Science.gov

Sample records for receptor m33 occurs

  1. The M33 Chemokine Receptor Homolog of Murine Cytomegalovirus Exhibits a Differential Tissue-Specific Role during In Vivo Replication and Latency▿

    PubMed Central

    Cardin, Rhonda D.; Schaefer, Gregory C.; Allen, Janelle R.; Davis-Poynter, Nicholas J.; Farrell, Helen E.

    2009-01-01

    M33, encoded by murine cytomegalovirus (MCMV), is a member of the UL33 homolog G-protein-coupled receptor (GPCR) family and is conserved across all the betaherpesviruses. Infection of mice with recombinant viruses lacking M33 or containing specific signaling domain mutations in M33 results in significantly diminished MCMV infection of the salivary glands. To determine the role of M33 in viral dissemination and/or infection in other tissues, viral infection with wild-type K181 virus and an M33 mutant virus, ΔM33BT2, was characterized using two different routes of inoculation. Following both intraperitoneal (i.p.) and intranasal (i.n.) inoculation, M33 was attenuated for infection of the spleen and pancreas as early as 7 days after infection. Following i.p. inoculation, ΔM33BT2 exhibited a severe defect in latency as measured by a diminished capacity to reactivate from spleens and lungs in reactivation assays (P < 0.001). Subsequent PCR analysis revealed markedly reduced ΔM33BT2 viral DNA levels in the latently infected spleens, lungs, and bone marrow. Following i.n. inoculation, latent ΔM33BT2 viral DNA was significantly reduced in the spleen and, in agreement with results from i.p. inoculation, did not reactivate from the spleen (P < 0.001). Furthermore, in vivo complementation of ΔM33BT2 virus replication and/or dissemination to the salivary glands and pancreas was achieved by coinfection with wild-type virus. Overall, our data suggest a critical tissue-specific role for M33 during infection in the salivary glands, spleen, and pancreas but not the lungs. Our data suggest that M33 contributes to the efficient establishment or maintenance of long-term latent MCMV infection. PMID:19439478

  2. Chemical Evolution Model of M33

    NASA Astrophysics Data System (ADS)

    Robles-Valdez, F.; Carigi, L.

    2011-10-01

    We present a chemical evolution model (CEM) of M33 and we find that M33, which is smaller than both M31 and MW, shows a lower gas infall rate, SFR efficiency, and IMF M_{up}. Therefore the CEMs for large spiral galaxies (Carigi et al. 2005; Meneses-Goytia et al. 2011) can be scaled to a smaller galaxy.

  3. The Planetary Nebula System of M33

    NASA Astrophysics Data System (ADS)

    Ciardullo, Robin; Durrell, Patrick R.; Laychak, Mary Beth; Herrmann, Kimberly A.; Moody, Kenneth; Jacoby, George H.; Feldmeier, John J.

    2004-10-01

    We report the results of a photometric and spectroscopic survey for planetary nebulae (PNs) over the entire body of the Local Group spiral galaxy M33. We use our sample of 152 PNs to show that the bright end of the galaxy's [O III] λ5007 planetary nebula luminosity function (PNLF) has the same sharp cutoff seen in other galaxies. The apparent magnitude of this cutoff, along with the IRAS DIRBE foreground extinction estimate of E(B-V)=0.041, implies a distance modulus for the galaxy of (m-M)0=24.86+0.07-0.11 (0.94+0.03-0.05 Mpc). Although this value is ~15% larger than the galaxy's Cepheid distance, the discrepancy likely arises from differing assumptions about the system's internal extinction. Our photometry, which extends more than 3 mag down the PNLF, also reveals that the faint end of M33's PNLF is nonmonotonic, with an inflection point ~2 mag below the PNLF's bright limit. We argue that this feature is due to the galaxy's large population of high core mass planetaries and that its amplitude may eventually be a useful diagnostic for studies of stellar populations. Fiber-coupled spectroscopy of 140 of the PN candidates confirms that M33's PN population rotates along with the old disk, with a small asymmetric drift of ~10 km s-1. Remarkably, the population's line-of-sight velocity dispersion varies little over ~4 optical disk scale lengths, with σrad~20 km s-1. We show that this is due to a combination of factors, including a decline in the radial component of the velocity ellipsoid at small galactocentric radii and a gradient in the ratio of the vertical to radial velocity dispersion. We use our data to derive the dynamical scale length of M33's disk and the disk's mass-to-light ratio. Our most likely solution suggests that the surface mass density of M33's disk decreases exponentially, but with a scale length that is ~2.3 times larger than that of the system's IR luminosity. The large scale length also implies that the disk's V-band mass-to-light ratio changes

  4. Naturally occurring and synthetic peptides acting on nicotinic acetylcholine receptors.

    PubMed

    Kasheverov, Igor E; Utkin, Yuri N; Tsetlin, Victor I

    2009-01-01

    Nicotinic acetylcholine receptors (nAChRs) are pentameric membrane-bound proteins belonging to the large family of ligand-gated ion channels. nAChRs possess various binding sites which interact with compounds of different chemical nature, including peptides. Historically first peptides found to act on nAChR were synthetic fragments of snake alpha-neurotoxins, competitive receptor antagonists. Later it was shown that fragments of glycoprotein from rabies virus, having homology to alpha-neurotoxins, and polypeptide neurotoxins waglerins from the venom of Wagler's pit viper Trimeresurus (Tropidolaemus) wagleri bind in a similar way, waglerins being efficient blockers of muscle-type nAChRs. Neuropeptide substance P appears to interact with the channel moiety of nAChR. beta-Amyloid, a peptide forming senile plaques in Alzheimer's disease, also can bind to nAChR, although the mode of binding is still unclear. However, the most well-studied peptides interacting with the ligand-binding sites of nAChRs are so-called alpha-conotoxins, peptide neurotoxins from marine snails of Conus genus. First alpha-conotoxins were discovered in the late 1970s, and now it is a rapidly growing family due to isolation of peptides from multiple Conus species, as well as to cloning, and chemical synthesis of new analogues. Because of their unique selectivity towards distinct nAChR subtypes, alpha-conotoxins became valuable tools in nAChR research. Recent X-ray structures of alpha-conotoxin complexes with acetylcholine-binding protein, a model of nAChR ligand-binding domains, revealed the details of the nAChR ligand-binding sites and provided the basis for design of novel ligands.

  5. No supermassive black hole in M33?

    PubMed

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

    2001-08-10

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

  6. The molecular gas mass of M 33

    NASA Astrophysics Data System (ADS)

    Gratier, P.; Braine, J.; Schuster, K.; Rosolowsky, E.; Boquien, M.; Calzetti, D.; Combes, F.; Kramer, C.; Henkel, C.; Herpin, F.; Israel, F.; Koribalski, B. S.; Mookerjea, B.; Tabatabaei, F. S.; Röllig, M.; van der Tak, F. F. S.; van der Werf, P.; Wiedner, M.

    2017-03-01

    Do some environments favor efficient conversion of molecular gas into stars? To answer this, we need to be able to estimate the H2 mass. Traditionally, this is done using CO observations and a few assumptions but the Herschel observations which cover the far-IR dust spectrum make it possible to estimate the molecular gas mass independently of CO and thus to investigate whether and how the CO traces H2. Previous attempts to derive gas masses from dust emission suffered from biases. Generally, dust surface densities, H i column densities, and CO intensities are used to derive a gas-to-dust ratio (GDR) and the local CO intensity to H2 column density ratio (XCO), sometimes allowing for an additional CO-dark gas component (Kdark). We tested earlier methods, revealing degeneracies among the parameters, and then used a sophisticated Bayesian formalism to derive the most likely values for each of the parameters mentioned above as a function of position in the nearby prototypical low metallicity (12 + log (O/H) 8.4) spiral galaxy M 33. The data are from the IRAM Large Program mapping in the CO(2-1) line along with high-resolution H i and Herschel dust continuum observations. Solving for GDR, XCO, and Kdark in macropixels 500 pc in size, each containing many individual measurements of the CO, H i, and dust emission, we find that (i) allowing for CO dark gas (Kdark) significantly improves fits; (ii) Kdark decreases with galactocentric distance; (iii) GDR is slightly higher than initially expected and increases with galactocentric distance; (iv) the total amount of dark gas closely follows the radially decreasing CO emission, as might be expected if the dark gas is H2 where CO is photodissociated. The total amount of H2, including dark gas, yields an average XCO of twice the galactic value of 2 × 1020 cm-2/ K km s-1, with about 55% of this traced directly through CO. The rather constant fraction of dark gas suggests that there is no large population of diffuse H2 clouds

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

    PubMed

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

    2015-06-02

    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.

  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. Dust properties in H II regions in M 33

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

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

  10. The M33 Synoptic Stellar Survey. II. Mira Variables

    NASA Astrophysics Data System (ADS)

    Yuan, Wenlong; He, Shiyuan; Macri, Lucas M.; Long, James; Huang, Jianhua Z.

    2017-04-01

    We present the discovery of 1847 Mira candidates in the Local Group galaxy M33 using a novel semi-parametric periodogram technique coupled with a random forest classifier. The algorithms were applied to ∼2.4 × 105 I-band light curves previously obtained by the M33 Synoptic Stellar Survey. We derive preliminary period–luminosity relations at optical, near-infrared, and mid-infrared wavelengths and compare them to the corresponding relations in the Large Magellanic Cloud.

  11. The Structure of Halo Gas around M33

    NASA Astrophysics Data System (ADS)

    Keenan, Olivia C.; Davies, Jonathan I.; Taylor, Rhys; Minchin, Robert F.

    2017-03-01

    Understanding the distribution of gas in and around galaxies is vital for our interpretation of galaxy formation and evolution. As part of the Arecibo Galaxy Environment Survey (AGES) we have observed the neutral hydrogen (HI) gas in and around the nearby Local Group galaxy M33 to a greater depth than previous observations. As part of this project we investigated the absence of optically detected dwarf galaxies in its neighbourhood, which is contrary to predictions of galaxy formation models. We observed 22 discrete clouds, 11 of which were previously undetected and none of which have optically detected counterparts. We find one particularly interesting hydrogen cloud, which has many similar characteristics to hydrogen distributed in the disk of a galaxy. This cloud, if it is at the distance of M33, has a HI mass of around 107 M⊙ and a diameter of 18 kpc, making it larger in size than M33 itself.

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

    SciTech Connect

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

    2010-11-10

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

  13. Receptor mutation is not a common mechanism of naturally occurring glucocorticoid resistance in leukaemia cell lines.

    PubMed

    Beesley, Alex H; Weller, Renae E; Senanayake, Saranga; Welch, Mathew; Kees, Ursula R

    2009-02-01

    Glucocorticoids (GCs) are among the most important drugs for the treatment of acute lymphoblastic leukaemia (ALL). Cell lines cultured in high GC concentrations typically contain mutated glucocorticoid receptor (GR), something that is rarely found in primary ALL specimens. We studied naturally occurring mechanisms of GC resistance and examined sensitivity to GC in 15 T-ALL cell lines grown without prior exposure to drugs. Resistance could not be attributed to mutations in GR or variations in levels of its expression. We conclude that this panel of cell lines provides a suitable in vitro model since it reflects GC resistance in primary ALL.

  14. NEW UBVRI PHOTOMETRY OF 234 M33 STAR CLUSTERS

    SciTech Connect

    Ma Jun

    2013-04-15

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

  15. Discovery of a Probable Nova in M33

    NASA Astrophysics Data System (ADS)

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

    2014-08-01

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

  16. Functional Studies on Twenty Novel Naturally Occurring Melanocortin-4 Receptor Mutations

    PubMed Central

    Wang, Zhi-Qiang; Tao, Ya-Xiong

    2011-01-01

    The melanocortin-4 receptor (MC4R) is a G protein-coupled receptor critically involved in regulating energy balance. MC4R activation results in decreased food intake and increased energy expenditure. Genetic and pharmacological studies demonstrated that the MC4R regulation of energy balance is conserved from fish to mammals. In humans, more than 150 naturally occurring mutations in the MC4R gene have been identified. Functional study of mutant MC4Rs is an important component in proving the causal link between MC4R mutation and obesity as well as the basis of personalized medicine. In this article, we studied 20 MC4R mutations that were either not characterized or not fully characterized. We showed that 11 mutants had decreased or absent cell surface expression. D126Y was defective in ligand binding. Three mutants were constitutively active but had decreased cell surface expression. Eleven mutants had decreased basal signaling, with two mutants defective only in this parameter, suggesting that impaired basal signaling might also be a cause of obesity. Five mutants had normal functions. In summary, we provided detailed functional data for further studies on identifying therapeutic approaches for personalized medicine to treat patients harboring these mutations. PMID:21729752

  17. Inhibition of T cell receptor signaling by cholesterol sulfate, a naturally occurring derivative of membrane cholesterol

    PubMed Central

    Wang, Feng; Beck-García, Katharina; Zorzin, Carina; Schamel, Wolfgang W. A.; Davis, Mark M.

    2016-01-01

    Most adaptive immune responses require the activation of specific T cells through the T cell antigen receptor–CD3 complex (TCR). Here we show that cholesterol sulfate (CS), a naturally occurring analog of cholesterol, inhibits CD3 ITAM phosphorylation, a crucial first step in T cell activation. Biochemical studies show that CS disrupted TCR multimers, apparently by displacing cholesterol, known to bind TCRβ. Moreover, CS-deficient mice displayed a heightened sensitivity to a self-antigen, whereas increasing CS content by intrathymic injection inhibited thymic selection, indicating that this molecule is an intrinsic regulator of thymocyte development. These results reveal a regulatory role for CS in TCR signaling and thymic selection, highlighting the importance of the membrane microenvironment in modulating cell surface receptor activation. PMID:27213689

  18. Biased Signaling in Naturally Occurring Mutations in Human Melanocortin-3 Receptor Gene

    PubMed Central

    Yang, Fan; Huang, Hui; Tao, Ya-Xiong

    2015-01-01

    The melanocortin-3 receptor (MC3R) is primarily expressed in the hypothalamus and plays an important role in the regulation of energy homeostasis. Recently, some studies demonstrated that MC3R also signals through mitogen-activated protein kinases (MAPKs), especially extracellular signal-regulated kinases 1 and 2 (ERK1/2). ERK1/2 signaling is known to alter gene expression, potentially contributing to the prolonged action of melanocortins on energy homeostasis regulation. In the present study, we performed detailed functional studies on 8 novel naturally occurring MC3R mutations recently reported, and the effects of endogenous MC3R agonist, α-melanocyte stimulating hormone (MSH), on ERK1/2 signaling on all 22 naturally occurring MC3R mutations reported to date. We found that mutants D158Y and L299V were potential pathogenic causes to obesity. Four residues, F82, D158, L249 and L299, played critical roles in different aspects of MC3R function. α-MSH exhibited balanced activity in Gs-cAMP and ERK1/2 signaling pathways in 15 of the 22 mutant MC3Rs. The other 7 mutant MC3Rs were biased to either one of the signaling pathways. In summary, we provided novel data about the structure-function relationship of MC3R, identifying residues important for receptor function. We also demonstrated that some mutations exhibited biased signaling, preferentially activating one intracellular signaling pathway, adding a new layer of complexity to MC3R pharmacology. PMID:25798062

  19. Cepheids and Long Period Variables in M 33

    NASA Astrophysics Data System (ADS)

    Pellerin, Anne; Macri, Lucas M.; Bradshaw, Andrew K.; Stanek, Krzysztof Z.

    2009-09-01

    We are conducting a long-term photometric survey of the nearby galaxy M 33 to discover Cepheids, eclipsing binaries, and long-period variables. The dataset combines previously-obtained optical images from the DIRECT project with new observations acquired at the WIYN 3.5 m telescope. The entire data set spans over 7 years with excellent synoptic coverage which will enable the discovery and characterization of stars displaying variability over a wide range of timescales (days, weeks, months, years). In this preliminary work we show representative light curves of different variables we found so far in two fields, color-magnitude diagrams, and optical Cepheid Period-Luminosity relations for M 33. The ultimate goal of the project is to provide an absolute calibration of the Cepheid Period-Luminosity relation, and to study its metallicity dependence at optical wavelengths.

  20. 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.

  1. A high-resolution mosaic of HI in M33

    NASA Astrophysics Data System (ADS)

    Thilker, D. A.; Braun, R.; Walterbos, R. A. M.

    2000-12-01

    We have completed a high-resolution VLA/WSRT survey of HI in M33. Our data comprise the most detailed HI observations ever obtained for a spiral galaxy other than the Milky Way and reveal many striking properties of the neutral atomic gas. Spatial resolution of 20 pc (assuming a distance of 840 kpc) permits identification of expanding bubbles smaller than those cataloged by Deul & den Hartog, in addition to HI counterparts of discrete dust clouds. Likewise, we find a complex morphological relationship between HI and HII components. Velocity sampling of 1.3 km/s was achieved, thereby permitting the study of line profile variations as a function of environment within M33. A possible dark companion to M33 has been discovered using our WSRT observations. Deep 100m-class, single dish observations or D-configuration VLA images are needed to follow-up this lead, and exclude the possibility of a Galactic HVC explanation. This poster summarizes our initial analysis of the new dataset.

  2. The Red Supergiants of M33: Determining Physical Properties

    NASA Astrophysics Data System (ADS)

    Beck, Madeleine; Massey, Philip

    2017-01-01

    We investigate a sample of red supergiants in the nearby unbarred spiral galaxy M33 with the goals of (1) determining the physical properties of these stars, (2) understanding the effects of metallicity on massive star evolution, and (3) comparing results to current models proposed by the Geneva group. M33 provides an ideal environment in which to conduct this examination because of a gradient of metallicity within its disk as well as its proximity to the Milky Way, which allows us to observe a complete sample of red supergiants. We employ MARCS atmosphere models and fit spectral features of our stars to determine effective temperatures and spectral types, then we use this information in combination with photometry to calculate bolometric luminosities. After placing these objects on the H-R diagram, we notice some discrepancies with what the Geneva solar-metallicity evolutionary tracks (Ekstrom et al. 2012) predict, namely that the tracks may not extend to cool enough temperatures and high enough luminosities and masses to comply with what we see observationally. We propose this may be the result of a mismatch between M33’s metallicity and the solar-metallicity Geneva models; we hope to make comparisons in the future as these new evolutionary tracks become available. This work was supported by the NSF through grant numbers AST-1461200 and AST-1612874.

  3. 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

  4. Naturally occurring PDGF receptor inhibitors with potential anti-atherosclerotic properties.

    PubMed

    Ricci, Chiara; Ferri, Nicola

    2015-07-01

    Platelet-derived growth factor (PDGF) represents one of the most prominent inducer of smooth muscle cell (SMC) migration and proliferation. Homo- and heterodimers of PDGF-A, PDGF-B, PDGF-C and PDGF-D subunits act by binding to homo- or heterodimers of the PDGF tyrosine kinase receptors, PDGFR-α and PDGFR-β. The essential role of PDGFR signaling on restenosis post-angioplasty or atherosclerosis has been demonstrated by using blocking antibodies to PDGF or the tyrosine kinase inhibitor imatinib. More specifically, molecular studies have defined the intracellular signaling pathways activated by PDGF, inducing the cell cycle progression and the migration of SMCs. Considering the relevant role of PDGF in atherogenesis, several studies have been performed to investigate the effect of naturally occurring compounds on both in vitro and in vivo experimental models of atherogenesis. The present review will briefly summarize the pathophysiological role of PDGF and the studies of natural inhibitors tested in in vivo experimental models of restenosis in response to vascular injury and/or atherosclerosis.

  5. STRUCTURAL PARAMETERS FOR 10 HALO GLOBULAR CLUSTERS IN M33

    SciTech Connect

    Ma, Jun

    2015-05-15

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

  6. PHOTOMETRIC PROPERTIES OF THE M33 STAR CLUSTER SYSTEM

    SciTech Connect

    San Roman, Izaskun; Sarajedini, Ata; Aparicio, Antonio E-mail: ata@astro.ufl.ed

    2010-09-10

    We present a catalog of 2990 extended sources in a 1{sup 0} x 1{sup 0} area centered on M33 using the MegaCam camera on the 3.6 m Canada-France-Hawaii Telescope. The catalog includes 599 new candidate stellar clusters, 204 previously confirmed clusters, 1969 likely background galaxies, and 218 unknown extended objects. We present ugriz integrated magnitudes of the candidates and confirmed star clusters (SCs) as well as the full width at half maximum, ellipticity, and stellarity. Based on the properties of the confirmed SCs, we select a sub-sample of highly probable clusters composed of 246 objects. The integrated photometry of the complete cluster catalog reveals a wide range of colors of -0.4 < (g - r) < 1.5 and -1.0 < (r - i) < 1.0 with no obvious cluster subpopulations. Comparisons with models of simple stellar populations suggest a large range of ages some as old as {approx}10 Gyr. In addition, we find a sequence in the color-color diagrams that deviates from the expected direction of evolution. This feature could be associated with very young clusters (<10{sup 7} yr) possessing significant nebular emission. Analysis of the radial density distribution suggests that the cluster system of M33 has suffered from significant depletion possibly due to interactions with M31. We also detect a gap in the cluster distribution in the color-color diagram at (g - r) {approx_equal} 0.3 and (u - g) {approx_equal} 0.8. This gap could be interpreted as an evolutionary effect. This complete catalog provides promising targets for deep photometry and high-resolution spectroscopy to study the structure and star formation history of M33.

