin receptor

    PubMed Central

    1995-01-01

    Receptor molecules play a major role in the desensitization of agonist- stimulated cellular responses. For G protein-coupled receptors, rapid desensitization occurs via receptor phosphorylation, sequestration, and internalization, yet the cellular compartments in which these events occur and their interrelationships are unclear. In this work, we focus on the cholecystokinin (CCK) receptor, which has been well characterized with respect to phosphorylation. We have used novel fluorescent and electron-dense CCK receptor ligands and an antibody to probe receptor localization in a CCK receptor-bearing CHO cell line. In the unstimulated state, receptors were diffusely distributed over the plasmalemma. Agonist occupation stimulated endocytosis via both clathrin-dependent and independent pathways. The former was predominant, leading to endosomal and lysosomal compartments, as well as recycling to the plasmalemma. The clathrin-independent processes led to a smooth vesicular compartment adjacent to the plasmalemma resembling caveolae, which did not transport ligand deeper within the cell. Potassium depletion largely eliminated clathrin-dependent endocytosis, while not interfering with agonist-stimulated receptor movement into subplasmalemmal smooth vesicle compartments. These cellular endocytic events can be related to the established cycle of CCK receptor phosphorylation and dephosphorylation, which we have previously described (Klueppelberg, U. G., L. K. Gates, F. S. Gorelick, and L. J. Miller. 1991. J. Biol. Chem. 266:2403-2408; Lutz, M. P., D. I. Pinon, L. K. Gates, S. Shenolikar, and L. J. Miller. 1993. J. Biol. Chem. 268:12136-12142). The rapid onset and peak of receptor phosphorylation after agonist occupation correlates best with a plasmalemmal localization, while stimulated receptor phosphatase activity correlates best with receptor residence in intracellular compartments. We postulate that the smooth vesicular compartment adjacent to the plasmalemma functions for

  2. Comparative Toxicology of Libby Amphibole and Naturally Occurring Asbestos

    EPA Science Inventory

    Summary sentence: Comparative toxicology of Libby amphibole (LA) and site-specific naturally occurring asbestos (NOA) provides new insights on physical properties influencing health effects and mechanisms of asbestos-induced inflammation, fibrosis, and tumorigenesis.Introduction/...

  3. Internet Censorship in China: Where Does the Filtering Occur?

    NASA Astrophysics Data System (ADS)

    Xu, Xueyang; Mao, Z. Morley; Halderman, J. Alex

    China filters Internet traffic in and out of the country. In order to circumvent the firewall, it is helpful to know where the filtering occurs. In this work, we explore the AS-level topology of China's network, and probe the firewall to find the locations of filtering devices. We find that even though most filtering occurs in border ASes, choke points also exist in many provincial networks. The result suggests that two major ISPs in China have different approaches placing filtering devices.

  4. Laminin receptors for neurite formation

    SciTech Connect

    Kleinman, H.K.; Ogle, R.C.; Cannon, F.B.; Little, C.D.; Sweeney, T.M.; Luckenbill-Edds, L.

    1988-02-01

    Laminin, a basement membrane glycoprotein promotes both cell attachment and neurite outgrowth. Separate domains on laminin elicit these responses, suggesting that distinct receptors occur on the surface of cells. NG108-15 neuroblastoma-glioma cells rapidly extend long processes in the presence of laminin. The authors report here that /sup 125/I-labeled laminin specifically binds to these cells and to three membrane proteins of 67, 110, and 180 kDa. These proteins were isolated by affinity chromatography on laminin-Sepharose. The 67-kDa protein reacted with antibody to the previously characterized receptor for cell attachment to laminin. Antibodies to the 110-kDa and 180-kDa bands demonstrated that the 110-kDa protein was found in a variety of epithelial cell lines and in brain, whereas the 180-kDa protein was neural specific. Antibodies prepared against the 110-kDa and 180-kDa proteins inhibited neurite outgrowth induced by the neurite-promoting domain of laminin, whereas antibodies to the 67-kDa laminin receptor had no effect on neurite outgrowth. They conclude that neuronal cells have multiple cell-surface laminin receptors and that the 110-kDa and 180-kDa proteins are involved in neurite formation.

  5. Distribution of cholinergic receptors in the rat and human neocortex.

    PubMed

    Zilles, K; Schröder, H; Schröder, U; Horvath, E; Werner, L; Luiten, P G; Maelicke, A; Strosberg, A D

    1989-01-01

    Autoradiographic labelling of muscarinic (M1, M2, NMS binding sites) and nicotinic receptors shows an inhomogeneous distribution over architectonically identified cortical areas of the rat brain with highest concentrations in the medial prefrontal and frontal areas. Beside this general trend the areal patterns of different receptors are slightly varying. The laminar distribution of these receptors in the rat and human neocortex is characterized by two different patterns, one with highest receptor densities in the supragranular layers (M1 receptors, NMS binding sites), the other with a preferential labelling of layer IV and (with a lower intensity) layer V (M2 and nicotinic receptors). M1 receptors and NMS binding sites are codistributed at the laminar level with each other and with GABAA, D1, 5-HT1 and glutamate receptors; M2 receptors are codistributed only with nicotinic receptors. Immuno-histochemical studies with antibodies against muscarinic and nicotinic receptors demonstrate that these structures occur mainly in pyramidal and spiny stellate cells and to a lesser extent (13%) in a variety of interneurons. The immunoreactivity is visible in the perikaryon, dendrites and postsynaptic membranes. Neurons are found in the human neocortex, which react exclusively with one of the two antibodies, but a fraction of the neurons (about 30%) contains antigenic sites reacting with both antibodies. This is interpreted as colocalization of nicotinic and muscarinic receptors in some cortical neurons.

  6. A search for presynaptic inhibitory histamine receptors in guinea-pig tissues: Further H3 receptors but no evidence for H4 receptors.

    PubMed

    Petri, Doris; Schlicker, Eberhard

    2016-07-01

    The histamine H4 receptor is coupled to Gi/o proteins and expressed on inflammatory cells and lymphoid tissues; it was suggested that this receptor also occurs in the brain or on peripheral neurones. Since many Gi/o protein-coupled receptors, including the H3 receptor, serve as presynaptic inhibitory receptors, we studied whether the sympathetic neurones supplying four peripheral tissues and the cholinergic neurones in the hippocampus from the guinea-pig are equipped with release-modulating H4 and H3 receptors. For this purpose, we preincubated tissue pieces from the aorta, atrium, renal cortex and vas deferens with (3)H-noradrenaline and hippocampal slices with (3)H-choline and determined the electrically evoked tritium overflow. The stimulation-evoked overflow in the five superfused tissues was inhibited by the muscarinic receptor agonist oxotremorine, which served as a positive control, but not affected by the H4 receptor agonist 4-methylhistamine. The H3 receptor agonist R-α-methylhistamine inhibited noradrenaline release in the peripheral tissues without affecting acetylcholine release in the hippocampal slices. Thioperamide shifted the concentration-response curve of histamine in the aorta and the renal cortex to the right, yielding apparent pA2 values of 8.0 and 8.1, respectively, which are close to its affinity at other H3 receptors but higher by one log unit than its pKi at the H4 receptor of the guinea-pig. In conclusion, histamine H4 receptors could not be identified in five experimental models of the guinea-pig that are suited for the detection of presynaptic inhibitory receptors whereas H3 receptors could be shown in the peripheral tissues but not in the hippocampus. This article is part of the Special Issue entitled 'Histamine Receptors'.

  7. Feedback, receptor clustering, and receptor restriction to single cells yield large Turing spaces for ligand-receptor-based Turing models

    NASA Astrophysics Data System (ADS)

    Kurics, Tamás; Menshykau, Denis; Iber, Dagmar

    2014-08-01

    Turing mechanisms can yield a large variety of patterns from noisy, homogenous initial conditions and have been proposed as patterning mechanism for many developmental processes. However, the molecular components that give rise to Turing patterns have remained elusive, and the small size of the parameter space that permits Turing patterns to emerge makes it difficult to explain how Turing patterns could evolve. We have recently shown that Turing patterns can be obtained with a single ligand if the ligand-receptor interaction is taken into account. Here we show that the general properties of ligand-receptor systems result in very large Turing spaces. Thus, the restriction of receptors to single cells, negative feedbacks, regulatory interactions among different ligand-receptor systems, and the clustering of receptors on the cell surface all greatly enlarge the Turing space. We further show that the feedbacks that occur in the FGF10-SHH network that controls lung branching morphogenesis are sufficient to result in large Turing spaces. We conclude that the cellular restriction of receptors provides a mechanism to sufficiently increase the size of the Turing space to make the evolution of Turing patterns likely. Additional feedbacks may then have further enlarged the Turing space. Given their robustness and flexibility, we propose that receptor-ligand-based Turing mechanisms present a general mechanism for patterning in biology.

  8. Feedback, receptor clustering, and receptor restriction to single cells yield large Turing spaces for ligand-receptor-based Turing models.

    PubMed

    Kurics, Tamás; Menshykau, Denis; Iber, Dagmar

    2014-08-01

    Turing mechanisms can yield a large variety of patterns from noisy, homogenous initial conditions and have been proposed as patterning mechanism for many developmental processes. However, the molecular components that give rise to Turing patterns have remained elusive, and the small size of the parameter space that permits Turing patterns to emerge makes it difficult to explain how Turing patterns could evolve. We have recently shown that Turing patterns can be obtained with a single ligand if the ligand-receptor interaction is taken into account. Here we show that the general properties of ligand-receptor systems result in very large Turing spaces. Thus, the restriction of receptors to single cells, negative feedbacks, regulatory interactions among different ligand-receptor systems, and the clustering of receptors on the cell surface all greatly enlarge the Turing space. We further show that the feedbacks that occur in the FGF10-SHH network that controls lung branching morphogenesis are sufficient to result in large Turing spaces. We conclude that the cellular restriction of receptors provides a mechanism to sufficiently increase the size of the Turing space to make the evolution of Turing patterns likely. Additional feedbacks may then have further enlarged the Turing space. Given their robustness and flexibility, we propose that receptor-ligand-based Turing mechanisms present a general mechanism for patterning in biology. PMID:25215767

  9. Evolutionary diversification of the trypanosome haptoglobin-haemoglobin receptor from an ancestral haemoglobin receptor

    PubMed Central

    Lane-Serff, Harriet; MacGregor, Paula; Peacock, Lori; Macleod, Olivia JS; Kay, Christopher; Gibson, Wendy; Higgins, Matthew K; Carrington, Mark

    2016-01-01

    The haptoglobin-haemoglobin receptor of the African trypanosome species, Trypanosoma brucei, is expressed when the parasite is in the bloodstream of the mammalian host, allowing it to acquire haem through the uptake of haptoglobin-haemoglobin complexes. Here we show that in Trypanosoma congolense this receptor is instead expressed in the epimastigote developmental stage that occurs in the tsetse fly, where it acts as a haemoglobin receptor. We also present the structure of the T. congolense receptor in complex with haemoglobin. This allows us to propose an evolutionary history for this receptor, charting the structural and cellular changes that took place as it adapted from a role in the insect to a new role in the mammalian host. DOI: http://dx.doi.org/10.7554/eLife.13044.001 PMID:27083048

  10. On co-design of filter and fault estimator against randomly occurring nonlinearities and randomly occurring deception attacks

    NASA Astrophysics Data System (ADS)

    Hu, Jun; Liu, Steven; Ji, Donghai; Li, Shanqiang

    2016-07-01

    In this paper, the co-design problem of filter and fault estimator is studied for a class of time-varying non-linear stochastic systems subject to randomly occurring nonlinearities and randomly occurring deception attacks. Two mutually independent random variables obeying the Bernoulli distribution are employed to characterize the phenomena of the randomly occurring nonlinearities and randomly occurring deception attacks, respectively. By using the augmentation approach, the co-design problem of the robust filter and fault estimator is converted into the recursive filter design problem. A new compensation scheme is proposed such that, for both randomly occurring nonlinearities and randomly occurring deception attacks, an upper bound of the filtering error covariance is obtained and such an upper bound is minimized by properly designing the filter gain at each sampling instant. Moreover, the explicit form of the filter gain is given based on the solution to two Riccati-like difference equations. It is shown that the proposed co-design algorithm is of a recursive form that is suitable for online computation. Finally, a simulation example is given to illustrate the usefulness of the developed filtering approach.

  11. Solution assembly of cytokine receptor ectodomain complexes

    SciTech Connect

    Wu, Zining; Ciardelli, T.L.; Johnson, K.W.

    1995-09-01

    For the majority of single transmembrane-spanning cell surface receptors, signal transmission across the lipid bilayer barrier involves several discrete components of molecular recognition. The interaction between ligand and the extracellular segment of its cognate receptor (ectodomain) initiates either homomeric or heteromeric association of receptor subunits. Specific recognition among these subunits may then occur between ectodomain regions, within the membrane by interhelical contact or inside the cell between cytoplasmic domains. Any or all of these interactions may contribute to the stability of the signaling complex. It is the characteristics of ligand binding by the ectodomains of these receptors that controls the heteromeric or homomeric nature and the stoichiometry of the complex. Cytokines and their receptors belong to a growing family of macromolecular systems that exhibit these functional features and share many structural similarities as well. Interleukin-2 is a multifunctional cytokine that represents, perhaps, the most complex example to date of ligand recognition among the hematopoietin receptor family. It is the cooperative binding of IL-2 by all three proteins on the surface of activated T-lymphocytes, however, that ultimately results in crosslinking of the {beta}- and {gamma}-subunits and signaling via association of their cytoplasmic domains. Although the high-affinity IL-2R functions as a heterotrimer, heterodimers of the receptor subunits are also physiologically important. The {alpha}/{beta} heterodimer or {open_quotes}pseudo-high affinity{close_quotes} receptor captures IL-2 as a preformed cell surface complex while the {beta}/{gamma} intermediate affinity site exists, in the absence of the {alpha} subunit, on the majority of natural killer cells. We have begun to study stable complexes of cytokine receptor ectodomains of defined composition and that mimic the ligand binding characteristics of the equivalent cell surface receptor sites.

  12. Arsenic poisoning in dairy cattle from naturally occurring arsenic pyrites.

    PubMed

    Hopkirk, R G

    1987-10-01

    An outbreak of arsenic poisoning occurred in which most of a 200 cow dairy herd were affected and six died. The source of the arsenic was naturally occurring arsenic pyrites from the Waiotapu Stream, near Rotorua. Arsenic levels in the nearby soil were as high as 6618 ppm. There was little evidence to suggest that treatment affected the course of the disease. Haematology was of little use in diagnosis, post-mortem signs were not always consistent and persistence of the element in the liver appeared short. Control of further outbreaks have been based on practical measures to minimise the intake of contaminated soil and free laying water by the stock. PMID:16031332

  13. Arsenic poisoning in dairy cattle from naturally occurring arsenic pyrites.

    PubMed

    Hopkirk, R G

    1987-10-01

    An outbreak of arsenic poisoning occurred in which most of a 200 cow dairy herd were affected and six died. The source of the arsenic was naturally occurring arsenic pyrites from the Waiotapu Stream, near Rotorua. Arsenic levels in the nearby soil were as high as 6618 ppm. There was little evidence to suggest that treatment affected the course of the disease. Haematology was of little use in diagnosis, post-mortem signs were not always consistent and persistence of the element in the liver appeared short. Control of further outbreaks have been based on practical measures to minimise the intake of contaminated soil and free laying water by the stock.

  14. Crustacean retinoid-X receptor isoforms: distinctive DNA binding and receptor-receptor interaction with a cognate ecdysteroid receptor.

    PubMed

    Wu, Xiaohui; Hopkins, Penny M; Palli, Subba R; Durica, David S

    2004-04-15

    We have identified cDNA clones that encode homologs of the ecdysteroid receptor (EcR) and retinoid-X receptor (RXR)/USP classes of nuclear receptors from the fiddler crab Uca pugilator (UpEcR and UpRXR). Several UpRXR cDNA splicing variants were found in coding regions that could potentially influence function. A five-amino acid (aa) insertion/deletion is located in the "T" box in the hinge region. Another 33-aa insertion/deletion is found inside the ligand-binding domain (LBD), between helix 1 and helix 3. Ribonuclease protection assays (RPA) showed that four UpRXR transcripts [UpRXR(+5+33), UpRXR(-5+33), UpRXR(+5-33) and UpRXR(-5-33)] were present in regenerating limb buds. UpRXR(-5+33) was the most abundant transcript present in regenerating limb buds in both early blastema and late premolt growth stages. Expression vectors for these UpRXR variants and UpEcR were constructed, and the proteins expressed in E. coli and in vitro expression systems. The expressed crab nuclear receptors were then characterized by electrophoretic mobility shift assay (EMSA) and glutathione S-transferase (GST) pull down experiments. EMSA results showed that UpEcR/UpRXR(-5+33) heterocomplexes bound with a series of hormone response elements (HREs) including eip28/29, IRper-1, DR-4, and IRhsp-1 with appreciable affinity. Competition EMSA also showed that the affinity decreased as sequence composition deviated from a perfect consensus element. Binding to IRper-1 HREs occurred only if the heterodimer partner UpRXR contained the 33-aa LBD insertion. UpRXR lacking both the 5-aa and 33-aa insertion bound to a DR-1G HRE in the absence of UpEcR. The results of GST-pull down experiments showed that UpEcR interacted only with UpRXR variants containing the 33-aa insertion, and not with those lacking the 33-aa insertion. These in vitro receptor protein-DNA and receptor protein-protein interactions occurred in the absence of hormone (20-hydroxyecdysone and 9-cis retinoid acid, 9-cis RA

  15. Naturally occurring variability in the envelope glycoprotein of HIV-1 and development of cell entry inhibitors.

    PubMed

    Brower, Evan T; Schön, Arne; Freire, Ernesto

    2010-03-23

    Naturally occurring genetic variability across HIV-1 subtypes causes amino acid polymorphisms in encoded HIV-1 proteins including the envelope glycoproteins associated with viral entry. The effects of amino acid polymorphisms on the mechanism of HIV-1 entry into cells, a process initiated by the binding of the viral envelope glycoprotein gp120 to the cellular CD4 receptor, are largely unknown. In this study, we demonstrate that amino acid polymorphisms affect the structural stability and domain cooperativity of gp120 and that those differences are reflected in the binding mechanism of the viral envelope glycoprotein to the cell surface receptor and coreceptor. Moreover, subtype differences also affect the binding behavior of experimental HIV cell entry inhibitors. While gp120-A has a slightly lower denaturation temperature than gp120-B, the most notable stability difference is that for gp120-B the van't Hoff to calorimetric enthalpy ratio (DeltaH(vH)/DeltaH) is 0.95 whereas for gp120-A is 0.6, indicative of more cooperative domain/domain interactions in gp120-B, as this protein more closely approaches a two-state transition. Isothermal titration calorimetry demonstrates that CD4 and 17b (a surrogate antibody for the chemokine coreceptor) exhibit 7- and 3-fold weaker binding affinities for gp120-A. The binding of these proteins as well as that of the experimental entry inhibitor NBD-556 induces smaller conformational changes in gp120-A as evidenced by significantly smaller binding enthalpies and binding entropies. Together, these results describe the effects of gp120 polymorphisms on binding to host cell receptors and emphasize that guidelines for developing future entry inhibitors must recognize and deal with genomic differences between HIV strains.

  16. Bacterial chemotaxis to xenobiotic chemicals and naturally-occurring analogs.

    PubMed

    Parales, Rebecca E; Luu, Rita A; Hughes, Jonathan G; Ditty, Jayna L

    2015-06-01

    The study of chemotaxis to xenobiotic chemicals in soil bacteria has revealed that the core mechanism for transduction of chemotactic signals is conserved. Responses to chemicals degraded by specialized catabolic pathways are often coordinately regulated with degradation genes, and in some cases auxiliary processes such as transport are integrated into the sensory process. In addition, degradation genes and associated chemotaxis genes carried on transmissible plasmids may facilitate the dissemination and evolution of catabolic and sensory systems. However, the strategies and receptors used by bacteria to sense chemicals are difficult to predict solely by bioinformatics, and much work is needed to uncover the range of chemicals detected and the specific functions of the numerous chemoreceptors present in catabolically versatile soil bacteria.

  17. Complex high affinity interactions occur between MHCI and superantigens

    NASA Technical Reports Server (NTRS)

    Chapes, S. K.; Herpich, A. R.; Spooner, B. S. (Principal Investigator)

    1998-01-01

    Staphylococcal enterotoxins A and C1 (SEA or SEC1) bound to major histocompatibility-I (MHCI) molecules with high affinity (binding constants ranging from 1.1 microM to 79 nM). SEA and SEC1 directly bound MHCI molecules that had been captured by monoclonal antibodies specific for H-2Kk, H-2Dk, or both. In addition, MHCI-specific antibodies inhibited the binding of SEC1 to LM929 cells and SEA competitively inhibited SEC1 binding; indicating that the superantigens bound to MHCI on the cell surface. The affinity and number of superantigen binding sites differed depending on whether MHCI was expressed in the membrane of LM929 cells or whether it was captured. These data support the hypothesis that MHCI molecules can serve as superantigen receptors.

  18. Social and Economic Polarization: Is It Occurring among Blacks?

    ERIC Educational Resources Information Center

    Farley, Reynolds; Bianchi, Suzanne M.

    An emerging hypothesis about black progress since the civil rights movement in the United States postulates that economic polarization is occurring in the black community. This hypothesis, which incorporates conflicting earlier theories of declining versus persistent racial differences, suggests that talented and well-educated blacks are competing…

  19. Naturally occurring fatty acids: source, chemistry and uses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Natural occurring fatty acids are a large and complex class of compounds found in plants and animals. Fatty acids are abundant and of interest because of their renewability, biodegradability, biocompatibility, low cost, and fascinating chemistry. Of the many fatty acids, only 20-25 of them are widel...

  20. Integrative Priming Occurs Rapidly and Uncontrollably during Lexical Processing

    ERIC Educational Resources Information Center

    Estes, Zachary; Jones, Lara L.

    2009-01-01

    Lexical priming, whereby a prime word facilitates recognition of a related target word (e.g., "nurse" [right arrrow] "doctor"), is typically attributed to association strength, semantic similarity, or compound familiarity. Here, the authors demonstrate a novel type of lexical priming that occurs among unassociated, dissimilar, and unfamiliar…

  1. URBAN STORMWATER TRACING WITH THE NATURALLY OCCURRING DEUTERIUM ISOTOPE

    EPA Science Inventory

    Measurements of the naturally-occurring deuterium isotope assist the tracing of water components during wet-weather flows in an urban watershed. A transect of installations in the vadose and saturated zones was completed in the vicinity of a small stream and storm sewer. High-r...

  2. 33 CFR 330.3 - Activities occurring before certain dates.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... waters of the United States outside the limits of navigable waters of the United States that occurred before the phase-in dates which extended Section 404 jurisdiction to all waters of the United States. The phase-in dates were: After July 25, 1975, discharges into navigable waters......

  3. 33 CFR 330.3 - Activities occurring before certain dates.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... waters of the United States outside the limits of navigable waters of the United States that occurred before the phase-in dates which extended Section 404 jurisdiction to all waters of the United States. The phase-in dates were: After July 25, 1975, discharges into navigable waters......

  4. 33 CFR 330.3 - Activities occurring before certain dates.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... waters of the United States outside the limits of navigable waters of the United States that occurred before the phase-in dates which extended Section 404 jurisdiction to all waters of the United States. The phase-in dates were: After July 25, 1975, discharges into navigable waters......

  5. 33 CFR 330.3 - Activities occurring before certain dates.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... waters of the United States outside the limits of navigable waters of the United States that occurred before the phase-in dates which extended Section 404 jurisdiction to all waters of the United States. The phase-in dates were: After July 25, 1975, discharges into navigable waters......

  6. RUN OUTS OCCUR WHEN IRON HAS UNSEATED MOLDING SAND AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    RUN OUTS OCCUR WHEN IRON HAS UNSEATED MOLDING SAND AND RUN OUT OF THE MOLD UNDER POURING JACKETS AND SPILLS ONTO THE MOLDING PLATFORM. WORKERS GENERALLY WAIT SEVERAL MINUTES FOR THE IRON TO SOLIDIFY AND, WHILE IT IS STILL RED-HOT, REMOVE IT FROM THE PLATFORM AND SCRAP THE MOLD. - Southern Ductile Casting Company, Centerville Foundry, 101 Airport Road, Centreville, Bibb County, AL

  7. Mineralogical Characteristics of Carbonate Rock-Hosted Naturally Occurring Asbestos

    NASA Astrophysics Data System (ADS)

    Shin, E.; Roh, Y.

    2012-12-01

    Naturally Occurring Asbestos (NOA) occurs in rocks and soils as a result of natural weathering and human activities. The parent rocks of asbestos have been associated with ultramafic and mafic rocks, and carbonate rock. The previous studies on naturally occurring asbestos were mainly limited to ultramafic and mafic rock-hosted asbestos and studies on carbonate rock-hosted asbestos are relatively rare in South Korea. Therefore, this study was aimed to characterize mineralogy of carbonate rock-hosted NOA at Muju and Jangsu, Jeonbuk province and Seosan and Asan, Chungnam province. The rock types at the four sites are consisting mainly of Precambrian metasedimentary rock. XRD and PLM analyses showed fibrous minerals in the sites were tremolite and actinolite of acicular and columnar forms. SEM-EDS analyses showed that asbestiform tremolite and actinolite had various ratios of length and diameters over 12:1, and needle and columnar forms. A columnar forms of tremolite and actinolite were showed small acicular at the edge of the particle. Its main chemical compositions are mainly Si, O, Mg, Ca, which were identical to tremolite. Actinolite contains Fe in addition to Si, O, Mg, Ca. EPMA analyses of asbestos occurred at Muju indicated that chemical composition are 55% SiO2, 23.2% MgO, 13.1 % CaO, and 0.61 % FeO and the chemical formula calculated as (K0.01Na0.01)Ca2.01(Mg4.94Fe0.05) (Al0.004Si7.98)O22(OH)2, which is close to ideal tremolite. In addition to tremolite, actinolite was also occurred at Seosan, Chungnam. XRD analyses showed that antigorite was existed at Muju, but PLM and SEM analyses showed the antigorite was platy structure, not asbestiform. These results indicate that asbestiform tremolite and actinolite with acicular forms contains in carbonate rocks at Muju and Jangsu, Jeonbuk and Seosan and Asan, Chungnam province South Korea.

  8. Clonal deletion of thymocytes can occur in the cortex with no involvement of the medulla

    PubMed Central

    McCaughtry, Tom M.; Baldwin, Troy A.; Wilken, Matthew S.; Hogquist, Kristin A.

    2008-01-01

    The thymic medulla is generally held to be a specialized environment for negative selection. However, many self-reactive thymocytes first encounter ubiquitous self-antigens in the cortex. Cortical epithelial cells are vital for positive selection, but whether such cells can also promote negative selection is controversial. We used the HYcd4 model, where T cell receptor for antigen (TCR) expression is appropriately timed and a ubiquitous self-antigen drives clonal deletion in male mice. We demonstrated unambiguously that this deletion event occurs in the thymic cortex. However, the kinetics in vivo indicated that apoptosis was activated asynchronously relative to TCR activation. We found that radioresistant antigen-presenting cells and, specifically, cortical epithelial cells do not efficiently induce apoptosis, although they do cause TCR activation. Rather, thymocytes undergoing clonal deletion were preferentially associated with rare CD11c+ cortical dendritic cells, and elimination of such cells impaired deletion. PMID:18936237

  9. Historical overview of nuclear receptors.

    PubMed

    Gustafsson, Jan-Ake

    2016-03-01

    This review summarizes the birth of the field of nuclear receptors, from Jensen's discovery of estrogen receptor alpha, Gustafsson's discovery of the three-domain structure of the glucocorticoid receptor, the discovery of the glucocorticoid response element and the first partial cloning of the glucocorticoid receptor. Furthermore the discovery of the novel receptors called orphan receptors is described.

  10. Bordetella pertussis naturally occurring isolates with altered lipooligosaccharide structure fail to fully mature human dendritic cells.

    PubMed

    Brummelman, Jolanda; Veerman, Rosanne E; Hamstra, Hendrik Jan; Deuss, Anna J M; Schuijt, Tim J; Sloots, Arjen; Kuipers, Betsy; van Els, Cécile A C M; van der Ley, Peter; Mooi, Frits R; Han, Wanda G H; Pinelli, Elena

    2015-01-01

    Bordetella pertussis is a Gram-negative bacterium and the causative agent of whooping cough. Despite high vaccination coverage, outbreaks are being increasingly reported worldwide. Possible explanations include adaptation of this pathogen, which may interfere with recognition by the innate immune system. Here, we describe innate immune recognition and responses to different B. pertussis clinical isolates. By using HEK-Blue cells transfected with different pattern recognition receptors, we found that 3 out of 19 clinical isolates failed to activate Toll-like receptor 4 (TLR4). These findings were confirmed by using the monocytic MM6 cell line. Although incubation with high concentrations of these 3 strains resulted in significant activation of the MM6 cells, it was found to occur mainly through interaction with TLR2 and not through TLR4. When using live bacteria, these 3 strains also failed to activate TLR4 on HEK-Blue cells, and activation of MM6 cells or human monocyte-derived dendritic cells was significantly lower than activation induced by the other 16 strains. Mass spectrum analysis of the lipid A moieties from these 3 strains indicated an altered structure of this molecule. Gene sequence analysis revealed mutations in genes involved in lipid A synthesis. Findings from this study indicate that B. pertussis isolates that do not activate TLR4 occur naturally and that this phenotype may give this bacterium an advantage in tempering the innate immune response and establishing infection. Knowledge on the strategies used by this pathogen in evading the host immune response is essential for the improvement of current vaccines or for the development of new ones.

  11. Regulation and ontogeny of subtypes of muscarinic receptors and muscarinic receptor-mediated

    SciTech Connect

    Lee, W.

    1989-01-01

    The densities of total and M1 muscarinic receptors were measured using the muscarinic receptor antagonists {sup 3}H-quinuclidinyl benzilate and {sup 3}H-pirenzepine, respectively. Thus, the difference between the density of {sup 3}H-quinuclidinyl benzilate and {sup 3}H-pirenzepine binding sites represents the density of M2 sites. In addition, there is no observable change in either acetylcholine-stimulated phosphoinositide breakdown (suggested to be an M1 receptor-mediated response) or in carbachol-mediated inhibition of cyclic AMP accumulation (suggested to be an M2 receptor-mediated response) in slices of cortex+dorsal hippocampus following chronic atropine administration. In other experiments, it has been shown that the M1 and M2 receptors in rat cortex have different ontogenetic profiles. The M2 receptor is present at adult levels at birth, while the M1 receptor develops slowly from low levels at postnatal week 1 to adult levels at postnatal week 3. The expression of acetylcholine-stimulated phosphoinositide breakdown parallels the development of M1 receptors, while the development of carbachol-mediated inhibition of cyclic AMP accumulation occurs abruptly between weeks 2 and 3 postnatally.

  12. Anti-NMDA Receptor Encephalitis in a Pregnant Woman

    PubMed Central

    Kim, Jiyoung; Park, Seung Ha; Jung, Yu Ri; Park, Soon Won; Jung, Dae Soo

    2015-01-01

    Anti N-methyl-D-aspartate (NMDA) receptor encephalitis is one of the most common types of autoimmune synaptic encephalitis. Anti-NMDA receptor encephalitis commonly occurs in young women with ovarian teratoma. It has variable clinical manifestations and treatment responses. Sometimes it is misdiagnosed as a psychiatric disorder or viral encephalitis. To the best of our knowledge, anti-NMDA receptor encephalitis is a rare condition in pregnant women. We report a case of anti-NMDA receptor encephalitis in a pregnant woman who presented with abnormal behavior, epileptic seizure, and hypoventilation. PMID:26157673

  13. Standardizing Scavenger Receptor Nomenclature

    PubMed Central

    PrabhuDas, Mercy; Bowdish, Dawn; Drickamer, Kurt; Febbraio, Maria; Herz, Joachim; Kobzik, Lester; Krieger, Monty; Loike, John; Means, Terry K.; Moestrup, Soren K.; Post, Steven; Sawamura, Tatsuya; Silverstein, Samuel; Wang, Xiang-Yang; El Khoury, Joseph

    2014-01-01

    Scavenger receptors constitute a large family of proteins that are structurally diverse and participate in a wide range of biological functions. These receptors are expressed predominantly by myeloid cells and recognize a variety of ligands, including endogenous and modified host-derived molecules and microbial pathogens. There are currently eight classes of scavenger receptors, many of which have multiple names, leading to inconsistencies and confusion in the literature. To address this problem, a workshop was organized by the U.S. National Institute of Allergy and Infectious Diseases, National Institutes of Health to help develop a clear definition of scavenger receptors and a standardized nomenclature based on that definition. Fifteen experts in the scavenger receptor field attended the workshop and, after extensive discussion, reached a consensus regarding the definition of scavenger receptors and a proposed scavenger receptor nomenclature. Scavenger receptors were defined as cell surface receptors that typically bind multiple ligands and promote the removal of non-self or altered-self targets. They often function by mechanisms that include endocytosis, phagocytosis, adhesion, and signaling that ultimately lead to the elimination of degraded or harmful substances. Based on this definition, nomenclature and classification of these receptors into 10 classes were proposed. The discussion and nomenclature recommendations described in this report only refer to mammalian scavenger receptors. The purpose of this article is to describe the proposed mammalian nomenclature and classification developed at the workshop and to solicit additional feedback from the broader research community. PMID:24563502

  14. Issues related to regulatory control of naturally occurring radioactive materials

    SciTech Connect

    Chen, S.Y.

    1997-04-01

    Nearly 80% of human radiation exposure is from naturally occurring radioactive materials (NORM). While exposure from man-made sources of radiation has been well regulated, no consistent regulatory controls exist for NORM. Because elevated radiation levels have resulted from NORM enhancement activities such as occur in the petroleum, fertilizer, mining, and processing industries, some form of regulatory control is in order. In the US, regulation of NORM by federal agencies such as the Nuclear Regulatory Commission or the Environmental Protection Agency is not anticipated in the near future because there are no authorizing federal statutes. Important issues for addressing the control of NORM include source characterization and generation, radiation protection concerns, waste management and disposition, and the regulatory framework.

  15. Stress fractures of the second metatarsal base occur in nondancers.

    PubMed

    Chuckpaiwong, Bavornrit; Cook, Chad; Nunley, James A

    2007-08-01

    Stress fractures of the base of the second metatarsal are common in ballet dancers and essentially are unreported in nondancers. We presumed base of the second metatarsal stress fractures in nondancers occur in a wide variety of individuals regardless of demographics, are highly associated with athletic activities, and have specific examination findings and poor clinical outcomes. Using a retrospective chart review, we identified 12 stress fractures at the base of the second metatarsal (nine patients) in nondancers. Our review suggests second metatarsal base stress fractures occur in nondancers in a diverse population, and nonoperative treatment provides limited success. Advanced radiographic study, specifically MRI, is useful to assist the early diagnosis and prognostication. All of the stress fractures were treated nonoperatively; six fractures (50%) developed nonunion and five underwent subsequent surgery. The surgery for nonunion provided successful outcomes; however, risk factors such as low bone mass and comorbidities may have played important roles in the prognosis.

  16. The Natural Occurring Compounds Targeting Endoplasmic Reticulum Stress.

    PubMed

    Liu, Hai; Yang, Jianqiong; Li, Linfu; Shi, Weimei; Yuan, Xiaoliang; Wu, Longhuo

    2016-01-01

    ER stress has been implicated in pathophysiological development of many diseases. Persistent overwhelming stimuli trigger ER stress to initiate apoptosis, autophagy, and cell death. IRE1-JNK and eIF2α-CHOP signaling pathways are the two important players of ER stress, which is also modulated by ROS production, calcium disturbance, and inflammatory factors. ER stress has been developed as a novel strategy for diseases management. Recently, a vast of research focuses on the natural occurring compounds targeting ER stress, which results in medical benefits to human diseases. These small reported molecules mainly include polyphenols, alkaloids, and saponins. Many of them have been developed for use in clinical applications. To better understand the pharmacological mechanism of these molecules in ER stress in diseases, efforts have been made to discover and deliver medical merits. In this paper, we will summarize the natural occurring compounds targeting ER stress. PMID:27563337

  17. The Natural Occurring Compounds Targeting Endoplasmic Reticulum Stress

    PubMed Central

    Liu, Hai; Yang, Jianqiong; Li, Linfu; Shi, Weimei

    2016-01-01

    ER stress has been implicated in pathophysiological development of many diseases. Persistent overwhelming stimuli trigger ER stress to initiate apoptosis, autophagy, and cell death. IRE1-JNK and eIF2α-CHOP signaling pathways are the two important players of ER stress, which is also modulated by ROS production, calcium disturbance, and inflammatory factors. ER stress has been developed as a novel strategy for diseases management. Recently, a vast of research focuses on the natural occurring compounds targeting ER stress, which results in medical benefits to human diseases. These small reported molecules mainly include polyphenols, alkaloids, and saponins. Many of them have been developed for use in clinical applications. To better understand the pharmacological mechanism of these molecules in ER stress in diseases, efforts have been made to discover and deliver medical merits. In this paper, we will summarize the natural occurring compounds targeting ER stress. PMID:27563337

  18. Naturally occurring iridoids and secoiridoids. An updated review, part 4.

    PubMed

    Dinda, Biswanath; Debnath, Sudhan; Banik, Rajarshi

    2011-01-01

    A compilation of new naturally occurring iridoids and secoiridoids including their glycosides, esters, aglycones, derivatives and dimers reported during mid 2008-2010 is provided with available physical and spectral data: mp, [α](D), UV, IR, circular dichroism (CD), (1)H- and (13)C-NMR as well as natural source with family and references. The important bioactivity of new and known iridoids and secoiridoids reported during this period is also highlighted.

  19. Analytical evaluation of integrals occurring in bound-free transitions

    SciTech Connect

    Burlon, R.; Leone, C.; Basile, S.; Trombetta, F.; Ferrante, G.

    1988-01-15

    A class of three-dimensional integrals on spatial coordinates of the type occurring in treatments of multiphoton ionization of atoms and of other bound-free transitions is evaluated in closed form for both hydrogenic and Slater-type wave functions. The reported method of evaluation is illustrated with a number of examples, including the multiphoton ionization of hydrogen by a very intense laser field, when the ejected electrons have absorbed more photons than the minimum required to reach the continuum.

  20. Sensory-motor transformations for speech occur bilaterally.

    PubMed

    Cogan, Gregory B; Thesen, Thomas; Carlson, Chad; Doyle, Werner; Devinsky, Orrin; Pesaran, Bijan

    2014-03-01

    Historically, the study of speech processing has emphasized a strong link between auditory perceptual input and motor production output. A kind of 'parity' is essential, as both perception- and production-based representations must form a unified interface to facilitate access to higher-order language processes such as syntax and semantics, believed to be computed in the dominant, typically left hemisphere. Although various theories have been proposed to unite perception and production, the underlying neural mechanisms are unclear. Early models of speech and language processing proposed that perceptual processing occurred in the left posterior superior temporal gyrus (Wernicke's area) and motor production processes occurred in the left inferior frontal gyrus (Broca's area). Sensory activity was proposed to link to production activity through connecting fibre tracts, forming the left lateralized speech sensory-motor system. Although recent evidence indicates that speech perception occurs bilaterally, prevailing models maintain that the speech sensory-motor system is left lateralized and facilitates the transformation from sensory-based auditory representations to motor-based production representations. However, evidence for the lateralized computation of sensory-motor speech transformations is indirect and primarily comes from stroke patients that have speech repetition deficits (conduction aphasia) and studies using covert speech and haemodynamic functional imaging. Whether the speech sensory-motor system is lateralized, like higher-order language processes, or bilateral, like speech perception, is controversial. Here we use direct neural recordings in subjects performing sensory-motor tasks involving overt speech production to show that sensory-motor transformations occur bilaterally. We demonstrate that electrodes over bilateral inferior frontal, inferior parietal, superior temporal, premotor and somatosensory cortices exhibit robust sensory-motor neural

  1. Occurence of ore metals in some terrestrial geothermal systems

    SciTech Connect

    Browne, P.

    1984-02-01

    Drilling programs and the study of active geothermal systems have shown that the reservoir rocks in many fields contain minor quantities of base and precious metals. Commonly, base-metal sulfides occur in the subsurface but, where present, Au, Ag, Hg, As, Tl and Sb rich precipitates deposit near, or at, the surface. Although in some fields (Geysers, Larderello, Tongonan) some of the ore minerals (and others) are relict, there is evidence that they are now depositing in a few systems. Recent work on active hydrothermal systems in New Zealand shows that: (1) Sphalerite, galena, chalcopyrite (forming veins and disseminated discrete crystals) plus rare pentlandite, cobaltite and arsenopyrite, occur at Broadlands, NZ. Rare quantities of base-metal sulfides also occur in cores and cuttings from the geothermal fields of Waiotapu, Kawerau, Tauhara, and Ngawha. Further, Kakimoto (1983) has identified cassiterite, native silver, and trace gold in cores from Tauhara, in the south-eastern part of the Wairakei field. Bore temperatures at the depths from which these minerals were recovered are mostly between 220/sup 0/ and 300/sup 0/C, but at Broadlands are locally as low as 120/sup 0/C. The host rocks are Quaternary calc-alkali, silicic lavas and pyroclastic rocks, andesites, dacite and deep Mesozoic greywackes and argillites; however, there is no obvious relationship between mineralization and stratigraphy, permeability or well output. The deposition of amorphous precious metal precipitates (Au, Ag, Hg, As, Sb, Tl) from hot springs and well discharges has taken place at Broadlands, Waiotapu and Rotokawa; it also occurs at Kawerau. Water discharging from Frying Pan Lake, Waimangu, is presently depositing siliceous sinter containing up to 4.1% tungsten.

