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Sample records for receptor m33 occurs

  1. Receptor Editing Occurs Frequently during Normal B Cell Development

    PubMed Central

    Retter, Marc W.; Nemazee, David

    1998-01-01

    Allelic exclusion is established in development through a feedback mechanism in which the assembled immunoglobulin (Ig) suppresses further V(D)J rearrangement. But Ig expression sometimes fails to prevent further rearrangement. In autoantibody transgenic mice, reactivity of immature B cells with autoantigen can induce receptor editing, in which allelic exclusion is transiently prevented or reversed through nested light chain gene rearrangement, often resulting in altered B cell receptor specificity. To determine the extent of receptor editing in a normal, non-Ig transgenic immune system, we took advantage of the fact that λ light chain genes usually rearrange after κ genes. This allowed us to analyze κ loci in IgMλ+ cells to determine how frequently in-frame κ genes fail to suppress λ gene rearrangements. To do this, we analyzed recombined VκJκ genes inactivated by subsequent recombining sequence (RS) rearrangement. RS rearrangements delete portions of the κ locus by a V(D)J recombinase-dependent mechanism, suggesting that they play a role in receptor editing. We show that RS recombination is frequently induced by, and inactivates, functionally rearranged κ loci, as nearly half (47%) of the RS-inactivated VκJκ joins were in-frame. These findings suggest that receptor editing occurs at a surprisingly high frequency in normal B cells. PMID:9763602

  2. 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.

  3. Neon and Oxygen Abundances in M33

    NASA Astrophysics Data System (ADS)

    Crockett, Nathan R.; Garnett, Donald R.; Massey, Philip; Jacoby, George

    2006-02-01

    We present new spectroscopic observations of 13 H II regions in the Local Group spiral galaxy M33. The regions observed range from 1 to 7 kpc in distance from the nucleus. Of the 13 H II regions observed, the [O III] λ4363 line was detected in six regions. Electron temperatures were thus able to be determined directly from the spectra using the [O III] λλ4959, 5007/λ4363 line ratio. Based on these temperature measurements, oxygen and neon abundances and their radial gradients were calculated. For neon, a gradient of -0.016+/-0.017 dex kpc-1 was computed, which agrees with the Ne/H gradient derived previously from ISO spectra. A gradient of -0.012+/-0.011 dex kpc-1 was computed for O/H, much shallower than was derived in previous studies. The newly calculated O/H and Ne/H gradients are in much better agreement with each other, as expected from predictions of stellar nucleosynthesis. We examine the correlation between the WC/WN ratio and metallicity, and find that the new M33 abundances do not impact the observed correlation significantly. We also identify two new He II-emitting H II regions in M33, the first to be discovered in a spiral galaxy other than the Milky Way. In both cases the nebular He II emission is not associated with Wolf-Rayet stars. Therefore, caution is warranted in interpreting the relationship between nebular He II emission and Wolf-Rayet stars when both are observed in the integrated spectrum of an H II region.

  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. Detail Chemical Composition of M33 Globular Clusters

    NASA Astrophysics Data System (ADS)

    McWilliam, Andrew

    2008-08-01

    I propose to perform the first high-resolution detailed chemical abundance study of globular clusters (GCs) in the Local Group spiral galaxy M33 with Keck HIRES. My integrated-light technique permits detailed chemical abundance measurement (and approximate ages) for old populations at larger distance than ever done before. The basic goal is to accurately define the chemical abundance properties of the M33 GC system, for a comparison with the Milky Way, LMC, SMC and Local Group dwarf galaxies. Abundances of Fe, (alpha)-elements, Na and Al will constrain the relative contributions of Type Ia and Type II SNe and probe ~1 Gyr enrichment timescales. The s-process elements (e.g. Zr, Y, Ba, La), made by AGB stars, will probe timescales of several Gyr. These elements are sensitive to whether chemical enrichment occurred slowly, or in a burst, and whether the enrichment was global, or occurred in disparate systems, such as dwarf galaxies that were later accreted. The project will provide basic information to advance an understanding of chemical enrichment and nucleosynthesis, and galaxy evolution.

  6. 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.

  7. Spectroscopy of planetary nebulae in M 33

    NASA Astrophysics Data System (ADS)

    Magrini, L.; Perinotto, M.; Corradi, R. L. M.; Mampaso, A.

    2003-03-01

    Spectroscopic observations of 48 emission-line objects of M 33 have been obtained with the multi-object, wide field, fibre spectrograph AF2/WYFFOS at the 4.2 m WHT telescope (La Palma, Spain). Line intensities and logarithmic extinction, cbeta , are presented for 42 objects. Their location in the Sabbadin & D'Odorico diagnostic diagram (Hα /[S II] vs. Hα /[N II]) suggests that >70% of the candidates are Planetary Nebulae (PNe). Chemical abundances and nebular physical parameters have been derived for the three of the six PNe where the 4363 Å, [O II]i emission line was measurable. These are disc PNe, located within a galactocentric distance of 4.1 kpc, and, to date, they are the farthest PNe with a direct chemical abundance determination. No discrepancy in the helium, Oxygen and Argon abundances has been found in comparison with corresponding abundances of PNe in our Galaxy. Only a lower limit to the sulphur abundance has been obtained since we could not detect any [S III] line. N/H appears to be lower than the Galactic value; some possible explanations for this under-abundance are discussed. Based on observations obtained at the 4.2 m WHT telescope operated on the island of La Palma by the Isaac Newton Group in the Spanish Observatorio del Roque de Los Muchachos of the Instituto de Astrofisica de Canarias.

  8. Primary Macrophage Chemotaxis Induced by Cannabinoid Receptor 2 Agonists Occurs Independently of the CB2 Receptor

    PubMed Central

    Taylor, Lewis; Christou, Ivy; Kapellos, Theodore S.; Buchan, Alice; Brodermann, Maximillian H.; Gianella-Borradori, Matteo; Russell, Angela; Iqbal, Asif J.; Greaves, David R.

    2015-01-01

    Activation of CB2 has been demonstrated to induce directed immune cell migration. However, the ability of CB2 to act as a chemoattractant receptor in macrophages remains largely unexplored. Using a real-time chemotaxis assay and a panel of chemically diverse and widely used CB2 agonists, we set out to examine whether CB2 modulates primary murine macrophage chemotaxis. We report that of 12 agonists tested, only JWH133, HU308, L-759,656 and L-759,633 acted as macrophage chemoattractants. Surprisingly, neither pharmacological inhibition nor genetic ablation of CB2 had any effect on CB2 agonist-induced macrophage chemotaxis. As chemotaxis was pertussis toxin sensitive in both WT and CB2-/- macrophages, we concluded that a non-CB1/CB2, Gi/o-coupled GPCR must be responsible for CB2 agonist-induced macrophage migration. The obvious candidate receptors GPR18 and GPR55 could not mediate JWH133 or HU308-induced cytoskeletal rearrangement or JWH133-induced β-arrestin recruitment in cells transfected with either receptor, demonstrating that neither are the unidentified GPCR. Taken together our results conclusively demonstrate that CB2 is not a chemoattractant receptor for murine macrophages. Furthermore we show for the first time that JWH133, HU308, L-759,656 and L-759,633 have off-target effects of functional consequence in primary cells and we believe that our findings have wide ranging implications for the entire cannabinoid field. PMID:26033291

  9. A Marvelous Star in M33

    NASA Astrophysics Data System (ADS)

    Polomski, Elisha; Gehrz, R. D.; McQuinn, K.; Paffel, F.; Woodward, C. E.

    2012-05-01

    The end stages of stellar evolution release heavy element enriched dust into the interstellar medium where it is eventually incorporated into star formation regions and later generations of stars. As low mass stars go through this process they bloat in size, pulsate, and expel dust and gas before ultimately transforming into planetary nebulae (PNe). A classic example of this stage of evolution is the well studied class of pulsating stars, the Mira variables. Prior to expelling a PNe, these objects go through a short (tens of thousands of years) stage of evolution where they undergo episodic mass loss and become enshrouded in dust. We report the discovery of an unusual Mira star within the M33 galaxy; IRAC 0134+3029. The source is heavily obscured in the visible, indicating large amounts of enshrouding dust. In addition, Spitzer Space Telescope spectroscopy and imaging show strong thermal emission as well as absorption features from silicates. Examination of the properties of IRAC 0134 suggests that it is the extragalactic analog of the well known "extreme" Mira OH26.5+0.6. We compare spectra and photometry of IRAC 0134 to observations of OH26.5+.6 as well as to the prototype of the Mira class, Omicron Ceti. We also discuss some contradictory archival observations of these objects and suggest possible explanations. This work is based upon observations made with the Spitzer Space Telescope, which is operated by the Jet Propulsion Laboratory, California Institute of Technology under NASA contract 1407. The authors were supported in part through contracts 1256406 and 1215746 issued by JPL/Caltech to the University of Minnesota.

  10. Human prostacyclin receptor structure and function from naturally-occurring and synthetic mutations.

    PubMed

    Stitham, Jeremiah; Arehart, Eric J; Gleim, Scott R; Douville, Karen L; Hwa, John

    2007-01-01

    Prostacyclin (PGI2) is released by vascular endothelial cells and serves as a potent vasodilator, inhibitor of platelet aggregation (anti-thrombotic), and moderator of vascular smooth muscle cell proliferation-migration-differentiation (anti-atherosclerotic). These actions are mediated via a seven transmembrane-spanning G-protein coupled receptor (GPCR), known as the human prostacyclin receptor or hIP. Animal studies using prostacyclin receptor knock-out (IP-/-) mice have revealed increased propensities towards thrombosis, intimal hyperplasia, atherosclerosis, restenosis, as well as reperfusion injury. Of further importance has been the world-wide withdrawal of selective COX-2 inhibitors, due to their discriminating suppression of COX-2-derived PGI2 and its cardioprotective effects, leading to increased cardiovascular events, including myocardial infarction and thrombotic stroke. Over the last decade, mutagenesis studies of the IP receptor, in conjunction with in vitro functional assays and molecular modeling, have provided critical insights into the molecular mechanisms of both agonist binding and receptor activation. Most recently, the discovery of naturally-occurring and dysfunctional mutations within the hIP has provided additional insights into the proposed cardioprotective role of prostacyclin. The aim of this review is to summarize the most recent findings regarding hIP receptor structure-function that have developed through the study of both synthetic and naturally-occurring mutations. PMID:17164137

  11. 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.

  12. Spectral energy distributions of H ii regions in M 33 (HerM33es)

    NASA Astrophysics Data System (ADS)

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

    2013-04-01

    Aims: Within the framework of the Herschel M 33 extended survey HerM33es and in combination with multi-wavelength data we study the spectral energy distribution (SED) of a set of H ii regions in the Local Group galaxy M 33 as a function of the morphology. We analyse the emission distribution in regions with different morphologies and present models to infer the Hα emission measure observed for H ii regions with well defined morphology. Methods: We present a catalogue of 119 H ii regions morphologically classified: 9 filled, 47 mixed, 36 shell, and 27 clear shell H ii regions. For each object we extracted the photometry at twelve available wavelength bands, covering a wide wavelength range from FUV-1516 Å (GALEX) to IR-250 μm (Herschel), and we obtained the SED for each object. We also obtained emission line profiles in vertical and horizontal directions across the regions to study the location of the stellar, ionised gas, and dust components. We constructed a simple geometrical model for the clear shell regions, whose properties allowed us to infer the electron density of these regions. Results: We find trends for the SEDs related to the morphology of the regions, showing that the star and gas-dust configuration affects the ratios of the emission in different bands. The mixed and filled regions show higher emission at 24 μm, corresponding to warm dust, than the shells and clear shells. This could be due to the proximity of the dust to the stellar clusters in the case of filled and mixed regions. The far-IR peak for shells and clear shells seems to be located towards longer wavelengths, indicating that the dust is colder for this type of object. The logarithmic 100 μm/70 μm ratio for filled and mixed regions remains constant over one order of magnitude in Hα and FUV surface brightness, while the shells and clear shells exhibit a wider range of values of almost two orders of magnitude. We derive dust masses and dust temperatures for each H ii region by fitting

  13. Studying the Gravitational Dark Matter Wake of M33

    NASA Astrophysics Data System (ADS)

    Yingling, William; Besla, Gurtina

    2016-06-01

    Recent proper motions of M31 by Sohn et al. 2012 indicate that the Milky Way and Andromeda will coalesce in ~5.9 Gyr. We investigate the effects of dynamical friction exerted on M31's satellite galaxy M33 in the near future and throughout the impending Milky Way-Andromeda-M33 merger. We use the merger simulation presented in van der Marel, Besla, et al. (2012) with approximately 10^6 dark matter particles in order to analyze the density and morphology of the induced gravitational wake as M33 orbits within the dark matter halo of Andromeda and ultimately within the halo of the Andromeda-Milky Way merger remnant. We explore the mass, density and time evolution of the induced wake and its future consequences to M33's orbit and Andromeda's galactic disk.

  14. Spectroscopic Confirmation and Classification of the Recent M33 Nova Candidate, M33N 2010-12a

    NASA Astrophysics Data System (ADS)

    Shafter, A. W.; Ciardullo, R.; Bode, M. F.; Darnley, M. J.; Misselt, K. A.

    2010-12-01

    We report spectroscopic observations of the M33 nova candidate, M33N 2010-12a, recently discovered at m=16.6 (unfiltered) by T. Yusa on 2010 Dec. 17.42 UT (CBET #2595). At our request a spectrum (410-910 nm) of M33N 2010-12a was obtained by John Caldwell on 2010 Dec. 22.20 UT (~5 days post discovery) with the Marcario Low-Resolution Spectrograph on the 9.2m Hobby-Eberly Telescope.

  15. Spectroscopic Confirmation of the Recent Nova Candidate in M33 M33N 2009-01a

    NASA Astrophysics Data System (ADS)

    Shafter, A. W.; Ciardullo, R.; Bode, M. F.; Darnley, M. J.; Misselt, K. A.

    2009-01-01

    We report spectroscopic observations of the recent M33 nova candidate, M33N 2009-01a, which was discovered on 2009 Jan. 07.54 by K. Nishiyama and F. Kabashima (CBET #1659). At our request, a spectrum (410-950 nm) of M33N 2009-01a was obtained approximately a week after discovery on 2009 Jan. 14.15 UT by J. Caldwell with the 9.2m Hobby-Eberly Telescope (+ Marcario Low-Resolution Spectrograph).

  16. Chandra Acis Survey of M33 (ChASeM33): The unequal siblings NGC604 and IC131

    NASA Astrophysics Data System (ADS)

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

    2009-09-01

    We present results from the first detailed analysis of the diffuse X-ray emission in NGC604 and IC131. These regions are the only X-ray bright giant HII regions in M33 and were observed as part of ChASeM33. The main bubbles in NGC604 are filled with a hot thermal plasma of kT=0.5keV. The X-ray gas mass and unabsorbed X-ray luminosity in the western part of NGC604 are consistent with stellar mass-loss from 200 OB-stars and agree well with predictions from the standard bubble model. In the eastern part of NGC604 mass loss from young stars alone cannot account for the X-ray luminosity and another mechanism, such as off-center SNRs, is required to produce the additional luminosity. The X-ray spectrum of the extended emission in IC131 can be equally well fitted by an absorbed powerlaw (Γ=2.2) or an absorbed thermal plasma model (kT=4.3keV). Both models predict that more than 40% of the luminosity is emitted above 2keV. Compared to other HII regions, IC131 is extreme regarding its large extent of the X-ray emission (˜200pc), the lack of O stars, its high electron temperature (assuming thermal emission), and large fraction of hard X-rays. A thermal plasma of 4keV poses serious challenges to theoretical models, as it is unclear how such high electron temperatures can be obtained. In case the gas is non-thermal, it remains to be understood if the same mechanisms which create non-thermal X-rays or accelerate CRs in SNRs are applicable to these much larger scales. In both cases appropriate theoretical models are needed. Clearly, NGC604 and IC131 seem to be in completely different evolutionary stages. All O-type stars in IC131 seemed to have turned into SNe, whereas the western part of NGC604 awaits its first SNe to occur. Support for this work was provided by NASA through Chandra Award Number G06-7073A.

  17. 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.

  18. 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.

  19. Spectroscopic Observations of the Recent M33 Nova Candidate

    NASA Astrophysics Data System (ADS)

    Shafter, A. W.; Ciardullo, R.; Bode, M. F.; Darnley, M. J.; Misselt, K. A.

    2010-10-01

    We report spectroscopic observations of the recent M33 nova candidate (M33N 2010-10a?), which was discovered by K. Nishiyama and F. Kabashima (Miyaki-Argenteus Observatory, Japan) on 2010 Oct. 26.65 UT. At our request a spectrum (410-950 nm) of the nova candidate was obtained by John Caldwell on 2010 Oct. 28.37 UT (~2 days post discovery) with the Marcario Low-Resolution Spectrograph on the 9.2m Hobby-Eberly Telescope.

  20. 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.

  1. 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.

  2. ON THE SPECTROSCOPIC CLASSES OF NOVAE IN M33

    SciTech Connect

    Shafter, A. W.; Darnley, M. J.; Bode, M. F.; Ciardullo, R.

    2012-06-20

    We report the initial results from an ongoing multi-year spectroscopic survey of novae in M33. The survey resulted in the spectroscopic classification of six novae (M33N 2006-09a, 2007-09a, 2009-01a, 2010-10a, 2010-11a, and 2011-12a) and a determination of rates of decline (t{sub 2} times) for four of them (2006-09a, 2007-09a, 2009-01a, and 2010-10a). When these data are combined with existing spectroscopic data for two additional M33 novae (2003-09a and 2008-02a), we find that five of the eight novae with available spectroscopic class appear to be members of either the He/N or Fe IIb (hybrid) classes, with only two clear members of the Fe II spectroscopic class. This initial finding is very different from what would be expected based on the results for M31 and the Galaxy where Fe II novae dominate, and the He/N and Fe IIb classes together make up only {approx}20% of the total. It is plausible that the increased fraction of He/N and Fe IIb novae observed in M33 thus far may be the result of the younger stellar population that dominates this galaxy, which is expected to produce novae that harbor generally more massive white dwarfs than those typically associated with novae in M31 or the Milky Way.

  3. 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.

  4. 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

  5. Arecibo Search for Radio Pulses from M33

    NASA Astrophysics Data System (ADS)

    Crawford, Fronefield; Cordes, James M.; Spitler, Laura

    2016-01-01

    All radio pulsars that have been discovered to date are located within the Milky Way and its globular clusters, or in the Magellanic Clouds. The increased sensitivity of the wide-bandwidth Puerto Rico Ultimate Pulsar Processing Instrument (PUPPI) installed at the Arecibo Observatory makes detection of pulsars beyond the Magellanic Clouds a promising possibility. We are using the PUPPI backend and the 327 MHz receiver at Arecibo to try to detect giant radio pulses from neutron stars in the nearby spiral galaxy M33. Pulsars in M33 could be used to probe the local intergalactic medium and would help us study neutron star formation and pulsar evolution in another spiral galaxy. Using the Crab pulsar as a guide, we estimate that giant pulses from every Crab-like pulsar beaming toward us from the M33 optical disk ought to be detectable in our search, with several pulses detected in each hour of integration time. In this presentation I describe this project and provide an update on the status of the search.

  6. IRS Follow-up of Sources in M33

    NASA Astrophysics Data System (ADS)

    Houck, James R.; Roellig, Thomas; Buckalew, Brent; Gehrz, Robert D.; McQuinn, Kristy; Polomski, Elisha; Roellig, Thomas L.; Woodward, Charles

    2006-05-01

    We are currently engaged in a Guaranteed Time Observation (GTO) program (PID 5) to obtain MIPS and IRAC maps of M33 that will provide a global perspective on star formation, stellar evolution, and chemical evolution in the interstellar medium in a spiral galaxy. Combined with ground-based observations, these maps will provide a unified set of images that relate the locations of chemical enrichment, gas available to form stars, star formation, and evolved stars. We are proposing here to perform IRS spectroscopy using all of the IRS modules to follow-up on five embedded compact HII clusters which are located at various distances ranging up to 3.5 kpc from the center of M33. The low-resolution data will be particularly useful in identifying broad-band solid-state features, while the high-resolution module observations will be used to measure the strength of fine-structure emission lines, providing a wealth of information on the excitation levels and electron densities in the targets, without the complicating effects of extinction that hampers optical studies of these highly-enshrouded objects. Our proposed observations will allow important new insight into how star formation environments change across the face of the spiral galaxy M33.

  7. [Ci](1-0) observations in M33 A study of CO dark H2 gas in M33

    NASA Astrophysics Data System (ADS)

    Glück, C.; Mookerjea, B.; Okada, Y.; Buchbender, C.; Röllig, M.; Stutzki, J.

    2016-05-01

    Based on [Ci] (1-0) observations and complementary Hi, 12/13CO (1-0), 12CO (2-1) and [Cii] data we estimated the column density and fraction of molecular hydrogen in GMCs along the major axis of the galaxy M33. We found that on average 75%± 14% of the hydrogen is in molecular form. Roughly 40-45% of the H2 is both traced by [Cii] and CO, while ˜ 15% by the [Ci] lines. The found CO-dark H2 gas fractions are within the predictions by Wolfire et al. (2010) for a half solar metallicity, Z = 0.5 Z⊙, as in M33.

  8. M33 X-7: ChASeM33 Reveals the First Eclipsing Black Hole X-Ray Binary

    NASA Astrophysics Data System (ADS)

    Pietsch, W.; Haberl, F.; Sasaki, M.; Gaetz, T. J.; Plucinsky, P. P.; Ghavamian, P.; Long, K. S.; Pannuti, T. G.

    2006-07-01

    The first observations conducted as part of the Chandra ACIS survey of M33 (ChASeM33) sampled the eclipsing X-ray binary M33 X-7 over a large part of the 3.45 day orbital period and have resolved eclipse ingress and egress for the first time. The occurrence of the X-ray eclipse allows us to determine an improved ephemeris of mid-eclipse and binary period as HJD (2,453,639.119+/-0.005)+/-N(3.453014+/-0.000020) and constrain the eclipse half-angle to 26.5d+/-1.1d. There are indications for a shortening of the orbital period. The X-ray spectrum is best described by a disk blackbody spectrum typical for black hole X-ray binaries in the Galaxy. We find a flat power density spectrum, and no significant regular pulsations were found in the frequency range of 10-4 to 0.15 Hz. HST WFPC2 images resolve the optical counterpart, which can be identified as an O6 III star with the help of extinction and color corrections derived from the X-ray absorption. Based on the optical light curve, the mass of the compact object in the system most likely exceeds 9 Msolar. This mass, the shape of the X-ray spectrum, and the short-term X-ray time variability identify M33 X-7 as the first eclipsing black hole high-mass X-ray binary.

  9. 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.

  10. 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. PMID:21227907

  11. The UV interstellar extinction in nearby galaxies: M33

    NASA Astrophysics Data System (ADS)

    Bianchi, Luciana

    2001-07-01

    We previously used HST to determine the UV extinction curve in M31. Our result in M31, together with other studies of the Magellanic Clouds and Milky Way, suggests that dust properties vary in different environments and from galaxy to galaxy. Thus average Galactic dust properties cannot be usefully employed to correct for dust effects in different galaxies. We propose to enlarge our sample by studying the UV extinction properties of dust in M33, sampling different galactocentric distances and levels of star formation activity. The extinction curves will be derived by comparing stars with the same spectral type, but different extinction amounts, in M33. This eliminates uncertainties in using standard stars from other galaxies, that may have different intrinsic spectra. For the targets we have U, B, V and UV photometry, and accurate spectral types from ground based spectra. UV extinction gives information on the properties of dust, which is an important tracer of global heavy element abundances. The steepness of the FUV extinction affects the ionisation and molecular chemistry of a galaxy. Knowledge of the extinction curve also allows accurate corrections of observed fluxes: ultimately, relating dust properties to global galaxy parameters will enable better extinction corrections in distant galaxies and AGN. We also request WFPC2 parallel imaging to continue our stellar population studies.

  12. Selective Phthalate Activation of Naturally Occurring Human Constitutive Androstane Receptor Splice Variants and the Pregnane X Receptor

    PubMed Central

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

    2011-01-01

    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. PMID:21227907

  13. 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.

  14. A Deep XMM-Newton Legacy Survey of M33

    NASA Astrophysics Data System (ADS)

    Williams, Benjamin

    We propose for financial support that will allow us to reduce and analyze all XMM- Newton data relevant to an A09 deep XMM-Newton legacy survey of M33 covering the entire optical disk with a total of 700000 seconds of exposure time. These data will allow us to determine how the temperature and energetics of the hot interstellar medium (ISM) are affected by star formation, constrain the nature and dynamical masses of new pulsating and eclipsing X-ray binaries, and perform detailed statistical and spectral studies on the largest known extragalactic population of X-ray supernova remnants (SNRs). The support proposed here is crucial for the full analysis and publication of the entire data set. Measurements and model fitting of the spectra and timing of all of the discrete sources detected in our data will constrain the nature and dynamical masses of new pulsating and eclipsing X-ray binaries, as well as provide new insight into the origins of the X-ray SNRs. Spatially-resolved, spectral studies of the diffuse emission will allow us to determine how the temperature and energetics of the hot interstellar medium (ISM) are affected by star formation. Several members of our team have already performed similar analysis to those proposed using data from the deep Chandra ACIS-I survey of M33 (ChASeM33), and we intend to hire a postdoctoral research associate who has experience working with large XMM-Newton data sets. Therefore the techniques for making the measurements are well-understood; however, the deep Chandra ACIS-I survey of M33 does not provide sufficient soft response for detailed spectral measurements of the diffuse gas emission from dozens of individual star forming regions. To reliably determine the temperature structure of the interstellar gas of these regions, our simulations show that we need to go a factor of 10 deeper in the soft X-ray band than existing X-ray data, which will be achieved with our proposed observations. Furthermore, XMM-Newton studies of X

  15. THE M 33 SYNOPTIC STELLAR SURVEY. I. CEPHEID VARIABLES

    SciTech Connect

    Pellerin, Anne; Macri, Lucas M. E-mail: lmacri@physics.tamu.edu

    2011-04-01

    We have conducted a ground-based BVI synoptic survey of the Local Group galaxy M 33 which covers most of its disk and spans a period of 7 years. The survey targets luminous, long-period variables such as Cepheids and Miras and combines images from the DIRECT project and follow-up observations at the WIYN 3.5 m telescope. This paper, the first in a series, presents the discovery and characterization of 564 Cepheid variables, which represent a factor of two increase over previous samples with calibrated point-spread function (PSF) photometry. We also describe the details of the observations and analysis of the survey data, including the use of archival Hubble Space Telescope images to characterize biases in our ground-based PSF photometry.

  16. Bipolar Outflow Offset from the Nucleus of M33

    NASA Astrophysics Data System (ADS)

    Roming, P. W. A.; Moody, J. W.; Hintz, M. L.; Wu, K.; Soria, R.

    2002-12-01

    Using long-slit spectra centered in wavelength about Hα , we have produced a velocity map of a 0.5' x 2' hourglass shaped object centered 38" southeast of the optical center of M33. The velocity resolution is 1.1 km/s. We have also produced electron temperature, electron density, and shock heating maps of the same region using the [NII](λ 6548), [NII](λ 6583), Hα , [SII](λ 6717), and [SII](λ 6731) lines. The data reveal that the gas is flowing away from the center of this hourglass shaped object and that the electron temperature and density of the region is relatively low. The shock heating maps indicate that very little of the gas in the region is shock heated. Using this new data and previously published UV, IR, and radio data we investigate possible scenarios that could explain this large scale, low velocity outflow.

  17. 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.

  18. The stellar populations of M33's outer regions - IV. Inflow history and chemical evolution

    NASA Astrophysics Data System (ADS)

    Barker, Michael K.; Sarajedini, A.

    2008-10-01

    We have modelled the observed colour-magnitude diagram (CMD) at one location in M33's outskirts under the framework of a simple chemical evolution scenario which adopts instantaneous and delayed recycling for the nucleosynthetic products of Type II and Ia supernovae. In this scenario, interstellar gas forms stars at a rate modulated by the Kennicutt-Schmidt relation and gas outflow occurs at a rate proportional to the star formation rate (SFR). With this approach, we put broad constraints on the role of gas flows during this region's evolution and compare its [α/Fe] versus [Fe/H] relation with that of other Local Group systems. We find that models with gas inflow are significantly better than the closed-box model at reproducing the observed distribution of stars in the CMD. The best models have a majority of gas inflow taking place in the last 7 Gyr, and relatively little in the last 3 Gyr. These models predict most stars in this region to have [α/Fe] ratios lower than the bulk of the Milky Way's halo. The predictions for the present-day SFR, gas mass and oxygen abundance compare favourably to independent empirical estimates. Our results paint a picture in which M33's outer disc formed from the protracted inflow of gas over several Gyr with at least half of the total inflow occurring since z ~ 1.

  19. THE NEUTRAL HYDROGEN BRIDGE BETWEEN M31 AND M33

    SciTech Connect

    Lockman, Felix J.; Free, Nicole L.; Shields, Joseph C.

    2012-08-15

    The Green Bank Telescope has been used to search for 21 cm H I emission over a large area between the galaxies M31 and M33 in an attempt to confirm at 9.'1 angular resolution the detection by Braun and Thilker of a very extensive neutral gas 'bridge' between the two systems at the level N{sub HI} Almost-Equal-To 10{sup 17} cm{sup -2}. We detect H I emission at several locations up to 120 kpc in projected distance from M31, at least half the distance to M33, with velocities similar to that of the galaxies, confirming the essence of the Braun and Thilker discovery. The H I does not appear to be associated with the extraplanar high-velocity clouds of either galaxy. In two places we measure N{sub HI} > 3 Multiplication-Sign 10{sup 18} cm{sup -2}, indicative of concentrations of H I with {approx}10{sup 5} M{sub Sun} on scales {approx}< 2 kpc, but over most of the field we have only 5{sigma} upper limits of N{sub HI} {<=} 1.4 Multiplication-Sign 10{sup 18} cm{sup -2}. In very deep measurements in two directions H I lines were detected at a few 10{sup 17} cm{sup -2}. The absence of emission at another location to a 5{sigma} limit N{sub HI} {<=} 1.5 Multiplication-Sign 10{sup 17} cm{sup -2} suggests that the H I bridge is either patchy or confined to within {approx}125 kpc of M31. The measurements also cover two of M31's dwarf galaxies, And II and And XV, but in neither case is there evidence for associated H I at the 5{sigma} level of 1.4 Multiplication-Sign 10{sup 4} M{sub Sun} for And II and 9.3 Multiplication-Sign 10{sup 3} M{sub Sun} for And XV.

  20. 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.

  1. HI and Hα Mapping of M31 & M33

    NASA Astrophysics Data System (ADS)

    Kam, Z. S.; Carignan, C.; Chemin, L.; Hernandez, O.; de Denus-Baillargeon, M.; Djabo, Y.

    2011-12-01

    abstract-type="normal">RésuméWe performed a deep Hi and Hα mapping of M31 and M33 in order to get accurate kinematical data of those two galaxies and also to make a comparison between the Hi and Hα kinematics. The Hi data were obtained with the DRAO interferometer and the Hα data with the Fabry-Perot system of the Observatoire du mont Mégantic using an EMCCD as a detector. These data will give us the best possible datasets to derive accurate rotation curves and mass models for those two Local Group spirals and provide some new data for the Hii regions studies of these galaxies. While the Hi observations are of low resolution (~1 arcmin), the high resolution of the Hα data (~1 arcsec) should allow us to get much more details in the central regions, allowing at the same time a much better determination of the kinematical parameters. Hence, the inner part of the rotation curve, so inportant to constraint properly the mass models, will be determined more accurately.

  2. 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.

  3. 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.

  4. 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

  5. Tethering naturally occurring peptide toxins for cell-autonomous modulation of ion channels and receptors in vivo.

    PubMed

    Ibañez-Tallon, Inés; Wen, Hua; Miwa, Julie M; Xing, Jie; Tekinay, Ayse B; Ono, Fumihito; Brehm, Paul; Heintz, Nathaniel

    2004-08-01

    The physiologies of cells depend on electrochemical signals carried by ion channels and receptors. Venomous animals produce an enormous variety of peptide toxins with high affinity for specific ion channels and receptors. The mammalian prototoxin lynx1 shares with alpha-bungarotoxin the ability to bind and modulate nicotinic receptors (nAChRs); however, lynx1 is tethered to the membrane via a GPI anchor. We show here that several classes of neurotoxins, including bungarotoxins and cobratoxins, retain their selective antagonistic properties when tethered to the membrane. Targeted elimination of nAChR function in zebrafish can be achieved with tethered alpha-bungarotoxin, silencing synaptic transmission without perturbing synapse formation. These studies harness the pharmacological properties of peptide toxins for use in genetic experiments. When combined with specific methods of cell and temporal expression, the extension of this approach to hundreds of naturally occurring peptide toxins opens a new landscape for cell-autonomous regulation of cellular physiology in vivo. PMID:15294139

  6. 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. PMID:21813711

  7. A Naturally Occurring GIP Receptor Variant Undergoes Enhanced Agonist-Induced Desensitization, Which Impairs GIP Control of Adipose Insulin Sensitivity

    PubMed Central

    Mohammad, Sameer; Patel, Rajesh T.; Bruno, Joanne; Panhwar, Muhammad Siyab; Wen, Jennifer

    2014-01-01

    Glucose-dependent insulinotropic polypeptide (GIP), an incretin hormone secreted from gastrointestinal K cells in response to food intake, has an important role in the control of whole-body metabolism. GIP signals through activation of the GIP receptor (GIPR), a G-protein-coupled receptor (GPCR). Dysregulation of this pathway has been implicated in the development of metabolic disease. Here we demonstrate that GIPR is constitutively trafficked between the plasma membrane and intracellular compartments of both GIP-stimulated and unstimulated adipocytes. GIP induces a downregulation of plasma membrane GIPR by slowing GIPR recycling without affecting internalization kinetics. This transient reduction in the expression of GIPR in the plasma membrane correlates with desensitization to the effects of GIP. A naturally occurring variant of GIPR (E354Q) associated with an increased incidence of insulin resistance, type 2 diabetes, and cardiovascular disease in humans responds to GIP stimulation with an exaggerated downregulation from the plasma membrane and a delayed recovery of GIP sensitivity following cessation of GIP stimulation. This perturbation in the desensitization-resensitization cycle of the GIPR variant, revealed in studies of cultured adipocytes, may contribute to the link of the E354Q variant to metabolic disease. PMID:25047836

  8. 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

  9. Shedding of epidermal growth factor receptor is a regulated process that occurs with overexpression in malignant cells.

    PubMed

    Perez-Torres, Marianela; Valle, Blanca L; Maihle, Nita J; Negron-Vega, Lisandra; Nieves-Alicea, Rene; Cora, Elsa M

    2008-10-01

    Soluble isoforms of the epidermal growth factor receptor (sEGFR) previously have been identified in the conditioned culture media (CCM) of the vulvar adenocarcinoma cell line, A431 and within exosomes of the keratinocyte cell line HaCaT. Here, we report that the extracellular domain (ECD) of EGFR is shed from the cell surface of human carcinoma cell lines that express 7x10(5) receptors/cell or more. We purified this proteolytic isoform of EGFR (PI-sEGFR) from the CCM of MDA-MB-468 breast cancer cells. The amino acid sequence of PI-sEGFR was determined by reverse-phase HPLC nano-electrospray tandem mass spectrometry of peptides generated by trypsin, chymotrypsin or GluC digestion. The PI-sEGFR protein is identical in amino acid sequence to the EGFR ECD. The release of PI-sEGFR from MDA-MB-468 cells is enhanced by phorbol 12-myristate 13-acetate, heat-inactivated fetal bovine serum, pervanadate, and EGFR ligands (i.e., EGF and TGF-alpha). In addition, 4-aminophenylmercuric acetate, an activator of metalloproteases, increased PI-sEGFR levels in the CCM of MDA-MB-468 cells. Inhibitors of metalloproteases decreased the constitutive shedding of EGFR while the PMA-induced shedding was inhibited by metalloprotease inhibitors, by the two serine protease inhibitors leupeptin and 3,4-dichloroisocoumarin (DCI), and by the aspartyl inhibitor pepstatin. These results suggest that PI-sEGFR arises by proteolytic cleavage of EGFR via a mechanism that is regulated by both PKC- and phosphorylation-dependent pathways. Our results further suggest that when proteolytic shedding of EGFR does occur, it is correlated with a highly malignant phenotype. PMID:18687326

  10. Spectroscopy and photometry of the nova candidate M33N 2013-12a

    NASA Astrophysics Data System (ADS)

    Fabrika, S.; Barsukova, E. A.; Valeev, A. F.; Sholukhova, O.; Hornoch, K.; Shafter, A. W.; Henze, M.