  7. Nova M33N 2012-10a

    NASA Astrophysics Data System (ADS)

    Alothman, Nourah

    In this thesis I present a study and measurement of a Nova in M33 galaxy type N 2012-10a (which is type of binary star) using data that were collected by the ROTSE IIIb robotic telescope and another observatory. I study the fundamental properties of the light curve and determined the brightness and the velocity of this type of nova. I analyzed the spectra that were measured by the Hobby-Eberly Telescope (HET) at the McDonald Observatory. In addition, I compared this type of nova to other types of Novae.

  8. M33 @ Observatorio Astrofísico de Javalambre

    NASA Astrophysics Data System (ADS)

    Vázquez Ramió, H.; Ederoclite, A.; Lamadrid, J. L.; Blanco Siffert, B.; San Roman, I.; Cristóbal-Hornillos, D.; Varela, J.; Coelho, P.; Moles, M.; Cenarro, A. J.; Marín-Franch, A.; Díaz-Martín, C. M.; Iglesias Marzoa, R.; Tilve, V.; Rodríguez, S.; Maícas, N.; López San Juan, C.; Viironen, K.; Vilella Rojo, G.; Logroño García, R.; Abril Ibánez, J.

    2017-03-01

    M33, the Triangulum Galaxy, is a spiral galaxy in the Local Group. Given its brightness and its vicinity with Andromeda Galaxy (M31), it is one of the best studied objects of the Northern hemisphere. In this poster, we present observations carried out with the JAST/T80 at the Observatorio Astrofísico de Javalambre. The extraordinary field of view of this telescope allows us to study the stellar populations of the galaxy with a single observation. Moreover, repeated observations have provided us the possibility to follow a variety of variable stars, among them the nova ASASSN-15th.

  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. H-alpha Photometric Survey of M33

    NASA Astrophysics Data System (ADS)

    Blaha, Cindy; Massey, P.; Hodge, P.; Martin, R.; Gavilan, L.; Adhikari, A.

    2006-12-01

    We present the results of a photometric survey of optical emission line regions in M33. Using data from the Local Group Galaxy Survey (LGGS see Massey et al, 2006)), we created continuum-subtracted H-alpha, [OIII] and [SII] emission line images and used flux contours on the H-alpha images to define emission line regions. To date, we have obtained photometric measurements for over 2850 H -alpha emission regions, with a faint flux limit of 10 -15 ergs-sec-1-cm-2 in the outer regions of the galaxy. Our global H Ι region luminosity function displays a broad peak centered at a luminosity of 6 x 10 35 ergs-sec-1 and extends to fainter luminosities than previously published surveys. We used the H-alpha-defined emission regions to determine fluxes for the [OIII] and [SII] images and created RGB images combining the calibrated emission images from all three filters. These RGB emission line images are being used with our [OIII]/ H-alpha and [SII]/ H-alpha line ratios and published catalogs to develop visual diagnostic tools to identify H II regions, planetary nebulae and supernova remnants in M33. Additional results from the LGGS data are being presented elsewhere at this meeting; see Massey et al and McNeill et al.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. A naturally occurring insertion of a single amino acid rewires transcriptional regulation by glucocorticoid receptor isoforms.

    PubMed

    Thomas-Chollier, Morgane; Watson, Lisa C; Cooper, Samantha B; Pufall, Miles A; Liu, Jennifer S; Borzym, Katja; Vingron, Martin; Yamamoto, Keith R; Meijsing, Sebastiaan H

    2013-10-29

    In addition to guiding proteins to defined genomic loci, DNA can act as an allosteric ligand that influences protein structure and activity. Here we compared genome-wide binding, transcriptional regulation, and, using NMR, the conformation of two glucocorticoid receptor (GR) isoforms that differ by a single amino acid insertion in the lever arm, a domain that adopts DNA sequence-specific conformations. We show that these isoforms differentially regulate gene expression levels through two mechanisms: differential DNA binding and altered communication between GR domains. Our studies suggest a versatile role for DNA in both modulating GR activity and also in directing the use of GR isoforms. We propose that the lever arm is a "fulcrum" for bidirectional allosteric signaling, conferring conformational changes in the DNA reading head that influence DNA sequence selectivity, as well as conferring changes in the dimerization domain that connect functionally with remote regulatory surfaces, thereby influencing which genes are regulated and the magnitude of their regulation.

  18. Naturally Occurring Eccentric Cleavage Products of Provitamin A β-Carotene Function as Antagonists of Retinoic Acid Receptors*

    PubMed Central

    Eroglu, Abdulkerim; Hruszkewycz, Damian P.; dela Sena, Carlo; Narayanasamy, Sureshbabu; Riedl, Ken M.; Kopec, Rachel E.; Schwartz, Steven J.; Curley, Robert W.; Harrison, Earl H.

    2012-01-01

    β-Carotene is the major dietary source of provitamin A. Central cleavage of β-carotene catalyzed by β-carotene oxygenase 1 yields two molecules of retinaldehyde. Subsequent oxidation produces all-trans-retinoic acid (ATRA), which functions as a ligand for a family of nuclear transcription factors, the retinoic acid receptors (RARs). Eccentric cleavage of β-carotene at non-central double bonds is catalyzed by other enzymes and can also occur non-enzymatically. The products of these reactions are β-apocarotenals and β-apocarotenones, whose biological functions in mammals are unknown. We used reporter gene assays to show that none of the β-apocarotenoids significantly activated RARs. Importantly, however, β-apo-14′-carotenal, β-apo-14′-carotenoic acid, and β-apo-13-carotenone antagonized ATRA-induced transactivation of RARs. Competitive radioligand binding assays demonstrated that these putative RAR antagonists compete directly with retinoic acid for high affinity binding to purified receptors. Molecular modeling studies confirmed that β-apo-13-carotenone can interact directly with the ligand binding site of the retinoid receptors. β-Apo-13-carotenone and the β-apo-14′-carotenoids inhibited ATRA-induced expression of retinoid responsive genes in Hep G2 cells. Finally, we developed an LC/MS method and found 3–5 nm β-apo-13-carotenone was present in human plasma. These findings suggest that β-apocarotenoids function as naturally occurring retinoid antagonists. The antagonism of retinoid signaling by these metabolites may have implications for the activities of dietary β-carotene as a provitamin A and as a modulator of risk for cardiovascular disease and cancer. PMID:22418437

  19. Spitzer observations of M33 and the hot star, HII region connection

    NASA Astrophysics Data System (ADS)

    Rubin, Robert H.; Simpson, Janet P.; Colgan, Sean W. J.; Dufour, Reginald J.; Brunner, Gregory; McNabb, Ian A.; Pauldrach, Adalbert W. A.; Erickson, Edwin F.; Haas, Michael R.; Citron, Robert I.

    2008-06-01

    We have observed emission lines of [SIV] 10.51, H(7-6) 12.37, [NeII] 12.81, [NeIII] 15.56 and [SIII] 18.71 μm in a number of extragalactic HII regions with the Spitzer Space Telescope. A previous paper presented our data and analysis for the substantially face-on spiral galaxy M83. Here we report our results for the Local Group spiral galaxy M33. The nebulae selected cover a wide range of galactocentric radii (RG). The observations were made with the Infrared Spectrograph with the short wavelength, high-resolution module. The above set of five lines is observed cospatially, thus permitting a reliable comparison of the fluxes. From the measured fluxes, we determine the ionic abundance ratios including Ne++/Ne+, S3+/S++, and S++/Ne+ and find that there is a correlation of increasingly higher ionization with larger RG. By sampling the dominant ionization states of Ne (Ne+, Ne++) and S (S++, S3+) for HII regions, we can estimate the Ne/H, S/H and Ne/S ratios. We find from linear least-squares fits that there is a decrease in metallicity with increasing RG: dlog(Ne/H)/dRG = -0.058 +/- 0.014 and dlog(S/H)/dRG = -0.052 +/- 0.021 dex kpc-1. There is no apparent variation in the Ne/S ratio with RG. Unlike our previous similar study of M83, where we conjectured that this ratio was an upper limit, for M33 the derived ratios are likely a robust indication of Ne/S. This occurs because the HII regions have lower metallicity and higher ionization than those in M83. Both Ne and S are primary elements produced in α-chain reactions, following C and O burning in stars, making their yields depend very little on the stellar metallicity. Thus, it is expected that the Ne/S ratio remains relatively constant throughout a galaxy. The median (average) Ne/S ratio derived for HII regions in M33 is 16.3 (16.9), just slightly higher than the Orion Nebula value of 14.3. The same methodology is applied to Spitzer observations recently published for three massive HII regions: NGC 3603 (Milky Way

  20. Observations of M33 H II Regions: the Ne/S ratio, metallicity, and ionization variations

    NASA Astrophysics Data System (ADS)

    Rubin, R. H.; Simpson, J. P.; McNabb, I. A.; Brunner, G.; Colgan, S. W. J.; Dufour, R. J.; Pauldrach, A. W. A.; Browne, A. D.; Zhang, R.; Csongradi, E. J.

    2009-01-01

    We have observed emission lines of [S IV] 10.51, H(7--6) 12.37, [Ne II] 12.81, [Ne III] 15.56, and [S III] 18.71 μm in a number of extragalactic H II regions with the Spitzer Space Telescope. A previous paper presented our data and analysis for the substantially face-on spiral galaxy M83. Here we report our results for the local group spiral galaxy M33. The nebulae selected cover a wide range of galactocentric radii (R_G). The observations were made with the Infrared Spectrograph with the short wavelength, high resolution module. The above set of five lines is observed cospatially, thus permitting a reliable comparison of the fluxes. From the measured fluxes, we determine the ionic abundance ratios including Ne++/Ne^+, S3+/S++, and S++/Ne^+ and find that there is a correlation of increasingly higher ionization with larger R_G. By sampling the dominant ionization states of Ne (Ne^+, Ne++) and S (S++, S3+) for H II regions, we can estimate the Ne/H, S/H, and Ne/S ratios. We find that there is a decrease in metallicity with increasing R_G. There is no apparent variation in the Ne/S ratio with R_G. Unlike our previous similar study of M83, where we conjectured that this ratio was an upper limit, for M33 the derived ratios are likely a robust indication of Ne/S. This occurs because the H II regions have lower metallicity and higher ionization than those in M83. Both Ne and S are primary elements produced in α-chain reactions, following C and O burning in stars, making their yields depend very little on the stellar metallicity. Thus, it is expected that Ne/S remains relatively constant throughout a galaxy. The median (average) Ne/S ratio derived for H II regions in M33 is 16.3 (16.9), just slightly higher than the Orion Nebula value of 14.3. These values are in sharp contrast with the much lower ``canonical", but controversial, solar value of ˜5. A recent nucleosynthesis, galactic chemical evolution model predicts a Ne/S abundance of ˜9. Our observations may also be

  1. A naturally occurring GIP receptor variant undergoes enhanced agonist-induced desensitization, which impairs GIP control of adipose insulin sensitivity.

    PubMed

    Mohammad, Sameer; Patel, Rajesh T; Bruno, Joanne; Panhwar, Muhammad Siyab; Wen, Jennifer; McGraw, Timothy E

    2014-10-01

    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.

  2. T Cell Receptor-induced Activation and Apoptosis In Cycling Human T Cells Occur throughout the Cell Cycle

    PubMed Central

    Karas, Michael; Zaks, Tal Z.; JL, Liu; LeRoith, Derek

    1999-01-01

    Previous studies have found conflicting associations between susceptibility to activation-induced cell death and the cell cycle in T cells. However, most of the studies used potentially toxic pharmacological agents for cell cycle synchronization. A panel of human melanoma tumor-reactive T cell lines, a CD8+ HER-2/neu-reactive T cell clone, and the leukemic T cell line Jurkat were separated by centrifugal elutriation. Fractions enriched for the G0–G1, S, and G2–M phases of the cell cycle were assayed for T cell receptor-mediated activation as measured by intracellular Ca2+ flux, cytolytic recognition of tumor targets, and induction of Fas ligand mRNA. Susceptibility to apoptosis induced by recombinant Fas ligand and activation-induced cell death were also studied. None of the parameters studied was specific to a certain phase of the cell cycle, leading us to conclude that in nontransformed human T cells, both activation and apoptosis through T cell receptor activation can occur in all phases of the cell cycle. PMID:10588669

  3. 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.

  4. 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).

  5. 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.

  6. 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...

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

    SciTech Connect

    Ma Jun

    2012-08-15

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

  8. Endocytosis and ligand dissociation and degradation mediated by the hepatic galactosyl receptor occur via two different pathways

    SciTech Connect

    Weigel, P.H.; Clarke, B.L.; Oka, J.A.

    1986-05-01

    Isolated rat hepatocytes express two distinct populations of surface Galactosyl receptor activity, measured by the binding of /sup 125/I-asialo-orosomucoid (ASOR), which they designate State 1 and State 2. Freshly isolated cells express only state 1 receptors. Cells equilibrated at 37/sup 0/C also express State 2 receptors, which represent 50-80% of the total surface activity. In the absence of ligand, State 2 receptor activity is reversibly decreased by metabolic energy poisons, low temperature and microtubule drugs, whereas State 1 receptor activity is unaffected. Endocytosis of /sup 125/I-ASOR by State 1 receptors is followed by a slow dissociation of /sup 125/I-ASOR from receptor but the immediate release of acid soluble degradation products. In contrast, State 2 receptors mediate endocytosis which involves a rapid dissociation step but a 20 min lag, prior to the release of degradation products. Both pathways follow first order kinetics and are functional under steady state conditions indicating coordinated receptor recycling. Degradation mediated by both pathways is inhibited by leupeptin and chloroquine. The State 1 and 2 pathways can be further differentiated by the greater sensitivity of the latter to microtubule drugs. These results suggest that there are either structurally different native receptors or that identical receptors are directed into two different functional pathways, for example by interaction with different types of coated pits.

  9. The J-PLUS survey: understanding the formation and evolution of M 33

    NASA Astrophysics Data System (ADS)

    San Roman, I.; Marín-Franch, A.; Ederoclite, A.; Cenarro, A. J.; Vázquez-Ramió, H.; J-PLUS Team

    2015-05-01

    It is widely accepted that large disk galaxies derive from the merger and accretion of many smaller subsystems. However, it is less clear how low-mass spiral galaxies fit into this picture. The best way to answer this question is to study the nearest example of a dwarf spiral galaxy, M 33. We propose to perform a detailed photometric analysis of the resolved and unresolved stellar population of M 33 using data from the Javalambre Photometric Local Universe Survey (J-PLUS). Using a set of 12 broad-, intermediate- and narrow-band filters, J-PLUS will cover a wavelength range between 330-1000 nm, reaching magnitudes of r ˜ 22. We will take advantage of the IFU-like capabilities of the survey to determine the properties of the spatially resolved and unresolved components of the galaxy. In particular, we will perform a 2-D analysis of the underlying population as well as a detailed study of M 33 star cluster system. Spectral fitting diagnostics of the resolved and unresolved populations will allow us to determine ages, metallicities and masses of the galactic disk, spheroidal components and cluster system. We will analyze two regions covering a total area of 3.2 deg^{2}. One field will be centered on M 33 covering the disk and the outskirts. A second field will cover the line connecting M 33 with M 31 to map the stellar substructure surrounding M 33. This study will provide key insights into the star formation history of low-mass galaxies as well as place M 33 within the context of galaxy formation process.

  10. The X-ray Source Population of M33 as seen by XMM-Newton

    NASA Astrophysics Data System (ADS)

    Garofali, Kristen; Williams, Benjamin F.; Wold, Brian; Haberl, Frank; Blair, William P.; Gaetz, Terrance J.; Kuntz, K. D.; Long, Knox S.; Pannuti, Thomas; Pietsch, Wolfgang; Plucinsky, Paul P.; Winkler, P. Frank

    2015-01-01

    We present results from the deepest survey of M33 with XMM-Newton to date. The survey consists of 8 overlapping EPIC fields covering an area beyond the D25 isophote down to a limiting sensitivity of L(0.2-4.5 keV) > 4e+34 erg/s. This larger field of view coupled with the higher soft sensitivity of XMM-Newton provides an excellent complement to the Chandra ACIS Survey of M33 (ChASeM33). Comparison of our source catalog with the Chandra survey allows us to identify variable sources as well as previously undetected soft sources. Our coverage of the full M33 disk reveals many new sources including SNRs previously undetected in X-rays. The radial coverage extends far enough to provide high-quality background statistics, including a radial density distribution of bright sources which suggests that roughly 15% of sources with L > 3.6e+35 erg/s are likely to be associated with M33. The accurate background statistics allow us to perform a simultaneous fit of our background and observed luminosity functions, which yields a slope consistent with the presence of a significant population of HMXBs. The combined XMM-Newton and Chandra data will allow the most detailed study of the X-ray population of a late-type spiral possible with currently-available facilities. We will show preliminary work in studying new HMXB candidates using HST.

  11. The X-ray Source Population of M33 as seen by XMM-Newton

    NASA Astrophysics Data System (ADS)

    Garofali, Kristen

    2014-08-01

    We present results from a deep XMM-Newton survey of M33 consisting of 8 pointings extending beyond the D25 isophote sensitive to L(0.2-4.5 keV) > 4e+34 erg/s. The large area coupled with the XMM soft response complement the deep Chandra Survey of M33. Cross-correlation of the surveys allows us to identify variable sources and previously undetected soft sources. Our coverage reveals many new sources including at least one previously unclassified SNR. The radial coverage provides high-quality background statistics, including a radial density distribution of sources that suggests roughly 15% (~60) of sources with inferred L > 3.6e+35 erg/s are in M33. Our background-corrected log(N)--log(S) reveals a relatively flat power law index (0.3-0.7) consistent with a substantial population of HMXBs.

  12. Naturally occurring amino acid substitutions at Arg1174 in the human insulin receptor result in differential effects on receptor biosynthesis and hybrid formation, leading to discordant clinical phenotypes.

    PubMed

    Rau, H; Kocova, M; O'Rahilly, S; Whitehead, J P

    2000-07-01

    Missense mutations in the tyrosine kinase domain of the human insulin receptor frequently result in a dominantly inherited form of insulin resistance. We noted a marked disparity in the clinical phenotypes of our study subjects with different missense mutations at the same residue (Arg1174) of the insulin receptor. Subjects with a tryptophan substitution (W) were only moderately hyperinsulinemic, whereas those with a glutamine substitution (Q) had severe clinical and biochemical insulin resistance. Studies were undertaken to explore the molecular mechanisms underlying these differences. Both W and Q mutant receptors bound insulin normally but were kinase inactive. The W mutation resulted in more rapid degradation of newly synthesized mutant receptor, which contrasted with the near-normal biosynthesis of the Q receptor. The propensity of the W receptor to form hybrids with the cotransfected wild-type (WT) receptor was also markedly impaired compared with the Q receptor, to an extent greater than could be explained by lower steady-state expression. Thus, the more clinically benign consequences of the heterozygous W mutant receptor are likely to relate to its impaired biosynthesis and/or reduced capacity to form hybrids with WT receptors. In addition to providing an explanation for the milder phenotype of 1174W versus 1174Q carriers, these studies provide further support for the notion that the dominant-negative effect of insulin receptor tyrosine kinase mutations involves the competition between inactive mutant homodimers and WT/mutant hybrids with active WT homodimers for both ligands and intracellular substrates.

  13. 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.

  14. Flat-spectrum radio source C1 in M33 is a background radio galaxy

    SciTech Connect

    Reynolds, S.P.; Fix, J.D.

    1988-10-01

    A candidate Crab-like supernova remnant in M33 discovered in a high-resolution survey of compact radio sources (Reynolds and Fix, 1987) has been observed. VLA observations at 1465 and 4885 MHz show that it is simply the flat-spectrum core of a completely normal double-lobed radio galaxy. This eliminates the last candidate Crab-like object in M33 whose size and brightness do not at all resemble those of the Crab Nebula, and confirms the dearth of Crab-like supernova remnants reported earlier. 7 references.

  15. VizieR Online Data Catalog: The M33 synoptic stellar survey. I. (Pellerin+, 2011)

    NASA Astrophysics Data System (ADS)

    Pellerin, A.; Macri, L. M.