  2. Sensory-motor transformations for speech occur bilaterally.

    PubMed

    Cogan, Gregory B; Thesen, Thomas; Carlson, Chad; Doyle, Werner; Devinsky, Orrin; Pesaran, Bijan

    2014-03-01

    Historically, the study of speech processing has emphasized a strong link between auditory perceptual input and motor production output. A kind of 'parity' is essential, as both perception- and production-based representations must form a unified interface to facilitate access to higher-order language processes such as syntax and semantics, believed to be computed in the dominant, typically left hemisphere. Although various theories have been proposed to unite perception and production, the underlying neural mechanisms are unclear. Early models of speech and language processing proposed that perceptual processing occurred in the left posterior superior temporal gyrus (Wernicke's area) and motor production processes occurred in the left inferior frontal gyrus (Broca's area). Sensory activity was proposed to link to production activity through connecting fibre tracts, forming the left lateralized speech sensory-motor system. Although recent evidence indicates that speech perception occurs bilaterally, prevailing models maintain that the speech sensory-motor system is left lateralized and facilitates the transformation from sensory-based auditory representations to motor-based production representations. However, evidence for the lateralized computation of sensory-motor speech transformations is indirect and primarily comes from stroke patients that have speech repetition deficits (conduction aphasia) and studies using covert speech and haemodynamic functional imaging. Whether the speech sensory-motor system is lateralized, like higher-order language processes, or bilateral, like speech perception, is controversial. Here we use direct neural recordings in subjects performing sensory-motor tasks involving overt speech production to show that sensory-motor transformations occur bilaterally. We demonstrate that electrodes over bilateral inferior frontal, inferior parietal, superior temporal, premotor and somatosensory cortices exhibit robust sensory-motor neural

  3. Where and when does reconnection occur in the tail?

    NASA Astrophysics Data System (ADS)

    McPherron, Robert L.

    2016-05-01

    We comment on the question of when and where reconnection begins in the tail and how it is related to the onset of auroral expansion. This question was addressed in a workshop dedicated to Unsolved Problems in Magnetospheric Physics held in Scarborough, UK, in September 2015. The answer is that it typically occurs first in the midtail a little beyond 20 Re somewhat before midnight about 55 min after a southward turning of the solar wind magnetic field. It appears to be a consequence of plasma sheet thinning down to the scale of an ion gyroradius. The onset of the activation and expansion of auroral activity and accompanying magnetic signatures typically occur within 1 or 2 min of the appearance of signatures of midtail reconnection. The unanswered question is which comes first and whether reconnection is the cause of the auroral expansion. We point out that older observations clearly established that plasmoids (flux ropes) are released from near 20 Re within a few minutes of the usual signatures of expansion onset. This is only possible if reconnection occurs close to the Earth. More detailed observations with modern spacecraft have led to the development of new explanations for the cause of the substorm expansion that appear to neglect older observations. We conclude that it is essential to carefully define the various terms used in the study of substorms and to develop quantitative methods that enable statistical studies of the various processes associated with auroral expansion onset.

  4. Pathologic features of naturally occurring juvenile polyarteritis in beagle dogs.

    PubMed

    Snyder, P W; Kazacos, E A; Scott-Moncrieff, J C; HogenEsch, H; Carlton, W W; Glickman, L T; Felsburg, P J

    1995-07-01

    Eighteen young Beagle dogs (eight males and 10 females), ages 6-40 months, with canine juvenile polyarteritis syndrome (CJPS), a naturally occurring vasculitis and perivasculitis of unknown etiology, were necropsied, and their tissues were examined by histopathologic and histochemical methods. The condition is characterized by recurring episodes of an acute onset of fever (> 40 C) and neck pain that persist for 3-7 days. The major histopathologic alterations were a systemic vasculitis and perivasculitis. During the febrile, painful period of CJPS, the vascular lesions ranged from a histiocytic-lymphocytic periarterial infiltration to transmural arterial inflammation with concomitant fibrinoid necrosis and vascular thrombosis. Massive periarterial accumulations of inflammatory cells were common and often extended into adjacent tissues. The small- to medium-sized muscular arteries of the heart, cranial mediastinum, and cervical spinal meninges were consistently involved. Vasculitis occasionally occurred in other organ systems. The vascular lesions in dogs examined during clinically normal periods consisted of intimal and medial fibrosis, ruptured elastic laminae, and mild perivasculitis; these lesions were probably related to previous episodes of vasculitis. Eight dogs that had experienced repeated acute episodes also developed splenic, hepatic, and renal amyloidosis. The clinical signs, laboratory abnormalities, and the vascular lesions suggest that the condition may be immune-system mediated. CJPS may serve as a naturally occurring animal model of human immune-system-mediated vasculitides such as polyarteritis nodosa, infantile polyarteritis, and Kawasaki disease.

  5. Skin picking disorder with co-occurring body dysmorphic disorder.

    PubMed

    Grant, Jon E; Redden, Sarah A; Leppink, Eric W; Odlaug, Brian L

    2015-09-01

    There is clinical overlap between skin picking disorder (SPD) and body dysmorphic disorder (BDD), but little research has examined clinical and cognitive correlates of the two disorders when they co-occur. Of 55 participants with SPD recruited for a neurocognitive study and two pharmacological studies, 16 (29.1%) had co-occurring BDD. SPD participants with and without BDD were compared to each other and to 40 healthy volunteers on measures of symptom severity, social functioning, and cognitive assessments using the Stop-signal task (assessing response impulsivity) and the Intra-dimensional/Extra-dimensional Set Shift task (assessing cognitive flexibility). Individuals with SPD and BDD exhibited significantly worse picking, significantly worse overall psychosocial functioning, and significantly greater dysfunction on aspects of cognitive flexibility. These results indicate that when SPD co-occurs with BDD unique clinical and cognitive aspects of SPD may be more pronounced. Future work should explore possible subgroups in SPD and whether these predict different treatment outcomes. PMID:26070103

  6. 5-HT(1A) receptors transactivate the platelet-derived growth factor receptor type beta in neuronal cells.

    PubMed

    Kruk, Jeff S; Vasefi, Maryam S; Liu, Hui; Heikkila, John J; Beazely, Michael A

    2013-01-01

    In the absence of ligand, certain growth factor receptors can be activated via G-protein coupled receptor (GPCR) activation in a process termed transactivation. Serotonin (5-HT) receptors can transactivate platelet-derived growth factor (PDGF) β receptors in smooth muscle cells, but it is not known if similar pathways occur in neuronal cells. Here we show that 5-HT can transiently increase the phosphorylation of PDGFβ receptors through 5-HT(1A) receptors in a time- and dose-dependent manner in SH-SY5Y neuroblastoma cells. 5-HT also transactivates PDGFβ receptors in primary cortical neurons. This transactivation pathway is pertussis-toxin sensitive and Src tyrosine kinase-dependent. This pathway is also dependent on phospholipase C activity and intracellular calcium signaling. Several studies involving PDGFβ receptor transactivation by GPCRs have also demonstrated a PDGFβ receptor-dependent increase in the phosphorylation of ERK1/2. Yet in SH-SY5Y cells, 5-HT treatment causes a PDGFβ receptor-independent increase in ERK1/2 phosphorylation. This crosstalk between 5-HT and PDGFβ receptors identifies a potentially important signaling link between the serotonergic system and growth factor signaling in neurons. PMID:23006663

  7. Mechanism of A2 adenosine receptor activation. I. Blockade of A2 adenosine receptors by photoaffinity labeling

    SciTech Connect

    Lohse, M.J.; Klotz, K.N.; Schwabe, U.

    1991-04-01

    It has previously been shown that covalent incorporation of the photoreactive adenosine derivative (R)-2-azido-N6-p-hydroxy-phenylisopropyladenosine ((R)-AHPIA) into the A1 adenosine receptor of intact fat cells leads to a persistent activation of this receptor, resulting in a reduction of cellular cAMP levels. In contrast, covalent incorporation of (R)-AHPIA into human platelet membranes, which contain only stimulatory A2 adenosine receptors, reduces adenylate cyclase stimulation via these receptors. This effect of (R)-AHPIA is specific for the A2 receptor and can be prevented by the adenosine receptor antagonist theophylline. Binding studies indicate that up to 90% of A2 receptors can be blocked by photoincorporation of (R)-AHPIA. However, the remaining 10-20% of A2 receptors are sufficient to mediate an adenylate cyclase stimulation of up to 50% of the control value. Similarly, the activation via these 10-20% of receptors occurs with a half-life that is only 2 times longer than that in control membranes. This indicates the presence of a receptor reserve, with respect to both the extent and the rate of adenylate cyclase stimulation. These observations require a modification of the models of receptor-adenylate cyclase coupling.

  8. Modes of glutamate receptor gating

    PubMed Central

    Popescu, Gabriela K

    2012-01-01

    Abstract The time course of excitatory synaptic currents, the major means of fast communication between neurons of the central nervous system, is encoded in the dynamic behaviour of post-synaptic glutamate-activated channels. First-pass attempts to explain the glutamate-elicited currents with mathematical models produced reaction mechanisms that included only the most basic functionally defined states: resting vs. liganded, closed vs. open, responsive vs. desensitized. In contrast, single-molecule observations afforded by the patch-clamp technique revealed an unanticipated kinetic multiplicity of transitions: from microseconds-lasting flickers to minutes-long modes. How these kinetically defined events impact the shape of the synaptic response, how they relate to rearrangements in receptor structure, and whether and how they are physiologically controlled represent currently active research directions. Modal gating, which refers to the slowest, least frequently observed ion-channel transitions, has been demonstrated for representatives of all ion channel families. However, reaction schemes have been largely confined to the short- and medium-range time scales. For glutamate receptors as well, modal gating has only recently come under rigorous scrutiny. This article reviews the evidence for modal gating of glutamate receptors and the still developing hypotheses about the mechanism(s) by which modal shifts occur and the ways in which they may impact the time course of synaptic transmission. PMID:22106181

  9. P2X receptors.

    PubMed

    North, R Alan

    2016-08-01

    Extracellular adenosine 5'-triphosphate (ATP) activates cell surface P2X and P2Y receptors. P2X receptors are membrane ion channels preferably permeable to sodium, potassium and calcium that open within milliseconds of the binding of ATP. In molecular architecture, they form a unique structural family. The receptor is a trimer, the binding of ATP between subunits causes them to flex together within the ectodomain and separate in the membrane-spanning region so as to open a central channel. P2X receptors have a widespread tissue distribution. On some smooth muscle cells, P2X receptors mediate the fast excitatory junction potential that leads to depolarization and contraction. In the central nervous system, activation of P2X receptors allows calcium to enter neurons and this can evoke slower neuromodulatory responses such as the trafficking of receptors for the neurotransmitter glutamate. In primary afferent nerves, P2X receptors are critical for the initiation of action potentials when they respond to ATP released from sensory cells such as taste buds, chemoreceptors or urothelium. In immune cells, activation of P2X receptors triggers the release of pro-inflammatory cytokines such as interleukin 1β. The development of selective blockers of different P2X receptors has led to clinical trials of their effectiveness in the management of cough, pain, inflammation and certain neurodegenerative diseases.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377721

  10. Leaching Properties of Naturally Occurring Heavy Metals from Soils

    NASA Astrophysics Data System (ADS)

    Zhang, M.; Hoshino, M.; Yoshikawa, M.; Hara, J.; Sugita, H.

    2014-12-01

    The major threats to human health from heavy metals are associated with exposure to arsenic, lead, cadmium, chromium, mercury, as well as some other elements. The effects of such heavy metals on human health have been extensively studied and reviewed by international organizations such as WHO. Due to their toxicity, heavy metal contaminations have been regulated by national environmental standards in many countries, and/or laws such as the Soil Contamination Countermeasures Act in Japan. Leaching of naturally occurring heavy metals from the soils, especially those around abandoned metal mines into surrounding water systems, either groundwater or surface water systems, is one of the major pathways of exposure. Therefore, understanding the leaching properties of toxic heavy metals from naturally polluted soils is of fundamentally importance for effectively managing abandoned metal mines, excavated rocks discharged from infrastructure constructions such as tunneling, and/or selecting a pertinent countermeasure against pollution when it is necessary. In this study, soil samples taken from the surroundings of abandoned metal mines in different regions in Japan were collected and analyzed. The samples contained multiple heavy metals such as lead, arsenic and chromium. Standard leaching test and sequential leaching test considering different forms of contaminants, such as trivalent and pentavalent arsenics, and trivalent and hexavalent chromiums, together with standard test for evaluating total concentration, X-ray Fluorescence Analysis (XRF), X-ray diffraction analysis (XRD) and Cation Exchange Capacity (CEC) tests were performed. In addition, sequential leaching tests were performed to evaluate long-term leaching properties of lead from representative samples. This presentation introduces the details of the above experimental study, discusses the relationships among leaching properties and chemical and mineral compositions, indicates the difficulties associated with

  11. Frog Virus 3 DNA Replication Occurs in Two Stages

    PubMed Central

    Goorha, R.

    1982-01-01

    Viral DNA synthesis in frog virus 3 (FV3)-infected cells occurs both in the nucleus and in the cytoplasm (Goorha et al., Virology 84:32-51, 1978). Relationships between viral DNA molecules synthesized in these two compartments and their role in the virus replication were examined. The data presented here suggest that (i) FV3 DNA replicated in two stages and (ii) nucleus and cytoplasm were the sites of stages 1 and 2 of DNA replication, respectively. Stages 1 and 2 were further distinguished by their temporal appearance during infection and by the sizes of the replicating DNA as determined by sedimentation in neutral sucrose gradients. In stage 1, replicating molecules, between the size of unit and twice the unit length, were produced early in infection (2 h postinfection). In contrast, stage 2 of DNA replication occurred only after 3 h postinfection, and replicating molecules were large concatemers. Results of pulse-chase experiments showed that the concatemeric DNA served as the precursor for the production of mature FV3 DNA. Denaturation of concatemeric DNA with alkali or digestion with S1 nuclease reduced it to less than genome size molecules, indicating the presence of extensive single-stranded regions. Analysis of replicating DNA by equilibrium centrifugation in CsCl gradients after a pulse-chase suggested that these single-stranded regions were subsequently repaired. Based on these and previous data, a scheme of FV3 replication is presented. According to this scheme, FV3 utilizes the nucleus for early transcription and stage 1 of DNA replication. The viral DNA is then transported to the cytoplasm, where it participates in stage 2 DNA replication to form a concatemeric replication complex. The processing of concatemers to produce mature viral DNA and virus assembly also occurs in the cytoplasm. This mode of replication is strikingly different from any other known DNA virus. PMID:7109033

  12. Myelodysplastic Syndrome Occurring in a Patient with Gorlin Syndrome.

    PubMed

    Mull, Jamie L; Madden, Lisa M; Bayliss, Susan J

    2016-07-01

    We report a case of myelodysplastic syndrome (MDS) occurring in an African American boy with Gorlin syndrome with a novel PTCH1 mutation. Before developing MDS, the patient had been treated with chemotherapy and radiation for a medulloblastoma. He received a bone marrow transplant for the MDS and eventually died of treatment complications. Secondary hematologic malignancies are a known complication of certain chemotherapeutics, although whether a patient with Gorlin syndrome has a greater propensity for the development of such malignancies is unclear. PMID:27241746

  13. An Update on Antitumor Activity of Naturally Occurring Chalcones

    PubMed Central

    Zhang, En-Hui; Wang, Ru-Feng; Guo, Shu-Zhen; Liu, Bin

    2013-01-01

    Chalcones, which have characteristic 1,3-diaryl-2-propen-1-one skeleton, are mainly produced in roots, rhizomes, heartwood, leaves, and seeds of genera Angelica, Sophora, Glycyrrhiza, Humulus, Scutellaria, Parartocarpus, Ficus, Dorstenia, Morus, Artocarpus, and so forth. They have become of interest in the research and development of natural antitumor agents over the past decades due to their broad range of mechanisms including anti-initiation, induction of apoptosis, antiproliferation, antimetastasis, antiangiogenesis, and so forth. This review summarizes the studies on the antitumor activity of naturally occurring chalcones and their underlying mechanisms in detail during the past decades. PMID:23690855

  14. Synthetic muscle promoters: activities exceeding naturally occurring regulatory sequences

    NASA Technical Reports Server (NTRS)

    Li, X.; Eastman, E. M.; Schwartz, R. J.; Draghia-Akli, R.

    1999-01-01

    Relatively low levels of expression from naturally occurring promoters have limited the use of muscle as a gene therapy target. Myogenic restricted gene promoters display complex organization usually involving combinations of several myogenic regulatory elements. By random assembly of E-box, MEF-2, TEF-1, and SRE sites into synthetic promoter recombinant libraries, and screening of hundreds of individual clones for transcriptional activity in vitro and in vivo, several artificial promoters were isolated whose transcriptional potencies greatly exceed those of natural myogenic and viral gene promoters.

  15. Transmission of Naturally Occurring Lymphoma in Macaque Monkeys

    NASA Astrophysics Data System (ADS)

    Hunt, Ronald D.; Blake, Beverly J.; Chalifoux, Laura V.; Sehgal, Prabhat K.; King, Norval W.; Letvin, Norman L.

    1983-08-01

    Spontaneously occurring rhesus monkey lymphomas were transmitted into healthy rhesus monkeys by using tumor cell suspensions. The naturally arising tumors included an immunoblastic sarcoma and an undifferentiated lymphoma. Recipient animals developed undifferentiated lymphomas, poorly differentiated lymphomas, or parenchymal lymphoproliferative abnormalities suggestive of early lesions of lymphoma. Some of these animals developed such opportunistic infections as cytomegalovirus hepatitis and cryptosporidiosis. They also showed evidence of an abnormal circulating peripheral blood mononuclear cell. These findings, all characteristic of the acquired immune deficiency syndrome (AIDS) of macaques, suggest a link between these transmissible lymphomas and AIDS in macaque monkeys.

  16. Naturally occurring crystalline phases: analogues for radioactive waste forms

    SciTech Connect

    Haaker, R.F.; Ewing, R.C.

    1981-01-01

    Naturally occurring mineral analogues to crystalline phases that are constituents of crystalline radioactive waste forms provide a basis for comparison by which the long-term stability of these phases may be estimated. The crystal structures and the crystal chemistry of the following natural analogues are presented: baddeleyite, hematite, nepheline; pollucite, scheelite;sodalite, spinel, apatite, monazite, uraninite, hollandite-priderite, perovskite, and zirconolite. For each phase in geochemistry, occurrence, alteration and radiation effects are described. A selected bibliography for each phase is included.

  17. Pseudo-Kaposi sarcoma (acroangiodermatitis): occurring after bullous erysipelas.

    PubMed

    Kutlubay, Zekayi; Yardimci, Gürkan; Engin, Burhan; Demirkesen, Cuyan; Aydin, Övgü; Khatib, Rashid; Tuzun, Yalçın

    2015-05-01

    Pseudo-Kaposi sarcoma is a benign reactive vascular proliferative disorder, which can be seen at any age. It occurs when the chronic venous pressure changes result in vascular proliferation in the upper and mid dermis. This disease is divided into two subtypes: the most frequent subtype is the Mali type and seen in early ages. The Mali type is seen in chronic venous insufficiency and in those patients with arteriovenous shunts. The rare subtype is the Stewart-Bluefarb type. This disease must be distinguished from Kaposi sarcoma because of their clinical resemblance. Herein, we present a patient with pseudo-Kaposi sarcoma, which developed after bullous erysipelas.

  18. Photoprotective substance occurs primarily in outer layers of fish skin

    USGS Publications Warehouse

    Fabacher, D.L.; Little, E.E.

    1998-01-01

    Methanol extracts of dorsal skin layers, eyes, gills, and livers from ultraviolet-B (UVB) radiation-sensitive and UVB-tolerant species of freshwater fish were examined for a substance that appears to be photoprotective. Significantly larger amounts of this substance were found in extracts of outer dorsal skin layers from both UVB-sensitive and UVB-tolerant fish when compared with extracts of inner dorsal skin layers. This substance occurred in minor amounts or was not detected in eye, gill, and liver extracts. The apparent primary function of this substance in fish is to protect the cells in outer dorsal skin layers from harmful levels of UVB radiation.

  19. An update on antitumor activity of naturally occurring chalcones.

    PubMed

    Zhang, En-Hui; Wang, Ru-Feng; Guo, Shu-Zhen; Liu, Bin

    2013-01-01

    Chalcones, which have characteristic 1,3-diaryl-2-propen-1-one skeleton, are mainly produced in roots, rhizomes, heartwood, leaves, and seeds of genera Angelica, Sophora, Glycyrrhiza, Humulus, Scutellaria, Parartocarpus, Ficus, Dorstenia, Morus, Artocarpus, and so forth. They have become of interest in the research and development of natural antitumor agents over the past decades due to their broad range of mechanisms including anti-initiation, induction of apoptosis, antiproliferation, antimetastasis, antiangiogenesis, and so forth. This review summarizes the studies on the antitumor activity of naturally occurring chalcones and their underlying mechanisms in detail during the past decades.

  20. Opioid receptors in the gastrointestinal tract

    PubMed Central

    Holzer, Peter

    2011-01-01

    Opium is arguably one of the oldest herbal medicines, being used as analgesic, sedative and antidiarrheal drug for thousands of years. These effects mirror the actions of the endogenous opioid system and are mediated by the principal μ-, κ- and δ-opioid receptors. In the gut, met-enkephalin, leu-enkephalin, β-endorphin and dynorphin occur in both neurons and endocrine cells. When released, opioid peptides activate opioid receptors on the enteric circuitry controlling motility and secretion. As a result, inhibition of gastric emptying, increase in sphincter tone, induction of stationary motor patterns and blockade of peristalsis ensue. Together with inhibition of ion and fluid secretion, these effects cause constipation, one of the most frequent and troublesome adverse reactions of opioid analgesic therapy. Although laxatives are most frequently used to ameliorate opioid-induced bowel dysfunction, their efficacy is unsatisfactory. Specific antagonism of peripheral opioid receptors is a more rational approach. This goal is addressed by the use of opioid receptor antagonists with limited absorption such as oral prolonged-release naloxone and opioid receptor antagonists that do not penetrate the blood-brain barrier such as methylnaltrexone and alvimopan. Preliminary evidence indicates that peripherally restricted opioid receptor antagonists may act as prokinetic drugs in their own right. PMID:19345246

  1. Engineering death receptor ligands for cancer therapy.

    PubMed

    Wajant, Harald; Gerspach, Jeannette; Pfizenmaier, Klaus

    2013-05-28

    CD95, TNFR1, TRAILR1 and TRAILR2 belong to a subgroup of TNF receptors which is characterized by a conserved cell death-inducing protein domain that connects these receptors to the apoptotic machinery of the cell. Activation of death receptors in malignant cells attracts increasing attention as a principle to fight cancer. Besides agonistic antibodies the major way to stimulate death receptors is the use of their naturally occurring "death ligands" CD95L, TNF and TRAIL. However, dependent from the concept followed to develop a death ligand-based therapy various limiting aspects have to be taken into consideration on the way to a "bedside" usable drug. Problems arise in particular from the cell associated transmembrane nature of the death ligands, the poor serum half life of the soluble fragments derived from the transmembrane ligands, the ubiquitous expression of the death receptors and the existence of additional non-death receptors of the death ligands. Here, we summarize strategies how these limitations can be overcome by genetic engineering.

  2. Inhibition of TRPV1 channels by a naturally occurring omega-9 fatty acid reduces pain and itch

    PubMed Central

    Morales-Lázaro, Sara L.; Llorente, Itzel; Sierra-Ramírez, Félix; López-Romero, Ana E.; Ortíz-Rentería, Miguel; Serrano-Flores, Barbara; Simon, Sidney A.; Islas, León D.; Rosenbaum, Tamara

    2016-01-01

    The transient receptor potential vanilloid 1 (TRPV1) ion channel is mainly found in primary nociceptive afferents whose activity has been linked to pathophysiological conditions including pain, itch and inflammation. Consequently, it is important to identify naturally occurring antagonists of this channel. Here we show that a naturally occurring monounsaturated fatty acid, oleic acid, inhibits TRPV1 activity, and also pain and itch responses in mice by interacting with the vanilloid (capsaicin)-binding pocket and promoting the stabilization of a closed state conformation. Moreover, we report an itch-inducing molecule, cyclic phosphatidic acid, that activates TRPV1 and whose pruritic activity, as well as that of histamine, occurs through the activation of this ion channel. These findings provide insights into the molecular basis of oleic acid inhibition of TRPV1 and also into a way of reducing the pathophysiological effects resulting from its activation. PMID:27721373

  3. Naturally occurring organic osmolytes: from cell physiology to disease prevention.

    PubMed

    Khan, Shagufta H; Ahmad, Nihal; Ahmad, Faizan; Kumar, Raj

    2010-12-01

    Osmolytes are naturally occurring organic compounds, which represent different chemical classes including amino acids, methylamines, and polyols. By accumulating high concentrations of osmolytes, organisms adapt to perturbations that can cause structural changes in their cellular proteins. Osmolytes shift equilibrium toward natively-folded conformations by raising the free energy of the unfolded state. As osmolytes predominantly affect the protein backbone, the balance between osmolyte-backbone interactions and amino acid side chain-solvent interactions determines protein folding. Abnormal cell volume regulation significantly contributes to the pathophysiology of several disorders, and cells respond to these changes by importing, exporting, or synthesizing osmolytes to maintain volume homeostasis. In recent years, it has become quite evident that cells regulate many biological processes such as protein folding, protein disaggregation, and protein-protein interactions via accumulation of specific osmolytes. Many genetic diseases are attributed to the problems associated with protein misfolding/aggregation, and it has been shown that certain osmolytes can protect these proteins from misfolding. Thus, osmolytes can be utilized as therapeutic targets for such diseases. In this review article, we discuss the role of naturally occurring osmolytes in protein stability, underlying mechanisms, and their potential use as therapeutic molecules. PMID:21190292

  4. Daily intakes of naturally occurring radioisotopes in typical Korean foods.

    PubMed

    Choi, Min-Seok; Lin, Xiu-Jing; Lee, Sun Ah; Kim, Wan; Kang, Hee-Dong; Doh, Sih-Hong; Kim, Do-Sung; Lee, Dong-Myung

    2008-08-01

    The concentrations of naturally occurring radioisotopes ((232)Th, (228)Th, (230)Th, (228)Ra, (226)Ra, and (40)K) in typical Korean foods were evaluated. The daily intakes of these radioisotopes were calculated by comparing concentrations in typical Korean foods and the daily consumption rates of these foods. Daily intakes were as follows: (232)Th, 0.00-0.23; (228)Th, 0.00-2.04; (230)Th, 0.00-0.26; (228)Ra, 0.02-2.73; (226)Ra, 0.01-4.37 mBq/day; and (40)K, 0.01-5.71 Bq/day. The total daily intake of the naturally occurring radioisotopes measured in this study from food was 39.46 Bq/day. The total annual internal dose resulting from ingestion of radioisotopes in food was 109.83 muSv/y, and the radioisotope with the highest daily intake was (40)K. These values were same level compiled in other countries.

  5. Insights into secondary reactions occurring during atmospheric ablation of micrometeoroids

    NASA Astrophysics Data System (ADS)

    Court, Richard W.; Tan, Jonathan

    2016-06-01

    Ablation of micrometeoroids during atmospheric entry yields volatile gases such as water, carbon dioxide, and sulfur dioxide, capable of altering atmospheric chemistry and hence the climate and habitability of the planetary surface. While laboratory experiments have revealed the yields of these gases during laboratory simulations of ablation, the reactions responsible for the generation of these gases have remained unclear, with a typical assumption being that species simply undergo thermal decomposition without engaging in more complex chemistry. Here, pyrolysis-Fourier transform infrared spectroscopy reveals that mixtures of meteorite-relevant materials undergo secondary reactions during simulated ablation, with organic matter capable of taking part in carbothermic reduction of iron oxides and sulfates, resulting in yields of volatile gases that differ from those predicted by simple thermal decomposition. Sulfates are most susceptible to carbothermic reduction, producing greater yields of sulfur dioxide and carbon dioxide at lower temperatures than would be expected from simple thermal decomposition, even when mixed with meteoritically relevant abundances of low-reactivity Type IV kerogen. Iron oxides were less susceptible, with elevated yields of water, carbon dioxide, and carbon monoxide only occurring when mixed with high abundances of more reactive Type III kerogen. We use these insights to reinterpret previous ablation simulation experiments and to predict the reactions capable of occurring during ablation of carbonaceous micrometeoroids in atmospheres of different compositions.

  6. Aggregatibacter actinomycetemcomitans leukotoxin cytotoxicity occurs through bilayer destabilization

    PubMed Central

    Brown, Angela C.; Boesze-Battaglia, Kathleen; Du, Yurong; Stefano, Frank P.; Kieba, Irene R.; Epand, Raquel F.; Kakalis, Lazaros; Yeagle, Philip L.; Epand, Richard M.; Lally, Edward T.

    2012-01-01

    Summary The Gram-negative bacterium, Aggregatibacter actinomycetemcomitans, is a common inhabitant of the human upper aerodigestive tract. The organism produces an RTX (Repeats in ToXin) toxin (LtxA) that kills human white blood cells. LtxA is believed to be a membrane-damaging toxin, but details of the cell surface interaction for this and several other RTX toxins have yet to be elucidated. Initial morphological studies suggested that LtxA was bending the target cell membrane. Because the ability of a membrane to bend is a function of its lipid composition, we assessed the proficiency of LtxA to release of a fluorescent dye from a panel of liposomes composed of various lipids. Liposomes composed of lipids that form nonlamellar phases were susceptible to LtxA-induced damage while liposomes composed of lipids that do not form non-bilayer structures were not. Differential scanning calorimetry demonstrated that the toxin decreased the temperature at which the lipid transitions from a bilayer to a nonlamellar phase, while 31P nuclear magnetic resonance studies showed that the LtxA-induced transition from a bilayer to an inverted hexagonal phase occurs through the formation of an isotropic intermediate phase. These results indicate that LtxA cytotoxicity occurs through a process of membrane destabilization. PMID:22309134

  7. Macaques Exhibit a Naturally-Occurring Depression Similar to Humans

    PubMed Central

    Xu, Fan; Wu, Qingyuan; Xie, Liang; Gong, Wei; Zhang, Jianguo; Zheng, Peng; Zhou, Qinmin; Ji, Yongjia; Wang, Tao; Li, Xin; Fang, Liang; Li, Qi; Yang, Deyu; Li, Juan; Melgiri, Narayan D.; Shively, Carol; Xie, Peng

    2015-01-01

    Rodent models have dominated preclinical investigations into the mechanisms of depression. However, these models-which rely on subjecting individual rodents to physical stressors - do not realistically resemble the etiopathological development of depression, which occurs naturally in a social context. A non-human primate model that better reflects the social ethological aspects of depression would be more advantageous to investigating pathophysiological mechanisms and developing antidepressant therapeutics. Here, we describe and model a naturally-occurring depressive state in a non-human primate species, the cynomolgus monkey (Macaca fascicularis), in a realistic social ethological context and associate the depressed behavioral phenotype with significant serum metabolic perturbations. One to two subjects per stable social colony (17–22 subjects) manifested a depressive phenotype that may be attributed to psychosocial stress. In accordance with rodent and human studies, the serum metabolic phenotype of depressed and healthy subjects significantly differed, supporting the model's face validity. However, application of the fast-acting antidepressant ketamine failed to demonstrate predictive validity. This study proposes a non-human primate depression model in a realistic social ethological context that can better approximate the psychosocial stressors underlying depression. PMID:25783476

  8. On the mechanical friction losses occurring in automotive differential gearboxes.

    PubMed

    Antoni, Grégory

    2014-01-01

    In the automobile industry, the mechanical losses resulting from friction are largely responsible for various kinds of surface damage, such as the scuffing occurring in some mechanical assemblies. These scuffing processes seem to be due to a local loss of lubrication between certain mechanical elements of the same assembly, leading to a sharp increase in the friction, which can lead to a surface and volume damage in some of them, and even can cause, in the worst case, the whole destruction of the mechanical system if it has continued to operate. Predicting and checking the occurrence of this kind of undesirable phenomena, especially in some principal systems of the vehicle, represents nowadays, a crucial challenge in terms of automobile reliability and safety. This study focuses on the mechanical friction losses liable to occur in differential automobile gearboxes, which can lead in the long term to the scuffing of these mechanical systems. The friction losses involved were modeled, using a simple analytical approach, which is presented and discussed.

  9. Effects of later-occurring nonlinguistic sounds on speech categorization.

    PubMed

    Wade, Travis; Holt, Lori L

    2005-09-01

    Nonspeech stimuli influence phonetic categorization, but effects observed so far have been limited to precursors' influence on perception of following speech. However, both preceding and following speech affect phonetic categorization. This asymmetry raises questions about whether general auditory processes play a role in context-dependent speech perception. This study tested whether the asymmetry stems from methodological issues or genuine mechanistic limitations. To determine whether and how backward effects of nonspeech context on speech may occur, one experiment examined perception of CVC words with [ga]-[da] series onsets followed by one of two possible embedded tones and one of two possible final consonants. When the tone was separated from the target onset by 100 ms, contrastive effects of tone frequency similar to those of previous studies were observed; however, when the tone was moved closer to the target segment assimilative effects were observed. In another experiment, contrastive effects of a following tone were observed in both CVC words and CV nonwords, although the size of the effects depended on syllable structure. Results are discussed with respect to contrastive mechanisms not speech-specific but operating at a relatively high level, taking into account spectrotemporal patterns occurring over extended periods before and after target events. PMID:16240828

  10. Economic losses occurring due to brucellosis in Indian livestock populations.

    PubMed

    Singh, B B; Dhand, N K; Gill, J P S

    2015-05-01

    Brucellosis is a serious public health issue in India. Estimation of economic losses occurring due to brucellosis is required to help formulate prevention and control strategies, but has not been done in India. We estimated economic losses due to brucellosis by sourcing prevalence data from epidemiological surveys conducted in India. Data for livestock populations were obtained from official records. Probability distributions were used for many of the input parameters to account for uncertainty and variability. The analysis revealed that brucellosis in livestock is responsible for a median loss of US $ 3.4 billion (5th-95th percentile 2.8-4.2 billion). The disease in cattle and buffalo accounted for 95.6% of the total losses occurring due to brucellosis in livestock populations. The disease is responsible for a loss of US $ 6.8 per cattle, US$18.2 per buffalo, US $ 0.7 per sheep, US $ 0.5 per goat and US $ 0.6 per pig. These losses are additional to the economic and social consequences of the disease in humans. The results suggest that the disease causes significant economic losses in the country and should be controlled on a priority basis.

  11. Predictors, treatment, and outcomes of STEMI occurring in hospitalized patients.

    PubMed

    Dai, Xuming; Kaul, Prashant; Smith, Sidney C; Stouffer, George A

    2016-03-01

    ST-segment elevation myocardial infarction (STEMI) is most commonly caused by an acute thrombotic occlusion of a coronary artery. For patients in whom the onset of STEMI occurs outside of hospital (outpatient STEMI), early reperfusion therapy with either fibrinolysis or primary percutaneous coronary intervention reduces complications and improves survival, compared with delayed reperfusion. STEMI systems of care are defined as integrated groups of separate entities focused on reperfusion therapy for STEMI, generally including emergency medical services, emergency medicine, cardiology, nursing, and hospital administration. These systems of care have been successful at reducing total ischaemia time and outpatient STEMI mortality. By contrast, much less is known about STEMI that occurs in hospitalized patients (inpatient STEMI), which has unique clinical features and much worse outcomes than outpatient STEMI. Inpatient STEMI is associated with older age, a higher female:male ratio, and more comorbidities than outpatient STEMI. Delays in diagnosis and infrequent use of reperfusion therapy probably also contribute to unfavourable outcomes for inpatient STEMI.

  12. Beauveria caledonica is a naturally occurring pathogen of forest beetles.

    PubMed

    Glare, Travis R; Reay, Stephen D; Nelson, Tracey L; Moore, Roger

    2008-03-01

    In New Zealand, two introduced scolytid beetles, Hylastes ater and Hylurgus ligniperda (Curculionidae: Scolytinae) are pests in pine plantations. Investigation of the naturally occurring pathogens of these exotic pests revealed that both are attacked by Beauveria caledonica, a species originally isolated and described from soil in Scotland. The isolates in New Zealand were identical in morphology and conserved DNA region (rDNA, elongation factor alpha) sequence to isolates held in the USDA-ARS insect pathogens culture collection. In bioassay, the B. caledonica isolates were highly pathogenic to adults of H. ligniperda and larvae of Tenebrio molitor. Sporulation was observed on cadavers, confirming the species can utilise the cadavers. As both species were likely to have been introduced to New Zealand from Europe, a search was made for B. caledonica in the northern UK and Ireland. The fungus was found as a naturally-occurring pathogen of the weevil pest, Hylobius abietis (Curculionidae: Scolytinae), developing in spruce and other beetles in forests in both regions. PMID:18308525

  13. Leaching of technologically enhanced naturally occurring radioactive materials.

    PubMed

    Chau, Nguyen Dinh; Chruściel, Edward

    2007-08-01

    A form of waste associated with mining activities is related to the type of deposit being mined and to the procedure of exploitation and enrichment adopted. The wastes usually contain relatively large amounts of technologically enhanced naturally occurring radioactive materials (TENORM). The TENORM are often stored on the surface. Consequently, they can be leached as a result of interaction with aqueous solutions of different chemical composition. This further leads to pollution of water and soil in the vicinity of the stored wastes. The paper presents the results of laboratory investigation aimed at quantifying the leaching process of samples originating from uranium dumps and storage reservoirs associated with brine pumped from coal mines. The leaching process was investigated with respect to selected elements: uranium isotopes, radium isotopes, iron, barium and sodium. The samples were exposed to aqueous solutions of different chemical composition. The experiments revealed that TENORM in form of sulphate compounds are the most resistant against leaching. The leaching coefficient for radium isotopes varies from a few thousandth percent to a few hundredth percent. On the other hand, for TENORM occurring in sand or sludge, the leaching coefficient for uranium and radium isotopes ranged from a few hundredth percent to a few percent. PMID:17482828

  14. On the Mechanical Friction Losses Occurring in Automotive Differential Gearboxes

    PubMed Central

    Antoni, Grégory

    2014-01-01

    In the automobile industry, the mechanical losses resulting from friction are largely responsible for various kinds of surface damage, such as the scuffing occurring in some mechanical assemblies. These scuffing processes seem to be due to a local loss of lubrication between certain mechanical elements of the same assembly, leading to a sharp increase in the friction, which can lead to a surface and volume damage in some of them, and even can cause, in the worst case, the whole destruction of the mechanical system if it has continued to operate. Predicting and checking the occurrence of this kind of undesirable phenomena, especially in some principal systems of the vehicle, represents nowadays, a crucial challenge in terms of automobile reliability and safety. This study focuses on the mechanical friction losses liable to occur in differential automobile gearboxes, which can lead in the long term to the scuffing of these mechanical systems. The friction losses involved were modeled, using a simple analytical approach, which is presented and discussed. PMID:24719579

  15. Radiological protection in North American naturally occurring radioactive material industries.

    PubMed

    Chambers, D B

    2015-06-01

    All soils and rocks contain naturally occurring radioactive material (NORM). Many ores and raw materials contain relatively high levels of natural radionuclides, and processing such materials can further increase the concentrations of natural radionuclides, sometimes referred to as 'technologically enhanced naturally occurring radioactive material' (TENORM). Examples of NORM minerals include uranium ores, monazite (a source of rare earth minerals), and phosphate rock used to produce phosphate fertiliser. Such activities have the potential to result in above background radiation exposure to workers and the public. The objective of this paper is to review the sources and exposure from NORM in North American industries, and provide a perspective on the potential radiological hazards to workers and the environment. Proper consideration of NORM issues is important and needs to be integrated in the assessment of these projects. Concerns over radioactivity and radiation amongst non-governmental organisations and the local public have resulted in the cancellation of NORM mining and mineral extraction projects, as well as inhibition of the safe use of by-product materials from various NORM industries. This paper also briefly comments on the current regulatory framework for NORM (TENORM) in Canada and the USA, as well as the potential implications of the recent activities of the International Commission on Radiological Protection for NORM industries. PMID:25816274

  16. Naturally Occurring Radioactive Materials in Cargo at US Borders

    SciTech Connect

    Kouzes, Richard T.; Ely, James H.; Evans, John C.; Hensley, Walter K.; Lepel, Elwood A.; McDonald, Joseph C.; Schweppe, John E.; Siciliano, Edward R.; Strom, Daniel J.; Woodring, Mitchell L.

    2006-01-01

    In the U.S. and other countries, large numbers of vehicles pass through border crossings each day. The illicit movement of radioactive sources is a concern that has resulted in the installation of radiation detection and identification instruments at border crossing points. This activity is judged to be necessary because of the possibility of an act of terrorism involving a radioactive source that may include any number of dangerous radionuclides. The problem of detecting, identifying, and interdicting illicit radioactive sources is complicated by the fact that many materials present in cargo are somewhat radioactive. Some cargo contains naturally occurring radioactive material or technologically-enhanced naturally occurring radioactive material that may trigger radiation portal monitor alarms. Man-made radioactive sources, especially medical isotopes, are also frequently observed and produce alarms. Such nuisance alarms can be an operational limiting factor for screening of cargo at border crossings. Information about the nature of the radioactive materials in cargo that can interfere with the detection of radionuclides of concern is necessary. This paper provides such information for North American cargo, but the information may also be of use to border control officials in other countries. (PIET-43741-TM-361)

  17. Serum concentration of sialic acids in naturally occurring ovine babesiosis.

    PubMed

    Esmaeilnejad, Bijan; Tavassoli, Mousa; Asri-Rezaei, Siamak; Dalir-Naghadeh, Bahram; Abtahi Froushani, Seyyed Meysam; Arjmand, Jafar; Golabi, Mostafa

    2014-10-01

    This study is designated to assess the effect of the severity of Babesia ovis infection on sialic acid concentration in blood sera in naturally infected sheep. Infected animals (diseased group) comprised 38 Iranian fat-tailed sheep, about 1-3 years old, naturally infected with B. ovis, divided into four subgroups with respect to parasitemia rates (low 0.1-0.3 %, moderate 0.4-0.9 %, high 1-2.5 %, and very high >2.5 %). The parasitological diagnosis was confirmed using PCR analysis. As a control group, ten clinically healthy sheep reared under the same management and environmental conditions were also sampled. Hematological parameters and the concentrations of total sialic acid (TSA), lipid-bound sialic acid (LBSA), and protein-bound sialic acid (PBSA) were measured in both groups. Compared to controls, sialic acid concentrations showed significant increase (p < 0.05) in infected sheep. Parasitemia rate was positively correlated with sialic acid concentrations. This study demonstrated that B. ovis infection induced marked and persistent elevations of serum sialic acid concentrations. It seems that increase of serum sialic acid concentrations during parasitemia alter receptor-ligand interactions, which are known to play important role in immune response. Furthermore, sialic acid would indirectly inhibit the action of leukocytes and consequently promote the evasion of the immune response and persistence of the parasite in the host. This factor could influence the parasite-host cell adhesion, but further detailed biochemical investigations are needed to precisely explain the exact role of sialic acid in invasion process of the parasite to the host cells.