    2014-01-01

    We report optical spectroscopy and photometry of a recent M33 nova candidate (M33N 2013-12a = PNV J01331092+3037511) detected by the Lick Observatory Supernova Search ( http://www.cbat.eps.harvard.edu/unconf/followups/J01331092+3037511.html ).

  11. 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...

  12. 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

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

    NASA Astrophysics Data System (ADS)

    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

    2007-10-01

    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.

  14. A comprehensive analysis and functional characterization of naturally occurring non-synonymous variants of nuclear receptor PXR.

    PubMed

    Rana, Manjul; Devi, Suneeta; Gourinath, Samudrala; Goswami, Ravinder; Tyagi, Rakesh K

    2016-09-01

    Pregnane & Xenobiotic Receptor (PXR) acts as a xenosensing transcriptional regulator of many drug metabolizing enzymes and transporters of the 'detoxification machinery' that coordinate in elimination of xenobiotics and endobiotics from the cellular milieu. It is an accepted view that some individuals or specific populations display considerable differences in their ability to metabolize different drugs, dietary constituents, herbals etc. In this context we speculated that polymorphisms in PXR gene might contribute to variability in cytochrome P450 (CYP450) metabolizing enzymes of phase I, drug metabolizing components of phase II and efflux components of the detoxification machinery. Therefore, in this study, we have undertaken a comprehensive functional analysis of seventeen naturally occurring non-synonymous variants of human PXR. When compared, we observed that some of the PXR SNP variants exhibit distinct functional and dynamic responses on parameters which included transcriptional function, sub-cellular localization, mitotic chromatin binding, DNA-binding properties and other molecular interactions. One of the unique SNP located within the DNA-binding domain of PXR was found to be functionally null and distinct on other parameters. Similarly, some of the non-synonymous SNPs in PXR imparted reduced transactivation function as compared to wild type PXR. Interestingly, PXR is reported to be a mitotic chromatin binding protein and such an association has been correlated to an emerging concept of 'transcription memory' and altered transcription output. In view of the observations made herein our data suggest that some of the natural PXR variants may have adverse physiological consequences owing to its influence on the expression levels and functional output of drug-metabolizing enzymes and transporters. The present study is expected to explain not only the observed inter-individual responses to different drugs but may also highlight the mechanistic details and

  15. 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).

  16. 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.

  17. 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).

  18. 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.

  19. Activation of alpha6-containing GABAA receptors by pentobarbital occurs through a different mechanism than activation by GABA.

    PubMed

    Fisher, Matthew T; Fisher, Janet L

    2010-03-01

    The GABA(A) receptors are ligand-gated chloride channels which are the targets for many clinically used sedatives, including the barbiturates. The barbiturate pentobarbital acts through multiple sites on the GABA(A) receptor. At low concentrations (muM), it acts as a positive allosteric modulator while at higher concentrations it can directly activate the receptor. This agonist action is influenced by the subunit composition of the receptor, and pentobarbital is a more effective agonist than GABA only at receptors containing an alpha6 subunit. The conformational change that translates GABA binding into channel opening is known to involve a lysine residue located in an extracellular domain between the 2nd and 3rd transmembrane domains. Mutations of this residue disrupt activation of the channel by GABA and have been linked to inherited epilepsy. Pentobarbital binds to the receptor at a different agonist site than GABA, but could use a common signal transduction mechanism to gate the channel. To address this question, we compared the effect of a mutating the homologous lysine residue in the alpha1 or alpha6 subunits (K278 or K277, respectively) to methionine on direct activation of recombinant GABA(A) receptors by GABA or pentobarbital. We found that this mutation reduced GABA sensitivity for both alpha1 and alpha6 subunits, but affected pentobarbital sensitivity only for the alpha1 subunit. This suggests that pentobarbital acts through a distinct signal transduction pathway at the alpha6 subunit, which may account for its greater efficacy compared to GABA at receptors containing this subunit. PMID:20109529

  20. 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

  1. 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...

  2. 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

  3. 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.

  4. 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. PMID:26741298

  5. Time variability of the X-ray sources in M33

    NASA Technical Reports Server (NTRS)

    Peres, G.; Reale, F.; Collura, A.; Fabbiano, G.

    1989-01-01

    The results of a variability study of the X-ray sources detected by the Einstein Observatory in the galaxy M33 are reported. Two of the 15 known sources are variable above the 99.73 percent confidence level. The light curve of one of these sources, M33 X-7, exhibits a variability pattern of high and low states, suggesting an eclipsing binary X-ray source. Such a finding would be the first identification of a close accreting binary system with an X-ray source in an external galaxy other than the Magellanic Clouds. The data suggest a binary period of 1.7857 day and an eclipse duration of about 0.4 day. The nuclear source M33 X-8 varies only in the softest part of the spectrum. The observations suggest a rapid variability and show a rapid flare with a rise time shorter than three days together with longer timescale variability.

  6. Age and Mass Estimates for 41 Star Clusters in M33

    NASA Astrophysics Data System (ADS)

    Ma, Jun; Zhou, Xu; Chen, Jian-Sheng

    2004-04-01

    In this second paper of our series, we estimate the age of 41 star clusters, which were detected by Melnick & D'odorico in the nearby spiral galaxy M33, by comparing the integrated photometric measurements with theoretical stellar population synthesis models of Bruzual & Charlot. Also, we calculate the mass of these star clusters using the theoretical M/L_V ratio. The results show that, these star clusters formed continuously in M33 from ˜ 7× 106 -- 1010 years and have masses between ˜ 103 and 2 ×106 M⊙. M33 frames were observed as a part of the BATC Multicolor Survey of the sky in 13 intermediate-band filters from 3800 to 10 000 Å. The relation between age and mass confirms that the sample star cluster masses systematically decrease from the oldest to the youngest.

  7. 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.

  8. Mutant forms of tumour necrosis factor receptor I that occur in TNF-receptor-associated periodic syndrome retain signalling functions but show abnormal behaviour

    PubMed Central

    Todd, Ian; Radford, Paul M; Draper-Morgan, Kelly-Ann; McIntosh, Richard; Bainbridge, Susan; Dickinson, Peter; Jamhawi, Lama; Sansaridis, Marios; Huggins, Mary L; Tighe, Patrick J; Powell, Richard J

    2004-01-01

    Tumour necrosis factor (TNF)-receptor-associated periodic syndrome (TRAPS) is a hereditary autoinflammatory disorder involving autosomal-dominant missense mutations in TNF receptor superfamily 1A (TNFRSF1A) ectodomains. To elucidate the molecular effects of TRAPS-related mutations, we transfected HEK-293 cells to produce lines stably expressing high levels of either wild-type (WT) or single mutant recombinant forms of TNFRSF1A. Mutants with single amino acid substitutions in the first cysteine-rich domain (CRD1) were produced both as full-length receptor proteins and as truncated forms lacking the cytoplasmic signalling domain (Δsig). High-level expression of either WT or mutant full-length TNFRSF1A spontaneously induced apoptosis and interleukin-8 production, indicating that the mutations in CRD1 did not abrogate signalling. Consistent with this, WT and mutant full-length TNFRSF1A formed cytoplasmic aggregates that co-localized with ubiquitin and chaperones, and with the signal transducer TRADD, but not with the inhibitor, silencer of death domain (SODD). Furthermore, as expected, WT and mutant Δsig forms of TNFRSF1A did not induce apoptosis or interleukin-8 production. However, whereas the WT full-length TNFRSF1A was expressed both in the cytoplasm and on the cell surface, the mutant receptors showed strong cytoplasmic expression but reduced cell-surface expression. The WT and mutant Δsig forms of TNFRSF1A were all expressed at the cell surface, but a proportion of the mutant receptors were also retained in the cytoplasm and co-localized with BiP. Furthermore, the mutant forms of surface-expressed Δsig TNFRSF1A were defective in binding TNF-α. We conclude that TRAPS-related CRD1 mutants of TNFRSF1A possess signalling properties associated with the cytoplasmic death domain, but other behavioural features of the mutant receptors are abnormal, including intracellular trafficking and TNF binding. PMID:15312137

  9. Cellular uptake of the antitumor agent Dp44mT occurs via a carrier/receptor-mediated mechanism.

    PubMed

    Merlot, Angelica M; Pantarat, Namfon; Menezes, Sharleen V; Sahni, Sumit; Richardson, Des R; Kalinowski, Danuta S

    2013-12-01

    The chelator di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) shows potent and selective anticancer and antimetastatic activity. However, the mechanism by which it is initially transported into cells to induce cytotoxicity is unknown. Hence, the current investigation examined the cellular uptake of ¹⁴C-Dp44mT relative to two structurally related ligands, namely the aroylhydrazone ¹⁴C-pyridoxal isonicotinoyl hydrazone (¹⁴C-PIH) and the thiosemicarbazone (¹⁴C-2-benzoylpyridine 4-ethyl-3-thiosemicarbazone (¹⁴C-Bp4eT). In marked contrast to the cellular uptake of ¹⁴C-PIH and ¹⁴C-Bp4eT, which were linear as a function of concentration, ¹⁴C-Dp44mT uptake was saturable using SK-N-MC neuroepithelioma cells (Bmax, 4.28 × 10⁷ molecules of chelator/cell; and Kd, 2.45 μM). Together with the fact that ¹⁴C-Dp44mT uptake was temperature-dependent and significantly (P < 0.01) decreased by competing unlabeled Dp44mT, these observations indicated a saturable transport mechanism consistent with carrier/receptor-mediated transport. Other unlabeled ligands that shared the saturated N4 structural moiety with Dp44mT significantly (P < 0.01) inhibited ¹⁴C-Dp44mT uptake, illustrating its importance for carrier/receptor recognition. Nevertheless, unlabeled Dp44mT most markedly decreased (¹⁴C-Dp44mT uptake, demonstrating that the putative carrier/receptor shows high selectivity for Dp44mT. Interestingly, in contrast to ¹⁴C-Dp44mT, uptake of its Fe complex [Fe(¹⁴C-Dp44mT)₂] was not saturable as a function of concentration and was much greater than the ligand alone, indicating an alternate mode of transport. Studies examining the tissue distribution of ¹⁴C-Dp44mT injected intravenously into a mouse tumor model demonstrated the ¹⁴C label was primarily identified in the excretory system. Collectively, these findings examining the mechanism of Dp44mT uptake and its distribution and excretion have clinical implications for its

  10. 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

  11. 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.

  12. 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.

  13. Platelet Antistaphylococcal Responses Occur through P2X1 and P2Y12 Receptor-Induced Activation and Kinocidin Release▿

    PubMed Central

    Trier, Darin A.; Gank, Kimberly D.; Kupferwasser, Deborah; Yount, Nannette Y.; French, William J.; Michelson, Alan D.; Kupferwasser, Leon I.; Xiong, Yan Q.; Bayer, Arnold S.; Yeaman, Michael R.

    2008-01-01

    Platelets (PLTs) act in antimicrobial host defense by releasing PLT microbicidal proteins (PMPs) or PLT kinocidins (PKs). Receptors mediating staphylocidal efficacy and PMP or PK release versus isogenic PMP-susceptible (ISP479C) and -resistant (ISP479R) Staphylococcus aureus strains were examined in vitro. Isolated PLTs were incubated with ISP479C or ISP479R (PLT/S. aureus ratio range, 1:1 to 10,000:1) in the presence or absence of a panel of PLT inhibitors, including P2X and P2Y receptor antagonists of increasingly narrow specificity, and PLT adhesion receptors (CD41, CD42b, and CD62P). PLT-to-S. aureus exposure ratios of ≥10:1 yielded significant reductions in the viability of both strains. Results from reversed-phase high-performance liquid chromatography indicated that staphylocidal PLT releasates contained PMPs and PKs. At ratios below 10:1, the PLT antistaphylococcal efficacy relative to the intrinsic S. aureus PMP-susceptible or -resistant phenotype diminished. Apyrase (an agent of ADP degradation), suramin (a general P2 receptor antagonist), pyridoxal 5′-phosphonucleotide derivative (a specific P2X1 antagonist), and cangrelor (a specific P2Y12 antagonist) mitigated the PLT staphylocidal response against both strains, correlating with reduced levels of PMP and PK release. Specific inhibition occurred in the presence and absence of homologous plasma. The antagonism of the thromboxane A2, cyclooxygenase-1/cyclooxygenase-2, or phospholipase C pathway or the hindrance of surface adhesion receptors failed to impede PLT anti-S. aureus responses. These results suggest a multifactorial PLT anti-S. aureus response mechanism involving (i) a PLT-to-S. aureus ratio sufficient for activation; (ii) the ensuing degranulation of PMPs, PKs, ADP, and/or ATP; (iii) the activation of P2X1/P2Y12 receptors on adjacent PLTs; and (iv) the recursive amplification of PMP and PK release from these PLTs. PMID:18824536

  14. 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

  15. 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

  16. Death Receptor-Induced Apoptosis Signalling Regulation by Ezrin Is Cell Type Dependent and Occurs in a DISC-Independent Manner in Colon Cancer Cells

    PubMed Central

    Iessi, Elisabetta; Zischler, Luciana; Etringer, Aurélie; Bergeret, Marion; Morlé, Aymeric; Jacquemin, Guillaume; Morizot, Alexandre; Shirley, Sarah; Lalaoui, Najoua; Elifio-Esposito, Selene L.; Fais, Stefano; Garrido, Carmen; Solary, Eric; Micheau, Olivier

    2015-01-01

    Ezrin belongs to the ERM (ezrin-radixin-moesin) protein family and has been demonstrated to regulate early steps of Fas receptor signalling in lymphoid cells, but its contribution to TRAIL-induced cell death regulation in adherent cancer cells remains unknown. In this study we report that regulation of FasL and TRAIL-induced cell death by ezrin is cell type dependant. Ezrin is a positive regulator of apoptosis in T-lymphoma cell line Jurkat, but a negative regulator in colon cancer cells. Using ezrin phosphorylation or actin-binding mutants, we provide evidence that negative regulation of death receptor-induced apoptosis by ezrin occurs in a cytoskeleton- and DISC-independent manner, in colon cancer cells. Remarkably, inhibition of apoptosis induced by these ligands was found to be tightly associated with regulation of ezrin phosphorylation on serine 66, the tumor suppressor gene WWOX and activation of PKA. Deficiency in WWOX expression in the liver cancer SK-HEP1 or the pancreatic Mia PaCa-2 cell lines as well as WWOX silencing or modulation of PKA activation by pharmacological regulators, in the colon cancer cell line SW480, abrogated regulation of TRAIL signalling by ezrin. Altogether our results show that death receptor pro-apoptotic signalling regulation by ezrin can occur downstream of the DISC in colon cancer cells. PMID:26010871

  17. Dense Gas and Star Formation Along the Major Axis of M33 (HERM33ES)

    NASA Astrophysics Data System (ADS)

    Buchbender, C.; Kramer, C.; Rosolowsky, E.

    2011-05-01

    Using the IRAM 30m telescope we observed and detected HCN and HCO^+ 1-0 towards 6 positions along the major axis of the nearby spiral galaxy M33, at radial distances of up to 3.4 kpc. M33, viewed at an intermediate inclination from a distance of 840 kpc, is an ideal source to study these molecules in an environment not affected by an active galactic nucleus (AGN). Unlike the Galaxy, which is seen edge-on, M33's inclination of 56 degrees allows to determine precise positions and velocities inside its large scale disk. Furthermore, at this distance M33 is still near enough that individual giant molecular clouds (GMCs) can be resolved by the 28" beam of the IRAM 30m at the frequencies of HCN and HCO^+, which translates to 114 pc spatial resolution. HCN, HCO^+, and 13CO were observed at an RMS level of about 0.7 mK at 2 km/s resolution. Additionally, the frequencies of the isotopmeres of HCN and HCO^+, HNC and HOC^+ also fall within the bandwidth of our observation setup. By stacking all observed spectra, paying the price of losing the positional information, we could lower the baseline RMS even further to 0.27 mK and detected HNC and HOC^+ as well as CCH at a very low level of ≈ 3 σ. Having high critical densities they trace the dense gas and thus also star formation (SF). HCN shows a tight correlation with SF that holds for galactic GMCs to the nuclear environment of distant star-burst (SB) galaxies as has been shown by Gao & Solomon 2004 and Wu et al. 2005. Furthermore, the ratio of HCO^+ to HCN is a popular tool in extra-galactic astronomy to investigate the predominant radiation mechanism (X-Ray - AGN , UV - SB) in galactic nuclei. Interestingly, we find HCN-to-HCO^+ ratios in the range of 0.7-2.8. This includes typical values found towards AGN and SB dominated galactic nuclei suggesting that on local scale this interpretation does not hold, since M33 is neither dominated by intense X-ray radiation nor by the influence of a nearby AGN. These observations are

  18. NRO M33 All-Disk Survey of Giant Molecular Clouds (NRO MAGiC): Properties of Giant Molecular Clouds in M33

    NASA Astrophysics Data System (ADS)

    Onodera, S.; Kuno, N.; Tosaki, T.; Muraoka, K.; Miura, R.; Kohno, K.; Nakanishi, K.; Sawada, T.; Komugi, S.; Kaneko, H.; Hirota, A.; Kawabe, R.

    2013-10-01

    We present the results of the CO-line mapping observations of the local group galaxy M33 as part of the NRO legacy project, NRO M33 All-Disk Survey of Giant Molecular Clouds (NRO MAGiC). The observations were performed using the 45-m telescope of the Nobeyama Radio Observatory and the ASTE 10-m telescope. We find that the star formation rate have very wide range of 109-106 M⊙ yr-1pc-2 among GMCs, while 12CO(J=1-0) intensity is nearly constant. This indicates that the Schmidt-Kenicutt law becomes invalid for the scale of GMCs (˜80pc). We identify 74 major GMCs in the observing field of ASTE from the 12CO(J=1-0) data, and detected 12CO(J=3-2) emission in 65 GMCs among them. We find that the correlation between the 12CO(J=3-2) intensity and the star formation rate still holds at the scale of GMCs. This result show that the star-forming activity is closely associated with warm and dense gases that are traced with the 12CO(J=3-2) line, even in the scale of GMCs. We also find that the GMCs with a high star-forming activity tend to show a high integrated intensity ratio R3-2/1-0. Moreover, we also observe a mass-dependent trend of R3-2/1-0 for the GMCs with a low star-forming activity. From these results, we speculate that the R3-2/1-0 values of the GMCs with a low star-forming activity mainly depend on the dense gas fraction and not on the temperature, and therefore, the dense gas fraction increases with the mass of GMCs, at least in the GMCs with a low star-forming activity.

  19. 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.

  20. 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.

  1. The Naturally Occurring Luteinizing Hormone Surge Is Diminished in Mice Lacking Estrogen Receptor Beta in the Ovary1

    PubMed Central

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

    2013-01-01

    ABSTRACT 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. PMID:24337314

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. Cocaine-induced dendritic remodeling occurs in both D1 and D2 dopamine receptor-expressing neurons in the nucleus accumbens.

    PubMed

    Li, Juan; Liu, Nuyun; Lu, Kangrong; Zhang, Lei; Gu, Jingjing; Guo, Fukun; An, Shengli; Zhang, Lin; Zhang, Lu

    2012-05-31

    Repeated exposure to cocaine can induce persistent alterations in the brain's reward system, including increases in the number of dendrites and spine density on medium-sized spiny neurons (MSNs) in the nucleus accumbens (NAc). The structural remodeling of dendrites and spines in the NAc is thought to play a critical role in cocaine addiction. MSNs in the NAc can be classified by expression of either D1 or D2 dopamine receptors, which are localized to the direct and indirect pathway, respectively. It is unknown whether the dendritic changes induced by repeated cocaine treatment occur in MSNs of the direct or indirect pathway. Because the traditional Golgi-Cox impregnation of neurons precludes identifying particular subpopulations of MSNs, we performed dendritic morphology analysis after biocytin-labeling and Golgi-Cox impregnation. We found that the biocytin staining MSNs showed higher dendritic spine density and higher number of dendrites than that in Golgi impregnation group. In addition, we found that the increasing spine density induced by repeated cocaine treatment in female mice was higher than that in male mice. Next we used biocytin staining and dynorphin/D2 receptor colocalization to determine which cell type(s) displayed dendritic changes after repeated cocaine treatment. We found that cocaine-induced changes in dendritic parameters occurred in MSNs of both the direct (D1-expressing) and indirect (D2-expressing) pathways. PMID:22561554

  7. 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.

  8. Clouds of neutral hydrogen between M31 and M33 and around the Milky Way

    NASA Astrophysics Data System (ADS)

    Wolfe, Spencer A.; Pisano, D. J.; Lockman, F. J.; McGaugh, S. S.; Shaya, E. J.

    2014-01-01

    Large spiral galaxies like our own Milky Way must acquire fresh gas to continue forming new stars. The gas that resides between galaxies may be a source of this material, but we know little about the gas’ structure or extent. I will present my thesis research, which attempts to answer these questions, based on our Green Bank Telescope (GBT) observations of the very faint M31-M33 neutral hydrogen (HI) stream that was first discovered a decade ago using the Westerbork Synthesis Radio Telescope. Our spectral line observations have over five times higher spatial resolution and roughly three times higher velocity resolution than the Westerbork data. These are the most sensitive observations of the 21 cm line conducted with the GBT. I will discuss our observing and reduction techniques used to reach the sensitivities needed to study the HI stream in detail. We find that the gas is actually composed of small clouds only a few kiloparsecs in diameter. The kinematics of the clouds also suggests that they are associated with M31 and M33 and not each galaxy’s respective High Velocity Cloud (HVC) population. Most, if not all, of the clouds do not appear to have stars associated with them. Thus, we believe that these clouds are part of a condensing intergalactic filament and may be a source of future star formation for M31 and M33. In addition, I will briefly present my research on the High Velocity and Intermediate Velocity Clouds around our Milky Way using the Galactic All-Sky Survey (GASS) at 21 cm that was conducted with the Parkes 64m radio telescope. I will discuss the basic properties of this gas and some interesting features seen in the survey.

  9. 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.

  10. 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.

  11. Giant Molecular Clouds in M33. I. BIMA All-Disk Survey

    NASA Astrophysics Data System (ADS)

    Engargiola, G.; Plambeck, R. L.; Rosolowsky, E.; Blitz, L.

    2003-12-01

    We present the first interferometric 12CO (J=1-->0) map of the entire Hα disk of M33. The 13" diameter synthesized beam corresponds to a linear resolution of 50 pc, sufficient to distinguish individual giant molecular clouds (GMCs). From these data we generated a catalog of 148 GMCs with an expectation that no more than 15 of the sources are spurious. The catalog is complete down to GMC masses of 1.5×105Msolar and contains a total mass of 2.3×107Msolar. Single-dish observations of CO in selected fields imply that our survey detects ~50% of the CO flux, hence that the total molecular mass of M33 is 4.5×107Msolar, approximately 2% of the H I mass. The GMCs in our catalog are confined largely to the central region (R<4 kpc). They show a remarkable spatial and kinematic correlation with overdense H I filaments; the geometry suggests that the formation of GMCs follows that of the filaments. The GMCs exhibit a mass spectrum dN/dM~M-2.6+/-0.3, considerably steeper than that found in the Milky Way and in the LMC. Combined with the total mass, this steep function implies that the GMCs in M33 form with a characteristic mass of ~7×104 Msolar. More than 2/3 of the GMCs have associated H II regions, implying that the GMCs have a short quiescent period. Our results suggest the rapid assembly of molecular clouds from atomic gas, with prompt onset of massive star formation.

  12. 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.

  13. Positions and Spectral Energy Distributions of 41 Star Clusters in M33

    NASA Astrophysics Data System (ADS)

    Ma, Jun; Zhou, Xu; Chen, Jian-Sheng; Wu, Hong; Jiang, Zhao-Ji; Xue, Sui-Jian; Zhu, Jin

    2002-06-01

    We present accurate positions and multi-color photometry for 41 star clusters detected by Melnick & D'odorico in the nearby spiral galaxy M33 as a part of the BATC Color Survey of the sky in 13 intermediate-band filters from 3800 to 10,000 Å. The coordinates of the clusters are found from the HST Guide Star Catalog. By aperture photometry, we obtain the spectral energy distributions of the clusters. Using the relations between the BATC intermediate-band system and UBVRI broadband system, we derive their V magnitudes and B-V colors and find that most of them are blue, which is consistent with previous findings.

  14. 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.

  15. Spectrum of Var C in M33 in its maximum light

    NASA Astrophysics Data System (ADS)

    Valeev, A.; Fabrika, S.; Sholukhova, O.

    2013-11-01

    The classical LBV star Var C in M33 has entered a luminous (or low excitation) state as it was described in ATels #5362, #5403. We have taken spectra of the star with the Russian BTA telescope using SCORPIO spectrograph. The spectra were obtained on 5 Oct 2013 with spectral resolution of 13Å (3800-7200 Å range), on 01 Nov and 02 Nov with resolution of 2.2Å (in 4100-5800 Å and 5800-7400 Å ranges respectively).

  16. 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).

  17. The star formation history in the far outer disc of M33

    NASA Astrophysics Data System (ADS)

    Barker, Michael K.; Ferguson, A. M. N.; Cole, A. A.; Ibata, R.; Irwin, M.; Lewis, G. F.; Smecker-Hane, T. A.; Tanvir, N. R.

    2011-01-01

    The outer regions of disc galaxies are becoming increasingly recognized as key testing sites for models of disc assembly and evolution. Important issues are the epoch at which the bulk of the stars in these regions formed and how discs grow radially over time. To address these issues, we use Hubble Space Telescope Advanced Camera for Surveys imaging to study the star formation history (SFH) of two fields at 9.1 and 11.6 kpc along M33's northern major axis. These fields lie at ˜ 4 and 5 V-band disc scalelengths and straddle the break in M33's surface brightness profile. The colour-magnitude diagrams (CMDs) reach the ancient main-sequence turn-off with a signal-to-noise ratio of ˜ 5. From detailed modelling of the CMDs, we find that the majority of stars in both fields combined formed at z < 1. The mean age in the inner field, S1, is ˜ 3 ± 1 Gyr and the mean metallicity is [M/H]˜- 0.5 ± 0.2 dex. The SFH of S1 unambiguously reveals how the inside-out growth previously measured for M33's inner disc out to ? extends out to the disc edge at ?. In comparison, the outer field, S2, is older (mean age ˜ 7 ± 2 Gyr), more metal-poor (mean [M/H]˜- 0.8 ± 0.3 dex), and contains ˜ 30 times less stellar mass. These results provide the most compelling evidence yet that M33's age gradient reverses at large radii near the disc break and that this reversal is accompanied by a break in stellar mass surface density. We discuss several possible interpretations of this behaviour including radial stellar mixing, warping of the gaseous disc, a change in star formation efficiency and a transition to another structural component. These results offer one of the most detailed views yet of the peripheral regions of any disc galaxy and provide a much needed observational constraint on the last major epoch of star formation in the outer disc.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Common variable immunodeficiency revisited: normal generation of naturally occurring dendritic cells that respond to Toll-like receptors 7 and 9

    PubMed Central

    Taraldsrud, E; Fevang, B; Aukrust, P; Beiske, K H; Fløisand, Y; Frøland, S; Rollag, H; Olweus, J

    2014-01-01

    Patients with common variable immunodeficiency (CVID) have reduced numbers and frequencies of dendritic cells (DCs) in blood, and there is also evidence for defective activation through Toll-like receptors (TLRs). Collectively, these observations may point to a primary defect in the generation of functional DCs. Here, we measured frequencies of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) in peripheral blood of 26 CVID patients and 16 healthy controls. The results show that the patients have reduced absolute counts of both subsets. However, the decreased numbers in peripheral blood were not reflected in reduced frequencies of CD34+ pDC progenitors in the bone marrow. Moreover, studies at the single cell level showed that DCs from CVID patients and healthy controls produced similar amounts of interferon-α or interleukin-12 and expressed similar levels of activation markers in response to human cytomegalovirus and ligands for TLR-7 and TLR-9. The study represents the most thorough functional characterization to date, and the first to assess bone marrow progenitor output, of naturally occurring DCs in CVID. In conclusion, it seems unlikely that CVID is secondary to insufficient production of naturally occurring DCs or a defect in their signalling through TLR-7 or TLR-9. PMID:24237110

  3. The integrated radio continuum spectrum of M33 - Evidence for free-free absorption by cool ionized gas

    NASA Technical Reports Server (NTRS)

    Israel, F. P.; Mahoney, M. J.; Howarth, N.

    1992-01-01

    We present measurements of the integrated radio continuum flux density of M33 at frequencies between 22 and 610 MHz and discuss the radio continuum spectrum of M33 between 22 MHz and 10 GHz. This spectrum has a turnover between 500 and 900 MHz, depending on the steepness of the high frequency radio spectrum of M33. Below 500 MHz the spectrum is relatively flat. We discuss possible mechanisms to explain this spectral shape and consider efficient free-free absorption of nonthermal emission by a cool (not greater than 1000 K) ionized gas to be a very likely possibility. The surface filling factor of both the nonthermal and the thermal material appears to be small (of order 0.001), which could be explained by magnetic field/density fluctuations in the M 33 interstellar medium. We briefly speculate on the possible presence of a nuclear radio source with a steep spectrum.

  4. Star formation in M33 from HST multi-band imaging

    NASA Astrophysics Data System (ADS)

    Tolea, A.; Bianchi, L.

    2004-12-01

    We present results from an on-going study of stellar populations in the Local Group Galaxy M33. By comparing the multi-band photometry to model colors, we derive effective temperature and luminosity of the stellar objects, and information on the extinction by dust, in 27 fields sampling different environments across the galaxy. Two methods are used and the results compared. The stellar physical parameters are used to characterize the stellar populations in the observed fields which include several OB associations. We also reveal several massive star candidates. For more information and preprints, see http://dolomiti.pha.jhu.edu The work was supported by NASA grants HST-GO-9127 and NAG5-9219.

  5. 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

  6. 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

  7. Immunohistochemical quantification of the cobalamin transport protein, cell surface receptor and Ki-67 in naturally occurring canine and feline malignant tumors and in adjacent normal tissues

    PubMed Central

    Sysel, Annette M.; Valli, Victor E.; Bauer, Joseph A.

    2015-01-01

    Cancer cells have an obligate need for cobalamin (vitamin B12) to enable DNA synthesis necessary for cellular replication. This study quantified the immunohistochemical expression of the cobalamin transport protein (transcobalamin II; TCII), cell surface receptor (transcobalamin II-R; TCII-R) and proliferation protein (Ki-67) in naturally occurring canine and feline malignant tumors, and compared these results to expression in corresponding adjacent normal tissues. All malignant tumor tissues stained positively for TCII, TCII-R and Ki-67 proteins; expression varied both within and between tumor types. Expression of TCII, TCII-R and Ki-67 was significantly higher in malignant tumor tissues than in corresponding adjacent normal tissues in both species. There was a strong correlation between TCII and TCII-R expression, and a modest correlation between TCII-R and Ki-67 expression in both species; a modest association between TCII and Ki-67 expression was present in canine tissues only. These results demonstrate a quantifiable, synchronous up-regulation of TCII and TCII-R expression by proliferating canine and feline malignant tumors. The potential to utilize these proteins as biomarkers to identify neoplastic tissues, streamline therapeutic options, evaluate response to anti-tumor therapy and monitor for recurrent disease has important implications in the advancement of cancer management for both human and companion animal patients. PMID:25633912

  8. 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

  9. THE STELLAR ARCHEOLOGY OF THE M33 DISK: RECENT STAR-FORMING HISTORY AND CONSTRAINTS ON THE TIMING OF AN INTERACTION WITH M31

    SciTech Connect

    Davidge, T. J.; Puzia, T. H. E-mail: tpuzia@gmail.com

    2011-09-10

    Images recorded with MegaCam are used to investigate the recent (t {<=} 0.25 Gyr) star-forming history (SFH) of the Local Group Sc galaxy M33. The data sample the entire star-forming disk, as well as areas immediately to the north and south of the galaxy. The properties of the stellar disk change near R{sub GC} = 8 kpc. Within this radius the luminosity function of main-sequence stars indicates that the star formation rate (SFR) has been constant with time during at least the past 250 Myr, while at larger radii the SFR has declined during this same time period. That the recent SFR in the inner disk has been constant suggests that M33 has evolved in isolation for at least the past {approx}0.5 Gyr, thereby providing a constraint on the timing of any recent interaction with M31. The color of the main-sequence ridgeline changes with radius, suggesting a gradient in extinction of size {Delta}A{sub V} /{Delta}R{sub GC} = -0.05 mag kpc{sup -1}. The fractional contribution that young stars make to the total mass of the stellar disk changes with radius, peaking near 8 kpc. Evidence is also presented of systematic spatial variations in the SFH of the disk, such that the SFR during the past 100 Myr in the southern half of the galaxy has been {approx}0.4 dex higher than in the northern half. Finally, structures with sizes spanning many kpc that contain blue objects-presumably main-sequence stars that formed during intermediate epochs-are identified near the disk boundary. It is argued that these are tidal features that were pulled from the main body of M33 and-in some cases-are the fossil remnants of star formation that occurred in an extended disk during intermediate epochs.

  10. 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

  11. 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.

  12. Ultraviolet spectroscopy of the brightest supergiants in M31 and M33

    NASA Technical Reports Server (NTRS)

    Humphreys, R. M.; Blaha, C.; Dodorico, S.; Gull, T. R.; Benevenuti, P.

    1983-01-01

    Ultraviolet spectroscopy from the IUE, in combination with groundbased visual and infrared photometry, are to determine the energy distributions of the luminous blue variables, the Hubble-Sandage variables, in M31 and M33. The observed energy distributions, especially in the ultraviolet, show that these stars are suffering interstellar reddening. When corrected for interstellar extinction, the integrated energy distributions yield the total luminosities and black body temperatures of the stars. The resulting bolometric magnitudes and temperatures confirm that these peculiar stars are indeed very luminous, hot stars. They occupy the same regions of the sub B01 vs. log T sub e diagram as do eta Car, P Cyg and S Dor in our galaxy and the LMC. Many of the Hubble-Sandage variables have excess infrared radiation which is attributed to free-free emission from their extended atmospheres. Rough mass loss estimates from the infrared excess yield rates of 0.00001 M sub annual/yr. The ultraviolet spectra of the H-S variables are also compared with similar spectra of eta Car, P Cyg and S For.

  13. 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.

  14. HER kinase axis receptor dimer partner switching occurs in response to EGFR tyrosine kinase inhibition despite failure to block cellular proliferation.