    2011-05-01

    The DIRECT project obtained BVI observations of M33 over ~200 nights between 1996 September and 1999 November. Most of the survey was carried out at the F.L. Whipple Observatory (FLWO) 1.2m telescope on Mount Hopkins, Arizona, with additional images obtained at the Michigan-Dartmouth-MIT 1.3m telescope on Kitt Peak, Arizona. The project observed 11 different fields, each 11.5'x11.5' in size, which covered most of the M33 disk (see Figure 1). We collected additional images at the WIYN 3.5m telescope between 2002 August and 2006 December. (5 data files).

  16. 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.

  17. Structure of the human histamine H3 receptor gene (HRH3) and identification of naturally occurring variations.

    PubMed

    Wiedemann, P; Bönisch, H; Oerters, F; Brüss, M

    2002-04-01

    Neurotransmitter release is modulated by presynaptic histamine H(3) receptors located on histaminergic, noradrenergic and other nonhistaminergic neurons of the central and peripheral nervous system. Here, we report the determination of the structure of the human histamine H(3) receptor gene (HRH3) and the identification of a missense mutation (Ala280Val) in a patient with Shy-Drager syndrome. The coding region of the gene consists of three exons interrupted by two introns of approximately 1 kb in size. Exon boundaries only partly correspond to transmembrane domain organization. The homozygous Ala280Val variation in the third intracellular loop of the histamine H(3) receptor of a patient with Shy-Drager syndrome may be related to the etiology of the illness due to altered norepinephrine release. Furthermore, knowledge of the gene structure allows the verification of alternative splicing of the receptor. The corresponding histamine H(3) receptor isoforms as reported for the guinea pig and rat histamine H(3) receptor in different brain regions are not found in the human brain.

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

    PubMed

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

    2013-05-09

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

  19. 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...

  20. 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.

  1. Decreased agonist, but not antagonist, binding to the naturally occurring Thr92Lys variant of the h5-HT7(a) receptor.

    PubMed

    Brüss, Michael; Kiel, Sibylle; Bönisch, Heinz; Kostanian, Arevat; Göthert, Manfred

    2005-08-01

    In the present study on transfected human embryonic kidney (HEK)293 cells, we aimed at establishing whether expression of the naturally occurring Thr92Lys variation of the Gs-coupled h5-HT7(a) receptor leads to changes of ligand binding properties, of agonist-evoked cAMP formation and/or of antagonist-mediated blockade of the latter. Binding of [3H]5-carboxamidotryptamine ([3H]5-CT) to membranes and stimulated [3H]cAMP accumulation in whole cells were determined. Saturation binding experiments in membranes of transiently transfected cells expressing either the wild-type or the variant receptor revealed a single binding site in both cases and no difference in Bmax between both receptor isoforms. In competition binding experiments in membranes of stably transfected cells, the Thr92Lys variant exhibited a 2.8-11 times lower binding affinity of the ligands 5-hydroxytryptamine (5-HT), 5-CT, 5-methoxy-3-(1,2,3,6-tetrahydropyridin-4yl)-1H-indole (RU24969), (+/-)-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT) and sumatriptan compared to the wild-type receptor. However, the variant did not differ from the wild-type with respect to the binding properties of the antagonists (R)-3-(2-(2-(4-methylpiperidin-1-yl)ethyl)-pyrrolodine-1-sulfonyl)phenol hydrochloride (SB-269970), risperidone, mesulergine and clozapine. In agreement with the decreased binding affinity of 5-HT, 5-CT, RU24969 and 8-OH-DPAT for the variant receptor, these agonists were less potent in stimulating [3H]cAMP accumulation in cells stably expressing the Thr92Lys h5-HT7(a) receptor. Sumatriptan did not stimulate cAMP accumulation in spite of its affinity for both receptor isoforms pointing to a putative weak antagonistic property of this drug at the h5-HT7 receptor. SB-269970 and clozapine were equipotent at both the variant and the wild-type receptor in producing a rightward shift of the 5-HT concentration-response curve for its stimulant effect on [3H]cAMP accumulation. In view of, e.g., the

  2. A detailed view of a molecular cloud in the far outer disk of M 33. Molecular cloud formation in M 33

    NASA Astrophysics Data System (ADS)

    Braine, J.; Gratier, P.; Contreras, Y.; Schuster, K. F.; Brouillet, N.

    2012-12-01

    The amount of H2 present in spiral galaxies remains uncertain, particularly in the dim outer regions and in low-metallicity environments. We present high-resolution CO(1-0) observations with the Plateau de Bure interferometer of the most distant molecular cloud in the local group galaxy M 33. The cloud is a single entity rather than a set of smaller clouds within the broad beam of the original single-dish observations. The interferometer and single-dish fluxes are very similar and the line widths are indistinguishable, despite the difference in beamsize. At a spatial resolution of 10 pc, beyond the optical radius of the M 33, the CO brightness temperature reaches 2.4 Kelvins. A virial mass estimate for the cloud yields a mass of 4.3 × 104 M⊙ and a ratio N(H2)/ICO(1-0) ≃ 3.5 × 1020 cm-2/(K km s-1). While no velocity gradient is seen where the emission is strong, the velocity is redshifted to the extreme SW and blue-shifted to the far NE. If the orientation of the cloud is along the plane of the disk (i.e. not perpendicular), then these velocities correspond to slow infall or accretion. The rather modest infall rate would be about 2 × 10-4 M⊙ yr-1. Based on observations carried out with the IRAM Plateau de Bure Interferometer. IRAM is supported by INSU/CNRS (France), MPG (Germany) and IGN (Spain).Data cube in FITS files is only available at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/548/A52

  3. Disruption and reformation of the acetylcholine receptor clusters of cultured rat myotubes occur in two distinct stages.

    PubMed

    Pumplin, D W; Bloch, R J

    1987-01-01

    We have examined the redistribution of acetylcholine receptor (AChR) intramembrane particles (IMPs) when AChR clusters of cultured rat myotubes are experimentally disrupted and allowed to reform. In control myotubes, the AChR IMPs are evenly distributed within the AChR domains of cluster membrane. Shortly after addition of azide to disrupt clusters, IMPs become unevenly scattered, with some microaggregation. After longer treatment, IMPs are depleted from AChR domains with no further change in IMP distribution. Contact domains of clusters are relatively poor in IMPs both before and after cluster dispersal. Upon visualization with fluorescent alpha-bungarotoxin, some AChR in azide-treated samples appear as small, bright spots. These spots do not correspond to microaggregates seen in freeze-fracture replicas, and probably represent receptors that have been internalized. The internalization rate is insufficient to account completely for the loss of IMPs from clusters, however. During reformation of AChR clusters upon removal of azide, IMP concentration in receptor domains increases. At early stages of reformation, IMPs appear in small groups containing compact microaggregates. At later times, AChR domains enlarge and IMPs within them assume the evenly spaced distribution characteristic of control clusters. These observations suggest that the disruption of clusters is accompanied by mobilization of AChR from a fixed array, allowing AChR IMPs to diffuse away from the clusters, to form microaggregates, and to become internalized. Cluster reformation appears to be the reverse of this process. Our results are thus consistent with a two-step model for AChR clustering, in which the concentration of IMPs into a small membrane region precedes their rearrangement into evenly spaced sites.

  4. Spectroscopy of luminous blue stars in M31 and M33

    SciTech Connect

    Humphreys, R.M.; Massey, P.; Freedman, W.L. Kitt Peak National Observatory, Tucson, AZ Mount Wilson and Las Campanas Observatories, Pasadena, CA )

    1990-01-01

    Spectra have been obtained for classification of 42 candidate supergiants and 12 probable OB stars in M31 and eight early-type stars in M33. Twenty-six of those in M31 and six in M33 are confirmed as apparent single members with spectral types ranging from O8 to F8. Their interstellar extinction and luminosities are derived from published photographic and CCD photometry for all of the confirmed members. The preliminary and still incomplete HR diagram obtained for M31 shows an apparent lack of the most massive stars, stars with initial masses greater than 60 solar masses. The effects of incompleteness and observational selection on the interpretation of this HR diagram are discussed. 42 refs.

  5. Point and Condensed Hα Sources in the Interior of M33

    NASA Astrophysics Data System (ADS)

    Moody, J. Ward; Hintz, Eric G.; Roming, Peter; Joner, Michael D.; Bucklein, Brian

    2017-01-01

    A variety of interesting objects such as Wolf-Rayet stars, tight OB associations, planetary nebula, x-ray binaries, etc. can be discovered as point or condensed sources in Hα surveys. How these objects distribute through a galaxy sheds light on the galaxy star formation rate and history, mass distribution, and dynamics. The nearby galaxy M33 is an excellent place to study the distribution of Hα-bright point sources in a flocculant spiral galaxy. We have reprocessed an archived WIYN continuum-subtracted Hα image of the inner 6.5' of the nearby galaxy M33 and, employing both eye and machine searches, have tabulated sources with a flux greater than 1 x 10-15 erg cm-2sec-1. We have identified 152 unresolved point sources and 122 marginally resolved condensed sources, 38 of which have not been previously cataloged. We present a map of these sources and discuss their probable identifications.

  6. Microarcsecond proper motions of extragalactic water vapor masers in M33

    NASA Technical Reports Server (NTRS)

    Greenhill, L. J.; Moran, J. M.; Reid, M. J.; Menten, K. M.; Hirabayashi, H.

    1993-01-01

    A second-epoch spectral line VLBI synthesis map of the H2O maser associated with the H II region IC 133 in the galaxy M33 is presented. Thirty-two spatially distinct maser features were identified, and a second center of maser activity within the IC 133 complex, IC 133 West, which is displaced about 0.3 arcsec from IC 133 Main, was discovered. A comparison of the two available maps of IC 133 is used to estimate the right ascension components of proper motion over a period of 479 d for five maser features to accuracies of between 7 and 16 micro-as. The dispersions in transverse and radial velocities for the maser features are consistent with the accepted distance to M33 of 720 kpc, where the data admit a fractional uncertainty in distance of 50 percent.

  7. Sesamin: A Naturally Occurring Lignan Inhibits CYP3A4 by Antagonizing the Pregnane X Receptor Activation.

    PubMed

    Lim, Yun-Ping; Ma, Chia-Yun; Liu, Cheng-Ling; Lin, Yu-Hsien; Hu, Miao-Lin; Chen, Jih-Jung; Hung, Dong-Zong; Hsieh, Wen-Tsong; Huang, Jin-Ding

    2012-01-01

    Inconsistent expression and regulation of drug-metabolizing enzymes (DMEs) are common causes of adverse drug effects in some drugs with a narrow therapeutic index (TI). An important cytochrome, cytochrome P450 3A4 (CYP3A4), is predominantly regulated by a nuclear receptor, pregnane X receptor (PXR). Sesamin, a major lignan constituent in sesame seeds and oil, exhibits a variety of biological functions; however, the effect of sesamin on the modulation of CYP3A4 is not well understood. In this study, the effects of sesamin on the PXR-CYP3A4 pathway were characterized, as well as the underlying mechanisms of those effects. Sesamin potently attenuated CYP3A4 induction in a dose-dependent manner by blocking the activation of PXR. The PXR inducer-mediated inhibition of CYP3A4 was further evidenced by the ability of sesamin to attenuate the effects of several PXR ligands in the CYP3A4 reporter assay. Further mechanistic studies showed that sesamin inhibited PXR by interrupting the interacting with coregulators. These results may lead to the development of new therapeutic and dietary approaches to reduce the frequency of inducer-drug interaction. Sesamin was established as a novel inhibitor of PXR and may be useful for modulating DMEs expression and drug efficacies. Modification of CYP3A4 expression and activity by consumption of sesamin may have important implications for drug safety.

  8. 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.

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

    SciTech Connect

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

    2009-10-20

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

  10. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  12. VizieR Online Data Catalog: M33 WR and Of-type Stars (Neugent+, 2014)

    NASA Astrophysics Data System (ADS)

    Neugent, K. F.; Massey, P.

    2017-03-01

    Our ability to undertake this project was in a large part due to the existence of the multi-object fiber-fed spectrograph Hectospec (Fabricant et al. 2005PASP..117.1411F) on the 6.5 m MMT. Its large field of view (1° in diameter) was well matched to our survey areas of M31 and M33. Hectospec's 300 fibers and their allowed close spacing (20'') let us observe a multitude of candidates using only four pointing configurations. We were assigned 2.5 nights of dark time in the Fall of 2012 through NOAO (2012B-0129). When designing the fiber configurations, we were able to assign 71% of our M31 WRs using two configurations and 77% of our M33 WRs using an additional two configurations, making a total of four configurations. We were able to observe five of the remaining M33 candidates as part of the present study, and recently obtained spectra of the sixth star as part of our follow-up study of the binaries we identify here. (1 data file).

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

    SciTech Connect

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

    2015-02-10

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

  14. 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.

  15. 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

  16. 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

  17. Role of CCK-A receptor in the regulation of pancreatic bicarbonate secretion in conscious rats: a study in naturally occurring CCK-A receptor gene knockout rats.

    PubMed

    Miyasaka, K; Suzuki, S; Kanai, S; Masuda, M; Funakoshi, A

    1999-10-01

    Whether cholecystokinin (CCK) has a direct action on duct cells and the role of CCK-A receptor in bicarbonate secretion were examined by comparing the results obtained from OLETF (CCK-A receptor-deficient rats) and control (LETO) rats. Rats were prepared with cannulae for draining bile and pancreatic juice separately, with two duodenal cannulae and an external jugular vein cannula. The experiments were conducted without anesthesia. The responses of bicarbonate secretion to intravenous infusion of CCK, acetyl-beta-methylcholine (Ach), and 2-deoxy-D-glucose (2DG), and to intraduodenal infusion of HCl and a liquid meal were examined. To examine the synergistic effect between CCK and secretin, the effect of CCK during a background secretin infusion was examined in LETO rats. CCK did not stimulate bicarbonate secretion in either strain, nor in LETO rats with secretin infusion. When gastric acid secretion was prevented by administration of omeprazole, Ach did not increase bicarbonate secretion, but 2DG did in both strains. Intraduodenal infusion of HCI and a liquid meal significantly increased bicarbonate secretion in both strains; however, the responses were much less in OLETF than LETO rats. In conclusion, intravenous injection of CCK did not stimulate bicarbonate secretion, and the lack of CCK-A receptor decreased bicarbonate secretion in response to luminal stimulants.

  18. THE M31 VELOCITY VECTOR. III. FUTURE MILKY WAY M31-M33 ORBITAL EVOLUTION, MERGING, AND FATE OF THE SUN

    SciTech Connect

    Van der Marel, Roeland P.; Sohn, Sangmo Tony; Anderson, Jay; Besla, Gurtina; Cox, T. J.

    2012-07-01

    We study the future orbital evolution and merging of the Milky Way (MW)-M31-M33 system, using a combination of collisionless N-body simulations and semi-analytic orbit integrations. Monte Carlo simulations are used to explore the consequences of varying all relevant initial phase-space and mass parameters within their observational uncertainties. The observed M31 transverse velocity from Papers I and II implies that the MW and M31 will merge t = 5.86{sup +1.61}{sub -0.72} Gyr from now. The first pericenter occurs at t = 3.87{sup +0.42}{sub -0.32} Gyr, at a pericenter distance of r = 31.0{sup +38.0}{sub -19.8} kpc. In 41% of Monte Carlo orbits, M31 makes a direct hit with the MW, defined here as a first-pericenter distance less than 25 kpc. For the M31-M33 system, the first-pericenter time and distance are t = 0.85{sup +0.18}{sub -0.13} Gyr and r = 80.8{sup +42.2}{sub -31.7} kpc. By the time M31 gets to its first pericenter with the MW, M33 is close to its second pericenter with M31. For the MW-M33 system, the first-pericenter time and distance are t = 3.70{sup +0.74}{sub -0.46} Gyr and r = 176.0{sup +239.0}{sub -136.9} kpc. The most likely outcome is for the MW and M31 to merge first, with M33 settling onto an orbit around them that may decay toward a merger later. However, there is a 9% probability that M33 makes a direct hit with the MW at its first pericenter, before M31 gets to or collides with the MW. Also, there is a 7% probability that M33 gets ejected from the Local Group, temporarily or permanently. The radial mass profile of the MW-M31 merger remnant is significantly more extended than the original profiles of either the MW or M31, and suggests that the merger remnant will resemble an elliptical galaxy. The Sun will most likely ({approx}85% probability) end up at a larger radius from the center of the MW-M31 merger remnant than its current distance from the MW center, possibly further than 50 kpc ({approx}10% probability). There is a {approx}20

  19. The HII Regions and OB Stars of M33 and NCG 6822.

    NASA Astrophysics Data System (ADS)

    Patel, Kanan

    1995-01-01

    We have used Hα and photometric data for two morphologically distinct Local Group galaxies, the spiral M33 and dwarf irregular NGC 6822, to study the distribution of the luminous blue O and B (OB) stars and HII regions in the galaxies as well as to determine whether individual regions of the galaxies are separately and/or collectively in a state of ionization balance. In the case of M33, we have concentrated on the inner 1 kpc region of the galaxy. Using the H alpha data, three distinct ionized gas environments (bright, halo and field) defined by the surface brightness of the Hα emission have been identified. We find that ~50% of the OB stars are located in the field, so that 1/2 of the lifetime of OB stars must be spent outside recognizable HII regions. We show that a possible origin for the large field OB population is that they were born in and subsequently percolated out of the ~10 ^3 giant molecular clouds with masses _sp{~}>10 ^3Modot predicted to exist within the inner kpc of the galaxy. Using UBV photometry and stellar ionization models, we predict Hα fluxes in the bright, halo and field regions. Our findings suggest that star formation rates obtained from luminosities must underestimate the true star formation rate within the inner region of M33. In the case of NGC 6822, four distinct components of the Hα emission (bright, halo, diffuse and field) differentiated by their surface brightnesses have been identified. We find that only 1/4 of the OB stars are found in the combined bright halo regions, suggesting that OB stars spend roughly 3/4 of their lifetimes outside "classical" HII regions. Molecular cloud lifetimes after forming OB stars could be as low as ~1 -3 times 10^6 yrs or 1/4 the typical main sequence lifetimes of OB stars if stars escape from bright HII regions by destroying their parent clouds. Additionally, the field population of OB stars cannot have originated in and percolated out of existing HII regions. Comparing the observed H

  20. Heredity and cardiometabolic risk: naturally occurring polymorphisms in the human neuropeptide Y2 receptor promoter disrupt multiple transcriptional response motifs

    PubMed Central

    Wei, Zhiyun; Zhang, Kuixing; Wen, Gen; Balasubramanian, Karthika; Shih, Peian B.; Rao, Fangwen; Friese, Ryan S.; Miramontes-Gonzalez, Jose P.; Schmid-Schoenbein, Geert W.; Kim, Hyung-Suk; Mahata, Sushil K.; O’Connor, Daniel T.

    2013-01-01

    Objectives The neuropeptide Y2 G-protein-coupled receptor (NPY2R) relays signals from PYY or neuropeptide Y toward satiety and control of body mass. Targeted ablation of the NPY2R locus in mice yields obesity, and studies of NPY2R promoter genetic variation in more than 10 000 human participants indicate its involvement in control of obesity and BMI. Here we searched for genetic variation across the human NPY2R locus and probed its functional effects, especially in the proximal promoter. Methods and results Twin pair studies indicated substantial heritability for multiple cardiometabolic traits, including BMI, SBP, DBP, and PYY, an endogenous agonist at NPY2R. Systematic polymorphism discovery by resequencing across NPY2R uncovered 21 genetic variants, 10 of which were common [minor allele frequency (MAF) >5%], creating one to two linkage disequilibrium blocks in multiple biogeographic ancestries. In vivo, NPY2R haplotypes were associated with both BMI (P =3.75E–04) and PYY (P =4.01E–06). Computational approaches revealed that proximal promoter variants G-1606A, C-599T, and A-224G disrupt predicted IRF1 (A>G), FOXI1 (T>C), and SNAI1 (A>G) response elements. In neuroendocrine cells transfected with NPY2R promoter/luciferase reporter plasmids, all three variants and their resulting haplotypes influenced transcription (G-1606A, P <2.97E–06; C-599T, P <1.17E–06; A-224G, P <2.04E–06), and transcription was differentially augmented or impaired by coexpression of either the cognate full-length transcription factors or their specific siRNAs at each site. Endogenous expression of transcripts for NPY2R, IRF1, and SNAI1 was documented in neuroendocrine cells, and the NPY2R mRNA was differentially expressed in two neuroendocrine tissues (adrenal gland, brainstem) of a rodent model of hypertension and the metabolic syndrome, the spontaneously hypertensive rat. Conclusion We conclude that common genetic variation in the proximal NPY2R promoter influences transcription

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. A Search for Miras in M33 Using Sparsely-Sampled Time Series Photometry

    NASA Astrophysics Data System (ADS)

    Yuan, Wenlong; Macri, Lucas M.; He, Shiyuan; Long, James; Huang, Jianhua

    2017-01-01

    The Mira Period-Luminosity relations (PLRs) at near- and mid-infrared wavelengths are promising distance indicators, with brighter absolute magnitudes than Cepheids, comparable PLR dispersions and ubiquitous presence in all galaxy types. We developed a semi-parametric Gaussian process periodogram method for sparsely-sampled Mira light curves and applied it to I-band observations of M33. We discovered more than 1800 Miras, which were subsequently classified using machine-learning techniques. We present an overview of the Gaussian process model, the Random Forest classifiers, and the resulting PLRs.