  18. Proline-Directed Androgen Receptor Phosphorylation

    PubMed Central

    Gao, Yanfei; Chen, Shaoyong

    2015-01-01

    The androgen receptor (AR) has been identified for decades and mediates essential steroid functions. Like most of biological molecules, AR functional activities are modulated by post-translational modifications. This review is focused on the reported activities and significance of AR phosphorylation, with particular emphasis on proline-directed serine/threonine phosphorylation that occurs predominantly on the receptor. The marked enrichment of AR phosphorylation in the most diverse N-terminal domain suggests that targeting AR phosphorylation can be synergistic to antagonizing the C-terminal domain by clinical antiandrogens. PMID:25866551

  19. The type I interleukin-1 receptor mediates fever in the rat as shown by interleukin-1 receptor subtype selective ligands.

    PubMed

    Malinowsky, D; Chai, Z; Bristulf, J; Simoncsits, A; Bartfai, T

    1995-12-01

    The interleukin-1 (IL-1) system possesses two distinct receptors (type I and type II) which, together with the accessory protein, mediate a multitude of responses to IL-1 alpha and IL-1 beta, including fever. So far, no receptor subtype-specific ligands have been described. Since both types of IL-1 receptors occur in the thermoregulatory areas it was unclear which IL-1 receptor type mediates fever. We report here that for a series of deletion mutants of human recombinant IL-1 beta (hrIL-1 beta), the affinity of these ligands for the type I IL-1 receptor correlates with their efficacy to evoke the fever response (hrIL-1 beta > des-SND52-54 > des-QGE48-50 > des-I56). Thus, the results suggest that agonist occupancy of the type I IL-1 receptor is essential for IL-1 beta-mediated fever.

  20. Meat toughening does not occur when rigor shortening is prevented.

    PubMed

    Koohmaraie, M; Doumit, M E; Wheeler, T L

    1996-12-01

    The objective of this experiment was to test the hypothesis that meat toughening during the first 24 h postmortem results from sarcomere shortening during rigor mortis development. Eleven market-weight lambs were used to measure changes in shear force of clamped longissimus during rigor development. Within 15 min of exsanguination, while attached at both ends, each longissimus was separated from the vertebrae body and clamped between three sets of metal plates to prevent muscle shortening (six clamped sections per lamb). Five of the clamped sections were placed at -1.1 degrees C for 0, 3, 6, 12, or 24 h. After storage at their respective times at -1.1 degrees C, the samples were placed at -30 degrees C for 90 min and then at -5 degrees C for 8 d. The sixth section (168-h section) was stored at -1.1 degrees C for the first 24 h, at 4 degrees C for 144 h, and then treated the same as other sampling times. Sections were sampled for pH, sarcomere length, shear force, and Western blot analyses before and after storage at -5 degrees C. Shear force values were the same (P > .05) from 0 to 24 h (4.5 kg at 0 h to 4.9 kg at 24 h) then declined (P < .05) to 3.3 kg at 168 h postmortem. As evident by lack of statistical difference in the sarcomere lengths, we were successful in holding the muscle length constant. Western blot analyses of nebulin, vinculin, and troponin-T indicated that minimum degradation occurred through 12 h, was slightly increased by 24 h, and was relatively extensive by 168 h postmortem. Although limited proteolysis occurred during storage at -5 degrees C for 8 d, this by itself had no effect on shear force. Results indicate that shear force values do not increase during rigor development when muscle is prevented from shortening; thus, the toughening that occurs during the first 24 h of slaughter is most likely due to sarcomere shortening.

  1. Effect of long term dexamethasone treatment on the glucocorticoid receptor

    SciTech Connect

    Silva, C.M.; DeLorenzo, T.M.; Cidlowski, J.A.

    1986-05-01

    The ability of dexamethasone(dex) to induce alkaline phosphatase activity was found to decrease with chronic hormone exposure. In order to better understand this adaptive resistance, the structure of the receptor from control cells and cells under long term dex (10/sup -6/M) treatment was analyzed. Native isoelectric focusing showed that receptor from dex treated cells focused at more basic pI than receptor from control cells. Denaturing two-dimensional gel analysis resulted in the characteristic 4-5 spots of (/sup 3/H)dexamethasone mesylate (DM) binding of receptor from control cells, but no (/sup 3/H)DM binding could be seen for receptor from dex treated cells. In order to study DNA-binding characteristics, gels were renatured, transferred to nitrocellulose and probed with (/sup 32/P)MMTV-GRE. Receptor from control cells showed 5 spots of DNA-binding at 101 kDa molecular weight and a pI range of 7.42 to 7.32. However, receptor from dex treated cells showed less intense DNA-binding which occurred only at the more basic range of pIs (7.42 to 7.39). Furthermore, no nuclear receptor sites could be measured in the dex treated cells, whereas 20,000 sites were measured in control cells. Even after being taken off hormone treatment for 12 days, cells could regenerate only 50% of their receptors. In conclusion, this system is conducive to studying the mechanism of receptor regulation.

  2. Molecular evolution of GPCRs: Ghrelin/ghrelin receptors.

    PubMed

    Kaiya, Hiroyuki; Kangawa, Kenji; Miyazato, Mikiya

    2014-06-01

    After the discovery in 1996 of the GH secretagogue-receptor type-1a (GHS-R1a) as an orphan G-protein coupled receptor, many research groups attempted to identify the endogenous ligand. Finally, Kojima and colleagues successfully isolated the peptide ligand from rat stomach extracts, determined its structure, and named it ghrelin. The GHS-R1a is now accepted to be the ghrelin receptor. The existence of the ghrelin system has been demonstrated in many animal classes through biochemical and molecular biological strategies as well as through genome projects. Our work, focused on identifying the ghrelin receptor and its ligand ghrelin in laboratory animals, particularly nonmammalian vertebrates, has provided new insights into the molecular evolution of the ghrelin receptor. In mammals, it is assumed that the ghrelin receptor evolution is in line with the plate tectonics theory. In contrast, the evolution of the ghrelin receptor in nonmammalian vertebrates differs from that of mammals: multiplicity of the ghrelin receptor isoforms is observed in nonmammalian vertebrates only. This multiplicity is due to genome duplication and polyploidization events that particularly occurred in Teleostei. Furthermore, it is likely that the evolution of the ghrelin receptor is distinct from that of its ligand, ghrelin, because only one ghrelin isoform has been detected in all species examined so far. In this review, we summarize current knowledge related to the molecular evolution of the ghrelin receptor in mammalian and nonmammalian vertebrates. PMID:24353285

  3. A novel T cell receptor single-chain signaling complex mediates antigen-specific T cell activity and tumor control

    PubMed Central

    Stone, Jennifer D.; Harris, Daniel T.; Soto, Carolina M.; Chervin, Adam S.; Aggen, David H.; Roy, Edward J.; Kranz, David M.

    2014-01-01

    Adoptive transfer of genetically modified T cells to treat cancer has shown promise in several clinical trials. Two main strategies have been applied to redirect T cells against cancer: 1) introduction of a full-length T cell receptor (TCR) specific for a tumor-associated peptide-MHC, or 2) introduction of a chimeric antigen receptor (CAR), including an antibody fragment specific for a tumor cell surface antigen, linked intracellularly to T cell signaling domains. Each strategy has advantages and disadvantages for clinical applications. Here, we present data on the in vitro and in vivo effectiveness of a single-chain signaling receptor incorporating a TCR variable fragment as the targeting element (referred to as TCR-SCS). This receptor contained a single-chain TCR (Vβ-linker-Vα) from a high-affinity TCR called m33, linked to the intracellular signaling domains of CD28 and CD3ζ. This format avoided mispairing with endogenous TCR chains, and mediated specific T cell activity when expressed in either CD4 or CD8 T cells. TCR-SCS-transduced CD8-negative cells showed an intriguing sensitivity, compared to full-length TCRs, to higher densities of less stable pepMHC targets. T cells that expressed this peptide-specific receptor persisted in vivo, and exhibited polyfunctional responses. Growth of metastatic antigen-positive tumors was significantly inhibited by T cells that expressed this receptor, and tumor cells that escaped were antigen loss variants. TCR-SCS receptors represent an alternative targeting receptor strategy that combines the advantages of single-chain expression, avoidance of TCR chain mispairing, and targeting of intracellular antigens presented in complex with MHC proteins. PMID:25082071

  4. Vampire bat reproductive control by a naturally occurring phytooestrogen.

    PubMed

    Serrano, Hector; Pérez-Rivero, Juan-José; Aguilar-Setién, Alvaro; de-Paz, Octavio; Villa-Godoy, Alejandro

    2007-01-01

    Rabies transmission by wild animals has not being controlled satisfactorily. One major rabies vector to humans and cattle is the hematophagous vampire bat Desmodus rotundus whose distribution is still increasing in the Americas. Of all of the strategies currently in place to control this vector, none of them are really specific and some have ecological impacts. In the present study we used a naturally occurring phytoestrogen on a small vampire bat colony. After collection, bats were fed bovine blood containing 200 microg coumestrol for a 30-day period. After treatment, gonads were excised and processed for histological evaluation. Data indicate that coumestrol adversely affects gonad histology and has a possible impact on the fertility of both male and female vampire bats.

  5. Active experiments, magnetospheric modification, and a naturally occurring analogue

    NASA Technical Reports Server (NTRS)

    Kivelson, M. G.; Russell, C. T.

    1973-01-01

    Recently, a scheme has been proposed which would modify the magnetosphere by injecting plasma near the equator beyond the plasmapause and initiating wave-particle instabilities. The expected effects have been examined theoretically. Injection of plasma into this region is also a naturally occurring phenomenon produced by the cross-tail electric fields which are associated with geomagnetic activity. For further investigation of magnetospheric instabilities, the advantages of examining artificially injected plasma (control of time and location of injection and of the volume of plasma injected) contrast with the advantages of studying natural enhancements (no extra payload, frequent occurrence). Thus, the two types of experiments are complementary. In preliminary studies of natural plasma enhancements both ULF and ELF emissions have been observed. The ELF noise is consistent with generation by the electron cyclotron instability.

  6. Additive CHARMM force field for naturally occurring modified ribonucleotides

    PubMed Central

    Xu, You; Vanommeslaeghe, Kenno; Aleksandrov, Alexey; MacKerell, Alexander D.

    2016-01-01

    More than 100 naturally occurring modified nucleotides have been found in RNA molecules, in particular in tRNAs. We have determined molecular mechanics force field parameters compatible with the CHARMM36 all‐atom additive force field for all these modifications using the CHARMM force field parametrization strategy. Emphasis was placed on fine tuning of the partial atomic charges and torsion angle parameters. Quantum mechanics calculations on model compounds provided the initial set of target data, and extensive molecular dynamics simulations of nucleotides and oligonucleotides in aqueous solutions were used for further refinement against experimental data. The presented parameters will allow for computational studies of a wide range of RNAs containing modified nucleotides, including the ribosome and transfer RNAs. © 2016 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc. PMID:26841080

  7. Resolutions of Problems that Occurred in SPEAR3 Magnet Production

    SciTech Connect

    Li, Nanyang

    2005-05-27

    Some problems occurred during the SPEAR3 magnet production at IHEP, China. It was very hard to find resolution from existing knowledge of those problems. It was possible that similar problems might have happen in building accelerator magnet in other institutes before, but they were not addressed in public papers. These problems were discussed and solved by engineers from both SLAC and IHEP after conducting certain experiments. Traditionally, the magnet design and measurement data have been always well documented and addressed in papers, but the production experiences have not been recorded adequately. It is the goal of this paper to record the problems and their resolutions during SPEAR3 magnet production at IHEP China, which will certainly benefit future magnet projects.

  8. Second-Degree Atrioventricular Block Occurring After Tooth Extraction.

    PubMed

    Kamatani, Takaaki; Akizuki, Ayako; Kondo, Seiji; Shirota, Tatsuo

    2016-01-01

    Although cardiac arrhythmias are occasionally associated with dental extractions and dental anesthesia, atrioventricular block is rarely seen during dental procedures. We report a rare case of type I second-degree atrioventricular block (Wenckebach phenomenon) occurring after bilateral extraction of impacted mandibular third molars under general anesthesia in a 16-year-old Japanese girl. Under consultation with a cardiovascular physician, we carefully monitored the patient's vital signs postoperatively, including blood pressure, oxygen saturation, and electrocardiogram, using a bedside monitor. Her postoperative course was uneventful. A 12-lead electrocardiogram the following day revealed no abnormality. In this case, we hypothesize that extubation of the nasotracheal tube or oral/pharyngeal suction might have triggered a vagal reflex that caused type I second-degree atrioventricular block. Our experience indicates that standard cardiovascular monitoring should be used for patients undergoing dental treatment under general anesthesia, even for young, healthy patients, to prevent and detect cardiovascular emergencies. PMID:27585419

  9. Modeling solid-state transformations occurring in dissolution testing.

    PubMed

    Laaksonen, Timo; Aaltonen, Jaakko

    2013-04-15

    Changes in the solid-state form can occur during dissolution testing of drugs. This can often complicate interpretation of results. Additionally, there can be several mechanisms through which such a change proceeds, e.g. solvent-mediated transformation or crystal growth within the drug material itself. Here, a mathematical model was constructed to study the dissolution testing of a material, which undergoes such changes. The model consisted of two processes: the recrystallization of the drug from a supersaturated liquid state caused by the dissolution of the more soluble solid form and the crystal growth of the stable solid form at the surface of the drug formulation. Comparison to experimental data on theophylline dissolution showed that the results obtained with the model matched real solid-state changes and that it was able to distinguish between cases where the transformation was controlled either by solvent-mediated crystallization or solid-state crystal growth. PMID:23506958

  10. Inactivation of phospholipase A2 by naturally occurring biflavonoid, ochnaflavone.

    PubMed

    Chang, H W; Baek, S H; Chung, K W; Son, K H; Kim, H P; Kang, S S

    1994-11-30

    Ochnaflavone, a medicinal herb product isolated from Lonicera japonica, strongly inhibited rat platelet phospholipase A2 (IC50, about 3 microM). Inactivation was concentration and pH dependent (maximum inactivation occurred between pH 9.0 and 10.0). Ochnaflavone inhibited the enzyme by a noncompetitive manner, with the apparent Ki value of 3 x 10(-5) M. Reversibility was studied directly by dialysis method; the inhibition was irreversible. In addition, the inhibitory activity of ochnaflavone is rather specific against group II phospholipase A2 than group I phospholipase A2 (IC50, about 20 microM). Addition of excess Ca2+ concentration up to 8 mM did not antagonize the inhibitory activity of ochnaflavone. These results indicate that the inhibition of phospholipase A2 by ochnaflavone may result from direct interaction with the enzyme.

  11. Crocoite: An unusual mode of occurence for lead in coal

    USGS Publications Warehouse

    Li, Z.; Moore, T.A.; Weaver, S.D.; Finkelman, R.B.

    2001-01-01

    What is believed to be a very unusual mode of occurrence for lead in coal has been identified as crocoite (PbCrO4). As part of a larger study on trace elements and mineralogy in the Cretaceous Main Seam in New Zealand, crocoite was found in raw coal samples within the lower part of the coal seam. X-ray diffraction (XRD) and bulk chemical data from a SEM equipped with an energy dispersive X-ray analyser (EDXA) have confirmed the identity of this mineral. This is apparently the first time that crocoite has been reported in coal. Crocoite usually occurs only in the oxidised zone of lead mineral deposits. The occurrence of this mineral in the Main Seam coal implies that the deposit was exposed to an oxidising environment at some stage, most likely after coalification. Published by Elsevier Science B.V.

  12. How did the 1906 San Francisco earthquake occur?

    USGS Publications Warehouse

    Thatcher, W.

    1976-01-01

    The 1906 earthquake in San Francisco was of magnitude 8.3 and was the most destructive in the history of the United States. Because this part of California is now much more heavily populated, intense studies have been made of the 1906 earthquake in an effort to understand how it occurred and, more importantly, what likelihood there is of future large earthquakes near San Francisco. Great emphasis has been put on geodetic data- ground surveys of the region have been made frequently since 1853 (see "The California geodimeter network: measuring movement along the San Andreas fault" by J.C Savage, Earthquake Information Bulletin, vol. 6 no. 3, May-June 1974).  

  13. Second-Degree Atrioventricular Block Occurring After Tooth Extraction.

    PubMed

    Kamatani, Takaaki; Akizuki, Ayako; Kondo, Seiji; Shirota, Tatsuo

    2016-01-01

    Although cardiac arrhythmias are occasionally associated with dental extractions and dental anesthesia, atrioventricular block is rarely seen during dental procedures. We report a rare case of type I second-degree atrioventricular block (Wenckebach phenomenon) occurring after bilateral extraction of impacted mandibular third molars under general anesthesia in a 16-year-old Japanese girl. Under consultation with a cardiovascular physician, we carefully monitored the patient's vital signs postoperatively, including blood pressure, oxygen saturation, and electrocardiogram, using a bedside monitor. Her postoperative course was uneventful. A 12-lead electrocardiogram the following day revealed no abnormality. In this case, we hypothesize that extubation of the nasotracheal tube or oral/pharyngeal suction might have triggered a vagal reflex that caused type I second-degree atrioventricular block. Our experience indicates that standard cardiovascular monitoring should be used for patients undergoing dental treatment under general anesthesia, even for young, healthy patients, to prevent and detect cardiovascular emergencies.

  14. Hot water epilepsy occurring at temperature below the core temperature.

    PubMed

    Auvin, Stéphane; Lamblin, Marie-Dominique; Pandit, Florence; Bastos, Maria; Derambure, Philippe; Vallée, Louis

    2006-05-01

    A 6-year-old girl had water reflex epilepsy occurring at lower temperature than the core temperature. Seizures episodes consisted of a loss of consciousness absence followed by left predominant hypotonia with right fronto-temporal high voltage slow waves on the ictal-EEG. Seizures were only observed when the water was poured on scalp or face. Neuropsychological evaluation showed frontal dysfunction (Rey's figure). MRI study was normal. Oxcarbazepine permitted the disappearance of seizures and an improvement of executive disorders. In this case, the pathophysiological mechanism cannot be a hyperthermic related event. The temperature control as treatment of hot-water epilepsy could be used after the exploration of its implication in seizure induction.

  15. A comprehensive analysis of the geomagnetic storms occurred dur

    NASA Astrophysics Data System (ADS)

    Ghamry, Essam; Lethy, Ahmed; Arafa-Hamed, Tareq; Abd Elaal, Esmat

    2016-06-01

    The Geomagnetic storms are considered as one of the major natural hazards. Egyptian geomagnetic observatories observed multiple geomagnetic storms during 18 February to 2 March 2014. During this period, four interplanetary shocks successively hit the Earth's magnetosphere, leading to four geomagnetic storms. The storm onsets occurred on 18, 20, 23 and 27 February. A non-substorm Pi2 pulsation was observed on 26 February. This Pi2 pulsation was detected in Egyptian observatories (Misallat and Abu Simbel), Kakioka station in Japan and Carson City station in US with nearly identical waveforms. Van Allen Probe missions observed non-compressional Pc4 pulsations on the recovery phase of the third storm. This Pc4 event is may be likely attributed to the decay of the ring current in the recovery phase.

  16. Vampire bat reproductive control by a naturally occurring phytooestrogen.

    PubMed

    Serrano, Hector; Pérez-Rivero, Juan-José; Aguilar-Setién, Alvaro; de-Paz, Octavio; Villa-Godoy, Alejandro

    2007-01-01

    Rabies transmission by wild animals has not being controlled satisfactorily. One major rabies vector to humans and cattle is the hematophagous vampire bat Desmodus rotundus whose distribution is still increasing in the Americas. Of all of the strategies currently in place to control this vector, none of them are really specific and some have ecological impacts. In the present study we used a naturally occurring phytoestrogen on a small vampire bat colony. After collection, bats were fed bovine blood containing 200 microg coumestrol for a 30-day period. After treatment, gonads were excised and processed for histological evaluation. Data indicate that coumestrol adversely affects gonad histology and has a possible impact on the fertility of both male and female vampire bats. PMID:17394795

  17. Additive CHARMM force field for naturally occurring modified ribonucleotides.

    PubMed

    Xu, You; Vanommeslaeghe, Kenno; Aleksandrov, Alexey; MacKerell, Alexander D; Nilsson, Lennart

    2016-04-15

    More than 100 naturally occurring modified nucleotides have been found in RNA molecules, in particular in tRNAs. We have determined molecular mechanics force field parameters compatible with the CHARMM36 all-atom additive force field for all these modifications using the CHARMM force field parametrization strategy. Emphasis was placed on fine tuning of the partial atomic charges and torsion angle parameters. Quantum mechanics calculations on model compounds provided the initial set of target data, and extensive molecular dynamics simulations of nucleotides and oligonucleotides in aqueous solutions were used for further refinement against experimental data. The presented parameters will allow for computational studies of a wide range of RNAs containing modified nucleotides, including the ribosome and transfer RNAs. PMID:26841080

  18. When does MMR loss occur during HNPCC progression?

    PubMed

    Shibata, Darryl

    2006-01-01

    Inactivation of DNA mismatch repair (MMR) is the hallmark of hereditary nonpolyposis colorectal cancer (HNPCC) and sporadic colorectal cancers with microsatellite instability (MSI+). MMR loss results in a markedly elevated mutation rate, and many MS mutations are found in MSI+ cancers. In theory, it is possible to estimate the interval between MMR loss and cancer removal by counting numbers of cancer MS mutations--the more MS mutations, the longer the intervals since MMR loss. Using this somatic molecular clock approach, MMR loss is estimated to precede transformation (clonal expansion) and likely occurs in normal appearing colon. Surprising, ages at MMR loss are more consistent with MMR loss as a relatively late event during progression to MSI+ cancer. PMID:17192057

  19. Is anyone regulating naturally occurring radioactive material? A state survey

    SciTech Connect

    Gross, E.M.; Barisas, S.G.

    1993-08-01

    As far as we know, naturally occurring radioactive material (NORM) has surrounded humankind since the beginning of time. However, recent data demonstrating that certain activities concentrate NORM have increased concern regarding its proper handling and disposal and precipitated the development of new NORM-related regulations. The regulation of NORM affects the management of government facilities as well as a broad range of industrial processes. Recognizing that NORM regulation at the federal level is extremely limited, Argonne National Laboratory (ANL) conducted a 50-state survey to determine the extent to which states have assumed the responsibility for regulating NORM as well as the NORM standards that are currently being applied at the state level. Though the survey indicates that NORM regulation comprises a broad spectrum of controls from full licensing requirements to virtually no regulation at afl, a trend is emerging toward recognition of the need for increased regulation of potential NORM hazards, particularly in the absence of federal standards.

  20. Improving medication administration error reporting systems. Why do errors occur?

    PubMed

    Wakefield, B J; Wakefield, D S; Uden-Holman, T

    2000-01-01

    Monitoring medication administration errors (MAE) is often included as part of the hospital's risk management program. While observation of actual medication administration is the most accurate way to identify errors, hospitals typically rely on voluntary incident reporting processes. Although incident reporting systems are more economical than other methods of error detection, incident reporting can also be a time-consuming process depending on the complexity or "user-friendliness" of the reporting system. Accurate incident reporting systems are also dependent on the ability of the practitioner to: 1) recognize an error has actually occurred; 2) believe the error is significant enough to warrant reporting; and 3) overcome the embarrassment of having committed a MAE and the fear of punishment for reporting a mistake (either one's own or another's mistake).

  1. Additive CHARMM force field for naturally occurring modified ribonucleotides.

    PubMed

    Xu, You; Vanommeslaeghe, Kenno; Aleksandrov, Alexey; MacKerell, Alexander D; Nilsson, Lennart

    2016-04-15

    More than 100 naturally occurring modified nucleotides have been found in RNA molecules, in particular in tRNAs. We have determined molecular mechanics force field parameters compatible with the CHARMM36 all-atom additive force field for all these modifications using the CHARMM force field parametrization strategy. Emphasis was placed on fine tuning of the partial atomic charges and torsion angle parameters. Quantum mechanics calculations on model compounds provided the initial set of target data, and extensive molecular dynamics simulations of nucleotides and oligonucleotides in aqueous solutions were used for further refinement against experimental data. The presented parameters will allow for computational studies of a wide range of RNAs containing modified nucleotides, including the ribosome and transfer RNAs.

  2. Naturally occurring animal models of human hepatitis E virus infection.

    PubMed

    Yugo, Danielle M; Cossaboom, Caitlin M; Meng, Xiang-Jin

    2014-01-01

    Hepatitis E virus (HEV) is a single-stranded, positive-sense RNA virus in the family Hepeviridae. Hepatitis E caused by HEV is a clinically important global disease. There are currently four well-characterized genotypes of HEV in mammalian species, although numerous novel strains of HEV likely belonging to either new genotypes or species have recently been identified from several other animal species. HEV genotypes 1 and 2 are limited to infection in humans, whereas genotypes 3 and 4 infect an expanding host range of animal species and are zoonotic to humans. Historical animal models include various species of nonhuman primates, which have been indispensable for the discovery of human HEV and for understanding its pathogenesis and course of infection. With the genetic identification and characterization of animal strains of HEV, a number of naturally occurring animal models such as swine, chicken, and rabbit have recently been developed for various aspects of HEV research, including vaccine trials, pathogenicity, cross-species infection, mechanism of virus replication, and molecular biology studies. Unfortunately, the current available animal models for HEV are still inadequate for certain aspects of HEV research. For instance, an animal model is still lacking to study the underlying mechanism of severe and fulminant hepatitis E during pregnancy. Also, an animal model that can mimic chronic HEV infection is critically needed to study the mechanism leading to chronicity in immunocompromised individuals. Genetic identification of additional novel animal strains of HEV may lead to the development of better naturally occurring animal models for HEV. This article reviews the current understanding of animal models of HEV infection in both natural and experimental infection settings and identifies key research needs and limitations.

  3. Mud Flow Characteristics Occurred in Izuoshima Island, 2013

    NASA Astrophysics Data System (ADS)

    Takebayashi, H.; Egashira, S.; Fujita, M.

    2015-12-01

    Landslides and mud flows were occurred in the west part of the Izuoshima Island, Japan on 16 October 2013. The Izuoshima Island is a volcanic island and the land surface is covered by the volcanic ash sediment in 1m depth. Hence, the mud flow with high sediment concentration was formed. The laminar layer is formed in the debris flow from the bed to the fluid surface. On the other hand, the laminar flow is restricted near the bed in the mud flow and the turbulence flow is formed on the laminar flow layer. As a result, the equilibrium slope of the mud flow becomes smaller comparing to the debris flow. In this study, the numerical analysis mud flow model considering the effect of turbulence flow on the equilibrium slope of the mud flow is developed. Subsequently, the model is applied to the mud flow occurred in the Izuoshima Island and discussed the applicability of the model and the flow characteristics of the mud flow. The differences of the horizontal flow areas between the simulated results and the field data are compared and it was found that the outline of the horizontal shape of the flow areas is reproduced well. Furthermore, the horizontal distribution of the erosion and deposition area is reproduced by the numerical analysis well except for the residential area (Kandachi area). Kandachi area is judged as the erosion area by the field observation, but the sediment was deposited in the numerical analysis. It is considered that the 1.5hour heavy rain over 100mm/h after the mud flow makes the discrepancy. The difference of the horizontal distribution of the maximum flow surface elevation between the simulated results and the field data are compared and it was found that the simulated flow depth is overestimated slightly, because of the wider erosion area due to the coarse resolution elevation data. The averaged velocity and the depth of the mud flow was enough large to collapse the houses.

  4. Structural changes occurring during atresia in sheep ovarian follicles.

    PubMed

    Hay, M R; Cran, D G; Moor, R M

    1976-07-01

    The structural changes that characterize primary, secondary and tertiary atresia in sheep Graafian follicles have been studied by means of histological, histochemical and ultrastructural techniques. In primary atresia vacuoles representing swollen endoplasmic reticulum are prominent along the antral border together with disorganized granulosa cells containing pyknotic nuclei. Phagocytic cells, which increase in number as atresia progresses, were seen within the membrana granulosa and are considered to be transformed granulosa cells. Even in follicles classified as nonatretic, a few antral vacuoles and occasional pyknotic nuclei are present. During secondary atresia there is a large increase in the number of cells with pyknotic nuclei; many of these nuclei had been extruded and had fused to form the characteristic Feulgen-positive atretic bodies found along the edge of the antral cavity. These bodies usually have a diameter of up to 15 mum but occasionally reached as much as 400 mum. A second area of degeneration is frequently present in the membrana granulosa, two or three cell layers from the basal lamina, and it is at this level that exfoliation of granulosa cells occurs in tertiary atresia. In contrast to the membrana granulosa, there are during secondary atresia, only slight indications of degeneration in the cumulus. In tertiary atresia the membrana granulosa is highly disorganized; the atretic bodies are often fewer in number than at earlier stages. The basal lamina remains essentially intact. It is at this stage that the first clear signs of degeneration occur in the theca interna. Despite some disintegration of the cumulus, the integrity of the oocyte is maintained and its nucleus remains vesicular. Changes in the thecal microcirculation may plan a key role in atresia: adjacent to the basal lamina of non-atretic follicles, there is a well-developed capillary network which is significantly reduced as atresia progresses. PMID:991198

  5. VARIATION OCCURRING IN GROUP A STREPTOCOCCI DURING HUMAN INFECTION

    PubMed Central

    Rothbard, Sidney; Watson, Robert F.

    1948-01-01

    A study was made of the variation occurring in group A streptococci during the natural course of infection in man. From 54 patients with 56 different group A streptococcal infections of the upper respiratory tract, 251 strains of streptococci, isolated at weekly intervals following infection, were tested for their capacity to resist the bacteriostatic action of normal human blood. In 52 of the infections the streptococci were of recognized serological types and were also tested for variation in their ability to produce the type-specific M protein antigen. Strains isolated in the 1st week of infection were uniformly highly resistant to bacteriostasis and elaborated large amounts of M substance. In 42 per cent of the 52 infections, strains isolated in the convalescent and carrier stages showed an increasing susceptibility to bacteriostasis correlated with a progressive loss of M substance; whereas in the remaining 58 per cent resistance to bacteriostasis and the capacity to produce M protein were maintained throughout the observation period. In 3 different infections, the streptococci became so degraded that no M protein could be demonstrated in acid extracts of these variants. Concomitantly these strains became highly susceptible to bacteriostasis. Spontaneous reversion did not occur, but serial mouse passage reestablished these functions. These degraded variants had the same T antigen as their respective original strains. No evidence was obtained that variation of group A streptococci in resistance to bacteriostasis or in the ability to produce the type-specific M antigen was associated (a) with the appearance of type-specific bacteriostatic antibodies; (b) with any particular serological type of streptococcus; (c) with the production of streptococcal proteinase which digests the M protein; (d) with the therapeutic administration of sulfadiazine; or (e) with the development of complications. The possible relationship of these observations to the problem of the

  6. The human thyrotropin receptor: a heptahelical receptor capable of stimulating members of all four G protein families.

    PubMed Central

    Laugwitz, K L; Allgeier, A; Offermanns, S; Spicher, K; Van Sande, J; Dumont, J E; Schultz, G

    1996-01-01

    Thyrotropin is the primary hormone that, via one heptahelical receptor, regulates thyroid cell functions such as secretion, specific gene expression, and growth. In human thyroid, thyrotropin receptor activation leads to stimulation of the adenylyl cyclase and phospholipase C cascades. However, the G proteins involved in thyrotropin receptor action have been only partially defined. In membranes of human thyroid gland, we immunologically identified alpha subunits of the G proteins Gs short, Gs long, Gi1, Gi2, Gi3, G(o) (Go2 and another form of Go, presumably Go1), Gq, G11, G12, and G13. Activation of the thyrotropin (TSH) receptor by bovine TSH led to increased incorporation of the photoreactive GTP analogue [alpha-32P]GTP azidoanilide into immunoprecipitated alpha subunits of all G proteins detected in thyroid membranes. This effect was receptor-dependent and not due to direct G protein stimulation because it was mimicked by TSH receptor-stimulating antibodies of patients suffering from Grave disease and was abolished by a receptor-blocking antiserum from a patient with autoimmune hypothyroidism. The TSH-induced activation of individual G proteins occurred with EC50 values of 5-50 milliunits/ml, indicating that the activated TSH receptor coupled with similar potency to different G proteins. When human thyroid slices were pretreated with pertussis toxin, the TSH receptor-mediated accumulation of cAMP increased by approximately 35% with TSH at 1 milliunits/ml, indicating that the TSH receptor coupled to Gs and G(i). Taken together, these findings show that, at least in human thyroid membranes, in which the protein is expressed at its physiological levels, the TSH receptor resembles a naturally occurring example of a general G protein-activating receptor. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8552586

  7. Gravity receptors and responses

    NASA Technical Reports Server (NTRS)

    Brown, Allan H.

    1989-01-01

    The overall process of gravity sensing and response processes in plants may be divided conveniently into at least four components or stages: Stimulus susception (a physical event, characteristically the input to the G receptor system of environmental information about the G force magnitude, its vector direction, or both); information perception (an influence of susception on some biological structure or process that can be described as the transformation of environmental information into a biologicallly meaningful change); information transport (the export, if required, of an influence (often chemical) to cells and organs other than those at the sensor location); and biological response (almost always (in plants) a growth change of some kind). Some analysts of the process identify, between information perception and information transport, an additional stage, transduction, which would emphasize the importance of a transformation from one form of information to another, for example from mechanical statolith displacement to an electric, chemical, or other alteration that was its indirect result. These four (or five) stages are temporally sequential. Even if all that occurs at each stage can not be confidently identified, it seems evident that during transduction and transport, matters dealt with are found relatively late in the information flow rather than at the perception stage. As more and more is learned about the roles played by plant hormones which condition the G responses, the mechanism(s) of perception which should be are not necessarily better understood. However, if by asking the right questions and being lucky with experiments perhaps the discovery of how some process (such as sedimentation of protoplasmic organelles) dictates what happens down stream in the information flow sequence may be made.

  8. [A case of malignant hyperthermia occuring in a dental clinic].

    PubMed

    Martel, A; Spigelblatt, L; Perreault, L; Rosenfeld, R

    1979-01-01

    Malignant hyperthermia, a life-threatening complication of anaesthesia, occurred in a 5 1/2-year-old girl undergoing dental surgery in a dental clinic. During induction, after 20 mg of succinylcholine, the anaesthetist noted a moderate rigidity of the mandible that did not interfere with the tracheal intubation. However, after 45 minutes, the temperature rose to 38.8 degrees C, pulse was rapid at 160 per minute and the child was slightly cyanosed. The diagnosis of malignant hyperthermia was made (the temperature eventually reached 40.8 degrees C). The child was immediately treated with refrigeration, procainamide and sodium bicarbonate. She was then moved to a hospital centre where the treatment was continued and she recovered completely. After extensive investigation, we found that the paternal grandfather of the child died at age 58, several hours after a bilateral lumbar sympathectomy under general anaesthesia. The cause of the death, as confirmed by hospital records, was malignant hyperthermia. No genetic counselling was given at that time; this omission has since been corrected. Early diagnosis and the availability on the premises of the necessary drugs and equipment to treat such a complication probably saved this child's life. In 1975, "La Corporation Professionnelle des Médecins du Québec" published standards for practice of anaesthesia outside a hospital setting. The compliance of the dental clinic with such standards has contributed to the avoidance of a catastrophe. PMID:761114

  9. Sexual conflict and cooperation under naturally occurring male enforced monogamy.

    PubMed

    Montrose, V T; Harris, W E; Moore, P J

    2004-03-01

    An evolutionary conflict often exists between the sexes in regard to female mating patterns. Females can benefit from polyandry, whereas males mating with polyandrous females lose reproductive opportunities because of sperm competition. Where this conflict occurs, the evolution of mechanisms whereby males can control female remating, often at a fitness cost to the female, are expected to evolve. The fitness cost to the female will be increased in systems where a few high status males monopolise mating opportunities and thus have limited sperm supplies. Here we show that in the cockroach Nauphoeta cinerea, a species where males enforce female monogamy in the first reproductive cycle, males that have become sperm depleted continue to be able to manipulate female remating behaviour. Although the manipulation severely decreases fecundity in females mated to sperm-depleted males, males benefit, increasing their relative fitness by preventing other males from reproducing. Our results suggest that there is selection on maintaining the mechanism of manipulation rather than maintaining sperm numbers. Taken with previous research on sexual conflict in N. cinerea, this study suggests that the causes and consequences of sexual conflict are complex and can change across the life history of an individual.

  10. Analysis of coal slag for naturally occurring radioactive material.

    PubMed

    Spitz, H B; Rajaretnam, G

    1998-07-01

    Samples of aerosolized coal slag were collected during an abrasive blasting operation to determine the concentration of naturally occurring radioactive materials (NORM) in the respirable and nonrespirable fractions. Each slag fraction was analyzed using alpha and gamma spectrometry. Since the slag is insoluble, it was necessary to dissolve samples completely by fusion with potassium fluoride and, after additional transposing and separation, mount the precipitate containing radium (Ra), the main radioactive component in NORM, on a membrane filter for alpha counting. The concentration of 226Ra in coal slag was independent of the particle size fraction and equal to 2.28 picocuries/gram (pCi/g) +/- 0.43 pCi/g, which is approximately twice the typical concentration of NORM in uncontaminated soil. Analysis of NORM by gamma spectrometry identified low concentrations of uranium, thorium, and potassium, all primordial radioactive materials that are commonly encountered in normal background soil. Integral exposure to workers from inhalation of NORM during abrasive blasting with coal slag is extremely low and could be essentially eliminated by use of appropriate respiratory protection. External radiation exposure to workers handling large quantities of NORM-contaminated coal slag during shipping or storage is also low, but would vary depending on the concentration of NORM in the slag.

  11. Naturally occurring and forced azimuthal modes in a turbulent jet

    NASA Technical Reports Server (NTRS)

    Raman, Ganesh; Rice, Edward J.; Reshotko, Eli

    1991-01-01

    Naturally occurring instability modes in an axisymmetric jet were studied using the modal frequency technique. The evolution of the modal spectrum was obtained for a jet with a Reynolds number based on a diameter of 400,000 for both laminar and turbulent nozzle boundary layers. In the early evolution of the jet the axisymmetric mode was predominant, with the azimuthal modes growing rapidly but dominating only the end of the potential core. The growth of the azimuthal was observed closer to the nozzle exit for the jet in the laminar boundary layer case than for the turbulent. Target modes for efficient excitation of the jet were determined and two cases of excitation were studied. First, a jet was excited simultaneously by two helical modes, m equals plus 1 and m equals minus 1 at a Strouhal number based on jet diameter of 0.15 and the axisymmetric mode, m equals 0 at a jet diameter of 0.6. Second, m equals plus one and m equals minus 1 at jet diameter equals 0.3 and m equals 0 at jet diameter equals 0.6 were excited simultaneously. The downstream evolution of the hydrodynamic modes and the spreading rate of the jet were documented for each case. Higher jet spreading rates, accompanied by distorted jet cross sections were observed for the cases where combinations of axisymmetric and helical forcings were applied.