    PubMed

    Jain, Anjali; Penuel, Elicia; Mink, Sheldon; Schmidt, Joanna; Hodge, Amanda; Favero, Kristin; Tindell, Charles; Agus, David B

    2010-03-01

    The human epidermal receptor (HER) axis consists of a dynamic, interconnected family of receptors that make critical contributions to a number of malignancies. Therapeutics targeting epidermal growth factor receptor (EGFR) are unable to effectively inhibit tumor growth in a majority of cases. These tumors are assumed to possess primary resistance to anti-EGFR therapies, but the consequence of inhibiting EGFR in these tumors is unclear. We established isogenic cell lines by prolonged gefitinib treatment at concentrations that are in excess of that which is required for complete EGFR kinase inhibition but only minimally affected growth. Subsequently, we monitored the ligand-dependent HER profiles based on receptor expression, phosphorylation, and dimerization in conjunction with measurements of cellular susceptibility to gefitinib. Chronic EGFR kinase inhibition rapidly switched the HER network from dependence on EGFR to HER2. However, both receptors activated the critical signaling proteins AKT and mitogen-activated protein kinase, and in both cases, HER3 was the common association partner. Remarkably, the switch in receptor dimers caused diminished susceptibility to EGFR-targeted inhibitors gefitinib and cetuximab but acquired susceptibility to the HER2-targeted inhibitor pertuzumab. Overall, our study indicates that the EGFR pathway is responsive to EGFR inhibiting therapies that are not dependent on EGFR for their growth and survival, thus challenging the current definition of primary therapeutic resistance. Furthermore, EGFR kinase inhibition induces HER kinase receptors to engage in alternative dimerization that can ultimately influence therapeutic selection and responsiveness. PMID:20160029

  15. 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.

  16. 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.

  17. Unmasking of CD22 Co-receptor on Germinal Center B-cells Occurs by Alternative Mechanisms in Mouse and Man.

    PubMed

    Macauley, Matthew S; Kawasaki, Norihito; Peng, Wenjie; Wang, Shui-Hua; He, Yuan; Arlian, Britni M; McBride, Ryan; Kannagi, Reiji; Khoo, Kay-Hooi; Paulson, James C

    2015-12-11

    CD22 is an inhibitory B-cell co-receptor whose function is modulated by sialic acid (Sia)-bearing glycan ligands. Glycan remodeling in the germinal center (GC) alters CD22 ligands, with as yet no ascribed biological consequence. Here, we show in both mice and humans that loss of high affinity ligands on GC B-cells unmasks the binding site of CD22 relative to naive and memory B-cells, promoting recognition of trans ligands. The conserved modulation of CD22 ligands on GC B-cells is striking because high affinity glycan ligands of CD22 are species-specific. In both species, the high affinity ligand is based on the sequence Siaα2-6Galβ1-4GlcNAc, which terminates N-glycans. The human ligand has N-acetylneuraminic acid (Neu5Ac) as the sialic acid, and the high affinity ligand on naive B-cells contains 6-O-sulfate on the GlcNAc. On human GC B-cells, this sulfate modification is lost, giving rise to lower affinity CD22 ligands. Ligands of CD22 on naive murine B-cells do not contain the 6-O-sulfate modification. Instead, the high affinity ligand for mouse CD22 has N-glycolylneuraminic acid (Neu5Gc) as the sialic acid, which is replaced on GC B-cells with Neu5Ac. Human naive and memory B-cells express sulfated glycans as high affinity CD22 ligands, which are lost on GC B-cells. In mice, Neu5Gc-containing glycans serve as high affinity CD22 ligands that are replaced by Neu5Ac-containing glycans on GC B-cells. Our results demonstrate that loss of high affinity CD22 ligands on GC B-cells occurs in both mice and humans through alternative mechanisms, unmasking CD22 relative to naive and memory B-cells. PMID:26507663

  18. 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.

  19. HER-kinase Axis Receptor Dimer Partner Switching Occurs in Response to EGFR Tyrosine Kinase Inhibition Despite Failure to Block Cellular Proliferation

    PubMed Central

    Jain, Anjali; Penuel, Elicia; Mink, Sheldon; Schmidt, Joanna; Hodge, Amanda; Favero, Kristin; Tindell, Charles; Agus, David B.

    2010-01-01

    The HER-axis consists of a dynamic, interconnected family of receptors that make critical contributions to a number of malignancies. Therapeutics targeting EGFR, are unable to effectively inhibit tumor growth in a majority of cases. These tumors are assumed to possess primary resistance to anti-EGFR therapies but the consequence of inhibiting EGFR in these tumors is unclear. We established isogenic cell lines by prolonged gefitinib treatment at concentrations that are in excess of that which is required for complete EGFR kinase inhibition but only minimally effected growth. Subsequently, we monitored the ligand-dependent HER profiles based on receptor expression, phosphorylation and dimerization in conjunction with measurements of cellular susceptibility to gefitinib. Chronic EGFR kinase inhibition rapidly switched the HER network from dependence on EGFR to HER2. However, both receptors activated the critical signaling proteins, AKT and MAPK and in both cases HER3 was the common association partner. Remarkably, the switch in receptor dimers caused diminished susceptibility to EGFR-targeted inhibitors, gefitinib and cetuximab, but acquired susceptibility to the HER2-targeted inhibitor, pertuzumab. Overall, our study indicates that the EGFR pathway is responsive to EGFR inhibiting therapies that are not dependent on EGFR for their growth and survival thus challenging the current definition of primary therapeutic resistance. Further, EGFR kinase inhibition induces HER-kinase receptors to engage in alternative dimerization that can ultimately influence therapeutic selection and responsiveness. PMID:20160029

  20. 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

  1. 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

  2. The Stellar Populations in the Outer Regions of M33. III. Star Formation History

    NASA Astrophysics Data System (ADS)

    Barker, Michael K.; Sarajedini, Ata; Geisler, Doug; Harding, Paul; Schommer, Robert

    2007-03-01

    We present a detailed analysis of the star formation history (SFH) of three fields in M33 located approximately four to six visual scale lengths from its nucleus. These fields were imaged with the Advanced Camera for Surveys on the Hubble Space Telescope and reach ~2.5 mag below the red clump of core helium-burning stars. The observed color-magnitude diagrams are modeled as linear combinations of individual synthetic populations with different ages and metallicities. To gain a better understanding of the systematic errors, we have conducted the analysis with two different sets of stellar evolutionary tracks, which we designate as Padova and Teramo. The precise details of the results depend on which tracks are used, but we can make several conclusions that are fairly robust despite the differences. Both sets of tracks predict the mean age to increase and the mean metallicity to decrease with radius. Allowing age and metallicity to be free parameters and assuming that star formation began ~14 Gyr ago, we find that the mean age of all stars and stellar remnants increases from ~6 to ~8 Gyr, and the mean global metallicity decreases from approximately -0.7 to approximately -0.9. The fraction of stars formed by 4.5 Gyr ago increases from ~65% to ~80%. The mean star formation rate 80-800 Myr ago decreases from ~30% of the lifetime average to just ~5%. The random errors on these estimates are ~10%, 1.0 Gyr, and 0.1 dex. By comparing the results of the two sets of stellar tracks for the real data and for test populations with known SFHs, we have estimated the systematic errors to be 15%, 1.0 Gyr, and 0.2 dex. These do not include uncertainties in the bolometric corrections or variations in α-element abundance, which deserve future study. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS5

  3. 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.

  4. Eclipsing Binaries as Accurate Extragalactic Distance Indicators: Refining the Distance to the Triangulum Spiral Galaxy M33

    NASA Astrophysics Data System (ADS)

    Guinan, Edward F.; Prsa, A.; Fitzpatrick, E. L.; Bonanos, A. Z.; Engle, S. G.; Devinney, E. J.; Recker, G.

    2013-06-01

    For over decade we have been using eclipsing binaries (EBs) to determine accurate distances to Local Group Galaxies such as the Magellanic Clouds & M31 (cf. Fitzpatrick et al. 2003; Vilardell et al. 2010). We (and others) have demonstrated that carefully selected EBs can serve as excellent "Standard Candles." Distances measured from EBs are basically geometric and are essentially free from assumptions and uncertainties that complicate other less direct methods. The radii of the stars are determined to better than a few percent from the time-tested analyses of their light and radial velocity curves. With accurate determinations of radii, Teff (or calibrated flux SEDs) and ISM absorption, it is possible to calculate reliable distances with uncertainties of < 5%. M33 is an important face-on spiral galaxy that still has a large range in its measured distance of ~750 - 960 kpc. We carried out HST/COS and STIS FUV-Near-IR (1150 - 8500A) spectrophotometry & WFPC-2 photometry of the19th mag (O7V +O7V) eclipsing binary D33 J013346.2+304439.9 in M33 to try to improve its distance.This EB was used previously by Bonanos et al. (2006) to determine a distance = 964 +/- 54 kpc. Analysis of the HST FUV-NIR data will yield more accurate Teff, Av, and [Fe/H] measures. These quantities, when combined with the results from existing light and radial velocity curves of Bonanos et al. permit the refined distance to be found with more certainty. We discuss the results and compare them with other recent M33 distances. When a reliable distance is found, M33 could replace the LMC as the primary exgalactic distance calibrator since this Sa spiral has chemical and physical properties more in common with the galaxies used to determine the Hubble Law and Ho. This research supported by HST NASA grants HST-GO-10919 & HST-GO-11725.

  5. 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.

  6. THE ABUNDANCE SCATTER IN M33 FROM H II REGIONS: IS THERE ANY EVIDENCE FOR AZIMUTHAL METALLICITY VARIATIONS?

    SciTech Connect

    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] {lambda}4363 auroral line displays a scatter of approximately 0.06 dex, a much smaller value than recently reported by Rosolowsky and Simon in this galaxy. The analysis of the abundances for a large sample of H II regions derived from the R{sub 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 {approx}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{sub 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.

  7. The Metabotropic Glutamate Receptor, mGlu5, Is Required for Extinction Learning That Occurs in the Absence of a Context Change

    PubMed Central

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

    2015-01-01

    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. © 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc. PMID:25160592

  8. 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. PMID:22511319

  9. Tyrosine phosphorylation-dependent activation of phosphatidylinositide 3-kinase occurs upstream of Ca2+-signalling induced by Fcgamma receptor cross-linking in human neutrophils.

    PubMed Central

    Vossebeld, P J; Homburg, C H; Schweizer, R C; Ibarrola, I; Kessler, J; Koenderman, L; Roos, D; Verhoeven, A J

    1997-01-01

    The effect of wortmannin on IgG-receptor (FcgammaR)-mediated stimulation of human neutrophils was investigated. The Ca2+ influx induced by clustering of both Fcgamma receptors was inhibited by wortmannin, as was the release of Ca2+ from intracellular stores. Wortmannin also inhibited, with the same efficacy, the accumulation of Ins(1,4,5)P3 observed after FcgammaR stimulation, but did not affect the increase in Ins(1,4,5)P3 induced by the chemotactic peptide, formyl-methionine-leucine-phenylalanine. Because wortmannin is, in the concentrations used here, an inhibitor of PtdIns 3-kinase, these results suggested a role for PtdIns 3-kinase upstream of Ca2+ signalling, induced by FcgammaR cross-linking. Support for this notion was obtained by investigating the effect of another inhibitor of PtdIns 3-kinase, LY 294002, and by studying the kinetics of PtdIns 3-kinase activation. We found translocation of PtdIns 3-kinase to the plasma membrane and increased PtdIns 3-kinase activity in the membrane as soon as 5 s after FcgammaR cross-linking, even before the onset of the Ca2+ response. Moreover, the translocation of PtdIns 3-kinase to the plasma membrane was inhibited by co-cross-linking of either FcgammaRIIa and FcgammaRIIIb with the tyrosine phosphatase, CD45, indicating a requirement for protein tyrosine phosphorylation in the recruitment of PtdIns 3-kinase to the plasma membrane. Taken together, our results suggest a role for PtdIns 3-kinase in early signal transduction events after FcgammaR cross-linking in human neutrophils. PMID:9173906

  10. 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.

  11. 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.

  12. 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).

  13. Dynamical signatures of a ΛCDM-halo and the distribution of the baryons in M 33

    NASA Astrophysics Data System (ADS)

    Corbelli, Edvige; Thilker, David; Zibetti, Stefano; Giovanardi, Carlo; Salucci, Paolo

    2014-12-01

    Aims: We determine the mass distribution of stars, gas, and dark matter in M 33 to test cosmological models of galaxy formation and evolution. Methods: We map the neutral atomic gas content of M 33 using high resolution Very Large Array and Green Bank Telescope observations of the 21 cm HI line emission. A tilted ring model is fitted to the HI datacube to determine the varying spatial orientation of the extended gaseous disk and the rotation curve. We derive the stellar mass surface density map of M 33's optical disk via pixel-SED fitting methods based on population synthesis models that allow for positional changes in star formation history. Stellar and gas maps are used in the dynamical analysis of the rotation curve to constrain the dark halo properties. Results: The disk of M 33 warps from 8 kpc outward without substantial change of its inclination with respect to the line of sight; the line of nodes rotates clockwise toward the direction of M 31. Rotational velocities rise steeply with radius in the inner disk, reaching 100 km s-1 in 4 kpc, then the rotation curve becomes more perturbed and flatter with velocities as high as 120-130 km s-1 out to 2.7 R25. The stellar surface density map highlights a star-forming disk with a varying mass-to-light ratio. At larger radii, a dynamically relevant fraction of the baryons are in gaseous form. A dark matter halo with a Navarro-Frenk-White density profile, as predicted by hierarchical clustering and structure formation in a ΛCDM cosmology, provides the best fits to the rotation curve. Dark matter is relevant at all radii in shaping the rotation curve and the most likely dark halo has a concentration C ≃ 9.5 and a total mass of 4.3(±1.0) × 1011 M⊙. This imples a baryonic fraction of order 0.02 and the evolutionary history of this galaxy should therefore account for loss of a large fraction of its original baryonic content. Appendices are available in electronic form at http://www.aanda.org

  14. Bryostatin-1, a Naturally Occurring Antineoplastic Agent, Acts as a Toll-like Receptor 4 (TLR-4) Ligand and Induces Unique Cytokines and Chemokines in Dendritic Cells*

    PubMed Central

    Ariza, Maria Eugenia; Ramakrishnan, Rupal; Singh, Narendra P.; Chauhan, Ashok; Nagarkatti, Prakash S.; Nagarkatti, Mitzi

    2011-01-01

    Bryostatin-1 (Bryo-1), a natural macrocyclic lactone, is clinically used as an anti-cancer agent. In this study, we demonstrate for the first time that Bryo-1 acts as a Toll-like receptor 4 (TLR4) ligand. Interestingly, activation of bone marrow-derived dendritic cells (in vitro with Bryo-1) led to a TLR4-dependent biphasic activation of nuclear factor-κB (NF-κB) and the unique induction of cytokines (IL-5, IL-6, and IL-10) and chemokines, including RANTES (regulated on activation normal T cell expressed and secreted) and macrophage inflammatory protein 1α (MIP1-α). In addition, EMSA demonstrated that Bryo-1-mediated induction of RANTES was regulated by NF-κB and the interferon regulatory factors (IRF)-1, IRF-3, and IRF-7 to the RANTES independently of myeloid differentiation primary response gene-88 (MyD88). Bryo-1 was able to induce the transcriptional activation of IRF-3 through the TLR4/MD2-dependent pathway. In vivo administration of Bryo-1 triggered a TLR-4-dependent T helper cell 2 (Th2) cytokine response and expanded a subset of myeloid dendritic cells that expressed a CD11chighCD8α− CD11b+CD4+ phenotype. This study demonstrates that Bryo-1 can act as a TLR4 ligand and activate innate immunity. Moreover, the ability of Bryo-1 to trigger RANTES and MIP1-α suggests that Bryo-1 could potentially be used to prevent HIV-1 infection. Finally, induction of a Th2 response by Bryo-1 may help treat inflammatory diseases mediated by Th1 cells. Together, our studies have a major impact on the clinical use of Bryo-1 as an anti-cancer and immunopotentiating agent. PMID:21036898

  15. Induction of apoptosis through B-cell receptor cross-linking occurs via de novo generated C16-ceramide and involves mitochondria.

    PubMed

    Kroesen, B J; Pettus, B; Luberto, C; Busman, M; Sietsma, H; de Leij, L; Hannun, Y A

    2001-04-27

    B-cells, triggered via their surface B-cell receptor (BcR), start an apoptotic program known as activation-induced cell death (AICD), and it is widely believed that this phenomenon plays a role in the restriction and focusing of the immune response. Although both ceramide and caspases have been proposed to be involved in AICD, the contribution of either and the exact molecular events through which AICD commences are still unknown. Here we show that in Ramos B-cells, BcR-triggered cell death is associated with an early rise of C16 ceramide that derives from activation of the de novo pathway, as demonstrated using a specific inhibitor of ceramide synthase, fumonisin B1 (FB1), and using pulse labeling with the metabolic sphingolipid precursor, palmitate. There was no evidence for activation of sphingomyelinases or hydrolysis of sphingomyelin. Importantly, FB1 inhibited several specific apoptotic hallmarks such as poly(A)DP-ribose polymerase cleavage and DNA fragmentation. Electron microscopy revealed morphological evidence of mitochondrial damage, suggesting the involvement of mitochondria in BcR-triggered apoptosis, and this was inhibited by FB1. Moreover, a loss of mitochondrial membrane potential was observed in Ramos cells after BcR cross-linking, which was inhibited by the addition of FB1. Interestingly, benzyloxycarbonyl-Val-Ala-dl-Asp, a broad spectrum caspase inhibitor did not inhibit BcR-induced mitochondrial membrane permeability transition but did block DNA fragmentation. These results suggest a crucial role for de novo generated C16 ceramide in the execution of AICD, and they further suggest an ordered and more specific sequence of biochemical events in which de novo generated C16 ceramide is involved in mitochondrial damage resulting in a downstream activation of caspases and apoptosis. PMID:11278517

  16. A High-avidity WT1-reactive T-Cell Receptor Mediates Recognition of Peptide and Processed Antigen but not Naturally Occurring WT1-positive Tumor Cells.

    PubMed

    Jaigirdar, Adnan; Rosenberg, Steven A; Parkhurst, Maria

    2016-04-01

    Wilms tumor gene 1 (WT1) is an attractive target antigen for cancer immunotherapy because it is overexpressed in many hematologic malignancies and solid tumors but has limited, low-level expression in normal adult tissues. Multiple HLA class I and class II restricted epitopes have been identified in WT1, and multiple investigators are pursuing the treatment of cancer patients with WT1-based vaccines and adoptively transferred WT1-reactive T cells. Here we isolated an HLA-A*0201-restricted WT1-reactive T-cell receptor (TCR) by stimulating peripheral blood lymphocytes of healthy donors with the peptide WT1:126-134 in vitro. This TCR mediated peptide recognition down to a concentration of ∼0.1 ng/mL when pulsed onto T2 cells as well as recognition of HLA-A*0201 target cells transfected with full-length WT1 cDNA. However, it did not mediate consistent recognition of many HLA-A*0201 tumor cell lines or freshly isolated leukemia cells that endogeneously expressed WT1. We dissected this pattern of recognition further and observed that WT1:126-134 was more efficiently processed by immunoproteasomes compared with standard proteasomes. However, pretreatment of WT1 tumor cell lines with interferon gamma did not appreciably enhance recognition by our TCR. In addition, we highly overexpressed WT1 in several leukemia cell lines by electroporation with full-length WT1 cDNA. Some of these lines were still not recognized by our TCR suggesting possible antigen processing defects in some leukemias. These results suggest WT1:126-134 may not be a suitable target for T-cell based tumor immunotherapies. PMID:26938944

  17. 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.

  18. 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.

  19. 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. PMID:23904253

  20. 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.

  1. Wolf-Rayet stars and giant H II regions in M33 - Casual associations or meaningful relationships

    NASA Astrophysics Data System (ADS)

    Conti, P. S.; Massey, P.

    1981-10-01

    The discovery is reported of 14 new Wolf-Rayet stars in the Local Group galaxy M33, of which six are surrounded by small H II regions and have spectra and M(v) similar to field W-R stars in the Galaxy. In addition, eight of the stars are found to be among the brightest in the giant H II regions NGC 588, 592, 595 and 604, and similar to the superluminous W-R's found in 30 Dor in the Large Magellanic Cloud and HD 97950 in NGC 3603. It is concluded after a discussion of statistics pertaining to the W-R types known in M33 that selection effects still dominate the discovery process, and it is suggested that the morphological similarities among superluminous W-R star spectra and the dynamics of giant H II regions imply a shared evolutionary pattern where the nebulae may be dominated by the effects of a few massive, unstable objects with W-R spectra.

  2. The Close Binary Frequency of Wolf-Rayet Stars as a Function of Metallicity in M31 and M33

    NASA Astrophysics Data System (ADS)

    Neugent, Kathryn F.; Massey, Philip

    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. 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.

  3. NRO M 33 All-Disk Survey of Giant Molecular Clouds (NRO MAGiC). II Dense Gas Formation

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

    We report the results of our observations of the 12 CO (J = 1-0) and 12 CO (J = 3-2) line emission of 74 major giant molecular clouds (GMCs) within the galactocentric distance of 5.1 kpc in the Local Group galaxy M 33. The observations have been conducted as part of the Nobeyama Radio Observatory M 33 All-disk survey of Giant Molecular Clouds project (NRO MAGiC). The spatial resolutions are 80 pc for 12 CO (J = 1-0) and 100 pc for 12 CO (J = 3-2). We detect 12 CO (J = 3-2) emission of 65 GMCs successfully. Furthermore, we find that the correlation between the surface density of the star formation rate, which is derived from a linear combination of Hα and 24 μ m emissions, and the 12 CO (J = 3-2) integrated intensity still holds at this scale. This result shows that the star-forming activity is closely associated with warm and dense gases that are traced with the 12 CO (J = 3-2) line, even in the scale of GMCs. We also find that the GMCs with a high star-forming activity tend to show a high integrated intensity ratio (R3-2/1-0). Moreover, we also observe a mass-dependent trend of R3-2/1- 0 for the GMCs with a low star-forming activity. From these results, we speculate that the R3-2/1-0 values of the GMCs with a low star-forming activity mainly depend on the dense gas fraction and not on the temperature, and therefore, the dense gas fraction increases with the mass of GMCs, at least in the GMCs with a low star-forming activity.

  4. 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. PMID:20962778

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

    NASA Astrophysics Data System (ADS)

    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, 15.65Msolar black hole orbiting an underluminous, 70Msolar main-sequence companion in a slightly eccentric 3.45-day orbit (Msolar, 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 85Msolar-99Msolar and a secondary body of 28Msolar-32Msolar, 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 ~16Msolar 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.

  6. 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.

  7. 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

  8. The Heating of Mid-infrared Dust in the Nearby Galaxy M33: A Testbed for Tracing Galaxy Evolution

    NASA Astrophysics Data System (ADS)

    Calapa, Marie D.; Calzetti, Daniela; Draine, Bruce T.; Boquien, Médéric; Kramer, Carsten; Xilouris, Manolis; Verley, Simon; Braine, Jonathan; Relaño, Monica; van der Werf, Paul; Israel, Frank; Hermelo, Israel; Albrecht, Marcus

    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 & 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

  9. LUMINOUS AND VARIABLE STARS IN M31 AND M33. I. THE WARM HYPERGIANTS AND POST-RED SUPERGIANT EVOLUTION

    SciTech Connect

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

    2013-08-10

    The progenitors of Type IIP supernovae (SNe) have an apparent upper limit to their initial masses of about 20 M{sub Sun }, 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 Multiplication-Sign 10{sup -6} to 10{sup -4} M{sub Sun} yr{sup -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.

  10. 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.

  11. 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.

  12. KPOT_ckrame01_1: Herschel M33 extended survey (HERMES): star-formation interplay with the ISM

    NASA Astrophysics Data System (ADS)

    Kramer, C.

    2007-10-01

    In the local universe, most of the observable matter is contained in stellar objects shaping the morphology and dynamics of their "parent" galaxy. In view of the dominance of stellar mass, a better understanding of star formation and its consequences is mandatory and forms a central topic of contemporary astrophysical research. There exist a large number of high linear resolution studies related to individual star forming regions of the Galaxy as well as of low linear resolution studies of external galaxies. For a complete view onto the physical and chemical processes driving star formation and galactic evolution it is, however, essential to combine local conditions affecting individual star formation with properties only becoming apparent on global scales. The optimal target providing such a complete view is a galaxy that is actively forming stars, that is not seen edge-on (like our Galaxy), that has been studied at radio, optical and X-ray wavelengths, and that is sufficiently nearby to also permit studies on small scales. For our carefully chosen template galaxy, we plan to use HIFI to obtain fully-sampled large-scale [CII] (and H2O) maps. PACS will add important interstellar cooling lines, [OI], [NII], [NIII]. And SPIRE & PACS will be used to map the dust spectral energy distribution over the entire galaxy. Observing a deep, extended strip along the major axis of our template galaxy M33, will allow us to study the ionized, atomic, and molecular phases of the interstellar medium, its life cycle and thermal balance, tracing the formation of molecular clouds and of stars. Aside of insights related to the local processes in the galaxy itself, the mapped source will set a standard, providing a basis for the interpretation of phenomena encountered in other targets of the Local Group and in more distant galaxies.

  13. Eclipsing Binaries in the Local Group: III - Unprecedented Accuracy in Distance Determination to M33 and Calibration of the Cosmic Distance Scale

    NASA Astrophysics Data System (ADS)

    Guinan, Edward

    2009-07-01

    The Great Spiral Galaxy in Triangulum {M33} is a crucial calibrator for the Cosmic Distance Scale, and thus for determining the age and evolution of the Universe. M33 is viewed face-on, has a simple geometry, large and diverse stellar populations, and morphologies similar to our Galaxy and other more distant galaxies used for distance determinations. Yet currently the M33 distance {d 830 +/- 120 kpc} still has measurement dispersions of 10-15%. Moreover, the distance to M33 derived from Cepheids, RR Lyrae stars, H2O masers, RGB stars, and EBs is currently discrepant by 15% {Bonanos et al. 2006}. In our work on the LMC and M31 distances we have demonstrated that double-line eclipsing binaries serve as excellent "standard candles." Distances derived from eclipsing binaries are basically geometric and essentially free from many assumptions and uncertainties that plague other less direct methods, such as metallicity differences and calibration zeropoints. The absolute radii of the component stars of eclipsing binaries can be determined to better than a few percent from the time-tested analyses of their light and radial velocity curves. With accurate determinations of radii, temperatures, and ISM absorption it is possible to determine reliable distances. In Cycle 15 we extended our program of using eclipsing binaries as standard candles to M33 using ACS/SBS and WFPC/2 spectrophotometry of a well suited 19th mag O7+O7 eclipsing binary system. Although insightful, ACS/SBC data alone do not provide sufficient accuracy for the unambigous determination of individual temperatures, [Fe/H], and ISM extinction, which are central to distance determination. We propose a 4 orbit follow-up spectrophotometry with the newly installed HST/COS G140L and the repaired HST/STIS G230L and G430L to obtain the single missing key element of this program. These quantities, when combined with the results from existing light and radial velocity curves for the target {cf. Bonanos et al. 2006

  14. 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.

  15. 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

  16. 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

  17. A Multi-ionic Kinematic Investigation of NGC 595, a Giant Extragalactic H II Region in M33

    NASA Astrophysics Data System (ADS)

    Lagrois, Dominic; Joncas, Gilles

    2009-08-01

    Spectro-interferometric observations of the Hα, [O III], and [S II] optical emission lines are combined with radio observations of the 21 cm line in order to obtain a reliable kinematic image of NGC 595, the second largest giant extragalactic H II region in M33. The Hα and [O III] observations reveal that the nebula is exposed to two distinct kinematical regimes. While symmetric, broad velocity profiles dominate a sizeable fraction of the ionized extent, evidence for line splitting is detected in a small region near the most massive stars of the star cluster. A quantitative investigation proposes that two expanding wind-blown bubbles could be held responsible for the observed line splitting. The kinematics of the ionized material presenting one-component velocity profiles likely indicates that Champagne flows are present at the periphery of the molecular component leading to accelerated ionized material in the ambient interstellar medium. In areas not dominated by the photoionization of the molecular clouds, the H+ and S+ material shows a kinematical behavior roughly in agreement with the atomic gas. Mean nonthermal line widths show relatively large, supersonic values especially in [O III]. Models of structure functions indicate that the Hα and [O III] components could be exposed to different turbulent motions which could explain the broadening excess observed for the latter ion. On the full ionized extent of the nebula, the S+ material shows narrower line widths than the two other ions. Combined with the absence of line splitting, these peculiar characteristics indicate that the [S II] component is likely located at the periphery of the nebula and probably does not coexist with Hα and [O III]. The shape of the [S II] structure function is in agreement with a relatively low number of large-scale velocity gradients which partially explains the narrower profiles observed. The mean electron density in the nebula is estimated at 162 ± 106(1σ) cm-3, in agreement

  18. Naturally occurring chemical carcinogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Natural products are chemicals found in nature which have unique pharmacological effects. Humans are exposed to many of these bioactive naturally occurring chemicals via the air breathed, the water drunk and the food eaten. Exposure also occurs in clinical settings. Naturally occurring chemicals ...

  19. Vasoactive Intestinal Polypeptide (VIP)-Expressing Neurons in the Suprachiasmatic Nucleus Provide Sparse GABAergic Outputs to Local Neurons with Circadian Regulation Occurring Distal to the Opening of Postsynaptic GABAA Ionotropic Receptors

    PubMed Central

    Fan, Junmei; Zeng, Hongkui; Olson, David P.; Huber, Kimberly M.

    2015-01-01

    GABAergic synaptic transmission plays an important role in resetting and synchronizing circadian rhythms in the suprachiasmatic nucleus (SCN). Although the circadian modulation of intrinsic membrane currents and biochemical signaling have been examined in the SCN, the modulation of specific synaptic pathways within the SCN is unexplored. In addition, little is known about the functional properties of these pathways, including which ones involve GABAA receptors (GABAA-Rs). In brain slices obtained from mice, we examined synaptic responses originating from the SCN neurons expressing vasoactive intestinal peptide (VIP+ neurons). Focusing on the local projection within the ventromedial SCN, we found that VIP+ afferents provided input onto 49% of neurons with a preference for VIP-negative (VIP−) neurons. Responses were mediated by GABAA-Rs. The projection was sparsely connected and preferentially targeted a subset of SCN neurons unrelated to postsynaptic VIP expression. For most aspects of VIP+ network output, there was no circadian regulation. Excitability and spontaneous firing of the presynaptic VIP+ neurons were unchanged between day and night, and their network connectivity and synaptic function up through the evoked synaptic conductance were also unchanged. On the other hand, VIP+ input onto VIP− neurons became less inhibitory at night suggesting a postsynaptic alteration in the coupling of GABAA-R conductances to action potential firing. These data suggest that components of the VIP network and its synaptic output up through GABAA-R opening are invariant during the circadian cycle, but the effect on action potential firing is modulated by postsynaptic processes occurring after GABAA-R channel opening. PMID:25653351

  20. 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

  1. Optical Spectrophotometric Monitoring of the Extreme Luminous Blue Variable Star GR 290 (Romano's Star) in M 33

    NASA Astrophysics Data System (ADS)

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

    2011-01-01

    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 = ~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 Å 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-1. The shape of the 4630-4713 Å emission blend and of other emission lines resembles that of WN9 stars; the blend deconvolution shows that the He II 4686 Å has a strong broad component with FWHM ~= 1700 km s-1. During 2003-2010 the star underwent large spectral variations, best seen in the 4630-4686 Å emission feature. Using the late-WN spectral types of Crowther & 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 Å line and the optical continuum formed in a central Wolf-Rayet region, while the narrow emission line spectrum originated in an extended, slowly expanding

  2. H-alpha survey of M33 with the six-meter telescope Morphology of the general diffuse emission, evidence for a chaotic medium of bubbles and filaments

    NASA Astrophysics Data System (ADS)

    Courtes, G.; Petit, H.; Petit, M.; Sivan, J.-P.; Dodonov, S.

    1987-03-01

    A complete photographic H-alpha survey of M33 has been carried out with the f/1 focal reducer of Courtes (1964, 1972), attached to the prime focus of the 6-m telescope of the Soviet Special Astrophysical Observatory. A list of 748 distinct H II regions has been compiled from the survey photographs. 410 nebulae are newly identified objects. The others were previously cataloged by Boulesteix et al. (1974). The photographs are presented together with identification charts. They reveal an impressive, entirely new appearance for the ionized gas in M33. The 'classical' H II regions are seen bathing in a very chaotic background of H-alpha emission: rings, loops, and arc-shaped and filamentary structures are present everywhere all over the galaxy in and between the arms.

  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. 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.

  5. DIRECT Distances to Nearby Galaxies Using Detached Eclipsing Binaries and Cepheids. VII. Additional Variables in the Field M33A Discovered with Image Subtraction

    NASA Astrophysics Data System (ADS)

    Mochejska, B. J.; Kaluzny, J.; Stanek, K. Z.; Sasselov, D. D.; Szentgyorgyi, A. H.

    2001-04-01

    DIRECT is a project to directly obtain the distances to two Local Group galaxies, M31 and M33, which occupy a crucial position near the bottom of the cosmological distance ladder. As the first step of the DIRECT project, we have searched for detached eclipsing binaries (DEBs) and new Cepheids in the M31 and M33 galaxies with 1 m class telescopes. In this paper, we present a catalog of variable stars discovered in the data from the follow-up observations of the DEB system D33J013346.2+304439.9 in field M33A (α=23.55d, δ=30.72d J2000.0), collected with the Kitt Peak National Observatory's 2.1 m telescope. In our search covering an area of 108 arcmin2, we have found 434 variable stars: 63 eclipsing binaries, 305 Cepheids, and 66 other periodic, possible long-period, or nonperiodic variables. Of these variables, 280 are newly discovered, mainly short-period and/or faint Cepheids. Their light curves were extracted using the ISIS image subtraction package. For 85% of the variables, we present light curves in standard V and B magnitudes, with the remaining 15% expressed in units of differential flux. We have discovered a population of first-overtone Cepheid candidates, and for eight of them we present strong arguments in favor of this interpretation. We also report on the detection of a nonlinearity in the KPNO T2KA and T1KA cameras. The catalog of variables, as well as their photometry (~7.8×104 BV measurements) and finding charts, is available electronically via anonymous ftp and the World Wide Web. The complete set of the CCD frames is available upon request. Based on observations obtained with the 2.1 m telescope at the Kitt Peak National Observatory.

  6. DIRECT Distances to Nearby Galaxies Using Detached Eclipsing Binaries and Cepheids. VIII. Additional Variables in the Field M33B Discovered with Image Subtraction

    NASA Astrophysics Data System (ADS)

    Mochejska, B. J.; Kaluzny, J.; Stanek, K. Z.; Sasselov, D. D.; Szentgyorgyi, A. H.

    2001-11-01

    DIRECT is a project to obtain directly the distances to two Local Group galaxies, M31 and M33, which occupy a crucial position near the bottom of the cosmological distance ladder. As the first step of the DIRECT project we have searched for detached eclipsing binaries (DEBs) and new Cepheids in the M31 and M33 galaxies with 1 m class telescopes. In this eighth paper we present a catalog of variable stars discovered in the data from the follow-up observations of DEB system D33J013337.0+303032.8 in field M33B [(α,δ)=(23.48d,30.57d), J2000.0], collected with the Kitt Peak National Observatory 2.1 m telescope. In our search covering an area of 108 arcmin2 we have found 895 variable stars: 96 eclipsing binaries, 349 Cepheids, and 450 other periodic, possibly long-period or nonperiodic variables. Of these variables 612 are newly discovered. Their light curves were extracted using the ISIS image subtraction package. For 77% of the variables we present light curves in standard V and B magnitudes, with the remaining 23% expressed in units of differential flux. We have discovered a population of first-overtone Cepheid candidates, and for six of them we present strong arguments in favor of this interpretation. The catalog of variables, as well as their photometry (about 9.2×104 BV measurements) and finding charts, is available electronically via anonymous ftp and the World Wide Web. The complete set of the CCD frames is available upon request. Based on observations obtained with the 2.1 m telescope at Kitt Peak National Observatory, National Optical Astronomy Observatory, which is operated by the Association of Universities for Research in Astronomy, Inc., under cooperative agreement with the National Science Foundation.