  8. New quasar survey with WIRO: Color-selection of quasar candidates behind M33

    NASA Astrophysics Data System (ADS)

    Harvey, William Bradford; Bassett, Neil; Deam, Sophie; Dixon, Don; Griffith, Emily; Lee, Daniel; Lyke, Bradley; Haze Nunez, Evan; Parziale, Ryan; Witherspoon, Catherine; Myers, Adam D.; Findlay, Joseph; Kobulnicky, Henry A.; Dale, Daniel A.

    2017-01-01

    We report new quasar candidates in the extended gaseous region of the Triangulum (M33) Galaxy as observed with WIRO (The Wyoming Infrared Observatory) in the ugri bands during the Summer of 2016. Our survey produced a sample of 14042 point sources to a limiting depth of g ≤ 21.7 in a region of ~16 square degrees, 34 of which are UVX-selected, known quasars with redshifts up to z < 2.2. Color-color plots were created using extinction-corrected magnitudes of ugri as well as NUV and W1 as taken from GALEX (Galaxy Evolution Explorer) and WISE (Wide-field Infrared Survey Explorer) respectively. Using a series of color cuts in NUV, u, g, r, i, and W1 bands, we recover high-quality quasar candidates. Based on optical colors alone we project ~30 new candidates per square degree. Spectroscopic follow-up of these candidates could yield new, bright quasars behind M33. This work is supported by the National Science Foundation under REU grant AST 1560461.

  9. Uv Observations of the Hubble-Sandage Variables in M31 and M33

    NASA Astrophysics Data System (ADS)

    Humphreys, Roberta

    1991-07-01

    The Hubble-Sandage variables in M31 and M33 are luminous blue variables (LBVs) -- very luminous, eruptively unstable stars in the same general class as S Dor, Eta Car, and P Cyg. UV observations of H-S variables will significantly enhance the limited information available to us concerning the evolution and structure of the most massive stars. ---- LBVs are important in several major astrophysical connections and are only beginning to be understood. Since the LBV stage of evolution is brief, only a few examples are available in our Galaxy and in the Magellanic Clouds, close enough for UV observations with IUE. Therefore our coverage of the wide parameter space embraced by LBVs has been so sparse that theoretical development has been hindered. ---- With the ST, we can significantly increase this coverage by adding the H-S variables in M31 and M33 to the set of "useful" LBVs. UV spectroscopy is needed to determine their temperatures, luminosities, and mass-loss rates. These parameters are required to clarify their relations to other LBVs and very massive stars in general, and to provide more information on evolutionary origin of LBVs, physical causes of the violent eruptions, and other problems.

  10. New quasar surveys with WIRO: UV variability of known quasars behind M33

    NASA Astrophysics Data System (ADS)

    Deam, Sophie; Bassett, Neil; Dixon, Don; Griffith, Emily; Harvey, William Bradford; Lee, Daniel; Lyke, Bradley; Haze Nunez, Evan; Parziale, Ryan; Witherspoon, Catherine; Myers, Adam D.; Findlay, Joseph; Kobulnicky, Henry A.; Dale, Daniel A.

    2017-01-01

    Bright quasars are of particular interest when detected through the extended gaseous regions of local galaxies. Spectroscopy of UV-bright quasars, in particular, can be used to map the properties of the gas surrounding foreground galaxies in absorption. As our atmosphere absorbs UV flux, UV-bright quasars behind galaxies have been a regular target of spectroscopic campaigns with HST. The utility of such quasars is usually predicated on their UV emission at a single epoch. But, some quasars vary significantly in the UV, so objects which have shown a recent increase in UV flux may also be good candidates for spectroscopic follow-up with HST. We have analyzed the changes in u-band measurements of known quasars within a recent observational survey of quasars behind M33. Imaging in the u-band of a region around M33 containing ~35 known quasars was conducted at the Wyoming Infrared Observatory (WIRO) in the summer of 2016. We report on the known quasars which show the most u-band variability between our WIRO campaign and earlier SDSS observations. By correlating u-band observations with GALEX NUV, we determine the likelihood that an increase in u-band flux is a good indicator of an increase in flux further in the UV. This work is supported by the National Science Foundation under REU grant AST 1560461.

  11. 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.

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

    SciTech Connect

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

    2010-09-01

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

  13. Internalization of Tissue Factor-Rich Microvesicles by Platelets Occurs Independently of GPIIb-IIIa, and Involves CD36 Receptor, Serotonin Transporter and Cytoskeletal Assembly.

    PubMed

    Lopez-Vilchez, Irene; Diaz-Ricart, Maribel; Galan, Ana M; Roque, Merce; Caballo, Carolina; Molina, Patricia; White, James G; Escolar, Gines

    2016-02-01

    Platelets are important in hemostasis, but also detect particles and pathogens in the circulation. Phagocytic and endocytic activities of platelets are widely recognized; however, receptors and mechanisms involved remain poorly understood. We previously demonstrated that platelets internalize and store phospholipid microvesicles enriched in human tissue factor (TF+MVs) and that platelet-associated TF enhances thrombus formation at sites of vascular damage. Here, we investigate the mechanisms implied in the interactions of TF+MVs with platelets and the effects of specific inhibitory strategies. Aggregometry and electron microscopy were used to assess platelet activation and TF+MVs uptake. Cytoskeletal assembly and activation of phosphoinositide 3-kinase (PI3K) and RhoA were analyzed by western blot and ELISA. Exposure of platelets to TF+MVs caused reversible platelet aggregation, actin polymerization and association of contractile proteins to the cytoskeleton being maximal at 1 min. The same kinetics were observed for activation of PI3K and translocation of RhoA to the cytoskeleton. Inhibitory strategies to block glycoprotein IIb-IIIa (GPIIb-IIIa), scavenger receptor CD36, serotonin transporter (SERT) and PI3K, fully prevented platelet aggregation by TF+MVs. Ultrastructural techniques revealed that uptake of TF+MVs was efficiently prevented by anti-CD36 and SERT inhibitor, but only moderately interfered by GPIIb-IIIa blockade. We conclude that internalization of TF+MVs by platelets occurs independently of receptors related to their main hemostatic function (GPIIb-IIIa), involves the scavenger receptor CD36, SERT and engages PI3-Kinase activation and cytoskeletal assembly. CD36 and SERT appear as potential therapeutic targets to interfere with the association of TF+MVs with platelets and possibly downregulate their prothrombotic phenotype.

  14. Detection of the Second Eclipsing High-Mass X-Ray Binary in M 33

    NASA Astrophysics Data System (ADS)

    Pietsch, Wolfgang; Haberl, Frank; Gaetz, Terrance J.; Hartman, Joel D.; Plucinsky, Paul P.; Tüllmann, Ralph; Williams, Benjamin F.; Shporer, Avi; Mazeh, Tsevi; Pannuti, Thomas G.

    2009-03-01

    Chandra data of the X-ray source [PMH2004] 47 were obtained in the ACIS Survey of M 33 (ChASeM33) in 2006. During one of the observations, the source varied from a high state to a low state and back, in two other observations it varied from a low state to respectively intermediate states. These transitions are interpreted as eclipse ingresses and egresses of a compact object in a high-mass X-ray binary (HMXB) system. The phase of mideclipse is given by HJD 245 3997.476 ± 0.006, the eclipse half angle is 30fdg6 ± 1fdg2. Adding XMM-Newton observations of [PMH2004] 47 in 2001 we determine the binary period to be 1.732479 ± 0.000027 days. This period is also consistent with ROSAT HRI observations of the source in 1994. No short-term periodicity compatible with a rotation period of the compact object is detected. There are indications for a long-term variability similar to that detected for Her X-1. During the high state the spectrum of the source is hard (power-law spectrum with photon index ~0.85) with an unabsorbed luminosity of 2 ×1037 erg s-1 (0.2-4.5 keV). We identify as an optical counterpart a V ~ 21.0 mag star with T eff>19000 K, log(g)>2.5. The Canada-France-Hawaii Telescope optical light curves for this star show an ellipsoidal variation with the same period as the X-ray light curve. The optical light curve together with the X-ray eclipse can be modeled by a compact object with a mass consistent with a neutron star or a black hole in an HMXB. However, the hard power-law X-ray spectrum favors a neutron star as the compact object in this second eclipsing X-ray binary in M 33. Assuming a neutron star with a canonical mass of 1.4 M sun and the best-fit companion temperature of 33,000 K, a system inclination i = 72° and a companion mass of 10.9 M sun are implied.

  15. HST/COS Observations of Ionized Gas Accretion at the Disk–Halo Interface of M33

    NASA Astrophysics Data System (ADS)

    Zheng, Y.; Peek, J. E. G.; Werk, J. K.; Putman, M. E.

    2017-01-01

    We report the detection of accreting ionized gas at the disk–halo interface of the nearby galaxy M33. We analyze Hubble Space Telescope/Cosmic Origins Spectrograph absorption-line spectra of seven ultraviolet-bright stars evenly distributed across the disk of M33. We find Si iv absorption components consistently redshifted relative to the bulk M33's ISM absorption along all the sightlines. The Si iv detection indicates an enriched, disk-wide, ionized gas inflow toward the disk. This inflow is most likely multi-phase as the redshifted components can also be observed in ions with lower ionization states (e.g., S ii, P ii, Fe ii, Si ii). Kinematic modeling of the inflow is consistent with an accreting layer at the disk–halo interface of M33, which has an accretion velocity of {110}-20+15 {km} {{{s}}}-1 at a distance of {1.5}-1.0+1.0 kpc above the disk. The modeling indicates a total mass of ∼3.9 × 107 M⊙ for the accreting material at the disk–halo interface on the near side of the M33 disk, with an accretion rate of ∼2.9 M⊙ yr‑1. The high accretion rate and the level of metal enrichment suggest the inflow is likely to be the fallback of M33 gas from a galactic fountain and/or the gas pulled loosed during a close interaction between M31 and M33. Our study of M33 is the first to unambiguously reveal the existence of a disk-wide, ionized gas inflow beyond the Milky Way, providing a better understanding of gas accretion in the vicinity of a galaxy disk.

  16. Decrease in fibronectin occurs coincident with the increased expression of its integrin receptor alpha5beta1 in stress-deprived ligaments.

    PubMed Central

    AbiEzzi, S. S.; Foulk, R. A.; Harwood, F. L.; Akeson, W. H.; Amiel, D.

    1997-01-01

    Stress deprivation secondary to immobilization leads to atrophic changes in periarticular soft tissues. The changes in ligaments include a disorganization of collagen and cellular ultrastructure with varied biochemical alterations resulting in a functionally weaker tissue. This study tests the hypothesis that alterations in fibronectin (Fn) and the expression of its integrin receptor alpha5beta1 in ligament fibroblasts accompany the extracellular matrix remodeling which occurs in stress-deprived knee ligaments. The left knees of eighteen New Zealand white rabbits were surgically immobilized in acute flexion. Fibroblasts within three nine week and three twelve week stress-deprived anterior cruciate ligaments (ACLs) and medial collateral ligaments (MCLs) demonstrated markedly increased immunostaining for the beta1 and alpha5 integrin subunits, as compared to fibroblasts in the contralateral unoperated control ligaments. The effects of stress deprivation on the concentration of Fn was measured by competitive ELISA on the remaining twelve rabbits. Decreases in Fn of 54.0 percent and 63.7 percent occurred in the ACL after nine and twelve weeks of stress deprivation when compared to contralateral controls. The MCL had less of a decrease, losing 37.7 percent and 41.7 percent at nine and twelve weeks, respectively. These results suggest an important role for the Fn-specific integrin receptor alpha5beta1 in remodeling stress-deprived periarticular ligamentous tissue, and the importance of maintaining normal stresses on periarticular ligaments to prevent the degradation of extracellular matrix components such as Fn. Images Figure 1 Figure 2 Figure 3 PMID:9234981

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

    NASA Astrophysics Data System (ADS)

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

    2015-02-01

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

  18. 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.

  19. 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.

  20. A VLA Search for Radio Signals from M31 and M33

    NASA Astrophysics Data System (ADS)

    Gray, Robert H.; Mooley, Kunal

    2017-03-01

    Observing nearby galaxies would facilitate the search for artificial radio signals by sampling several billions of stars simultaneously, but few efforts have been made to exploit this opportunity. An added attraction is that the Milky Way is the second largest member of the Local Group, so our galaxy might be a probable target for hypothetical broadcasters in nearby galaxies. We present the first relatively high spectral resolution (<1 kHz) 21 cm band search for intelligent radio signals of complete galaxies in the Local Group with the Jansky VLA, observing the galaxies M31 (Andromeda) and M33 (Triangulum)—the first and third largest members of the group, respectively—sampling more stars than any prior search of this kind. We used 122 Hz channels over a 1 MHz spectral window in the target galaxy velocity frame of reference, and 15 Hz channels over a 125 kHz window in our local standard of rest. No narrowband signals were detected above a signal-to-noise ratio of 7, suggesting the absence of continuous narrowband flux greater than approximately 0.24 and 1.33 Jy in the respective spectral windows illuminating our part of the Milky Way during our observations in 2014 December and 2015 January. This is also the first study in which the upgraded VLA has been used for SETI.

  1. First images of water vapor masers in the galaxy M33

    NASA Technical Reports Server (NTRS)

    Greenhill, L. J.; Moran, J. M.; Reid, M. J.; Gwinn, C. R.; Menten, K. M.

    1990-01-01

    The first successful VLBI observations of 10 extragalactic H2O masers in the M33 galaxy are reported. A spectral-line VLBI synthesis map is constructed, the first of any extragalactic H2O maser sources. The map has the lowest noise of any K-band spectral line VLBI map yet produced. The maser emission extends over about 300 milliarcseconds and is divided into 14 distinct spatial components, the strongest of which has a correlated flux density of about 0.7 Jy. The relative positions of some of these components are determined accurately enough to provide first-epoch measurements for proper motion studies. The characteristics of the maser are similar to those of the most powerful maser in the Galaxy, W49N. A compact H II region is found close to the maser which is 1 pc in diameter and whose emission measure is about 6 x 10 to the 7th pc/cm exp 6. This region is the compact component of a more extended H II complex that extends over about 100 pc.

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

    SciTech Connect

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

    2010-04-01

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

  3. Beta-adrenergic receptors support attention to extinction learning that occurs in the absence, but not the presence, of a context change

    PubMed Central

    André, Marion Agnès Emma; Wolf, Oliver T.; Manahan-Vaughan, Denise

    2015-01-01

    The noradrenergic (NA)-system is an important regulator of cognitive function. It contributes to extinction learning (EL), and in disorders where EL is impaired NA-dysfunction has been postulated. We explored whether NA acting on beta-adrenergic-receptors (β-AR), regulates EL that depends on context, but is not fear-associated. We assessed behavior in an “AAA” or “ABA” paradigm: rats were trained for 3 days in a T-maze (context-A) to learn that a reward is consistently found in the goal arm, despite low reward probability. This was followed on day 4 by EL (unrewarded), whereby in the ABA-paradigm, EL was reinforced by a context change (B), and in the AAA-paradigm, no context change occurred. On day 5, re-exposure to the A-context (unrewarded) occurred. Typically, in control “AAA” animals EL occurred on day 4 that progressed further on day 5. In control “ABA” animals, EL also occurred on day 4, followed by renewal of the previously learned (A) behavior on day 5, that was succeeded (on day 5) by extinction of this behavior, as the animals realised that no food reward would be given. Treatment with the β-AR-antagonist, propranolol, prior to EL on day 4, impaired EL in the AAA-paradigm. In the “ABA” paradigm, antagonist treatment on day 4, had no effect on extinction that was reinforced by a context change (B). Furthermore, β-AR-antagonism prior to renewal testing (on day 5) in the ABA-paradigm, resulted in normal renewal behavior, although subsequent extinction of responses during day 5 was prevented by the antagonist. Thus, under both treatment conditions, β-AR-antagonism prevented extinction of the behavior learned in the “A” context. β-AR-blockade during an overt context change did not prevent EL, whereas β-AR were required for EL in an unchanging context. These data suggest that β-AR may support EL by reinforcing attention towards relevant changes in the previously learned experience, and that this process supports extinction

  4. Molecular and atomic gas in the Local Group galaxy M 33

    NASA Astrophysics Data System (ADS)

    Gratier, P.; Braine, J.; Rodriguez-Fernandez, N. J.; Schuster, K. F.; Kramer, C.; Xilouris, E. M.; Tabatabaei, F. S.; Henkel, C.; Corbelli, E.; Israel, F.; van der Werf, P. P.; Calzetti, D.; Garcia-Burillo, S.; Sievers, A.; Combes, F.; Wiklind, T.; Brouillet, N.; Herpin, F.; Bontemps, S.; Aalto, S.; Koribalski, B.; van der Tak, F.; Wiedner, M. C.; Röllig, M.; Mookerjea, B.

    2010-11-01

    We present high-resolution large-scale observations of the molecular and atomic gas in the Local Group galaxy M 33. The observations were carried out using the HEterodyne Receiver Array (HERA) at the 30 m IRAM telescope in the CO(2-1) line, achieving a resolution of 12” × 2.6 km s-1, enabling individual giant molecular clouds (GMCs) to be resolved. The observed region is 650 square arcminutes mainly along the major axis and out to a radius of 8.5 kpc, and covers entirely the 2' × 40' radial strip observed with the HIFI and PACS Spectrometers as part of the HERM33ES Herschel key program. The achieved sensitivity in main-beam temperature is 20-50 mK at 2.6 km s-1 velocity resolution. The CO(2-1) luminosity of the observed region is 1.7±0.1 × 107 K km s-1 pc2 and is estimated to be 2.8±0.3 × 107 K km s-1 pc2 for the entire galaxy, corresponding to H2 masses of 1.9 × 108 Msun and 3.3 × 108 Msun respectively (including He), calculated with N(H2)/ICO(1-0) twice the Galactic value due to the half-solar metallicity of M 33. The H i 21 cm VLA archive observations were reduced, and the mosaic was imaged and cleaned using the multi-scale task in the CASA software package, yielding a series of datacubes with resolutions ranging from 5” to 25”. The H i mass within a radius of 8.5 kpc is estimated to be 1.4 × 109 Msun. The azimuthally averaged CO surface brightness decreases exponentially with a scale length of 1.9±0.1 kpc whereas the atomic gas surface density is constant at ΣH I = 6±2 Msun pc-2 deprojected to face-on. For an N(H2)/ICO(1-0) conversion factor twice that of the Milky Way, the central kiloparsec H2 surface density is ΣH2 = 8.5±0.2 Msun pc-2. The star formation rate per unit molecular gas (SF efficiency, the rate of transformation of molecular gas into stars), as traced by the ratio of CO to Hα and FIR brightness, is constant with radius. The SFE, with a N(H2)/ICO(1-0) factor twice galactic, appears 2-4 times greater than for large spiral

  5. Star formation in M 33: the radial and local relations with the gas

    NASA Astrophysics Data System (ADS)

    Verley, S.; Corbelli, E.; Giovanardi, C.; Hunt, L. K.