  12. Does Temporal Integration Occur for Unrecognizable Words in Visual Crowding?

    PubMed Central

    Zhou, Jifan; Lee, Chia-Lin; Li, Kuei-An; Tien, Yung-Hsuan; Yeh, Su-Ling

    2016-01-01

    Visual crowding—the inability to see an object when it is surrounded by flankers in the periphery—does not block semantic activation: unrecognizable words due to visual crowding still generated robust semantic priming in subsequent lexical decision tasks. Based on the previous finding, the current study further explored whether unrecognizable crowded words can be temporally integrated into a phrase. By showing one word at a time, we presented Chinese four-word idioms with either a congruent or incongruent ending word in order to examine whether the three preceding crowded words can be temporally integrated to form a semantic context so as to affect the processing of the ending word. Results from both behavioral (Experiment 1) and Event-Related Potential (Experiment 2 and 3) measures showed congruency effect in only the non-crowded condition, which does not support the existence of unconscious multi-word integration. Aside from four-word idioms, we also found that two-word (modifier + adjective combination) integration—the simplest kind of temporal semantic integration—did not occur in visual crowding (Experiment 4). Our findings suggest that integration of temporally separated words might require conscious awareness, at least under the timing conditions tested in the current study. PMID:26890366

  13. Discovering Psychological Principles by Mining Naturally Occurring Data Sets.

    PubMed

    Goldstone, Robert L; Lupyan, Gary

    2016-07-01

    The very expertise with which psychologists wield their tools for achieving laboratory control may have had the unwelcome effect of blinding psychologists to the possibilities of discovering principles of behavior without conducting experiments. When creatively interrogated, a diverse range of large, real-world data sets provides powerful diagnostic tools for revealing principles of human judgment, perception, categorization, decision-making, language use, inference, problem solving, and representation. Examples of these data sets include patterns of website links, dictionaries, logs of group interactions, collections of images and image tags, text corpora, history of financial transactions, trends in twitter tag usage and propagation, patents, consumer product sales, performance in high-stakes sporting events, dialect maps, and scientific citations. The goal of this issue is to present some exemplary case studies of mining naturally existing data sets to reveal important principles and phenomena in cognitive science, and to discuss some of the underlying issues involved with conducting traditional experiments, analyses of naturally occurring data, computational modeling, and the synthesis of all three methods. PMID:27404718

  14. Degradation of tyrosinase induced by phenylthiourea occurs following Golgi maturation.

    PubMed

    Hall, Andrea M; Orlow, Seth J

    2005-04-01

    Tyrosinase, the rate-limiting enzyme of melanin synthesis, is a di-copper metalloprotein that catalyzes the conversion of L-tyrosine to L-DOPAquinone. Phenylthiourea (PTU) is a well-known inhibitor of tyrosinase and melanin synthesis and is known to interact with sweet potato catechol oxidase, an enzyme possessing copper binding domain homology to tyrosinase. While PTU is frequently used to induce hypopigmentation in biological systems, little is known about its effects on tyrosinase and other melanogenic proteins. We have found that PTU induces degradation of tyrosinase but not of other melanogenic proteins including the tyrosinase-related metalloproteins tyrosinase-related protein (Tyrp)1 and Tyrp2. Using pulse-chase analysis coupled with glycosidase digestion, we observed that tyrosinase degradation occurs following complete maturation of the protein and that degradation was reversed by cysteine protease inhibitor E64 but not proteasome inhibitor N-acetyl-L-leucinyl-L-leucinyl-L-norleucinal. We conclude that PTU specifically induces tyrosinse degradation following Golgi maturation. Our data suggest that in addition to well-known ER-directed quality control, tyrosinase is also subject to post-Golgi quality control. PMID:15760341

  15. Discovering Psychological Principles by Mining Naturally Occurring Data Sets.

    PubMed

    Goldstone, Robert L; Lupyan, Gary

    2016-07-01

    The very expertise with which psychologists wield their tools for achieving laboratory control may have had the unwelcome effect of blinding psychologists to the possibilities of discovering principles of behavior without conducting experiments. When creatively interrogated, a diverse range of large, real-world data sets provides powerful diagnostic tools for revealing principles of human judgment, perception, categorization, decision-making, language use, inference, problem solving, and representation. Examples of these data sets include patterns of website links, dictionaries, logs of group interactions, collections of images and image tags, text corpora, history of financial transactions, trends in twitter tag usage and propagation, patents, consumer product sales, performance in high-stakes sporting events, dialect maps, and scientific citations. The goal of this issue is to present some exemplary case studies of mining naturally existing data sets to reveal important principles and phenomena in cognitive science, and to discuss some of the underlying issues involved with conducting traditional experiments, analyses of naturally occurring data, computational modeling, and the synthesis of all three methods.

  16. Solution of naturally-occurring glasses in the geological environment

    SciTech Connect

    Glass, B.P.

    1982-12-01

    As part of a study to investigate the feasibility of putting nuclear wastes in glass containers and burying them on land or dumping them in the ocean, we have made a study of the amount of solution experienced by naturally occurring glasses from two land sites and thirty-four deep-sea sites. The glasses used in this study are microtektites from three strewn fields (Australasian, Ivory Coast, and North American) and from the Zhamanshin impact crater in southern Siberia. The microtektites range in age from 0.7 to 35 m.y. and they have a wide range in composition. Although several criteria for determining the amount of solution were considered, most of the conclusions are based on two criteria: (1) width of cracks, and (2) elevation of silica-rich inclusions above the adjacent microtektite surface. The amount of solution was determined for about 170 microtektites; and measured amounts of solution range from 0.2 to at least 28 {mu}m, but most are less than 5 {mu}m. There appears to be no systematic relationship between age and amount of solution. 21 refs., 7 tabs.

  17. Identifying Naturally Occurring Retirement Communities: A Spatial Analysis

    PubMed Central

    Rivera-Hernandez, Maricruz; Yamashita, Takashi; Kinney, Jennifer M.

    2016-01-01

    Objectives Guided by the concept of “aging in place” and potential policy implications, the study analyzed naturally occurring retirement communities (NORCs; 40% or greater house owners and renters aged 65 years and older) and whether there were spatiotemporal patterns in Ohio between 2000 and 2010. Method Data were derived from the 2000 and 2010 census tracts. Geovisualization was used to visually examine the distribution of NORCs in 2000 and 2010. Global Moran’s I was used to quantify the spatial distribution of NORCs in Ohio and Local Moran’s I was used to identify clusters of NORCs (i.e., hot spots). Results The number of NORCs slightly decreased despite the overall increase of the older population from 2000 to 2010. NORCs were identified in one of the 3 most populous counties (i.e., Cuyahoga) and its neighboring counties. A number of hot spots were identified in Cuyahoga County (among Ohio’s most populous and NORC-rich counties), both in 2000 and 2010. There were different patterns including emerging, disappearing, and enduring NORCs and disproportionate distributions of NORCs across the state between 2000 and 2010. Discussion Locating NORCs could aid governments to create “aging in place” sensitive policies to address issues of independence, social care, health care, volunteerism, and community participation. PMID:24958694

  18. Psychosocial diagnoses occurring after patients present with fatigue

    PubMed Central

    MacKean, Peter Reagh; Stewart, Moira; Maddocks, Heather L.

    2016-01-01

    Abstract Objective To discover the frequency of psychosocial and other diagnoses occurring at the end of a visit when patients present to their FPs with concerns about fatigue. Design Cross-sectional study of patient-FP encounters for fatigue. Setting Ten FP practices in southwestern Ontario. Participants A total of 259 encounters involving 167 patients presenting to their FPs between March 1, 2006, and June 30, 2010, with concerns about fatigue. Main outcome measures The frequency of psychological and social diagnoses made at the end of visits, and whether diagnoses were made by FPs at the end of the visits versus whether the code for fatigue remained. The associations between patient age, sex, fatigue presenting with other symptoms, or the presence of previous chronic conditions and the outcomes was tested. Results Psychosocial diagnoses were made 23.9% of the time. Among psychosocial diagnoses made, depressive disorder and anxiety disorder or anxiety state were diagnosed more often in women (P = .048). Slightly less than 30% of the time, the cause of patients’ fatigue remained undiagnosed at the end of the encounter. A diagnosis was made more often in men. Conclusion Causes of fatigue frequently remain undiagnosed; however, when there is a diagnosis, psychosocial diagnoses are common. Therefore, it would be appropriate for FPs to screen for psychosocial issues when their patients present with fatigue, unless some other diagnosis is evident. Depression and anxiety could be considered particularly among female patients with fatigue. PMID:27521412

  19. Characteristics of Cherenkov radiation in naturally occurring ice

    NASA Astrophysics Data System (ADS)

    Mikkelsen, R. E.; Poulsen, T.; Uggerhøj, U. I.; Klein, S. R.

    2016-03-01

    We revisit the theory of Cherenkov radiation in uniaxial crystals. Historically, a number of flawed attempts have been made at explaining this radiation phenomenon, and a consistent error-free description is nowhere available. We apply our calculation to a large modern day telescope—IceCube. Located in Antarctica, this detector makes use of the naturally occurring ice as a medium to generate Cherenkov radiation. However, due to the high pressure at the depth of the detector site, large volumes of hexagonal ice crystals are formed. We calculate how this affects the Cherenkov radiation yield and angular dependence. We conclude that the effect is small, at most about a percent, and would only be relevant in future high-precision instruments like e.g. Precision IceCube Next Generation Upgrade (PINGU). For radio-Cherenkov experiments which use the presence of a clear Cherenkov cone to determine the arrival direction, any variation in emission angle will directly and linearly translate into a change in apparent neutrino direction. In closing, we also describe a simple experiment to test this formalism and calculate the impact of anisotropy on light yields from lead tungstate crystals as used, for example, in the CMS calorimeter at the CERN LHC.

  20. Pioneer round of translation occurs during serum starvation

    SciTech Connect

    Oh, Nara; Kim, Kyoung Mi; Cho, Hana; Choe, Junho; Kim, Yoon Ki

    2007-10-12

    The pioneer round of translation plays a role in translation initiation of newly spliced and exon junction complex (EJC)-bound mRNAs. Nuclear cap-binding protein complex CBP80/20 binds to those mRNAs at the 5'-end, recruiting translation initiation complex. As a consequence of the pioneer round of translation, the bound EJCs are dissociated from mRNAs and CBP80/20 is replaced by the cytoplasmic cap-binding protein eIF4E. Steady-state translation directed by eIF4E allows for an immediate and rapid response to changes in physiological conditions. Here, we show that nonsense-mediated mRNA decay (NMD), which restricts only to the pioneer round of translation but not to steady-state translation, efficiently occurs even during serum starvation, in which steady-state translation is drastically abolished. Accordingly, CBP80 remains in the nucleus and processing bodies are unaffected in their abundance and number in serum-starved conditions. These results suggest that mRNAs enter the pioneer round of translation during serum starvation and are targeted for NMD if they contain premature termination codons.

  1. Mass transfer trends occurring in engineered ex vivo tissue scaffolds.

    PubMed

    Moore, Marc; Sarntinoranont, Malisa; McFetridge, Peter

    2012-08-01

    In vivo the vasculature provides an effective delivery system for cellular nutrients; however, artificial scaffolds have no such mechanism, and the ensuing limitations in mass transfer result in limited regeneration. In these investigations, the regional mass transfer properties that occur through a model scaffold derived from the human umbilical vein (HUV) were assessed. Our aim was to define the heterogeneous behavior associated with these regional variations, and to establish if different decellularization technologies can modulate transport conditions to improve microenvironmental conditions that enhance cell integration. The effect of three decellularization methods [Triton X-100 (TX100), sodium dodecyl sulfate (SDS), and acetone/ethanol (ACE/EtOH)] on mass transfer, cellular migration, proliferation, and metabolic activity were assessed. Results show that regional variation in tissue structure and composition significantly affects both mass transfer and cell function. ACE/EtOH decellularization was shown to increase albumin mass flux through the intima and proximate-medial region (0-250 μm) when compared with sections decellularized with TX100 or SDS; although, mass flux remained constant over all regions of the full tissue thickness when using TX100. Scaffolds decellularized with TX100 were shown to promote cell migration up to 146% further relative to SDS decellularized samples. These results show that depending on scaffold derivation and expectations for cellular integration, specificities of the decellularization chemistry affect the scaffold molecular architecture resulting in variable effects on mass transfer and cellular response.

  2. Learning as a phenomenon occurring in a critical state

    PubMed Central

    de Arcangelis, Lucilla; Herrmann, Hans J.

    2010-01-01

    Recent physiological measurements have provided clear evidence about scale-free avalanche brain activity and EEG spectra, feeding the classical enigma of how such a chaotic system can ever learn or respond in a controlled and reproducible way. Models for learning, like neural networks or perceptrons, have traditionally avoided strong fluctuations. Conversely, we propose that brain activity having features typical of systems at a critical point represents a crucial ingredient for learning. We present here a study that provides unique insights toward the understanding of the problem. Our model is able to reproduce quantitatively the experimentally observed critical state of the brain and, at the same time, learns and remembers logical rules including the exclusive OR, which has posed difficulties to several previous attempts. We implement the model on a network with topological properties close to the functionality network in real brains. Learning occurs via plastic adaptation of synaptic strengths and exhibits universal features. We find that the learning performance and the average time required to learn are controlled by the strength of plastic adaptation, in a way independent of the specific task assigned to the system. Even complex rules can be learned provided that the plastic adaptation is sufficiently slow. PMID:20160107

  3. Educational utilization of outstanding spherulitic rhyolite occurred in Cheongsong, Korea

    NASA Astrophysics Data System (ADS)

    Jang, Y. D.; Woo, H.

    2015-12-01

    Cheongsong is located in the central eastern area of South Korea. Unique spherulitic rhyolites occur in this region as dykes formed about 48 to 50 million years ago. Composed of quartz and feldspar these spherulitic rhyolites show various flowerlike shapes, such as chrysanthemum, dandelion, rose, carnation, sunflower, dahlia and so on, so they are called 'flower stones'. The spherulite indicates that it was undercooled caused by very fast cooling at a shallow depth near the surface and the variety of shapes resulted from the difference of crystallizing conditions. According to the condition, minerals start to crystallize homogeneously or heterogeneously and develop as rounded or fibrous shapes, representing beautiful patterns when combined. These spherulitic structures are very rare not only in Korea but also globally, being valuable for research and preservation because of their rarity, beauty and diversity. Cheongsong therefore applies to the UGG (UNESCO Global Geopark) in an attempt to popularize the flower stones and use them as education materials which can also be incorporated in other valuable sites. The exhibition center provides diverse types of flower stones in which visitors could learn about rhyolitic volcanism, crystallization and spherulite and can experience the process of changing a rough stone into a flower stone. A geotrail course has also been created, showing each type of flower stone on the outcrop and providing educational programs about geological mechanisms of the stones with a trained guide.

  4. Does Temporal Integration Occur for Unrecognizable Words in Visual Crowding?

    PubMed

    Zhou, Jifan; Lee, Chia-Lin; Li, Kuei-An; Tien, Yung-Hsuan; Yeh, Su-Ling

    2016-01-01

    Visual crowding-the inability to see an object when it is surrounded by flankers in the periphery-does not block semantic activation: unrecognizable words due to visual crowding still generated robust semantic priming in subsequent lexical decision tasks. Based on the previous finding, the current study further explored whether unrecognizable crowded words can be temporally integrated into a phrase. By showing one word at a time, we presented Chinese four-word idioms with either a congruent or incongruent ending word in order to examine whether the three preceding crowded words can be temporally integrated to form a semantic context so as to affect the processing of the ending word. Results from both behavioral (Experiment 1) and Event-Related Potential (Experiment 2 and 3) measures showed congruency effect in only the non-crowded condition, which does not support the existence of unconscious multi-word integration. Aside from four-word idioms, we also found that two-word (modifier + adjective combination) integration-the simplest kind of temporal semantic integration-did not occur in visual crowding (Experiment 4). Our findings suggest that integration of temporally separated words might require conscious awareness, at least under the timing conditions tested in the current study.

  5. Bladder Uptake of Liposomes after Intravesical Administration Occurs by Endocytosis

    PubMed Central

    Rajaganapathy, Bharathi Raja; Chancellor, Michael B.; Nirmal, Jayabalan; Dang, Loan; Tyagi, Pradeep

    2015-01-01

    Liposomes have been used therapeutically and as a local drug delivery system in the bladder. However, the exact mechanism for the uptake of liposomes by bladder cells is unclear. In the present study, we investigated the role of endocytosis in the uptake of liposomes by cultured human UROtsa cells of urothelium and rat bladder. UROtsa cells were incubated in serum-free media with liposomes containing colloidal gold particles for 2 h either at 37°C or at 4°C. Transmission Electron Microscopy (TEM) images of cells incubated at 37°C found endocytic vesicles containing gold inside the cells. In contrast, only extracellular binding was noticed in cells incubated with liposomes at 4°C. Absence of liposome internalization at 4°C indicates the need of energy dependent endocytosis as the primary mechanism of entry of liposomes into the urothelium. Flow cytometry analysis revealed that the uptake of liposomes at 37°C occurs via clathrin mediated endocytosis. Based on these observations, we propose that clathrin mediated endocytosis is the main route of entry for liposomes into the urothelial layer of the bladder and the findings here support the usefulness of liposomes in intravesical drug delivery. PMID:25811468

  6. Antimicrobial evaluation of selected naturally occurring oxyprenylated secondary metabolites.

    PubMed

    Di Giulio, Mara; Genovese, Salvatore; Fiorito, Serena; Epifano, Francesco; Nostro, Antonia; Cellini, Luigina

    2016-08-01

    This study tested the antimicrobial activity of eight selected naturally occurring oxyprenylated secondary metabolites against Staphylococcus aureus ATCC 29213, S. epidermidis ATCC 35984, Escherichia coli ATCC 8739, Pseudomonas aeruginosa ATCC 9027 and Candida albicans ATCC 10231. Results showed a moderate antimicrobial activity. The most active compounds were 3-(4-geranyloxyphenyl)-1-ethanol (4) and 3-(4-isopentenyloxyphenyl)-1-propanol (5) that were tested on mature and in-formation biofilms of all micro-organisms, moreover the cytotoxic activity was evaluated. Except for S. epidermidis, both compounds reduced significantly (p < 0.05) the microbial biofilm formation at 1/2 MIC and 1/4 MIC, in particular, compounds 4 and 5 at each concentration, inhibited E. coli biofilm formation to a greater extent, the biofilm formation was never more than 44% in respect to the control, moreover both compounds showed a low cytotoxic effect. Oxyprenylated derivatives may be of great interest for the development of novel antimicrobial therapeutic strategies and the synthesis of semi-synthetic analogues with anti-biofilm efficacy. PMID:27498831

  7. Spatial and temporal gene expression patterns occur during corm development.

    PubMed

    de Castro, L A; Carneiro, M; Neshich, D de C; de Paiva, G R

    1992-12-01

    We investigated gene expression patterns that occur during taro corm development. Two-dimensional gel electrophoresis identified several different prevalent proteins that accumulate during corm development. Microsequencing studies indicated that some of these proteins are related to taste-modifying proteins, such as curculin and miraculin, and proteins found in other storage organs, such as sporamin and the Kunitz trypsin inhibitor. A curculin-encoding cDNA clone, designated as TC1, was identified that corresponds to a highly prevalent 1-kb corm mRNA. The TC1 mRNA accumulates during corm development, is more prevalent in corm apical than basal regions, and is either absent, or present at low concentrations, in other vegetative organs such as the leaf and root. In situ hybridization experiments showed that the TC1 mRNA is highly concentrated in corm storage parenchyma cells and is absent, or present in reduced concentrations, in other corm cells and tissues. Our results show that corm development is associated with the differentiation of specialized cells and tissues, and that these differentiation events are coupled with the temporal and spatial expression of corm-specific genes. PMID:1467653

  8. Ventilatory adaptation to hypoxia occurs in serotonin-depleted rats.

    PubMed

    Olson, E B

    1987-08-01

    To test the hypothesis that serotonin mediated respiratory activity is involved in ventilatory adaptation to hypoxia, rats were treated with parachlorophenylalanine (PCPA), a potent, long-acting inhibitor of tryptophan hydroxylase, the rate-limiting enzyme in the biosynthesis of serotonin. In normoxia, a single, intraperitoneal injection of 300 mg PCPA/kg body weight decreased the Paco2 from a control level at 39.1 +/- 0.6 Torr (mean +/- 95% confidence limits) to 34.0 +/- 0.6 Torr measured during a period from 1 to 48 h following PCPA treatment. This PCPA-produced hyperventilation corresponds to an increase of 3.7 +/- 0.5 in the VA (BTPS)/Vco2 (STPD) ratio. Hyperventilation during ventilatory adaptation to hypoxia (PIO2 approximately equal to 90 Torr) was superimposed in an additive fashion on the underlying hyperventilation due to PCPA pretreatment. Specifically, PCPA pretreatment caused an average 3.5 +/- 1.2 increase in the VA/VCO2 ratio determined in acute (1 h) hypoxia, chronic (24 h) hypoxia and acute return to normoxia following chronic hypoxia. Since ventilatory adaptation to hypoxia occurred in rats treated with PCPA, the prolonged, serotonin mediated respiratory activity described by Millhorn et al. (1980b) is probably not important in ventilatory acclimatization to - or deacclimatization from - hypoxia. PMID:2957766

  9. Characterisation of pleural inflammation occurring after primary spontaneous pneumothorax.

    PubMed

    De Smedt, A; Vanderlinden, E; Demanet, C; De Waele, M; Goossens, A; Noppen, M

    2004-06-01

    The aim of this study was to examine the inflammatory reaction occurring in the pleural space of patients suffering from primary spontaneous pneumothorax (PSP) using pleural lavage, which was performed in patients with PSP and in healthy control subjects (essential hyperhidrosis patients undergoing thoracoscopy for sympathicolysis treatment). Cellular and solute composition of lavage fluid, peripheral blood and parietal pleural biopsies were analysed. PSP lavage fluid showed an increase in all differentiated leucocytes, but most strikingly eosinophils and neutrophils. In the blood of patients with PSP, the total number of leucocytes and the absolute number of eosinophils, neutrophils and monocytes were also significantly increased. The time in which air was present in the pleural space was positively correlated with the increase of eosinophils in lavage fluid, parietal pleura and blood. Eosinophilic cationic protein was elevated after PSP and strongly correlated with the absolute number of lavage eosinophils. Chemo and cytokine analysis in lavage fluid showed differences in concentrations of interleukin (IL)-5, IL-6, IL-8, IL-12p40, tumour necrosis factor-alpha and RANTES, but not of eotaxin. Surprisingly, high levels of lipopolysaccharide binding protein were also measured. Primary spontaneous pnumothorax is associated with a substantial pleural inflammatory reaction. The authors hypothesise that mechanical stretch factors, lipopolysaccharide binding protein/lipopolysaccharide complexes or other environmental components trigger pleural inflammation after primary spontaneous pnumothorax. PMID:15219004

  10. Naturally-occurring anti-Jka in infant twins.

    PubMed

    Rumsey, D H; Nance, S J; Rubino, M; Sandler, S G

    1999-01-01

    Anti-Jka was detected by solid-phase red cell adherence (SPRCA) antibody detection and identification tests in the plasma of a 9-month-old female infant during a routine presurgical evaluation. The patient and her nonidentical twin sister, who also had anti-Jka in her plasma, were products of an uncomplicated in vitro fertilization, full-term pregnancy, and vaginal delivery. Neither twin had been transfused, recently infected, or treated with medication. Their mother had no prior pregnancies or transfusions. Red blood cells (RBCs) from the patient and her sister typed as Jk(a-b+) by direct hemagglutination, and this phenotype was confirmed by negative adsorption and elution studies. Both infants' plasma samples were strongly reactive with 20 examples of Jk(a+) RBCs and nonreactive with 20 examples of Jk(a-) RBCs by SPRCA assays. Anti-Jka was not detected in either twins' plasma by indirect antiglobulin tests by tube method in low-ionic- strength saline solution or polyethylene glycol, or with ficin- or papain-treated RBCs. Monocyte monolayer assays using Jk(a+) RBCs sensitized by either twins' serum were nonreactive (0%). RBCs from both parents typed as Jk(a+b+). Both parents' antibody detection test results by SPRCA assay were negative. The absence of a history of exposure to allogeneic RBCs or possible passive transfer of maternal or other alloantibody classifies these antibodies as naturally-occurring anti-Jka.

  11. Coaggregation occurs between microorganisms isolated from different environments.

    PubMed

    Stevens, Michael R E; Luo, Ting L; Vornhagen, Jay; Jakubovics, Nicholas S; Gilsdorf, Janet R; Marrs, Carl F; Møretrø, Trond; Rickard, Alexander H

    2015-11-01

    Coaggregation, the specific recognition and adherence of different microbial species, is thought to enhance biofilm formation. To date, no studies have focused on the ability of microorganisms isolated from a broad range of environments to coaggregate with each other and it is unclear whether coaggregation promotes the transmission of microorganisms between environmental niches. We aimed to evaluate the coaggregation ability of 29 bacteria and one fungus, isolated from a range of different environments, and to characterize the cell-surface polymers that mediate coaggregation between selected pairs. Strains were categorized as belonging to one of the four microbial archetypes: aquatic, broad environment, human opportunistic pathogen or human oral. A total of 23 of the 30 strains (77%) coaggregated with at least one other and 21/30 (70%) coaggregated with strains belonging to other archetypes. Nasopharyngeal bacteria belonging to the human opportunistic pathogen archetype showed the least number of coaggregations, and five Haemophilus influenzae strains did not coaggregate. Protease and sugar treatments indicated that coaggregation between strains of different archetypes was often mediated by lectin-saccharide interactions (9 of 15 evaluated pairs). In conclusion, coaggregation can occur between taxonomically disparate species isolated from discrete environments. We propose that these organisms be labeled as 'cross-environment coaggregating organisms'. The ability to coaggregate may aid species to colonize non-indigenous biofilms. PMID:26475462

  12. On the torque reversal occurred in X-ray binaries

    NASA Astrophysics Data System (ADS)

    Gong, Biping

    The effect of torque reversal has been observed in a number of X-ray binaries, such as 4U1627-67, Her X-1, Cen X-3, GX 1+4, OAO 1657-415, and Vela X-1. Here we suggest that it originates in a simply mechanism, residual Doppler shift. In a binary system with periodic signals sending to an observer, the drift of the signal frequency actually changes with the varying orbital velocity, projected to line of sight at different phases of orbit. And it has been taken for granted that the net red-shift and blue-shift of an full orbit circle be cancelled out, so that the effect of Doppler shift to the signal in binary motion cannot be accumulated over the orbital period. However, taking the propagation time at each velocity state into account, the symmetry of the velocity distribution over the orbital phase is broken. Consequently, the net Doppler shift left in an orbit is non-zero. It is this Newtonian second Doppler effect that responsible for the torque reversal occurred in X-ray binaries.

  13. Activation of EphA receptors mediates the recruitment of the adaptor protein Slap, contributing to the downregulation of N-methyl-D-aspartate receptors.

    PubMed

    Semerdjieva, Sophia; Abdul-Razak, Hayder H; Salim, Sharifah S; Yáñez-Muñoz, Rafael J; Chen, Philip E; Tarabykin, Victor; Alifragis, Pavlos

    2013-04-01

    Regulation of the activity of N-methyl-d-aspartate receptors (NMDARs) at glutamatergic synapses is essential for certain forms of synaptic plasticity underlying learning and memory and is also associated with neurotoxicity and neurodegenerative diseases. In this report, we investigate the role of Src-like adaptor protein (Slap) in NMDA receptor signaling. We present data showing that in dissociated neuronal cultures, activation of ephrin (Eph) receptors by chimeric preclustered eph-Fc ligands leads to recruitment of Slap and NMDA receptors at the sites of Eph receptor activation. Interestingly, our data suggest that prolonged activation of EphA receptors is as efficient in recruiting Slap and NMDA receptors as prolonged activation of EphB receptors. Using established heterologous systems, we examined whether Slap is an integral part of NMDA receptor signaling. Our results showed that Slap does not alter baseline activity of NMDA receptors and does not affect Src-dependent potentiation of NMDA receptor currents in Xenopus oocytes. We also demonstrate that Slap reduces excitotoxic cell death triggered by activation of NMDARs in HEK293 cells. Finally, we present evidence showing reduced levels of NMDA receptors in the presence of Slap occurring in an activity-dependent manner, suggesting that Slap is part of a mechanism that homeostatically modulates the levels of NMDA receptors.

  14. [Occurence of diarylheptanoids in Corylus species native to Hungary].

    PubMed

    Riethmüller, Eszter; Tóth, Gergő; Alberti, Agnes; Végh, Krisztina; Béni, Szabolcs; Balogh, György Tibor; Kéry, Agnes

    2015-01-01

    Since the last decade naturally occurring diarylheptanoids have been in the focus of scientific interest due to their various. beneficial biological effects. Besides the outstanding importance of the curcuminoids isolated from members of the Curcuma genus (Zingiberaceae), several different diarylheptanoids identified in Alnus species (Betulaceae) have been proved to possess notable pharmacological effects. Chemoprotective, neuroprotective, hepatoprotective, antiviral, antibacterial, antiinflammatory and antioxidant activities suggest their potential role in clinical practice. The aim of our study was the phytochemical investigation of the Corylus (Betulaceae) species native to Hungary: the Common hazel (Corylus avellana L.), the Turkish hazel (Corylus colurna L.) and the Filbert (Corylus maxima Mill.) in order to characterise their phenolic-profile. Although these plants have been used in traditional medicine for long time, literature data regarding their phytochemical composition is limited to the flavonoid and hydroxycinnamic-acid derivatives of C. avellana leaves. No previous studies have been published reporting the presence of diarylheptanoid compounds in any of the Corylus species. Soxhlet extraction with solvents of increasing polarity was performed on the bark and leaves of the mentioned three Corylus species. The phenolic-profile of the methanolic and ethyl acetate extracts was investigated by HPLC-DAD-ESI-TOF-MS and HPLC-DAD-ESI-MS/MS methods. Altogether 37 different phenolic compounds were detected in the extracts: twenty diarylheptanoids (1-20), nine flavonols (21-29) and eight other phenolics: caffeic and quinic acid derivatives and flavanones (30-37). The main compounds of the extracts were identified as myricetin- quercetin- and kaempferol-3-O-rhanmosides.

  15. Co-occurring disorders: policy and practice in Germany.

    PubMed

    Hintz, Thomas; Mann, Karl

    2006-01-01

    The occurrence of substance use disorders (SUD) with other mental disorders-what is often referred to as co-occurring disorders (COD)-is a common phenomenon, but for a long time, little attention has been paid to this problem in Germany. During the last 25 years, however, COD awareness has increased due to a shift toward community-based services. Scientific research has also demonstrated the significance and clinical relevance of COD. High prevalence rates and evidence of poor clinical outcomes were found in German studies. Many practitioners as well as policymakers acknowledge that changes in systems of care are necessary to meet the requirements of COD patients. The traditional German system is currently divided into addiction services and mental health services (predominantly in inpatient settings), often resulting in ineffective sequential treatment for COD patients. Research demonstrates that integrative treatment models are more appropriate, and the division of services should be reorganized to help COD patients appropriately. Efforts have already been made to restructure healthcare systems toward a more flexible approach with improved networking between in- and outpatient services. A further issue is the general attitude toward SUD patients. Many practitioners continue to hold negative opinions (eg, "SUD patients are only weak-minded") or feel insecure when confronted with SUD. This results in SUD problems being frequently ignored or depreciated. Educational programs have been intensive over recent years to address this problem (eg, Fachkunde Sucht, an advanced training program on SUD). In general, treatment conditions for COD patients are improving, but further efforts are necessary. Guidelines and treatment strategies for COD patients have been recently published in Germany.

  16. Co-occurring psychiatric disorders in women with addictions.

    PubMed

    Chander, Geetanjali; McCaul, Mary E

    2003-09-01

    There is clinically important comorbidity between psychiatric and substance use disorders, particularly in women. Women with affective and anxiety disorders are more likely to present with alcohol or drug abuse/dependence. In turn, substance-abusing women are more likely to experience clinically significant depression and anxiety. Emerging evidence is pointing to an etiological role for anxiety disorders in the development of substance abuse/dependence; however, etiologic evidence is not as clear-cut for major depressive disorder. PTSD appears to be a particularly important factor for alcohol and drug dependence in women who have experienced childhood or adult sexual and or physical abuse. Although pharmacotherapy for affective or anxiety disorders is useful for ameliorating psychiatric symptoms, research is mixed on the effectiveness for improving alcohol- and drug-related outcomes. There is some limited evidence that women-specific services can improve treatment retention, substance use outcomes, and possibly psychosocial functioning compared with traditional mixed-gender programs. However, it is clear that women with co-occurring psychiatric and substance use problems are challenging to engage and retain in care. Physicians providing women's reproductive health services can serve a vital role in the identification and referral of substance-abusing women. Particular attention should be focused on screening and assessment of alcohol and drug use and problem severity among women who have identified psychiatric disorders or who are receiving antidepressant or anxiolytic medications. Recognition and referral for both psychiatric and substance use disorders are critical for long-term health and psychosocial improvement.

  17. Naturally Occurring Variants of the Dysglycemic Peptide Pancreastatin

    PubMed Central

    Allu, Prasanna K. R.; Chirasani, Venkat R.; Ghosh, Dhiman; Mani, Anitha; Bera, Amal K.; Maji, Samir K.; Senapati, Sanjib; Mullasari, Ajit S.; Mahapatra, Nitish R.

    2014-01-01

    Pancreastatin (PST), a chromogranin A-derived peptide, is a potent physiological inhibitor of glucose-induced insulin secretion. PST also triggers glycogenolysis in liver and reduces glucose uptake in adipocytes and hepatocytes. Here, we probed for genetic variations in PST sequence and identified two variants within its functionally important carboxyl terminus domain: E287K and G297S. To understand functional implications of these amino acid substitutions, we tested the effects of wild-type (PST-WT), PST-287K, and PST-297S peptides on various cellular processes/events. The rank order of efficacy to inhibit insulin-stimulated glucose uptake was: PST-297S > PST-287K > PST-WT. The PST peptides also displayed the same order of efficacy for enhancing intracellular nitric oxide and Ca2+ levels in various cell types. In addition, PST peptides activated gluconeogenic genes in the following order: PST-297S ≈ PST-287K > PST-WT. Consistent with these in vitro results, the common PST variant allele Ser-297 was associated with significantly higher (by ∼17 mg/dl, as compared with the wild-type Gly-297 allele) plasma glucose level in our study population (n = 410). Molecular modeling and molecular dynamics simulations predicted the following rank order of α-helical content: PST-297S > PST-287K > PST-WT. Corroboratively, circular dichroism analysis of PST peptides revealed significant differences in global structures (e.g. the order of propensity to form α-helix was: PST-297S ≈ PST-287K > PST-WT). This study provides a molecular basis for enhanced potencies/efficacies of human PST variants (likely to occur in ∼300 million people worldwide) and has quantitative implications for inter-individual variations in glucose/insulin homeostasis. PMID:24338022

  18. Death in pediatric Cushing syndrome is uncommon but still occurs

    PubMed Central

    Gkourogianni, Alexandra; Lodish, Maya B.; Zilbermint, Mihail; Lyssikatos, Charalampos; Belyavskaya, Elena; Keil, Margaret F.; Stratakis, Constantine A.

    2014-01-01

    Cushing syndrome (CS) in children is rare. Delayed diagnosis and treatment of CS may be associated with increased morbidity and, unfortunately, mortality. We performed a retrospective review of all patients with CS under the age of 18 referred to the NIH from 1998 to 2013 in order to describe deceased patients among cases of pediatric CS referred to the National Institutes of Health (NIH). The deaths of 4 children (3 females and 1 male), aged 7.5–15.5 years (mean age 11.2 years) with length of disease 2–4 years were recorded among 160 (2.5%) children seen at, or referred to the NIH over the last 15 years. All died at different institutions, prior to coming to the NIH (two of them) or after leaving NIH (two of them). Presenting symptoms included increasing weight and decreasing height gain, facial plethora, dorsocervical fat pad (webbed neck), striae, headache, vision disturbances and depression and other mood or behavior changes; there were no differences between how these patients presented and the others in our cohort. The causes of CS in the deceased patients were also not different, in fact, they spanned the entire spectrum of CS: pituitary disease (on of them), ectopic corticotropin production (one of them), and primary adrenal hyperplasia (1). In one patient, the cause of CS could not be verified. Three died of sepsis and one due to residual disease and complications of the primary tumor. Conclusions Despite advances in early diagnosis and treatment of pediatric CS, a 2.5% mortality rate was identified in a large cohort of patients with this condition referred to an experienced, tertiary care referral center (although these deaths occurred elsewhere). Pediatricians need to recognize the possibility of death, primarily due to sepsis, in a patient with pediatric CS and act accordingly. PMID:25241829

  19. Role of naturally occurring gas hydrates in sediment transport

    SciTech Connect

    McIver, R.D.

    1982-06-01

    Naturally occurring gas hydrates have the potential to store enormous volumes of both gas and water in semi-solid form in ocean-bottom sediments and then to release that gas and water when the hydrate's equilibrium condition are disturbed. Therefore, hydrates provide a potential mechanism for transporting large volumes of sediments. Under the combined low bottom-water temperatures and moderate hydrostatic pressures that exist over most of the continental slopes and all of the continental rises and abyssal plains, hydrocarbon gases at or near saturation in the interstitial waters of the near-bottom sediments will form hydrates. The gas can either be autochthonous, microbially produced gas, or allochthonous, catagenic gas from deeper sediments. Equilibrium conditions that stabilize hydrated sediments may be disturbed, for example, by continued sedimentation or by lowering of sea level. In either case, some of the solid gas-water matrix decomposes. Released gas and water volume exceeds the volume occupied by the hydrate, so the internal pressure rises - drastically if large volumes of hydrate are decomposed. Part of the once rigid sediment is converted to a gas- and water-rich, relatively low density mud. When the internal pressure, due to the presence of the compressed gas or to buoyancy, is sufficiently high, the overlying sediment may be lifted and/or breached, and the less dense, gas-cut mud may break through. Such hydrate-related phenomena can cause mud diapirs, mud volcanos, mud slides, or turbidite flows, depending on sediment configuration and bottom topography. 4 figures.

  20. Accurate assessment and identification of naturally occurring cellular cobalamins

    PubMed Central

    Hannibal, Luciana; Axhemi, Armend; Glushchenko, Alla V.; Moreira, Edward S.; Brasch, Nicola E.; Jacobsen, Donald W.

    2009-01-01

    Background Accurate assessment of cobalamin profiles in human serum, cells, and tissues may have clinical diagnostic value. However, non-alkyl forms of cobalamin undergo β-axial ligand exchange reactions during extraction, which leads to inaccurate profiles having little or no diagnostic value. Methods Experiments were designed to: 1) assess β-axial ligand exchange chemistry during the extraction and isolation of cobalamins from cultured bovine aortic endothelial cells, human foreskin fibroblasts, and human hepatoma HepG2 cells, and 2) to establish extraction conditions that would provide a more accurate assessment of endogenous forms containing both exchangeable and non-exchangeable β-axial ligands. Results The cobalamin profile of cells grown in the presence of [57Co]-cyanocobalamin as a source of vitamin B12 shows that the following derivatives are present: [57Co]-aquacobalamin, [57Co]-glutathionylcobalamin, [57Co]-sulfitocobalamin, [57Co]-cyanocobalamin, [57Co]-adenosylcobalamin, [57Co]-methylcobalamin, as well as other yet unidentified corrinoids. When the extraction is performed in the presence of excess cold aquacobalamin acting as a scavenger cobalamin (i.e., “cold trapping”), the recovery of both [57Co]-glutathionylcobalamin and [57Co]-sulfitocobalamin decreases to low but consistent levels. In contrast, the [57Co]-nitrocobalamin observed in extracts prepared without excess aquacobalamin is undetectable in extracts prepared with cold trapping. Conclusions This demonstrates that β-ligand exchange occurs with non-covalently bound β-ligands. The exception to this observation is cyanocobalamin with a non-covalent but non-exchangeable− CNT group. It is now possible to obtain accurate profiles of cellular cobalamins. PMID:18973458

  1. Antituberculosis Activity of a Naturally Occurring Flavonoid, Isorhamnetin.

    PubMed

    Jnawali, Hum Nath; Jeon, Dasom; Jeong, Min-Cheol; Lee, Eunjung; Jin, Bongwhan; Ryoo, Sungweon; Yoo, Jungheon; Jung, In Duk; Lee, Seung Jun; Park, Yeong-Min; Kim, Yangmee

    2016-04-22

    Isorhamnetin (1) is a naturally occurring flavonoid having anticancer and anti-inflammatory properties. The present study demonstrated that 1 had antimycobacterial effects on Mycobacterium tuberculosis H37Rv, multi-drug- and extensively drug-resistant clinical isolates with minimum inhibitory concentrations of 158 and 316 μM, respectively. Mycobacteria mainly affect the lungs, causing an intense local inflammatory response that is critical to the pathogenesis of tuberculosis. We investigated the effects of 1 on interferon (IFN)-γ-stimulated human lung fibroblast MRC-5 cells. Isorhamnetin suppressed the release of tumor necrosis factor (TNF)-α and interleukin (IL)-12. A nontoxic dose of 1 reduced mRNA expression of TNF-α, IL-1β, IL-6, IL-12, and matrix metalloproteinase-1 in IFN-γ-stimulated cells. Isorhamnetin inhibited IFN-γ-mediated stimulation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase and showed high-affinity binding to these kinases (binding constants: 4.46 × 10(6) M(-1) and 7.6 × 10(6) M(-1), respectively). The 4'-hydroxy group and the 3'-methoxy group of the B-ring and the 5-hydroxy group of the A-ring of 1 play key roles in these binding interactions. A mouse in vivo study of lipopolysaccharide-induced lung inflammation revealed that a nontoxic dose of 1 reduced the levels of IL-1β, IL-6, IL-12, and INF-γ in lung tissue. These data provide the first evidence that 1 could be developed as a potent antituberculosis drug. PMID:26974691

  2. Loss of BAP1 Expression Occurs Frequently in Intrahepatic Cholangiocarcinoma

    PubMed Central

    Andrici, Juliana; Goeppert, Benjamin; Sioson, Loretta; Clarkson, Adele; Renner, Marcus; Stenzinger, Albrecht; Tayao, Michael; Watson, Nicole; Farzin, Mahtab; Toon, Christopher W.; Smith, Ross C.; Mittal, Anubhav; Samra, Jaswinder S.; Hugh, Thomas J.; Chou, Angela; Lawlor, Rita T.; Weichert, Wilko; Schirmacher, Peter; Sperandio, Nicola; Ruzzenente, Andrea; Scarpa, Aldo; Gill, Anthony J.

    2016-01-01

    Abstract BRCA1-associated protein 1 (BAP1) is a deubiquitinating enzyme that functions as a tumor suppressor gene. Double hit BAP1 inactivation has been reported in a range of tumor types, including intrahepatic cholangiocarcinoma (ICC), sometimes in association with germline mutation. We performed immunohistochemistry for BAP1 on a well-characterized cohort of 211 ICC patients undergoing surgical resection with curative intent at 3 institutions based in 3 different countries. The median age at diagnosis was 65 years (range, 36.5–86) and 108 (51%) were men. Negative staining for BAP1 (defined as completely absent nuclear staining in the presence of positive internal controls in nonneoplastic cells) occurred in 55 ICCs (26%). BAP1 loss predicted a strong trend toward improved median survival of 40.80 months (95% CI, 28.14–53.46) versus 24.87 months (95% CI, 18.73–31.01), P = 0.059). In a multivariate model including age, sex, BAP1 status, tumor stage, tumor grade, lymphovascular invasion, and tumor size, female sex was associated with improved survival (hazard ratio [HR] 0.54; 95% CI, 0.34–0.85), while advanced tumor stage and lymphovascular invasion (HR 1.89; 95% CI, 1.09–3.28) correlated with decreased survival. In a multivariate analysis, high grade tumors were associated with BAP1 loss (odds ratio [OR] 3.32; 95% CI, 1.29–8.55), while lymphatic invasion was inversely associated with BAP1 loss (OR 0.36; 95% CI, 0.13–0.99). In conclusion, we observed a trend toward improved prognosis in ICC associated with absent expression of BAP1 and an association of BAP1 loss with higher histological grade and absent lymphatic invasion. Female sex was associated with improved survival while advanced tumor stage and lymphatic invasion were associated with decreased survival. PMID:26765459

  3. [Occurence of diarylheptanoids in Corylus species native to Hungary].