  7. 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.

  8. "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

  9. 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

  10. Detection of [O I] λ6300 and Other Diagnostic Emission Lines in the Diffuse Ionized Gas of M33 with Gemini-North

    NASA Astrophysics Data System (ADS)

    Voges, E. S.; Walterbos, R. A. M.

    2006-06-01

    We present spectroscopic observations of diffuse ionized gas (DIG) in M33 near the H II region NGC 604. We present the first detection of [O I] λ6300 in the DIG of M33, one of the critical lines for distinguishing photoionization from shock ionization models. We measure [O I]/Hα in the range of 0.04-0.10 and an increase in this ratio with decreasing emission measure. Our measurements of [S II]/Hα and [N II]/Hα also rise with decreasing emission measure, while our [O III]/Hβ measurements remain fairly constant. We have one tentative detection of He I in the region of brightest emission measure, with a ratio of He I/Hα = 0.033 +/- 0.019, indicating that the helium is at least partially ionized. We compare our observed emission-line ratios to photoionization models and find that field star ionization models do not fit our data well. Leaky H II region models are consistent with our data, without the need to invoke additional ionization mechanisms to fit our [O I] or [O III] measurements. The closest large H II region is NGC 604 and is therefore a likely candidate for the source of the ionizing photons for the gas in this region.

  11. Naturally occurring cardiac glycosides.

    PubMed

    Radford, D J; Gillies, A D; Hinds, J A; Duffy, P

    1986-05-12

    Cardiac glycoside poisoning from the ingestion of plants, particularly of oleanders, occurs with reasonable frequency in tropical and subtropical areas. We have assessed a variety of plant specimens for their cardiac glycoside content by means of radioimmunoassays with antibodies that differ in their specificity for cardiac glycosides. Significant amounts of immunoreactive cardiac glycoside were found to be present in the ornamental shrubs: yellow oleander (Thevetia peruviana); oleander (Nerium oleander); wintersweet (Carissa spectabilis); bushman's poison (Carissa acokanthera); sea-mango (Cerbera manghas); and frangipani (Plumeria rubra); and in the milkweeds: redheaded cotton-bush (Asclepias curassavica); balloon cotton (Asclepias fruiticosa); king's crown (Calotropis procera); and rubber vine (Cryptostegia grandifolia). The venom gland of the cane toad (Bufo marinus) also contained large quantities of cardiac glycosides. The competitive immunoassay method permits the rapid screening of specimens that are suspected to contain cardiac glycosides. Awareness of the existence of these plant and animal toxins and their dangers allows them to be avoided and poisoning prevented. The method is also useful for the confirmation of the presence of cardiac glycosides in serum in cases of poisoning. PMID:3086679

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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.

  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. 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.

  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. Detecting change as it occurs

    NASA Technical Reports Server (NTRS)

    Radok, Uwe; Brown, Timothy J.

    1992-01-01

    Traditionally climate changes have been detected from long series of observations and long after they have happened. Our 'inverse sequential' procedure, for detecting change as soon as it occurs, describes the existing or most recent data by their frequency distribution. Its parameter(s) are estimated both from the existing set of observations and from the same set augmented by 1,2,....j new observations. Individual-value probability products ('likelihoods') are used to form ratios which yield two probabilities for erroneously accepting the existing parameter(s) as valid for the augmented data set, and vice versa. A genuine parameter change is signaled when these probabilities (or a more stable compound probability) show a progressive decrease. New parameter values can then be estimated from the new observations alone using standard statistical techniques. The inverse sequential procedure will be illustrated for global annual mean temperatures (assumed normally distributed), and for annual numbers of North Atlantic hurricanes (assumed to represent Poisson distributions). The procedure was developed, but not yet tested, for linear or exponential trends, and for chi-squared means or degrees of freedom, a special measure of autocorrelation.

  4. 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

  5. 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

  6. WHERE DOES WATERBORNE GIARDIASIS OCCUR, AND WHY

    EPA Science Inventory

    Over 60 outbreaks of waterborne giardiasis occurred in the United States between 1965 and 1982, mainly in the Northeast, the Rocky Mountain states, and the Pacific states. Outbreaks most often occurred as a result of inadequate or interrupted treatment. Disinfection problems and ...

  7. 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

  8. ST elevation occurring during stress testing

    PubMed Central

    Malouf, Diana; Mugmon, Marc

    2016-01-01

    A case is presented of significant reversible ST elevation occurring during treadmill testing, and the coronary anatomy and subsequent course are described, indicating that ischemia is a potential cause of this electrocardiographic finding. PMID:27124164

  9. Human external ophthalmomyiasis occurring in Barbados.

    PubMed

    Levett, P N; Brooker, L; Reifer, C; Prussia, P R; Eberhard, M L

    2004-06-01

    Human infection with the sheep nasal botfly Oestrus ovis occurs sporadically. In most cases, there is a history of a strike in the eye by the adult fly. Human O. ovis has been reported rarely from the Americas. We report the first case of O. ovis infection in the Caribbean region, which occurred in an urban area of Barbados. The patient responded to removal of the larvae from the conjunctiva and symptomatic treatment. PMID:15352754

  10. 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…

  11. 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…

  12. 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

  13. Changes in joint laxity occurring during pregnancy.

    PubMed Central

    Calguneri, M; Bird, H A; Wright, V

    1982-01-01

    We have studied changes in peripheral joint laxity occurring during pregnancy in 68 females using both the finger hyperextensometer to quantify laxity at the metacarpophalangeal joint of the index finger and Beighton et al.'s modification of the Carter and Wilkinson scoring system. Although the latter system recorded no change, the more sensitive hyperextensometer demonstrated a significant increase in joint laxity during the last trimester of pregnancy (0.02 greater than p greater than 0.01) over the readings from the same individuals after parturition. When primigravidae and multigravidae were compared, a highly significant increase in laxity was found in women having their second baby over those having their first (0.01 greater than p greater than 0.001), though no further increase in laxity occurred in subsequent pregnancies. PMID:7073339

  14. 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

  15. Naturally Occuring Fish Poisons from Plants

    NASA Astrophysics Data System (ADS)

    Cannon, Jonathan G.; Burton, Robert A.; Wood, Steven G.; Owen, Noel L.

    2004-10-01

    Since prehistoric times, cultures throughout the world have used piscicidal (fish poisoning) plants for fishing. In recent times, scientists have identified many of the plant compounds responsible for killing the fish and have found that these compounds possess other important biological properties, such as insecticidal and anti-cancer activities. This article reviews some of the chemical research that has been performed on naturally occurring fish poisons, including plant sources, methods of use, toxicity, and mechanisms of action of piscicides.

  16. 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

  17. Naturally occurring anti M complicating ABO grouping.

    PubMed

    Khalid, Safoorah; Dantes, Roelyn; Varghese, Sunu; Al Hakawati, Imadeddin

    2011-01-01

    Anti M is considered a naturally occurring antibody that is usually active at temperatures below 37°C and is thus of no clinical significance. This antibody, if present in an individual, can lead to a discrepancy between forward and reverse ABO grouping and thus creates diagnostic difficulties for blood bank staff. We report a case of a 58-year-old lady who had an unexpected reaction in reverse grouping due to anti M that posed a problem for us in the interpretation of results of her blood group. We also reviewed the literature to find out the significance of such discrepancy in blood grouping. PMID:21393909

  18. Cannabinoid receptors in invertebrates.

    PubMed

    McPartland, J M; Agraval, J; Gleeson, D; Heasman, K; Glass, M

    2006-03-01

    Two cannabinoid receptors, CB1 and CB2, are expressed in mammals, birds, reptiles, and fish. The presence of cannabinoid receptors in invertebrates has been controversial, due to conflicting evidence. We conducted a systematic review of the literature, using expanded search parameters. Evidence presented in the literature varied in validity, ranging from crude in vivo behavioural assays to robust in silico ortholog discovery. No research existed for several clades of invertebrates; we therefore tested for cannabinoid receptors in seven representative species, using tritiated ligand binding assays with [3H]CP55,940 displaced by the CB1-selective antagonist SR141716A. Specific binding of [3H]CP55,940 was found in neural membranes of Ciona intestinalis (Deuterstoma, a positive control), Lumbricusterrestris (Lophotrochozoa), and three ecdysozoans: Peripatoides novae-zealandiae (Onychophora), Jasus edwardi (Crustacea) and Panagrellus redivivus (Nematoda); the potency of displacement by SR141716A was comparable to measurements on rat cerebellum. No specific binding was observed in Actinothoe albocincta (Cnidaria) or Tethya aurantium (Porifera). The phylogenetic distribution of cannabinoid receptors may address taxonomic questions; previous studies suggested that the loss of CB1 was a synapomorphy shared by ecdysozoans. Our discovery of cannabinoid receptors in some nematodes, onychophorans, and crustaceans does not contradict the Ecdysozoa hypothesis, but gives it no support. We hypothesize that cannabinoid receptors evolved in the last common ancestor of bilaterians, with secondary loss occurring in insects and other clades. Conflicting data regarding Cnidarians precludes hypotheses regarding the last common ancestor of eumetazoans. No cannabinoid receptors are expressed in sponges, which probably diverged before the origin of the eumetazoan ancestor. PMID:16599912

  19. 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

  20. Medicinal significance of naturally occurring cyclotetrapeptides.

    PubMed

    Abdalla, Muna Ali

    2016-10-01

    Bioactive natural products are serendipitous drug candidates, which stimulate synthetic approaches for improving and supporting drug discovery and development. Therefore, the search for bioactive metabolites from different natural sources continues to play an important role in fashioning new medicinal agents. Several cyclic peptides were produced by organisms, such as β-defensins, gramicidin S, and tyrocidine A, and exhibited a wide range of bioactivities, such as antiviral activity against HIV-1, influenza A viruses, or antibacterial activity. Cyclic tetrapeptides are a class of natural products that were found to have a broad range of biological activities, promising pharmacokinetic properties, as well as interesting conformational dynamics and ability of slow inter-conversion to several different structures. Cyclooligopeptides, particularly medium ring-sized peptides, were obtained from marine microorganisms and exhibited a wide range of pharmacological properties, including antimicrobial and anti-dinoflagellate activities, cytotoxicity, and inhibitory activity against enzyme sortase B. Most of the naturally occurring cyclotetrapeptides are obtained from fungi. Some natural cyclic tetrapeptides were found to inhibit histone deacetylase (HDAC), which regulate the expression of genes. These compounds are very useful as cancer therapeutics. Various analogues of the natural cyclotetrapeptides were successfully synthesized to find novel lead compounds for pharmacological and biotechnological applications. Therefore, in this review, previously reported novel natural cyclotetrapeptides are briefly discussed, along with their important biological activities as drug candidates, together with their promising therapeutic properties. Moreover, their future perspective in drug discovery as potential therapeutic agents will be determined. PMID:27300506

  1. 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

  2. Naturally occurring hydroxytyrosol: synthesis and anticancer potential.

    PubMed

    Bernini, R; Merendino, N; Romani, A; Velotti, F

    2013-01-01

    Several epidemiological and animal studies have suggested that polyphenols, a group of secondary plant metabolites occurring mainly in the plant kingdom, may have a protective effect against some chronic degenerative diseases such as cancer. Polyphenols are part of the human diet, being present in vegetal food and beverages. Among them, an olive biophenol named hydroxytyrosol [2-(3,4- dihydroxyphenyl)ethanol, HTyr] has recently received particular attention because of its antioxidant, antiproliferative, pro-apoptotic, and anti-inflammatory activities, which have the potential to specifically counteract all cancer hallmarks, thus representing the expectant biological activities underlying the anti-tumor properties of this polyphenol. After a description of the synthetic procedures to prepare pure HTyr, this review takes into consideration the chemopreventive and chemotherapeutic potential of HTyr as the result of its antioxidant, antiproliferative and anti-inflammatory activities. In particular, the review is focused on the current knowledge of the main cellular and molecular mechanisms used by HTyr to affect carcinogenesis, highlighting the specific oncogenic and inflammatory signaling pathways potentially targeted by HTyr. PMID:23244583

  3. Does Shear Thickening Occur in Semisolid Metals?

    NASA Astrophysics Data System (ADS)

    Atkinson, Helen V.; Favier, Veronique

    2016-04-01

    In the various forms of semisolid processing such as thixoforming and thixoforging, the entry into the die occurs in a fraction of a second so it is the transient rheological behavior which governs the initial stages of flow. In experiments in the literature, this rheological behavior is probed through applying rapid transitions in shear rate under isothermal conditions. There is contradictory evidence as to whether the behavior during these transitions is shear thinning or shear thickening, although it is clear that once in the die the material is thinning. Here the data in the literature are reanalyzed to obtain a rationalization of the contradictions which has not previously been available. It is argued that if a suspension is initially in a disagglomerated state ( i.e., one which is initially sheared), the instantaneous behavior with a jump-up in shear rate is shear thickening (even if the long-term steady-state behavior is shear thinning) provided the fraction solid is greater than about 0.36 and the final shear rate at the end of the jump is greater than about 100 s-1. If the jump-up in shear rate is made from rest then yield masks the shear thickening.

  4. 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

  5. Sundew adhesive: a naturally occurring hydrogel.

    PubMed

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

    2015-06-01

    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

  6. 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

  7. 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

  8. 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.

  9. Dopamine receptor heteromeric complexes and their emerging functions.

    PubMed

    George, Susan R; Kern, Andras; Smith, Roy G; Franco, Rafael

    2014-01-01

    Dopamine neurotransmission is traditionally accepted as occurring through the five dopamine receptors that transduce its signal. Recent evidence has demonstrated that the range of physiologically relevant dopamine signaling complexes is greatly expanded by the ability of dopamine receptors to interact with other dopamine receptors and with receptors of other endogenous signaling ligands. These novel heteromeric complexes have functional properties distinct from the component receptors or are able to modulate the canonical signaling and function of the cognate receptors. These dopamine receptor heteromers provide new insight into physiological mechanisms and pathophysiological processes involving dopamine. PMID:24968781

  10. Abscisic acid influx into human nucleated cells occurs through the anion exchanger AE2.

    PubMed

    Vigliarolo, Tiziana; Zocchi, Elena; Fresia, Chiara; Booz, Valeria; Guida, Lucrezia

    2016-06-01

    Abscisic acid (ABA) is a hormone conserved from cyanobacteria to higher plants, where it regulates responses to environmental stimuli. ABA also plays a role in mammalian physiology, pointedly in inflammatory responses and in glycemic control. As the animal ABA receptor is on the intracellular side of the plasma membrane, a transporter is required for the hormone's action. Here we demonstrate that ABA transport in human nucleated cells occurs via the anion exchanger AE2. Together with the recent demonstration that ABA influx into human erythrocytes occurs via Band 3, this result identifies the AE family members as the mammalian ABA transporters. PMID:27015766

  11. 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.

  12. 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

  13. 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

  14. A Naturally-Occurring Transcript Variant of MARCO Reveals the SRCR Domain is Critical for Function

    PubMed Central

    Novakowski, Kyle E.; Huynh, Angela; Han, SeongJun; Dorrington, Michael G.; Yin, Charles; Tu, Zhongyuan; Pelka, Peter; Whyte, Peter; Guarné, Alba; Sakamoto, Kaori; Bowdish, Dawn M.E.

    2016-01-01

    Macrophage receptor with collagenous structure (MARCO) is a Class A Scavenger Receptor (cA-SR) that recognizes and phagocytoses of a wide variety of pathogens. Most cA-SRs that contain a C-terminal Scavenger Receptor Cysteine Rich (SRCR) domain use the proximal collagenous domain to bind ligands. In contrast, for the role of the SRCR domain of MARCO in phagocytosis, adhesion and pro-inflammatory signalling is less clear. The discovery of a naturally-occurring transcript variant lacking the SRCR domain, MARCOII, provided the opportunity to study the role of the SRCR domain of MARCO. We tested whether the SRCR domain is required for ligand binding, promoting downstream signalling, and enhancing cellular adhesion. Unlike cells expressing full-length MARCO, ligand binding was abolished in MARCOII-expressing cells. Furthermore, co-expression of MARCO and MARCOII impaired phagocytic function, indicating that MARCOII acts as a dominant negative variant. Unlike MARCO, expression of MARCOII did not enhance Toll-Like Receptor 2 (TLR2)-mediated pro-inflammatory signalling in response to bacterial stimulation. MARCO-expressing cells were more adherent and exhibited a dendritic-like phenotype, while MARCOII-expressing cells were less adherent and did not exhibit changes in morphology. These data suggest the SRCR domain of MARCO is the key domain in modulating ligand binding, enhancing downstream pro-inflammatory signalling, and MARCO-mediated cellular adhesion. PMID:26888252

  15. Physiology and pathology of NMDA receptors.

    PubMed

    Petrović, M; Horák, M; Sedlácek, M; Vyklický, L

    2005-01-01

    Ionotropic glutamate receptors of the N-methyl-D-aspartate (NMDA) subtype are highly expressed in the central nervous system and are involved in excitatory synaptic transmission and synaptic plasticity. Prolonged activation of NMDA receptors can lead to excitotoxicity, which is implicated in the pathogenesis of neurodegeneration occurring in various acute and chronic disorders of the central nervous system. Recent advances in understanding the function, pharmacology, genetics and structure of NMDA receptors has promoted a search for new compounds that could be therapeutically used. These compounds act on agonist binding sites, either apart from them or directly within the ion channel pore. Members of the last group are called open channel blockers, and some of them, such as memantine and ketamine, are already clinically used. Kinetic modeling of NMDA receptor activity was employed to define the effects of various groups of modulators. Quantifying the action of these substances by kinetic parameters can help us to reveal the molecular mechanism of action at the receptor and to characterize the dependence of its action on the mode of NMDA receptor activation. Two modes are considered: phasic activation, induced by synaptically released glutamate, and tonic activation, which is expected to occur under pathological conditions when low, but sustained levels of glutamate activate NMDA receptors. The aim of our review is to summarize the recent data about the structural and functional properties of NMDA receptors and their role in long-term potentiation and excitotoxicity. PMID:16315761

  16. Intracellular insulin-receptor dissociation and segregation in a rat fibroblast cell line transfected with a human insulin receptor gene

    SciTech Connect

    Levy, J.R.; Olefsky, J.M.

    1988-05-05

    The cellular processing of insulin and insulin receptors was studied using a rat fibroblast cell line that had been transfected with a normal human insulin receptor gene, expressing approximately 500 times the normal number of native fibroblasts insulin receptors. These cells bind and internalize insulin normally. Biochemically assays based on the selective precipitation by polyethylene glycol of intact insulin-receptor complexes but not of free intracellular insulin were developed to study the time course of intracellular insulin-receptor dissociation. Fibroblasts were incubated with radiolabeled insulin at 4/sup 0/C, and internalization of insulin-receptor complexes was initiated by warming the cells to 37/sup 0/C. Within 2 min, 90% of the internalized radioactivity was composed of intact insulin-receptor complexes. The dissociation of insulin from internalized insulin-receptor complexes was markedly inhibited by monensin and chloroquine. Furthermore, chloroquine markedly increased the number of cross-linkable intracellular insulin-receptor complexes, as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiography. These findings suggest that acidification of intracellular vesicles is responsible for insulin-receptor dissociation. Physical segregation of dissociated intracellular insulin from its receptor was monitored. The results are consistent with the view that segregation of insulin and receptor occurs 5-10 min after initiation of dissociation. These studies demonstrate the intracellular itinerary of insulin-receptor complexes, including internalization, dissociation of insulin from the internalized receptor within an acidified compartment, segregation of insulin from the receptor, and subsequent ligand degradation.

  17. Gβ promotes pheromone receptor polarization and yeast chemotropism by inhibiting receptor phosphorylation.

    PubMed

    Ismael, Amber; Tian, Wei; Waszczak, Nicholas; Wang, Xin; Cao, Youfang; Suchkov, Dmitry; Bar, Eli; Metodiev, Metodi V; Liang, Jie; Arkowitz, Robert A; Stone, David E

    2016-01-01

    Gradient-directed cell migration (chemotaxis) and growth (chemotropism) are processes that are essential to the development and life cycles of all species. Cells use surface receptors to sense the shallow chemical gradients that elicit chemotaxis and chemotropism. Slight asymmetries in receptor activation are amplified by downstream signaling systems, which ultimately induce dynamic reorganization of the cytoskeleton. During the mating response of budding yeast, a model chemotropic system, the pheromone receptors on the plasma membrane polarize to the side of the cell closest to the stimulus. Although receptor polarization occurs before and independently of actin cable-dependent delivery of vesicles to the plasma membrane (directed secretion), it requires receptor internalization. Phosphorylation of pheromone receptors by yeast casein kinase 1 or 2 (Yck1/2) stimulates their internalization. We showed that the pheromone-responsive Gβγ dimer promotes the polarization of the pheromone receptor by interacting with Yck1/2 and locally inhibiting receptor phosphorylation. We also found that receptor phosphorylation is essential for chemotropism, independently of its role in inducing receptor internalization. A mathematical model supports the idea that the interaction between Gβγ and Yck1/2 results in differential phosphorylation and internalization of the pheromone receptor and accounts for its polarization before the initiation of directed secretion. PMID:27072657

  18. 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…

  19. Kinematics and mass modelling of M33: Hα observations

    NASA Astrophysics Data System (ADS)

    Kam, Z. S.; Carignan, C.; Chemin, L.; Amram, P.; Epinat, B.

    2015-06-01

    As part of a long-term project to revisit the kinematics and dynamics of the large disc galaxies of the Local Group, we present the first deep, wide-field (˜42 arcmin × 56 arcmin) 3D-spectroscopic survey of the ionized gas disc of Messier 33. Fabry-Perot interferometry has been used to map its Hα distribution and kinematics at unprecedented angular resolution (≲3 arcsec) and resolving power (˜12 600), with the 1.6 m telescope at the Observatoire du Mont Mégantic. The ionized gas distribution follows a complex, large-scale spiral structure, unsurprisingly coincident with the already-known spiral structures of the neutral and molecular gas discs. The kinematical analysis of the velocity field shows that the rotation centre of the Hα disc is distant from the photometric centre by ˜168 pc (sky-projected distance) and that the kinematical major-axis position angle and disc inclination are in excellent agreement with photometric values. The Hα rotation curve agrees very well with the H I rotation curves for 0 < R < 6.5 kpc, but the Hα velocities are 10-20 km s-1 higher for R > 6.5 kpc. The reason for this discrepancy is not well understood. The velocity dispersion profile is relatively flat around 16 km s-1, which is at the low end of velocity dispersions of nearby star-forming galactic discs. A strong relation is also found between the Hα velocity dispersion and the Hα intensity. Mass models were obtained using the Hα rotation curve but, as expected, the dark matter halo's parameters are not very well constrained since the optical rotation curve only extends out to 8 kpc.

  20. 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

  1. 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

  2. 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

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. Implications of epidermal growth factor (EGF) induced egf receptor aggregation.

    PubMed Central

    Wofsy, C; Goldstein, B; Lund, K; Wiley, H S

    1992-01-01

    To investigate the role of receptor aggregation in EGF binding, we construct a mathematical model describing receptor dimerization (and higher levels of aggregation) that permits an analysis of the influence of receptor aggregation on ligand binding. We answer two questions: (a) Can Scatchard plots of EGF binding data be analyzed productively in terms of two noninteracting receptor populations with different affinities if EGF induced receptor aggregation occurs? No. If two affinities characterize aggregated and monomeric EGF receptors, we show that the Scatchard plot should have curvature characteristic of positively cooperative binding, the opposite of that observed. Thus, the interpretation that the high affinity population represents aggregated receptors and the low affinity population nonaggregated receptors is wrong. If the two populations are interpreted without reference to receptor aggregation, an important determinant of Scatchard plot shape is ignored. (b) Can a model for EGF receptor aggregation and EGF binding be consistent with the "negative curvature" (i.e., curvature characteristic of negatively cooperative binding) observed in most Scatchard plots of EGF binding data? Yes. In addition, the restrictions on the model parameters required to obtain negatively curved Scatchard plots provide new information about binding and aggregation. In particular, EGF binding to aggregated receptors must be negatively cooperative, i.e., binding to a receptor in a dimer (or higher oligomer) having one receptor already bound occurs with lower affinity than the initial binding event. A third question we consider is whether the model we present can be used to detect the presence of mechanisms other than receptor aggregation that are contributing to Scatchard plot curvature. For the membrane and cell binding data we analyzed, the best least squares fits of the model to each of the four data sets deviate systematically from the data, indicating that additional factors are

  9. 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/...

  10. Unilateral eruptive vellus hair cysts occurring on the face.

    PubMed

    Lew, B-L; Lee, M-H; Haw, C-R

    2006-11-01

    Eruptive vellus hair cysts (EVHC) are small, cystic papules that usually occur on the chest and extremities. Their aetiology is unknown. Fewer than 10 cases of a variant form of EVHC that occur exclusively on the face have been reported. We describe a case of EVHC limited to the right side of the face. To the best of our knowledge, no case of unilateral EVHC has been reported. PMID:17062051

  11. 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.

  12. 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'. PMID:26211976

  13. Bombesin-Like Receptor 3: Physiology of a Functional Orphan.

    PubMed

    Xiao, Cuiying; Reitman, Marc L

    2016-09-01

    Bombesin-like receptor 3 (BRS-3) is an X-linked orphan Gq-coupled receptor that regulates food intake, metabolic rate, body temperature, heart rate, blood pressure, and insulin secretion. Most BRS-3 actions occur via the brain, through mechanisms including regulating sympathetic outflow. Ablation of Brs3 causes obesity, while synthetic agonists produce weight loss. PMID:27055378

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. Effects of naturally occurring coumarins on hepatic drug-metabolizing enzymes inmice

    SciTech Connect

    Kleiner, Heather E. Xia, Xiaojun; Sonoda, Junichiro; Zhang, Jun; Pontius, Elizabeth; Abey, Jane; Evans, Ronald M.; Moore, David D.; DiGiovanni, John

    2008-10-15

    Cytochromes P450 (P450s) and glutathione S-transferases (GSTs) constitute two important enzyme families involved in carcinogen metabolism. Generally, P450s play activation or detoxifying roles while GSTs act primarily as detoxifying enzymes. We previously demonstrated that oral administration of the linear furanocoumarins, isopimpinellin and imperatorin, modulated P450 and GST activities in various tissues of mice. The purpose of the present study was to compare a broader range of naturally occurring coumarins (simple coumarins, and furanocoumarins of the linear and angular type) for their abilities to modulate hepatic drug-metabolizing enzymes when administered orally to mice. We now report that all of the different coumarins tested (coumarin, limettin, auraptene, angelicin, bergamottin, imperatorin and isopimpinellin) induced hepatic GST activities, whereas the linear furanocoumarins possessed the greatest abilities to induce hepatic P450 activities, in particular P450 2B and 3A. In both cases, this corresponded to an increase in protein expression of the enzymes. Induction of P4502B10, 3A11, and 2C9 by xenobiotics often is a result of activation of the pregnane X receptor (PXR) and/or constitutive androstane receptor (CAR). Using a pregnane X receptor reporter system, our results demonstrated that isopimpinellin activated both PXR and its human ortholog SXR by recruiting coactivator SRC-1 in transfected cells. In CAR transfection assays, isopimpinellin counteracted the inhibitory effect of androstanol on full-length mCAR, a Gal4-mCAR ligand-binding domain fusion, and restored coactivator binding. Orally administered isopimpinellin induced hepatic mRNA expression of Cyp2b10, Cyp3a11, and GSTa in CAR(+/+) wild-type mice. In contrast, the induction of Cyp2b10 mRNA by isopimpinellin was attenuated in the CAR(-/-) mice, suggesting that isopimpinellin induces Cyp2b10 via the CAR receptor. Overall, the current data indicate that naturally occurring coumarins have

  19. Radiosequence analysis of the human progestin receptor charged with ( sup 3 H)promegestone. A comparison with the glucocorticoid receptor

    SciTech Connect

    Stroemstedt, P.E.B.; Berkenstam, A.; Joernvall, H.G.; Gustafsson, J.A.; Carlstedt-Duke, J. )

    1990-08-05

    Partially purified preparations of the human progestin receptor and the human and rat glucocorticoid receptor proteins were covalently charged with the synthetic progestin, ({sup 3}H)promegestone, by photoaffinity labeling. After labeling, the denaturated protein was cleaved and the mixture of peptides subjected to radiosequence analysis as previously described for the rat glucocorticoid receptor protein. The radioactivity labels identified, corresponded to Met-759 and Met-909 after photoaffinity labeling of the human progestin receptor, and Met-622 and Cys-754 after labeling of the rat glucocorticoid receptor. The residues labeled in the glucocorticoid receptor are the same as those previously reported to bind triamcinolone actonide. The corresponding residues were also labeled in the human glucocorticoid receptor. Met-759 of the progestin receptor and Met-622 of the rat glucocorticoid receptor are positioned within a segment with an overall high degree of sequence similarity and are equivalent. However, Met-909 (progestin receptor) and Cys-754 (glucocorticoid receptor) do not occur within equivalent segments of the two proteins. Thus, although the two classes of steroid hormone share a common structure within the A-ring, there are subtle differences in their interaction with the two separate receptor proteins.

  20. Antibodies to cardiac receptors.

    PubMed

    Boivin-Jahns, V; Schlipp, A; Hartmann, S; Panjwani, P; Klingel, K; Lohse, M J; Ertl, G; Jahns, R

    2012-12-01

    Inflammation of cardiac tissue is generally associated with an activation of the host's immune system. On the one hand, this activation is mandatory to protect the heart by fighting the invading microbial agents or toxins and by engaging myocardial reparation and healing processes. On the other hand, uncontrolled activation of the immune defense has the risk of an arousal of auto- or cross-reactive immune cells, which in some cases bring more harm than good. Dependent on the individual genetic predisposition, such heart-directed autoimmune reactions most likely occur as a result of myocyte apoptosis or necrosis and subsequent liberation of self-antigens previously hidden to the immune system. During the past two decades, evidence for a pathogenic relevance of autoimmunity in human heart disease has substantially increased. Conformational cardiac (auto)antibodies affecting cardiac function and, in particular, (auto)antibodies that target G protein-coupled cardiac membrane receptors are thought to play a key role in the development of heart failure. Clinical pilot studies even suggest that such antibodies negatively affect survival in heart failure patients. However, the true prevalence and clinical impact of many cardiac (auto)antibodies in human heart diseases are still unclear, as are the events triggering their formation, their titer course, and their patterns of clearance and/or persistence. The present article summarizes current knowledge in the field of cardiac receptor (auto)antibodies including recent efforts to address some of the aforementioned gaps of knowledge, thereby attempting to pave the way for novel, more specific therapeutic approaches. PMID:23183584

  1. Evolution of melanocortin receptors in cartilaginous fish: melanocortin receptors and the stress axis in elasmobranches.

    PubMed

    Liang, Liang; Reinick, Christina; Angleson, Joseph K; Dores, Robert M

    2013-01-15

    There is general agreement that the presence of five melanocortin receptor genes in tetrapods is the result of two genome duplications that occurred prior to the emergence of the gnathostomes, and at least one local gene duplication that occurred early in the radiation of the ancestral gnathostomes. Hence, it is assumed that representatives from the extant classes of gnathostomes (i.e., Chondrichthyes, Actinopterygii, Sarcopterygii) should also have five paralogous melanocortin genes. Current studies on cartilaginous fishes indicate that while there is evidence for five paralogous melanocortin receptor genes in this class, to date all five paralogs have not been detected in the genome of a single species. This mini-review will discuss the ligand selectivity properties of the melanocortin-3 receptor of the elephant shark (subclass Holocephali) and the ligand selectivity properties of the melanocortin-3 receptor, melanocortin-4 receptor, and the melanocortin-5 receptor of the dogfish (subclass Elasmobranchii). The potential relationship of these melanocortin receptors to the hypothalamus/pituitary/interrenal axis will be discussed. PMID:22964529

  2. 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.

  3. Naturally-occurring chemical analogues for repository-derived radionuclides

    SciTech Connect

    Miller, B.

    1996-12-01

    Studies of natural systems are a valuable means of gaining information on the behavior of elements and radionuclides in the geosphere or biosphere that may be used to support performance assessments for radioactive waste repositories. However, these natural system studies face the problem that some of the chemical and isotopic species that occur in radioactive wastes do not occur naturally. Therefore, when attempting to study transport processes for these species other, naturally-occurring species must be examined as {open_quote}chemical analogues{close_quote} for the waste species. Chemical analogues are chosen on the basis of some similarity with the chemical behavior of the waste species in relevant physico-chemical environments. This is a tricky procedure and each system must be considered on a case-by-case basis, although some guidelines can be established and these are given here.

  4. When Does A Gait Transition Occur During Human Locomotion?

    PubMed Central

    Hreljac, Alan; Imamura, Rodney T.; Escamilla, Rafael F.; Edwards, W. Brent

    2007-01-01

    When a treadmill accelerates continuously, the walk-run transition has generally been assumed to occur at the instant when a flight phase is first observed, while the run-walk transition has been assumed to occur at the instant of the first double support period. There is no theoretical or empirical evidence to suggest that gait transitions occur at the instant of these events, nor even whether transitions are abrupt events. The purpose of this study was to determine whether the gait transitions during human locomotion occur abruptly, and if so, to determine the instant during a stride at which a transition occurs. The time history of the vertical velocity of the hip (vhip) and the angular velocity of the ankle (ωankle) were compared between constant speed strides (walking or running) and strides at and near the walk-run and run-walk transitions to determine if and when the transition strides resemble the stride of the corresponding constant speed strides. For both the walk-run and run-walk transitions, the stride prior to the transition resembled the original gait pattern, while the stride following the transition resembled the new gait pattern. The transition stride, however, did not resemble either a walking or a running stride during either of the transition directions. It was concluded that gait transitions are initiated at about midstance of the transition stride, but the transition is not completed until after an adjustment period of between one step and one stride. Thus, gait transitions are not abrupt events during human locomotion. Key pointsGait transitions are not abrupt events.Initiation of a gait transitions occur at about midstance of the transition stride.Gait transitions are completed approximately at the next heelstrike of the ipsilateral foot.Time period between initiation and completion of transition does not resemble either a walk or a run. PMID:24149222

  5. 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

  6. Dialysis disequilibrium syndrome occurring during continuous renal replacement therapy

    PubMed Central

    Tuchman, Shamir; Khademian, Zarir P.; Mistry, Kirtida

    2013-01-01

    The dialysis disequilibrium syndrome (DDS) is characterized by progressive neurological symptoms and signs attributable to cerebral edema that occurs due to fluid shifts into the brain following a relatively rapid decrease in serum osmolality during hemodialysis (HD). Since continuous renal replacement therapy (CRRT) is less efficient at solute clearance than intermittent HD, it seems logical that this mode of therapy is less likely to cause DDS. This entity has not been previously reported to occur with this modality. Here, we report two cases of DDS associated with CRRT that provide insights into its pathophysiological mechanisms and suggest strategies for its prevention. PMID:26120445

  7. Addressing Naturally Occurring Asbestos in the Mining Industry

    NASA Astrophysics Data System (ADS)

    Bieber, D. W.