    2010-02-01

    Aims: In the Local Group spiral galaxy M 33, we investigate the correlation between the star formation rate (SFR) surface density, Σ_SFR, and the gas density Σ_gas (molecular, atomic, and total). We also explore whether there are other physical quantities, such as the hydrostatic pressure and dust optical depth, which establish a good correlation with Σ_SFR. Methods: We use the Hα, far-ultraviolet (FUV), and bolometric emission maps to infer the SFR locally at different spatial scales, and in radial bins using azimuthally averaged values. Most of the local analysis is done using the highest spatial resolution allowed by gas surveys, 180 pc. The Kennicutt-Schmidt (KS) law, Σ_SFR ∝ Σ_gas^n is analyzed by three statistical methods. Results: At all spatial scales, with Hα emission as a SFR tracer, the KS indices n are always steeper than those derived with the FUV and bolometric emissions. We attribute this to the lack of Hα emission in low luminosity regions where most stars form in small clusters with an incomplete initial mass function at their high mass end. For azimuthally averaged values the depletion timescale for the molecular gas is constant, and the KS index is n_H_2=1.1 ±0.1. Locally, at a spatial resolution of 180 pc, the correlation between Σ_SFR and Σ_gas is generally poor, even though it is tighter with the molecular and total gas than with the atomic gas alone. Considering only positions where the CO J=1-0 line is above the 2-σ detection threshold and taking into account uncertainties in Σ_H_2 and Σ_SFR, we obtain a steeper KS index than obtained with radial averages: n_H_2=2.22 ±0.07 (for FUV and bolometric SFR tracers), flatter than that relative to the total gas (n_Htot=2.59 ±0.05). The gas depletion timescale is therefore larger in regions of lower Σ_SFR. Lower KS indices (n_H_2=1.46 ±0.34 and n_H_2=1.12) are found using different fitting techniques, which do not account for individual position uncertainties. At coarser spatial

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

    SciTech Connect

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

    2010-10-20

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

  7. Characterization of endoglucanase from Paenibacillus sp. M33, a novel isolate from a freshwater swamp forest.

    PubMed

    Kanchanadumkerng, Pimpikar; Sakka, Makiko; Sakka, Kazuo; Wiwat, Chanpen

    2017-02-01

    The newly isolated Paenibacillus sp. M33 from freshwater swamp forest soil in Thailand demonstrated its potential as a cellulose degrader. One of its endoglucanase genes from Paenibacillus sp., celP, was cloned to study the molecular characteristics of its gene product. The celP gene was recognized firstly by degenerate primer designed from Paenibacillus endoglucanase gene, and subsequently identified flanking region by inverse PCR technique. The celP gene consists of an open reading frame of 1707 bp encoding for 569 amino acids including 33-amino acids signal sequence. CelP is a member of glycoside hydrolase family 5 appended with a family 46 carbohydrate-binding module. CelP from recombinant Escherichia coli was purified by affinity chromatography. SDS-PAGE analysis of purified CelP showed a protein band at about 60 kDa. The purified enzyme gave a specific CMCase activity of 0.03 μmol min(-1)  mg(-1) . It had higher activities on lichenan (0.19 μmol min(-1)  mg(-1) ) and barley β-glucan (0.14 μmol min(-1)  mg(-1) ). Maximum activity on lichenan was obtained at 50 °C, pH 5.0. CelP was stable over a pH range of 3.0-10.0 and retained 80% activity when incubated at 50 °C for 1 h. The properties of its CelP endoglucanase, especially substrate specificity, will make it useful in various biotechnological applications including biomass hydrolysis.

  8. 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.

  9. 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

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

    PubMed Central

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

    2005-01-01

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

  11. A naturally occurring mutation of the opsin gene (T4R) in dogs affects glycosylation and stability of the G protein-coupled receptor.

    PubMed

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

    2004-12-17

    Rho (rhodopsin; opsin plus 11-cis-retinal) is a prototypical G protein-coupled receptor responsible for the capture of a photon in retinal photoreceptor cells. A large number of mutations in the opsin gene associated with autosomal dominant retinitis pigmentosa have been identified. The naturally occurring T4R opsin mutation in the English mastiff dog leads to a progressive retinal degeneration that closely resembles human retinitis pigmentosa caused by the T4K mutation in the opsin gene. Using genetic approaches and biochemical assays, we explored the properties of the T4R mutant protein. Employing immunoaffinity-purified Rho from affected RHO(T4R/T4R) dog retina, we found that the mutation abolished glycosylation at Asn(2), whereas glycosylation at Asn(15) was unaffected, and the mutant opsin localized normally to the rod outer segments. Moreover, we found that T4R Rho(*) lost its chromophore faster as measured by the decay of meta-rhodopsin II and that it was less resistant to heat denaturation. Detergent-solubilized T4R opsin regenerated poorly and interacted abnormally with the G protein transducin (G(t)). Structurally, the mutation affected mainly the "plug" at the intradiscal (extracellular) side of Rho, which is possibly responsible for protecting the chromophore from the access of bulk water. The T4R mutation may represent a novel molecular mechanism of degeneration where the unliganded form of the mutant opsin exerts a detrimental effect by losing its structural integrity.

  12. Analysis of mitogen-activated protein kinase activation by naturally occurring splice variants of TrkC, the receptor for neurotrophin-3.

    PubMed

    Gunn-Moore, F J; Williams, A G; Tavaré, J M

    1997-02-15

    TrkC is a receptor tyrosine kinase that binds neurotrophin-3 (NT-3) with high affinity. A number of naturally occurring splice variants of TrkC exist, including one (TrkC kil4) with a 14 amino acid insertion between subdomains VII and VIII of the tyrosine kinase domain. This kinase insert blocks the ability of NT-3 to stimulate neurite outgrowth in PC12 cells and proliferation in fibroblasts. The inserts also block the ability of TrkC to form a high-affinity complex with Shc and phospholipase C gamma (PLC gamma) and the activation of PtdIns 3-kinase, and attenuates the sustained activation of mitogen-activated protein kinase (MAPK). In the current study we set out to determine whether the attenuation of the activation of MAPK by the insert was the result of the inability of TrkC to activate the Shc-Ras pathway, PtdIns 3-kinase activation, PLC gamma activation, or a combination thereof. Experiments with the use of cell-permeant inhibitors argue against a major role for PLC gamma and PtdIns 3-kinase in the activation of MAPK by TrkC. The introduction of the 14 amino acid kinase insert appeared to slow the kinetics of NT-3-stimulated Shc phosphorylation and Shc-Grb2 association and reduce their magnitude; an effect which was associated with a delayed, and only transient, activation of MAPK. Taken together, our data suggest that the apparent defect in MAPK activation caused by the kinase insert may result predominantly from an inhibition of high-affinity Shc binding, although a role for PLC gamma and PtdIns 3-kinase cannot be completely excluded.

  13. 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.

  14. Naturally occurring Toll-like receptor 11 (TLR11) and Toll-like receptor 12 (TLR12) polymorphisms are not associated with Toxoplasma gondii infection in wild wood mice.

    PubMed

    Morger, Jennifer; Bajnok, Jaroslav; Boyce, Kellyanne; Craig, Philip S; Rogan, Michael T; Lun, Zhao-Rong; Hide, Geoff; Tschirren, Barbara

    2014-08-01

    Toxoplasma gondii is a highly successful parasite with a worldwide prevalence. Small rodents are the main intermediate hosts, and there is growing evidence that T. gondii modifies their behaviour. Chronically infected rodents show impaired learning capacity, enhanced activity, and, most importantly, a reduction of the innate fear towards cat odour. This modification of host behaviour ensures a successful transmission of T. gondii from rodents to felids, the definitive hosts of the parasite. Given the negative fitness consequences of this behavioural manipulation, as well as an increased mortality during the acute phase of infection, we expect rodents to evolve potent resistance mechanisms that prevent or control infection. Indeed, studies in laboratory mice have identified candidate genes for T. gondii resistance. Of particular importance appear to be the innate immune receptors Toll-like receptor 11 (TLR11) and Toll-like receptor 12 (TLR12), which recognise T. gondii profilin and initiate immune responses against the parasite. Here we analyse the genetic diversity of TLR11 and TLR12 in a natural population of wood mice (Apodemus sylvaticus), and test for associations between TLR11 and TLR12 polymorphisms and T. gondii infection, as well as for epistatic interactions between TLR11 and TLR12 on infection status. We found that both TLR11 and TLR12 were polymorphic in wood mice, with four and nine amino acid haplotypes, respectively. However, we found no evidence that TLR11 or TLR12 genotypes or haplotypes were significantly associated with Toxoplasma infection. Despite the importance of TLR11 and TLR12 in T. gondii recognition and immune defence initiation, naturally occurring polymorphisms at TLR11 and TLR12 thus appear to play a minor role in mediating qualitative resistance to T. gondii in natural host populations of A. sylvaticus. This highlights the importance of assessing the role of candidate genes for parasite resistance identified in a laboratory setting in

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

    PubMed Central

    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.

    2015-01-01

    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

  16. Accurate Parameters for the Most Massive Stars in the Local Universe: the Brightest Eclipsing Binaries in M33

    NASA Astrophysics Data System (ADS)

    Prieto, José L.; Bonanos, Alceste; Stanek, Krzysztof

    2007-08-01

    Eclipsing binaries are the only systems that provide accurate fundamental parameters of distant stars. Currently, only a handful of accurate measurements of stars with masses between 40-80 Msun have been made. We propose to make accurate measurements of the masses, radii and luminosities of the most massive eclipsing binaries in M33. The results of this study will provide much needed constraints on theories that model the formation and evolution of massive stars and binary systems. Furthermore, it will provide vital statistics on the occurrence of massive binary twins, like the 80+80 solar masses WR 20a system and the 30+30 solar masses detached eclipsing binary in M33.

  17. 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.

  18. A Deep XMM-Newton Survey of M33: Point-source Catalog, Source Detection, and Characterization of Overlapping Fields

    NASA Astrophysics Data System (ADS)

    Williams, Benjamin F.; Wold, Brian; Haberl, Frank; Garofali, Kristen; Blair, William P.; Gaetz, Terrance J.; Kuntz, K. D.; Long, Knox S.; Pannuti, Thomas G.; Pietsch, Wolfgang; Plucinsky, Paul P.; Winkler, P. Frank

    2015-05-01

    We have obtained a deep 8 field XMM-Newton mosaic of M33 covering the galaxy out to the D25 isophote and beyond to a limiting 0.2-4.5 keV unabsorbed flux of 5 × 10-16 erg cm-2 s-1 (L \\gt 4 × 1034 erg s-1 at the distance of M33). These data allow complete coverage of the galaxy with high sensitivity to soft sources such as diffuse hot gas and supernova remnants (SNRs). Here, we describe the methods we used to identify and characterize 1296 point sources in the 8 fields. We compare our resulting source catalog to the literature, note variable sources, construct hardness ratios, classify soft sources, analyze the source density profile, and measure the X-ray luminosity function (XLF). As a result of the large effective area of XMM-Newton below 1 keV, the survey contains many new soft X-ray sources. The radial source density profile and XLF for the sources suggest that only ˜15% of the 391 bright sources with L \\gt 3.6 × 1035 erg s-1 are likely to be associated with M33, and more than a third of these are known SNRs. The log(N)-log(S) distribution, when corrected for background contamination, is a relatively flat power law with a differential index of 1.5, which suggests that many of the other M33 sources may be high-mass X-ray binaries. Finally, we note the discovery of an interesting new transient X-ray source, which we are unable to classify.

  19. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

  1. The UK Infrared Telescope M 33 monitoring project - V. The star formation history across the galactic disc

    NASA Astrophysics Data System (ADS)

    Javadi, Atefeh; van Loon, Jacco Th.; Khosroshahi, Habib G.; Tabatabaei, Fatemeh; Hamedani Golshan, Roya; Rashidi, Maryam

    2017-01-01

    We have conducted a near-infrared monitoring campaign at the UK Infrared Telescope of the Local Group spiral galaxy M 33 (Triangulum). On the basis of their variability, we have identified stars in the very final stage of their evolution, and for which the luminosity is more directly related to the birth mass than the more numerous less-evolved giant stars that continue to increase in luminosity. In this fifth paper of the series, we construct the birth mass function and hence derive the star formation history across the galactic disc of M 33. The star formation rate has varied between ˜0.010 ± 0.001 (˜0.012 ± 0.007) and 0.060±0.005 (0.052±0.009) M⊙ yr-1 kpc-2 statistically (systematically) in the central square kiloparsec of M 33, comparable with the values derived previously with another camera. The total star formation rate in M 33 within a galactocentric radius of 14 kpc has varied between ˜0.110 ± 0.005 (˜0.174 ± 0.060) and ˜0.560 ± 0.028 (˜0.503 ± 0.100) M⊙ yr-1 statistically (systematically). We find evidence of two epochs during which the star formation rate was enhanced by a factor of a few - one that started ˜6 Gyr ago and lasted ˜3 Gyr and produced ≥71 per cent of the total mass in stars, and one ˜250 Myr ago that lasted ˜200 Myr and formed ≤13 per cent of the mass in stars. Radial star formation history profiles suggest that the inner disc of M 33 was formed in an inside-out formation scenario. The outskirts of the disc are dominated by the old population, which may be the result of dynamical effects over many Gyr. We find correspondence to spiral structure for all stars, but enhanced only for stars younger than ˜100 Myr; this suggests that the spiral arms are transient features and not a part of a global density wave potential.

  2. The naturally occurring mutation Y197C does not affect the expression or signaling of the human histamine H3 receptor.

    PubMed

    Flores-Clemente, Cecilia; Escamilla-Sánchez, Juan; Arias, Juan-Manuel; Arias-Montaño, José-Antonio

    2017-02-22

    There is evidence for genetic polymorphism within the human histamine H3 receptor (hH3R), and a Tyr to Cys exchange at position 197 (Y197C), located in the amino terminus of the fifth transmembrane domain, has been reported. In this work we compared the expression and the pharmacological and signaling properties of wild-type (hH3RWT) and mutant (hH3RY197C) receptors transiently expressed in CHO-K1 cells. The hH3RY197C cDNA was created by overlap extension PCR amplification. Receptor expression and affinity were assessed by N-α-[methyl-(3)H]-histamine binding to cell membranes and intact cells. Receptor function was evaluated by stimulation of [(35)S]-GTPγS binding to cell membranes and by inhibition of forskolin-induced cAMP accumulation in intact cells. The hH3RWT and hH3RY197C were expressed at similar levels (761±68 and 663±66fmol/mg protein for membranes, and 13,434±1533 and 15,894±1884 receptors per cell, respectively). There were no significant differences in the affinities for H3R agonists or antagonists/inverse agonists between the hH3RWT and hH3RY197C, and the H3R agonist RAMH was similarly efficacious and potent to stimulate [(35)S]-GTPγS binding and to inhibit forskolin-induced cAMP accumulation. These results indicate that the Y197C mutation does not affect the expression, ligand affinity or signaling of the human H3 receptor.

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

    PubMed

    Viñals, Xavier; Moreno, Estefanía; 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

    2015-07-01

    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.

  4. 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

  5. GPCR responses in vascular smooth muscle can occur predominantly through dual transactivation of kinase receptors and not classical Gαq protein signalling pathways.

    PubMed

    Little, Peter J

    2013-05-30

    GPCR signalling is well known to proceed through several linear pathways involving activation of G proteins and their downstream signalling pathways such as activation of phospholipase C. In addition, GPCRs signal via transactivation of Protein Tyrosine Kinase receptors such as that for Epidermal Growth Factor (EGF) and Platelet-Derived Growth Factor (PDGF) where GPCR agonists mediate increase levels of phosphorylated Erk (pErk) the immediate downstream product of the activation of EGF receptor. It has recently been shown that this paradigm can be extended to include the GPCR transactivation of a Protein Serine/Threonine Kinase receptor, specifically the Transforming Growth Factor β Type I receptor (also known as Alk V) (TβRI) in which case GPCR activation leads to the formation of carboxy terminal polyphosphorylated Smad2 (phosphoSmad2) being the immediate downstream product of the activation of TβRI. Growth factor and hormone regulation of proteoglycan synthesis in vascular smooth muscle cells represent one component of an in vitro model of atherosclerosis because modified proteoglycans show enhanced binding to lipoproteins as the initiating step in atherosclerosis. In the example of proteoglycan synthesis stimulated by GPCR agonists such as thrombin and endothelin-1, the transactivation pathways for the EGF receptor and TβRI are both active and together account for essentially all of the response to the GPCRs. In contrast, signalling downstream of GPCRs such as increased inositol 1,4,5 trisphosphate (IP3) and intracellular calcium do not have any effect on GPCR stimulated proteoglycan synthesis. These data lead to the conclusion that dual transactivation pathways for protein tyrosine and serine/threonine kinase receptors may play a far greater role in GPCR signalling than currently recognised.

  6. Antibody uptake into neurons occurs primarily via clathrin-dependent Fcγ receptor endocytosis and is a prerequisite for acute tau protein clearance.

    PubMed

    Congdon, Erin E; Gu, Jiaping; Sait, Hameetha B R; Sigurdsson, Einar M

    2013-12-06

    Tau immunotherapy is effective in transgenic mice, but the mechanisms of Tau clearance are not well known. To this end, Tau antibody uptake was analyzed in brain slice cultures and primary neurons. Internalization was rapid (<1 h), saturable, and substantial compared with control mouse IgG. Furthermore, temperature reduction to 4 °C, an excess of unlabeled mouse IgG, or an excess of Tau antibodies reduced uptake in slices by 63, 41, and 62%, respectively (p = 0.002, 0.04, and 0.005). Uptake strongly correlated with total and insoluble Tau levels (r(2) = 0.77 and 0.87 and p = 0.002 and 0.0002), suggesting that Tau aggregates influence antibody internalization and/or retention within neurons. Inhibiting phagocytosis did not reduce uptake in slices or neuronal cultures, indicating limited microglial involvement. In contrast, clathrin-specific inhibitors reduced uptake in neurons (≤ 78%, p < 0.0001) and slices (≤ 35%, p = 0.03), demonstrating receptor-mediated endocytosis as the primary uptake pathway. Fluid phase endocytosis accounted for the remainder of antibody uptake in primary neurons, based on co-staining with internalized dextran. The receptor-mediated uptake is to a large extent via low affinity FcγII/III receptors and can be blocked in slices (43%, p = 0.04) and neurons (53%, p = 0.008) with an antibody against these receptors. Importantly, antibody internalization appears to be necessary for Tau reduction in primary neurons. Overall, these findings clarify that Tau antibody uptake is primarily receptor-mediated, that these antibodies are mainly found in neurons with Tau aggregates, and that their intracellular interaction leads to clearance of Tau pathology, all of which have major implications for therapeutic development of this approach.

  7. 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.

  8. 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).

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

    PubMed

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

    2005-04-15

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

  10. Observations of M31 and M33 with the Fermi Large Area Telescope: A Galactic Center Excess in Andromeda?

    NASA Astrophysics Data System (ADS)

    Ackermann, M.; Ajello, M.; Albert, A.; Baldini, L.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Bellazzini, R.; Bissaldi, E.; Bloom, E. D.; Bonino, R.; Bottacini, E.; Brandt, T. J.; Bregeon, J.; Bruel, P.; Buehler, R.; Cameron, R. A.; Caputo, R.; Caragiulo, M.; Caraveo, P. A.; Cavazzuti, E.; Cecchi, C.; Charles, E.; Chekhtman, A.; Chiaro, G.; Ciprini, S.; Costanza, F.; Cutini, S.; D’Ammando, F.; de Palma, F.; Desiante, R.; Digel, S. W.; Di Lalla, N.; Di Mauro, M.; Di Venere, L.; Favuzzi, C.; Funk, S.; Fusco, P.; Gargano, F.; Giglietto, N.; Giordano, F.; Giroletti, M.; Glanzman, T.; Green, D.; Grenier, I. A.; Guillemot, L.; Guiriec, S.; Hayashi, K.; Hou, X.; Jóhannesson, G.; Kamae, T.; Knödlseder, J.; Kong, A. K. H.; Kuss, M.; La Mura, G.; Larsson, S.; Latronico, L.; Li, J.; Longo, F.; Loparco, F.; Lubrano, P.; Maldera, S.; Malyshev, D.; Manfreda, A.; Martin, P.; Mazziotta, M. N.; Michelson, P. F.; Mirabal, N.; Mitthumsiri, W.; Mizuno, T.; Monzani, M. E.; Morselli, A.; Moskalenko, I. V.; Negro, M.; Nuss, E.; Ohsugi, T.; Omodei, N.; Orlando, E.; Ormes, J. F.; Paneque, D.; Persic, M.; Pesce-Rollins, M.; Piron, F.; Porter, T. A.; Principe, G.; Rainò, S.; Rando, R.; Razzano, M.; Reimer, O.; Sánchez-Conde, M.; Sgrò, C.; Simone, D.; Siskind, E. J.; Spada, F.; Spandre, G.; Spinelli, P.; Tanaka, K.; Tibaldo, L.; Torres, D. F.; Troja, E.; Uchiyama, Y.; Wang, J. C.; Wood, K. S.; Wood, M.; Zaharijas, G.; Zhou, M.