    PubMed

    Riethmüller, Eszter; Tóth, Gergő; Alberti, Agnes; Végh, Krisztina; Béni, Szabolcs; Balogh, György Tibor; Kéry, Agnes

    2015-01-01

    Since the last decade naturally occurring diarylheptanoids have been in the focus of scientific interest due to their various. beneficial biological effects. Besides the outstanding importance of the curcuminoids isolated from members of the Curcuma genus (Zingiberaceae), several different diarylheptanoids identified in Alnus species (Betulaceae) have been proved to possess notable pharmacological effects. Chemoprotective, neuroprotective, hepatoprotective, antiviral, antibacterial, antiinflammatory and antioxidant activities suggest their potential role in clinical practice. The aim of our study was the phytochemical investigation of the Corylus (Betulaceae) species native to Hungary: the Common hazel (Corylus avellana L.), the Turkish hazel (Corylus colurna L.) and the Filbert (Corylus maxima Mill.) in order to characterise their phenolic-profile. Although these plants have been used in traditional medicine for long time, literature data regarding their phytochemical composition is limited to the flavonoid and hydroxycinnamic-acid derivatives of C. avellana leaves. No previous studies have been published reporting the presence of diarylheptanoid compounds in any of the Corylus species. Soxhlet extraction with solvents of increasing polarity was performed on the bark and leaves of the mentioned three Corylus species. The phenolic-profile of the methanolic and ethyl acetate extracts was investigated by HPLC-DAD-ESI-TOF-MS and HPLC-DAD-ESI-MS/MS methods. Altogether 37 different phenolic compounds were detected in the extracts: twenty diarylheptanoids (1-20), nine flavonols (21-29) and eight other phenolics: caffeic and quinic acid derivatives and flavanones (30-37). The main compounds of the extracts were identified as myricetin- quercetin- and kaempferol-3-O-rhanmosides. PMID:26137784

  4. Androgen receptor gene mutation, rearrangement, polymorphism.

    PubMed

    Eisermann, Kurtis; Wang, Dan; Jing, Yifeng; Pascal, Laura E; Wang, Zhou

    2013-09-01

    Genetic aberrations of the androgen receptor (AR) caused by mutations, rearrangements, and polymorphisms result in a mutant receptor that has varied functions compared to wild type AR. To date, over 1,000 mutations have been reported in the AR with most of these being associated with androgen insensitivity syndrome (AIS). While mutations of AR associated with prostate cancer occur less often in early stage localized disease, mutations in castration-resistant prostate cancer (CRPC) patients treated with anti-androgens occur more frequently with 10-30% of these patients having some form of mutation in the AR. Resistance to anti-androgen therapy usually results from gain-of-function mutations in the LBD such as is seen with bicalutamide and more recently with enzalutamide (MDV3100). Thus, it is crucial to investigate these new AR mutations arising from drug resistance to anti-androgens and other small molecule pharmacological agents.

  5. Palmitoylation of the GluR6 kainate receptor.

    PubMed Central

    Pickering, D S; Taverna, F A; Salter, M W; Hampson, D R

    1995-01-01

    The G-protein-coupled metabotropic glutamate receptor mGluR1 alpha and the ionotropic glutamate receptor GluR6 were examined for posttranslational palmitoylation. Recombinant receptors were expressed in baculovirus-infected insect cells or in human embryonic kidney cells and were metabolically labeled with [3H]palmitic acid. The metabotropic mGluR1 alpha receptor was not labeled whereas the GluR6 kainate receptor was labeled after incubation with [3H]palmitate. The [3H]palmitate labeling of GluR6 was eliminated by treatment with hydroxylamine, indicating that the labeling was due to palmitoylation at a cysteine residue via a thioester bond. Site-directed mutagenesis was used to demonstrate that palmitoylation of GluR6 occurs at two cysteine residues, C827 and C840, located in the carboxyl-terminal domain of the molecule. A comparison of the electrophysiological properties of the wild-type and unpalmitoylated mutant receptor (C827A, C840A) showed that the kainate-gated currents produced by the unpalmitoylated mutant receptor were indistinguishable from those of the wild-type GluR6. The unpalmitoylated mutant was a better substrate for protein kinase C than the wild-type GluR6 receptor. These data indicate that palmitoylation may not modulate kainate channel function directly but instead affect function indirectly by regulating the phosphorylation state of the receptor. Images Fig. 1 Fig. 2 Fig. 3 Fig. 5 PMID:8618850

  6. Conserved site for neurosteroid modulation of GABA A receptors.

    PubMed

    Hosie, Alastair M; Clarke, Laura; da Silva, Helena; Smart, Trevor G

    2009-01-01

    This study addresses whether the potentiation site for neurosteroids on GABA(A) receptors is conserved amongst different GABA(A) receptor isoforms. The neurosteroid potentiation site was previously identified in the alpha1beta2gamma2S receptor by mutation of Q241 to methionine or leucine, which reduced the potentiation of GABA currents by the naturally occurring neurosteroids, allopregnanolone or tetrahydrodeoxycorticosterone (THDOC). By using heterologous expression of GABA(A) receptors in HEK cells, in combination with whole-cell patch clamp recording methods, a relatively consistent potentiation by allopregnanolone of GABA-activated currents was evident for receptors composed of one alpha subunit isoform (alpha2-5) assembled with beta3 and gamma2S subunits. Using mutant alphabetagamma receptors, the neurosteroid potentiation was universally dependent on the conserved glutamine residue in M1 of the respective alpha subunit. Studying wild-type and mutant receptors composed of alpha4beta3delta subunits revealed that the delta subunit is unlikely to contribute to the neurosteroid potentiation binding site and probably affects the efficacy of potentiation. Thus, in keeping with the ability of neurosteroids to potentiate GABA currents via a broad variety of GABA(A) receptor isoforms in neurons, the potentiation site is structurally highly conserved on this important neurotransmitter receptor family.

  7. Oligomerization of TAS2R bitter taste receptors.

    PubMed

    Kuhn, Christina; Bufe, Bernd; Batram, Claudia; Meyerhof, Wolfgang

    2010-06-01

    A family of 25 G protein-coupled receptors, TAS2Rs, mediates bitter taste in humans. Many of the members of this family are coexpressed in a subpopulation of taste receptor cells on the tongue, thereby allowing the possibility of receptor-receptor interactions with potential influences on their function. In this study, we used several experimental approaches to investigate whether TAS2Rs can form oligomers and if this has an effect on receptor function. Coimmunoprecipitations clearly demonstrated that TAS2Rs can physically interact in HEK293T cells. Further bioluminescence resonance energy transfer analysis of all 325 possible binary combinations of TAS2Rs established that the vast majority of TAS2R pairs form oligomers, both homomers and heteromers. Subsequent screenings of coexpressed bitter receptors with 104 different tastants did not reveal any heteromer-specific agonists. Additional studies also showed no obvious influence of TAS2R hetero-oligomerization on plasma membrane localization or pharmacological properties of the receptors. Thus, our results show that receptor oligomerization occurs between TAS2R bitter taste receptors; however, functional consequences of hetero-oligomerization were not obvious.

  8. The growth hormone receptor: mechanism of activation and clinical implications.

    PubMed

    Brooks, Andrew J; Waters, Michael J

    2010-09-01

    Growth hormone is widely used clinically to promote growth and anabolism and for other purposes. Its actions are mediated via the growth hormone receptor, both directly by tyrosine kinase activation and indirectly by induction of insulin-like growth factor 1 (IGF-1). Insensitivity to growth hormone (Laron syndrome) can result from mutations in the growth hormone receptor and can be treated with IGF-1. This treatment is, however, not fully effective owing to the loss of the direct actions of growth hormone and altered availability of exogenous IGF-1. Excessive activation of the growth hormone receptor by circulating growth hormone results in gigantism and acromegaly, whereas cell transformation and cancer can occur in response to autocrine activation of the receptor. Advances in understanding the mechanism of receptor activation have led to a model in which the growth hormone receptor exists as a constitutive dimer. Binding of the hormone realigns the subunits by rotation and closer apposition, resulting in juxtaposition of the catalytic domains of the associated tyrosine-protein kinase JAK2 below the cell membrane. This change results in activation of JAK2 by transphosphorylation, then phosphorylation of receptor tyrosines in the cytoplasmic domain, which enables binding of adaptor proteins, as well as direct phosphorylation of target proteins. This model is discussed in the light of salient information from closely related class 1 cytokine receptors, such as the erythropoietin, prolactin and thrombopoietin receptors. PMID:20664532

  9. Pharmacology and function of melatonin receptors

    SciTech Connect

    Dubocovich, M.L.

    1988-09-01

    The hormone melatonin is secreted primarily from the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone, through an action in the brain, appears to be involved in the regulation of various neural and endocrine processes that are cued by the daily change in photoperiod. This article reviews the pharmacological characteristics and function of melatonin receptors in the central nervous system, and the role of melatonin in mediating physiological functions in mammals. Melatonin and melatonin agonists, at picomolar concentrations, inhibit the release of dopamine from retina through activation of a site that is pharmacologically different from a serotonin receptor. These inhibitory effects are antagonized by the novel melatonin receptor antagonist luzindole (N-0774), which suggests that melatonin activates a presynaptic melatonin receptor. In chicken and rabbit retina, the pharmacological characteristics of the presynaptic melatonin receptor and the site labeled by 2-(125I)iodomelatonin are identical. It is proposed that 2-(125I)iodomelatonin binding sites (e.g., chicken brain) that possess the pharmacological characteristics of the retinal melatonin receptor site (order of affinities: 2-iodomelatonin greater than 6-chloromelatonin greater than or equal to melatonin greater than or equal to 6,7-di-chloro-2-methylmelatonin greater than 6-hydroxymelatonin greater than or equal to 6-methoxymelatonin greater than N-acetyltryptamine greater than or equal to luzindole greater than N-acetyl-5-hydroxytryptamine greater than 5-methoxytryptamine much greater than 5-hydroxytryptamine) be classified as ML-1 (melatonin 1). The 2-(125I)iodomelatonin binding site of hamster brain membranes possesses different binding and pharmacological characteristics from the retinal melatonin receptor site and should be classified as ML-2. 64 references.

  10. Changes in the body posture of women occurring with age

    PubMed Central

    2013-01-01

    Background A current topic in the field of geriatrics still needing a great deal of study is the changes in body posture occurring with age. Symptoms of these changes can be observed starting between the ages of 40–50 years with a slow progression that increases after 60 years of age. The aims of this study were to evaluate parameters characterizing the posture of women over the age of 60 years compared with a control group and to determine the dynamics of body posture changes in the following decades. Methods The study included 260 randomly selected women. The study group consisted of 130 women between the ages of 60–90 years (Older Women). The control group (Younger Women) consisted of 130 women between the ages of 20–25 years (posture stabilization period). The photogrammetric method was used to evaluate body posture using the phenomenon of the projection chamber. The study was conducted according to generally accepted principles. Results In the analysis of parameters characterizing individual slope curves, results were varied among different age groups. The lumbar spine slope did not show significant differences between different age groups (p = 0.6952), while statistically significant differences (p = 0.0000) were found in the thoracic-lumbar spine slope (p = 0.0033) and upper thoracic spine slope. Body angle was shown to increase with age (p = 0.0000). Thoracic kyphosis depth significantly deepened with age (p = 0.0002), however, the thoracic kyphosis angle decreased with age (p = 0.0000). An increase in asymmetries was noticed, provided by a significantly higher angle of the shoulder line (p = 0.0199) and the difference in height of the lower shoulder blade angle (p = 0.0007) measurements in the group of older women. Conclusions Changes in the parameters describing body posture throughout consecutive decades were observed. Therapy for women over the age of 60 years should involve strengthening of the erector spinae

  11. Committed effective dose from naturally occuring radionuclides in shellfish

    NASA Astrophysics Data System (ADS)

    Khandaker, Mayeen Uddin; Wahib, Norfadira Binti; Amin, Yusoff Mohd.; Bradley, D. A.

    2013-07-01

    Recognizing their importance in the average Malaysian daily diet, the radioactivity concentrations in mollusc- and crustacean-based food have been determined for key naturally occuring radionuclides. Fresh samples collected from various maritime locations around peninsular Malaysia have been processed using standard procedures; the radionuclide concentrations being determined using an HPGe γ-ray spectrometer. For molluscs, assuming secular equilibrium, the range of activities of 238U (226Ra), 232Th (228Ra) and 40K were found to be 3.28±0.35 to 5.34±0.52, 1.20±0.21 to 2.44±0.21 and 118±6 to 281±14 Bq kg-1 dry weight, respectively. The respective values for crustaceans were 3.02±0.57 to 4.70±0.52, 1.38±0.21 to 2.40±0.35 and 216±11 to 316±15 Bq kg-1. The estimated average daily intake of radioactivity from consumption of molluscs are 0.37 Bq kg-1 for 238U (226Ra), 0.16 Bq kg-1 for 232Th (228Ra) and 18 Bq kg-1 for 40K; the respective daily intake values from crustaceans are 0.36 Bq kg-1, 0.16 Bq kg-1 and 23 Bq kg-1. Associated annual committed effective doses from molluscs are estimated to be in the range 21.3 to 34.7 μSv for 226Ra, 19.3 to 39.1 μSv for 228Ra and 17.0 to 40.4 μSv for 40K. For crustaceans, the respective dose ranges are 19.6 to 30.5 μSv, 22.0 to 38.4 μSv and 31.1 to 45.5 μSv, being some several times world average values.

  12. Identification of Telomerase-activating Blends From Naturally Occurring Compounds.

    PubMed

    Ait-Ghezala, Ghania; Hassan, Samira; Tweed, Miles; Paris, Daniel; Crynen, Gogce; Zakirova, Zuchra; Crynen, Stefan; Crawford, Fiona

    2016-06-01

    telomerase activity, and combinations of the top-ranking compounds were able to increase telomerase activity significantly, from 51% to 290%, relative to controls. Conclusions • The results have confirmed that many naturally occurring compounds hold the potential to activate telomerase and that certain of those compounds have demonstrated synergistic effects to produce more potent blends. Given the relationship between telomere shortening, aging, and the decline of tissue function, it is reasonable to hypothesize that such telomerase-activating blends may have health-promoting benefits, particularly in relation to aging-associated conditions. Further investigation of such blends in human studies that are designed to evaluate safety and the effects on telomere length are thus warranted.

  13. Identification of Telomerase-activating Blends From Naturally Occurring Compounds.

    PubMed

    Ait-Ghezala, Ghania; Hassan, Samira; Tweed, Miles; Paris, Daniel; Crynen, Gogce; Zakirova, Zuchra; Crynen, Stefan; Crawford, Fiona

    2016-06-01

    telomerase activity, and combinations of the top-ranking compounds were able to increase telomerase activity significantly, from 51% to 290%, relative to controls. Conclusions • The results have confirmed that many naturally occurring compounds hold the potential to activate telomerase and that certain of those compounds have demonstrated synergistic effects to produce more potent blends. Given the relationship between telomere shortening, aging, and the decline of tissue function, it is reasonable to hypothesize that such telomerase-activating blends may have health-promoting benefits, particularly in relation to aging-associated conditions. Further investigation of such blends in human studies that are designed to evaluate safety and the effects on telomere length are thus warranted. PMID:27433836

  14. Nortestosterone is not a naturally occurring compound in male cattle.

    PubMed

    McEvoy, J D; McCaughey, W J; Cooper, J; Kennedy, D G; McCartan, B M

    1999-01-01

    Nortestosterone (beta-NT) is a hormonal growth promoter banned from livestock production in the EU. Following injection, the major metabolite in cattle is the 17 alpha-epimer (alpha-NT). However, this also occurs naturally in pregnant cattle. It is not known whether alpha-NT is also endogenous to intact or castrated male cattle. Three surveys were undertaken to assess whether alpha-NT is naturally produced in this subset of the population. Bile samples from a total of 1,281 cattle (73 bulls and 1,208 steers) from 366 herds were collected at slaughter and initially screened by using a semi-automated EIA with multi-analyte immunoaffinity chromatography (IAC) clean-up. Bile samples from a further 38 male cattle (10 bulls and 28 steers) were analysed by high-resolution gas chromatography-mass spectrometry (GC-MS) with IAC pretreatment. Only samples containing more than 2 ng/ml alpha-NT were subjected to GC-MS. With 2 ng/ml alpha-NT as a threshold for confirmatory testing, the false positive rate of the screening EIA was 1.8%. Bulls (n = 16) and steers (n = 179) from government farms (n = 2) and which were not treated with exogenous beta-NT, did not have measurable concentrations of alpha-NT in their bile. Bulls (n = 35) and steers (n = 606) taken from herds (n = 204) which had no previous history of illegal growth promoter abuse also did not have alpha-NT in their bile. Of 32 bulls and 451 steers of unknown treatment history sampled from herds (n = 160), 56 steers from 19 herds contained GC-MS confirmed concentrations of alpha-NT higher than the limit of quantification of the assay LOQ (0.7 ng/ml). Of these animals, two had beta-NT-containing injection sites and five had residues of the beta-agonists clenbuterol and mabuterol. Examination of the animal movement and ownership histories of the 56 confirmed positive animals strongly suggested that exogenous beta-NT had been administered at the presenting farm. It is concluded that alpha-NT is not endogenous to this subset

  15. Manufactured Home Testing in Simulated and Naturally Occurring High Winds

    SciTech Connect

    W. D. Richins; T. K. Larson

    2006-08-01

    A typical double-wide manufactured home was tested in simulated and naturally occurring high winds to understand structural behavior and improve performance during severe windstorms. Seven (7) lateral load tests were conducted on a double-wide manufactured home at a remote field test site in Wyoming. An extensive instrumentation package monitored the overall behavior of the home and collected data vital to validating computational software for the manufactured housing industry. The tests were designed to approach the design load of the home without causing structural damage, thus allowing the behavior of the home to be accessed when the home was later exposed to high winds (to 80-mph). The data generally show near-linear initial system response with significant non-linear behavior as the applied loads increase. Load transfer across the marriage line is primarily compression. Racking, while present, is very small. Interface slip and shear displacement along the marriage line are nearly insignificant. Horizontal global displacements reached 0.6 inch. These tests were designed primarily to collect data necessary to calibrate a desktop analysis and design software tool, MHTool, under development at the Idaho National Laboratory specifically for manufactured housing. Currently available analysis tools are, for the most part, based on methods developed for “stick built” structures and are inappropriate for manufactured homes. The special materials utilized in manufactured homes, such as rigid adhesives used in the connection of the sheathing materials to the studs, significantly alter the behavior of manufactured homes under lateral loads. Previous full scale tests of laterally loaded manufactured homes confirm the contention that conventional analysis methods are not applicable. System behavior dominates the structural action of manufactured homes and its prediction requires a three dimensional analysis of the complete unit, including tiedowns. This project was

  16. Do "whiplash injuries" occur in low-speed rear impacts?

    PubMed

    Castro, W H; Schilgen, M; Meyer, S; Weber, M; Peuker, C; Wörtler, K

    1997-01-01

    A study was conducted to find out whether in a rear-impact motor vehicle accident, velocity changes in the impact vehicle of between 10 and 15 km/h can cause so-called "whiplash injuries". An assessment of the actual injury mechanism of such whiplash injuries and comparison of vehicle rear-end collisions with amusement park bumper car collisions was also carried out. The study was based on experimental biochemical, kinematic, and clinical analysis with volunteers. In Europe between DM 10 and 20 billion each year is paid out by insurance companies alone for whiplash injuries, although various studies show that the biodynamic stresses arising in the case of slight to moderate vehicle damage may not be high enough to cause such injuries. Most of these experimental studies with cadavers, dummies, and some with volunteers were performed with velocity changes below 10 km/h. About 65% of the insurance claims, however, take place in cases with velocity changes of up to 15 km/h. Fourteen made volunteers (aged 28-47 years; average 33.2 years) and five female volunteers (aged 26-37 years; average 32.8 years) participated in 17 vehicle rear-end collisions and 3 bumper car collisions. All cars were fitted with normal European bumper systems. Before, 1 day after and 4-5 weeks after each vehicle crash test and in two of the three bumper car crash tests a clinical examination, a computerized motion analysis, and an MRI examination with Gd-DTPA of the cervical spine of the test persons were performed. During each crash test, in which the test persons were completely screened-off visually and acoustically, the muscle tension of various neck muscles was recorded by surface electromyography (EMG). The kinematic responses of the test persons and the forces occurring were measured by accelerometers. The kinematic analyses were performed with movement markers and a screening frequency of 700 Hz. To record the acceleration effects of the target vehicle and the bullet vehicle, vehicle

  17. Signaling by Sensory Receptors

    PubMed Central

    Julius, David; Nathans, Jeremy

    2012-01-01

    Sensory systems detect small molecules, mechanical perturbations, or radiation via the activation of receptor proteins and downstream signaling cascades in specialized sensory cells. In vertebrates, the two principal categories of sensory receptors are ion channels, which mediate mechanosensation, thermosensation, and acid and salt taste; and G-protein-coupled receptors (GPCRs), which mediate vision, olfaction, and sweet, bitter, and umami tastes. GPCR-based signaling in rods and cones illustrates the fundamental principles of rapid activation and inactivation, signal amplification, and gain control. Channel-based sensory systems illustrate the integration of diverse modulatory signals at the receptor, as seen in the thermosensory/pain system, and the rapid response kinetics that are possible with direct mechanical gating of a channel. Comparisons of sensory receptor gene sequences reveal numerous examples in which gene duplication and sequence divergence have created novel sensory specificities. This is the evolutionary basis for the observed diversity in temperature- and ligand-dependent gating among thermosensory channels, spectral tuning among visual pigments, and odorant binding among olfactory receptors. The coding of complex external stimuli by a limited number of sensory receptor types has led to the evolution of modality-specific and species-specific patterns of retention or loss of sensory information, a filtering operation that selectively emphasizes features in the stimulus that enhance survival in a particular ecological niche. The many specialized anatomic structures, such as the eye and ear, that house primary sensory neurons further enhance the detection of relevant stimuli. PMID:22110046

  18. Biased and G Protein-Independent Signaling of Chemokine Receptors

    PubMed Central

    Steen, Anne; Larsen, Olav; Thiele, Stefanie; Rosenkilde, Mette M.

    2014-01-01

    Biased signaling or functional selectivity occurs when a 7TM-receptor preferentially activates one of several available pathways. It can be divided into three distinct forms: ligand bias, receptor bias, and tissue or cell bias, where it is mediated by different ligands (on the same receptor), different receptors (with the same ligand), or different tissues or cells (for the same ligand–receptor pair). Most often biased signaling is differentiated into G protein-dependent and β-arrestin-dependent signaling. Yet, it may also cover signaling differences within these groups. Moreover, it may not be absolute, i.e., full versus no activation. Here we discuss biased signaling in the chemokine system, including the structural basis for biased signaling in chemokine receptors, as well as in class A 7TM receptors in general. This includes overall helical movements and the contributions of micro-switches based on recently published 7TM crystals and molecular dynamics studies. All three forms of biased signaling are abundant in the chemokine system. This challenges our understanding of “classic” redundancy inevitably ascribed to this system, where multiple chemokines bind to the same receptor and where a single chemokine may bind to several receptors – in both cases with the same functional outcome. The ubiquitous biased signaling confers a hitherto unknown specificity to the chemokine system with a complex interaction pattern that is better described as promiscuous with context-defined roles and different functional outcomes in a ligand-, receptor-, or cell/tissue-defined manner. As the low number of successful drug development plans implies, there are great difficulties in targeting chemokine receptors; in particular with regard to receptor antagonists as anti-inflammatory drugs. Un-defined and putative non-selective targeting of the complete cellular signaling system could be the underlying cause of lack of success. Therefore, biased ligands could be the solution

  19. Naturally occurring muscle pain during exercise: assessment and experimental evidence.

    PubMed

    Cook, D B; O'Connor, P J; Eubanks, S A; Smith, J C; Lee, M

    1997-08-01

    The objectives were: (i) to present a method for assessing muscle pain during exercise, (ii) to provide reliability and validity data in support of the measurement tool, (iii) to test whether leg muscle pain threshold during exercise was related to a commonly used measure of pain threshold pain during test, (iv) to examine the relationship between pain and exertion ratings, (v) to test whether leg muscle pain is related to performance, and (vi) to test whether a large dose of aspirin would delay leg muscle pain threshold and/or reduce pain ratings during exercise. In study 1, seven females and seven males completed three 1-min cycling bouts at three different randomly ordered power outputs. Pain was assessed using a 10-point pain scale. High intraclass correlations (R from 0.88 to 0.98) indicated that pain intensity could be rated reliably using the scale. In study 2, 11 college-aged males (age 21.3 +/- 1.3 yr) performed a ramped (24 W.min-1) maximal cycle ergometry test. A button was depressed when leg muscle pain threshold was reached. Pain threshold occurred near 50% of maximal capacity: 50.3 (+/- 12.9% Wmax), 48.6 (+/- 14.8% VO2max), and 55.8 (+/- 12.9% RPEmax). Pain intensity ratings obtained following pain threshold were positively accelerating function of the relative exercise intensity. Volitional exhaustion was associated with pain ratings of 8.2 (+/- 2.5), a value most closely associated with the verbal anchor "very strong pain." In study 3, participants completed the same maximal exercise test as in study 2 as well as leg cycling at 60 rpm for 8 s at four randomly ordered power outputs (100, 150, 200, and 250 W) on a separate day. Pain and RPE ratings were significantly lower during the 8-s bouts compared to those obtained at the same power outputs during the maximal cycle test. The results suggest that noxious metabolites of muscle contraction play a role in leg muscle pain during exercise. In study 4, moderately active male subjects (N = 19) completed

  20. Naturally occurring asbestos: a recurring public policy challenge.

    PubMed

    Lee, R J; Strohmeier, B R; Bunker, K L; Van Orden, D R

    2008-05-01

    The potential environmental hazards and associated public health issues related to exposure to respirable dusts from the vicinity of natural in-place asbestos deposits (commonly referred to as naturally occurring asbestos, NOA) have gained the regulatory and media spotlight in many areas around the United States, such as Libby, MT, Fairfax County, VA, and El Dorado Hills, CA, among others. NOA deposits may be present in a variety of geologic formations. It has been suggested that airborne asbestos may be released from NOA deposits, and absent appropriate engineering controls, may pose a potential health hazard if these rocks are crushed or exposed to natural weathering and erosion or to human activities that create dust. The issue that needs to be addressed at a policy level is the method of assessing exposures to elongated rock fragments ubiquitous in dust clouds in these same environments and the associated risk. Elongated rock fragments and single crystal minerals present in NOA have been construed by some as having attributes, including the health effects, of asbestos fibers. However, the Occupational Safety and Health Administration (OSHA), Mine Safety and Health Administration (MSHA), and the Consumer Products Safety Commission (CPSC) found that the scientific evidence did not support this assumption. As in many environmental fields of study, the evidence is often disputed. Regulatory policy is not uniform on the subject of rock fragments, even within single agencies. The core of the issue is whether the risk parameters associated with exposures to commercial asbestos can or should be applied to rock fragments meeting an arbitrary set of particle dimensions used for counting asbestos fibers. Inappropriate inclusion of particles or fragments results in dilution of risk and needless expenditure of resources. On the other hand, inappropriate exclusion of particles or fragments may result in increased and unnecessary risk. Some of the fastest growing counties in

  1. Naturally occurring asbestos: a recurring public policy challenge.

    PubMed

    Lee, R J; Strohmeier, B R; Bunker, K L; Van Orden, D R

    2008-05-01

    The potential environmental hazards and associated public health issues related to exposure to respirable dusts from the vicinity of natural in-place asbestos deposits (commonly referred to as naturally occurring asbestos, NOA) have gained the regulatory and media spotlight in many areas around the United States, such as Libby, MT, Fairfax County, VA, and El Dorado Hills, CA, among others. NOA deposits may be present in a variety of geologic formations. It has been suggested that airborne asbestos may be released from NOA deposits, and absent appropriate engineering controls, may pose a potential health hazard if these rocks are crushed or exposed to natural weathering and erosion or to human activities that create dust. The issue that needs to be addressed at a policy level is the method of assessing exposures to elongated rock fragments ubiquitous in dust clouds in these same environments and the associated risk. Elongated rock fragments and single crystal minerals present in NOA have been construed by some as having attributes, including the health effects, of asbestos fibers. However, the Occupational Safety and Health Administration (OSHA), Mine Safety and Health Administration (MSHA), and the Consumer Products Safety Commission (CPSC) found that the scientific evidence did not support this assumption. As in many environmental fields of study, the evidence is often disputed. Regulatory policy is not uniform on the subject of rock fragments, even within single agencies. The core of the issue is whether the risk parameters associated with exposures to commercial asbestos can or should be applied to rock fragments meeting an arbitrary set of particle dimensions used for counting asbestos fibers. Inappropriate inclusion of particles or fragments results in dilution of risk and needless expenditure of resources. On the other hand, inappropriate exclusion of particles or fragments may result in increased and unnecessary risk. Some of the fastest growing counties in

  2. Androgen receptors in prostate cancer.

    PubMed

    Culig, Z; Klocker, H; Bartsch, G; Hobisch, A

    2002-09-01

    The androgen receptor (AR), a transcription factor that mediates the action of androgens in target tissues, is expressed in nearly all prostate cancers. Carcinoma of the prostate is the most frequently diagnosed neoplasm in men in industrialized countries. Palliative treatment for non-organ-confined prostate cancer aims to down-regulate the concentration of circulating androgen or to block the transcription activation function of the AR. AR function during endocrine therapy was studied in tumor cells LNCaP subjected to long-term steroid depletion; newly generated sublines could be stimulated by lower concentrations of androgen than parental cells and showed up-regulation of AR expression and activity as well as resistance to apoptosis. Androgenic hormones regulate the expression of key cell cycle regulators, cyclin-dependent kinase 2 and 4, and that of the cell cycle inhibitor p27. Inhibition of AR expression could be achieved by potential chemopreventive agents flufenamic acid, resveratrol, quercetin, polyunsaturated fatty acids and interleukin-1beta, and by the application of AR antisense oligonucleotides. In the clinical situation, AR gene amplification and point mutations were reported in patients with metastatic disease. These mutations generate receptors which could be activated by other steroid hormones and non-steroidal antiandrogens. In the absence of androgen, the AR could be activated by various growth-promoting (growth factors, epidermal growth factor receptor-related oncogene HER-2/neu) and pleiotropic (protein kinase A activators, interleukin-6) compounds as well as by inducers of differentiation (phenylbutyrate). AR function is modulated by a number of coactivators and corepressors. The three coactivators, TIF-2, SRC-1 and RAC3, are up-regulated in relapsed prostate cancer. New experimental therapies for prostate cancer are aimed to down-regulate AR expression and to overcome difficulties which occur because of the acquisition of agonistic properties

  3. Chimeric antigen receptors: driving immunology towards synthetic biology.

    PubMed

    Sadelain, Michel

    2016-08-01

    The advent of second generation chimeric antigen receptors and the CD19 paradigm have ushered a new therapeutic modality in oncology. In contrast to earlier forms of adoptive cell therapy, which were based on the isolation and expansion of naturally occurring T cells, CAR therapy is based on the design and manufacture of engineered T cells with optimized properties. A new armamentarium, comprising not only CARs but also chimeric costimulatory receptors, chimeric cytokine receptors, inhibitory receptors and synthetic Notch receptors, expressed in naïve, central memory or stem cell-like memory T cells, is being developed for clinical use in a wide range of cancers. Immunological principles are thus finding a new purpose thanks to advances in genetic engineering, synthetic biology and cell manufacturing sciences. PMID:27372731

  4. Chimeric antigen receptors: driving immunology towards synthetic biology.

    PubMed

    Sadelain, Michel

    2016-08-01

    The advent of second generation chimeric antigen receptors and the CD19 paradigm have ushered a new therapeutic modality in oncology. In contrast to earlier forms of adoptive cell therapy, which were based on the isolation and expansion of naturally occurring T cells, CAR therapy is based on the design and manufacture of engineered T cells with optimized properties. A new armamentarium, comprising not only CARs but also chimeric costimulatory receptors, chimeric cytokine receptors, inhibitory receptors and synthetic Notch receptors, expressed in naïve, central memory or stem cell-like memory T cells, is being developed for clinical use in a wide range of cancers. Immunological principles are thus finding a new purpose thanks to advances in genetic engineering, synthetic biology and cell manufacturing sciences.

  5. Human polyomavirus receptor distribution in brain parenchyma contrasts with receptor distribution in kidney and choroid plexus.

    PubMed

    Haley, Sheila A; O'Hara, Bethany A; Nelson, Christian D S; Brittingham, Frances L P; Henriksen, Kammi J; Stopa, Edward G; Atwood, Walter J

    2015-08-01

    The human polyomavirus, JCPyV, is the causative agent of progressive multifocal leukoencephalopathy, a rare demyelinating disease that occurs in the setting of prolonged immunosuppression. After initial asymptomatic infection, the virus establishes lifelong persistence in the kidney and possibly other extraneural sites. In rare instances, the virus traffics to the central nervous system, where oligodendrocytes, astrocytes, and glial precursors are susceptible to lytic infection, resulting in progressive multifocal leukoencephalopathy. The mechanisms by which the virus traffics to the central nervous system from peripheral sites remain unknown. Lactoseries tetrasaccharide c (LSTc), a pentasaccharide containing a terminal α2,6-linked sialic acid, is the major attachment receptor for polyomavirus. In addition to LSTc, type 2 serotonin receptors are required for facilitating virus entry into susceptible cells. We studied the distribution of virus receptors in kidney and brain using lectins, antibodies, and labeled virus. The distribution of LSTc, serotonin receptors, and virus binding sites overlapped in kidney and in the choroid plexus. In brain parenchyma, serotonin receptors were expressed on oligodendrocytes and astrocytes, but these cells were negative for LSTc and did not bind virus. LSTc was instead found on microglia and vascular endothelium, to which virus bound abundantly. Receptor distribution was not changed in the brains of patients with progressive multifocal leukoencephalopathy. Virus infection of oligodendrocytes and astrocytes during disease progression is LSTc independent. PMID:26056932

  6. Human Polyomavirus Receptor Distribution in Brain Parenchyma Contrasts with Receptor Distribution in Kidney and Choroid Plexus

    PubMed Central

    Haley, Sheila A.; O'Hara, Bethany A.; Nelson, Christian D.S.; Brittingham, Frances L.P.; Henriksen, Kammi J.; Stopa, Edward G.; Atwood, Walter J.

    2016-01-01

    The human polyomavirus, JCPyV, is the causative agent of progressive multifocal leukoencephalopathy, a rare demyelinating disease that occurs in the setting of prolonged immunosuppression. After initial asymptomatic infection, the virus establishes lifelong persistence in the kidney and possibly other extraneural sites. In rare instances, the virus traffics to the central nervous system, where oligodendrocytes, astrocytes, and glial precursors are susceptible to lytic infection, resulting in progressive multifocal leukoencephalopathy. The mechanisms by which the virus traffics to the central nervous system from peripheral sites remain unknown. Lactoseries tetrasaccharide c (LSTc), a pentasaccharide containing a terminal α2,6–linked sialic acid, is the major attachment receptor for polyomavirus. In addition to LSTc, type 2 serotonin receptors are required for facilitating virus entry into susceptible cells. We studied the distribution of virus receptors in kidney and brain using lectins, antibodies, and labeled virus. The distribution of LSTc, serotonin receptors, and virus binding sites overlapped in kidney and in the choroid plexus. In brain parenchyma, serotonin receptors were expressed on oligodendrocytes and astrocytes, but these cells were negative for LSTc and did not bind virus. LSTc was instead found on microglia and vascular endothelium, to which virus bound abundantly. Receptor distribution was not changed in the brains of patients with progressive multifocal leukoencephalopathy. Virus infection of oligodendrocytes and astrocytes during disease progression is LSTc independent. PMID:26056932

  7. Naturally-occurring TGR5 agonists modulating glucagon-like peptide-1 biosynthesis and secretion.

    PubMed

    Jafri, Laila; Saleem, Samreen; Calderwood, Danielle; Gillespie, Anna; Mirza, Bushra; Green, Brian D

    2016-04-01

    Selective GLP-1 secretagogues represent a novel potential therapy for type 2 diabetes mellitus. This study examined the GLP-1 secretory activity of the ethnomedicinal plant, Fagonia cretica, which is postulated to possess anti-diabetic activity. After extraction and fractionation extracts and purified compounds were tested for GLP-1 and GIP secretory activity in pGIP/neo STC-1 cells. Intracellular levels of incretin hormones and their gene expression were also determined. Crude F. cretica extracts stimulated both GLP-1 and GIP secretion, increased cellular hormone content, and upregulated gene expression of proglucagon, GIP and prohormone convertase. However, ethyl acetate partitioning significantly enriched GLP-1 secretory activity and this fraction underwent bioactivity-guided fractionation. Three isolated compounds were potent and selective GLP-1 secretagogues: quinovic acid (QA) and two QA derivatives, QA-3β-O-β-D-glycopyranoside and QA-3β-O-β-D-glucopyranosyl-(28→1)-β-D-glucopyranosyl ester. All QA compounds activated the TGR5 receptor and increased intracellular incretin levels and gene expression. QA derivatives were more potent GLP-1 secretagogues than QA. This is the first time that QA and its naturally-occurring derivatives have been shown to activate TGR5 and stimulate GLP-1 secretion. These data provide a plausible mechanism for the ethnomedicinal use of F. cretica and may assist in the ongoing development of selective GLP-1 agonists. PMID:26820940

  8. Anabolic and Antiresorptive Modulation of Bone Homeostasis by the Epigenetic Modulator Sulforaphane, a Naturally Occurring Isothiocyanate.

    PubMed

    Thaler, Roman; Maurizi, Antonio; Roschger, Paul; Sturmlechner, Ines; Khani, Farzaneh; Spitzer, Silvia; Rumpler, Monika; Zwerina, Jochen; Karlic, Heidrun; Dudakovic, Amel; Klaushofer, Klaus; Teti, Anna; Rucci, Nadia; Varga, Franz; van Wijnen, Andre J

    2016-03-25

    Bone degenerative pathologies like osteoporosis may be initiated by age-related shifts in anabolic and catabolic responses that control bone homeostasis. Here we show that sulforaphane (SFN), a naturally occurring isothiocyanate, promotes osteoblast differentiation by epigenetic mechanisms. SFN enhances active DNA demethylation viaTet1andTet2and promotes preosteoblast differentiation by enhancing extracellular matrix mineralization and the expression of osteoblastic markers (Runx2,Col1a1,Bglap2,Sp7,Atf4, andAlpl). SFN decreases the expression of the osteoclast activator receptor activator of nuclear factor-κB ligand (RANKL) in osteocytes and mouse calvarial explants and preferentially induces apoptosis in preosteoclastic cells via up-regulation of theTet1/Fas/Caspase 8 and Caspase 3/7 pathway. These mechanistic effects correlate with higher bone volume (∼20%) in both normal and ovariectomized mice treated with SFN for 5 weeks compared with untreated mice as determined by microcomputed tomography. This effect is due to a higher trabecular number in these mice. Importantly, no shifts in mineral density distribution are observed upon SFN treatment as measured by quantitative backscattered electron imaging. Our data indicate that the food-derived compound SFN epigenetically stimulates osteoblast activity and diminishes osteoclast bone resorption, shifting the balance of bone homeostasis and favoring bone acquisition and/or mitigation of bone resorptionin vivo Thus, SFN is a member of a new class of epigenetic compounds that could be considered for novel strategies to counteract osteoporosis. PMID:26757819

  9. A receptor binding assay applied to monitoring the neurotoxicity of parathion to Peromyscus after oral exposure

    USGS Publications Warehouse

    Jett, D.A.; Eldefrawi, A.T.; Eldefrawi, M.E.

    1993-01-01

    Many naturally occurring toxins, as well as pesticides, metals, and other compounds that occur in our environment from anthropogenic activities, stimulate or antagonize neuro-receptors to produce acute and/or chronic toxicities. Recent advances in laboratory instrumentation and the availability of a variety of radiolabeled ligands and type-specific drugs for numerous receptors make it possible to easily screen large numbers of samples and detect changes in sensitivity and density of receptor types and subtypes. A receptor binding assay for examining the chronic dietary toxicity of parathion will be used as a model to describe the methodology.