    2012-12-01

    Mining companies deal with naturally occurring asbestos (NOA) issues on their sites in two ways, avoidance and management. Avoidance simply means that to the extent practical, new mines are located in areas where NOA is unlikely to occur. Where mines are located in areas where NOA may be present, mines implement management procedures to identify and control potential sources of NOA. Management practices may include procedures set forth in regulations such as California's Air Toxicity Control Measure that deals with surface mining, voluntary procedures, or a combination of both. The mining industry generally recognizes that addressing NOA issues is a cost of doing business.;

  8. 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. PMID:25797032

  9. 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.

  10. 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.

  11. 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. PMID:25889452

  12. Targeted downregulation of platelet CLEC-2 occurs through Syk-independent internalization

    PubMed Central

    Lorenz, Viola; Stegner, David; Stritt, Simon; Vögtle, Timo; Kiefer, Friedemann; Witke, Walter; Schymeinsky, Jürgen; Watson, Steve P.; Walzog, Barbara

    2015-01-01

    Platelet aggregation at sites of vascular injury is not only essential for hemostasis, but may also cause acute ischemic disease states such as myocardial infarction or stroke. The hemi-immunoreceptor tyrosine-based activation motif–containing C-type lectinlike receptor 2 (CLEC-2) mediates powerful platelet activation through a Src- and spleen tyrosine kinase (Syk)–dependent tyrosine phosphorylation cascade. Thereby, CLEC-2 not only contributes to thrombus formation and stabilization but also plays a central role in blood-lymphatic vessel development, tumor metastasis, and prevention of inflammatory bleeding, making it a potential pharmacologic target to modulate these processes. We have previously shown that injection of the anti–CLEC-2 antibody, INU1, results in virtually complete immunodepletion of platelet CLEC-2 in mice, which is, however, preceded by a severe transient thrombocytopenia thereby limiting its potential therapeutic use. The mechanisms underlying this targeted CLEC-2 downregulation have remained elusive. Here, we show that INU1-induced CLEC-2 immunodepletion occurs through Src-family kinase–dependent receptor internalization in vitro and in vivo, presumably followed by intracellular degradation. In mice with platelet-specific Syk deficiency, INU1-induced CLEC-2 internalization/degradation was fully preserved whereas the associated thrombocytopenia was largely prevented. These results show for the first time that CLEC-2 can be downregulated from the platelet surface through internalization in vitro and in vivo and that this can be mechanistically uncoupled from the associated antibody-induced thrombocytopenia. PMID:25795918

  13. Targeted downregulation of platelet CLEC-2 occurs through Syk-independent internalization.

    PubMed

    Lorenz, Viola; Stegner, David; Stritt, Simon; Vögtle, Timo; Kiefer, Friedemann; Witke, Walter; Schymeinsky, Jürgen; Watson, Steve P; Walzog, Barbara; Nieswandt, Bernhard

    2015-06-25

    Platelet aggregation at sites of vascular injury is not only essential for hemostasis, but may also cause acute ischemic disease states such as myocardial infarction or stroke. The hemi-immunoreceptor tyrosine-based activation motif-containing C-type lectinlike receptor 2 (CLEC-2) mediates powerful platelet activation through a Src- and spleen tyrosine kinase (Syk)-dependent tyrosine phosphorylation cascade. Thereby, CLEC-2 not only contributes to thrombus formation and stabilization but also plays a central role in blood-lymphatic vessel development, tumor metastasis, and prevention of inflammatory bleeding, making it a potential pharmacologic target to modulate these processes. We have previously shown that injection of the anti-CLEC-2 antibody, INU1, results in virtually complete immunodepletion of platelet CLEC-2 in mice, which is, however, preceded by a severe transient thrombocytopenia thereby limiting its potential therapeutic use. The mechanisms underlying this targeted CLEC-2 downregulation have remained elusive. Here, we show that INU1-induced CLEC-2 immunodepletion occurs through Src-family kinase-dependent receptor internalization in vitro and in vivo, presumably followed by intracellular degradation. In mice with platelet-specific Syk deficiency, INU1-induced CLEC-2 internalization/degradation was fully preserved whereas the associated thrombocytopenia was largely prevented. These results show for the first time that CLEC-2 can be downregulated from the platelet surface through internalization in vitro and in vivo and that this can be mechanistically uncoupled from the associated antibody-induced thrombocytopenia. PMID:25795918

  14. 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…

  15. 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...

  16. Changes occurring to minimally disturbed soil and to plant covers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    During the transition to organic production certain materials and practices, as described under US law, can not be used. During the transition period growers may, or may not, disturb the soil. There is little known about changes that occur if the soil is minimally disturbed during the transition t...

  17. 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...

  18. 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

  19. 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…

  20. Tardive dyskinesia occurring in a young woman after withdrawal of an atypical antipsychotic drug

    PubMed Central

    Alblowi, Mohammed A.; Alosaimi, Fahad D.

    2015-01-01

    Tardive dyskinesia (TD) is one of the most serious and disturbing side-effects of dopamine receptor antagonists. It affects 20-50% of patients on long-term antipsychotic therapy. The pathophysiology of TD remains poorly understood, and treatment is often challenging. Here, we present a 32-year-old woman presenting with a 9-month history of TD occurring after risperidone withdrawal, and characterized almost exclusively by tongue protrusion. After being seen by different specialties and undergoing multiple investigations, she was eventually correctly diagnosed with TD by a specialist team and successfully treated with amantadine. Vigilance and awareness of this condition and its risk factors are required to make the correct diagnosis, especially in cases with unusual presentations caused by atypical antipsychotics, and treatment can be challenging. PMID:26492119

  1. 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.

  2. 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

  3. Bordetella pertussis Naturally Occurring Isolates with Altered Lipooligosaccharide Structure Fail To Fully Mature Human Dendritic Cells

    PubMed Central

    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.

    2014-01-01

    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. PMID:25348634

  4. Oxytocin neuron activation prevents hypertension that occurs with chronic intermittent hypoxia/hypercapnia in rats.

    PubMed

    Jameson, Heather; Bateman, Ryan; Byrne, Peter; Dyavanapalli, Jhansi; Wang, Xin; Jain, Vivek; Mendelowitz, David

    2016-06-01

    Hypertension is a common outcome associated with obstructive sleep apnea (OSA), a prevalent yet poorly treated cardiovascular disease. Recent studies showed oxytocin (OXT), released from hypothalamic paraventricular nucleus (PVN) neurons, activates cardiac vagal neurons in the dorsal motor nucleus of the vagus (DMNX) and may blunt cardiovascular responses to stress. This study tests whether the release of OXT from PVN fibers in the DMNX is diminished with chronic intermittent hypoxia-hypercapnia (CIH/H) exposure, an animal model of OSA, and whether activation of PVN OXT neurons restores OXT release in the DMNX and prevents the hypertension resulting from CIH/H. To assess OXT release from PVN fibers, Chinese hamster ovarian (CHO) cells were engineered to be highly sensitive to OXT by stable expression of the human recombinant OXT receptor and the calcium indicator R-GECO1. PVN fibers in the DMNX were selectively photoactivated in vitro by expression of channelrhodopsin. The release of OXT onto CHO cells in the DMNX was blunted in rats exposed to 21 days of CIH/H. Chronic activation of PVN OXT neurons in vivo, using designer receptors exclusively activated by designer drugs, restored the release of OXT onto CHO cells in the DMNX. Chronic PVN OXT neuron activation in vivo also prevented the hypertension that occurred in conscious unrestrained telemetry-equipped sham rats exposed to 3 wk of CIH/H. These results demonstrate that chronic activation of OXT neurons restores the release of OXT from PVN fibers in the DMNX and prevents the hypertension that occurs with 3 wk of CIH/H exposure. PMID:27016581

  5. 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

  6. Lamin B receptor

    PubMed Central

    Olins, Ada L; Rhodes, Gale; Welch, David B Mark; Zwerger, Monika

    2010-01-01

    Lamin B receptor (LBR) is an integral membrane protein of the interphase nuclear envelope (NE). The N-terminal end resides in the nucleoplasm, binding to lamin B and heterochromatin, with the interactions disrupted during mitosis. The C-terminal end resides within the inner nuclear membrane, retreating with the ER away from condensing chromosomes during mitotic NE breakdown. Some of these properties are interpretable in terms of our current structural knowledge of LBR, but many of the structural features remain unknown. LBR apparently has an evolutionary history which brought together at least two ancient conserved structural domains (i.e., Tudor and sterol reductase). This convergence may have occurred with the emergence of the chordates and echinoderms. It is not clear what survival values have maintained LBR structure during evolution. But it seems likely that roles in post-mitotic nuclear reformation, interphase NE growth and compartmentalization of nuclear architecture might have provided some evolutionary advantage to preservation of the LBR gene. PMID:21327105

  7. 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

  8. 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

  9. Management of iatrogenic crystalline lens injury occurred during intravitreal injection.

    PubMed

    Erdogan, Gurkan; Gunay, Betul Onal; Unlu, Cihan; Gunay, Murat; Ergin, Ahmet

    2016-08-01

    To evaluate the approach to management of iatrogenic crystalline lens injury occurred during intravitreal injection (IVI). The patients who were managed operatively or followed-up without intervention after the iatrogenic lens injury due to IVI were included in the study. Capsular breaks remained either quiescent or resulted in cataract formation in the patients with inadvertent crystalline lens capsule damage. Phacoemulsification surgery was performed in patients with cataract formation with lower fluidic settings. A total of 9 cases included in the study. Seven cases underwent phacoemulsification with intraocular lens implantation. Two cases remained as quiescent lens injury during the follow-up. In 2 cases, dislocation of lens fragments occurred during phacoemulsification where pars plana vitrectomy was performed at the same session. After iatrogenic crystalline lens injury, capsular damage could remain quiescent or progress to cataract formation. Although phacoemulsification surgery can be performed with appropriate parameters, lens fragment dislocation can be observed in cases with traumatic lens damage secondary to IVI. PMID:26631401

  10. Naturally occurring tumours in the basal metazoan Hydra.

    PubMed

    Domazet-Lošo, Tomislav; Klimovich, Alexander; Anokhin, Boris; Anton-Erxleben, Friederike; Hamm, Mailin J; Lange, Christina; Bosch, Thomas C G

    2014-01-01

    The molecular nature of tumours is well studied in vertebrates, although their evolutionary origin remains unknown. In particular, there is no evidence for naturally occurring tumours in pre-bilaterian animals, such as sponges and cnidarians. This is somewhat surprising given that recent computational studies have predicted that most metazoans might be prone to develop tumours. Here we provide first evidence for naturally occurring tumours in two species of Hydra. Histological, cellular and molecular data reveal that these tumours are transplantable and might originate by differentiation arrest of female gametes. Growth of tumour cells is independent from the cellular environment. Tumour-bearing polyps have significantly reduced fitness. In addition, Hydra tumours show a greatly altered transcriptome that mimics expression shifts in vertebrate cancers. Therefore, this study shows that spontaneous tumours have deep evolutionary roots and that early branching animals may be informative in revealing the fundamental mechanisms of tumorigenesis. PMID:24957317

  11. 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

  12. Pharmacotherapy of Co-Occurring Schizophrenia and Substance Use Disorders

    PubMed Central

    Akerman, Sarah C.; Brunette, Mary F.; Noordsy, Douglas L.

    2016-01-01

    Substance use disorders, common in patients with schizophrenia, can lead to poor outcomes. Here we review the literature on the use of antipsychotics in patients with co-occurring schizophrenia and substance use disorder as well as evidence for the use of adjunctive pharmacological treatments targeting substance use in these patients. We also discuss a neurobiological formulation suggesting that the cooccurrence of these disorders may be related to a dysfunction in the dopamine mediated brain reward circuitry. Typical antipsychotics do not appear to decrease substance use in this population. Randomized, controlled trials provide some support for use of the atypical antipsychotic clozapine for co-occurring cannabis use disorder, naltrexone and disulfiram for alcohol use disorder, and also nicotine replacement therapy, sustained-release bupropion and varenicline for tobacco use disorder. Nonetheless, data regarding treatment in patients with these co-occurring disorders are still limited, and many studies reported to date have been either underpowered or did not include a control condition. Further research is needed to evaluate optimal pharmacotherapeutic strategies for this population. PMID:27226947

  13. 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.

  14. 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

  15. 5-HT3 Receptors

    PubMed Central

    Thompson, A. J.; Lummis, S. C. R.

    2009-01-01

    The 5-HT3 receptor is a member of the Cys-loop family of ligand-gated ion channels. These receptors are located in both the peripheral and central nervous systems, where functional receptors are constructed from five subunits. These subunits may be the same (homopentameric 5-HT3A receptors) or different (heteropentameric receptors, usually comprising of 5-HT3A and 5-HT3B receptor subunits), with the latter having a number of distinct properties. The 5-HT3 receptor binding site is comprised of six loops from two adjacent subunits, and critical ligand binding amino acids in these loops have been largely identified. There are a range of selective agonists and antagonists for these receptors and the pharmacophore is reasonably well understood. There are also a wide range of compounds that can modulate receptor activity. Studies have suggested many diverse potential disease targets that might be amenable to alleviation by 5-HT3 receptor selective compounds but to date only two applications have been fully realised in the clinic: the treatment of emesis and irritable-bowel syndrome. PMID:17073663

  16. 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

  17. 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

  18. 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

  19. Chemical reactions occurring during direct solar reduction of CO2.

    PubMed

    Lyma, J L; Jensen, R J

    2001-09-28

    At high temperatures carbon dioxide may absorb solar radiation and react to form carbon monoxide and molecular oxygen. The CO, so produced, may be converted by well-established means to a combustible fuel, such as methanol. We intend to make a future demonstration of the solar reduction of CO2 based on these processes. This paper, however, addresses only the problem of preserving, or even enhancing, the initial photolytic CO by quenching the hot gas with colder H2O or CO2. We present model calculations with a reaction mechanism used extensively in other calculations. If a CO2 gas stream is heated and photolyzed by intense solar radiation and then allowed to cool slowly, it will react back to the initial CO2 by a series of elementary chemical reactions. The back reaction to CO2 can be terminated with the rapid addition of CO2, water, or a mixture. Calculations show that a three-fold quench with pure CO2 will stop the reactions and preserve over 90% of the initial photolytic CO. We find that water has one of two effects. It can either increase the CO level, or it can catalyze the recombination of O and CO to CO2. The gas temperature is the determining factor. If the quench gas is not sufficient to keep the temperature below approximately 1100 K, a chain-branching reaction dominates and the reaction to CO2 occurs. If the temperature stays below that level a chain terminating reaction dominates and the CO is increased. The former case occurs below approximately a fourfold quench with a water/CO2 mixture. The later case occurs when the quench is greater than fourfold. We conclude that CO2, H2O, or a mixture may quench the hot gas stream photolyzed by solar radiation and preserve the photolytic CO. PMID:11589409

  20. Treatment of Nodular Fasciitis Occurring on the Face

    PubMed Central

    Oh, Byung Ho; Kim, Jihee; Zheng, Zhenlong; Roh, Mi Ryung

    2015-01-01

    Background Surgical excision is generally recommended for the treatment of nodular fasciitis (NF) to rule out sarcoma. However, in cases of NF occurring on the face, the reported recurrence rate is higher and the surgical approach may result in considerable aesthetic concern. Objective To describe our experience with NF occurring on the face and evaluate the outcomes of surgical and nonsurgical methods of treatment. Methods We performed a retrospective review of 16 patients with NF on the face. The patients were treated with surgical excision or nonsurgical methods such as triamcinolone intralesional injection (TA ILI) and pinhole method with a carbon dioxide (CO2) laser. Results Among the 16 patients, surgical treatment was performed in 9 and recurrence occurred in 7 of these 9 patients (77.8%). The recurred lesions showed regression after repeated TA ILI. On the other hand, five patients underwent nonsurgical treatment after the histologic exclusion of malignancy. Their lesions showed regression after repeated pinhole treatment and TA ILI. In one case, NF spontaneously regressed. On a visual analogue scale, the nonsurgical approach showed superior results. However, the values were not statistically significant (6.90±1.56 vs. 5.61±1.36; p=0.163). The satisfaction level was lower in patients who experienced recurrence after surgical excision. Conclusion Surgical treatment for NF on the face showed a noticeable recurrence rate and resulted in scarring. Therefore, considering the possibility of spontaneous regression, the nonsurgical method can be considered as an alternative treatment option for NF on the face. PMID:26719638

  1. 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

  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. 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.

  4. 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.

  5. Iliac arterial-enteric fistulas occurring after pelvic irradiation

    SciTech Connect

    Vetto, J.T.; Culp, S.C.; Smythe, T.B.; Chang, A.E.; Sindelar, W.F.; Sugarbaker, P.H.; Heit, H.A.; Giordano, J.M.; Kozloff, L.

    1987-05-01

    Fistulas from the iliac artery to the bowel constitute a condition that is often lethal. Excluding fistulas related to vascular grafts, a review of previously reported cases shows that they are most often due to atherosclerotic iliac aneurysms. Three unusual cases of this condition that occurred after high-dose pelvic irradiation for treatment of cancer are presented; in no case was recurrent tumor evident. These cases suggest that high-dose pelvic irradiation can predispose to the formation of iliac arterial-enteric fistulas, particularly if sepsis or inflammation develops. The definitive surgical management of these fistulas entails bowel resection, arterial ligation, and extra-anatomic bypass.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. State estimation for networked systems with randomly occurring quantisations

    NASA Astrophysics Data System (ADS)

    He, Xiao; Wang, Zidong; Ji, Y. D.; Zhou, D. H.

    2013-07-01

    In this article, the state estimation problem is investigated for a class of discrete-time networked systems with randomly occurring quantisations. Logarithmic quantisers with different quantisation laws are considered and a Bernoulli distributed stochastic sequence is utilised to determine which quantiser is used at a certain time instant. After converting the quantisation effects into sector-bounded parameter uncertainties, a sufficient condition ensuring the existence of desirable estimators is proposed by using Lyapunov function approach, and parameters of the desired estimator are further obtained. Simulation is carried out on a networked three-tank system in order to illustrate the applicability of the proposed state estimation technique.

  11. 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

  12. Platelet-derived growth factor (PDGF)-AB-mediated phosphorylation of PDGF beta receptors.

    PubMed Central

    Coats, S R; Love, H D; Pledger, W J

    1994-01-01

    Platelet-derived growth factor (PDGF) stimulates the proliferation of Balb/c-3T3 fibroblasts through binding and subsequent activation of PDGF receptors. Activation of the PDGF receptors has been proposed to involve receptor dimerization. PDGF-AB has been shown to bind PDGF alpha and beta receptor subunits to form PDGF alpha beta and alpha alpha receptor dimers. In this paper we demonstrate that, following the down-regulation of PDGF alpha receptors, the binding of PDGF-AB to beta receptors occurred at 37 degrees C but not at 4 degrees C. PDGF-AB stimulated the phosphorylation of PDGF beta receptor monomers in cells depleted of PDGF alpha receptors by prior exposure to PDGF-AA. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8297345

  13. GABAB Receptors, Schizophrenia and Sleep Dysfunction

    PubMed Central

    Kantrowitz, Joshua; Citrome, Leslie; Javitt, Daniel

    2016-01-01

    Evidence for an intrinsic relationship between sleep, cognition and the symptomatic manifestations of schizophrenia is accumulating. This review presents evidence for the possible utility of GABAB receptor agonists for the treatment of subjective and objective sleep abnormalities related to schizophrenia. At the phenotypic level, sleep disturbance occurs in 16–30% of patients with schizophrenia and is related to reduced quality of life and poor coping skills. On the neurophysiological level, studies suggest that sleep deficits reflect a core component of schizophrenia. Specifically, slow-wave sleep deficits, which are inversely correlated with cognition scores, are seen. Moreover, sleep plays an increasingly well documented role in memory consolidation in schizophrenia. Correlations of slow-wave sleep deficits with impaired reaction time and declarative memory have also been reported. Thus, both behavioural insomnia and sleep architecture are critical therapeutic targets in patients with schizophrenia. However, long-term treatment with antipsychotics often results in residual sleep dysfunction and does not improve slow-wave sleep, and adjunctive GABAA receptor modulators, such as benzodiazepines and zolpidem, can impair sleep architecture and cognition in schizophrenia. GABAB receptor agonists have therapeutic potential in schizophrenia. These agents have minimal effect on rapid eye movement sleep while increasing slow-wave sleep. Preclinical associations with increased expression of genes related to slow-wave sleep production and circadian rhythm function have also been reported. GABAB receptor deficits result in a sustained hyperdopaminergic state and can be reversed by a GABAB receptor agonist. Genetic, postmortem and electrophysiological studies also associate GABAB receptors with schizophrenia. While studies thus far have not shown significant effects, prior focus on the use of GABAB receptor agonists has been on the positive symptoms of schizophrenia, with

  14. Novel hormone "receptors".

    PubMed

    Nemere, Ilka; Hintze, Korry

    2008-02-01

    Our concepts of hormone receptors have, until recently, been narrowly defined. In the last few years, an increasing number of reports identify novel proteins, such as enzymes, acting as receptors. In this review we cover the novel receptors for the hormones atrial naturetic hormone, enterostatin, hepcidin, thyroid hormones, estradiol, progesterone, and the vitamin D metabolites 1,25(OH)(2)D(3) and 24,25(OH)(2)D(3). PMID:17546587

  15. [Nuclear receptors PPARalpha].

    PubMed

    Soska, V

    2006-06-01

    Mechanism of the fibrates action is mediated by nuclear PPARalpha receptors (Peroxisome Proliferator-Activated Receptor). These receptors regulate a number of genes that are involved both in lipids and lipoproteins metabolism and other mediators (e.g. inflammatory mediatores). Due to PPARalpha activation by fibrates, triglycerides and small dense LDL concentration is decreased, HDL cholesterol is increased and both inflammation and prothrombotic status are reduced. These effects are very important in patients with metabolic syndrom. PMID:16871768

  16. Fenugreek: a naturally occurring edible spice as an anticancer agent.

    PubMed

    Shabbeer, Shabana; Sobolewski, Michelle; Anchoori, Ravi Kumar; Kachhap, Sushant; Hidalgo, Manuel; Jimeno, Antonio; Davidson, Nancy; Carducci, Michael A; Khan, Saeed R

    2009-02-01

    In recent years, various dietary components that can potentially be used for the prevention and treatment of cancer have been identified. In this study, we demonstrate that extract (FE) from the seeds of the plant Trigonella foenum graecum, commonly called fenugreek, are cytotoxic in vitro to a panel of cancer but not normal cells. Treatment with 10-15 ug/mL of FE for 72 h was growth inhibitory to breast, pancreatic and prostate cancer cell lines (PCa). When tested at higher doses (15-20 ug/mL), FE continued to be growth inhibitory to PCa cell lines but not to either primary prostate or hTert-immortalized prostate cells. At least part of the growth inhibition is due to induction of cell death, as seen by incorporation of Ethidium Bromide III into cancer cells exposed to FE. Molecular changes induced in PCa cells are: in DU-145 cells: downregulation of mutant p53, and in PC-3 cells upregulation of p21 and inhibition of TGFbeta induced phosphorylation of Akt. The surprising finding of our studies is that death of cancer cells occurs despite growth stimulatory pathways being simultaneously upregulated (phosphorylated) by FE. Thus, these studies add another biologically active agent to our armamentarium of naturally occurring agents with therapeutic potential. PMID:19197146

  17. Macaques exhibit a naturally-occurring depression similar to humans.

    PubMed

    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

  18. Regulation of naturally occurring radioactive materials in Australia.

    PubMed

    Jeffries, Cameron; Akber, Riaz; Johnston, Andrew; Cassels, Brad

    2011-07-01

    In order to promote uniformity between jurisdictions, the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) has developed the National Directory for Radiation Protection, which is a regulatory framework that all Australian governments have agreed to adopt. There is a large and diverse range of industries involved in mining or mineral processing, and the production of fossil fuels in Australia. Enhanced levels of naturally occurring radionuclides can be associated with mineral extraction and processing, other industries (e.g. metal recycling) and some products (e.g. plasterboard). ARPANSA, in conjunction with industry and State regulators, has undertaken a review and assessment of naturally occurring radioactive material (NORM) management in Australian industries. This review has resulted in guidance on the management of NORM that will be included in the National Directory for Radiation Protection. The first NORM safety guide provides the framework for NORM management and addresses specific NORM issues in oil and gas production, bauxite, aluminium and phosphate industries. Over time further guidance material for other NORM-related industries will be developed. This presentation will provide an overview of the regulatory approach to managing NORM industries in Australia. PMID:21515621

  19. 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.

  20. Interaction between manufactured gold nanoparticles and naturally occurring organic macromolecules.

    PubMed

    Diegoli, Sara; Manciulea, Adriana L; Begum, Shakiela; Jones, Ian P; Lead, Jamie R; Preece, Jon A

    2008-08-25

    The increasing exploitation of nanomaterials into many consumer and other products is raising concerns as these nanomaterials are likely to be released into the environment. Due to our lack of knowledge about the environmental chemistry, transport and ecotoxicology of nanomaterials, it is of paramount importance to study how natural aquatic colloids can interact with manufactured gold nanoparticles as these interactions will determine their environmental fate and behaviour. In this context, our work aims to quantify the effect of naturally occurring riverine macromolecules--International Humic Substances Society (IHSS) Suwannee River Humic Acid Standard (SRHA)--on citrate- and acrylate-stabilized gold nanoparticles. The influence of SRHA on the stability of the gold colloids was studied as a function of pH by UV-visible absorption spectroscopy, dynamic light scattering (DLS) and transmission electron microscopy (TEM). At high ionic strengths (0.1 M), extensive and rapid aggregation occurred, while more subtle effects were observed at lower ionic strength values. Evidence was found that SRHA enhances particle stability at extreme pH values (ionic strength<0.01 M) by substituting and/or over-coating the original stabilizer on the gold nanoparticle surface, thus affecting surface charge and chemistry. These findings have important implications for the fate and behaviour of nanoparticles in the environment and their ecotoxicity. PMID:18534664

  1. Dry-Heat Inactivation Kinetics of Naturally Occurring Spore Populations

    PubMed Central

    Bond, W. W.; Favero, M. S.; Petersen, N. J.; Marshall, J. H.

    1970-01-01

    Twenty-three soil samples were collected from areas of the United States where major spacecraft assembly and launch facilities are in operation. Soil samples were treated with ethyl alcohol, ultrasonic energy, and gross filtration. The resultant suspensions consisted of viable, naturally occurring bacterial spores and were used to inoculate stainless-steel strips. The strips were suspended in a forced air oven and assays were made at 5-min intervals for the number of viable spores. Most survivor curves were nonlinear. Subsequently, spore crops of heat-sensitive and heat-resistant soil isolates were found to have linear survivor curves at 125 C which were unaffected by the presence or absence of sterile soil particles from the parent sample. When two spore crops, one of which was heat-resistant and the other heat-sensitive, were mixed, the resultant nonlinear curves were unaffected by the presence or absence of sterile parent soil. Therefore, the survivor curves obtained originally with the soils were the result of heterogeneous spore populations rather than of protection afforded by soil particles in our test system. These results question the rationale both of assuming logarithmic death and of using decimal-reduction values obtained with subcultured standard reference spores in the derivation of dry-heat sterilization cycles for items contaminated with naturally occurring spore populations. PMID:5498605

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

    NASA Astrophysics Data System (ADS)

    Court, Richard W.; Tan, Jonathan

    2016-05-01

    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.

  3. 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

  4. Southeastern Australia's Submarine Landslides : a Model for Their Occurence

    NASA Astrophysics Data System (ADS)

    Hubble, T.; Clarke, S. L.; Yu, P.; Airey, D.; Keene, J.

    2012-12-01

    Recent work has identified an extensive region of the eastern Australian Continental Margin offshore Northern NSW and Southern Queensland which has experienced intense submarine erosion dominated by large-scale, submarine-landsliding that has removed enormous amounts of Neogene to recent sediment from the upper and middle continental slope. Preliminary findings demonstrate that i) some upper slope slides are geologically very young (< 20 kA), ii) the most recent slides occurred in relatively shallow depths and were volumetrically large enough (~3 cu km) to have been capable of generating damaging tsunami if shed as single masses and iii) the mid-slope slides are comprised of compacted Neogene sediments; iv) some of the mid-slope slide scars are huge (several 10's of cu km); and v) some of the mid-slope slide masses probably remained largely intact during sliding, potentially generated megatsunami, and are suspected to located on the abyssal Tasman Sea plain adjacent to the margin. A conceptual model that accounts for the apparent onset of sliding approximately 15 million years ago and the continuing deconstruction of the margin has been developed. This model posits that erosion of material from the middle and lower slope by deep, cold-water, ocean currents originating in Antartica occurred contemporaneously with an increase in the frequency and intensity of earthquakes due to increasing tectonic interaction between Australia and Asia. These two processes acted together to initiate and then sustain the submarine landsliding.

  5. 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

  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. 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

  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. PMID:24719579

  9. 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

  10. Infrasound observation of seismic events occurring in North Korea

    NASA Astrophysics Data System (ADS)

    Park, Y.; Che, I.; Nam, S.; Kim, Y.; Lee, J.

    2012-12-01

    Seismic events of North Korea were analyzed by using data set from the regional network including 31 seismic stations and 5 seismo-acoustic arrays of Korea Institute of Geoscience and Mineral Resources(KIGAM) and 7 Korea-China joint seismic stations in China. Infrasonic data were analysed using the PMCC method, to detect blast-associated infrasonic signals. Phase velocity and back-azimuth of infrasound signals varied between 250 to 400 m/s and ±10° respectively. Seismo-acoustic analysis was conducted to discriminate 375 events which are 38.1 percent of the total seismic events. More than 60 percent of seismo-acoustic events occurred around the Pyeongyang and Wonsan area of North Korea. In the case of the events occurred in the southeastern part of North Korea, the percentage was relatively small. The seismo-acoustic location were improved by using grid-search method. This method was based the observed travel times and azimuths of infrasonic signals and seismic parameter.

  11. Desensitization-resistant and -sensitive GPCR-mediated inhibition of GABA release occurs by Ca2+-dependent and -independent mechanisms at a hypothalamic synapse.

    PubMed

    Pennock, Reagan L; Hentges, Shane T

    2016-06-01

    Whereas the activation of Gαi/o-coupled receptors commonly results in postsynaptic responses that show acute desensitization, the presynaptic inhibition of transmitter release caused by many Gαi/o-coupled receptors is maintained during agonist exposure. However, an exception has been noted where GABAB receptor (GABABR)-mediated inhibition of inhibitory postsynaptic currents (IPSCs) recorded in mouse proopiomelanocortin (POMC) neurons exhibit acute desensitization in ∼25% of experiments. To determine whether differential effector coupling confers sensitivity to desensitization, voltage-clamp recordings were made from POMC neurons to compare the mechanism by which μ-opioid receptors (MORs) and GABABRs inhibit transmitter release. Neither MOR- nor GABABR-mediated inhibition of release relied on the activation of presynaptic K(+) channels. Both receptors maintained the ability to inhibit release in the absence of external Ca(2+) or in the presence of ionomycin-induced Ca(2+) influx, indicating that inhibition of release can occur through a Ca(2+)-independent mechanism. Replacing Ca(2+) with Sr(2+) to disrupt G-protein-mediated inhibition of release occurring directly at the release machinery did not alter MOR- or GABAB -mediated inhibition of IPSCs, suggesting that reductions in evoked release can occur through the inhibition of Ca(2+) channels. Additionally, both receptors inhibited evoked IPSCs in the presence of selective blockers of N- or P/Q-type Ca(2+) channels. Altogether, the results show that MORs and GABABRs can inhibit transmitter release through the inhibition of calcium influx and by direct actions at the release machinery. Furthermore, since both the desensitizing and nondesensitizing presynaptic receptors are similarly coupled, differential effector coupling is unlikely responsible for differential desensitization of the inhibition of release. PMID:26912590

  12. Cell-Surface Receptors Transactivation Mediated by G Protein-Coupled Receptors

    PubMed Central

    Cattaneo, Fabio; Guerra, Germano; Parisi, Melania; De Marinis, Marta; Tafuri, Domenico; Cinelli, Mariapia; Ammendola, Rosario

    2014-01-01

    G protein-coupled receptors (GPCRs) are seven transmembrane-spanning proteins belonging to a large family of cell-surface receptors involved in many intracellular signaling cascades. Despite GPCRs lack intrinsic tyrosine kinase activity, tyrosine phosphorylation of a tyrosine kinase receptor (RTK) occurs in response to binding of specific agonists of several such receptors, triggering intracellular mitogenic cascades. This suggests that the notion that GPCRs are associated with the regulation of post-mitotic cell functions is no longer believable. Crosstalk between GPCR and RTK may occur by different molecular mechanism such as the activation of metalloproteases, which can induce the metalloprotease-dependent release of RTK ligands, or in a ligand-independent manner involving membrane associated non-receptor tyrosine kinases, such as c-Src. Reactive oxygen species (ROS) are also implicated as signaling intermediates in RTKs transactivation. Intracellular concentration of ROS increases transiently in cells stimulated with GPCR agonists and their deliberated and regulated generation is mainly catalyzed by enzymes that belong to nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family. Oxidation and/or reduction of cysteine sulfhydryl groups of phosphatases tightly controls the activity of RTKs and ROS-mediated inhibition of cellular phosphatases results in an equilibrium shift from the non-phosphorylated to the phosphorylated state of RTKs. Many GPCR agonists activate phospholipase C, which catalyze the hydrolysis of phosphatidylinositol 4,5-bis-phosphate to produce inositol 1,4,5-triphosphate and diacylglicerol. The consequent mobilization of Ca2+ from endoplasmic reticulum leads to the activation of protein kinase C (PKC) isoforms. PKCα mediates feedback inhibition of RTK transactivation during GPCR stimulation. Recent data have expanded the coverage of transactivation to include Serine/Threonine kinase receptors and Toll-like receptors. Herein, we

  13. Implementing Residential Integrated Treatment for Co-occurring Disorders

    PubMed Central

    McKee, Shari A.; Harris, Grant T.; Cormier, Catherine A.

    2013-01-01

    Objective: Much is now known about effective treatment for co-occurring substance abuse and psychiatric difficulties and many evidence-based practice recommendations have been disseminated. Implementation of these recommended interventions in daily clinical practice has been more of a struggle. This article describes successful implementation of integrated treatment for co-occurring disorders in a small residential program. Methods: A traditional 28-day addiction service was transformed into a 3-month integrated treatment program and 155 individuals with co-occurring disorders agreed to participate in its evaluation. The transformation entailed a completely new manualized service, training in a number of clinical interventions for all program clinicians, ongoing clinical supervision, and formal measurement of clients’ backgrounds, substance abuse, quality of life, mental health symptoms, self-esteem, and satisfaction with the program. We also obtained collateral informants’ reports on participants’ symptoms, substance use, and quality of life. Fidelity to the treatment model was continuously assessed, as were participants’ knowledge and skill acquisition. In addition, impact of the implementation on the program clinicians’ morale and attitudes toward evidence-based practices was assessed, as was staff turnover and per diem costs. Results: Despite very problematic clinical and sociodemographic histories, the 86 participants who completed the program showed clinically significant mental health symptom improvement, acquisition of knowledge and skill, and high self-esteem and satisfaction with the program. Program fidelity, clinician morale, commitment to the program, and attitudes toward evidence-based practice were uniformly high. These successes were achieved while maintaining the lowest per–inpatient day cost of all hospital inpatient units. Conclusions: The findings support the contention that evidence-based integrated treatment can be implemented with

  14. Designing a Nanotube Using Naturally Occurring Protein Building Blocks

    PubMed Central

    Tsai, Chung-Jung; Zheng, Jie; Nussinov, Ruth

    2006-01-01

    Here our goal is to carry out nanotube design using naturally occurring protein building blocks. Inspection of the protein structural database reveals the richness of the conformations of proteins, their parts, and their chemistry. Given target functional protein nanotube geometry, our strategy involves scanning a library of candidate building blocks, combinatorially assembling them into the shape and testing its stability. Since self-assembly takes place on time scales not affordable for computations, here we propose a strategy for the very first step in protein nanotube design: we map the candidate building blocks onto a planar sheet and wrap the sheet around a cylinder with the target dimensions. We provide examples of three nanotubes, two peptide and one protein, in atomistic model detail for which there are experimental data. The nanotube models can be used to verify a nanostructure observed by low-resolution experiments, and to study the mechanism of tube formation. PMID:16683021

  15. 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

  16. 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

  17. 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

  18. 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

  19. Purifying food-grade, naturally occurring CO/sub 2/

    SciTech Connect

    Nobles, J.E.; Stancik, J.W.