    2017-02-01

    The Fermi Large Area Telescope (LAT) has opened the way for comparative studies of cosmic rays (CRs) and high-energy objects in the Milky Way (MW) and in other, external, star-forming galaxies. Using 2 yr of observations with the Fermi LAT, Local Group galaxy M31 was detected as a marginally extended gamma-ray source, while only an upper limit has been derived for the other nearby galaxy M33. We revisited the gamma-ray emission in the direction of M31 and M33 using more than 7 yr of LAT Pass 8 data in the energy range 0.1{--}100 {GeV}, presenting detailed morphological and spectral analyses. M33 remains undetected, and we computed an upper limit of 2.0× {10}-12 {erg} {{cm}}-2 {{{s}}}-1 on the 0.1{--}100 {GeV} energy flux (95% confidence level). This revised upper limit remains consistent with the observed correlation between gamma-ray luminosity and star formation rate tracers and implies an average CR density in M33 that is at most half of that of the MW. M31 is detected with a significance of nearly 10σ . Its spectrum is consistent with a power law with photon index {{Γ }}=2.4+/- {0.1}{stat+{syst}} and a 0.1{--}100 {GeV} energy flux of (5.6+/- {0.6}{stat+{syst}})× {10}-12 {erg} {{cm}}-2 {{{s}}}-1. M31 is detected to be extended with a 4σ significance. The spatial distribution of the emission is consistent with a uniform-brightness disk with a radius of 0.°4 and no offset from the center of the galaxy, but nonuniform intensity distributions cannot be excluded. The flux from M31 appears confined to the inner regions of the galaxy and does not fill the disk of the galaxy or extend far from it. The gamma-ray signal is not correlated with regions rich in gas or star formation activity, which suggests that the emission is not interstellar in origin, unless the energetic particles radiating in gamma rays do not originate in recent star formation. Alternative and nonexclusive interpretations are that the emission results from a population of millisecond pulsars

  11. 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

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

    PubMed

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

    2015-02-01

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

  13. 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.

  14. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

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

  16. 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.

  17. A naturally occurring mutation in the human androgen receptor of a subject with complete androgen insensitivity confers binding and transactivation by estradiol.

    PubMed

    Bonagura, Thomas W; Deng, Min; Brown, Terry R

    2007-01-15

    The clinical phenotype of complete androgen insensitivity (CAIS) was associated with a mutation in the human androgen receptor (hAR) gene encoding the amino acid substitution, M745I, in the hAR protein. Transcriptional activation of hAR(M745I) by the synthetic androgen, methyltrienolone (R1881), was reduced compared to wild-type (wt) hAR. The transcriptional co-activator, androgen receptor associated protein 70 (ARA70), failed to enhance transactivation of hAR(M745I) at lower concentrations of R1881 (0.01-0.1 nM), whereas the p160 co-activators, SRC-1 and TIF2, stimulated activity. Transcriptional activity of hAR(M745I) was stimulated by 1 or 10 nM R1881 and activity was further enhanced by co-expression of ARA70 similar to that of the hAR(wt). Transcriptional activity of hAR(wt) was minimally stimulated by estradiol (E2) without or with co-expression of ARA70, whereas 10 or 100 nM E2 increased transactivation by hAR(M745I) of the androgen-responsive MMTV-luciferase reporter gene by 10-fold and activity was further enhanced by ARA70. Increasing concentrations of E2 competed more effectively for binding of R1881 to hAR(M745I) than to hAR(wt), indicative of the preferential binding of E2 to the mutant hAR. Partial tryptic digestion of hAR wt and M745I revealed that activation of the mutant protein was reduced in the presence of R1881. By contrast, tryptic digestion showed that the mutant hAR was activated by the binding of E2. In conclusion, the clinical phenotype of CAIS resulted from a hAR gene mutation encoding hAR(M745I) with reduced binding and transactivation by androgens, but the novel properties of enhanced affinity for and increased transactivation by estradiol.

  18. Reversible kallmann syndrome, delayed puberty, and isolated anosmia occurring in a single family with a mutation in the fibroblast growth factor receptor 1 gene.

    PubMed

    Pitteloud, Nelly; Acierno, James S; Meysing, Astrid U; Dwyer, Andrew A; Hayes, Frances J; Crowley, William F

    2005-03-01

    Kallmann syndrome (KS) is a clinically and genetically heterogeneous disorder. Recently, loss-of-function mutations in the fibroblast growth factor receptor 1 (FGFR1) gene have been shown to cause autosomal dominant KS. To date, the detailed reproductive phenotype of KS associated with mutations in the FGFR1 has yet to be described. We report a kindred comprising a male proband with KS and spontaneous reversibility, whose mother had delayed puberty and whose maternal grandfather isolated anosmia. The proband presented at age 18 yr with KS and was subsequently treated with testosterone (T) therapy. Upon discontinuation of T therapy, he recovered from his hypogonadotropic hypogonadism, as evidenced by a normal LH secretion pattern, sustained normal serum T levels, and active spermatogenesis. The three members of this single family harbor the same FGFR1 mutation (Arg(622)X) in the tyrosine kinase domain. This report demonstrates 1) the first genetic cause of the rare variant of reversible KS, 2) the reversal of hypogonadotropic hypogonadism in a proband carrying an FGFR1 mutation suggests a role of FGFR1 beyond embryonic GnRH neuron migration, and 3) a loss of function mutation in the FGFR1 gene causing delayed puberty.

  19. 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

    2010-11-04

    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.

  20. Lutein transport by Caco-2 TC-7 cells occurs partly by a facilitated process involving the scavenger receptor class B type I (SR-BI).

    PubMed

    Reboul, Emmanuelle; Abou, Lydia; Mikail, Céline; Ghiringhelli, Odette; André, Marc; Portugal, Henri; Jourdheuil-Rahmani, Dominique; Amiot, Marie-Josèphe; Lairon, Denis; Borel, Patrick

    2005-04-15

    The carotenoid lutein is thought to play a role in the human eye and to protect against age-related macular degeneration. Lutein transport in the human intestine has not been characterized. We examined lutein transport processes using Caco-2 TC-7 monolayers as a model for human intestinal epithelium. Purified lutein was mixed with phospholipids, lysophospholipids, cholesterol, mono-olein, oleic acid and taurocholate to obtain lutein-rich mixed micelles that mimicked those found under physiological conditions. The micelles were added to the apical side of Caco-2 TC-7 cell monolayers for 30 min or 3 h at 37 degrees C. Absorbed lutein, i.e. the sum of lutein recovered in the scraped cells and in the basolateral chamber, was quantified by HPLC. Transport rate was measured (i) as a function of time (from 15 to 60 min), (ii) as a function of micellar lutein concentration (from 1.5 to 15 microM), (iii) at 4 degrees C, (iv) in the basolateral to apical direction, (v) after trypsin pretreatment, (vi) in the presence of beta-carotene and/or lycopene, (vii) in the presence of increasing concentrations of antibody against SR-BI (scavenger receptor class B type 1) and (viii) in the presence of increasing concentrations of a chemical inhibitor of the selective transfer of lipids mediated by SR-BI, i.e. BLT1 (blocks lipid transport 1). The rate of transport of lutein as a function of time and as a function of concentration was saturable. It was significantly lower at 4 degrees C than at 37 degrees C (approx. 50%), in the basal to apical direction than in the opposite direction (approx. 85%), and after trypsin pretreatment (up to 45%). Co-incubation with beta-carotene, but not lycopene, decreased the lutein absorption rate (approx. 20%) significantly. Anti-SR-BI antibody and BLT1 significantly impaired the absorption rate (approx. 30% and 57% respectively). Overall, these results indicate that lutein absorption is, at least partly, protein-mediated and that some lutein is taken up

  1. Lutein transport by Caco-2 TC-7 cells occurs partly by a facilitated process involving the scavenger receptor class B type I (SR-BI)

    PubMed Central

    2004-01-01

    The carotenoid lutein is thought to play a role in the human eye and to protect against age-related macular degeneration. Lutein transport in the human intestine has not been characterized. We examined lutein transport processes using Caco-2 TC-7 monolayers as a model for human intestinal epithelium. Purified lutein was mixed with phospholipids, lysophospholipids, cholesterol, mono-olein, oleic acid and taurocholate to obtain lutein-rich mixed micelles that mimicked those found under physiological conditions. The micelles were added to the apical side of Caco-2 TC-7 cell monolayers for 30 min or 3 h at 37 °C. Absorbed lutein, i.e. the sum of lutein recovered in the scraped cells and in the basolateral chamber, was quantified by HPLC. Transport rate was measured (i) as a function of time (from 15 to 60 min), (ii) as a function of micellar lutein concentration (from 1.5 to 15 μM), (iii) at 4 °C, (iv) in the basolateral to apical direction, (v) after trypsin pretreatment, (vi) in the presence of β-carotene and/or lycopene, (vii) in the presence of increasing concentrations of antibody against SR-BI (scavenger receptor class B type 1) and (viii) in the presence of increasing concentrations of a chemical inhibitor of the selective transfer of lipids mediated by SR-BI, i.e. BLT1 (blocks lipid transport 1). The rate of transport of lutein as a function of time and as a function of concentration was saturable. It was significantly lower at 4 °C than at 37 °C (approx. 50%), in the basal to apical direction than in the opposite direction (approx. 85%), and after trypsin pretreatment (up to 45%). Co-incubation with β-carotene, but not lycopene, decreased the lutein absorption rate (approx. 20%) significantly. Anti-SR-BI antibody and BLT1 significantly impaired the absorption rate (approx. 30% and 57% respectively). Overall, these results indicate that lutein absorption is, at least partly, protein-mediated and that some lutein is taken up through SR

  2. Orbits of massive satellite galaxies - I. A close look at the Large Magellanic Cloud and a new orbital history for M33

    NASA Astrophysics Data System (ADS)

    Patel, Ekta; Besla, Gurtina; Sohn, Sangmo Tony

    2017-02-01

    The Milky Way (MW) and M31 both harbour massive satellite galaxies, the Large Magellanic Cloud (LMC) and M33, which may comprise up to 10 per cent of their host's total mass. Massive satellites can change the orbital barycentre of the host-satellite system by tens of kiloparsec and are cosmologically expected to harbour dwarf satellite galaxies of their own. Assessing the impact of these effects crucially depends on the orbital histories of the LMC and M33. Here, we revisit the dynamics of the MW-LMC system and present the first detailed analysis of the M31-M33 system utilizing high-precision proper motions and statistics from the dark-matter-only Illustris cosmological simulation. With the latest Hubble Space Telescope proper motion measurements of M31, we reliably constrain M33's interaction history with its host. In particular, like the LMC, M33 is either on its first passage (tinf < 2 Gyr ago) or if M31 is massive (≥2 × 1012 M⊙), it is on a long-period orbit of about 6 Gyr. Cosmological analogues of the LMC and M33 identified in Illustris support this picture and provide further insight about their host masses. We conclude that, cosmologically, massive satellites such as the LMC and M33 are likely completing their first orbits about their hosts. We also find that the orbital energies of such analogues prefer an MW halo mass ˜1.5 × 1012 M⊙ and an M31 halo mass ≥1.5 × 1012 M⊙. Despite conventional wisdom, we conclude it is highly improbable that M33 made a close (<100 kpc) approach to M31 recently (tperi < 3 Gyr ago). Such orbits are rare (<1 per cent) within the 4σ error space allowed by observations. This conclusion cannot be explained by perturbative effects through four-body encounters amongst the MW, M31, M33, and the LMC. This surprising result implies that we must search for a new explanation for M33's strongly warped gas and stellar discs.

  3. 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

  4. 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.

  5. 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.

  6. A survey of the Local Group of galaxies for symbiotic binary stars - I. First detection of symbiotic stars in M33

    NASA Astrophysics Data System (ADS)

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

    2017-02-01

    We present and discuss initial selection criteria and first results in M33 from a systematic search for extragalactic symbiotic stars. We show that the presence of diffuse ionized gas (DIG) emission can significantly contaminate the spectra of symbiotic star candidates. This important effect forces upon us a more stringent working definition of an extragalactic symbiotic star. We report the first detections and spectroscopic characterization of 12 symbiotic binaries in M33. We found that four of our systems contain carbon-rich giants. In another two of them, the giant seems to be a Zr-enhanced MS star, while the remaining six objects host M-type giants. The high number ratio of C to M giants in these binaries is consistent with the low metallicity of M33. The spatial and radial velocity distributions of these new symbiotic binaries are consistent with a wide range of progenitor star ages.

  7. The Contribution of Field OB Stars to the Ionization of the Diffuse Ionized Gas in M33

    NASA Astrophysics Data System (ADS)

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

    2000-10-01

    We present a study of the ionizing stars associated with the diffuse ionized gas (DIG) and H II regions in the nearby spiral galaxy M33. We compare our Schmidt Hα image to the far-ultraviolet (FUV, 1520 Å) image from the Ultraviolet Imaging Telescope (UIT). The Hα/FUV ratio is higher in H II regions than in the DIG, suggesting an older population of ionizing stars in the DIG. Assuming ionization equilibrium, we convert the Hα flux to the number of Lyman continuum photons NLyc. When compared to models of evolving stellar populations, the NLyc/FUV ratio in H II regions is consistent with a young burst, while the DIG ratio resembles an older burst population, or a steady state population built up by constant star formation, which is probably a more accurate description of the stellar population in the field. The UIT data is complemented with archival FUV and optical images of a small portion of the disk of M33 obtained with WFPC2 on board the Hubble Space Telescope (HST). These images overlap low- and mid-luminosity H II regions as well as DIG, so we can investigate the stellar population in these environments. Using the HST FUV and optical photometry, we assign spectral types to the stars observed in DIG and H II regions. The photometry indicates that ionizing stars are present in the DIG. We compare the predicted ionizing flux with the amount required to produce the observed Hα emission, and we find that field OB stars in the HST images can account for 40%+/-12% of the ionization of the DIG, while the stars in H II regions can provide 107%+/-26% of the Hα luminosity of the H II regions. Due to the limited coverage of the HST data, we cannot determine if stars outside the HST fields ionize some of the DIG located in the HST fields, nor can we determine if photons from stars inside the HST fields leak out of the area covered by the HST fields. We do not find any correlation between leakage of ionizing photons and Hα luminosity for the H II regions in our HST

  8. 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

  9. 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

  10. The Araucaria Project. A Distance Determination to the Local Group Spiral M33 from Near-infrared Photometry of Cepheid Variables

    NASA Astrophysics Data System (ADS)

    Gieren, Wolfgang; Górski, Marek; Pietrzyński, Grzegorz; Konorski, Piotr; Suchomska, Ksenia; Graczyk, Dariusz; Pilecki, Bogumil; Bresolin, Fabio; Kudritzki, Rolf-Peter; Storm, Jesper; Karczmarek, Paulina; Gallenne, Alexandre; Calderón, Paula; Geisler, Doug

    2013-08-01

    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. Based on observations obtained with the ESO VLT for program 382.D-0469(A).

  11. 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 ...

  12. Swift/UVOT Measurements of the UV Dust Extinction Curve and the Recent Star Formation History of the SMC and M33

    NASA Astrophysics Data System (ADS)

    Hagen, Lea M. Z.; Siegel, Michael; Hoversten, Erik A.; Gronwall, Caryl; Immler, Stefan; Vargas, Angelica

    2017-01-01

    The Swift Ultraviolet/Optical Telescope (UVOT) is uniquely suited to study star formation and dust extinction in nearby galaxies. I will discuss results from the Small Magellanic Cloud (SMC) and M33, for which we have unprecedented observations in three near-UV bands from 1700-3000Å at 2.5" resolution. We combine our UV imaging with archival optical and infrared data to model the spectral energy distributions of individual regions of each galaxy, simultaneously fitting for the dust extinction curve properties, total dust, stellar mass, and age. We have created the first-ever maps of the UV dust extinction curve, which show previously-unconfirmed spatial variation: both the slope and 2175Å bump vary considerably over the face of both the SMC and M33. I will discuss the implications of these results on studies of star formation and galaxy evolution at both low and high redshift.

  13. 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.

  14. 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

  15. 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.

  16. Two rare variations, D478N and D478E, that occur at the same amino acid residue in nicotinic acetylcholine receptor (nAChR) α2 subunit influence nAChR function.

    PubMed

    Dash, Bhagirathi; Li, Ming D

    2014-10-01

    There occur two rare variations, Asp(D)478Asn(N) and Asp(D)478Glu(E), in the putative cytoplasmic amphipathic α-helices of human nicotinic acetylcholine receptor (nAChR) α2 subunit as a result of mutation in the 1st (G → A: rs141072985) and 3rd (C → A: rs56344740) nucleotide of its 478th triplet codon (GAC). We assessed the effects of these two variations on the function of α2β2- and α2β4-nAChRs as they could alter the electronegativity and/or the structure of the cytoplasmic 'portals' (framed by subunit amphipathic α-helices) necessary for obligate ion permeation from extracellular space to cytoplasm. We injected decreasing ratio of subunit cRNAs (α:β; 10:1, 1:1 and 1:10) into Xenopus oocytes to express putative low-sensitivity (LS; 10:1), intermediate-sensitivity (IS; 1:1) and high sensitivity (HS; 1:10) isoforms of wild type and variant α2β2- and α2β4-nAChRs. Two-electrode voltage clamp analyses indicate that the agonist (ACh or nicotine) induced peak current responses (Imax) of α2β2-nAChR isoforms and those of α2β4-nAChR isoforms are increased (1.3-4.7-fold) as a result of D478E variation. The α2 subunit D478N variation only increases the Imax of IS (∼2-fold) or HS (1.4-2.1-fold) α2β2-nAChRs. Concentration-response curves constructed indicate no effect on agonist sensitivities of LS and HS isoforms of α2β2- or α2β4-nAChRs as a result of either variation in α2 subunit. Between the two variant nAChRs, α2(D478E)*-nAChR isoforms generally yield higher Imax than those of respective α2(D478N)*-nAChR isoforms. These effects could be attributed to alteration in cytoplasmic 'portals' and/or ion permeation through it owing to change in amino acid electronegativity (D → N) and side chain length (D → E) in nAChR α2 subunit.

  17. "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

  18. Naturally occurring insecticides.

    PubMed Central

    Soloway, S B

    1976-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2011-01-01

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

  20. 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

  1. 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.

  2. Commonly occurring plant flavonoids have estrogenic activity.

    PubMed

    Miksicek, R J

    1993-07-01

    A remarkable diversity of naturally occurring and synthetic compounds have been shown to mimic the biological effects of 17 beta-estradiol by virtue of their ability to bind to and activate the nuclear estrogen receptor. This report extends the family of nonsteroidal estrogens to include several multiply hydroxylated chalcones, flavanones, and flavones. The hormone-like activity of these natural plant products is indicated by their ability to stimulate an estrogen receptor-dependent transcriptional response and to promote growth of estrogen-dependent MCF7 cells in culture. The transcriptional response can be inhibited by the steroidal estrogen antagonist ICI-164,384 and is specific for the estrogen receptor. Evidence is presented to show that selected hydroxylated flavonoids interact directly with the estrogen receptor, based on their ability to compete for the binding of 17 beta-[3H]estradiol to the receptor in cell-free extracts. These compounds are less active, on a molar basis, than 17 beta-estradiol or the synthetic dihydroxystilbene estrogens, but they have potencies comparable to those of other known phytoestrogens. Together, these findings broaden our understanding of the structure-activity relationships for nonsteroidal estrogens and present a series of new chemical prototypes for the future development of potentially useful agonists and antagonists for this nuclear receptor. The wide distribution of weakly estrogenic flavonoid pigments in food crops and medicinal plants raises additional questions about the possible health risks and benefits of these compounds, meriting closer examination of their presence in the human diet.

  3. 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

  4. Serotonin 5-HT3 receptor-mediated vomiting occurs via the activation of Ca2+/CaMKII-dependent ERK1/2 signaling in the least shrew (Cryptotis parva).

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  6. 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.

  7. 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.

  8. 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.

  9. Repetition Blindness Occurs in Nonwords

    ERIC Educational Resources Information Center

    Harris, Catherine L.; Morris, Alison L.

    2004-01-01

    Theorists have predicted that repetition blindness (RB) should be absent for nonwords because they do not activate preexisting mental types. The authors hypothesized that RB would be observed for nonwords because RB can occur at a sublexical level. Four experiments showed that RB is observed for word-nonword pairs (noon noof), orthographically…

  10. Mucinous carcinoma occurring in the male breast.

    PubMed

    Ishida, Mitsuaki; Umeda, Tomoko; Kawai, Yuki; Mori, Tsuyoshi; Kubota, Yoshihiro; Abe, Hajime; Iwai, Muneo; Yoshida, Keiko; Kagotani, Akiko; Tani, Tohru; Okabe, Hidetoshi

    2014-02-01

    Male breast carcinoma is an uncommon neoplasm, accounting for 0.6% of all breast carcinomas. Invasive ductal carcinoma of no special type is the most common type of male breast carcinoma, and mucinous carcinoma occurring in the male breast is extremely rare. In the present study, we report a case of mucinous carcinoma of the male breast and discuss the clinicopathological features of this type of tumor. A 63-year-old Japanese male presented with a gradually enlarged nodule in the right breast. The resected breast specimen revealed pure mucinous carcinoma and immunohistochemical analyses demonstrated that tumor cells were positive for estrogen receptor (ER), but negative for progesterone receptor (PgR). In addition, HER2 expression was not amplified. Pure mucinous carcinoma is generally associated with a low incidence of lymph node or distant metastases, and excellent disease-free survival in females. However, certain cases of this type of tumor with axillary lymph node metastasis in the male breast have been reported. In addition, the immunoprofiles of mucinous carcinoma in males are fundamentally the same as those in females. More than 90% of cases show positive immunoreactivity for ER and/or PgR, and HER2 expression is not amplified. However, it has been reported that breast cancer in males is more frequently positive for ER than in females, and has less HER2 overexpression. The high rate of hormone receptor-positive breast cancer in males is considered to be due to similar conditions as those in breast cancer in postmenopausal women. The pathogenesis of male breast carcinoma, including mucinous carcinoma, remains unclear; therefore, additional clinicopathological studies are required.