  10. Delta opioid receptor analgesia: recent contributions from pharmacology and molecular approaches

    PubMed Central

    Gavériaux-Ruff, Claire; Kieffer, Brigitte Lina

    2012-01-01

    Delta opioid receptors represent a promising target for the development of novel analgesics. A number of tools have been developed recently that have significantly improved our knowledge of delta receptor function in pain control. These include several novel delta agonists with potent analgesic properties, as well as genetic mouse models with targeted mutations in the delta opioid receptor gene. Also, recent findings have further documented the regulation of delta receptor function at cellular level, which impacts on the pain-reducing activity of the receptor. These regulatory mechanisms occur at transcriptional and post-translational levels, along agonist-induced receptor activation, signaling and trafficking, or in interaction with other receptors and neuromodulatory systems. All these tools for in vivo research, as well as proposed mechanisms at molecular level, have tremendously increased our understanding of delta receptor physiology, and contribute to designing innovative strategies for the treatment of chronic pain and other diseases such as mood disorders. PMID:21836459

  11. Regulatory mechanisms that modulate signalling by G-protein-coupled receptors.

    PubMed Central

    Böhm, S K; Grady, E F; Bunnett, N W

    1997-01-01

    The large and functionally diverse group of G-protein-coupled receptors includes receptors for many different signalling molecules, including peptide and non-peptide hormones and neuro-transmitters, chemokines, prostanoids and proteinases. Their principal function is to transmit information about the extracellular environment to the interior of the cell by interacting with the heterotrimeric G-proteins, and they thereby participate in many aspects of regulation. Cellular responses to agonists of these receptors are usually rapidly attenuated. Mechanisms of signal attenuation include removal of agonists from the extracellular fluid, receptor desensitization, endocytosis and down-regulation. Agonists are removed by dilution, uptake by transporters and enzymic degradation. Receptor desensitization is mediated by receptor phosphorylation by G-protein receptor kinases and second-messenger kinases, interaction of phosphorylated receptors with arrestins and receptor uncoupling from G-proteins. Agonist-induced receptor endocytosis also contributes to desensitization by depleting the cell surface of high-affinity receptors, and recycling of internalized receptors contributes to resensitization of cellular responses. Receptor down-regulation is a form of desensitization that occurs during continuous, long-term exposure of cells to receptor agonists. Down-regulation, which may occur during the development of drug tolerance, is characterized by depletion of the cellular receptor content, and is probably mediated by alterations in the rates of receptor degradation and synthesis. These regulatory mechanisms are important, as they govern the ability of cells to respond to agonists. A greater understanding of the mechanisms that modulate signalling may lead to the development of new therapies and may help to explain the mechanism of drug tolerance. PMID:9078236

  12. Leukotriene receptor antagonist therapy

    PubMed Central

    Dempsey, O

    2000-01-01

    Leukotriene receptor antagonists (LTRA) are a new class of drugs for asthma treatment, available in tablet form. Their unique mechanism of action results in a combination of both bronchodilator and anti-inflammatory effects. While their optimal place in asthma management is still under review, LTRA represent an important advance in asthma pharmacotherapy.


Keywords: leukotriene receptor antagonist; asthma; montelukast; zafirlukast PMID:11085767

  13. Genetics of Taste Receptors

    PubMed Central

    Bachmanov, Alexander A.; Bosak, Natalia P.; Lin, Cailu; Matsumoto, Ichiro; Ohmoto, Makoto; Reed, Danielle R.; Nelson, Theodore M.

    2016-01-01

    Taste receptors function as one of the interfaces between internal and external milieus. Taste receptors for sweet and umami (T1R [taste receptor, type 1]), bitter (T2R [taste receptor, type 2]), and salty (ENaC [epithelial sodium channel]) have been discovered in the recent years, but transduction mechanisms of sour taste and ENaC-independent salt taste are still poorly understood. In addition to these five main taste qualities, the taste system detects such noncanonical “tastes” as water, fat, and complex carbohydrates, but their reception mechanisms require further research. Variations in taste receptor genes between and within vertebrate species contribute to individual and species differences in taste-related behaviors. These variations are shaped by evolutionary forces and reflect species adaptations to their chemical environments and feeding ecology. Principles of drug discovery can be applied to taste receptors as targets in order to develop novel taste compounds to satisfy demand in better artificial sweeteners, enhancers of sugar and sodium taste, and blockers of bitterness of food ingredients and oral medications. PMID:23886383

  14. Genetics of taste receptors.

    PubMed

    Bachmanov, Alexander A; Bosak, Natalia P; Lin, Cailu; Matsumoto, Ichiro; Ohmoto, Makoto; Reed, Danielle R; Nelson, Theodore M

    2014-01-01

    Taste receptors function as one of the interfaces between internal and external milieus. Taste receptors for sweet and umami (T1R [taste receptor, type 1]), bitter (T2R [taste receptor, type 2]), and salty (ENaC [epithelial sodium channel]) have been discovered in the recent years, but transduction mechanisms of sour taste and ENaC-independent salt taste are still poorly understood. In addition to these five main taste qualities, the taste system detects such noncanonical "tastes" as water, fat, and complex carbohydrates, but their reception mechanisms require further research. Variations in taste receptor genes between and within vertebrate species contribute to individual and species differences in taste-related behaviors. These variations are shaped by evolutionary forces and reflect species adaptations to their chemical environments and feeding ecology. Principles of drug discovery can be applied to taste receptors as targets in order to develop novel taste compounds to satisfy demand in better artificial sweeteners, enhancers of sugar and sodium taste, and blockers of bitterness of food ingredients and oral medications. PMID:23886383

  15. Roles of Eph receptors and ephrins in segmental patterning.

    PubMed Central

    Xu, Q; Mellitzer, G; Wilkinson, D G

    2000-01-01

    Eph receptor tyrosine kinases and their membrane-bound ligands, ephrins, have key roles in patterning and morphogenesis. Interactions between these molecules are promiscuous, but largely fall into two groups: EphA receptors bind to glycosylphosphatidyl inositol-anchored ephrin-A ligands, and EphB receptors bind to transmembrane ephrin-B proteins. Ephrin-B proteins transduce signals, such that bidirectional signalling can occur upon interaction with the Eph receptor. In many tissues, there are complementary and overlapping expression domains of interacting Eph receptors and ephrins. An important role of Eph receptors and ephrins is to mediate cell contact-dependent repulsion, and this has been implicated in the pathfinding of axons and neural crest cells, and the restriction of cell intermingling between hindbrain segments. Studies in an in vitro system show that bidirectional activation is required to prevent intermingling between cell populations, whereas unidirectional activation can restrict cell communication via gap junctions. Recent work indicates that Eph receptors can also upregulate cell adhesion, but the biochemical basis of repulsion versus adhesion responses is unclear. Eph receptors and ephrins have thus emerged as key regulators that, in parallel with cell adhesion molecules, underlie the establishment and maintenance of patterns of cellular organization. PMID:11128993

  16. Pouncing on the chemokine receptor Chimera.

    PubMed

    Mascolini, M

    1997-08-01

    Scientists are seeking to unravel the mystery of chemokine receptors in an attempt to develop treatments for HIV infection; however, receptor experts are realizing that the picture is more complicated than they first imagined. Scientists want to know, among other things, what parts of each coreceptor are essential for viral fusion with target cells, what makes macrophage-tropic viruses switch their preference to T-lymphocytes, why HIV goes after chemokine receptors in the first place, and how fusion and entry occur. Other issues discussed include whether blocking coreceptors for HIV will actually curb this disease, virus turnover in monkey studies showing that SIV may go through the cycle as many as 100 times per day, and studies showing that the first days of infection may predict the course of disease. Final comments concern the use of ritonavir plus indinavir in treatment combinations for children with HIV and the latest progress toward vaccine development. Understanding these and other puzzles might help scientists to develop drugs to block receptors active in HIV infection and perhaps curb HIV. More than 14 biotechnology and pharmaceutical firms are working to design coreceptor blockers, despite the opinions of several leading researchers that the drugs are not terribly promising. Dr. Anthony Fauci, director of the National Institute for Allergy and Infectious Disease (NIAID), notes that a famous attempt to block HIV's primary receptor failed, and David Ho, the man who demonstrated why CD4 would not work as therapy, is similarly cautious. According to Ho, drug makers will have no trouble developing compounds that keep HIV off chemokine receptors, such as CCR5 or CXCR4, but whether those compounds will slow disease progression is another question. PMID:11364629

  17. The low density lipoprotein receptor-related protein/alpha2-macroglobulin receptor is a receptor for connective tissue growth factor.

    PubMed

    Segarini, P R; Nesbitt, J E; Li, D; Hays, L G; Yates, J R; Carmichael, D F

    2001-11-01

    Connective tissue growth factor (CTGF) expression is regulated by transforming growth factor-beta (TGF-beta) and strong up-regulation occurs during wound healing; in situ hybridization data indicate that there are high levels of CTGF expression in fibrotic lesions. Recently the binding parameters of CTGF to both high and lower affinity cell surface binding components have been characterized. Affinity cross-linking and SDS-polyacrylamide gel electrophoresis analysis demonstrated the binding of CTGF to a cell surface protein with a mass of approximately 620 kDa. We report here the purification of this protein by affinity chromatography on CTGF coupled to Sepharose and sequence information obtained by mass spectroscopy. The binding protein was identified as the multiligand receptor, low density lipoprotein receptor-related protein/alpha2-macroglobulin receptor (LRP). The identification of LRP as a receptor for CTGF was validated by several studies: 1) binding competition with many ligands that bind to LRP, including receptor-associated protein; 2) immunoprecipitation of CTGF-receptor complex with LRP antibodies; and 3) cells that are genetically deficient for LRP were unable to bind CTGF. Last, CTGF is rapidly internalized and degraded and this process is LRP-dependent. In summary, our data indicate that LRP is a receptor for CTGF, and may play an important role in mediating CTGF biology.

  18. Reconstitution of interactions between tyrosine kinases and the high affinity IgE receptor which are controlled by receptor clustering.

    PubMed Central

    Scharenberg, A M; Lin, S; Cuenod, B; Yamamura, H; Kinet, J P

    1995-01-01

    High affinity IgE receptor (Fc epsilon RI) signaling after contact with antigen occurs in response to receptor clustering. This paper describes methodology, based on vaccinia virus driven protein expression, for probing signaling pathways and its application to Fc epsilon RI interactions with the lyn and syk tyrosine kinases. Reconstitution of the complete tetrameric Fc epsilon RI receptor, lyn and syk in a non-hematopoietic 'null' cell line is sufficient to reconstruct clustering-controlled receptor tyrosine phosphorylation and activation of syk, without apparent requirement for hematopoietic specific phosphatases. The src family kinase lyn phosphorylates Fc epsilon RI in response to receptor clustering, resulting in syk binding to the phosphorylated Fc epsilon RI. Lyn also participates in the tyrosine phosphorylation and activation of syk in a manner which is dependent on phosphorylated Fc epsilon RI. Using overexpression of active and dominant negative syk proteins in a mast cell line which naturally expresses Fc epsilon RI, we corroborate syk's role downstream of receptor phosphorylation, and demonstrate that syk SH2 domains protect receptor ITAMs from ongoing dephosphorylation. Based on these results, we propose that receptor clustering controls lyn-mediated Fc epsilon RI tyrosine phosphorylation by shifting a balance between phosphorylation and dephosphorylation towards accumulation of tyrosine phosphorylated Fc epsilon RI. Fc epsilon RI tyrosine phosphorylation functions to bring syk into a microenvironment where it becomes tyrosine phosphorylated and activated, thereby allowing clustering to indirectly control syk activity. Images PMID:7628439

  19. Collagenase-3 binds to a specific receptor and requires the low density lipoprotein receptor-related protein for internalization

    NASA Technical Reports Server (NTRS)

    Barmina, O. Y.; Walling, H. W.; Fiacco, G. J.; Freije, J. M.; Lopez-Otin, C.; Jeffrey, J. J.; Partridge, N. C.

    1999-01-01

    We have previously identified a specific receptor for collagenase-3 that mediates the binding, internalization, and degradation of this ligand in UMR 106-01 rat osteoblastic osteosarcoma cells. In the present study, we show that collagenase-3 binding is calcium-dependent and occurs in a variety of cell types, including osteoblastic and fibroblastic cells. We also present evidence supporting a two-step mechanism of collagenase-3 binding and internalization involving both a specific collagenase-3 receptor and the low density lipoprotein receptor-related protein. Ligand blot analysis shows that (125)I-collagenase-3 binds specifically to two proteins ( approximately 170 kDa and approximately 600 kDa) present in UMR 106-01 cells. Western blotting identified the 600-kDa protein as the low density lipoprotein receptor-related protein. Our data suggest that the 170-kDa protein is a specific collagenase-3 receptor. Low density lipoprotein receptor-related protein-null mouse embryo fibroblasts bind but fail to internalize collagenase-3, whereas UMR 106-01 and wild-type mouse embryo fibroblasts bind and internalize collagenase-3. Internalization, but not binding, is inhibited by the 39-kDa receptor-associated protein. We conclude that the internalization of collagenase-3 requires the participation of the low density lipoprotein receptor-related protein and propose a model in which the cell surface interaction of this ligand requires a sequential contribution from two receptors, with the collagenase-3 receptor acting as a high affinity primary binding site and the low density lipoprotein receptor-related protein mediating internalization.

  20. Ionotropic Crustacean Olfactory Receptors

    PubMed Central

    Corey, Elizabeth A.; Bobkov, Yuriy; Ukhanov, Kirill; Ache, Barry W.

    2013-01-01

    The nature of the olfactory receptor in crustaceans, a major group of arthropods, has remained elusive. We report that spiny lobsters, Panulirus argus, express ionotropic receptors (IRs), the insect chemosensory variants of ionotropic glutamate receptors. Unlike insects IRs, which are expressed in a specific subset of olfactory cells, two lobster IR subunits are expressed in most, if not all, lobster olfactory receptor neurons (ORNs), as confirmed by antibody labeling and in situ hybridization. Ligand-specific ORN responses visualized by calcium imaging are consistent with a restricted expression pattern found for other potential subunits, suggesting that cell-specific expression of uncommon IR subunits determines the ligand sensitivity of individual cells. IRs are the only type of olfactory receptor that we have detected in spiny lobster olfactory tissue, suggesting that they likely mediate olfactory signaling. Given long-standing evidence for G protein-mediated signaling in activation of lobster ORNs, this finding raises the interesting specter that IRs act in concert with second messenger-mediated signaling. PMID:23573266

  1. Taste Receptors in Innate Immunity

    PubMed Central

    Lee, Robert J.

    2014-01-01

    Taste receptors were first identified on the tongue, where they initiate a signaling pathway that communicates information to the brain about the nutrient content or potential toxicity of ingested foods. However, recent research has shown that taste receptors are also expressed in a myriad of other tissues, from the airway and gastrointestinal epithelia to the pancreas and brain. The functions of many of these extraoral taste receptors remain unknown, but emerging evidence suggests that bitter and sweet taste receptors in the airway are important sentinels of innate immunity. This review discusses taste receptor signaling, focusing on the G-protein coupled–receptors that detect bitter, sweet, and savory tastes, followed by an overview of extraoral taste receptors and in-depth discussion of studies demonstrating the roles of taste receptors in airway innate immunity. Future research on extraoral taste receptors has significant potential for identification of novel immune mechanisms and insights into host-pathogen interactions. PMID:25323130

  2. New insights into receptor regulation.

    PubMed

    Poste, G

    1984-11-01

    This review provides a brief summary of certain recent advances in our understanding of receptor regulation, signal transduction, and the diverse pathways by which receptor-ligand complexes are internalized and delivered to specific organelles, together with recycling of receptors back to the cell surface. Emphasis is also given to the importance of methodological advances in receptor isolation, immunologic analysis of receptor structure and function, the development of new instrumentation for microchemical characterization of very small amounts of receptor material, and the increasing use of genetic engineering techniques to isolate the genes for receptors and their regulatory subunits, to transfer such genes between cells, and to study receptor function by creating structurally modified receptors via subtle changes in gene structure. PMID:6151557

  3. Skeletal receptors for steroid-family regulating glycoprotein hormones: A multilevel, integrated physiological control system.

    PubMed

    Blair, Harry C; Robinson, Lisa J; Sun, Li; Isales, Carlos; Davies, Terry F; Zaidi, Mone

    2011-12-01

    Pituitary glycoprotein hormone receptors, including ACTH-R, TSH-R, and FSH-R, occur in bone. Their skeletal expression reflects that central endocrine control is evolutionarily recent. ACTH receptors, in osteoblasts or the adrenal cortex, drive VEGF synthesis. VEGF is essential to maintain vasculature. In bone, ACTH suppression by glucocorticoids can cause osteonecrosis. TSH receptors occur on osteoblasts and osteoclasts, in both cases reducing activity. Thus, TSH directly reduces skeletal turnover, consistent with evolutionary adaptation to stress. FSH receptors accelerate bone resorption, whereas estrogen promotes bone formation, the forces usually balancing. With ovarian failure, low estrogen with high FSH causes rapid bone loss. The skeletal FSH effect in the menopause seems paradoxical, but it is a logical adaptation in lactation, where prolonged FSH elevation also occurs. In addition to receptors, there is some synthesis of pituitary glycoproteins at distributed sites; this is not well studied, but it may further modify the paradigm of central endocrine regulation.

  4. Pregnancy reduces brain sigma receptor function

    PubMed Central

    Bergeron, Richard; de Montigny, Claude; Debonnel, Guy

    1999-01-01

    Sigma (σ) receptors have recently been cloned, though their endogenous ligand(s) remain unidentified. However, some neuroactive steroids, such as progesterone, have a high affinity for these receptors. Some σ ligands, such as DTG, (+)-pentazocine and DHEA, act as σ ‘agonists' by potentiating the neuronal response to NMDA. Others, such as haloperidol, NE-100 and progesterone, act as σ ‘antagonists' by reversing the potentiations induced by σ ‘agonists'.We compared the effects of σ ‘agonists' in four series of female rats: in controls, at day 18 of pregnancy, at day 5 post-partum, and in ovariectomized rats following a 3-week treatment with a high dose of progesterone.In pregnant rats and following a 3-week treatment with progesterone, 10 fold higher doses of DTG, (+)-pentazocine and DHEA were required to elicit a selective potentiation of the NMDA response comparable to that obtained in control females. Conversely, at day 5 post-partum and following the 3-week treatment with a progesterone and after a 5-day washout, the potentiation of the NMDA response induced by the σ ‘agonist' DTG was greater than in control females.The present data suggest that endogenous progesterone acts as an ‘antagonist' at σ receptors. The resulting changes in the function of σ receptors during pregnancy and post-partum may be implicated in emotional phenomena occurring during these periods. PMID:10482906

  5. ER to synapse trafficking of NMDA receptors

    PubMed Central

    Horak, Martin; Petralia, Ronald S.; Kaniakova, Martina; Sans, Nathalie

    2014-01-01

    Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. There are three distinct subtypes of ionotropic glutamate receptors (GluRs) that have been identified including 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid receptors (AMPARs), N-methyl-D-aspartate receptors (NMDARs) and kainate receptors. The most common GluRs in mature synapses are AMPARs that mediate the fast excitatory neurotransmission and NMDARs that mediate the slow excitatory neurotransmission. There have been large numbers of recent reports studying how a single neuron regulates synaptic numbers and types of AMPARs and NMDARs. Our current research is centered primarily on NMDARs and, therefore, we will focus in this review on recent knowledge of molecular mechanisms occurring (1) early in the biosynthetic pathway of NMDARs, (2) in the transport of NMDARs after their release from the endoplasmic reticulum (ER); and (3) at the plasma membrane including excitatory synapses. Because a growing body of evidence also indicates that abnormalities in NMDAR functioning are associated with a number of human psychiatric and neurological diseases, this review together with other chapters in this issue may help to enhance research and to gain further knowledge of normal synaptic physiology as well as of the etiology of many human brain diseases. PMID:25505872

  6. Functional ET(A)-ET(B) Receptor Cross-talk in Basilar Artery In Situ From ET(B) Receptor Deficient Rats.

    PubMed

    Yoon, SeongHun; Gariepy, Cheryl E; Yanagisawa, Masashi; Zuccarello, Mario; Rapoport, Robert M

    2016-03-01

    The role of endothelin (ET)(A)-ET(B) receptor cross-talk in limiting the ET(A) receptor antagonist inhibition of ET-1 constriction is revealed by the partial or complete dependency of the ET(A) receptor antagonist inhibition on functional removal of the ET(B) receptor. Although functional removal of the ET(B) receptor is generally accomplished with ET(B) receptor antagonist, a novel approach using rats containing a naturally occurring deletion mutation in the ET(B) receptor [rescued "spotting lethal" (sl) rats; ET(B)(sl/sl)] demonstrated increased ET(A) receptor antagonist inhibition of ET-1 constriction in vena cava. We investigated whether this deletion mutation was also sufficient to remove the ET(B) receptor dependency of the ET(A) receptor antagonist inhibition of ET-1 constriction in the basilar artery. Consistent with previous reports, ET-1 plasma levels were elevated in ET(B)(sl/sl) as compared with ET(B)(+/+) rats. ET(B) receptor antagonist failed to relax the ET-1 constricted basilar artery from ET(B)(+/+) and ET(B)(sl/sl) rats. Relaxation to combined ET(A) and ET(B) receptor antagonist was greater than relaxation to ET(A) receptor antagonist in the basilar artery from ET(B)(+/+) and, unexpectedly, ET(B)(sl/sl) rats. These findings confirm the presence of ET(A)-ET(B) receptor cross-talk in the basilar artery. We speculate that mutant ET(B) receptor expression produced by alternative splicing may be sufficient to allow cross-talk.

  7. Clinically used selective oestrogen receptor modulators increase LDL receptor activity in primary human lymphocytes

    PubMed Central

    Cerrato, F; Fernández-Suárez, M E; Alonso, R; Alonso, M; Vázquez, C; Pastor, O; Mata, P; Lasunción, M A; Gómez-Coronado, D

    2015-01-01

    Background and Purpose Treatment with selective oestrogen receptor modulators (SERMs) reduces low-density lipoprotein (LDL) cholesterol levels. We assessed the effect of tamoxifen, raloxifene and toremifene and their combinations with lovastatin on LDL receptor activity in lymphocytes from normolipidaemic and familial hypercholesterolaemic (FH) subjects, and human HepG2 hepatocytes and MOLT-4 lymphoblasts. Experimental Approach Lymphocytes were isolated from peripheral blood, treated with different compounds, and 1,1′-dioctadecyl-3,3,3,3′-tetramethylindocarbocyanine perchlorate (DiI)-labelled LDL uptake was analysed by flow cytometry. Key Results Tamoxifen, toremifene and raloxifene, in this order, stimulated DiI-LDL uptake by lymphocytes by inhibiting LDL-derived cholesterol trafficking and subsequent down-regulation of LDL receptor expression. Differently to what occurred in HepG2 and MOLT-4 cells, only tamoxifen consistently displayed a potentiating effect with lovastatin in primary lymphocytes. The SERM-mediated increase in LDL receptor activity was not altered by the anti-oestrogen ICI 182 780 nor was it reproduced by 17β-oestradiol. However, the tamoxifen-active metabolite endoxifen was equally effective as tamoxifen. The SERMs produced similar effects on LDL receptor activity in heterozygous FH lymphocytes as in normal lymphocytes, although none of them had a potentiating effect with lovastatin in heterozygous FH lymphocytes. The SERMs had no effect in homozygous FH lymphocytes. Conclusions and Implications Clinically used SERMs up-regulate LDL receptors in primary human lymphocytes. There is a mild enhancement between SERMs and lovastatin of lymphocyte LDLR activity, the potentiation being greater in HepG2 and MOLT-4 cells. The effect of SERMs is independent of oestrogen receptors but is preserved in the tamoxifen-active metabolite endoxifen. This mechanism may contribute to the cholesterol-lowering action of SERMs. PMID:25395200

  8. Olfactory receptor signaling.

    PubMed

    Antunes, Gabriela; Simoes de Souza, Fabio Marques

    2016-01-01

    The guanine nucleotide protein (G protein)-coupled receptors (GPCRs) superfamily represents the largest class of membrane protein in the human genome. More than a half of all GPCRs are dedicated to interact with odorants and are termed odorant-receptors (ORs). Linda Buck and Richard Axel, the Nobel Prize laureates in physiology or medicine in 2004, first cloned and characterized the gene family that encode ORs, establishing the foundations to the understanding of the molecular basis for odor recognition. In the last decades, a lot of progress has been done to unravel the functioning of the sense of smell. This chapter gives a general overview of the topic of olfactory receptor signaling and reviews recent advances in this field. PMID:26928542

  9. Progesterone Receptor Signaling Mechanisms.

    PubMed

    Grimm, Sandra L; Hartig, Sean M; Edwards, Dean P

    2016-09-25

    Progesterone receptor (PR) is a master regulator in female reproductive tissues that controls developmental processes and proliferation and differentiation during the reproductive cycle and pregnancy. PR also plays a role in progression of endocrine-dependent breast cancer. As a member of the nuclear receptor family of ligand-dependent transcription factors, the main action of PR is to regulate networks of target gene expression in response to binding its cognate steroid hormone, progesterone. This paper summarizes recent advances in understanding the structure-function properties of the receptor protein and the tissue/cell-type-specific PR signaling pathways that contribute to the biological actions of progesterone in the normal breast and in breast cancer. PMID:27380738

  10. Progress in detecting cell-surface protein receptors: the erythropoietin receptor example.

    PubMed

    Elliott, Steve; Sinclair, Angus; Collins, Helen; Rice, Linda; Jelkmann, Wolfgang

    2014-02-01

    Testing for the presence of specific cell-surface receptors (such as EGFR or HER2) on tumor cells is an integral part of cancer care in terms of treatment decisions and prognosis. Understanding the strengths and limitations of these tests is important because inaccurate results may occur if procedures designed to prevent false-negative or false-positive outcomes are not employed. This review discusses tests commonly used to identify and characterize cell-surface receptors, such as the erythropoietin receptor (EpoR). First, a summary is provided on the biology of the Epo/EpoR system, describing how EpoR is expressed on erythrocytic progenitors and precursors in the bone marrow where it mediates red blood cell production in response to Epo. Second, studies are described that investigated whether erythropoiesis-stimulating agents could stimulate tumor progression in cancer patients and whether EpoR is expressed and functional on tumor cells or on endothelial cells. The methods used in these studies included immunohistochemistry, Northern blotting, Western blotting, and binding assays. This review summarizes the strengths and limitations of these methods. Critically analyzing data from tests for cell-surface receptors such as EpoR requires understanding the techniques utilized and demonstrating that results are consistent with current knowledge about receptor biology. PMID:24337485

  11. CONTAMINANT INTERACTIONS WITH STEROID RECEPTORS: EVIDENCE FOR RECEPTOR BINDING.

    EPA Science Inventory

    Steroid receptors are important determinants of endocrine disrupter consequences. As the most frequently proposed mechanism of endocrine-disrupting contaminant (EDC) action, steroid receptors are not only targets of natural steroids but are also commonly sites of nonsteroidal com...

  12. Vasopressin receptor antagonists.

    PubMed

    Palmer, Biff F

    2015-01-01

    Arginine vasopressin (AVP) is the principal hormone involved in regulating the tonicity of body fluids. Less appreciated is the role that AVP plays in a variety of other physiologic functions including glucose metabolism, cardiovascular homeostasis, bone metabolism, and cognitive behavior. AVP receptor antagonists are now available and currently approved to treat hyponatremia. There is a great deal of interest in exploring the potential benefits that these drugs may play in blocking AVP-mediated effects in other organ systems. The purpose of this report is to provide an update on the expanding role of AVP receptor antagonists and what disease states these drugs may eventually be used for.

  13. Vasopressin receptor antagonists.

    PubMed

    Palmer, Biff F

    2015-01-01

    Arginine vasopressin (AVP) is the principal hormone involved in regulating the tonicity of body fluids. Less appreciated is the role that AVP plays in a variety of other physiologic functions including glucose metabolism, cardiovascular homeostasis, bone metabolism, and cognitive behavior. AVP receptor antagonists are now available and currently approved to treat hyponatremia. There is a great deal of interest in exploring the potential benefits that these drugs may play in blocking AVP-mediated effects in other organ systems. The purpose of this report is to provide an update on the expanding role of AVP receptor antagonists and what disease states these drugs may eventually be used for. PMID:25604388

  14. Biomimetic Receptors and Sensors

    PubMed Central

    Dickert, Franz L.

    2014-01-01

    In biomimetics, living systems are imitated to develop receptors for ions, molecules and bioparticles. The most pertinent idea is self-organization in analogy to evolution in nature, which created the key-lock principle. Today, modern science has been developing host-guest chemistry, a strategy of supramolecular chemistry for designing interactions of analytes with synthetic receptors. This can be realized, e.g., by self-assembled monolayers (SAMs) or molecular imprinting. The strategies are used for solid phase extraction (SPE), but preferably in developing recognition layers of chemical sensors. PMID:25436653

  15. A restricted population of CB1 cannabinoid receptors with neuroprotective activity

    PubMed Central

    Chiarlone, Anna; Bellocchio, Luigi; Blázquez, Cristina; Resel, Eva; Soria-Gómez, Edgar; Cannich, Astrid; Ferrero, José J.; Sagredo, Onintza; Benito, Cristina; Romero, Julián; Sánchez-Prieto, José; Lutz, Beat; Fernández-Ruiz, Javier; Galve-Roperh, Ismael; Guzmán, Manuel

    2014-01-01

    The CB1 cannabinoid receptor, the main molecular target of endocannabinoids and cannabis active components, is the most abundant G protein-coupled receptor in the mammalian brain. Of note, CB1 receptors are expressed at the synapses of two opposing (i.e., GABAergic/inhibitory and glutamatergic/excitatory) neuronal populations, so the activation of one and/or another receptor population may conceivably evoke different effects. Despite the widely reported neuroprotective activity of the CB1 receptor in animal models, the precise pathophysiological relevance of those two CB1 receptor pools in neurodegenerative processes is unknown. Here, we first induced excitotoxic damage in the mouse brain by (i) administering quinolinic acid to conditional mutant animals lacking CB1 receptors selectively in GABAergic or glutamatergic neurons, and (ii) manipulating corticostriatal glutamatergic projections remotely with a designer receptor exclusively activated by designer drug pharmacogenetic approach. We next examined the alterations that occur in the R6/2 mouse, a well-established model of Huntington disease, upon (i) fully knocking out CB1 receptors, and (ii) deleting CB1 receptors selectively in corticostriatal glutamatergic or striatal GABAergic neurons. The data unequivocally identify the restricted population of CB1 receptors located on glutamatergic terminals as an indispensable player in the neuroprotective activity of (endo)cannabinoids, therefore suggesting that this precise receptor pool constitutes a promising target for neuroprotective therapeutic strategies. PMID:24843137

  16. Models for the activation pathway of epidermal growth factor receptor protein-tyrosine kinase

    SciTech Connect

    Campion, S.R.; Niyogi, S.K. )

    1991-03-15

    Activation of the epidermal growth factor (EGF) receptor's intrinsic protein-tyrosine kinase activity, which occurs upon formation of the receptor-ligand complex, is the critical regulatory event affecting the subsequent EGF-dependent cellular responses leading to DNA synthesis and cell proliferation. The molecular mechanism by which EGF-dependent activation of receptor kinase activity takes place is not clearly understood. In this study, the growth factor-dependent activation of the EGF receptor tyrosine kinase was examined in vitro using detergent-solubilized, partially purified GEF receptors from A5431 human epidermoid carcinoma cells. Evaluation of the cooperativity observed in the EGF-dependent activation of soluble receptor tyrosine kinase would suggest a mechanism requiring the binding of the EGF peptide to both ligand binding sites on a receptor dimer to induce full receptor kinase activity. Equations describing potential cooperative kinase activation pathways have been examined. The theoretical system which best simulates the allosteric regulation observed in the experimental kinase activation data is that describing multiple essential activation. In addition, studies using mutant analogs of the EGF peptide ligand appear to confirm the requirement for an essential conformational change in the receptor-ligand complex to activate the receptor kinase activity. Several mutant growth factor analogues are able to occupy the ligand binding sites on the receptor without inducing the fully active receptor conformation.

  17. Nicotinic acetylcholine receptors: upregulation, age-related effects and associations with drug use

    PubMed Central

    Melroy-Greif, W. E.; Stitzel, J. A.; Ehringer, M. A.

    2016-01-01

    Nicotinic acetylcholine receptors are ligand-gated ion channels that exogenously bind nicotine. Nicotine produces rewarding effects by interacting with these receptors in the brain’s reward system. Unlike other receptors, chronic stimulation by an agonist induces an upregulation of receptor number that is not due to increased gene expression in adults; while upregulation also occurs during development and adolescence there have been some opposing findings regarding a change in corresponding gene expression. These receptors have also been well studied with regard to human genetic associations and, based on evidence suggesting shared genetic liabilities between substance use disorders, numerous studies have pointed to a role for this system in comorbid drug use. This review will focus on upregulation of these receptors in adulthood, adolescence and development, as well as the findings from human genetic association studies which point to different roles for these receptors in risk for initiation and continuation of drug use. PMID:26351737

  18. Opioid Receptors Mediate Direct Predictive Fear Learning: Evidence from One-Trial Blocking

    ERIC Educational Resources Information Center

    Cole, Sindy; McNally, Gavan P.

    2007-01-01

    Pavlovian fear learning depends on predictive error, so that fear learning occurs when the actual outcome of a conditioning trial exceeds the expected outcome. Previous research has shown that opioid receptors, including [mu]-opioid receptors in the ventrolateral quadrant of the midbrain periaqueductal gray (vlPAG), mediate such predictive fear…

  19. Bile acid receptor agonist GW4064 regulates PPARγ coactivator-1α expression through estrogen receptor-related receptor α.

    PubMed

    Dwivedi, Shailendra Kumar Dhar; Singh, Nidhi; Kumari, Rashmi; Mishra, Jay Sharan; Tripathi, Sarita; Banerjee, Priyam; Shah, Priyanka; Kukshal, Vandana; Tyagi, Abdul Malik; Gaikwad, Anil Nilkanth; Chaturvedi, Rajnish Kumar; Mishra, Durga Prasad; Trivedi, Arun Kumar; Sanyal, Somali; Chattopadhyay, Naibedya; Ramachandran, Ravishankar; Siddiqi, Mohammad Imran; Bandyopadhyay, Arun; Arora, Ashish; Lundåsen, Thomas; Anakk, Sayee Priyadarshini; Moore, David D; Sanyal, Sabyasachi

    2011-06-01

    Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is induced in energy-starved conditions and is a key regulator of energy homeostasis. This makes PGC-1α an attractive therapeutic target for metabolic syndrome and diabetes. In our effort to identify new regulators of PGC-1α expression, we found that GW4064, a widely used synthetic agonist for the nuclear bile acid receptor [farnesoid X receptor (FXR)] strongly enhances PGC-1α promoter reporter activity, mRNA, and protein expression. This induction in PGC-1α concomitantly enhances mitochondrial mass and expression of several PGC-1α target genes involved in mitochondrial function. Using FXR-rich or FXR-nonexpressing cell lines and tissues, we found that this effect of GW4064 is not mediated directly by FXR but occurs via activation of estrogen receptor-related receptor α (ERRα). Cell-based, biochemical and biophysical assays indicate GW4064 as an agonist of ERR proteins. Interestingly, FXR disruption alters GW4064 induction of PGC-1α mRNA in a tissue-dependent manner. Using FXR-null [FXR knockout (FXRKO)] mice, we determined that GW4064 induction of PGC-1α expression is not affected in oxidative soleus muscles of FXRKO mice but is compromised in the FXRKO liver. Mechanistic studies to explain these differences revealed that FXR physically interacts with ERR and protects them from repression by the atypical corepressor, small heterodimer partner in liver. Together, this interplay between ERRα-FXR-PGC-1α and small heterodimer partner offers new insights into the biological functions of ERRα and FXR, thus providing a knowledge base for therapeutics in energy balance-related pathophysiology.

  20. Receptor-ligand interactions: Advanced biomedical applications.

    PubMed

    Guryanov, Ivan; Fiorucci, Stefano; Tennikova, Tatiana

    2016-11-01

    Receptor-ligand interactions (RLIs) are at the base of all biological events occurring in living cells. The understanding of interactions between complementary macromolecules in biological systems represents a high-priority research area in bionanotechnology to design the artificial systems mimicking natural processes. This review summarizes and analyzes RLIs in some cutting-edge biomedical fields, in particular, for the preparation of novel stationary phases to separate complex biological mixtures in medical diagnostics, for the design of ultrasensitive biosensors for identification of biomarkers of various diseases at early stages, as well as in the development of innovative biomaterials and approaches for regenerative medicine. All these biotechnological fields are closely related, because their success depends on a proper choice, combination and spatial disposition of the single components of ligand-receptor pairs on the surface of appropriately designed support.

  1. Receptor-ligand interactions: Advanced biomedical applications.

    PubMed

    Guryanov, Ivan; Fiorucci, Stefano; Tennikova, Tatiana

    2016-11-01

    Receptor-ligand interactions (RLIs) are at the base of all biological events occurring in living cells. The understanding of interactions between complementary macromolecules in biological systems represents a high-priority research area in bionanotechnology to design the artificial systems mimicking natural processes. This review summarizes and analyzes RLIs in some cutting-edge biomedical fields, in particular, for the preparation of novel stationary phases to separate complex biological mixtures in medical diagnostics, for the design of ultrasensitive biosensors for identification of biomarkers of various diseases at early stages, as well as in the development of innovative biomaterials and approaches for regenerative medicine. All these biotechnological fields are closely related, because their success depends on a proper choice, combination and spatial disposition of the single components of ligand-receptor pairs on the surface of appropriately designed support. PMID:27524092

  2. Naturally Occurring Variability in the Envelope Glycoprotein of HIV-1 and the Development of Cell Entry Inhibitors

    PubMed Central

    Brower, Evan T.; Schön, Arne; Freire, Ernesto

    2010-01-01

    Naturally occurring genetic variability across HIV-1 subtypes causes amino acid polymorphisms in encoded HIV-1 proteins including the envelope glycoproteins associated with viral entry. The effects of amino acid polymorphisms on the mechanism of HIV-1 entry into cells, a process initiated by the binding of the viral envelope glycoprotein gp120 to the cellular CD4 receptor, are largely unknown. In this study, we demonstrate that amino acid polymorphisms affect the structural stability and domain cooperativity of gp120 and that those differences are reflected in the binding mechanism of the viral envelope glycoprotein to the cell surface receptor and coreceptor. Moreover, subtype differences also affect the binding behavior of experimental HIV cell entry inhibitors. While gp120-A has a slightly lower denaturation temperature than gp120-B, the most notable stability difference is that for gp120-B the van't Hoff to calorimetric enthalpy ratio (ΔHvH/ΔH) is 0.95 whereas for gp120-A is 0.6, indicative of more cooperative domain/domain interactions in gp120-B, as this protein more closely approaches a two-state transition. Isothermal titration calorimetry demonstrates that CD4 and 17b (a surrogate antibody for the chemokine coreceptor) exhibit 7 and 3-fold weaker binding affinities for gp120-A. The binding of these proteins as well as that of the experimental entry inhibitor NBD-556 induce smaller conformational changes in gp120-A as evidenced by significantly smaller binding enthalpies and binding entropies. Together, these results describe the effects of gp120 polymorphisms on binding to host cell receptors and emphasize that guidelines for developing future entry inhibitors must recognize and deal with genomic differences between HIV strains. PMID:20166763

  3. Rational Design of Potent Antagonists to the Human Growth Hormone Receptor

    NASA Astrophysics Data System (ADS)

    Fuh, Germaine; Cunningham, Brian C.; Fukunaga, Rikiro; Nagata, Shigekazu; Goeddel, David V.; Wells, James A.

    1992-06-01

    A hybrid receptor was constructed that contained the extracellular binding domain of the human growth hormone (hGH) receptor linked to the transmembrane and intracellular domains of the murine granulocyte colony-stimulating factor receptor. Addition of hGH to a myeloid leukemia cell line (FDC-P1) that expressed the hybrid receptor caused proliferation of these cells. The mechanism for signal transduction of the hybrid receptor required dimerization because monoclonal antibodies to the hGH receptor were agonists whereas their monovalent fragments were not. Receptor dimerization occurs sequentially-a receptor binds to site 1 on hGH, and then a second receptor molecule binds to site 2 on hGH. On the basis of this sequential mechanism, which may occur in many other cytokine receptors, inactive hGH analogs were designed that were potent antagonists to hGH-induced cell proliferation. Such antagonists could be useful for treating clinical conditions of hGH excess, such as acromegaly.

  4. Computational Biology of Olfactory Receptors

    PubMed Central

    Crasto, Chiquito J.

    2011-01-01

    Olfactory receptors, in addition to being involved in first step of the physiological processes that leads to olfaction, occupy an important place in mammalian genomes. ORs constitute super families in these genomes. Elucidating ol-factory receptor function at a molecular level can be aided by a computationally derived structure and an understanding of its interactions with odor molecules. Experimental functional analyses of olfactory receptors in conjunction with computational studies serve to validate findings and generate hypotheses. We present here a review of the research efforts in: creating computational models of olfactory receptors, identifying binding strategies for these receptors with odorant molecules, performing medium to long range simulation studies of odor ligands in the receptor binding region, and identifying amino acid positions within the receptor that are responsible for ligand-binding and olfactory receptor activation. Written as a primer and a teaching tool, this review will help researchers extend the methodologies described herein to other GPCRs. PMID:21984880

  5. Synaptic Neurotransmitter-Gated Receptors

    PubMed Central

    Smart, Trevor G.; Paoletti, Pierre

    2012-01-01

    Since the discovery of the major excitatory and inhibitory neurotransmitters and their receptors in the brain, many have deliberated over their likely structures and how these may relate to function. This was initially satisfied by the determination of the first amino acid sequences of the Cys-loop receptors that recognized acetylcholine, serotonin, GABA, and glycine, followed later by similar determinations for the glutamate receptors, comprising non-NMDA and NMDA subtypes. The last decade has seen a rapid advance resulting in the first structures of Cys-loop receptors, related bacterial and molluscan homologs, and glutamate receptors, determined down to atomic resolution. This now provides a basis for determining not just the complete structures of these important receptor classes, but also for understanding how various domains and residues interact during agonist binding, receptor activation, and channel opening, including allosteric modulation. This article reviews our current understanding of these mechanisms for the Cys-loop and glutamate receptor families. PMID:22233560

  6. Molecular Basis of Kainate Receptor Modulation by Sodium

    SciTech Connect

    Plested, Andrew J.R.; Vijayan, Ranjit; Biggin, Phillip C.; Mayer, Mark L.