    1983-12-26

    Technology to purify naturally occurring CO/sub 2/ into products suitable for enhanced oil recovery (EOR) and food grade CO/sub 2/ markets has been commercially demonstrated in a 20 MMscfd (1,100 ton/day) CO/sub 2/ processing facility owned and operated by Columbia Hydrocarbon Corp. The unit demonstrates that it is technically and economically feasible to process low grade natural gas to produce pipeline specification natural gas, raw CO/sub 2/, and food grade CO/sub 2/. The Selexol treating facility is located on a reclaimed coal strip mine with very restricted plot area. Only compression and dehydration equipment for the CO/sub 2/ is located there. The CO/sub 2/ is transported by pipeline to the Marmet site, approx. 7 miles away. This site contains the facilities for purifying the CO/sub 2/ and for storage.

  20. 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.

  1. 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.

  2. Recurrent Pleural Effusions Occurring in Association with Primary Pulmonary Amyloidosis

    PubMed Central

    Tada, Lauren; Anjum, Humayun; Linville, W. Kenneth; Surani, Salim

    2015-01-01

    Recurrent pleural effusions occurring in association with immunoglobulin light chain amyloidosis and not associated with amyloid cardiomyopathy are rare. These portend an overall poor prognosis with mean survival time of approximately 1.8 months. We hereby report a case of a 59-year-old Caucasian female with recurrent pleural effusions and an ultimate diagnosis of pulmonary amyloidosis in association with plasma cell myeloma. The optimal treatment for recurrent pleural effusions in amyloidosis has not been determined; however, our patient responded to therapy with Cyclophosphamide-Bortezomib- (Velcade-) Dexamethasone (CyBorD) and had no repeat hospitalizations or recurrence of pleural effusion at four-month follow-up after initiation of therapy. PMID:26448893

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. Metabolic mechanism of phenyllactic acid naturally occurring in Chinese pickles.

    PubMed

    Li, Xingfeng; Ning, Yawei; Liu, Dou; Yan, Aihong; Wang, Zhixin; Wang, Shijie; Miao, Ming; Zhu, Hong; Jia, Yingmin

    2015-11-01

    Phenyllactic acid, a phenolic acid phytochemical with the antimicrobial activity, was rarely reported in food besides honey and sourdough. This study evidenced a new food source of phenyllactic acid and elucidated its metabolic mechanism. Phenyllactic acid naturally occurred in Chinese pickles with concentrations ranged from 0.02 to 0.30 mM in 23 pickle samples including homemade and commercial ones. Then, lactic acid bacteria capable of metabolizing phenyllactic acid were screened from each homemade pickle and a promising strain was characterized as Lactobacillus plantarum. Moreover, the investigation of the metabolic mechanism of phenyllactic acid in pickles suggested that the yield of phenyllactic acid was positively related to the content of phenylalanine in food, and the addition of phenylalanine as precursor substance could significantly promote the production of phenyllactic acid. This investigation could provide some insights into the accumulation of phenyllactic acid in pickle for long storage life. PMID:25976820

  8. The growth hormone receptor.

    PubMed

    Waters, Michael J

    2016-06-01

    Once thought to be present only in liver, muscle and adipose tissue, the GH receptor is now known to be ubiquitously distributed, in accord with the many pleiotropic actions of GH. These include the regulation of metabolism, postnatal growth, cognition, immune, cardiac and renal systems and gut function. GH exerts these actions primarily through alterations in gene expression, initiated by activation of its membrane receptor and the resultant activation of the associated JAK2 (Janus kinase 2) and Src family kinases. Receptor activation involves hormone initiated movements within a receptor homodimer, rather than simple receptor dimerization. We have shown that binding of the hormone realigns the orientation of the two receptors both by relative rotation and by closer apposition just above the cell membrane. This is a consequence of the asymmetric placement of the binding sites on the hormone. Binding results in a conversion of parallel receptor transmembrane domains into a rotated crossover orientation, which produces separation of the lower part of the transmembrane helices. Because the JAK2 is bound to the Box1 motif proximal to the inner membrane, receptor activation results in separation of the two associated JAK2s, and in particular the removal of the inhibitory pseudokinase domain from the kinase domain of the other JAK2 (and vice versa). This brings the two kinase domains into position for trans-activation and initiates tyrosine phosphorylation of the receptor cytoplasmic domain and other substrates such as STAT5, the key transcription factor mediating most genomic actions of GH. There are a limited number of genomic actions initiated by the Src kinase family member which also associates with the upper cytoplasmic domain of the receptor, including important immune regulatory actions to dampen exuberant innate immune activation of cells involved in transplant rejection. These findings offer insights for developing specific receptor antagonists which may be

  9. 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.

  10. Kinetic plasma processes occurring in the outer plasmasphere

    NASA Technical Reports Server (NTRS)

    Wilson, Gordon R.

    1992-01-01

    One area of data analysis work that was begun under this contract is the fitting of the perpendicular velocity distributions of equatorially trapped ions with a Kappa function. This type of characterization of the trapped ions will be very useful for comparison with velocity distributions produced by the model. A second area of data analysis is to study data from consecutive passes when DE 1's apogee was near the magnetic equator and the spacecraft was often skimming along nearly the same L shell. In 1982 three such periods occurred in May, June, and July. For these consecutive events we have Kp histories, density measurements from a number of sources (Whistler data, DE SFR, ISEE SFR) and consecutive samples of ion pitch angle distributions along field lines. It is clear from this data how the pitch angle distributions evolve during a flux tube refilling event. Our modeling of the flow of plasma along closed field lines is following two basic tracks. The first is a study of the basic refilling process without the effect of wave-particle heating near the equator or the effect of large or abrupt field-aligned electric potential drops. This model includes the effects of Coulomb self-collisions and collisions with the O+ ions in the topside ionosphere. The second track is a study of the effects of wave produced pitch-angle scattering and perpendicular heating occurring near the magnetic equator, in connection with the development of large potential drops that result from electron heating and the development of density gradients.

  11. 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

  12. Detecting Concentration Changes with Cooperative Receptors

    NASA Astrophysics Data System (ADS)

    Bo, Stefano; Celani, Antonio

    2016-03-01

    Cells constantly need to monitor the state of the environment to detect changes and timely respond. The detection of concentration changes of a ligand by a set of receptors can be cast as a problem of hypothesis testing, and the cell viewed as a Neyman-Pearson detector. Within this framework, we investigate the role of receptor cooperativity in improving the cell's ability to detect changes. We find that cooperativity decreases the probability of missing an occurred change. This becomes especially beneficial when difficult detections have to be made. Concerning the influence of cooperativity on how fast a desired detection power is achieved, we find in general that there is an optimal value at finite levels of cooperation, even though easy discrimination tasks can be performed more rapidly by noncooperative receptors.

  13. 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.

  14. RECEPTOR MODEL DEVELOPMENT AND APPLICATION

    EPA Science Inventory

    Source apportionment (receptor) models are mathematical procedures for identifying and quantifying the sources of ambient air pollutants and their effects at a site (the receptor), primarily on the basis of species concentration measurements at the receptor, and generally without...

  15. HYBRID RECEPTOR MODELS

    EPA Science Inventory

    A hybrid receptor model is a specified mathematical procedure which uses not only the ambient species concentration measurements that form the input data for a pure receptor model, but in addition source emission rates or atmospheric dispersion or transformation information chara...

  16. Naturally occurring radioactive material in the oil and gas industry

    SciTech Connect

    Steingraber, W.A.

    1994-12-31

    Naturally occurring radioactive material (NORM) has been found in the Earth`s crust and soil, the water we drink, the food we eat, the air we breathe, and the tissues of every living organism. It is relatively easy to determine {open_quotes}concentrations{close_quotes}, or specific activity levels, in the range of 1 part per trillion for radioactive materials. With radioactive elements so abundant and detection possible at such low levels, the presence of NORM in oil and gas operations shouldn`t be surprising. In fact, this presence has been recognized since at least the 1930`s, but the phenomenon received only minimal attention in the United States until the mid-1980`s. At that time regulatory agencies in several oil- and gas-producing states began to focus on NORM in the exploration and production segment of the industry, expressing concern over potential health and safety implications. The most significant aspects of NORM in oil production operations include original source, transport media, composition/radionuclides present, measurement methods, health/safety issues, waste classification, and waste disposal. In addition, I will summarize industry-sponsored NORM data collection and analysis efforts being conducted to aid in development of sound policies and procedures to address environmental, health, and safety issues. Current activities by state and federal regulatory agencies relevant to NORM in the oil and gas industry will also be reviewed.

  17. Audiovisual temporal recalibration occurs independently at two different time scales.

    PubMed

    Van der Burg, Erik; Alais, David; Cass, John

    2015-01-01

    Combining signals across the senses improves precision and speed of perception, although this multisensory benefit declines for asynchronous signals. Multisensory events may produce synchronized stimuli at source but asynchronies inevitably arise due to distance, intensity, attention and neural latencies. Temporal recalibration is an adaptive phenomenon that serves to perceptually realign physically asynchronous signals. Recently, it was discovered that temporal recalibration occurs far more rapidly than previously thought and does not require minutes of adaptation. Using a classical audiovisual simultaneity task and a series of brief flashes and tones varying in onset asynchrony, perceived simultaneity on a given trial was found to shift in the direction of the preceding trial's asynchrony. Here we examine whether this inter-trial recalibration reflects the same process as prolonged adaptation by combining both paradigms: participants adapted to a fixed temporal lag for several minutes followed by a rapid series of test trials requiring a synchrony judgment. Interestingly, we find evidence of recalibration from prolonged adaptation and inter-trial recalibration within a single experiment. We show a dissociation in which sustained adaptation produces a large but decaying recalibration effect whilst inter-trial recalibration produces large transient effects whose sign matches that of the previous trial. PMID:26455577

  18. Spatial and temporal gene expression patterns occur during corm development.

    PubMed Central

    de Castro, L A; Carneiro, M; Neshich, D de C; de Paiva, G R

    1992-01-01

    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

  19. 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.

  20. Treatment of spontaneously occurring veterinary tumors with photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Panjehpour, Masoud; Legendre, Alfred; Sneed, Rick E.; Overholt, Bergein F.

    1992-06-01

    Chloroaluminum phthalocyanine tetrasulfonate was administered intravenously (1.0 mg/kg) to client owned cats and a dog with spontaneously occurring squamous cell carcinoma of head and neck. Light was delivered 48 hours post injection of the photosensitizer. An argon- pumped dye-laser was used to illuminate the lesions with 675 nm light delivered through a microlens fiber and/or a cylindrical diffuser. The light dose was 100 J/cm2 superficially or 300 J/cm interstitially. Eleven photodynamic therapy treatments in seven cats and one dog were performed. Two cats received a second treatment in approximately sixty days after the initial treatment. The superficial dose of light was increased to 200 J/cm2 for the second treatment. While the longest follow-up is twelve months, the responses are encouraging. The dog had a complete response. Among the cats, three showed complete response, three showed partial response and one showed no response. One cat expired two days post treatment. It is early to evaluate the response in two cats that received second treatments. Photodynamic therapy with chloroaluminum phthalocyanine tetrasulfonate was effective in treating squamous cell carcinoma in pet animals.

  1. Experimental nonenzymatic glycosylation of vitreous collagens occurs by two pathways.

    PubMed Central

    Pulido, J S

    1996-01-01

    PURPOSE: To study the process of nonenzymatic glycosolation of vitreous collagen in vitro to determine the contributions of the classic Maillard pathway and the oxidative pathway, as well as to evaluate possible inhibitors of both pathways. METHODS: Bovine vitreous collagen was extracted and then incubated with hexoses in vitro. The amount of advanced glycosylation end (AGE) products was measured by fluorometry under varying conditions in the presence and absence of glycosolation inhibitors. Oxygen consumption studies and electron spin resonance spectroscopy with and without free-radical inhibitors were performed to differentiate oxidative from nonoxidative glycosolation. RESULTS: Vitreous collagen undergoes nonenzymatic glycosolation in the presence of glucose or galactose in vitro. Oxygen consumption data show that oxygen is consumed in glucose and galactose solutions. Oxygen consumption is decreased by known free-radical inhibitors and rutin but not aminoguanidine. Electron spin resonance spectroscopy demonstrated the presence of a carbon-centered radical, and known free-radical inhibitors decreased the carbon-centered signal. CONCLUSIONS: Nonenzymatic glycosolation of vitreous collagen can occur not only by the classic nonoxidative pathway, but also by a second oxidative pathway that is susceptible to a number of inhibitors. PMID:8981718

  2. 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

  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. Documentation of Associated Injuries Occurring With Radial Head Fracture

    PubMed Central

    van Riet, Roger P.

    2008-01-01

    We believe a better way is needed to accurately describe the spectrum of associated injuries that commonly occur in conjunction with a radial head fracture. A review of our institution’s experience with 333 radial head fractures from 1997 to 2002 documented 88 (26%) associated injuries. Based on this clinical experience, our goal was to develop an accurate and comprehensive description of associated injuries. A shorthand suffix method first recognizes the type of radial head fracture with the traditional Mason classification, followed by abbreviations designating the articular injuries, coronoid (c) and olecranon (o), and the ligamentous injuries, lateral collateral ligament (l), medial collateral ligament (m), and distal radioulnar joint (d). The proposed system offers a logical and reproducible (98%) extension of the current Mason fracture classification to document the presence of additional articular and ligamentous injuries. This provides an opportunity to standardize the communication of fracture type with further details of other injuries that ultimately can help with better understanding of treatment outcome based on the precise injury complex. PMID:18196384

  5. Kinetochore assembly and heterochromatin formation occur autonomously in Schizosaccharomyces pombe.

    PubMed

    Brown, William R A; Thomas, Geraint; Lee, Nicholas C O; Blythe, Martin; Liti, Gianni; Warringer, Jonas; Loose, Matthew W

    2014-02-01

    Kinetochores in multicellular eukaryotes are usually associated with heterochromatin. Whether this heterochromatin simply promotes the cohesion necessary for accurate chromosome segregation at cell division or whether it also has a role in kinetochore assembly is unclear. Schizosaccharomyces pombe is an important experimental system for investigating centromere function, but all of the previous work with this species has exploited a single strain or its derivatives. The laboratory strain and most other S. pombe strains contain three chromosomes, but one recently discovered strain, CBS 2777, contains four. We show that the genome of CBS 2777 is related to that of the laboratory strain by a complex chromosome rearrangement. As a result, two of the kinetochores in CBS 2777 contain the central core sequences present in the laboratory strain centromeres, but lack adjacent heterochromatin. The closest block of heterochromatin to these rearranged kinetochores is ∼100 kb away at new telomeres. Despite lacking large amounts of adjacent heterochromatin, the rearranged kinetochores bind CENP-A(Cnp1) and CENP-C(Cnp3) in similar quantities and with similar specificities as those of the laboratory strain. The simplest interpretation of this result is that constitutive kinetochore assembly and heterochromatin formation occur autonomously. PMID:24449889

  6. Spontaneously occurring lymphohematopoietic tumors in three young Sprague Dawley rats.

    PubMed

    Yoshizawa, Katsuhiko; Kinoshita, Yuichi; Emoto, Yuko; Tsubura, Airo

    2016-05-01

    To assess the toxicological and pharmacological effects of chemicals, it is important to know what kinds of neoplasms naturally occur in the early life of laboratory animals. In the present study, we identified three spontaneous hematopoietic tumors in three of 52 young female Sprague-Dawley rats used in a pharmacological study. These cases included two rats (Case 1 and 2) from a sesame oil-treated group and one rat (Case 3) from a chemical-treated group in the same single gavage study. Case 1 rapidly lost body weight at 13 weeks of age without any clinical signs and died. Round lymphoid tumor cells were found in the spleen, liver, bone marrow, and pancreas. The tumor cells were immunohistochemically positive for CD3 and PCNA, which is suggestive of malignant T-cell lymphoma. Cases 2 and 3 had rapid body weight loss at 14 and 16 weeks of age, respectively, exhibited severe anemia, hypolocomotion, and decreased body temperature, and were euthanized due to a poor prognosis based on severe clinical signs. Pleomorphic large tumor cells were found in the spleen, liver, bone marrow, lymph nodes, heart, kidneys, lung, pancreas, adrenal glands, pituitary gland, ovaries, Harderian gland, and/or eyes. The tumor cells were immunoreactive for CD34, lysozyme, and PCNA, which is suggestive of myeloid leukemia. These cases might provide useful historical control information for rat toxicity studies. PMID:26830545

  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. 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

  9. Application of the Commission's recommendations to naturally occurring radioactive material.

    PubMed

    Lecomte, J-F

    2015-06-01

    Since publication of the 2007 Recommendations (ICRP Publication 103), the International Commission on Radiological Protection has focused on preparing a series of publications dedicated to different types of existing exposure situations, such as radon exposure, cosmic exposure in aviation, and exposure to naturally occurring radioactive material (NORM). The publication related to NORM will present the main types of corresponding activities, and describe the characteristics of NORM exposure. It will also develop a conceptual framework for the practical application of the Commission's system to NORM exposure. In particular, the publication will explain why NORM activities are generally considered to be existing exposure situations, and when some of them should be managed as planned exposure situations. It will indicate when the workers should be considered as occupationally exposed. It will also provide recommendations regarding application of the three principles of radiological protection. The need to consider the justification of the re-use or recycling of residues carefully will be highlighted. Guidance will be provided for selection of the reference level, and for implementation of the optimisation process through a graded approach including both prevention and mitigation of exposures. Flexibility will be recommended for the application of dose limits, notably when the situation is managed as a planned exposure situation. PMID:25816272

  10. Evaluation of cast creep occurring during simulated clubfoot correction.

    PubMed

    Cohen, Tamara L; Altiok, Haluk; Wang, Mei; McGrady, Linda M; Krzak, Joseph; Graf, Adam; Tarima, Sergey; Smith, Peter A; Harris, Gerald F

    2013-08-01

    The Ponseti method is a widely accepted and highly successful conservative treatment of pediatric clubfoot involving weekly manipulations and cast applications. Qualitative assessments have indicated the potential success of the technique with cast materials other than standard plaster of Paris. However, guidelines for clubfoot correction based on the mechanical response of these materials have yet to be investigated. The current study sought to characterize and compare the ability of three standard cast materials to maintain the Ponseti-corrected foot position by evaluating cast creep response. A dynamic cast testing device, built to model clubfoot correction, was wrapped in plaster of Paris, semi-rigid fiberglass, and rigid fiberglass. Three-dimensional motion responses to two joint stiffnesses were recorded. Rotational creep displacement and linearity of the limb-cast composite were analyzed. Minimal change in position over time was found for all materials. Among cast materials, the rotational creep displacement was significantly different (p < 0.0001). The most creep displacement occurred in the plaster of Paris (2.0°), then the semi-rigid fiberglass (1.0°), and then the rigid fiberglass (0.4°). Torque magnitude did not affect creep displacement response. Analysis of normalized rotation showed quasi-linear viscoelastic behavior. This study provided a mechanical evaluation of cast material performance as used for clubfoot correction. Creep displacement dependence on cast material and insensitivity to torque were discovered. This information may provide a quantitative and mechanical basis for future innovations for clubfoot care. PMID:23636764

  11. 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.

  12. 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

  13. Sequestering Naturally Occurring Liquid Carbon Dioxide in the Deep Ocean

    NASA Astrophysics Data System (ADS)

    Capron, M. E.

    2008-12-01

    Liquid carbon dioxide has been found as shallow as 1,500 meters in seafloor ooze. Did the liquid carbon dioxide originate from volcanic activity? Or did bacteria convert organic matter, which started as atmospheric carbon dioxide, into methane and liquid carbon dioxide? At typical ocean temperatures carbon dioxide coming out of solution below 600 meters will be liquid. Therefore, one likely mechanism for generating liquid carbon dioxide in seafloor ooze is the bacterial decomposition of organic matter. This paper examines quantitative and qualitative bacterial decomposition of aquatic biomass, with an emphasis on assessing and demonstrating feasibility. Calculations suggest natural processes sequestering liquid carbon dioxide in the seafloor can be sustainably increased to decrease atmospheric carbon dioxide concentrations. First, algae growing on the ocean surface absorb carbon dioxide. The algae are then gathered into a submerged container. Naturally occurring bacteria will digest the algae producing methane, liquid carbon dioxide, and ammonium. The ammonium can be recycled as a nutrient for growing more algae. Bacterial decomposition continues in dilute solutions with any biomass. The process does not require any particular biomass. Also, concentrating the biomass by removing water is not essential. The buoyancy provided by water allows relatively inexpensive tension fabric structures to contain the dilute algae and decomposition products. Calculations based on algae growth in open ponds and experience with bacterial decomposition at 1 to 5 bar pressures suggest the economics of the associated macro-algae growing and harvesting can favor increasing ocean species diversity.

  14. Naturally occurring murine norovirus infection in a large research institution.

    PubMed

    Perdue, Kathy A; Green, Kim Y; Copeland, Michelle; Barron, Elyssa; Mandel, Myrna; Faucette, Lawrence J; Williams, Elizabeth M; Sosnovtsev, Stanislav V; Elkins, William R; Ward, Jerrold M

    2007-07-01

    Murine norovirus (MNV) is a recently discovered infectious agent in mice and may be the most common naturally occurring infection of laboratory mice in North America. In 2005, we surveyed the Swiss Webster female sentinel mice in our institute's research facilities. Of the 4 facilities surveyed, 3 had sentinel mice that were positive for MNV antibodies, whereas our largest facility (which only receives mice directly from select vendors or by embryo rederivation directly into the facility) was apparently MNV-free. However, testing of sentinel mice in this large facility 1 y later found that 2% of the animals had developed MNV-specific antibodies. In a recently opened fifth facility, a serologic survey in 2006 identified MNV-antibody-positive Tac:SW sentinel mice that had received bedding from experimental mice on the same rack quadrant. Reverse transcription- polymerase chain reaction analysis of feces from the cages of these mice showed evidence for shedding of MNV. These sentinel mice were used to study the fecal excretion, antibody development, gross lesions upon necropsy, histopathology, and immunohistochemistry of the viral infection. None of the MNV-antibody-positive sentinel mice exhibited clinical signs or gross lesions, but these mice excreted virus in feces and developed antibodies to MNV. Histopathologic lesions consisted only of a few hepatic inflammatory foci in each liver section, some of which were immunoreactive with antibodies to MNV. MNV viral antigens also were present in the mesenteric lymph nodes. PMID:17645294

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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. PMID:26890366

  20. Does immune suppression during stress occur to promote physical performance?

    PubMed

    Martin, Lynn B; Brace, Amber J; Urban, Alexandra; Coon, Courtney A C; Liebl, Andrea L

    2012-12-01

    Two adaptationist hypotheses have been proposed to explain why stress, particularly elevation of stress hormones (i.e. glucocorticoids), tends to suppress immune functions. One is that immune suppression represents efforts to minimize autoimmune responses to self-antigens released as organisms cope with stressors (i.e. the autoimmune-avoidance hypothesis). The other is that immune suppression occurs to promote a shunting of resources to life processes more conducive to survival of the stressor (i.e. the re-allocation hypothesis). Here in wild-caught house sparrows (Passer domesticus), we tested the second hypothesis, asking whether sustained elevation of baseline glucocorticoids, due to captivity, caused a greater rate of decline in immune functions than flight performance. A greater decline in immune functions than flight performance would support the re-allocation hypothesis. As in previous studies, we found that captivity tended to alter baseline corticosterone, suggesting that house sparrows experience captivity as a stressor. Captivity also affected several constitutive and induced innate immune metrics: bacterial (Escherichia coli) killing activity of blood and oxidative burst of leukocytes both changed in a manner consistent with immune disregulation. In contrast, breast muscle size and vertical flight (hovering) duration improved over captivity. Collectively, these changes provide indirect support for the re-allocation hypothesis, although within individuals, changes in immune and physical performance were unrelated. PMID:22933612

  1. Biophysical characterization of naturally occurring titin M10 mutations

    PubMed Central

    Rudloff, Michael W; Woosley, Alec N; Wright, Nathan T

    2015-01-01

    The giant proteins titin and obscurin are important for sarcomeric organization, stretch response, and sarcomerogenesis in myofibrils. The extreme C-terminus of titin (the M10 domain) binds to the N-terminus of obscurin (the Ig1 domain) in the M-band. The high-resolution structure of human M10 has been solved, along with M10 bound to one of its two known molecular targets, the Ig1 domain of obscurin-like. Multiple M10 mutations are linked to limb-girdle muscular dystrophy type 2J (LGMD2J) and tibial muscular dystrophy (TMD). The effect of the M10 mutations on protein structure and function has not been thoroughly characterized. We have engineered all four of the naturally occurring human M10 missense mutants and biophysically characterized them in vitro. Two of the four mutated constructs are severely misfolded, and cannot bind to the obscurin Ig1 domain. One mutation, H66P, is folded at room temperature but unfolds at 37°C, rendering it binding incompetent. The I57N mutation shows no significant structural, dynamic, or binding differences from the wild-type domain. We suggest that this mutation is not directly responsible for muscle wasting disease, but is instead merely a silent mutation found in symptomatic patients. Understanding the biophysical basis of muscle wasting disease can help streamline potential future treatments. PMID:25739468

  2. 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

  3. 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

  4. Global distribution of naturally occurring marine hypoxia on continental margins

    NASA Astrophysics Data System (ADS)

    Helly, John J.; Levin, Lisa A.

    2004-09-01

    Hypoxia in the ocean influences biogeochemical cycling of elements, the distribution of marine species and the economic well being of many coastal countries. Previous delineations of hypoxic environments focus on those in enclosed seas where hypoxia may be exacerbated by anthropogenically induced eutrophication. Permanently hypoxic water masses in the open ocean, referred to as oxygen minimum zones, impinge on a much larger seafloor surface area along continental margins of the eastern Pacific, Indian and western Atlantic Oceans. We provide the first global quantification of naturally hypoxic continental margin floor by determining upper and lower oxygen minimum zone depth boundaries from hydrographic data and computing the area between the isobaths using seafloor topography. This approach reveals that there are over one million km 2 of permanently hypoxic shelf and bathyal sea floor, where dissolved oxygen is <0.5 ml l -1; over half (59%) occurs in the northern Indian Ocean. We also document strong variation in the intensity, vertical position and thickness of the OMZ as a function of latitude in the eastern Pacific Ocean and as a function of longitude in the northern Indian Ocean. Seafloor OMZs are regions of low biodiversity and are inhospitable to most commercially valuable marine resources, but support a fascinating array of protozoan and metazoan adaptations to hypoxic conditions.

  5. 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

  6. Do all programmed cell deaths occur via apoptosis?

    PubMed Central

    Schwartz, L M; Smith, S W; Jones, M E; Osborne, B A

    1993-01-01

    During development, large numbers of cells die by a nonpathological process referred to as programmed cell death. In many tissues, dying cells display similar changes in morphology and chromosomal DNA organization, which has been termed apoptosis. Apoptosis is such a widely documented phenomenon that many authors have assumed all programmed cell deaths occur by this process. Two well-characterized model systems for programmed cell death are (i) the death of T cells during negative selection in the mouse thymus and (ii) the loss of intersegmental muscles of the moth Manduca sexta at the end of metamorphosis. In this report we compare the patterns of cell death displayed by T cells and the intersegmental muscles and find that they differ in terms of cell-surface morphology, nuclear ultrastructure, DNA fragmentation, and polyubiquitin gene expression. Unlike the T cells, which are known to die via apoptosis, we find that the intersegmental muscles display few of the features that characterize apoptosis. These data suggest that more than one cell death mechanism is used during development. Images PMID:8430112

  7. 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.

  8. Functional co-operation between the subunits in heterodimeric platelet-derived growth factor receptor complexes.

    PubMed Central

    Emaduddin, M; Ekman, S; Rönnstrand, L; Heldin, C H

    1999-01-01

    To determine the importance of the phosphorylation capacity of receptor kinase as well as the ability to serve as docking sites for SH2-domain-containing signal transduction molecules, we established pig aortic endothelial cell lines stably expressing kinase-active platelet-derived growth factor (PDGF) alpha-receptors together with kinase-inactive beta-receptors, and vice versa. After stimulation with PDGF-AB, heterodimeric receptor complexes were formed in which the kinase-inactive receptor was phosphorylated by the kinase-active receptor, although less efficiently than in heterodimers of wild-type receptors. The kinase-active receptor was only minimally phosphorylated. Thus the phosphorylation within the receptor dimer occurred in trans between the components. Analyses of the abilities of heterodimeric receptor complexes of one kinase-active and one kinase-inactive receptor to mediate mitogenicity, chemotaxis and activation of mitogen-activated protein kinase revealed less efficient effects than those of heterodimers of wild-type receptors. Importantly, however, the fact that signalling capacities were retained illustrates a functional co-operation between the two receptor molecules in the dimer, where one receptor provides a functional kinase and the other acts as a substrate and provides docking sites for downstream signalling molecules. PMID:10417313

  9. Insulin receptor/IGF-I receptor hybrids are widely distributed in mammalian tissues: quantification of individual receptor species by selective immunoprecipitation and immunoblotting.

    PubMed

    Bailyes, E M; Navé, B T; Soos, M A; Orr, S R; Hayward, A C; Siddle, K

    1997-10-01

    The insulin receptor (IR) and type 1 insulin-like growth factor (IGF-I) receptor (IGFR) are both widely expressed in mammalian tissues, and are known to be capable of heteromeric assembly as insulin/IGF hybrid receptors, in addition to the classically described receptors. By selective immunoadsorption of radioligand/receptor complexes and by immunoblotting we have determined the fraction of insulin receptors and IGF receptors occurring as hybrids in different tissues. Microsomal membranes were isolated from tissue homogenates and solubilized with Triton X-100. Solubilized receptors were incubated with 125I-IGF-I, and radioligand/receptor complexes bound by IR-specific and IGFR-specific monoclonal antibodies were quantified. The fraction of IGF-I binding sites behaving as hybrids (anti-IR-bound/anti-IGFR-bound) was approx. 40% in liver and spleen, 70% in placenta, and 85-90% in skeletal muscle and heart, similar results being obtained in rabbit and human tissues. There was no correlation between the proportion of hybrids and the ratio of 125I-insulin/125I-IGF-I binding in different tissues. The fraction of 125I-insulin bound to hybrids was too low for accurate quantification, because of the relatively low affinity of hybrids for insulin. The fraction of insulin receptors present in hybrids was therefore determined by immunoblotting. Receptors in solubilized human placental microsomal membranes were precipitated with IR-specific or IGFR-specific monoclonal antibodies, and after SDS/PAGE, blots were prepared and probed with IR-specific and IGFR-specific antisera. It was found that 15% of IR and 80% of IGFR were present in hybrids. Consistent with these figures, the overall level of IR was estimated, by blotting with the respective antibodies at concentrations shown to give equal signals with equal amounts of receptor, to be 4-fold greater than IGFR. Overall it was concluded that a significant fraction of both IR and IGFR occurs as hybrids in most mammalian tissues

  10. Dihydropyridine receptor mutations cause hypokalemic periodic paralysis

    SciTech Connect

    Ptacek, L.J.; Leppert, M.F.; Tawil, R.

    1994-09-01

    Hypokalemic periodic paralysis (hypoKPP) is an autosomal dominant skeletal muscle disorder manifested by episodic weakness associated with low serum potassium. Genetic linkage analysis has localized the hypoKPP gene to chromosome 1q31-q32 near a dihydropyridine receptor (DHP) gene. This receptor functions as a voltage-gated calcium channel and is also critical for excitation-contraction coupling in a voltage-sensitive and calcium-independent manner. We have characterized patient-specific DHP receptor mutations in 11 probands of 33 independent hypoKPP kindreds that occur at one of two adjacent nucleotides within the same codon and predict substitution of a highly conserved arginine in the S4 segment of domain 4 with either histidine or glycine. In one kindred, the mutation arose de novo. Taken together, these data establish the DHP receptor as the hypoKPP gene. We are unaware of any other human diseases presently known to result from DHP receptor mutations.

  11. Loss of BAP1 Expression Occurs Frequently in Intrahepatic Cholangiocarcinoma.

    PubMed

    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

    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

  12. Oncogenic mutations in GNAQ occur early in uveal melanoma

    PubMed Central

    Onken, Michael D.; Worley, Lori A.; Long, Meghan D.; Duan, Shenghui; Council, M. Laurin; Bowcock, Anne M.; Harbour, J. William

    2008-01-01

    Purpose Early/initiating oncogenic mutations have been identified for many cancers, but such mutations remain unidentified in uveal melanoma (UM). An extensive search for such mutations was undertaken, focusing on the RAF/MEK/ERK pathway, which is often the target of initiating mutations in other types of cancer. Methods DNA samples from primary UMs were analyzed for mutations in 24 potential oncogenes that affect the RAF/MEK/ERK pathway. For GNAQ, a stimulatory αq G-protein subunit which was recently found to be mutated in uveal melanomas, re-sequencing was expanded to include 67 primary UMs and 22 peripheral blood samples. GNAQ status was analyzed for association with clinical, pathologic, chromosomal, immunohistochemical and transcriptional features. Results Activating mutations at codon 209 were identified in GNAQ in 33/67 (49%) primary UMs, including 2/9 (22%) iris melanomas and 31/58 (54%) posterior UMs. No mutations were found in the other 23 potential oncogenes. GNAQ mutations were not found in normal blood DNA samples. Consistent with GNAQ mutation being an early or initiating event, this mutation was not associated with any clinical, pathologic or molecular features associated with late tumor progression. Conclusions GNAQ mutations occur in about half of UMs, representing the most common known oncogenic mutation in this cancer. The presence of this mutation in tumors at all stages of malignant progression suggests that it is an early event in UM. Mutations in this G-protein provide new insights into UM pathogenesis and could lead to new therapeutic possibilities. PMID:18719078

  13. Naturally occurring allele diversity allows potato cultivation in northern latitudes.

    PubMed

    Kloosterman, Bjorn; Abelenda, José A; Gomez, María del Mar Carretero; Oortwijn, Marian; de Boer, Jan M; Kowitwanich, Krissana; Horvath, Beatrix M; van Eck, Herman J; Smaczniak, Cezary; Prat, Salomé; Visser, Richard G F; Bachem, Christian W B

    2013-03-14

    Potato (Solanum tuberosum L.) originates from the Andes and evolved short-day-dependent tuber formation as a vegetative propagation strategy. Here we describe the identification of a central regulator underlying a major-effect quantitative trait locus for plant maturity and initiation of tuber development. We show that this gene belongs to the family of DOF (DNA-binding with one finger) transcription factors and regulates tuberization and plant life cycle length, by acting as a mediator between the circadian clock and the StSP6A mobile tuberization signal. We also show that natural allelic variants evade post-translational light regulation, allowing cultivation outside the geographical centre of origin of potato. Potato is a member of the Solanaceae family and is one of the world's most important food crops. This annual plant originates from the Andean regions of South America. Potato develops tubers from underground stems called stolons. Its equatorial origin makes potato essentially short-day dependent for tuberization and potato will not make tubers in the long-day conditions of spring and summer in the northern latitudes. When introduced in temperate zones, wild material will form tubers in the course of the autumnal shortening of day-length. Thus, one of the first selected traits in potato leading to a European potato type is likely to have been long-day acclimation for tuberization. Potato breeders can exploit the naturally occurring variation in tuberization onset and life cycle length, allowing varietal breeding for different latitudes, harvest times and markets. PMID:23467094

  14. 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

  15. Does thermal convection occur in mammalian burrows during the night?

    NASA Astrophysics Data System (ADS)

    Ganot, Y.; Weisbrod, N.; Dragila, M. I.; Nachshon, U.