  11. 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).

  12. When Yawning Occurs in Elephants

    PubMed Central

    Rossman, Zoë T.; Hart, Benjamin L.; Greco, Brian J.; Young, Debbie; Padfield, Clare; Weidner, Lisa; Gates, Jennifer; Hart, Lynette A.

    2017-01-01

    Yawning is a widely recognized behavior in mammalian species. One would expect that elephants yawn, although to our knowledge, no one has reported observations of yawning in any species of elephant. After confirming a behavioral pattern matching the criteria of yawning in two Asian elephants (Elephas maximus) in a zoological setting, this study was pursued with nine captive African elephants (Loxodonta africana) at a private reserve in the Western Cape, South Africa, the Knysna Elephant Park. Observations were made in June–September and in December. In the daytime, handlers managed seven of the elephants for guided interactions with visitors. At night, all elephants were maintained in a large enclosure with six having limited outdoor access. With infrared illumination, the elephants were continuously recorded by video cameras. During the nights, the elephants typically had 1–3 recumbent sleeping/resting bouts, each lasting 1–2 h. Yawning was a regular occurrence upon arousal from a recumbency, especially in the final recumbency of the night. Yawning was significantly more frequent in some elephants. Yawning was rare during the daytime and during periods of standing around in the enclosure at night. In six occurrences of likely contagious yawning, one elephant yawned upon seeing another elephant yawning upon arousal from a final recumbency; we recorded the sex and age category of the participants. The generality of yawning in both African and Asian elephants in other environments was documented in video recordings from 39 zoological facilities. In summary, the study provides evidence that yawning does occur in both African and Asian elephants, and in African elephants, yawning was particularly associated with arousal from nighttime recumbencies. PMID:28293560

  13. When Yawning Occurs in Elephants.

    PubMed

    Rossman, Zoë T; Hart, Benjamin L; Greco, Brian J; Young, Debbie; Padfield, Clare; Weidner, Lisa; Gates, Jennifer; Hart, Lynette A

    2017-01-01

    Yawning is a widely recognized behavior in mammalian species. One would expect that elephants yawn, although to our knowledge, no one has reported observations of yawning in any species of elephant. After confirming a behavioral pattern matching the criteria of yawning in two Asian elephants (Elephas maximus) in a zoological setting, this study was pursued with nine captive African elephants (Loxodonta africana) at a private reserve in the Western Cape, South Africa, the Knysna Elephant Park. Observations were made in June-September and in December. In the daytime, handlers managed seven of the elephants for guided interactions with visitors. At night, all elephants were maintained in a large enclosure with six having limited outdoor access. With infrared illumination, the elephants were continuously recorded by video cameras. During the nights, the elephants typically had 1-3 recumbent sleeping/resting bouts, each lasting 1-2 h. Yawning was a regular occurrence upon arousal from a recumbency, especially in the final recumbency of the night. Yawning was significantly more frequent in some elephants. Yawning was rare during the daytime and during periods of standing around in the enclosure at night. In six occurrences of likely contagious yawning, one elephant yawned upon seeing another elephant yawning upon arousal from a final recumbency; we recorded the sex and age category of the participants. The generality of yawning in both African and Asian elephants in other environments was documented in video recordings from 39 zoological facilities. In summary, the study provides evidence that yawning does occur in both African and Asian elephants, and in African elephants, yawning was particularly associated with arousal from nighttime recumbencies.

  14. Partial Functional Complementation between Human and Mouse Cytomegalovirus Chemokine Receptor Homologues▿

    PubMed Central

    Farrell, Helen E.; Abraham, Alexander M.; Cardin, Rhonda D.; Sparre-Ulrich, Alexander H.; Rosenkilde, Mette M.; Spiess, Katja; Jensen, Tine H.; Kledal, Thomas N.; Davis-Poynter, Nicholas

    2011-01-01

    The human cytomegalovirus (CMV) proteins US28 and UL33 are homologous to chemokine receptors (CKRs). Knockout of the mouse CMV M33 protein (UL33 homologue) results in substantial attenuation of salivary gland infection/replication and reduced efficiency of reactivation from tissue explants. M33-mediated G protein-coupled signaling is critical for the salivary gland phenotype. In this report, we demonstrate that US28 and (to a lesser degree) UL33 restore reactivation from tissue explants and partially restore replication in salivary glands (compared to a signaling-deficient M33 mutant). These studies provide a novel small animal model for evaluation of therapies targeting the human CMV CKRs. PMID:21490099

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

    PubMed Central

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

    2016-01-01

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

  16. Estrogenic activity of naturally occurring anthocyanidins.

    PubMed

    Schmitt, E; Stopper, H

    2001-01-01

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

  17. TENORM (Technologically Enhanced Naturally Occurring Radioactive Materials)

    MedlinePlus

    Jump to main content US EPA United States Environmental Protection Agency Search Search Radiation Protection Share Facebook Twitter Google+ Pinterest Contact Us Technologically Enhanced Naturally Occurring Radioactive ...

  18. Luminous and Variable Stars in M31 and M33. IV. Luminous Blue Variables, Candidate LBVs, B[e] Supergiants, and the Warm Hypergiants: How to Tell Them Apart

    NASA Astrophysics Data System (ADS)

    Humphreys, Roberta M.; Gordon, Michael S.; Martin, John C.; Weis, Kerstin; Hahn, David

    2017-02-01

    In this series of papers we have presented the results of a spectroscopic survey of luminous stars in the nearby spirals M31 and M33. Here, we present spectroscopy of 132 additional stars. Most have emission-line spectra, including luminous blue variables (LBVs) and candidate LBVs, Fe ii emission line stars, the B[e] supergiants, and the warm hypergiants. Many of these objects are spectroscopically similar and are often confused with each other. We examine their similarities and differences and propose the following guidelines that can be used to help distinguish these stars in future work. (1) The B[e] supergiants have emission lines of [O i] and [Fe ii] in their spectra. Most of the spectroscopically confirmed sgB[e] stars also have warm circumstellar dust in their spectral energy distributions (SEDs). (2) Confirmed LBVs do not have the [O i] emission lines in their spectra. Some LBVs have [Fe ii] emission lines, but not all. Their SEDs show free–free emission in the near-infrared but no evidence for warm dust. Their most important and defining characteristic is the S Dor-type variability. (3) The warm hypergiants spectroscopically resemble the LBVs in their dense wind state and the B[e] supergiants. However, they are very dusty. Some have [Fe ii] and [O i] emission in their spectra like the sgB[e] stars, but are distinguished by their A- and F-type absorption-line spectra. In contrast, the B[e] supergiant spectra have strong continua and few if any apparent absorption lines. Candidate LBVs should share the spectral characteristics of the confirmed LBVs with low outflow velocities and the lack of warm circumstellar dust. Based on observations with the Multiple Mirror Telescope, a joint facility of the Smithsonian Institution and the University of Arizona and on observations obtained with the Large Binocular Telescope (LBT), an international collaboration among institutions in the United States, Italy, and Germany. LBT Corporation partners are The University of

  19. Allergies and Asthma: They Often Occur Together

    MedlinePlus

    ... occur together. The same substances that trigger your hay fever symptoms, such as pollen, dust mites and pet ... a major risk factor for allergic asthma. Having hay fever or other allergies yourself also increases your risk ...

  20. Naturally Occurring Radon and 120(h) transfers

    EPA Pesticide Factsheets

    This page contains a discussion regarding how the presence of naturally occurring radon on closing military bases affects the United States' ability to transfer parcels under §120(h) (3) and §120(h) (4).

  1. Molten Metal Explosions are Still Occurring

    DTIC Science & Technology

    2009-02-01

    recycling plant. Another recent 665 Light Metals 2009 Edited by: Geoff Bearne TMS (The Minerals, Metals & Materials Society), 2009 catastrophic...occurred recently in a recycling plant casting small ingots over a water tank. An explosion occurred that extensively damaged the machine and...have been held in Europe as a joint activity with the European Aluminium Association (EAA) and the International Aluminium Institute (IAI). These

  2. Trichotillomania and Co-occurring Anxiety

    PubMed Central

    Grant, Jon E.; Redden, Sarah A.; Leppink, Eric W.; Chamberlain, Samuel R.

    2017-01-01

    Background Trichotillomania appears to be a fairly common disorder, with high rates of co-occurring anxiety disorders. Many individuals with trichotillomania also report that pulling worsens during periods of increased anxiety. Even with these clinical links to anxiety, little research has explored whether trichotillomania with co-occurring anxiety is a meaningful subtype. Methods 165 adults with trichotillomania were examined on a variety of clinical measures including symptom severity, functioning, and comorbidity. Participants also underwent cognitive testing assessing motor inhibition and cognitive flexibility. Clinical features and cognitive functioning were compared between those with current co-occurring anxiety disorders (i.e. social anxiety, generalized anxiety disorder, panic disorder, and anxiety disorder NOS) (n=38) and those with no anxiety disorder (n=127). Results Participants with trichotillomania and co-occurring anxiety reported significantly worse hair pulling symptoms, were more likely to have co-occurring depression, and were more likely to have a first-degree relative with obsessive compulsive disorder. Those with anxiety disorders also exhibited significantly worse motor inhibitory performance on a task of motor inhibition (stop-signal task). Conclusions This study suggests that anxiety disorders affect the clinical presentation of hair pulling behavior. Further research is needed to validate our findings and to consider whether treatments should be specially tailored differently for adults with trichotillomania who have co-occurring anxiety disorders, or more pronounced cognitive impairment. PMID:27668531

  3. 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…

  4. Necrobiotic xanthogranuloma occurring in an eyelid scar.

    PubMed

    Rayner, S A; Duncombe, A S; Keefe, M; Theaker, J; Manners, R M

    2008-01-01

    We present a case report of necrobiotic xanthogranuloma (NXG) in a 76-year-old Caucasian lady occurring as a nodule in a blepharoplasty scar. NXG is a rare histiocytic disease with progressive orbital and systemic features. Management options of excision biopsy or chemotherapy are discussed.

  5. Preferential flow occurs in unsaturated conditions

    USGS Publications Warehouse

    Nimmo, John R.

    2012-01-01

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

  6. Ethical issues occurring within nursing education.

    PubMed

    Fowler, Marsha D; Davis, Anne J

    2013-03-01

    The large body of literature labeled "ethics in nursing education" is entirely devoted to curricular matters of ethics education in nursing schools, that is, to what ought to be the ethics content that is taught and what theory or issues ought to be included in all nursing curricula. Where the nursing literature actually focuses on particular ethical issues, it addresses only single topics. Absent from the literature, however, is any systematic analysis and explication of ethical issues or dilemmas that occur within the context of nursing education. The objective of this article is to identify the spectrum of ethical issues in nursing education to the end of prompting a systematic and thorough study of such issues, and to lay the groundwork for research by identifying and provisionally typologizing the ethical issues that occur within the context of academic nursing.

  7. 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.

  8. spin pumping occurred under nonlinear spin precession

    NASA Astrophysics Data System (ADS)

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

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

  9. 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

  10. Jerky Periods: Myoclonus Occurring Solely During Menses

    PubMed Central

    Buijink, Arthur W. G.; Gelauff, Jeannette M.; van der Salm, Sandra M. A.; Tijssen, Marina A. J.; van Rootselaar, Anne-Fleur

    2013-01-01

    Background In this case report, we describe an unusual case of a patient with myoclonus only occurring during menses. Case Report A 41-year-old female, known to have neurological sequelae after a car accident 1 year earlier, presented with myoclonic movements of the right arm and hand only during menses. Brain magnetic resonance imaging is compatible with head trauma. Electromyography shows brief irregular bursts with a duration of about 20 ms. Discussion This appears to be the first description of myoclonus appearing only during menses. We suggest a cortical origin for myoclonus. PMID:23724361

  11. Muscle damage occurring in wheelchair sports people.

    PubMed

    Ide, M; Ogata, H; Kobayashi, M; Wada, F

    1997-04-01

    Seven college-age healthy men exercised on a wheelchair treadmill to evaluate muscle damage that may occur from wheelchair propulsion. An experimental model in which a participant performs up-hill running in a wheelchair was prepared. Plasma creatinekinase (CK), myoglobin (Mb) and lactatedehydrogenase (LDH) were measured as parameters. Blood samples were taken pre-, immediately after-, 24 h after- and 72 h after the exercise. All of these parameters significantly increased after the exercise, but their time-courses were apparently varied. It is concluded that wheelchair propulsion causes muscle damage in certain situations such as up-hill running.

  12. Attention turns to naturally occurring methane seepage

    NASA Astrophysics Data System (ADS)

    Kvenvolden, Keith A.; Lorenson, Thomas D.; Reeburgh, William S.

    Methane is the most abundant organic compound in the Earth's atmosphere. As a powerful greenhouse gas, it has implications for global climate change. Sources of methane to the atmosphere are varied. Depending on the source, methane can contain either modern or ancient carbon. Methane exiting from swamps and wetlands contains modern carbon, whereas methane leaking from petroleum reservoirs contains ancient carbon. The total annual source of methane to the atmosphere has been constrained to about 540 teragrams (Tg) per year “Cicerone and Oremland, 1988”. Notably absent from any identified sources is the contribution of geologically sourced methane from naturally occurring seepage.

  13. 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

  14. Persulfate activation by naturally occurring trace minerals.

    PubMed

    Teel, Amy L; Ahmad, Mushtaque; Watts, Richard J

    2011-11-30

    The potential for 13 naturally occurring minerals to mediate the decomposition of persulfate and generate a range of reactive oxygen species was investigated to provide fundamental information on activation mechanisms when persulfate is used for in situ chemical oxidation (ISCO). Only four of the minerals (cobaltite, ilmenite, pyrite, and siderite) promoted the decomposition of persulfate more rapidly than persulfate-deionized water control systems. The other nine minerals decomposed persulfate at the same rate or more slowly than the control systems. Mineral-mediated persulfate activation was conducted with the addition of one of three probe compounds to detect the generation of reactive oxygen species: anisole (sulfate+hydroxyl radical), nitrobenzene (hydroxyl radical), and hexachloroethane (reductants and nucleophiles). The reduced mineral pyrite promoted rapid generation of sulfate+hydroxyl radical. However, the remainder of the minerals provided minimal potential for the generation of reactive oxygen species. The results of this research demonstrate that the majority of naturally occurring trace minerals do not activate persulfate to generate reactive oxygen species, and other mechanisms of activation are necessary to promote contaminant destruction in the subsurface during persulfate ISCO.

  15. Tetrahydroberberine, a pharmacologically active naturally occurring alkaloid.

    PubMed

    Pingali, Subramanya; Donahue, James P; Payton-Stewart, Florastina

    2015-04-01

    Tetrahydroberberine (systematic name: 9,10-dimethoxy-5,8,13,13a-tetrahydro-6H-benzo[g][1,3]benzodioxolo[5,6-a]quinolizine), C20H21NO4, a widely distributed naturally occurring alkaloid, has been crystallized as a racemic mixture about an inversion center. A bent conformation of the molecule is observed, with an angle of 24.72 (5)° between the arene rings at the two ends of the reduced quinolizinium core. The intermolecular hydrogen bonds that play an apparent role in crystal packing are 1,3-benzodioxole -CH2···OCH3 and -OCH3···OCH3 interactions between neighboring molecules.

  16. Does dietary learning occur outside awareness?

    PubMed

    Brunstrom, Jeffrey M

    2004-09-01

    Several forms of dietary learning have been identified in humans. These include flavor-flavor learning, flavor-postingestive learning (including flavor-caffeine learning), and learned satiety. Generally, learning is thought to occur in the absence of contingency (CS-US) or demand awareness. However, a review of the literature suggests that this conclusion may be premature because measures of awareness lack the rigor that is found in studies of other kinds of human learning. If associations do configure outside awareness then this should be regarded as a rare instance of automatic learning. Conversely, if awareness is important, then successful learning may be governed by an individual's beliefs and predilection to attend to stimulus relationships. For researchers of dietary learning this could be critical because it might explain why learning paradigms have a reputation for being unreliable. Since most food preferences are learned, asking questions about awareness can also tell us something fundamental about everyday dietary control.

  17. Hibernation in a primate: does sleep occur?

    PubMed Central

    Dausmann, Kathrin H.; Faherty, Sheena L.; Klopfer, Peter; Krystal, Andrew D.; Schopler, Robert; Yoder, Anne D.

    2016-01-01

    During hibernation, critical physiological processes are downregulated and thermogenically induced arousals are presumably needed periodically to fulfil those physiological demands. Among the processes incompatible with a hypome tabolic state is sleep. However, one hibernating primate, the dwarf lemur Cheirogaleus medius, experiences rapid eye movement (REM)-like states during hibernation, whenever passively reaching temperatures above 30°C, as occurs when it hibernates in poorly insulated tree hollows under tropical conditions. Here, we report electroencephalographic (EEG) recordings, temperature data and metabolic rates from two related species (C. crossleyi and C. sibreei), inhabiting high-altitude rainforests and hibernating underground, conditions that mirror, to some extent, those experienced by temperate hibernators. We compared the physiology of hibernation and spontaneous arousals in these animals to C. medius, as well as the much more distantly related non-primate hibernators, such as Arctic, golden-mantled and European ground squirrels. We observed a number of commonalities with non-primate temperate hibernators including: (i) monotonous ultra-low voltage EEG during torpor bouts in these relatively cold-weather hibernators, (ii) the absence of sleep during torpor bouts, (iii) the occurrence of spontaneous arousals out of torpor, during which sleep regularly occurred, (iv) relatively high early EEG non-REM during the arousal, and (v) a gradual transition to the torpid EEG state from non-REM sleep. Unlike C. medius, our study species did not display sleep-like states during torpor bouts, but instead exclusively exhibited them during arousals. During these short euthermic periods, non-REM as well as REM sleep-like stages were observed. Differences observed between these two species and their close relative, C. medius, for which data have been published, presumably reflect differences in hibernaculum temperature. PMID:27853604

  18. 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

  19. Naturally occurring contamination in the Mancos Shale.

    PubMed

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

    2012-02-07

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

  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.

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. Adenosine receptor neurobiology: overview.

    PubMed

    Chen, Jiang-Fan; Lee, Chien-fei; Chern, Yijuang

    2014-01-01

    Adenosine is a naturally occurring nucleoside that is distributed ubiquitously throughout the body as a metabolic intermediary. In the brain, adenosine functions as an important upstream neuromodulator of a broad spectrum of neurotransmitters, receptors, and signaling pathways. By acting through four G-protein-coupled receptors, adenosine contributes critically to homeostasis and neuromodulatory control of a variety of normal and abnormal brain functions, ranging from synaptic plasticity, to cognition, to sleep, to motor activity to neuroinflammation, and cell death. This review begun with an overview of the gene and genome structure and the expression pattern of adenosine receptors (ARs). We feature several new developments over the past decade in our understanding of AR functions in the brain, with special focus on the identification and characterization of canonical and noncanonical signaling pathways of ARs. We provide an update on functional insights from complementary genetic-knockout and pharmacological studies on the AR control of various brain functions. We also highlight several novel and recent developments of AR neurobiology, including (i) recent breakthrough in high resolution of three-dimension structure of adenosine A2A receptors (A2ARs) in several functional status, (ii) receptor-receptor heterodimerization, (iii) AR function in glial cells, and (iv) the druggability of AR. We concluded the review with the contention that these new developments extend and strengthen the support for A1 and A2ARs in brain as therapeutic targets for neurologic and psychiatric diseases.

  6. Iron deficiency occurs frequently in children with cystic fibrosis.

    PubMed

    Uijterschout, Lieke; Nuijsink, Marianne; Hendriks, Daniëlle; Vos, Rimke; Brus, Frank

    2014-05-01

    In adult CF patients iron deficiency (ID) is common and primarily functional due to chronic inflammation. No recent data are available on the cause of ID and iron deficiency anemia (IDA) in children with CF. Over the last decades onset of inflammation and pulmonary disease in children with CF is delayed by improved nutritional status. We questioned whether ID occurs in the same extent among children with CF as in adult CF patients. We therefore conducted a study to investigate the iron status of children with CF and to determine whether ID and IDA are associated with dietary iron intake, lung disease severity and Pseudomonas aeruginosa (PA) infection. Clinical charts of 53 children with CF aged 0-16 were reviewed. Follow-up varied from 1 to 14 years with 343 annual observations in total. Thirty-two children (60.4%) were iron deficient in at least 1 year and ID was present in 84 of 343 observations (24.5%). In 2011 ID was present in 9 children (17.0%). Ten children (18.9%) were anemic in at least 1 year and anemia was present in 13 of 328 observations (4.0%). IDA was present in at least 1 year in 6 children (11.3%). Ferritin (Fer) was positively associated with age. Higher Fer values found in older children represent an increased state of inflammation, rather than an improved iron status, and might increase the relative contribution of functional ID. This study shows that ID is common in relatively healthy, well-nourished children with CF. The mechanism of ID in children with CF is currently unknown. A prospective study using both soluble transferrin receptor and Fer as indicators for ID will provide more insight in the incidence and causes of ID in children with CF.