    2008-07-09

    Membrane proteins function in a polarized ionic environment with sodium-rich extracellular and potassium-rich intracellular solutions. Glutamate receptors that mediate excitatory synaptic transmission in the brain show unusual sensitivity to external ions, resulting in an apparent requirement for sodium in order for glutamate to activate kainate receptors. Here, we solve the structure of the Na{sup +}-binding sites and determine the mechanism by which allosteric anions and cations regulate ligand-binding dimer stability, and hence the rate of desensitization and receptor availability for gating by glutamate. We establish a stoichiometry for binding of 2 Na{sup +} to 1 Cl{sup -} and show that allosteric anions and cations bind at physically discrete sites with strong electric fields, that the binding sites are not saturated in CSF, and that the requirement of kainate receptors for Na{sup +} occurs simply because other cations bind with lower affinity and have lower efficacy compared to Na{sup +}.

  7. Multiscale Modeling of Virus Entry via Receptor-Mediated Endocytosis

    NASA Astrophysics Data System (ADS)

    Liu, Jin

    2012-11-01

    Virus infections are ubiquitous and remain major threats to human health worldwide. Viruses are intracellular parasites and must enter host cells to initiate infection. Receptor-mediated endocytosis is the most common entry pathway taken by viruses, the whole process is highly complex and dictated by various events, such as virus motions, membrane deformations, receptor diffusion and ligand-receptor reactions, occurring at multiple length and time scales. We develop a multiscale model for virus entry through receptor-mediated endocytosis. The binding of virus to cell surface is based on a mesoscale three dimensional stochastic adhesion model, the internalization (endocytosis) of virus and cellular membrane deformation is based on the discretization of Helfrich Hamiltonian in a curvilinear space using Monte Carlo method. The multiscale model is based on the combination of these two models. We will implement this model to study the herpes simplex virus entry into B78 cells and compare the model predictions with experimental measurements.

  8. Human placental calcitonin receptors.

    PubMed Central

    Nicholson, G C; D'Santos, C S; Evans, T; Moseley, J M; Kemp, B E; Michelangeli, V P; Martin, T J

    1988-01-01

    Receptors for the hypocalcaemic hormone, calcitonin (CT), have been identified in a membrane fraction prepared from term human placentae. Binding of 125I-labelled salmon CT (125I-sCT) to the membranes was time- and temperature-dependent, saturable (Bmax. 58 +/- 11 fmol/mg of protein), of high affinity (Kd 80 +/- 21 pM) and poorly reversible. Species-specific CTs and CT analogues competed for 125I-sCT binding with potencies proportional to their known biological potencies. Various unrelated peptide hormones did not compete, indicating that receptor binding was specific for CT. Photoaffinity labelling using a derivatized biologically active sCT analogue, [Arg11,18,3-nitrophenylazide-Lys14]sCT, identified a receptor component of Mr approximately 85,000, comparable with findings in osteoclasts and other target cells. The presence of CT receptors in the human placenta supports other evidence that CT may have a role in the regulation of placental function. PMID:2839149

  9. Nicotinic Receptors in Neurodegeneration

    PubMed Central

    Posadas, Inmaculada; López-Hernández, Beatriz; Ceña, Valentín

    2013-01-01

    Many studies have focused on expanding our knowledge of the structure and diversity of peripheral and central nicotinic receptors. Nicotinic acetylcholine receptors (nAChRs) are members of the Cys-loop superfamily of pentameric ligand-gated ion channels, which include GABA (A and C), serotonin, and glycine receptors. Currently, 9 alpha (α2-α10) and 3 beta (β2-β4) subunits have been identified in the central nervous system (CNS), and these subunits assemble to form a variety of functional nAChRs. The pentameric combination of several alpha and beta subunits leads to a great number of nicotinic receptors that vary in their properties, including their sensitivity to nicotine, permeability to calcium and propensity to desensitize. In the CNS, nAChRs play crucial roles in modulating presynaptic, postsynaptic, and extrasynaptic signaling, and have been found to be involved in a complex range of CNS disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, Tourette´s syndrome, anxiety, depression and epilepsy. Therefore, there is growing interest in the development of drugs that modulate nAChR functions with optimal benefits and minimal adverse effects. The present review describes the main characteristics of nAChRs in the CNS and focuses on the various compounds that have been tested and are currently in phase I and phase II trials for the treatment of neurodegenerative diseases including PD, AD and age-associated memory and mild cognitive impairment. PMID:24179465

  10. Retinoic Acid-mediated Nuclear Receptor Activation and Hepatocyte Proliferation

    PubMed Central

    Bushue, Nathan; Wan, Yu-Jui Yvonne

    2016-01-01

    Due to their well-known differentiation and apoptosis-inducing abilities, retinoic acid (RA) and its analogs have strong anti-cancer efficacy in human cancers. However, in vivo RA is a liver mitogen. While speculation has persisted that RA-mediated signaling is likely involved in hepatocyte proliferation during liver regeneration, direct evidence is still required. Findings in support of this proposition include observations that a release of retinyl palmitate (the precursor of RA) occurs in liver stellate cells following liver injury. Nevertheless, the biological action of this released vitamin A is virtually unknown. More likely is that the released vitamin A is converted to RA, the biological form, and then bound to a specific receptor (retinoid x receptor; RXRα), which is most abundantly expressed in the liver. Considering the mitogenic effects of RA, the RA-activated RXRα would likely then influence hepatocyte proliferation and liver tissue repair. At present, the mechanism by which RA stimulates hepatocyte proliferation is largely unknown. This review summarizes the activation of nuclear receptors (peroxisome proliferator activated receptor-α, pregnane x receptor, constitutive androstane receptor, and farnesoid x receptor) in an RXRα dependent manner to induce hepatocyte proliferation, providing a link between RA and its proliferative role.

  11. Spatial organization of tettigoniid auditory receptors: insights from neuronal tracing.

    PubMed

    Strauß, Johannes; Lehmann, Gerlind U C; Lehmann, Arne W; Lakes-Harlan, Reinhard

    2012-11-01

    The auditory sense organ of Tettigoniidae (Insecta, Orthoptera) is located in the foreleg tibia and consists of scolopidial sensilla which form a row termed crista acustica. The crista acustica is associated with the tympana and the auditory trachea. This ear is a highly ordered, tonotopic sensory system. As the neuroanatomy of the crista acustica has been documented for several species, the most distal somata and dendrites of receptor neurons have occasionally been described as forming an alternating or double row. We investigate the spatial arrangement of receptor cell bodies and dendrites by retrograde tracing with cobalt chloride solution. In six tettigoniid species studied, distal receptor neurons are consistently arranged in double-rows of somata rather than a linear sequence. This arrangement of neurons is shown to affect 30-50% of the overall auditory receptors. No strict correlation of somata positions between the anterio-posterior and dorso-ventral axis was evident within the distal crista acustica. Dendrites of distal receptors occasionally also occur in a double row or are even massed without clear order. Thus, a substantial part of auditory receptors can deviate from a strictly straight organization into a more complex morphology. The linear organization of dendrites is not a morphological criterion that allows hearing organs to be distinguished from nonhearing sense organs serially homologous to ears in all species. Both the crowded arrangement of receptor somata and dendrites may result from functional constraints relating to frequency discrimination, or from developmental constraints of auditory morphogenesis in postembryonic development.

  12. Why do cannabinoid receptors have more than one endogenous ligand?

    PubMed Central

    Di Marzo, Vincenzo; De Petrocellis, Luciano

    2012-01-01

    The endocannabinoid system was revealed following the understanding of the mechanism of action of marijuana's major psychotropic principle, Δ9-tetrahydrocannabinol, and includes two G-protein-coupled receptors (GPCRs; the cannabinoid CB1 and CB2 receptors), their endogenous ligands (the endocannabinoids, the best studied of which are anandamide and 2-arachidonoylglycerol (2-AG)), and the proteins that regulate the levels and activity of these receptors and ligands. However, other minor lipid metabolites different from, but chemically similar to, anandamide and 2-AG have also been suggested to act as endocannabinoids. Thus, unlike most other GPCRs, cannabinoid receptors appear to have more than one endogenous agonist, and it has been often wondered what could be the physiological meaning of this peculiarity. In 1999, it was proposed that anandamide might also activate other targets, and in particular the transient receptor potential of vanilloid type-1 (TRPV1) channels. Over the last decade, this interaction has been shown to occur both in peripheral tissues and brain, during both physiological and pathological conditions. TRPV1 channels can be activated also by another less abundant endocannabinoid, N-arachidonoyldopamine, but not by 2-AG, and have been proposed by some authors to act as ionotropic endocannabinoid receptors. This article will discuss the latest discoveries on this subject, and discuss, among others, how anandamide and 2-AG differential actions at TRPV1 and cannabinoid receptors contribute to making this signalling system a versatile tool available to organisms to fine-tune homeostasis. PMID:23108541

  13. Rabbit alveolar beta-adrenergic receptors increase with gestational age.

    PubMed

    Lewis, V; Goldfien, A C; Day, J P; Roberts, J M

    1990-01-01

    Pulmonary beta-adrenergic receptors, which mediate the actions of endogenous catecholamines, increase before birth, an important step in pulmonary maturation. This increase, which occurs primarily in the alveoli, may be hastened by corticosteroids. However, because the lung is composed of more than 40 cell types, we asked whether the normal distribution of beta-adrenergic receptors changes with gestational age in a way that seems physiologically relevant. We compared lungs from fetal rabbits at 26 and 31 days' gestation with lungs from adult rabbits by autoradiography with 125iodocyanopindolol, a beta-adrenergic antagonist. While the total silver grain concentration increased during gestation, the greatest proportional increase occurred in the alveoli. We conclude that pulmonary beta-adrenergic receptor concentration increases during gestation and that this increase is most dramatic for alveoli. This pattern is consistent with that previously observed after treatment of fetal rabbits in utero with corticosteroids.

  14. Modulation of neuritogenesis by astrocyte muscarinic receptors.

    PubMed

    Guizzetti, Marina; Moore, Nadia H; Giordano, Gennaro; Costa, Lucio G

    2008-11-14

    Astrocytes have been shown to release factors that have promoting or inhibiting effects on neuronal development. However, mechanisms controlling the release of such factors from astrocytes are not well established. Astrocytes express muscarinic receptors whose activation stimulates a robust intracellular signaling, although the role of these receptors in glial cells is not well understood. Acetylcholine and acetylcholine receptors are present in the brain before synaptogenesis occurs and are believed to be involved in neuronal maturation. The present study was undertaken to investigate whether stimulation of muscarinic receptors in astrocytes would modulate neurite outgrowth in hippocampal neurons. Rat hippocampal neurons, co-cultured with rat cortical astrocytes previously exposed to the cholinergic agonist carbachol, displayed longer neurites. The effect of carbachol in astrocytes was due to the activation of M3 muscarinic receptors. Exposure of astrocytes to carbachol increased the expression of the extracellular matrix proteins fibronectin and laminin-1 in these cells. This effect was mediated in part by an increase in laminin-1 and fibronectin mRNA levels and in part by the up-regulation of the production and release of plasminogen activator inhibitor-1, an inhibitor of the proteolytic degradation of the extracellular matrix. The inhibition of fibronectin activity strongly reduced the effect of carbachol on the elongation of all the neurites, whereas inhibition of laminin-1 activity reduced the elongation of minor neurites only. Plasminogen activator inhibitor-1 also induced neurite elongation through a direct effect on neurons. Taken together, these results demonstrate that cholinergic muscarinic stimulation of astrocytes induces the release of permissive factors that accelerate neuronal development.

  15. Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes

    PubMed Central

    1983-01-01

    At 4 degrees C transferrin bound to receptors on the reticulocyte plasma membrane, and at 37 degrees C receptor-mediated endocytosis of transferrin occurred. Uptake at 37 degrees C exceeded binding at 4 degrees C by 2.5-fold and saturated after 20-30 min. During uptake at 37 degrees C, bound transferrin was internalized into a trypsin- resistant space. Trypsinization at 4 degrees C destroyed surface receptors, but with subsequent incubation at 37 degrees C, surface receptors rapidly appeared (albeit in reduced numbers), and uptake occurred at a decreased level. After endocytosis, transferrin was released, apparently intact, into the extracellular space. At 37 degrees C colloidal gold-transferrin (AuTf) clustered in coated pits and then appeared inside various intracellular membrane-bounded compartments. Small vesicles and tubules were labeled after short (5-10 min) incubations at 37 degrees C. Larger multivesicular endosomes became heavily labeled after longer (20-35 min) incubations. Multivesicular endosomes apparently fused with the plasma membrane and released their contents by exocytosis. None of these organelles appeared to be lysosomal in nature, and 98% of intracellular AuTf was localized in acid phosphatase-negative compartments. AuTf, like transferrin, was released with subsequent incubation at 37 degrees C. Freeze-dried and freeze-fractured reticulocytes confirmed the distribution of AuTf in reticulocytes and revealed the presence of clathrin-coated patches amidst the spectrin coating the inner surface of the plasma membrane. These data suggest that transferrin is internalized via coated pits and vesicles and demonstrate that transferrin and its receptor are recycled back to the plasma membrane after endocytosis. PMID:6309857

  16. Cell Transmembrane Receptors Determine Tissue Pattern Stability

    NASA Astrophysics Data System (ADS)

    Beyer, Tilo; Meyer-Hermann, Michael

    2008-10-01

    The analysis of biological systems requires mathematical tools that represent their complexity from the molecular scale up to the tissue level. The formation of cell aggregates by chemotaxis is investigated using Delaunay object dynamics. It is found that when cells migrate fast such that the chemokine distribution is far from equilibrium, the details of the chemokine receptor dynamics can induce an internalization driven instability of cell aggregates. The instability occurs in a parameter regime relevant for lymphoid tissue and is similar to ectopic lymphoid structures.

  17. Cholinergic muscarinic receptors in rat cochlea.

    PubMed

    van Megen, Y J; Klaassen, A B; Rodrigues de Miranda, J F; Kuijpers, W

    1988-11-22

    Specific 3H-1-quinuclidinylbenzilate (3H-1-QNB) binding to rat cochlea homogenates occurs to a homogeneous class of binding sites with Kd = 0.13 +/- 0.01 nM and Bmax = 0.57 +/- 0.07 fmol per cochlea. Binding is stereoselectively inhibited by benzetimide enantiomers. Dexetimide was more effective than levetimide in displacing 3H-1-QNB from its binding sites (Ki = 4 x 10(-10) M and 6.5 x 10(-6) M, respectively). Pirenzepine inhibits 3H-1-QNB binding with low affinity (Ki = 2 x 10(-6) M), classifying the binding sites as muscarinic M2 receptors. PMID:3214711

  18. Palmitoylethanolamide, a naturally occurring lipid, is an orally effective intestinal anti-inflammatory agent

    PubMed Central

    Borrelli, Francesca; Romano, Barbara; Petrosino, Stefania; Pagano, Ester; Capasso, Raffaele; Coppola, Diana; Battista, Giovanni; Orlando, Pierangelo; Di Marzo, Vincenzo; Izzo, Angelo A

    2015-01-01

    BACKGROUND AND PURPOSE Palmitoylethanolamide (PEA) acts via several targets, including cannabinoid CB1 and CB2 receptors, transient receptor potential vanilloid type-1 (TRPV1) ion channels, peroxisome proliferator-activated receptor alpha (PPAR α) and orphan G protein-coupled receptor 55 (GRR55), all involved in the control of intestinal inflammation. Here, we investigated the effect of PEA in a murine model of colitis. EXPERIMENTAL APPROACH Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Inflammation was assessed by evaluating inflammatory markers/parameters and by histology; intestinal permeability by a fluorescent method; colonic cell proliferation by immunohistochemistry; PEA and endocannabinoid levels by liquid chromatography mass spectrometry; receptor and enzyme mRNA expression by quantitative RT-PCR. KEY RESULTS DNBS administration caused inflammatory damage, increased colonic levels of PEA and endocannabinoids, down-regulation of mRNA for TRPV1 and GPR55 but no changes in mRNA for CB1, CB2 and PPARα. Exogenous PEA (i.p. and/or p.o., 1 mg·kg−1) attenuated inflammation and intestinal permeability, stimulated colonic cell proliferation, and increased colonic TRPV1 and CB1 receptor expression. The anti-inflammatory effect of PEA was attenuated or abolished by CB2 receptor, GPR55 or PPARα antagonists and further increased by the TRPV1 antagonist capsazepine. CONCLUSIONS AND IMPLICATIONS PEA improves murine experimental colitis, the effect being mediated by CB2 receptors, GPR55 and PPARα, and modulated by TRPV1 channels. PMID:25205418

  19. Histamine H3 receptors--general characterization and their function in the cardiovascular system.

    PubMed

    Malinowska, B; Godlewski, G; Schlicker, E

    1998-06-01

    The histamine H3 receptor was initially identified as a presynaptic autoreceptor controlling histamine release and synthesis in the brain. It belongs to the superfamily of G protein-coupled receptors. The existence of the H3 receptor which has not yet been cloned was definitely established by the design of highly potent and selective agonists (R-(-)-alpha-methylhistamine, imetit) and antagonists (thioperamide, clobenpropit). These receptors also occur as heteroreceptors both in the central nervous system and on peripheral neurons of the gastrointestinal and bronchial tract, where they regulate the release of a variety of neurotransmitters. In the cardiovascular system, histamine H3 receptors are mainly located presynaptically on the postganglionic sympathetic nerve fibers innervating the blood vessels and the heart. Their activation leads to the inhibition of noradrenaline release and consequently to the reduction of the neurogenic vasopressor and cardiostimulatory responses. The presence of such receptors has been shown both in vitro (human, pig, guinea-pig, rabbit, rat isolated tissues) and in vivo (rat, guinea-pig). The vascular and cardiac presynaptic H3 receptors may be activated by endogenous histamine. The vascular H3 receptors appear to be operative in hypertension and interact with presynaptic alpha 2-adrenoceptors. Postsynaptic vasodilatatory H3 receptors have been detected in several vascular beds as well. H3 receptor ligands affect basal cardiovascular parameters in conscious and anesthetized guinea-pigs but not rats. Presynaptic H3 receptors may play a role in the pathophysiology of headache and cardiac ischemia.

  20. The role of mu opioid receptor desensitization and endocytosis in morphine tolerance and dependence.

    PubMed

    Martini, Lene; Whistler, Jennifer L

    2007-10-01

    Following activation, most G protein coupled receptors undergo regulation by a cascade of events that promote receptor desensitization and endocytosis. Following endocytosis, receptors can then be recycled to the plasma membrane, retained in an intracellular compartment, or targeted for degradation. For receptors that are recycled, like the mu opioid receptor (MOR), endocytosis serves as the first step toward resensitizing receptors. For receptors that are degraded, endocytosis serves as the first step toward receptor downregulation. Thus, for receptors like the MOR, the desensitization-endocytosis-resensitization cycle serves as a rapid and dynamic means to titrate signaling through the receptor. However, not all agonist ligands at the MOR promote the same degree of receptor desensitization and endocytosis. For example, the endogenous peptide ligands at the MOR induce rapid desensitization, endocytosis, and recycling. By contrast, morphine induces only weak or partial desensitization and little to no endocytosis. As a consequence, signal transduction promoted by morphine is less dynamic than that induced by endogenous ligands as well as other opioid agonists that promote endocytosis. The resulting imbalance of desensitization-endocytosis-resensitization has at least two consequences: (1) in cell types where morphine induces desensitization but not endocytosis and/or resensitization, desensitization is protracted; (2) in cell types where morphine induces neither desensitization nor endocytosis, prolonged signaling through the receptor leads to multiple cellular adaptations downstream of receptor-G protein coupling. Both protracted desensitization and adaptive cellular changes probably contribute to the pronounced in vivo tolerance and dependence that occur with chronic morphine treatment. As a consequence, facilitating receptor endocytosis, using either genetic or pharmacological approaches, can restore the balance of signaling through the receptor and affect the

  1. Neuropharmacology of the Naturally Occurring κ-Opioid Hallucinogen Salvinorin A

    PubMed Central

    Cunningham, Christopher W.; Rothman, Richard B.

    2011-01-01

    Salvia divinorum is a perennial sage native to Oaxaca, Mexico, that has been used traditionally in divination rituals and as a treatment for the “semimagical” disease panzón de borrego. Because of the intense “out-of-body” experiences reported after inhalation of the pyrolized smoke, S. divinorum has been gaining popularity as a recreational hallucinogen, and the United States and several other countries have regulated its use. Early studies isolated the neoclerodane diterpene salvinorin A as the principal psychoactive constituent responsible for these hallucinogenic effects. Since the finding that salvinorin A exerts its potent psychotropic actions through the activation of KOP receptors, there has been much interest in elucidating the underlying mechanisms behind its effects. These effects are particularly remarkable, because 1) salvinorin A is the first reported non-nitrogenous opioid receptor agonist, and 2) its effects are not mediated by the 5-HT2A receptor, the classic target of hallucinogens such as lysergic acid diethylamide and mescaline. Rigorous investigation into the structural features of salvinorin A responsible for opioid receptor affinity and selectivity has produced numerous receptor probes, affinity labels, and tools for evaluating the biological processes responsible for its observed psychological effects. Salvinorin A has therapeutic potential as a treatment for pain, mood and personality disorders, substance abuse, and gastrointestinal disturbances, and suggests that nonalkaloids are potential scaffolds for drug development for aminergic G-protein coupled receptors. PMID:21444610

  2. Diversification of TAM receptor function

    PubMed Central

    Zagórska, Anna; Través, Paqui G.; Lew, Erin D.; Dransfield, Ian; Lemke, Greg

    2014-01-01

    Apoptotic cell clearance is critical for both tissue homeostasis and the resolution of inflammation. We found that the TAM receptor tyrosine kinases Axl and Mer played distinct roles as phagocytic receptors in these two settings, where they exhibited divergent expression, regulation, and activity. Mer acted as a tolerogenic receptor in resting macrophages and in settings of immune suppression. Conversely, Axl was an inflammatory response receptor whose expression was induced by pro-inflammatory stimuli. Axl and Mer displayed distinct ligand specificities, ligand-receptor complex formation in tissues, and receptor shedding upon activation. These differences notwithstanding, phagocytosis by either protein was strictly dependent on receptor activation that was triggered by bridging TAM receptor–ligand complexes to the ‘eat-me’ signal phosphatidylserine on apoptotic cell surfaces. PMID:25194421

  3. Interactions between 3,4-methylenedioxymethamphetamine and σ1 Receptors

    PubMed Central

    Brammer, Matthew K.; Gilmore, Deborah L.; Matsumoto, Rae R.

    2006-01-01

    Methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) are structurally similar and represent a serious and growing health threat. Earlier studies in our laboratory have shown that methamphetamine interacts with σ receptors and that antagonism of these receptors can attenuate methamphetamine-induced locomotor stimulation and neurotoxicity. However, no research exists which characterizes the interaction between σ receptors and MDMA. Therefore, the goal of the present study was to determine whether σ receptors are involved in the actions of MDMA. In the first part of the study, competition and saturation binding assays were performed to measure the interaction of MDMA with σ receptors. The receptor binding assays revealed that MDMA interacts preferentially with the σ1 subtype, as compared to the σ2 subtype, and that this interaction occurs in a competitive manner. The second part of the study focused on behavioral measurements in male, Swiss Webster mice to determine whether a selective σ1 receptor antagonist, BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine, 0-30 mg/kg, i.p.) could attenuate the locomotor stimulant actions of MDMA (0-50 mg/kg, i.p.). BD1063 alone had no effect on locomotor activity, but dose-dependently attenuated the locomotor stimulant effects of (+)-MDMA and produced a significant shift to the right in the MDMA dose response curve. Together, the data support the functional relevance of the interaction of MDMA with σ1 receptors, and suggest that these receptors are involved in the stimulant actions of MDMA. PMID:17070798

  4. Pharmacology of the Adenosine A3 Receptor in the Vasculature and Essential Hypertension

    PubMed Central

    Ho, Ming-Fen; Low, Leanne M.; Rose’Meyer, Roselyn B.

    2016-01-01

    Background Essential hypertension is considered to be a multifactorial disorder and its aetiology has yet to be clearly identified. As the adenosine receptors have a significant role in mediating vasodilation, alterations in their structures or signalling pathways may be involved in the development of hypertension. This study aimed to measure the expression of adenosine A3 receptors in a range of cardiovascular tissues and determine whether they could be altered with essential hypertension, and to functionally test responses to adenosine A3 receptor agonists in coronary blood vessels using the isolated perfused heart preparation. Methods mRNA samples from cardiovascular tissues and a range of blood vessels were collected from 10 week old male spontaneously hypertensive rats and age-gender matched Wistar rats (n = 8). The Langendorff heart perfusion preparation was used to characterise adenosine A3 receptor mediated coronary vasodilation in the rat heart. Results Adenosine A3 receptor agonists induced coronary vasodilation. The expression of adenosine A3 receptors in cardiovascular tissues was altered in a tissue-specific pattern. Specifically, down-regulation of adenosine A3 receptor expression occurred in hypertensive hearts, which might be associated with attenuated vasodilator responses observed in coronary vessels to adenosine A3 receptor agonists. Conclusions This study demonstrated alterations in the expression of adenosine A3 receptors occurred in a tissue specific mode, and reduced adenosine A3 receptor mediated coronary vasodilation in hearts from spontaneously hypertensive rats. Our findings with regard to changes in the adenosine A3 receptor in hypertensive hearts suggest that adenosine A3 receptor might play a role in the physiopathology of essential hypertension and potentially open the way to pharmacologic manipulation of vasomotor activity by the use of adenosine A3 receptor agonists. PMID:26907173

  5. Contribution of Schwann Cells to Remyelination in a Naturally Occurring Canine Model of CNS Neuroinflammation.

    PubMed

    Kegler, Kristel; Spitzbarth, Ingo; Imbschweiler, Ilka; Wewetzer, Konstantin; Baumgärtner, Wolfgang; Seehusen, Frauke

    2015-01-01

    Gliogenesis under pathophysiological conditions is of particular clinical relevance since it may provide evidence for regeneration promoting cells recruitable for therapeutic purposes. There is evidence that neurotrophin receptor p75 (p75NTR)-expressing cells emerge in the lesioned CNS. However, the phenotype and identity of these cells, and signals triggering their in situ generation under normal conditions and certain pathological situations has remained enigmatic. In the present study, we used a spontaneous, idiopathic and inflammatory CNS condition in dogs with prominent lympho-histiocytic infiltration as a model to study the phenotype of Schwann cells and their relation to Schwann cell remyelination within the CNS. Furthermore, the phenotype of p75NTR-expressing cells within the injured CNS was compared to their counter-part in control sciatic nerve and after peripheral nerve injury. In addition, organotypic slice cultures were used to further elucidate the origin of p75NTR-positive cells. In cerebral and cerebellar white and grey matter lesions as well as in the brain stem, p75NTR-positive cells co-expressed the transcription factor Sox2, but not GAP-43, GFAP, Egr2/Krox20, periaxin and PDGFR-α. Interestingly, and contrary to the findings in control sciatic nerves, p75NTR-expressing cells only co-localized with Sox2 in degenerative neuropathy, thus suggesting that such cells might represent dedifferentiated Schwann cells both in the injured CNS and PNS. Moreover, effective Schwann cell remyelination represented by periaxin- and P0-positive mature myelinating Schwann cells, was strikingly associated with the presence of p75NTR/Sox2-expressing Schwann cells. Intriguingly, the emergence of dedifferentiated Schwann cells was not affected by astrocytes, and a macrophage-dominated inflammatory response provided an adequate environment for Schwann cells plasticity within the injured CNS. Furthermore, axonal damage was reduced in brain stem areas with p75NTR/Sox2

  6. Early detection of hepatocellular carcinoma co-occurring with hepatitis C virus infection: A mathematical model

    PubMed Central

    Zekri, Abdel-Rahman Nabawy; Youssef, Amira Salah El-Din; Bakr, Yasser Mabrouk; Gabr, Reham Mohamed; Ahmed, Ola Sayed; Elberry, Mostafa Hamed; Mayla, Ahmed Mahmoud; Abouelhoda, Mohamed; Bahnassy, Abeer A

    2016-01-01

    AIM: To develop a mathematical model for the early detection of hepatocellular carcinoma (HCC) with a panel of serum proteins in combination with α-fetoprotein (AFP). METHODS: Serum levels of interleukin (IL)-8, soluble intercellular adhesion molecule-1 (sICAM-1), soluble tumor necrosis factor receptor II (sTNF-RII), proteasome, and β-catenin were measured in 479 subjects categorized into four groups: (1) HCC concurrent with hepatitis C virus (HCV) infection (n = 192); (2) HCV related liver cirrhosis (LC) (n = 96); (3) Chronic hepatitis C (CHC) (n = 96); and (4) Healthy controls (n = 95). The R package and different modules for binary and multi-class classifiers based on generalized linear models were used to model the data. Predictive power was used to evaluate the performance of the model. Receiver operating characteristic curve analysis over pairs of groups was used to identify the best cutoffs differentiating the different groups. RESULTS: We revealed mathematical models, based on a binary classifier, made up of a unique panel of serum proteins that improved the individual performance of AFP in discriminating HCC patients from patients with chronic liver disease either with or without cirrhosis. We discriminated the HCC group from the cirrhotic liver group using a mathematical model (-11.3 + 7.38 × Prot + 0.00108 × sICAM + 0.2574 × β-catenin + 0.01597 × AFP) with a cutoff of 0.6552, which achieved 98.8% specificity and 89.1% sensitivity. For the discrimination of the HCC group from the CHC group, we used a mathematical model [-10.40 + 1.416 × proteasome + 0.002024 × IL + 0.004096 × sICAM-1 + (4.251 × 10-4) × sTNF + 0.02567 × β-catenin + 0.02442 × AFP] with a cutoff 0.744 and achieved 96.8% specificity and 89.7% sensitivity. Additionally, we derived an algorithm, based on a binary classifier, for resolving the multi-class classification problem by using three successive mathematical model predictions of liver disease status. CONCLUSION: Our

  7. Taste Receptor Genes

    PubMed Central

    Bachmanov, Alexander A.; Beauchamp, Gary K.

    2009-01-01

    In the past several years, tremendous progress has been achieved with the discovery and characterization of vertebrate taste receptors from the T1R and T2R families, which are involved in recognition of bitter, sweet, and umami taste stimuli. Individual differences in taste, at least in some cases, can be attributed to allelic variants of the T1R and T2R genes. Progress with understanding how T1R and T2R receptors interact with taste stimuli and with identifying their patterns of expression in taste cells sheds light on coding of taste information by the nervous system. Candidate mechanisms for detection of salts, acids, fat, complex carbohydrates, and water have also been proposed, but further studies are needed to prove their identity. PMID:17444812

  8. TSH RECEPTOR AUTOANTIBODIES

    PubMed Central

    Michalek, Krzysztof; Morshed, Syed A.; Latif, Rauf; Davies, Terry F.

    2009-01-01

    Thyrotropin receptor autoantibodies (TSHR-Abs) of the stimulating variety are the hallmark of Graves’ disease. The presence of immune defects leading to synthesis of TSHR-Abs causes hyperthyroidism and is associated with other extrathyroidal manifestations. Further characterization of these antibodies has now been made possible by the generation of monoclonal antibodies with this unique stimulating capacity as well as similar TSHR-Abs not associated with hyperthyroidism. Their present classification divides TSHR-Abs into stimulating, blocking (competing with TSH binding) and neutral (no signaling). Recent studies using monoclonal TSHR-Abs has revealed that stimulating and blocking antibodies bind to the receptor using mostly conformational epitopes, whilst neutral antibodies utilize exclusively linear peptides. Subtle differences in epitopes for stimulating and blocking antibodies account for the diversity of their biological actions. Recently non-classical signaling elicited by neutral antibodies has also been described, raising the need for a new classification of TSHR-Abs. PMID:19332151

  9. The interleukin-4 receptor: signal transduction by a hematopoietin receptor.

    PubMed

    Keegan, A D; Pierce, J H

    1994-02-01

    Over the last several years, the receptors for numerous cytokines have been molecularly characterized. Analysis of their amino acid sequences shows that some of these receptors bear certain motifs in their extracellular domains that define a family of receptors called the Hematopoietin receptor superfamily. Significant advances in characterizing the structure, function, and mechanisms of signal transduction have been made for several members of this family. The purpose of this review is to discuss the recent advances made for one of the family members, the interleukin (IL) 4 receptor. Other receptor systems have recently been reviewed elsewhere. The IL-4 receptor consists of, at the minimum, the cloned 140 kDa IL-4-binding chain with the potential for associating with other chains. The IL-4 receptor transduces its signal by activating a tyrosine kinase that phosphorylates cellular substrates, including the receptor itself, and the 170 kDa substrate called 4PS. Phosphorylated 4PS interacts with the SH2 domain of the enzyme PI-3'-kinase and increases its enzymatic activity. These early events in the IL-4 receptor initiated signaling pathway may trigger a series of signals that will ultimately lead to an IL-4 specific biologic outcome.

  10. Quantitative receptor autoradiography

    SciTech Connect

    Boast, C.A.; Snowhill, E.W.; Altar, C.A.

    1986-01-01

    Quantitative receptor autoradiography addresses the topic of technical and scientific advances in the sphere of quantitative autoradiography. The volume opens with a overview of the field from a historical and critical perspective. Following is a detailed discussion of in vitro data obtained from a variety of neurotransmitter systems. The next section explores applications of autoradiography, and the final two chapters consider experimental models. Methodological considerations are emphasized, including the use of computers for image analysis.

  11. Receptors for enterovirus 71

    PubMed Central

    Yamayoshi, Seiya; Fujii, Ken; Koike, Satoshi

    2014-01-01

    Enterovirus 71 (EV71) is one of the major causative agents of hand, foot and mouth disease (HFMD). Occasionally, EV71 infection is associated with severe neurological diseases, such as acute encephalitis, acute flaccid paralysis and cardiopulmonary failure. Several molecules act as cell surface receptors that stimulate EV71 infection, including scavenger receptor B2 (SCARB2), P-selectin glycoprotein ligand-1 (PSGL-1), sialylated glycan, heparan sulfate and annexin II (Anx2). SCARB2 plays critical roles in attachment, viral entry and uncoating, and it can facilitate efficient EV71 infection. The three-dimensional structures of the mature EV71 virion, procapsid and empty capsid, as well as the exofacial domain of SCARB2, have been elucidated. This structural information has greatly increased our understanding of the early steps of EV71 infection. Furthermore, SCARB2 plays essential roles in the development of EV71 neurological disease in vivo. Adult mice are not susceptible to infection by EV71, but transgenic mice that express human SCARB2 become susceptible to EV71 infection and develop similar neurological diseases to those found in humans. This mouse model facilitates the in vivo investigation of many issues related to EV71. PSGL-1, sialylated glycan, heparan sulfate and Anx2 are attachment receptors, which enhance viral infection by retaining the virus on the cell surface. These molecules also contribute to viral infection in vitro either by interacting with SCARB2 or independently of SCARB2. However, the cooperative effects of these receptors, and their contribution to EV71 pathogenicity in vivo, remain to be elucidated. PMID:26038749

  12. Distinct Phosphorylation Clusters Determine the Signaling Outcome of Free Fatty Acid Receptor 4/G Protein-Coupled Receptor 120.

    PubMed

    Prihandoko, Rudi; Alvarez-Curto, Elisa; Hudson, Brian D; Butcher, Adrian J; Ulven, Trond; Miller, Ashley M; Tobin, Andrew B; Milligan, Graeme

    2016-05-01

    It is established that long-chain free fatty acids includingω-3 fatty acids mediate an array of biologic responses through members of the free fatty acid (FFA) receptor family, which includes FFA4. However, the signaling mechanisms and modes of regulation of this receptor class remain unclear. Here, we employed mass spectrometry to determine that phosphorylation of mouse (m)FFAR4 occurs at five serine and threonine residues clustered in two separable regions of the C-terminal tail, designated cluster 1 (Thr(347), Thr(349), and Ser(350)) and cluster 2 (Ser(357)and Ser(361)). Mutation of these phosphoacceptor sites to alanine completely prevented phosphorylation of mFFA4 but did not limit receptor coupling to extracellular signal regulated protein kinase 1 and 2 (ERK1/2) activation. Rather, an inhibitor of Gq/11proteins completely prevented receptor signaling to ERK1/2. By contrast, the recruitment of arrestin 3, receptor internalization, and activation of Akt were regulated by mFFA4 phosphorylation. The analysis of mFFA4 phosphorylation-dependent signaling was extended further by selective mutations of the phosphoacceptor sites. Mutations within cluster 2 did not affect agonist activation of Akt but instead significantly compromised receptor internalization and arrestin 3 recruitment. Distinctly, mutation of the phosphoacceptor sites within cluster 1 had no effect on receptor internalization and had a less extensive effect on arrestin 3 recruitment but significantly uncoupled the receptor from Akt activation. These unique observations define differential effects on signaling mediated by phosphorylation at distinct locations. This hallmark feature supports the possibility that the signaling outcome of mFFA4 activation can be determined by the pattern of phosphorylation (phosphorylation barcode) at the C terminus of the receptor.

  13. [Lipoprotein receptors. Old acquaintances and newcomers].

    PubMed

    Ducobu, J

    1997-02-01

    Lipoprotein receptors are plasma membrane proteins of high affinity which interact with circulating lipoprotein particles. The well characterized LDL receptor continues to be analysed and some new findings on its intracellular mechanisms of action have emerged. New lipoprotein receptors have recently been described: the chylomicron remnant receptor or LDL-related protein (LRP), the lipolysis stimulated receptor (LSR), the very low density lipoprotein receptor (VLDLR), the HDL receptor (HDLR) and the scavenger receptor (SR). The molecular details of the receptors will facilitate the development of new therapeutic means to improve receptor-mediated clearance of lipoproteins.

  14. Liver X Receptor and Peroxisome Proliferator-Activated Receptor Agonist from Cornus alternifolia

    PubMed Central

    He, Yang-Qing; Ma, Guo-Yi; Peng, Jiang-nan; Ma, Zhan-Ying; Hamann, Mark T.

    2012-01-01

    Background Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptors superfamily and are transcription factors activated by specific ligands. Liver X receptors (LXR) belong to the nuclear hormone receptors and have been shown to play an important role in cholesterol homeostasis. From the previous screening of several medicinal plants for potential partial PPARγ agonists, the extracts of Cornus alternifolia were found to exhibit promising bioactivity. In this paper, we report the isolation and structural elucidation of four new compounds and their potential as ligands for PPAR. Methods The new compounds were extracted from the leaves of Cornus alternifolia and fractionated by high-performance liquid chromatography. Their structures were elucidated on the basis of spectroscopic evidence and analysis of their hydrolysis products. Results Three new iridoid glycosides including an iridolactone, alternosides A-C (1–3), a new megastigmane glycoside, cornalternoside (4) and 10 known compounds, were obtained from the leaves of Cornus alternifolia. Kaempferol-3-O-β-glucopyranoside (5) exhibited potent agonistic activities for PPARα, PPARγ and LXR with EC50 values of 0.62, 3.0 and 1.8 μ M, respectively. Conclusions We isolated four new and ten known compounds from Cornus alternifolia, and one known compound showed agonistic activities for PPARα, PPARγ and LXR. General significance Compound 1 is the first example of a naturally occurring iridoid glycoside containing a β-glucopyranoside moiety at C-6. PMID:22353334

  15. Fibroblast growth factor receptors, developmental corruption and malignant disease.

    PubMed

    Kelleher, Fergal C; O'Sullivan, Hazel; Smyth, Elizabeth; McDermott, Ray; Viterbo, Antonella

    2013-10-01

    Fibroblast growth factors (FGF) are a family of ligands that bind to four different types of cell surface receptor entitled, FGFR1, FGFR2, FGFR3 and FGFR4. These receptors differ in their ligand binding affinity and tissue distribution. The prototypical receptor structure is that of an extracellular region comprising three immunoglobulin (Ig)-like domains, a hydrophobic transmembrane segment and a split intracellular tyrosine kinase domain. Alternative gene splicing affecting the extracellular third Ig loop also creates different receptor isoforms entitled FGFRIIIb and FGFRIIIc. Somatic fibroblast growth factor receptor (FGFR) mutations are implicated in different types of cancer and germline FGFR mutations occur in developmental syndromes particularly those in which craniosynostosis is a feature. The mutations found in both conditions are often identical. Many somatic FGFR mutations in cancer are gain-of-function mutations of established preclinical oncogenic potential. Gene amplification can also occur with 19-22% of squamous cell lung cancers for example having amplification of FGFR1. Ontologic comparators can be informative such as aberrant spermatogenesis being implicated in both spermatocytic seminomas and Apert syndrome. The former arises from somatic FGFR3 mutations and Apert syndrome arises from germline FGFR2 mutations. Finally, therapeutics directed at inhibiting the FGF/FGFR interaction are a promising subject for clinical trials.

  16. Modeling multivalent ligand-receptor interactions with steric constraints on configurations of cell surface receptor aggregates

    SciTech Connect

    Monine, Michael; Posner, Richard; Savage, Paul; Faeder, James; Hlavacek, William S

    2008-01-01

    Signal transduction generally involves multivalent protein-protein interactions, which can produce various protein complexes and post-translational modifications. The reaction networks that characterize these interactions tend to be so large as to challenge conventional simulation procedures. To address this challenge, a kinetic Monte Carlo (KMC) method has been developed that can take advantage of a model specification in terms of reaction rules for molecular interactions. A set of rules implicitly defines the reactions that can occur as a result of the interactions represented by the rules. With the rule-based KMC method, explicit generation of the underlying chemical reaction network implied by rules is avoided. Here, we apply and extend this method to characterize the interactions of a trivalent ligand with a bivalent cell-surface receptor. This system is also studied experimentally. We consider the following kinetic models: an equivalent-site model, an extension of this model, which takes into account steric constraints on the configurations of receptor aggregates, and finally, a model that accounts for cyclic receptor aggregates. Simulation results for the equivalent-site model are consistent with an equilibrium continuum model. Using these models, we investigate the effects of steric constraints and the formation of cyclic aggregates on the kinetics and equilibria of small and large aggregate formation and the percolation phase transition that occurs in this system.