    2010-12-01

    Burrowing is a common habit of mammals in arid zones, yet knowledge of environmental conditions within animal burrows, and especially of the way burrows are ventilated, is scarce. The ventilation rate of a burrow controls air composition within the burrow by driving gas exchange between the lower part of the burrow where the animal typically lives, and the atmosphere. Ventilation can be achieved by the following mechanisms: (1) diffusion; (2) external winds; (3) movement of the inhabitant within the burrow (the 'piston-effect'); and (4) natural thermal convection, a process by which a natural thermal gradient between burrow and atmosphere creates a density gradient which induces air flow. Here we investigate the role of thermal convection in burrow ventilation. For this purpose, artificial burrows (65 cm in depth and 7 cm in diameter) were drilled in loess soil in the Negev Desert of Israel and a network of thermocouples was installed to continuously monitor and record temperature distribution within these burrows. The results show that free convection occurs on a daily basis during the night and early morning. During these times, burrow air temperature was warmer than atmospheric air, and temperature readings pointed to the regular occurrence of convection flow in a thermosyphon pattern. Volume fluxes were calculated based on analytical solution and empirical correlations. For the artificial burrows investigated, an average CO2 volume flux of about 15 liter/hour was calculated during the night when convective conditions prevailed. For comparison, CO2 volume flux by steady-state diffusion alone is 3 orders of magnitude lower.

  16. 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

  17. 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.

  18. [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

  19. The human D2 dopamine receptor synergizes with the A2A adenosine receptor to stimulate adenylyl cyclase in PC12 cells.

    PubMed

    Kudlacek, Oliver; Just, Herwig; Korkhov, Vladimir M; Vartian, Nina; Klinger, Markus; Pankevych, Halyna; Yang, Qiong; Nanoff, Christian; Freissmuth, Michael; Boehm, Stefan

    2003-07-01

    The adenosine A(2A) receptor and the dopamine D(2) receptor are prototypically coupled to G(s) and G(i)/G(o), respectively. In striatal intermediate spiny neurons, these receptors are colocalized in dendritic spines and act as mutual antagonists. This antagonism has been proposed to occur at the level of the receptors or of receptor-G protein coupling. We tested this model in PC12 cells which endogenously express A(2A) receptors. The human D(2) receptor was introduced into PC12 cells by stable transfection. A(2A)-agonist-mediated inhibition of D(2) agonist binding was absent in PC12 cell membranes but present in HEK293 cells transfected as a control. However, in the resulting PC12 cell lines, the action of the D(2) agonist quinpirole depended on the expression level of the D(2) receptor: at low and high receptor levels, the A(2A)-agonist-induced elevation of cAMP was enhanced and inhibited, respectively. Forskolin-stimulated cAMP formation was invariably inhibited by quinpirole. The effects of quinpirole were abolished by pretreatment with pertussis toxin. A(2A)-receptor-mediated cAMP formation was inhibited by other G(i)/G(o)-coupled receptors that were either endogenously present (P(2y12)-like receptor for ADP) or stably expressed after transfection (A(1) adenosine, metabotropic glutamate receptor-7A). Similarly, voltage activated Ca(2+) channels were inhibited by the endogenous P(2Y) receptor and by the heterologously expressed A(1) receptor but not by the D(2) receptor. These data indicate functional segregation of signaling components. Our observations are thus compatible with the proposed model that D(2) and A(2A) receptors are closely associated, but they highlight the fact that this interaction can also support synergism. PMID:12784121

  20. Laryngeal pressure receptors.

    PubMed

    Mathew, O P; Sant'Ambrogio, G; Fisher, J T; Sant'Ambrogio, F B

    1984-07-01

    We studied the response characteristics of laryngeal pressure receptors in anesthetized dogs, breathing through a tracheal cannula, by recording single unit action potentials from the peripheral cut end of the internal branch of the superior laryngeal nerve. The larynx, with the rest of the upper airway, was isolated and cannulated separately for the application of distending and collapsing pressures. We identified receptors responding to either negative or positive pressure and a few responding to both. All these receptors showed a marked dynamic sensitivity and had the characteristics of slowly adapting mechanoreceptors. The majority of pressure receptors were active at zero transmural pressure and the gain of their response to pressure was higher at lower values, suggesting a role for these receptors in eupnea. Reflex alterations in breathing pattern and upper airway muscle activity during upper airway pressure changes, previously reported, are presumably mediated by the receptors described here. Moreover, these receptors may play a role in certain pathological states, such as obstructive sleep apnea, in which the upper airway is transiently subjected to large collapsing pressure. PMID:6484319

  1. 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

  2. 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

  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. 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.

  5. 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

  6. 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

  7. 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

  8. Binding properties of androgen receptors. Evidence for identical receptors in rat testis, epididymis, and prostate.

    PubMed

    Wilson, E M; French, F S

    1976-09-25

    Androgen receptors in crude and partially purified 105,000 X g supernatant fractions from rat testis, epididymis, and prostate were studied in vitro using a charcoal adsorption assay and sucrose gradient centrifugation. Androgen metabolism was eliminated during receptor purification allowing determination of the kinetics of [3H]-androgen-receptor complex formation. In all three tissues, receptors were found to have essentially identical capabilities to bind androgen, with the affinity for [3H] dihydrotestosterone being somewhat higher than for [3H] testosterone. Equilibrium dissociation constants for [3H] dihydrotestosterone and [3H] testosterone (KD = 2 to 5 X 10(-10) M) were estimated from independently determined rates of association (ka congruent to 6 X 10(7) M-1 h-1 for [3H] dihydrotestosterone and 2 X 10(8) M-1 h-1 for [3H] testosterone) and dissociation (t 1/2 congruent to 40 hr for [3H] dihydrotestosterone and 15 h [3H] testosterone). Evaluation of the effect of temperature on androgen receptor binding of [3H]testosterone allowed estimation of several thermodynamic parameters, including activation energies of association and dissociation (delta H congruent to 14 kcal/mol), the apparent free energy (delta G congruent to -12 kcal/mol), enthalpy (delta H congruent to -2.5 kcal/mol), and entropy (delta S congruent to 35 cal col-1 K-1). Optimum receptor binding occurred at a pH of 8. Receptor stability was greatly enhanced when bound with androgen. Receptor specificity for testosterone and dihydrotestosterone was demonstrated by competitive binding assays. The potent synthetic androgen, 7 alpha, 17 alpha-dimethyl-19-nortestosterone, inhibited binding of [3H] testosterone or [3H] dihydrotesterone nearly as well as testosterone and dihydrotestosterone while larger amounts of 5 alpha-androstane-3alpha, 17 beta-diol and nonandrogenic steroids were required. Sedimentation coefficients of androgen receptors in all unfractionated supernatants were 4 and 5 to 8 S

  9. 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

  10. 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

  11. Assembly of naturally occurring glycosides, evolved tactics, and glycosylation methods.

    PubMed

    Yu, Biao; Sun, Jiansong; Yang, Xiaoyu

    2012-08-21

    Glycosylation of proteins and lipids is critical to many life processes. Secondary metabolites (or natural products), such as flavonoids, steroids, triterpenes, and antibiotics, are also frequently modified with saccharides. The resulting glycosides include diverse structures and functions, and some of them have pharmacological significance. The saccharide portions of the glycosides often have specific structural characteristics that depend on the aglycones. These molecules also form heterogeneous "glycoform" mixtures where molecules have similar glycosidic linkages but the saccharides vary in the length and type of monosaccharide unit. Thus, it is difficult to purify homogeneous glycosides in appreciable amounts from natural sources. Chemical synthesis provides a feasible access to the homogeneous glycosides and their congeners. Synthesis of a glycoside involves the synthesis of the aglycone, the saccharide, the connection of these two parts, and the overall manipulation of protecting groups. However, most synthetic efforts to date have focused on the aglycones, treating the attachment of saccharides onto the aglycones as a dispensable topic. The synthesis of the aglycone and the synthesis of the saccharide belong to two independent categories of chemistry, and different types of the aglycones and saccharides pose as specific synthetic subjects in their own disciplines. The only reaction that integrates the broad chemistry of glycoside synthesis is the glycosidic bond formation between the saccharide and the aglycone. Focusing on this glycosylation reaction in this Account, we string together our experience with the synthesis of the naturally occurring glycosides. We briefly describe the synthesis of 18 glycosides, including glycolipids, phenolic glycosides, steroid glycosides, and triterpene glycosides. Each molecule represents a prototypical structure of a family of the natural glycosides with interesting biological activities, and we emphasize the general

  12. 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

  13. 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.

  14. Spontaneous hypertension occurs with adipose tissue dysfunction in perilipin-1 null mice.

    PubMed

    Zou, Liangqiang; Wang, Weiyi; Liu, Shangxin; Zhao, Xiaojing; Lyv, Ying; Du, Congkuo; Su, Xueying; Geng, Bin; Xu, Guoheng

    2016-02-01

    Perilipin-1 (Plin1) coats lipid droplets exclusively in adipocytes and regulates two principle functions of adipose tissue, triglyceride storage and hydrolysis, which are disrupted upon Plin1 deficiency. In the present study, we investigated the alterations in systemic metabolites and hormones, vascular function and adipose function in spontaneous hypertensive mice lacking perilipin-1 (Plin1-/-). Plin1-/- mice developed spontaneous hypertension without obvious alterations in systemic metabolites and hormones. Plin1 expressed only in adipose cells but not in vascular cells, so its ablation would have no direct effect in situ on blood vessels. Instead, Plin1-/- mice showed dysfunctions of perivascular adipose tissue (PVAT), a fat depot that anatomically surrounds systemic arteries and has an anticontractile effect. In Plin1-/- mice, aortic and mesenteric PVAT were reduced in mass and adipocyte derived relaxing factor secretion, but increased in basal lipolysis, angiotensin II secretion, macrophage infiltration and oxidative stress. Such multiple culprits impaired the anticontractile effect of PVAT to promote vasoconstriction of aortic and mesenteric arteries of Plin1-/- mice. Furthermore, arterial vessels of Plin1-/- mice showed increasing angiotensin II receptor type 1, monocyte chemotactic protein-1 and interlukin-6 expression, structural damage of endothelial and smooth muscle cells, along with impaired endothelium-dependent relaxation. Hypertension in Plin1-/- mice might occur as a deleterious consequence of PVAT dysfunction. This finding provides the direct evidence that links dysfunctional PVAT to vascular dysfunction and hypertension, particularly in pathophysiological states. This hypertensive mouse model might mimic and explain the hypertension occurring in patients with adipose tissue dysfunction, particularly with Plin1 mutations. PMID:26521150

  15. 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

  16. 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

  17. Progesterone receptors in human breast cancer. Stoichiometric translocation and nuclear receptor processing.

    PubMed

    Mockus, M B; Horwitz, K B

    1983-04-25

    In a subline of T47D human breast cancer cells, progesterone receptors (PR) are synthesized at very high levels, but their synthesis is not estrogen-dependent. Despite the unusual control of synthesis, the physicochemical properties of PR are normal. These are, therefore, ideal cells to study PR regulation by progesterone, free of estrogen effects. In this paper, we show that nuclear translocation of PR is stoichiometric, and that an unusual and very rapid nuclear turnover, or processing step, characterizes receptor-DNA interactions. In intact T47D cells, PR are translocated to the nucleus only by progestins; 70-90% of cytoplasmic receptors are depleted at 37 degrees C within 5 min of progestin addition. After PR are translocated by 0.1 muM progesterone, they can be quantitatively recovered from nuclei only in the first 5 min; thereafter, a rapid nuclear processing step results in loss of 50-80% of the newly translocated sites. Rapid processing may be inherent to PR; it also occurs in PR of MCF-7 cells. The extent of receptor translocation and of nuclear receptor processing is dependent on the progesterone concentration and on the treatment time, and can be masked by endogenous hormones. Proteolytic enzyme inhibitors (leupeptin, antipain) do not prevent nuclear PR loss. G-C specific DNA intercalators that prevent nuclear estrogen receptor processing (actinomycin D, chromomycin A3) also fail to prevent PR loss, but some A-T specific DNA-binding dyes (chloroquine, primaquine, quinacrine) protect 50-75% of nuclear PR. We conclude that translocated nuclear PR can be quantitatively measured only at early time points because the nuclear receptors are rapidly processed. Furthermore, the processing step may involve an interaction of receptors with DNA since it can be partially blocked by DNA-binding agents. PMID:6833276

  18. Infrared monitoring of hydrothermal echanges occurring in a fracture

    NASA Astrophysics Data System (ADS)

    Neuville, Amélie; Flekkøy, Eirik; Galland, Olivier; Gundersen, Olav; Jørgen Måløy, Knut

    2014-05-01

    We aim to characterize the heat exchange that occurs when water flows through a fracture at a different temperature from that of the surrounding rock. This happens during many man-made or natural processes. For instance, injection of water in the context of geothermal power plants or sudden mechanical movements (e.g. rockfalls, landslides, earthquakes) that transport water. It is presently challenging to estimate the heat transfer and temperature inside a fractured medium where water is flowing, despite various numerical models which have been proposed [Neuville et al, 2010, 2013; Kolditz et Clauser, 1998; Heuer, 1991]. The difficulties arise from the complexity of the fracture network, the fracture topography, as well as complex hydraulic flow (e.g. recirculation) and heat exchanges. As a consequence, various hypotheses were made in the models. More experimental data are required in order to calibrate these models, validate or refute the hypotheses. Our work aims to provide temperature data at the fracture scale, in an experiment where the pressure gradient an fracture topography are controlled, with slow hydraulic flow. This required to develop a setup from scratch. An infrared camera and thermistors are used to monitor the temperature in space and time. Water is injected through a partly natural rough fracture with impermeable walls. The bottom part of the fracture is a larvikite stone with a rough surface (presumably this surface was obtained from mode I fracturing), and the top part is a layer which is transparent in the infrared range. As a consequence the infrared camera is expected to measure the temperature at the interface between this transparent layer and the water. The topography of the surface of the rock was reconstituted using a photogrammetry software [MicMac, IGN], and compared to measurements made with a mechanical profiler. Using this geometry we carefully localize the temperature observations (infrared camera and thermistors) and correlate the

  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. Mammalian sweet taste receptors.

    PubMed

    Nelson, G; Hoon, M A; Chandrashekar, J; Zhang, Y; Ryba, N J; Zuker, C S

    2001-08-10

    The sense of taste provides animals with valuable information about the quality and nutritional value of food. Previously, we identified a large family of mammalian taste receptors involved in bitter taste perception (the T2Rs). We now report the characterization of mammalian sweet taste receptors. First, transgenic rescue experiments prove that the Sac locus encodes T1R3, a member of the T1R family of candidate taste receptors. Second, using a heterologous expression system, we demonstrate that T1R2 and T1R3 combine to function as a sweet receptor, recognizing sweet-tasting molecules as diverse as sucrose, saccharin, dulcin, and acesulfame-K. Finally, we present a detailed analysis of the patterns of expression of T1Rs and T2Rs, thus providing a view of the representation of sweet and bitter taste at the periphery. PMID:11509186

  2. Galanin Receptors and Ligands

    PubMed Central

    Webling, Kristin E. B.; Runesson, Johan; Bartfai, Tamas; Langel, Ülo

    2012-01-01

    The neuropeptide galanin was first discovered 30 years ago. Today, the galanin family consists of galanin, galanin-like peptide (GALP), galanin-message associated peptide (GMAP), and alarin and this family has been shown to be involved in a wide variety of biological and pathological functions. The effect is mediated through three GPCR subtypes, GalR1-3. The limited number of specific ligands to the galanin receptor subtypes has hindered the understanding of the individual effects of each receptor subtype. This review aims to summarize the current data of the importance of the galanin receptor subtypes and receptor subtype specific agonists and antagonists and their involvement in different biological and pathological functions. PMID:23233848

  3. CHARACTERIZATION OF THE AH RECEPTOR

    EPA Science Inventory

    The rat liver cytosolic receptor protein containing the Ah-receptor protein was purified and studied using a photochemical assembly of 2,3,7,8-TCDD. The unbound receptor protein rapidly lost its capacity to bind 2,3,7,8-TCDD; however, the 2,3,7,8-TCDD bound Ah receptor did not re...

  4. Positive selection of natural poly-reactive B cells in the periphery occurs independent of heavy chain allelic inclusion.

    PubMed

    Xing, Ying; Ji, Qiuhe; Lin, Ying; Fu, Meng; Gao, Jixin; Zhang, Ping; Hu, Xingbin; Feng, Lei; Liu, Yufeng; Han, Hua; Li, Wei

    2015-01-01

    Natural autoreactive B cells are important mediators of autoimmune diseases. Receptor editing is known to play an important role in both central and peripheral B cell tolerance. However, the role of allelic inclusion in the development of natural autoreactive B cells is not clear. Previously, we generated μ chain (TgV(H)3B4I) and μ/κ chains (TgV(H/L)3B4) transgenic mice using transgene derived from the 3B4 hybridoma, which produce poly-reactive natural autoantibodies. In this study, we demonstrate that a considerable population of B cells edited their B cells receptors (BCRs) via light chain or heavy chain allelic inclusion during their development in TgV(H)3B4I mice. Additionally, allelic inclusion occurred more frequently in the periphery and promoted the differentiation of B cells into marginal zone or B-1a cells in TgV(H)3B4I mice. B cells from TgV(H/L)3B4 mice expressing the intact transgenic 3B4 BCR without receptor editing secreted poly-reactive 3B4 antibody. Interestingly, however, B cell that underwent allelic inclusion in TgV(H)3B4I mice also produced poly-reactive autoantibodies in vivo and in vitro. Our findings suggest that receptor editing plays a minor role in the positive selection of B cells expressing natural poly-reactive BCRs, which can be positively selected through heavy chain allelic inclusion to retain their poly-reactivity in the periphery. PMID:25993514

  5. Chemokine Receptor Oligomerization and Allostery

    PubMed Central

    Stephens, Bryan; Handel, Tracy M.

    2014-01-01

    Oligomerization of chemokine receptors has been reported to influence many aspects of receptor function through allosteric communication between receptor protomers. Allosteric interactions within chemokine receptor hetero-oligomers have been shown to cause negative cooperativity in the binding of chemokines and to inhibit receptor activation in the case of some receptor pairs. Other receptor pairs can cause enhanced signaling and even activate entirely new, hetero-oligomer-specific signaling complexes and responses downstream of receptor activation. Many mechanisms contribute to these effects including direct allosteric coupling between the receptors, G protein mediated allostery, G protein stealing, ligand sequestration and recruitment of new intracellular proteins by exposing unique binding interfaces on the oligomerized receptors. These effects present both challenges as well as exciting opportunities for drug discovery. One of the most difficult challenges will involve determining if and when hetero-oligomers versus homo-oligomers are involved in specific disease states. PMID:23415099

  6. 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

  7. 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

  8. Estradiol receptor: phosphorylation on tyrosine in uterus and interaction with anti-phosphotyrosine antibody.

    PubMed Central

    Migliaccio, A; Rotondi, A; Auricchio, F

    1986-01-01

    Estradiol receptor from rat uteri incubated with [32P] orthophosphate has been purified by diethylstilbestrol--Sepharose followed by heparin--Sepharose chromatography. The purified receptor, analyzed by centrifugation through sucrose gradients after incubation with monoclonal antibodies against purified estradiol receptor, appears to be labeled with 32P. The receptor preparation has been further purified by immunoaffinity chromatography and submitted to SDS--poly-acrylamide gel electrophoresis. A heavily 32P-labeled 68 kd protein and a very lightly 32P-labeled 48 kd protein, probably a proteolytic product of the 68 kd protein, were detected. Phosphoamino acid analysis of the receptor eluted from the immunoaffinity column shows that its 32P-labeling occurs exclusively on tyrosine. This is the first report on phosphorylation on tyrosine of a steroid receptor in tissue. It is consistent with our previous finding that a uterus estradiol receptor-kinase, which confers hormone binding ability to the estradiol receptor, in vitro phosphorylates this receptor exclusively on tyrosine. Calf uterus receptor binds with high specificity and affinity to monoclonal anti-phosphotyrosine antibodies covalently bound to Sepharose (Kd = 0.28 nM). Dephosphorylation of the receptor by nuclei containing the calf uterus nuclear phosphatase abolishes the interaction with antibodies. These results suggest that also in calf uterus, estradiol receptor is phosphorylated on tyrosine. Anti-phosphotyrosine antibodies bound to Sepharose have been used to partially purify the estradiol receptor from calf uterus. Images Fig. 2. Fig. 3. PMID:2431901

  9. 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

  10. Melatonin receptors and their regulation: biochemical and structural mechanisms.

    PubMed

    Witt-Enderby, Paula A; Bennett, Jennifer; Jarzynka, Michael J; Firestine, Steven; Melan, Melissa A

    2003-04-01

    There is growing evidence demonstrating the complexity of melatonin's role in modulating a diverse number of physiological processes. This complexity could be attributed to the fact that melatonin receptors belong to two distinct classes of proteins, that is, the G-protein coupled receptor superfamily (MT(1), MT(2)) and the quinone reductase enzyme family (MT(3)) which makes them unique at the molecular level. Also, within the G-protein coupled receptor family of proteins, the MT(1) and MT(2) receptors can couple to multiple and distinct signal transduction cascades whose activation can lead to unique cellular responses. Also, throughout the 24-hour cycle, the receptors' sensitivity to specific cues fluctuates and this sensitivity can be modulated in a homologous fashion, that is, by melatonin itself, and in a heterologous manner, that is, by other cues including the photoperiod or estrogen. This sensitivity of response may reflect changes in melatonin receptor density that also occurs throughout the 24-hour light/dark cycle but out of phase with circulating melatonin levels. The mechanisms that underlie the changes in melatonin receptor density and function are still not well-understood, but data is beginning to show that transcriptional events and G-protein uncoupling may be involved. Even though this area of research is still in its infancy, great strides are being made everyday in elucidating the mechanisms that underlie melatonin receptor function and regulation. The focus of this review is to highlight some of these discoveries in an attempt to reveal the uniqueness of the melatonin receptor family while at the same time provide thought-provoking ideas to further advance this area of research. Thus, a brief overview of each of the mammalian melatonin receptor subtypes and the signal transduction cascades to which they couple will be discussed with a greater emphasis placed on the mechanisms underlying their regulation and the domains within the receptors

  11. Attenuation of D-1 antagonist-induced D-1 receptor upregulation by conccomitant D-2 receptor blockade

    SciTech Connect

    Parashos, S.A.; Barone, P.; Tucci, I.; Chase, T.N.

    1987-11-16

    The effect of chronic selective D-1 and/or D-2 dopamine receptor blockade on regional D-1 receptor binding was studied in rat brain following chronic treatment with the specific D-1 antagonist SCH 23390 and/or the predominantly D-2 antagonist haloperidol. D-1 receptor density and affinity were evaluated by quantitative autoradiography using /sup 125/I-SCH 23982. Chronic SCH 23390 treatment increased D-1 receptor density by 30 to 40% in the striatum, accumbens and tuberculum olfactorium; receptor affinity remained unchanged. Haloperidol had no effect on D-1 receptor Bmax or Kd values, although, when administered with SCH 23390, reduced the D-1 receptor upregulation induced by the D-1 antagonist in striatum and tuberculum olfactorium, but not in nucleus accumbens, These results may be attributable to D-1/D-2 dopamine receptor interactions occurring in the striatum and tuberculum olfactorium and may have implications for the prevention and treatment of drug-induced extrapyramidal disorders. 34 references, 1 figure, 2 tables.

  12. 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.

  13. Regulation of plasminogen receptors.

    PubMed

    Herren, Thomas; Swaisgood, Carmen; Plow, Edward F

    2003-01-01

    Many eukaryotic and prokaryotic cells bind plasminogen in a specific and saturable manner. When plasminogen is bound to cell-surface proteins with C-terminal lysines via its lysine binding sites, its activation to plasmin is accelerated, and cell-bound plasmin is protected from inactivation by natural inhibitors. Plasmin mediates direct or indirect degradation of the extracellular matrix, and bound plasmin is used by cells to facilitate migration through extracellular matrices. Since cell migration and tissue remodelling are the underpinnings of many physiological and pathological responses, the modulation of plasminogen receptors may serve as a primary regulatory mechanism for control of many cellular responses. Specific examples of cell types on which plasminogen receptors undergo modulation include: fibroblasts, where modulation may contribute to cartilage and bone destruction in rheumatoid arthritis; leukemic cells, where enhanced plasminogen binding may contribute to the heightened fibrinolytic state in the patients; other tumor cells, where up-regulation may support invasion and metastasis; bacteria, where enhanced plasminogen binding may facilitate tissue destruction and invasion; platelets, where up-regulation of plasminogen binding may play a role in regulating clot lysis; and adipocytes, where the modulation of plasminogen receptor expression may regulate cell differentiation and fat accumulation. Two pathways for modulation of plasminogen receptors have been characterized: A protease-dependent pathway can either up-regulate or down-regulate plasminogen binding to cells by changing the availability of plasminogen-binding proteins with C-terminal lysines. New receptors may be generated by trypsin-like proteases, including plasmin, which create new C-terminal lysines; other enzymes may expose existing membrane proteins by altering the cell surface; or receptor function may be lost by removal of C-terminal lysines. The basic carboxypeptidases of blood

  14. 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

  15. 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

  16. Spontaneous openings of the acetylcholine receptor channel.

    PubMed Central

    Jackson, M B

    1984-01-01

    Patch clamp recordings from embryonic mouse muscle cells in culture revealed spontaneous openings of the acetylcholine receptor channel in the absence of exogenously applied cholinergic agent. The conductance of the spontaneous channel currents was, within experimental error, identical with the conductance of suberyldicholine-activated channel currents. The comparison of channel conductance was made with sodium and with cesium, each at two concentrations, with the same result. Treatment of the cells with alpha-bungarotoxin blocked the spontaneous channel currents. To determine whether the spontaneous openings were caused by an endogenous agent with cholinergic activity a reactive disulfide bond near the receptor binding site was reduced with dithiothreitol and alkylated with N-ethylmaleimide. This chemical modification reduced the effectiveness with which suberyldicholine and curare activated channel currents but did not reduce the frequency of spontaneous openings. These experiments indicate that the acetylcholine receptor briefly and infrequently fluctuates into an active state in the absence of agonist. Agonist activation of the receptor presumably accelerates this spontaneously occurring process. PMID:6328531

  17. ER to synapse trafficking of NMDA receptors.

    PubMed

    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

  18. The receptor preference of influenza viruses

    PubMed Central

    Meng, Bo; Marriott, Anthony C.; Dimmock, Nigel J.

    2010-01-01

    Please cite this paper as: Meng et al. (2010) The receptor preference of influenza viruses. Influenza and Other Respiratory Viruses 4(3), 147–153. Objectives  The cell surface receptor used by an influenza virus to infect that cell is an N‐acetyl neuraminic acid (NANA) residue terminally linked by an alpha2,3 or alpha2,6 bond to a carbohydrate moiety of a glycoprotein or glycolipid. Our aim was to determine a quick and technically simple method to determine cell receptor usage by whole influenza A virus particles. Methods  We employed surface plasmon resonance to detect the binding of viruses to fetuin, a naturally occurring glycoprotein that has both alpha2,3‐ and alpha2,6‐linked NANA, and free 3′‐sialyllactose or 6′‐sialyllactose to compete virus binding. All virus stocks were produced in embryonated chicken’s eggs. Results  The influenza viruses tested bound preferentially to NANAalpha2,3Gal or to NANAalpha2,6Gal, or showed no preference. Two PR8 viruses had different binding preferences. Binding preferences of viruses correlated well with their known biological properties. Conclusions  Our data suggest that it is not easy to predict receptor usage by influenza viruses. However, direct experimental determination as described here can inform experiments concerned with viral pathogenesis, biology and structure. In principle, the methodology can be used for any virus that binds to a terminal NANA residue. PMID:20409211

  19. Semisynthetic Neoclerodanes as Kappa Opioid Receptor Probes

    PubMed Central

    Lovell, Kimberly M.; Vasiljevik, Tamara; Araya, Juan J.; Lozama, Anthony; Prevatt-Smith, Katherine M.; Day, Victor W.; Dersch, Christina M.; Rothman, Richard B.; Butelman, Eduardo R.; Kreek, Mary Jeanne; Prisinzano, Thomas E.

    2012-01-01

    Modification of the furan ring of salvinorin A (1), the main active component of Salvia divinorum, has resulted in novel neoclerodane diterpenes with opioid receptor affinity and activity. Conversion of the furan ring to an aldehyde at the C-12 position (5) has allowed for the synthesis of analogues with new carbon-carbon bonds at that position. Previous methods for forming these bonds, such as Grignard and Stille conditions, have met with limited success. We report a palladium catalyzed Liebeskind-Srogl cross-coupling reaction of a thioester and a boronic acid that occurs at neutral pH and ambient temperature to produce ketone analogs at C-12. To the best of our knowledge, this is the first reported usage of the Liebeskind-Srogl reaction to diversify a natural product scaffold. We also describe a one-step protocol for the conversion of 1 to 12-epi-1 (3) through microwave irradiation. Previously, this synthetically challenging process has required multiple steps. Additionally, we report in this study that alkene 9 and aromatic analogues 12, 19, 23, 25, and 26 were discovered to retain affinity and selectivity at kappa opioid receptors (KOP). Finally, we report that the furan-2-yl analog of 1 (31) has similar affinity to 1. Collectively, these findings suggest that different aromatic groups appended directly to the decalin core may be well tolerated by KOP receptors, and may generate further ligands with affinity and activity at KOP receptors. PMID:22464684

  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. Ionotropic crustacean olfactory receptors.

    PubMed

    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

  2. Insulin receptor-like ectodomain genes and splice variants are found in both arthropods and human brain cDNA

    PubMed Central

    VÄSTERMARK, Åke; RASK-ANDERSEN, Mathias; SAWANT, Rahul S.; REITER, Jill L.; SCHIÖTH, Helgi B.; WILLIAMS, Michael J.

    2016-01-01

    Truncated receptor ectodomains have been described for several classes of cell surface receptors, including those that bind to growth factors, cytokines, immunoglobulins, and adhesion molecules. Soluble receptor isoforms are typically generated by proteolytic cleavage of the cell surface receptor or by alternative splicing of RNA transcripts arising from the same gene encoding the full-length receptor. Both the epidermal growth factor receptor (EGFR) and the insulin receptor (INSR) families produce soluble receptor splice variants in vertebrates and truncated forms of insulin receptor-like sequences have previously been described in Drosophila. The EGFR and INSR ectodomains share significant sequence homology with each other suggestive of a common evolutionary origin. We discovered novel truncated insulin receptor-like variants in several arthropod species. We performed a phylogenetic analysis of the conserved extracellular receptor L1 and L2 subdomains in invertebrate species. While the segregation of insulin receptor-like L1 and L2 domains indicated that an internal domain duplication had occurred only once, the generation of truncated insulin receptor-like sequences has occurred multiple times. The significance of this work is the previously unknown and widespread occurrence of truncated isoforms in arthropods, signifying that these isoforms play an important functional role, potentially related to such isoforms in mammals. PMID:27375681

  3. 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

  4. Endogenous retinoid X receptors can function as hormone receptors in pituitary cells.

    PubMed Central

    Davis, K D; Berrodin, T J; Stelmach, J E; Winkler, J D; Lazar, M A

    1994-01-01

    Retinoids regulate gene transcription by interacting with both retinoic acid (RA) receptors (RARs) and retinoid X receptors (RXRs). Since unliganded RXRs can act as heterodimerization partners for RARs and other nuclear hormone receptors, it is unclear whether ligand binding by RXRs actually regulates the expression of naturally occurring genes. To address this issue, we synthesized the RXR-selective retinoid SR11237 and confirmed its specificity in transient transfection and proteolytic susceptibility assays before using it to assess the contribution of ligand-activated RXRs to retinoid action. Unlike RAR ligands, SR11237 did not increase endogenous RAR beta mRNA levels in F9 embryonal carcinoma cells, even though it activated transcription of an RXR-responsive reporter gene in these cells. Thus, it is likely that RARs mediate the induction of RAR beta gene expression by RA. In contrast, the RXR-specific ligand induced rat growth hormone mRNA in GH3 pituitary cells, indicating that the effects of RA on growth hormone gene expression at least in part involve ligand binding to endogenous RXRs in vivo. Our results indicate that in addition to serving as cofactors for other nuclear hormone receptors, endogenous RXRs can function as ligand-dependent regulators of gene expression, i.e., classical nuclear hormone receptors. Images PMID:7935425

  5. 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

  6. 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

  7. Trafficking of Kainate Receptors

    PubMed Central

    Pahl, Steffen; Tapken, Daniel; Haering, Simon C.; Hollmann, Michael

    2014-01-01

    Ionotropic glutamate receptors (iGluRs) mediate the vast majority of excitatory neurotransmission in the central nervous system of vertebrates. In the protein family of iGluRs, kainate receptors (KARs) comprise the probably least well understood receptor class. Although KARs act as key players in the regulation of synaptic network activity, many properties and functions of these proteins remain elusive until now. Especially the precise pre-, extra-, and postsynaptic localization of KARs plays a critical role for neuronal function, as an unbalanced localization of KARs would ultimately lead to dysregulated neuronal excitability. Recently, important advances in the understanding of the regulation of surface expression, function, and agonist-dependent endocytosis of KARs have been achieved. Post-translational modifications like PKC-mediated phosphorylation and SUMOylation have been reported to critically influence surface expression and endocytosis, while newly discovered auxiliary proteins were shown to shape the functional properties of KARs. PMID:25141211

  8. Selective orexin receptor antagonists.

    PubMed

    Lebold, Terry P; Bonaventure, Pascal; Shireman, Brock T

    2013-09-01

    The orexin, or hypocretin, neuropeptides (orexin-A and orexin-B) are produced on neurons in the hypothalamus which project to key areas of the brain that control sleep-wake states, modulation of food intake, panic, anxiety, emotion, reward and addictive behaviors. These neuropeptides exert their effects on a pair of G-protein coupled receptors termed the orexin-1 (OX1) and orexin-2 (OX2) receptors. Emerging biology suggests the involvement of these receptors in psychiatric disorders as they are thought to play a key role in the regulation of multiple systems. This review is intended to highlight key selective OX1 or OX2 small-molecule antagonists. PMID:23891187

  9. 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

  10. Cutaneous temperature receptors.

    PubMed

    Spray, D C

    1986-01-01

    Specific thermoreceptors comprise an electrophysiologically distinct class of cutaneous receptors with a morphological substrate (free nerve endings) and plausible transduction mechanism (electrogenic Na pump with or without auxiliary temperature-dependent processes). Because responses to thermal and mechanical stimuli converge along the neural pathway, we have difficulty explaining the purity of cold and warm sensations; participation of dual-modality receptors in sensory discrimination cannot be ruled out. The field is now at a point where a leap in understanding would be achieved by intracellular recordings from the sensory receptor (for which patch clamp studies on isolated neuronal elements may provide the necessary technology) and from continued analysis of what information is lost and what retained in passage from one synapse to the next along the thermal pathway. PMID:3085583

  11. Neuropharmacology of dopamine receptors:

    PubMed Central

    Tarazi, Frank I.