  17. Receptor binding properties of amperozide.

    PubMed

    Svartengren, J; Simonsson, P

    1990-01-01

    The receptor pharmacology of amperozide was investigated with in vitro radioligand binding technique. Amperozide possessed a high affinity to the 5-HT2 receptors (Ki = 16.5 +/- 2.1 nM) and a moderate affinity to alpha 1-adrenergic receptors of rat cerebral cortical membranes (Ki = 172 +/- 14 nM). The affinity of amperozide for striatal and limbic dopamine D2 receptors was low and not significantly different (Ki +/- S.E.M. = 540 +/- 59 nM vs 403 +/- 42 nM; p less than 0.11, n = 4). The affinity for striatal and limbic 5-HT2 receptors was measured as well and found to be very close to the affinity to the cerebral cortical 5-HT2 receptor. The drug affinity for D2 and 5-HT2 receptors seems thus not to be influenced by the location of the receptor moiety. The affinity for several other rat brain receptors such as 5-HT1A, alpha 2-adrenergic, dopamine D1, muscarinic M1 and M2, opiate sigma and beta 2-adrenergic was low. The pseudo-Hill coefficient of the amperozide competition binding curve was consistently higher than one indicating antagonistic and complex interactions with the 5-HT2 receptor or with alpha 1-adrenergic and dopamine D2 receptors. The antagonistic properties of amperozide were investigated by its ability to antagonize the serotonin-induced formation of inositol-1-phosphate in human blood platelets. Amperozide inhibited this 5-HT2 receptor-mediated intracellular response with similar potency as ketanserin. These results suggest that amperozide is a selective 5-HT2 receptor antagonist.

  18. Identification of Phosphorylation Sites Regulating sst3 Somatostatin Receptor Trafficking.

    PubMed

    Lehmann, Andreas; Kliewer, Andrea; Günther, Thomas; Nagel, Falko; Schulz, Stefan

    2016-06-01

    The human somatostatin receptor 3 (sst3) is expressed in about 50% of all neuroendocrine tumors and hence a promising target for multireceptor somatostatin analogs. The sst3 receptor is unique among ssts in that it exhibits a very long intracellular C-terminal tail containing a huge number of potential phosphate acceptor sites. Consequently, our knowledge about the functional role of the C-terminal tail in sst3 receptor regulation is very limited. Here, we have generated a series of phosphorylation-deficient mutants that enabled us to determine crucial sites for its agonist-induced β-arrestin mobilization, internalization, and down-regulation. Based on this information, we generated phosphosite-specific antibodies for C-terminal Ser(337)/Thr(341), Thr(348), and Ser(361) that enabled us to investigate the temporal patterns of sst3 phosphorylation and dephosphorylation. We found that the endogenous ligand somatostatin induced a rapid and robust phosphorylation that was completely blocked by the sst3 antagonist NVP-ACQ090. The stable somatostatin analogs pasireotide and octreotide promoted clearly less phosphorylation compared with somatostatin. We also show that sst3 phosphorylation occurred within seconds to minutes, whereas dephosphorylation of the sst3 receptor occurred at a considerable slower rate. In addition, we also identified G protein-coupled receptor kinases 2 and 3 and protein phosphatase 1α and 1β as key regulators of sst3 phosphorylation and dephosphorylation, respectively. Thus, we here define the C-terminal phosphorylation motif of the human sst3 receptor that regulates its agonist-promoted phosphorylation, β-arrestin recruitment, and internalization of this clinically relevant receptor.

  19. Increased baseline occupancy of D2 receptors by dopamine in schizophrenia

    PubMed Central

    Abi-Dargham, Anissa; Rodenhiser, Janine; Printz, David; Zea-Ponce, Yolanda; Gil, Roberto; Kegeles, Lawrence S.; Weiss, Richard; Cooper, Thomas B.; Mann, J. John; Van Heertum, Ronald L.; Gorman, Jack M.; Laruelle, Marc

    2000-01-01

    The classical dopamine hypothesis of schizophrenia postulates a hyperactivity of dopaminergic transmission at the D2 receptor. We measured in vivo occupancy of striatal D2 receptors by dopamine in 18 untreated patients with schizophrenia and 18 matched controls, by comparing D2 receptor availability before and during pharmacologically induced acute dopamine depletion. Acute depletion of intrasynaptic dopamine resulted in a larger increase in D2 receptor availability in patients with schizophrenia (19% ± 11%) compared with control subjects (9% ± 7%, P = 0.003). The increased occupancy of D2 receptors by dopamine occurred both in first-episode neuroleptic-naive patients and in previously treated chronic patients experiencing an episode of illness exacerbation. In addition, elevated synaptic dopamine was predictive of good treatment response of positive symptoms to antipsychotic drugs. This finding provides direct evidence of increased stimulation of D2 receptors by dopamine in schizophrenia, consistent with increased phasic activity of dopaminergic neurons. PMID:10884434

  20. PKCε and allopregnanolone: functional cross-talk at the GABAA receptor level

    PubMed Central

    Puia, Giulia; Ravazzini, Federica; Castelnovo, Luca Franco; Magnaghi, Valerio

    2015-01-01

    Changes in GABAergic inhibition occur during physiological processes, during response to drugs and in various pathologies. These changes can be achieved through direct allosteric modifications at the γ-amino butyric acid (GABA) type A (GABAA) receptor protein level, or by altering the synthesis, trafficking and stability of the receptor. Neurosteroids (NSs) and protein kinase C (PKC) are potent modulators of GABAA receptors and their effects are presumably intermingled, even though evidence for this hypothesis is only partially explored. However, several PKC isoforms are able to phosphorylate the GABAA receptor, producing different functional effects. We focused on the ε isoform, that has been correlated to the sensitivity of the GABAA receptor to allosteric modulators and whose expression may be regulated in peripheral sensory neurons by NSs. The cross-talk between PKC-ε and NSs, leading to changes in GABAA receptor functionality, is considered and discussed in this perspective. PMID:25852476

  1. Structure-function analysis identifies highly sensitive strigolactone receptors in Striga.

    PubMed

    Toh, Shigeo; Holbrook-Smith, Duncan; Stogios, Peter J; Onopriyenko, Olena; Lumba, Shelley; Tsuchiya, Yuichiro; Savchenko, Alexei; McCourt, Peter

    2015-10-01

    Strigolactones are naturally occurring signaling molecules that affect plant development, fungi-plant interactions, and parasitic plant infestations. We characterized the function of 11 strigolactone receptors from the parasitic plant Striga hermonthica using chemical and structural biology. We found a clade of polyspecific receptors, including one that is sensitive to picomolar concentrations of strigolactone. A crystal structure of a highly sensitive strigolactone receptor from Striga revealed a larger binding pocket than that of the Arabidopsis receptor, which could explain the increased range of strigolactone sensitivity. Thus, the sensitivity of Striga to strigolactones from host plants is driven by receptor sensitivity. By expressing strigolactone receptors in Arabidopsis, we developed a bioassay that can be used to identify chemicals and crops with altered strigolactone levels. PMID:26450211

  2. Reversible Intercalation of Fluoride-Anion Receptor Complexes in Graphite

    NASA Technical Reports Server (NTRS)

    West, William C.; Whitacre, Jay F.; Leifer, Nicole; Greenbaum, Steve; Smart, Marshall; Bugga, Ratnakumar; Blanco, Mario; Narayanan, S. R.

    2007-01-01

    We have demonstrated a route to reversibly intercalate fluoride-anion receptor complexes in graphite via a nonaqueous electrochemical process. This approach may find application for a rechargeable lithium-fluoride dual-ion intercalating battery with high specific energy. The cell chemistry presented here uses graphite cathodes with LiF dissolved in a nonaqueous solvent through the aid of anion receptors. Cells have been demonstrated with reversible cathode specific capacity of approximately 80 mAh/g at discharge plateaus of upward of 4.8 V, with graphite staging of the intercalant observed via in situ synchrotron X-ray diffraction during charging. Electrochemical impedance spectroscopy and B-11 nuclear magnetic resonance studies suggest that cointercalation of the anion receptor with the fluoride occurs during charging, which likely limits the cathode specific capacity. The anion receptor type dictates the extent of graphite fluorination, and must be further optimized to realize high theoretical fluorination levels. To find these optimal anion receptors, we have designed an ab initio calculations-based scheme aimed at identifying receptors with favorable fluoride binding and release properties.

  3. Zinc as Allosteric Ion Channel Modulator: Ionotropic Receptors as Metalloproteins

    PubMed Central

    Peralta, Francisco Andrés; Huidobro-Toro, Juan Pablo

    2016-01-01

    Zinc is an essential metal to life. This transition metal is a structural component of many proteins and is actively involved in the catalytic activity of cell enzymes. In either case, these zinc-containing proteins are metalloproteins. However, the amino acid residues that serve as ligands for metal coordination are not necessarily the same in structural proteins compared to enzymes. While crystals of structural proteins that bind zinc reveal a higher preference for cysteine sulfhydryls rather than histidine imidazole rings, catalytic enzymes reveal the opposite, i.e., a greater preference for the histidines over cysteines for catalysis, plus the influence of carboxylic acids. Based on this paradigm, we reviewed the putative ligands of zinc in ionotropic receptors, where zinc has been described as an allosteric modulator of channel receptors. Although these receptors do not strictly qualify as metalloproteins since they do not normally bind zinc in structural domains, they do transitorily bind zinc at allosteric sites, modifying transiently the receptor channel’s ion permeability. The present contribution summarizes current information showing that zinc allosteric modulation of receptor channels occurs by the preferential metal coordination to imidazole rings as well as to the sulfhydryl groups of cysteine in addition to the carboxyl group of acid residues, as with enzymes and catalysis. It is remarkable that most channels, either voltage-sensitive or transmitter-gated receptor channels, are susceptible to zinc modulation either as positive or negative regulators. PMID:27384555

  4. Zinc as Allosteric Ion Channel Modulator: Ionotropic Receptors as Metalloproteins.

    PubMed

    Peralta, Francisco Andrés; Huidobro-Toro, Juan Pablo

    2016-01-01

    Zinc is an essential metal to life. This transition metal is a structural component of many proteins and is actively involved in the catalytic activity of cell enzymes. In either case, these zinc-containing proteins are metalloproteins. However, the amino acid residues that serve as ligands for metal coordination are not necessarily the same in structural proteins compared to enzymes. While crystals of structural proteins that bind zinc reveal a higher preference for cysteine sulfhydryls rather than histidine imidazole rings, catalytic enzymes reveal the opposite, i.e., a greater preference for the histidines over cysteines for catalysis, plus the influence of carboxylic acids. Based on this paradigm, we reviewed the putative ligands of zinc in ionotropic receptors, where zinc has been described as an allosteric modulator of channel receptors. Although these receptors do not strictly qualify as metalloproteins since they do not normally bind zinc in structural domains, they do transitorily bind zinc at allosteric sites, modifying transiently the receptor channel's ion permeability. The present contribution summarizes current information showing that zinc allosteric modulation of receptor channels occurs by the preferential metal coordination to imidazole rings as well as to the sulfhydryl groups of cysteine in addition to the carboxyl group of acid residues, as with enzymes and catalysis. It is remarkable that most channels, either voltage-sensitive or transmitter-gated receptor channels, are susceptible to zinc modulation either as positive or negative regulators. PMID:27384555

  5. Photoaffinity labeling of the somatostatin receptor: identification of molecular subtypes.

    PubMed

    Srikant, C B; Murthy, K K; Escher, E E; Patel, Y C

    1992-05-01

    Pharmacological studies have suggested that the somatostatin (SS) receptor is heterogeneous and may exhibit subtypes selective for SS-14 and SS-28. Whether this heterogeneity can be explained by separate molecular forms of the receptor protein is unclear. In the present study, we have developed a novel photosensitive azido derivative of the octapeptide SS analog Tyr3 SMS (EE 581) and used it as a photoaffinity probe to characterize the molecular components of the SS receptor in five receptor positive tissues (normal rat brain, pituitary, pancreas, and adrenal cortex, and mouse AtT-20 pituitary tumor cells). [125I]EE-581 labeled specific high affinity binding sites in all these tissues (Kd range 1.3-1.67 nM). Photoaffinity labeled membrane SS receptors were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography. Three specifically labeled SS receptor proteins of 80 kilodaltons (kDa), 58 kDa, and 32 kDa were identified and exhibited a tissue-specific distribution. The 58 kDa species was the exclusive form in pancreas, adrenal cortex, and AtT-20 cells and the dominant form in brain. The 32 kDa receptor protein was expressed as a minor form (ratio of 58 kDa:32 kDa 3:1), exclusively in brain. The 80 kDa receptor was found only in the pituitary where it occurred as the sole SS receptor species. Competition experiments showed that the 58 kDa and 32 kDa receptor proteins in brain reacted with SS-14 greater than SS-28; in contrast, the 58 kDa protein in AtT-20 cells bound SS-28 greater than SS-14 suggesting the existence of distinct subtypes of the 58 kDa receptor in these two tissues. These data represent the first systematic evaluation of the molecular forms of SS receptor proteins by photoaffinity labeling in different target tissues and provide direct evidence for molecular heterogeneity and SS-14/SS-28 selectivity; a major 58 kDa protein present in most tissues, an additional 32 kDa protein uniquely expressed in brain, and an

  6. Differential effects of exercise on brain opioid receptor binding and activation in rats.

    PubMed

    Arida, Ricardo Mario; Gomes da Silva, Sérgio; de Almeida, Alexandre Aparecido; Cavalheiro, Esper Abrão; Zavala-Tecuapetla, Cecilia; Brand, Serge; Rocha, Luisa

    2015-01-01

    Physical exercise stimulates the release of endogenous opioid peptides supposed to be responsible for changes in mood, anxiety, and performance. Exercise alters sensitivity to these effects that modify the efficacy at the opioid receptor. Although there is evidence that relates exercise to neuropeptide expression in the brain, the effects of exercise on opioid receptor binding and signal transduction mechanisms downstream of these receptors have not been explored. Here, we characterized the binding and G protein activation of mu opioid receptor, kappa opioid receptor or delta opioid receptor in several brain regions following acute (7 days) and chronic (30 days) exercise. As regards short- (acute) or long-term effects (chronic) of exercise, overall, higher opioid receptor binding was observed in acute-exercise animals and the opposite was found in the chronic-exercise animals. The binding of [(35) S]GTPγS under basal conditions (absence of agonists) was elevated in sensorimotor cortex and hippocampus, an effect more evident after chronic exercise. Divergence of findings was observed for mu opioid receptor, kappa opioid receptor, and delta opioid receptor receptor activation in our study. Our results support existing evidence of opioid receptor binding and G protein activation occurring differentially in brain regions in response to diverse exercise stimuli. We characterized the binding and G protein activation of mu, kappa, and delta opioid receptors in several brain regions following acute (7 days) and chronic (30 days) exercise. Higher opioid receptor binding was observed in the acute exercise animal group and opposite findings in the chronic exercise group. Higher G protein activation under basal conditions was noted in rats submitted to chronic exercise, as visible in the depicted pseudo-color autoradiograms. PMID:25330347

  7. Agonist- and antagonist-induced up-regulation of surface 5-HT3A receptors

    PubMed Central

    Morton, Russell A; Baptista-Hon, Daniel T; Hales, Tim G; Lovinger, David M

    2015-01-01

    Background and Purpose The 5-HT3 receptor is a member of the pentameric ligand-gated ion channel family and is pharmacologically targeted to treat irritable bowel syndrome and nausea/emesis. Furthermore, many antidepressants elevate extracellular concentrations of 5-HT. This study investigates the functional consequences of exposure of recombinant 5-HT3A receptors to agonists and antagonists. Experimental Approach We used HEK cells stably expressing recombinant 5-HT3A receptors and the ND7/23 (mouse neuroblastoma/dorsal root ganglion hybrid) cell line, which expresses endogenous 5-HT3 receptors. Surface expression of recombinant 5-HT3A receptors, modified to contain the bungarotoxin (BTX) binding sequence, was quantified using fluorescence microscopy to image BTX-conjugated fluorophores. Whole cell voltage-clamp electrophysiology was used to measure the density of current mediated by 5-HT3A receptors. Key Results 5-HT3A receptors were up-regulated by the prolonged presence of agonists (5-HT and m-chlorophenylbiguanide) and antagonists (MDL-72222 and morphine). The up-regulation of 5-HT3A receptors by 5-HT and MDL-72222 was time- and concentration-dependent but was independent of newly translated receptors. The phenomenon was observed for recombinant rodent and human 5-HT3A receptors and for endogenous 5-HT3 receptors in neuronal ND7/23 cells. Conclusions and Implications Up-regulation of 5-HT3A receptors, following exposure to either agonists or antagonists suggests that this phenomenon may occur in response to different therapeutic agents. Medications that elevate 5-HT levels, such as the antidepressant inhibitors of 5-HT reuptake and antiemetic inhibitors of 5-HT3 receptor function, may both raise receptor expression. However, this will require further investigation in vivo. PMID:25989383

  8. The pituitary V3 vasopressin receptor and the corticotroph phenotype in ectopic ACTH syndrome.

    PubMed

    de Keyzer, Y; Lenne, F; Auzan, C; Jégou, S; René, P; Vaudry, H; Kuhn, J M; Luton, J P; Clauser, E; Bertagna, X

    1996-03-01

    Ectopic ACTH secretion occurs in highly differentiated and rather indolent tumors like bronchial carcinoids or, in contrast, in various types of aggressive and poorly differentiated neuroendocrine tumors. We explored this phenomenon using the recently cloned human pituitary V3 vasopressin receptor as an alternate molecular marker of the corticotroph phenotype. Expression of V3 receptor, corticotrophin releasing hormone (CRH) receptor, and proopiomelanocortin (POMC) genes was examined in tumors of pituitary and nonpituitary origin. A comparative RT-PCR approach revealed signals for both V3 receptor and CHR receptor mRNAs in 17 of 18 ACTH-secreting pituitary adenomas, and 6 of 6 normal pituitaries; in six growth hormone- or prolactin-secreting adenomas, a very faint V3 receptor signal was observed in three cases, and CRH receptor signal was undetected in all. Six of eight bronchial carcinoids responsible for the ectopic ACTH syndrome had both POMC and V3 receptor signals as high as those in ACTH-secreting pituitary adenomas; in contrast, no POMC signal and only a very faint V3 receptor signal were detected in six of eight nonsecreting bronchial carcinoids. Northern blot analysis showed V3 receptor mRNA of identical size in ACTH-secreting bronchial carcinoids and pituitary tumors. Other types of nonpituitary tumors responsible for ectopic ACTH syndrome presented much lower levels of both POMC and V3 receptor gene expression than those found in ACTH-secreting bronchial carcinoids. In contrast with the V3 receptor, CRH receptor mRNA was detected in the majority of neuroendocrine tumors irrespective of their POMC status. These results show that expression of the V3 receptor gene participates in the corticotroph phenotype. Its striking association with ACTH-secreting bronchial carcinoids defines a subset of nonpituitary tumors in which ectopic POMC gene expression is but one aspect of a wider process of corticotroph cell differentiation, and opens new possibilities of

  9. Optimizing transmembrane domain helicity accelerates insulin receptor internalization and lateral mobility.

    PubMed Central

    Goncalves, E; Yamada, K; Thatte, H S; Backer, J M; Golan, D E; Kahn, C R; Shoelson, S E

    1993-01-01

    Transmembrane (TM) domains of integral membrane proteins are generally thought to be helical. However, a Gly-Pro sequence within the TM domain of the insulin receptor is predicted to act as a helix breaker. CD analyses of model TM peptides in a lipid-like environment show that substitution of Gly and Pro by Ala enhances helicity. On this basis, Gly933 and Pro934 within the TM domain of the intact human insulin receptor were mutated to Ala (G-->A, P-->A, GP-->AA) to assess effects of altered helicity on receptor functions. Mutated and wild-type receptors, expressed stably in cultured CHO cells at equivalent levels, were properly assembled, biosynthetically processed, and exhibited similar affinities for insulin. Receptor autophosphorylation and substrate kinase activity in intact cells and soluble receptor preparations were indistinguishable. In contrast, insulin-stimulated receptor internalization was accelerated 2-fold for the GP-->AA mutant, compared to a wild-type control or the G-->A and P-->A mutants. Insulin degradation, which occurs during receptor endocytosis and recycling, was similarly elevated in cells transfected with GP-->AA mutant receptors. Fluorescence photobleaching recovery measurements showed that the lateral mobility of GP-->AA mutant receptors was also increased 2- to 3-fold. These results suggest that lateral mobility directly influences rates of insulin-mediated receptor endocytosis and that rates of endocytosis and lateral mobility are retarded by a kinked TM domain in the wild-type receptor. Invariance of Gly-Pro within insulin receptor TM domain sequences suggests a physiologic advantage for submaximal rates of receptor internalization. Images Fig. 2 Fig. 3 PMID:8390680

  10. Differential effects of exercise on brain opioid receptor binding and activation in rats.

    PubMed

    Arida, Ricardo Mario; Gomes da Silva, Sérgio; de Almeida, Alexandre Aparecido; Cavalheiro, Esper Abrão; Zavala-Tecuapetla, Cecilia; Brand, Serge; Rocha, Luisa

    2015-01-01

    Physical exercise stimulates the release of endogenous opioid peptides supposed to be responsible for changes in mood, anxiety, and performance. Exercise alters sensitivity to these effects that modify the efficacy at the opioid receptor. Although there is evidence that relates exercise to neuropeptide expression in the brain, the effects of exercise on opioid receptor binding and signal transduction mechanisms downstream of these receptors have not been explored. Here, we characterized the binding and G protein activation of mu opioid receptor, kappa opioid receptor or delta opioid receptor in several brain regions following acute (7 days) and chronic (30 days) exercise. As regards short- (acute) or long-term effects (chronic) of exercise, overall, higher opioid receptor binding was observed in acute-exercise animals and the opposite was found in the chronic-exercise animals. The binding of [(35) S]GTPγS under basal conditions (absence of agonists) was elevated in sensorimotor cortex and hippocampus, an effect more evident after chronic exercise. Divergence of findings was observed for mu opioid receptor, kappa opioid receptor, and delta opioid receptor receptor activation in our study. Our results support existing evidence of opioid receptor binding and G protein activation occurring differentially in brain regions in response to diverse exercise stimuli. We characterized the binding and G protein activation of mu, kappa, and delta opioid receptors in several brain regions following acute (7 days) and chronic (30 days) exercise. Higher opioid receptor binding was observed in the acute exercise animal group and opposite findings in the chronic exercise group. Higher G protein activation under basal conditions was noted in rats submitted to chronic exercise, as visible in the depicted pseudo-color autoradiograms.

  11. Secretin receptor involvement in prion-infected cells and animals.

    PubMed

    Kimura, Tomohiro; Nishizawa, Keiko; Oguma, Ayumi; Nishimura, Yuki; Sakasegawa, Yuji; Teruya, Kenta; Nishijima, Ichiko; Doh-ura, Katsumi

    2015-07-01

    The cellular mechanisms behind prion biosynthesis and metabolism remain unclear. Here we show that secretin signaling via the secretin receptor regulates abnormal prion protein formation in prion-infected cells. Animal studies demonstrate that secretin receptor deficiency slightly, but significantly, prolongs incubation time in female but not male mice. This gender-specificity is consistent with our finding that prion-infected cells are derived from females. Therefore, our results provide initial insights into the reasons why age of disease onset in certain prion diseases is reported to occur slightly earlier in females than males. PMID:26037144

  12. Changes of lymphocyte beta-adrenergic receptors after surgical stress.

    PubMed

    Eandi, M; Buraglio, M; Arduino, C; Viano, I; Sansalvadore, G; Arbinolo, M A

    1984-01-01

    In this study the authors' purpose was to observe the effects of surgical stress on the number of lymphocyte beta-adrenergic receptors in hypertensive and normotensive subjects. It was noticed that after surgery a significant reduction occurred in the number of binding sites of lymphocytes of both hypertensive and normotensive subjects. The time course of recovery to the pre-operative values of binding sites varied between the two groups, being slower in normotensive than in hypertensive patients. This might suggest a different pattern of regulation of the beta-adrenergic receptor between hypertensive and normotensive subjects.

  13. Yokukansan Increases 5-HT1A Receptors in the Prefrontal Cortex and Enhances 5-HT1A Receptor Agonist-Induced Behavioral Responses in Socially Isolated Mice

    PubMed Central

    Ueki, Toshiyuki; Mizoguchi, Kazushige; Yamaguchi, Takuji; Nishi, Akinori; Ikarashi, Yasushi; Hattori, Tomohisa; Kase, Yoshio

    2015-01-01

    The traditional Japanese medicine yokukansan has an anxiolytic effect, which occurs after repeated administration. In this study, to investigate the underlying mechanisms, we examined the effects of repeated yokukansan administration on serotonin 1A (5-HT1A) receptor density and affinity and its expression at both mRNA and protein levels in the prefrontal cortex (PFC) of socially isolated mice. Moreover, we examined the effects of yokukansan on a 5-HT1A receptor-mediated behavioral response. Male mice were subjected to social isolation stress for 6 weeks and simultaneously treated with yokukansan. Thereafter, the density and affinity of 5-HT1A receptors were analyzed by a receptor-binding assay. Levels of 5-HT1A receptor protein and mRNA were also measured. Furthermore, (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT; a 5-HT1A receptor agonist) was injected intraperitoneally, and rearing behavior was examined. Social isolation stress alone did not affect 5-HT1A receptor density or affinity. However, yokukansan significantly increased receptor density and decreased affinity concomitant with unchanged protein and mRNA levels. Yokukansan also enhanced the 8-OH-DPAT-induced decrease in rearing behavior. These results suggest that yokukansan increases 5-HT1A receptors in the PFC of socially isolated mice and enhances their function, which might underlie its anxiolytic effects. PMID:26681968

  14. Sequence of a functional invertebrate GABAA receptor subunit which can form a chimeric receptor with a vertebrate alpha subunit.

    PubMed Central

    Harvey, R J; Vreugdenhil, E; Zaman, S H; Bhandal, N S; Usherwood, P N; Barnard, E A; Darlison, M G

    1991-01-01

    The sequence of an invertebrate GABAA receptor subunit is described. This was deduced from a cDNA which was isolated from the mollusc Lymnaea stagnalis and which corresponds to a transcript of extremely low abundance. The cDNA was isolated using short exonic sequences from part of the corresponding gene in combination with a variant of the polymerase chain reaction (PCR) known as RACE (rapid amplification of cDNA ends). The mature polypeptide has a predicted molecular weight of 54,569 Daltons and exhibits approximately 50% identity to vertebrate GABAA receptor beta subunits. The six intron-exon boundaries determined to date in the molluscan gene occur at the same relative positions as those found in vertebrate GABAA receptor genes. Functional expression, in Xenopus oocytes, of the molluscan cDNA alone results in the formation of GABA-activated chloride ion channels that have a finite open probability even in the absence of agonist. These GABA-evoked currents can be reversibly blocked by the vertebrate GABAA receptor antagonist bicuculline. Surprisingly, the molluscan beta subunit is capable of replacing vertebrate beta subunits in co-expression experiments with the bovine GABAA receptor alpha 1 subunit. These findings suggest that invertebrate GABAA receptors exist in vivo as hetero-oligomeric complexes. PMID:1655414

  15. Angiotensin II receptors in testes

    SciTech Connect

    Millan, M.A.; Aguilera, G.

    1988-05-01

    Receptors for angiotensin II (AII) were identified and characterized in testes of rats and several primate species. Autoradiographic analysis of the binding of 125I-labeled (Sar1,Ile8)AII to rat, rhesus monkey, cebus monkey, and human testicular slide-mounted frozen sections indicated specific binding to Leydig cells in the interstitium. In rat collagenase-dispersed interstitial cells fractionated by Percoll gradient, AII receptor content was parallel to that of hCG receptors, confirming that the AII receptors are in the Leydig cells. In rat dispersed Leydig cells, binding was specific for AII and its analogs and of high affinity (Kd, 4.8 nM), with a receptor concentration of 15 fmol/10(6) cells. Studies of AII receptors in rat testes during development reveals the presence of high receptor density in newborn rats which decreases toward the adult age (4934 +/- 309, 1460 +/- 228, 772 +/- 169, and 82 +/- 12 fmol/mg protein at 5, 15, 20, and 30 days of age, respectively) with no change in affinity. At all ages receptors were located in the interstitium, and the decrease in binding was parallel to the decrease in the interstitial to tubular ratio observed with age. AII receptor properties in membrane-rich fractions from prepuberal testes were similar in the rat and rhesus monkey. Binding was time and temperature dependent, reaching a plateau at 60 min at 37 C, and was increased by divalent cations, EGTA, and dithiothreitol up to 0.5 mM. In membranes from prepuberal monkey testes, AII receptors were specific for AII analogs and of high affinity (Kd, 4.2 nM) with a receptor concentration of 7599 +/- 1342 fmol/mg protein. The presence of AII receptors in Leydig cells in rat and primate testes in conjunction with reports of the presence of other components of the renin-angiotensin system in the testes suggests that the peptide has a physiological role in testicular function.

  16. Phosphorylation of the human leukemia inhibitory factor (LIF) receptor by mitogen-activated protein kinase and the regulation of LIF receptor function by heterologous receptor activation.

    PubMed Central

    Schiemann, W P; Graves, L M; Baumann, H; Morella, K K; Gearing, D P; Nielsen, M D; Krebs, E G; Nathanson, N M

    1995-01-01

    We used a bacterially expressed fusion protein containing the entire cytoplasmic domain of the human leukemia inhibitory factor (LIF) receptor to study its phosphorylation in response to LIF stimulation. The dose- and time-dependent relationships for phosphorylation of this construct in extracts of LIF-stimulated 3T3-L1 cells were superimposable with those for the stimulation of mitogen-activated protein kinase (MAPK). Indeed, phosphorylation of the cytoplasmic domain of the low-affinity LIF receptor alpha-subunit (LIFR) in Mono Q-fractionated, LIF-stimulated 3T3-L1 extracts occurred only in those fractions containing activated MAPK; Ser-1044 served as the major phosphorylation site in the human LIFR for MAPK both in agonist-stimulated 3T3-L1 lysates and by recombinant extracellular signal-regulated kinase 2 in vitro. Expression in rat H-35 hepatoma cells of LIFR or chimeric granulocyte-colony-stimulating factor receptor (G-CSFR)-LIFR mutants lacking Ser-1044 failed to affect cytokine-stimulated expression of a reporter gene under the control of the beta-fibrinogen gene promoter but eliminated the insulin-induced attenuation of cytokine-stimulated gene expression. Thus, our results identify the human LIFR as a substrate for MAPK and suggest a mechanism of heterologous receptor regulation of LIFR signaling occurring at Ser-1044. Images Fig. 2 Fig. 4 PMID:7777512

  17. Inflammation influences steroid hormone receptors targeted by progestins in endometrial stromal cells from women with endometriosis.

    PubMed

    Grandi, Giovanni; Mueller, Michael D; Papadia, Andrea; Kocbek, Vida; Bersinger, Nick A; Petraglia, Felice; Cagnacci, Angelo; McKinnon, Brett

    2016-09-01

    Endometriosis is an estrogen-dependent disease characterised by the growth of endometrial epithelial and stromal cells outside the uterus creating a chronic inflammatory environment that further contributes to disease progression. The first choice treatment for endometriosis is currently progestin mediated hormone modulation. In addition to their progestogenic activity however, progestins also have the potential to bind to other nuclear receptors influencing their local activity on endometriotic cells. This local activity will be dependent on the steroid hormone receptor expression that occurs in endometrial cells in a chronic inflammatory environment. We therefore aimed to quantify receptors targeted by progestins in endometrial stromal cells after exposure to inflammation. Using primary endometrial stromal cells isolated from women with endometriosis we examined the mRNA and protein expression of the progesterone receptors A and B, membrane progesterone receptors 1 and 2, androgen receptors, mineralocorticoid receptors and glucocorticoid receptors after exposure to the inflammatory cytokines tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β). The results indicate that both cytokines reduced the expression of progesterone receptors and increased the expression of the glucocorticoid receptors in the endometrial stromal cells. The change in expression of progestin targets in endometrial stromal cells in an inflammatory environment could contribute to the progesterone resistance observed in endometriotic cells and ultimately influence the design of hormonal therapies aimed at treating this disease. PMID:27371899

  18. Structural organization and chromosomal assignment of the human prostacyclin receptor gene

    SciTech Connect

    Ogawa, Yoshihiro; Tanaka, Issei; Inoue, Miho

    1995-05-01

    Prostacyclin receptor is a member of the prostanoid receptor family in the G protein-coupled receptor superfamily with seven transmembrane domains. The authors report here the isolation and structural organization of the human prostacyclin receptor gene. Southern blot analysis demonstrated a single copy of the human prostacyclin receptor gene in the human genome. The human prostacyclin receptor gene spanned approximately 7.0 kb and was composed of three exons separated by two introns. The first intron occurred in the 5`-untranslated region, 13 bp upstream to the ATG start codon. The second intron was located at the end of the sixth transmembrane domain, thereby separating it from the downstream coding region and the 3`-untranslated region. By primer extension analysis, the transcription initiation sites were mapped 870-872 bp upstream to the ATG start codon. The 1.2-kb human prostacyclin receptor 5`-flanking region lacked conventional TATA and CCAAT boxes, but it contained several cis-acting regulatory elements including an inverted CCAAT box (Y box) and two copies of SP-1 binding sites. Using human-rodent somatic hybrid cell DNA, the human prostacyclin receptor gene was assigned to human chromosome 19. The present study helps establish the genetic basis for prostacyclin receptor research and provides further insight into the molecular mechanisms underlying the prostanoid receptor family. 38 refs., 6 figs.

  19. Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases.

    PubMed

    Yuan, Hongjie; Low, Chian-Ming; Moody, Olivia A; Jenkins, Andrew; Traynelis, Stephen F

    2015-07-01

    The advent of whole exome/genome sequencing and the technology-driven reduction in the cost of next-generation sequencing as well as the introduction of diagnostic-targeted sequencing chips have resulted in an unprecedented volume of data directly linking patient genomic variability to disorders of the brain. This information has the potential to transform our understanding of neurologic disorders by improving diagnoses, illuminating the molecular heterogeneity underlying diseases, and identifying new targets for therapeutic treatment. There is a strong history of mutations in GABA receptor genes being involved in neurologic diseases, particularly the epilepsies. In addition, a substantial number of variants and mutations have been found in GABA receptor genes in patients with autism, schizophrenia, and addiction, suggesting potential links between the GABA receptors and these conditions. A new and unexpected outcome from sequencing efforts has been the surprising number of mutations found in glutamate receptor subunits, with the GRIN2A gene encoding the GluN2A N-methyl-d-aspartate receptor subunit being most often affected. These mutations are associated with multiple neurologic conditions, for which seizure disorders comprise the largest group. The GluN2A subunit appears to be a locus for epilepsy, which holds important therapeutic implications. Virtually all α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor mutations, most of which occur within GRIA3, are from patients with intellectual disabilities, suggesting a link to this condition. Similarly, the most common phenotype for kainate receptor variants is intellectual disability. Herein, we summarize the current understanding of disease-associated mutations in ionotropic GABA and glutamate receptor families, and discuss implications regarding the identification of human mutations and treatment of neurologic diseases. PMID:25904555

  20. Are CB1 Receptor Antagonists Nootropic or Cognitive Impairing Agents?

    PubMed Central

    Varvel, Stephen A.; Wise, Laura E.; Lichtman, Aron H.

    2010-01-01

    For more than a decade, a considerable amount of research has examined the effects of rimonabant (SR 141716) and other CB1 receptor antagonists in both in vivo and in vitro models of learning and memory. In addition to its utility in determining whether the effects of drugs are mediated though a CB1 receptor mechanism of action, these antagonists are useful in providing insight into the physiological function of the endogenous cannabinoid system. Several groups have reported that CB1 receptor antagonists enhance memory duration in a variety of spatial and operant paradigms, but not in all paradigms. Conversely, disruption of CB1 receptor signaling also impairs extinction learning in which the animal actively suppresses a learned response when reinforcement has been withheld. These extinction deficits occur in aversively motivated tasks, such as in fear conditioning or escape behavior in the Morris water maze task, but not in appetitively motivated tasks. Similarly, in electrophysiological models, CB1 receptor antagonists elicit a variety of effects, including enhancement of long-term potentiation (LTP), while disrupting long-term depression (LTD) and interfering with transient forms of plasticity, including depolarization-induced suppression of inhibition (DSI) and depolarization-induced suppression of excitation (DSE). The collective results of the in vivo and in vitro studies employing CB1 receptor antagonists, demonstrate that these receptors play integral roles in different components of cognitive processing. Functionally, pharmacological blockade of CB1 receptors may strengthen memory duration, but interferes with extinction of learned behaviors that are associated with traumatic or aversive memories. PMID:20539824

  1. Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases.

    PubMed

    Yuan, Hongjie; Low, Chian-Ming; Moody, Olivia A; Jenkins, Andrew; Traynelis, Stephen F

    2015-07-01

    The advent of whole exome/genome sequencing and the technology-driven reduction in the cost of next-generation sequencing as well as the introduction of diagnostic-targeted sequencing chips have resulted in an unprecedented volume of data directly linking patient genomic variability to disorders of the brain. This information has the potential to transform our understanding of neurologic disorders by improving diagnoses, illuminating the molecular heterogeneity underlying diseases, and identifying new targets for therapeutic treatment. There is a strong history of mutations in GABA receptor genes being involved in neurologic diseases, particularly the epilepsies. In addition, a substantial number of variants and mutations have been found in GABA receptor genes in patients with autism, schizophrenia, and addiction, suggesting potential links between the GABA receptors and these conditions. A new and unexpected outcome from sequencing efforts has been the surprising number of mutations found in glutamate receptor subunits, with the GRIN2A gene encoding the GluN2A N-methyl-d-aspartate receptor subunit being most often affected. These mutations are associated with multiple neurologic conditions, for which seizure disorders comprise the largest group. The GluN2A subunit appears to be a locus for epilepsy, which holds important therapeutic implications. Virtually all α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor mutations, most of which occur within GRIA3, are from patients with intellectual disabilities, suggesting a link to this condition. Similarly, the most common phenotype for kainate receptor variants is intellectual disability. Herein, we summarize the current understanding of disease-associated mutations in ionotropic GABA and glutamate receptor families, and discuss implications regarding the identification of human mutations and treatment of neurologic diseases.

  2. Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases

    PubMed Central

    Yuan, Hongjie; Low, Chian-Ming; Moody, Olivia A.; Jenkins, Andrew

    2015-01-01

    The advent of whole exome/genome sequencing and the technology-driven reduction in the cost of next-generation sequencing as well as the introduction of diagnostic-targeted sequencing chips have resulted in an unprecedented volume of data directly linking patient genomic variability to disorders of the brain. This information has the potential to transform our understanding of neurologic disorders by improving diagnoses, illuminating the molecular heterogeneity underlying diseases, and identifying new targets for therapeutic treatment. There is a strong history of mutations in GABA receptor genes being involved in neurologic diseases, particularly the epilepsies. In addition, a substantial number of variants and mutations have been found in GABA receptor genes in patients with autism, schizophrenia, and addiction, suggesting potential links between the GABA receptors and these conditions. A new and unexpected outcome from sequencing efforts has been the surprising number of mutations found in glutamate receptor subunits, with the GRIN2A gene encoding the GluN2A N-methyl-d-aspartate receptor subunit being most often affected. These mutations are associated with multiple neurologic conditions, for which seizure disorders comprise the largest group. The GluN2A subunit appears to be a locus for epilepsy, which holds important therapeutic implications. Virtually all α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor mutations, most of which occur within GRIA3, are from patients with intellectual disabilities, suggesting a link to this condition. Similarly, the most common phenotype for kainate receptor variants is intellectual disability. Herein, we summarize the current understanding of disease-associated mutations in ionotropic GABA and glutamate receptor families, and discuss implications regarding the identification of human mutations and treatment of neurologic diseases. PMID:25904555

  3. The human olfactory receptor repertoire

    PubMed Central

    Zozulya, Sergey; Echeverri, Fernando; Nguyen, Trieu

    2001-01-01

    Background The mammalian olfactory apparatus is able to recognize and distinguish thousands of structurally diverse volatile chemicals. This chemosensory function is mediated by a very large family of seven-transmembrane olfactory (odorant) receptors encoded by approximately 1,000 genes, the majority of which are believed to be pseudogenes in humans. Results The strategy of our sequence database mining for full-length, functional candidate odorant receptor genes was based on the high overall sequence similarity and presence of a number of conserved sequence motifs in all known mammalian odorant receptors as well as the absence of introns in their coding sequences. We report here the identification and physical cloning of 347 putative human full-length odorant receptor genes. Comparative sequence analysis of the predicted gene products allowed us to identify and define a number of consensus sequence motifs and structural features of this vast family of receptors. A new nomenclature for human odorant receptors based on their chromosomal localization and phylogenetic analysis is proposed. We believe that these sequences represent the essentially complete repertoire of functional human odorant receptors. Conclusions The identification and cloning of all functional human odorant receptor genes is an important initial step in understanding receptor-ligand specificity and combinatorial encoding of odorant stimuli in human olfaction. PMID:11423007

  4. Inhibition of Hedgehog-dependent tumors and cancer stem cells by a newly identified naturally occurring chemotype

    PubMed Central

    Infante, Paola; Alfonsi, Romina; Ingallina, Cinzia; Quaglio, Deborah; Ghirga, Francesca; D'Acquarica, Ilaria; Bernardi, Flavia; Di Magno, Laura; Canettieri, Gianluca; Screpanti, Isabella; Gulino, Alberto; Botta, Bruno; Mori, Mattia; Di Marcotullio, Lucia

    2016-01-01

    Hedgehog (Hh) inhibitors have emerged as valid tools in the treatment of a wide range of cancers. Indeed, aberrant activation of the Hh pathway occurring either by ligand-dependent or -independent mechanisms is a key driver in tumorigenesis. The smoothened (Smo) receptor is one of the main upstream transducers of the Hh signaling and is a validated target for the development of anticancer compounds, as underlined by the FDA-approved Smo antagonist Vismodegib (GDC-0449/Erivedge) for the treatment of basal cell carcinoma. However, Smo mutations that confer constitutive activity and