    2001-01-01

    There has been an extraordinary recent accumulation of information concerning the neurobiology and neuropharmacology of dopamine (DA) receptors in the mammalian central nervous system. Many new DA molecular entities have been cloned, their gene, peptide sequences and structures have been identified, their anatomical distributions in the mammalian brain described, and their pharmacology characterized. Progress has been made toward developing selective ligands and drug-candidates for different DA receptors. The new discoveries have greatly stimulated preclinical and clinical studies to explore the neuropharmacology of DA receptors and their implications in the neuropathophysiology of different neuropsychiatric diseases including schizophrenia, Parkinson’s disease and attention-deficit hyperactivity disorder. Accordingly, it seems timely to review the salient aspects of this specialized area of preclinical neuropharmacology and its relevance to clinical neuropsychiatry. PMID:24019715

  12. 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

  13. Mutational analysis of hsp90 binding to the progesterone receptor.

    PubMed

    Sullivan, W P; Toft, D O

    1993-09-25

    The 90-kDa heat shock protein, hsp90, is known to associate with steroid receptors that are in the inactive state. While the biochemical function of hsp90 is unclear, this association is believed to be significant because dissociation of hsp90 occurs when receptors are activated by hormone. Complexes between hsp90 and the progesterone receptor can be formed in vitro in rabbit reticulocyte lysate. This has been shown to be an ATP-dependent process, and dissociation of the complex occurs when progesterone is added to the system. We now show that hsp90 synthesized by in vitro translation in reticulocyte lysate can form complexes with progesterone receptor that are sensitive to hormone. This system was used to analyze several mutant forms of hsp90. A series of NH2-terminal deletions showed that amino acids 1-380 can be removed from hsp90 without substantial loss of receptor binding activity. However, several deletions in the COOH-terminal half of hsp90 resulted in a partial or complete loss of this activity. Two regions, amino acids 381-441 and 601-677, appear to be particularly important for receptor binding. These studies describe a convenient and reliable method for the initial screening of hsp90 mutants, and they provide important clues to the identification of domains on hsp90 that interact with other proteins. PMID:8376394

  14. Estrogen receptor scintigraphy.

    PubMed

    Scheidhauer, K; Scharl, A; Schicha, H

    1998-03-01

    Radio-labeled estrogen receptor ligands are tracers that can be used for functional receptor diagnosis. Their specificity towards receptors, together with the fact that only 50-70% of mammary carcinomas are receptor positive, renders them unsuitable for detection of primary tumors or metastases, and this means that estrogen receptor scintigraphy can be used neither for tumor screening nor for staging. However, both 18F-labeled and 123I-labeled estradiol derivatives are suitable for in vivo imaging of estrogen receptors. Their high specificity, established in animal experiments and in vitro studies has been reproduced in in vivo applications in humans. Tracers with positron radiation emitters are, however, hardly suitable for broad application owing to the short half-life of 18F, which would mean that users would need to be situated close to a cyclotron and a correspondingly equipped radiochemical laboratory. The number of available PET scanners, on the other hand, has increased over the last few years, especially in Germany, so that this, at least, does not present a limiting factor. All the same, 123I-labeled estradiol derivatives will find more widespread application, since the number of gamma-cameras incorporating modern multi-head systems is several times greater. The results of studies with 123I-E2-scintigraphy published to date are very promising, even given the initial technical problems mentioned above. As a method of examination, it could be optimised by using improved tracers with a higher tumor contrast and less disturbance from overlapping in diagnostically relevant locations, for instance, by selecting tracers with higher activities whose excretion is more renal than hepatobiliary. The use of modern multi-head camera systems can also be expected to improve the photon yield. PMID:9646642

  15. 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...

  16. Protective effect of naturally occurring anti-HER2 autoantibodies on breast cancer.

    PubMed

    Tabuchi, Yukiko; Shimoda, Masafumi; Kagara, Naofumi; Naoi, Yasuto; Tanei, Tomonori; Shimomura, Atsushi; Shimazu, Kenzo; Kim, Seung Jin; Noguchi, Shinzaburo

    2016-05-01

    Anti-HER2-autoantibodies (HER2-AAbs) are found in breast cancer patients as well as healthy individuals. However, the clinical relevance of the antibodies is unknown. We established an enzyme-linked immunosorbent assay with high sensitivity and quantified serum HER2-AAbs in 100 healthy women, 100 untreated patients with ductal carcinoma in situ (DCIS), and 500 untreated patients with invasive breast carcinoma (IBC). The associations between the levels of HER2-AAbs and breast cancer risk, and recurrence-free survival, were examined. High levels of HER2-AAbs were significantly associated with a reduced risk of DCIS (odds ratio [OR] 0.19, P = 4.6 × 10(-7)) or IBC (OR 0.31, P = 3.7 × 10(-7)). Subgroup analysis of IBC revealed a stronger association of HER2-AAbs with a reduced risk of the hormone receptor (HR)(-)/HER2(+) subtype (OR 0.12) than the other subtypes (HR(+)/HER2(-) [OR = 0.32], HR(+)/HER2(+) [OR 0.38], and HR(-)/HER2(-) [OR 0.29]). When we set the cutoff of HER2-AAbs at 20 ng/mL, recurrence-free survival of HER2-AAb-positive patients (N = 74) was significantly better than that of HER2-AAb-negative patients (N = 426) (P = 0.015). Univariate and multivariate analyses demonstrated that HER2-AAbs, as well as histological grade, were independently and significantly (P = 0.0065 and 0.049, respectively) associated with recurrence-free survival. Our exploratory study suggests a protective effect of naturally occurring HER2-AAbs on the development of primary and recurrent breast cancer. Further studies on HER2-AAbs are warranted. PMID:27113738

  17. 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…

  18. 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

  19. 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

  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. PMID:27524092

  1. Engineering AAV receptor footprints for gene therapy.

    PubMed

    Madigan, Victoria J; Asokan, Aravind

    2016-06-01

    Adeno-associated viruses (AAV) are currently at the forefront of human gene therapy clinical trials as recombinant vectors. Significant progress has been made in elucidating the structure, biology and tropisms of different naturally occurring AAV isolates in the past decade. In particular, a spectrum of AAV capsid interactions with host receptors have been identified and characterized. These studies have enabled a better understanding of key determinants of AAV cell recognition and entry in different hosts. This knowledge is now being applied toward engineering new, lab-derived AAV capsids with favorable transduction profiles. The current review conveys a structural perspective of capsid-glycan interactions and provides a roadmap for generating synthetic strains by engineering AAV receptor footprints. PMID:27262111

  2. 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.

  3. TRP Channels in Insect Stretch Receptors as Insecticide Targets.

    PubMed

    Nesterov, Alexandre; Spalthoff, Christian; Kandasamy, Ramani; Katana, Radoslav; Rankl, Nancy B; Andrés, Marta; Jähde, Philipp; Dorsch, John A; Stam, Lynn F; Braun, Franz-Josef; Warren, Ben; Salgado, Vincent L; Göpfert, Martin C

    2015-05-01

    Defining the molecular targets of insecticides is crucial for assessing their selectivity and potential impact on environment and health. Two commercial insecticides are now shown to target a transient receptor potential (TRP) ion channel complex that is unique to insect stretch receptor cells. Pymetrozine and pyrifluquinazon disturbed Drosophila coordination and hearing by acting on chordotonal stretch receptor neurons. This action required the two TRPs Nanchung (Nan) and Inactive (Iav), which co-occur exclusively within these cells. Nan and Iav together sufficed to confer cellular insecticide responses in vivo and in vitro, and the two insecticides were identified as specific agonists of Nan-Iav complexes that, by promoting cellular calcium influx, silence the stretch receptor cells. This establishes TRPs as insecticide targets and defines specific agonists of insect TRPs. It also shows that TRPs can render insecticides cell-type selective and puts forward TRP targets to reduce side effects on non-target species. PMID:25950634

  4. Molecular basis of kainate receptor modulation by sodium

    PubMed Central

    Plested, Andrew J. R.; Vijayan, Ranjit; Biggin, Philip C.; Mayer, Mark L.

    2008-01-01

    Summary Membrane proteins function in a polarized ionic environment with sodium-rich extracellular and potassium-rich intracellular solutions. Glutamate receptors which 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+ 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+ to 1 Cl− 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+ occurs simply because other cations bind with lower affinity, and have lower efficacy compared to Na+. PMID:18549784

  5. 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.

  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. Nuclear Receptors and Inflammatory Diseases

    PubMed Central

    Wang, Kun; Wan, Yu-Jui Yvonne

    2014-01-01

    It is well known that the steroid hormone glucocorticoid and its nuclear receptor regulate the inflammatory process, a crucial component in the pathophysiological process related to human diseases that include atherosclerosis, obesity and type II diabetes, inflammatory bowel disease, Alzheimer’s disease, multiple sclerosis, and liver tumors. Growing evidence demonstrates that orphan and adopted orphan nuclear receptors, such as peroxisome proliferator-activated receptors, liver × receptors, the farnesoid × receptor, NR4As, retinoid × receptors, and the pregnane × receptor, regulate the inflammatory and metabolic profiles in a ligand-dependent or -independent manner in human and animal models. This review summarizes the regulatory roles of these nuclear receptors in the inflammatory process and the underlying mechanisms. PMID:18375823

  8. AT1 receptors as mechanosensors.

    PubMed

    Mederos y Schnitzler, Michael; Storch, Ursula; Gudermann, Thomas

    2011-04-01

    G-protein-coupled receptors are appreciated as central components of neurohormonal signaling. Recently, it turned out that they may also play a role in mechanotransduction. The angiotensin II AT(1) receptor was the first G-protein-coupled receptor claimed to be a mechanosensor. In the meantime, several other G(q/11)-coupled receptors were found to be sensitive to mechanical stimuli. Furthermore, there is first evidence to support the concept that G(i/o)-coupled receptors are susceptible to mechanical stimulation as well. Mechanical receptor activation appears to be agonist-independent and is initiated by a conformational change of the receptor protein discernible from agonist-bound conformations. Mechanically induced receptor activation plays a physiological role for myogenic vasoconstriction and is involved in the pathogenesis of cardiac hypertrophy. PMID:21147033

  9. 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.

  10. 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. PMID:22807283

  11. Somatostatin receptors and somatostatin content in medullary thyroid carcinomas

    SciTech Connect

    Reubi, J.C.; Chayvialle, J.A.; Franc, B.; Cohen, R.; Calmettes, C.; Modigliani, E. )

    1991-04-01

    Human medullary thyroid carcinomas from 19 patients were analyzed for their content in somatostatin (SRIF) receptors using receptor autoradiography with a SRIF-28 analogue and the SRIF octapeptide (Tyr3)-SMS 201-995 as iodinated radioligands. Four out of 19 cases were SRIF receptor positive with the SRIF octapeptide radioligand. These cases as well as four additional tumors were also positive with the SRIF-28 radioligand 125I-(Leu8, D-Trp22, Tyr25)-SRIF-28. High affinity binding sites pharmacologically specific for bioactive SRIF analogues, specifically located on tumor tissue, were identified. In some cases the SRIF receptors were distributed in a non-homogeneous pattern, with labelling occurring preferentially in highly differentiated tumor regions. Numerous cases were shown to have a high tumoral SRIF content measured by radioimmunoassay or immunohistochemical technique. However, there was no correlation between SRIF receptor status and tumor levels of endogenous SRIF. No correlation was seen between the clinical outcome or the survival of the patients and their tumoral SRIF receptor content. Whereas some medullary thyroid carcinomas seem to be a target for SRIF, the SRIF function in these tumors remains unclear. SRIF receptors in a group of medullary thyroid carcinomas may be useful morphological marker of these tumors and of potential interest for their in vivo localization.

  12. 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

  13. GPCR heteromers and their allosteric receptor-receptor interactions.

    PubMed

    Fuxe, K; Borroto-Escuela, D O; Marcellino, D; Romero-Fernandez, W; Frankowska, M; Guidolin, D; Filip, M; Ferraro, L; Woods, A S; Tarakanov, A; Ciruela, F; Agnati, L F; Tanganelli, S

    2012-01-01

    The concept of intramembrane receptor-receptor interactions and evidence for their existences were introduced in the beginning of the 1980's, suggesting the existence of receptor heterodimerization. The discovery of GPCR heteromers and the receptor mosaic (higher order oligomers, more than two) has been related to the parallel development and application of a variety of resonance energy transfer techniques such as bioluminescence (BRET), fluorescence (FRET) and sequential energy transfer (SRET). The assembly of interacting GPCRs, heterodimers and receptor mosaic leads to changes in the agonist recognition, signaling, and trafficking of participating receptors via allosteric mechanisms, sometimes involving the appearance of cooperativity. The receptor interface in the GPCR heteromers is beginning to be characterized and the key role of electrostatic epitope-epitope interactions for the formation of the receptor heteromers will be discussed. Furthermore, a "guide-and-clasp" manner of receptor-receptor interactions has been proposed where the "adhesive guides" may be the triplet homologies. These interactions probably represent a general molecular mechanism for receptor-receptor interactions. It is proposed that changes in GPCR function (moonlighting) may develop through the intracellular loops and C-terminii of the GPCR heteromers as a result of dynamic allosteric interactions between different types of G proteins and other receptor interacting proteins in these domains of the receptors. The evidence for the existence of receptor heteromers opens up a new field for a better understanding of neurophysiology and neuropathology. Furthermore, novel therapeutic approaches could be possible based on the use of heteromers as targets for drug development based on their unique pharmacology. PMID:22335512

  14. New insights into structural determinants for prostanoid thromboxane A2 receptor- and prostacyclin receptor-G protein coupling.

    PubMed

    Chakraborty, Raja; Pydi, Sai Prasad; Gleim, Scott; Bhullar, Rajinder Pal; Hwa, John; Dakshinamurti, Shyamala; Chelikani, Prashen

    2013-01-01

    G protein-coupled receptors (GPCRs) interact with heterotrimeric G proteins and initiate a wide variety of signaling pathways. The molecular nature of GPCR-G protein interactions in the clinically important thromboxane A2 (TxA(2)) receptor (TP) and prostacyclin (PGI(2)) receptor (IP) is poorly understood. The TP activates its cognate G protein (Gαq) in response to the binding of thromboxane, while the IP signals through Gαs in response to the binding of prostacyclin. Here, we utilized a combination of approaches consisting of chimeric receptors, molecular modeling, and site-directed mutagenesis to precisely study the specificity of G protein coupling. Multiple chimeric receptors were constructed by replacing the TP intracellular loops (ICLs) with the ICL regions of the IP. Our results demonstrate that both the sequences and lengths of ICL2 and ICL3 influenced G protein specificity. Importantly, we identified a precise ICL region on the prostanoid receptors TP and IP that can switch G protein specificities. The validities of the chimeric technique and the derived molecular model were confirmed by introducing clinically relevant naturally occurring mutations (R60L in the TP and R212C in the IP). Our findings provide new molecular insights into prostanoid receptor-G protein interactions, which are of general significance for understanding the structural basis of G protein activation by GPCRs in basic health and cardiovascular disease. PMID:23109431

  15. New Insights into Structural Determinants for Prostanoid Thromboxane A2 Receptor- and Prostacyclin Receptor-G Protein Coupling

    PubMed Central

    Chakraborty, Raja; Pydi, Sai Prasad; Gleim, Scott; Bhullar, Rajinder Pal; Hwa, John; Dakshinamurti, Shyamala

    2013-01-01

    G protein-coupled receptors (GPCRs) interact with heterotrimeric G proteins and initiate a wide variety of signaling pathways. The molecular nature of GPCR-G protein interactions in the clinically important thromboxane A2 (TxA2) receptor (TP) and prostacyclin (PGI2) receptor (IP) is poorly understood. The TP activates its cognate G protein (Gαq) in response to the binding of thromboxane, while the IP signals through Gαs in response to the binding of prostacyclin. Here, we utilized a combination of approaches consisting of chimeric receptors, molecular modeling, and site-directed mutagenesis to precisely study the specificity of G protein coupling. Multiple chimeric receptors were constructed by replacing the TP intracellular loops (ICLs) with the ICL regions of the IP. Our results demonstrate that both the sequences and lengths of ICL2 and ICL3 influenced G protein specificity. Importantly, we identified a precise ICL region on the prostanoid receptors TP and IP that can switch G protein specificities. The validities of the chimeric technique and the derived molecular model were confirmed by introducing clinically relevant naturally occurring mutations (R60L in the TP and R212C in the IP). Our findings provide new molecular insights into prostanoid receptor-G protein interactions, which are of general significance for understanding the structural basis of G protein activation by GPCRs in basic health and cardiovascular disease. PMID:23109431

  16. Synapses, NMDA receptor activity and neuronal Aβ production in Alzheimer's disease.

    PubMed

    Bordji, Karim; Becerril-Ortega, Javier; Buisson, Alain

    2011-01-01

    A direct relationship has been established between synaptic activity and amyloid-β secretion. Dysregulation of neuronal calcium homeostasis was shown to increase production of amyloid-β, contributing to the initiation of Alzheimer's disease. Among the different routes of Ca(2+) entry, N-methyl-d-aspartate (NMDA) receptors, a subtype of ionotropic glutamate receptors, are especially involved in this process because of their ability to gate high levels of Ca(2+) influx. These receptors have been extensively studied for their crucial roles in synaptic plasticity that underlies learning and memory but also in neurotoxicity occurring during acute brain injuries and neurodegenerative diseases. For one decade, several studies provided evidence that NMDA receptor activation could have distinct consequences on neuronal fate, depending on their location. Synaptic NMDA receptor activation is neuroprotective, whereas extrasynaptic NMDA receptors trigger neuronal death and/or neurodegenerative processes. Recent data suggest that chronic activation of extrasynaptic NMDA receptors leads to a sustained neuronal amyloid-β release and could be involved in the pathogenesis of Alzheimer's disease. Thus, as for other neurological diseases, therapeutic targeting of extrasynaptic NMDA receptors could be a promising strategy. Following this concept, memantine, unlike other NMDA receptor antagonists was shown, to preferentially target the extrasynaptic NMDA receptor signaling pathways, while relatively sparing normal synaptic activity. This molecular mechanism could therefore explain why memantine is, to date, the only clinically approved NMDA receptor antagonist for the treatment of dementia. PMID:21568789

  17. Characterization of receptors for VIP on pancreatic acinar cell plasma membranes using covalent cross-linking

    SciTech Connect

    McArthur, K.E.; Wood, C.L.; O'Dorisio, M.S.; Zhou, Z.C.; Gardner, J.D.; Jensen, R.T.

    1987-03-01

    Vasoactive intestinal peptide (VIP) receptors on guinea pig pancreatic acini differ from those on all other tissues in containing a high-affinity VIP receptor and a low-affinity VIP receptor that has a high affinity for secretin. To characterize the molecular components of these receptors, /sup 125/I-VIP was covalently cross-linked to these receptors by four different cross-linking agents: disuccinimidyl suberate, ethylene glycol bis (succinimidyl succinate), dithiobis (succinimidylpropionate), and m-maleimidobenzoyl N-hydroxysuccinimide ester. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated a single major polypeptide band of M/sub r/ 45,000 and a minor polypeptide band of M/sub r/ 30,000 were cross-linked to /sup 125/I-VIP. Covalent cross-linking only occurred when a cross-linking agent was added, was inhibited by GTP, was inhibited by VIP receptor agonist or antagonists that interact with VIP receptors, and not by other pancreatic secretagogues that interact with difference receptors. Thus the high-affinity VIP receptor on pancreatic acinar cell membranes consists of a single major polypeptide of M/sub r/ 45,000, and this polypeptide is not a subunit of a larger disulfide-linked structure. Furthermore, either the low-affinity VIP/secretin-preferring receptor was not covalently cross-linked under the experimental conditions or it consist of a major polypeptide with the same molecular weight as the high-affinity VIP receptor.

  18. Expression of the transferrin receptor gene during the process of mononuclear phagocyte maturation

    SciTech Connect

    Hirata, T.; Bitterman, P.B.; Mornex, J.; Crystal, R.G.

    1986-02-15

    The expression of transferrin receptors by blood monocytes, human alveolar macrophages, and in vitro matured macrophages was evaluated by immunofluorescence, radioligand binding, and Northern analysis, using the monoclonal anti-human transferrin receptor antibody OKT9, (/sup 125/I)-labeled human transferrin and a (/sup 32/P)-labeled human transferrin receptor cDNA probe, respectively. By immunofluorescence, the majority of alveolar macrophages expressed transferrin receptors (86 +/- 3%). The radioligand binding assay demonstrated the affinity constant (K/sub a/) of the alveolar macrophage transferrin receptor was 4.4 +/- 0.7 x 10/sup 8/ M/sup -1/, and the number of receptors per cell was 4.4 +/- 1.2 x 10/sup 4/. In marked contrast, transferrin receptors were not present on the surface or in the cytoplasm of blood monocytes, the precursors of the alveolar macrophages. However, when monocytes were cultured in vitro and allowed to mature, > 80% expressed transferrin receptors by day 6, and the receptors could be detected by day 3. Consistent with these observations, a transferrin receptor mRNA with a molecular size of 4.9 kb was demonstrated in alveolar macrophages and in vitro matured macrophages but not in blood monocytes. Thus, although blood monocytes do not express the transferrin receptor gene, it is expressed by mature macrophages, an event that probably occurs relatively early in the process of monocyte differentiation to macrophages.

  19. 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

  20. 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

  1. P2X7 Receptors in Neurological and Cardiovascular Disorders

    PubMed Central

    Skaper, Stephen D.; Debetto, Patrizia; Giusti, Pietro

    2009-01-01

    P2X receptors are ATP-gated cation channels that mediate fast excitatory transmission in diverse regions of the brain and spinal cord. Several P2X receptor subtypes, including P2X7, have the unusual property of changing their ion selectivity during prolonged exposure to ATP, which results in a channel pore permeable to molecules as large as 900 daltons. The P2X7 receptor was originally described in cells of hematopoietic origin, and mediates the influx of Ca2+ and Na+ and Ca2+ and Na+ ions as well as the release of proinflammatory cytokines. P2X7 receptors may affect neuronal cell death through their ability to regulate the processing and release of interleukin-1β, a key mediator in neurodegeneration, chronic inflammation, and chronic pain. Activation of P2X7, a key mediator in neurodegeneration, chronic inflammation, and chronic pain. Activation of P2X7 receptors provides an inflammatory stimulus, and P2X7 receptor-deficient mice have substantially attenuated inflammatory responses, including models of neuropathic and chronic inflammatory pain. Moreover, P2X7 receptor activity, by regulating the release of proinflammatory cytokines, may be involved in the pathophysiology of depression. Apoptotic cell death occurs in a number of vascular diseases, including atherosclerosis, restenosis, and hypertension, and may be linked to the release of ATP from endothelial cells, P2X7 receptor activation, proinflammatory cytokine production, and endothelial cell apoptosis. In this context, the P2X7 receptor may be viewed as a gateway of communication between the nervous, immune, and cardiovascular systems. PMID:20029634

  2. Modulation of protein tyrosine phosphatase activity alters the subunit assembly in native N-methyl-D-aspartate receptor complex.

    PubMed

    Ferrani-Kile, Karima; Leslie, Steven W

    2005-07-01

    The N-methyl-D-aspartate (NMDA) receptor is crucial for development and neuroplasticity as well as excitotoxicity. The biochemical basis of the disassembly and reassembly of NMDA receptor has never been reported. Using coimmunoprecipitation, Western blotting, and mass spectrometry, we show that inhibition of tyrosine phosphatases triggers disassembly of NR1, NR2A, and NR2B in cortical NMDA receptor complexes. Furthermore, the disassembly of the NMDA receptor subunits is immediate, dose-dependent, and reversible and seems to occur through mechanisms linked to Src kinases. Together, these results define a novel role for tyrosine phosphatases in the complex mechanism of NMDA receptor regulation. PMID:15837820

  3. 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

  4. 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

  5. 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

  6. Neuropharmacology of the naturally occurring kappa-opioid hallucinogen salvinorin A.

    PubMed

    Cunningham, Christopher W; Rothman, Richard B; Prisinzano, Thomas E

    2011-06-01

    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-HT(2A) 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

  7. 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.

  8. Metabotropic Glutamate Receptors

    PubMed Central

    Dillon, James; Franks, Christopher J.; Murray, Caitriona; Edwards, Richard J.; Calahorro, Fernando; Ishihara, Takeshi; Katsura, Isao; Holden-Dye, Lindy; O'Connor, Vincent

    2015-01-01

    Glutamatergic neurotransmission is evolutionarily conserved across animal phyla. A major class of glutamate receptors consists of the metabotropic glutamate receptors (mGluRs). In C. elegans, three mGluR genes, mgl-1, mgl-2, and mgl-3, are organized into three subgroups, similar to their mammalian counterparts. Cellular reporters identified expression of the mgls in the nervous system of C. elegans and overlapping expression in the pharyngeal microcircuit that controls pharyngeal muscle activity and feeding behavior. The overlapping expression of mgls within this circuit allowed the investigation of receptor signaling per se and in the context of receptor interactions within a neural network that regulates feeding. We utilized the pharmacological manipulation of neuronally regulated pumping of the pharyngeal muscle in the wild-type and mutants to investigate MGL function. This defined a net mgl-1-dependent inhibition of pharyngeal pumping that is modulated by mgl-3 excitation. Optogenetic activation of the pharyngeal glutamatergic inputs combined with electrophysiological recordings from the isolated pharyngeal preparations provided further evidence for a presynaptic mgl-1-dependent regulation of pharyngeal activity. Analysis of mgl-1, mgl-2, and mgl-3 mutant feeding behavior in the intact organism after acute food removal identified a significant role for mgl-1 in the regulation of an adaptive feeding response. Our data describe the molecular and cellular organization of mgl-1, mgl-2, and mgl-3. Pharmacological analysis identified that, in these paradigms, mgl-1 and mgl-3, but not mgl-2, can modulate the pharyngeal microcircuit. Behavioral analysis identified mgl-1 as a significant determinant of the glutamate-dependent modulation of feeding, further highlighting the significance of mGluRs in complex C. elegans behavior. PMID:25869139

  9. Infectious Entry by Amphotropic as well as Ecotropic Murine Leukemia Viruses Occurs through an Endocytic Pathway

    PubMed Central

    Katen, Louis J.; Januszeski, Michael M.; Anderson, W. French; Hasenkrug, Kim J.; Evans, Leonard H.

    2001-01-01

    Infectious entry of enveloped viruses is thought to proceed by one of two mechanisms. pH-dependent viruses enter the cells by receptor-mediated endocytosis and are inhibited by transient treatment with agents that prevent acidification of vesicles in the endocytic pathway, while pH-independent viruses are not inhibited by such agents and are thought to enter the cell by direct fusion with the plasma membrane. Nearly all retroviruses, including amphotropic murine leukemia virus (MuLV) and human immunodeficiency virus type 1, are classified as pH independent. However, ecotropic MuLV is considered to be a pH-dependent virus. We have examined the infectious entry of ecotropic and amphotropic MuLVs and found that they were equally inhibited by NH4Cl and bafilomycin A. These agents inhibited both viruses only partially over the course of the experiments. Agents that block the acidification of endocytic vesicles also arrest vesicular trafficking. Thus, partial inhibition of the MuLVs could be the result of virus inactivation during arrest in this pathway. In support of this contention, we found that that the loss of infectivity of the MuLVs during treatment of target cells with the drugs closely corresponded to the loss of activity due to spontaneous inactivation at 37°C in the same period of time. Furthermore, the drugs had no effect on the efficiency of infection under conditions in which the duration of infection was held to a very short period to minimize the effects of spontaneous inactivation. These results indicate that the infectious processes of both ecotropic and amphotropic MuLVs were arrested rather than aborted by transient treatment of the cells with the drugs. We also found that infectious viruses were efficiently internalized during treatment. This indicated that the arrest occurred in an intracellular compartment and that the infectious process of both the amphotropic and ecotropic MuLVs very likely involved endocytosis. An important aspect of this study

  10. 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

  11. 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

  12. 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. PMID:23880303

  13. 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.

  14. Internalized insulin-receptor complexes are unidirectionally translocated to chloroquine-sensitive degradative sites. Dependence on metabolic energy

    SciTech Connect

    Berhanu, P.

    1988-04-25

    Insulin receptors on the surface of isolated rat adipocytes were photoaffinity labeled at 12 degrees C with the iodinated photoreactive insulin analogue, 125I-B2 (2-nitro-4-azidophenylacetyl)-des-PheB1-insulin, and the pathways in the intracellular processing of the labeled receptors were studied at 37 degrees C. During 37 degrees C incubations, the labeled 440-kDa insulin receptors were continuously internalized (as assessed by trypsin inaccessibility) and degraded such that up to 50% of the initially labeled receptors were lost by 120 min. Metabolic poisons (0.125-0.75 mM 2,4-dinitrophenol (DNP) and 1-10 mM NaF), which led to dose-dependent depletion of adipocyte ATP pools, inhibited receptor loss, and caused up to 3-fold increase in intracellular receptor accumulation. This effect was due to inhibition of intracellular receptor degradation, and there was no apparent effect of the metabolic poisons on initial internalization of the receptors. Following maximal intracellular accumulation of labeled insulin receptors in the presence of NaF or DNP, removal of these agents resulted in a subsequent, time-dependent degradation of the accumulated receptors. However, when the lysosomotropic agent, chloroquine (0.2 mM), was added immediately following removal of the metabolic poisons, further degradation of the intracellularly accumulated receptors was prevented, suggesting that the chloroquine-sensitive degradation of insulin receptors occurs distal to the site of inhibition by NaF or DNP. To confirm this, maximal intracellular accumulation of labeled receptors was first allowed to occur in the presence of chloroquine and the cells were then washed and reincubated in chloroquine-free media in the absence or presence of NaF or DNP. Under these conditions, degradation of the intracellularly accumulated receptors continued to occur, and NaF or DNP failed to block the degradation.

  15. 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

  16. 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

  17. 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. PMID:27101376

  18. Cholesterol signaling at the endoplasmic reticulum occurs in npc1(-/-) but not in npc1(-/-), LDLR(-/-) mice.

    PubMed

    Erickson, R P; Kiela, M; Garver, W S; Krishnan, K; Heidenreich, R A

    2001-06-01

    It remains controversial whether deficiency of the Niemann-Pick C1 (npc1) protein results in altered cholesterol signaling at the endoplasmic reticulum (ER). In this report, we have measured the processed, nuclear form of sterol regulatory element binding protein (SREBP)-1 in livers of npc1 wild-type, heterozygous, and homozygous deficient mice, alone, and in combination with deficiencies of the low density lipoprotein receptor (LDLR) or the multiple drug resistant (mdr)1a, P-glycoprotein. Cleavage of SREBPs to activated forms normally occurs when the ER is deficient in cholesterol. A large decrease in processed SREBP-1 was evident in fasted npc1(-/-) mice and npc1(-/-), mdr1a(-/-) mice, with no decrease evident in npc1(-/-), LDLR(-/-) mice. These results suggest that the increase in cellular cholesterol which occurs in npc1(-/-) and in npc1(-/-), mdr1a(-/-) mice includes the sites responsible for cholesterol signaling, while the similar increase in cholesterol found in npc1(-/-), LDLR(-/-) mice does not. PMID:11394880

  19. Naturally occurring rhodopsin mutation in the dog causes retinal dysfunction and degeneration mimicking human dominant retinitis pigmentosa

    PubMed Central

    Kijas, James W.; Cideciyan, Artur V.; Aleman, Tomas S.; Pianta, Michael J.; Pearce-Kelling, Susan E.; Miller, Brian J.; Jacobson, Samuel G.; Aguirre, Gustavo D.; Acland, Gregory M.

    2002-01-01

    Rhodopsin is the G protein-coupled receptor that is activated by light and initiates the transduction cascade leading to night (rod) vision. Naturally occurring pathogenic rhodopsin (RHO) mutations have been previously identified only in humans and are a common cause of dominantly inherited blindness from retinal degeneration. We identified English Mastiff dogs with a naturally occurring dominant retinal degeneration and determined the cause to be a point mutation in the RHO gene (Thr4Arg). Dogs with this mutant allele manifest a retinal phenotype that closely mimics that in humans with RHO mutations. The phenotypic features shared by dog and man include a dramatically slowed time course of recovery of rod photoreceptor function after light exposure and a distinctive topographic pattern to the retinal degeneration. The canine disease offers opportunities to explore the basis of prolonged photoreceptor recovery after light in RHO mutations and determine whether there are links between the dysfunction and apoptotic retinal cell death. The RHO mutant dog also becomes the large animal needed for preclinical trials of therapies for a major subset of human retinopathies. PMID:11972042

  20. 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.

  1. 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

  2. Estrogen receptor mutations in tamoxifen-resistant breast cancer.

    PubMed

    Karnik, P S; Kulkarni, S; Liu, X P; Budd, G T; Bukowski, R M

    1994-01-15

    Clinical resistance to antiestrogens like tamoxifen is a major problem in the treatment of hormone-dependent breast cancers. Since the estrogen receptor plays a central role in mediating the effects of estrogens and antiestrogens, we hypothesized that mutations in the estrogen receptor could be one mechanism by which breast tumors evolve from a hormone-dependent to a hormone-independent phenotype. The eight exons of the estrogen receptor complementary DNA from 20 tamoxifen-resistant and 20 tamoxifen-sensitive tumors were screened by Single Strand Conformation Polymorphism (SSCP), and the variant conformers were sequenced to identify the nucleotide changes. A 42-base pair replacement was found in exon 6 of a tamoxifen-resistant tumor. A single base pair deletion in exon 6 of a tamoxifen-resistant metastatic tumor but not in the primary tumor was detected in another case. If translated, both these mutations could generate truncated receptors with an intact DNA-binding domain and a defective hormone-binding domain that could constitutively activate transcription of previously estrogen-responsive genes. The remaining 18 of 20 tamoxifen-resistant tumors did not contain mutations in any of the 8 exons of the estrogen receptor complementary DNA. These results suggest that mutations in the estrogen receptor occur at a low frequency and do not account for most estrogen-independent, tamoxifen-resistant breast tumors. PMID:8275466

  3. 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

  4. Amiloride interacts with renal. cap alpha. - and. beta. -adrenergic receptors

    SciTech Connect

    Howard, M.J.; Mullen, M.D.; Insel, P.A.

    1987-07-01

    The authors have used radioligand binding techniques to assess whether amiloride and certain analogues of amiloride (ethylisopropyl amiloride and benzamil) can bind to adrenergic receptors in the kidney. They found that amiloride could compete for (/sup 3/H)rauwolscine (..cap alpha../sub 2/-adrenergic receptors), (/sup 3/H)prazosin (..cap alpha../sub 1/-adrenergic receptors), and (/sup 125/I)iodocyanopindolol (..beta..-adrenergic receptors) binding in rat renal cortical membranes with inhibitor constants of 13.6 /plus minus/ 5.7, 24.4 /plus minus/ 7.4, and 8.36 /plus minus/ 13.5 ..mu..M, respectively. Ethylisopropyl amiloride and benzamil were from 2- to 25-fold more potent than amiloride in competing for radioligand binding sites in studies with these membranes. In addition, amiloride and the two analogues competed for (/sup 3/H)prazosin sites on intact Madin-Darby canine kidney cells and amiloride blocked epinephrine-stimulated prostaglandin E/sub 2/ production in these cells. They conclude that amiloride competes for binding to several classes of renal adrenergic receptors with a rank order of potency of ..cap alpha../sub 2/ > ..cap alpha../sub 1/ > ..beta... Binding to, and antagonism of, adrenergic receptors occurs at concentrations of amiloride that are lower than previously observed nonspecific interactions of this agent.

  5. 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

  6. Yokukansan Increases 5-HT1A Receptors in the Prefrontal Cortex and Enhances 5-HT1A Receptor Agonist-Induced Behavioral Responses in Socially Isolated Mice