  7. A comparison of substorms occurring during magnetic storms with those occurring during quiet times

    NASA Astrophysics Data System (ADS)

    McPherron, R. L.; Hsu, T.-S.

    2002-09-01

    It has been suggested that there may be a fundamental difference between substorms that occur during magnetic storms and those that occur at other times. [1996] presented evidence that there is no obvious change in lobe field in "quiet time" substorms but that "storm time" substorms exhibit the classic pattern of storage and release of lobe field energy. This result led them to speculate that the former are caused by current sheet disruption, while the latter are caused by reconnection of lobe flux. In this paper we examine their hypothesis with a much larger data set using definitions of the two types of substorms similar to theirs, as well as additional more restrictive definitions of these classes of events. Our results show that the only differences between the various classes are the absolute value of the lobe field and the size of the changes. When the data are normalized to unit field amplitude, we find that the percent change during storm time and non-storm time substorms is nearly the same. The above conclusions are demonstrated with superposed epoch analysis of lobe field (Bt and Bz) for four classes of substorms: active times (Dst < -50 nT, mostly recovery phase), main phase substorms, non-storm times (Dst > -25 nT), and quiet time substorms (no evidence of storm in Dst). Epoch zero for the analysis was taken as the main substorm onset (Pi2 onset closest to sharp break in AL index). Our results suggest that there is no qualitative distinction between the various classes of substorms, and so they are all likely to be caused by the same mechanism.

  8. Human presynaptic receptors.

    PubMed

    Schlicker, Eberhard; Feuerstein, Thomas

    2017-04-01

    Presynaptic receptors are sites at which transmitters, locally formed mediators or hormones inhibit or facilitate the release of a given transmitter from its axon terminals. The interest in the identification of presynaptic receptors has faded in recent years and it may therefore be justified to give an overview of their occurrence in the autonomic and central nervous system; this review will focus on presynaptic receptors in human tissues. Autoreceptors are presynaptic receptors at which a given transmitter restrains its further release, though in some instances may also increase its release. Inhibitory autoreceptors represent a typical example of a negative feedback; they are tonically activated by the respective endogenous transmitter and/or are constitutively active. Autoreceptors also play a role under pathophysiological conditions, e.g. by limiting the massive noradrenaline release occurring during congestive heart failure. They can be used for therapeutic purposes; e.g., the α2-adrenoceptor antagonist mirtazapine is used as an antidepressant and the inverse histamine H3 receptor agonist pitolisant has been marketed as a new drug for the treatment of narcolepsy in 2016. Heteroreceptors are presynaptic receptors at which transmitters from adjacent neurons, locally formed mediators (e.g. endocannabinoids) or hormones (e.g. adrenaline) can inhibit or facilitate transmitter release; they may be subject to an endogenous tone. The constipating effect of the sympathetic nervous system or of the antihypertensive drug clonidine is related to the activation of inhibitory α2-adrenoceptors on postganglionic parasympathetic neurons. Part of the stimulating effect of adrenaline on the sympathetic nervous system during stress is related to its facilitatory effect on noradrenaline release via β2-adrenoceptors.

  9. 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.

  10. Estrogen receptors in breast carcinoma.

    PubMed

    Huaman, A

    1979-11-01

    On the basis of estrogen receptor assays, breast carcinomas are presently classified as estrogen-dependent tumors, which respond to endocrine therapy, and autonomous tumors, for which endocrine therapy is useless. This paper presents a short review of the biochemical principles of estrogen dependence, the procedures used to determine estrogen receptors, and the clinical applications of the findings of these assay procedures. Biobhemically, the estroogen dependence of normal breast cells is explained as a biochemical reaction occurring between the circulating estradiol and the breast cell, which occurs in 3 steps: 1) circulating estradiol penetrates the cellular membrane by passive diffusion, followed by 2) combining of estradiol with the estrogen-binding protein (estrophilin) and formation of an estrogen receptor complex which undergoes activation and translocation into the nucleus, to result in 3) the activated steroid receptor which combines with the nuclear charomatin and stimulates ribonucleic acid synthesis for the formation of estradiol binding proteins or estradiol receptors. The cytosol method of Wittliff et al. is described in brief and entails radioactive competitive analysis; the other available laboratory procedure is immunofluorescence of tumor sections. Quantification of estrogen receptor content can be used clinically to decide on ablative endocrine therapy, to determine the effectiveness of anti-estrogen administration, to determine the primary site of metastatic carcinoma, and as a screenng device.

  11. Opioid Receptors.

    PubMed

    Stein, Christoph

    2016-01-01

    Opioids are the oldest and most potent drugs for the treatment of severe pain. Their clinical application is undisputed in acute (e.g., postoperative) and cancer pain, but their long-term use in chronic pain has met increasing scrutiny. This article reviews mechanisms underlying opioid analgesia and other opioid actions. It discusses the structure, function, and plasticity of opioid receptors; the central and peripheral sites of analgesic actions and side effects; endogenous and exogenous opioid receptor ligands; and conventional and novel opioid compounds. Challenging clinical situations, such as the tension between chronic pain and addiction, are also illustrated.

  12. 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

  13. Cytokine receptors and hematopoietic differentiation.

    PubMed

    Robb, L

    2007-10-15

    Colony-stimulating factors and other cytokines signal via their cognate receptors to regulate hematopoiesis. In many developmental systems, inductive signalling determines cell fate and, by analogy with this, it has been postulated that cytokines, signalling via their cognate receptors, may play an instructive role in lineage specification in hematopoiesis. An alternative to this instructive hypothesis is the stochastic or permissive hypothesis. The latter proposes that commitment to a particular hematopoietic lineage is an event that occurs independently of extrinsic signals. It predicts that the role of cytokines is to provide nonspecific survival and proliferation signals. In this review, we look at the role of cytokine receptor signalling in hematopoiesis and consider the evidence for both hypotheses. Data from experiments that genetically manipulate receptor gene expression in vitro or in vivo are reviewed. Experiments in which cytokine receptors were installed in multipotential cells showed that, in some cases, stimulation with the cognate ligand could lead to alterations in lineage output. The creation of genetically manipulated mouse strains demonstrated that cytokine receptors are required for expansion and survival of single lineages but did not reveal a role in lineage commitment. We conclude that hematopoietic differentiation involves mainly stochastic events, but that cytokine receptors also have some instructive role.

  14. 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…

  15. 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.

  16. Dopamine receptor oligomerization visualized in living cells.

    PubMed

    O'Dowd, Brian F; Ji, Xiaodong; Alijaniaram, Mohammad; Rajaram, Ryan D; Kong, Michael M C; Rashid, Asim; Nguyen, Tuan; George, Susan R

    2005-11-04

    G protein-coupled receptors occur as dimers within arrays of oligomers. We visualized ensembles of dopamine receptor oligomers in living cells and evaluated the contributions of receptor conformation to the dynamics of oligomer association and dissociation, using a strategy of trafficking a receptor to another cellular compartment. We incorporated a nuclear localization sequence into the D1 dopamine receptor, which translocated from the cell surface to the nucleus. Receptor inverse agonists blocked this translocation, retaining the modified receptor, D1-nuclear localization signal (NLS), at the cell surface. D1 co-translocated with D1-NLS to the nucleus, indicating formation of homooligomers. (+)-Butaclamol retained both receptors at the cell surface, and removal of the drug allowed translocation of both receptors to the nucleus. Agonist-nonbinding D1(S198A/S199A)-NLS, containing two substituted serine residues in transmembrane 5 also oligomerized with D1, and both were retained on the cell surface by (+)-butaclamol. Drug removal disrupted these oligomerized receptors so that D1 remained at the cell surface while D1(S198A/S199A)-NLS trafficked to the nucleus. Thus, receptor conformational differences permitted oligomer disruption and showed that ligand-binding pocket occupancy by the inverse agonist induced a conformational change. We demonstrated robust heterooligomerization between the D2 dopamine receptor and the D1 receptor. The heterooligomers could not be disrupted by inverse agonists targeting either one of the receptor constituents. However, D2 did not heterooligomerize with the structurally modified D1(S198A/S199A), indicating an impaired interface for their interaction. Thus, we describe a novel method showing that a homogeneous receptor conformation maintains the structural integrity of oligomers, whereas conformational heterogeneity disrupts it.

  17. Roundabout receptors.

    PubMed

    Ypsilanti, Athéna R; Chedotal, Alain

    2014-01-01

    Roundabout receptors (Robo) and their Slit ligands were discovered in the 1990s and found to be key players in axon guidance. Slit was initially described s an extracellular matrix protein that was expressed by midline glia in Drosophila. A few years later, it was shown that, in vertebrates and invertebrates, Slits acted as chemorepellents for axons crossing the midline. Robo proteins were originally discovered in Drosophila in a mutant screen for genes involved in the regulation of midline crossing. This ligand-receptor pair has since been implicated in a variety of other neuronal and non-neuronal processes ranging from cell migration to angiogenesis, tumourigenesis and even organogenesis of tissues such as kidneys, lungs and breasts.

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. Angular cheilitis occurring during orthodontic treatment: a case series.

    PubMed

    Cross, David L; Short, Laura J

    2008-12-01

    Clinical experience has shown that angular cheilitis can occur during orthodontic treatment and may persist into retention, but the incidence of the condition is unknown. The purpose of this paper is to increase the awareness among clinicians of angular cheilitis occurring during orthodontic treatment. It also proposes a treatment regime which may be used.

  4. Differential neuropsychopharmacological influences of naturally occurring tropane alkaloids anisodamine versus scopolamine.

    PubMed

    Zhang, Wei-Wei; Song, Ming-Ke; Cui, Yong-Yao; Wang, Hao; Zhu, Liang; Niu, Yin-Yao; Yang, Li-Min; Lu, Yang; Chen, Hong-Zhuan

    2008-10-10

    Two naturally occurring tropane alkaloids, anisodamine and scopolamine, structurally dissimilar in one OH group, are well established as muscarinic acetylcholine receptor (mAChR) antagonists in clinic and basic research. However, experimental evidence for central effects of anisodamine is limited and conflicting compared with that of scopolamine. In the present study, Morris water maze test, long-term potentiation (LTP) recording and receptor radioligand binding assays were used to explore the disparity in neuropsychopharmacological influences of anisodamine versus scopolamine and possible mechanisms. Anisodamine, at 10-40-fold higher doses than those of scopolamine, did not produce any spatial cognitive deficits as scopolamine, but tended to improve cognition at the repeated high doses. LTP in vivo was then adopted to predict BBB permeability of the muscarinic antagonists following systemic drug administration. Contrary to scopolamine, anisodamine did not influence the formation of LTP in the CA(1) region of rat hippocampus at 40-fold higher dose than that of scopolamine. Additionally, receptor radioligand binding assays (RRLBA) revealed that the binding affinity of anisodamine to mice brain mAChR was much lower than that of scopolamine. The findings suggested that anisodamine did not impair cognition nor depress LTP primarily due to its poor BBB permeability. This work enlarged knowledge of structure-activity relationship among tropane alkaloids, meanwhile providing evidence for more reasonable drug prescription in clinic.

  5. Alcohol Dependence, Co-occurring Conditions and Attributable Burden

    PubMed Central

    Odlaug, B.L.; Gual, A.; DeCourcy, J.; Perry, R.; Pike, J.; Heron, L.; Rehm, J.

    2016-01-01

    Aims Alcohol dependence is associated with high rates of co-occurring disorders which impact health-related quality of life (HRQoL) and add to the cost-of-illness. This study investigated the burden of alcohol dependence and associated co-occurring conditions on health and productivity. Methods A cross-sectional survey was conducted in eight European countries. Physicians (Psychiatrists and General Practitioners) completed patient record forms, which included assessment of co-occurring conditions, and patients completed matching self-completion forms. Drinking risk level (DRL) was calculated and the relationship between DRL, co-occurring conditions, work productivity, hospitalisations and rehabilitation stays was explored. Results Data were collected for 2979 alcohol-dependent patients (mean age 48.8 ± 13.6 years; 70% male). In total, 77% of patients suffered from moderate-to-severe co-occurring psychiatric and/or somatic conditions. High DRL was significantly associated with depression, greater work productivity losses, increased hospitalisations and rehabilitation stays. Co-occurring conditions were significantly associated with poorer HRQoL and decreased work productivity, with a statistical trend towards an increased frequency of rehabilitation stays. Conclusions Alcohol-dependent patients manifest high rates of co-occurring psychiatric and somatic conditions, which are associated with impaired work productivity and HRQoL. The continued burden of illness observed in these already-diagnosed patients suggests an unmet need in both primary and secondary care. PMID:26246514

  6. Chemotactic peptide receptor modulation in polymorphonuclear leukocytes

    PubMed Central

    1980-01-01

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

  7. 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/...

  8. 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

    2016-04-12

    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.

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

    PubMed Central

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

    2016-01-01

    Gradient-directed cell migration (chemotaxis) and growth (chemotropism) are universal processes, which 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 receptor on the plasma membrane polarizes to the side of the cell closest to the stimulus. Although receptor polarization occurs before and independently of actin-cable dependent vesicle delivery (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, independent 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

  10. The acetylcholine receptor as a cellular receptor for rabies virus.

    PubMed

    Lentz, T L; Burrage, T G; Smith, A L; Tignor, G H

    1983-01-01

    Characterization of specific host cell receptors for enveloped viruses is a difficult problem because many enveloped viruses bind to a variety of substrates which are not obviously related to tissue tropisms in the intact host. Viruses with a limited cellular tropism in infected animals present useful models for studying the mechanisms by which virus attachment regulates the disease process. Rabies virus is a rhabdovirus which exhibits a marked neuronotropism in infected animals. Limited data suggest that spread occurs by transsynaptic transfer of virus. The results of recent experiments at Yale suggest that viral antigen is localized very soon after injection at neuromuscular junctions, the motor nerve endings on muscle tissue. On cultured muscle cells, similar co-localization with the acetylcholine receptor is seen both before and after virus multiplication. Pretreatment of these cells with some ligands of the acetylcholine receptor results in reduced viral infection. These findings suggest that a neurotransmitter receptor or a closely associated molecule may serve as a specific host cell receptor for rabies virus and thus may be responsible for the tissue tropism exhibited by this virus. In addition to clarifying aspects of rabies virus pathogenesis, these studies have broad implications regarding the mechanism by which other viruses or viral immunizations might mediate autoimmune diseases such as myasthenia gravis.

  11. CGRP and its receptors.

    PubMed

    Hay, Debbie L; Walker, Christopher S

    2017-02-24

    The calcitonin gene-related peptide (CGRP) neuropeptide system is an important but still evolving target for migraine. A fundamental consideration for all of the current drugs in clinical trials and for ongoing development in this area is the identity, expression pattern, and function of CGRP receptors because this knowledge informs safety and efficacy considerations. In recent years, only the calcitonin receptor-like receptor/receptor activity-modifying protein 1 (RAMP1) complex, known as the CGRP receptor, has generally been considered relevant. However, CGRP is capable of activating multiple receptors and could have more than one endogenous receptor. The recent identification of the CGRP-responsive calcitonin receptor/RAMP1 complex (AMY1 receptor - amylin subtype 1 receptor) in the trigeminovascular system warrants a deeper consideration of the molecular identity of CGRP receptor(s) involved in the pathophysiology, and thus potential treatment of migraine. This perspective considers some of the issues and implications.

  12. The LDL receptor.

    PubMed

    Goldstein, Joseph L; Brown, Michael S

    2009-04-01

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

  13. 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.

  14. 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

  15. 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.

  16. 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 are studied utilizing the modal frequency spectrum method. In the early evolution of the jet the axisymmetric mode was predominant, with the azimuthal modes growing quickly but dominating only after the end of the potential core. The growth of the azimuthal modes is seen nearer to the nozzle exit for the jet in the laminar boundary layer case than for the turbulent. Based on the results from these naturally occurring jet instability mode tests, target modes for efficient excitation were determined and two cases of excitation were examined.

  17. 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.;

  18. Tyrosine phosphorylation of glutamate receptors by non-receptor tyrosine kinases: roles in depression-like behavior

    PubMed Central

    Mao, Li-Min; Wang, John Q.

    2016-01-01

    Several key members of the non-receptor tyrosine kinase (nRTK) family are abundantly present within excitatory synapses in the mammalian brain. These neuron-enriched nRTKs interact with glutamate receptors and phosphorylate the receptors at tyrosine sites. The N-methyl-D-aspartate receptor is a direct substrate of nRTKs and has been extensively investigated in its phosphorylation responses to nRTKs. The α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor is the other glutamate receptor subtype that is subject to nRTK-mediated tyrosine phosphorylation. Recently, group I metabotropic glutamate receptors (mGluR1/5) were found to be sensitive to nRTKs. Robust tyrosine phosphorylation may occur in C-terminal tails of mGluR5. Tyrosine phosphorylation of glutamate receptors is either constitutive or induced activity-dependently by changing cellular and/or synaptic input. Through inducing tyrosine phosphorylation, nRTKs regulate trafficking, subcellular distribution, and function of modified receptors. Available data show that nRTK-glutamate receptor interactions and tyrosine phosphorylation of the receptors undergo drastic adaptations in mood disorders such as major depressive disorder. The remodeling of the nRTK-glutamate receptor interplay contributes to the long-lasting pathophysiology and symptomology of depression. This review summarizes the recent progress in tyrosine phosphorylation of glutamate receptors and analyzes the role of nRTKs in regulating glutamate receptors and depression-like behavior. PMID:26942227

  19. Binding of rabies virus to purified Torpedo acetylcholine receptor.

    PubMed

    Lentz, T L; Benson, R J; Klimowicz, D; Wilson, P T; Hawrot, E

    1986-12-01

    The binding of 125I- and 35S-labeled rabies virus (CVS strain) to affinity-purified acetylcholine receptor from Torpedo electric organ was demonstrated. The binding of rabies virus to the acetylcholine receptor increased with increasing receptor concentration, was dependent on the pH of the incubation medium, and was saturable with increasing virus concentration. Binding of radioactively labeled virus was effectively competed by unlabeled homologous virus particles. Binding of 35S-labeled rabies virus to the AChR was inhibited up to 50% by alpha-bungarotoxin and up to 30% by (+)-tubocurarine but was not affected by atropine. These results demonstrate direct binding of rabies virus to a well-defined neurotransmitter receptor, namely the acetylcholine receptor and indicate that at least a portion of the virus interaction occurs near the acetylcholine binding site on the receptor. These findings support the hypothesis that the acetylcholine receptor may serve as a rabies virus receptor in vivo.

  20. Secretin receptor oligomers form intracellularly during maturation through receptor core domains.

    PubMed

    Lisenbee, Cayle S; Miller, Laurence J

    2006-07-11

    Oligomerization of numerous G protein-coupled receptors has been documented, including the prototypic family B secretin receptor. The clinical significance of oligomerization of this receptor became clear with the recent observation that a misspliced form present in pancreatic cancer could associate with the wild-type receptor and act as a dominant negative inhibitor of its normal growth inhibitory function. Our goal was to explore the molecular mechanism of this interaction using bioluminescence (BRET) and fluorescence (FRET) resonance energy transfer and fluorescence microscopy with a variety of receptor constructs tagged with luciferase or cyan or yellow fluorescent proteins. BRET signals comparable to those obtained from cells coexpressing differentially tagged wild-type receptors were observed for similarly tagged secretin receptors in which all or part of the amino-terminal domain was deleted. As expected, neither of these constructs bound secretin, and only the partially truncated construct sorted to the plasma membrane. Receptors lacking the majority of the carboxyl-terminal domain, including that important for phosphorylation-mediated desensitization, also produced BRET signals above background. These findings suggested that the receptor's membrane-spanning core is responsible for secretin receptor oligomerization. Interestingly, alanine substitutions for a -GxxxG- helix interaction motif in transmembrane segment 7 created nonfunctional receptors that were capable of forming oligomers. Furthermore, treatment of receptor-expressing cells with brefeldin A did not eliminate the BRET signals, and morphologic FRET experiments confirmed the expected subcellular localizations of receptor oligomers. We conclude that secretin receptor oligomerization occurs through -GxxxG- motif-independent interactions of transmembrane segments during the maturation of nascent molecules.

  1. 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

  2. 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,…

  3. On Translating French Occurring in English into Spanish.

    ERIC Educational Resources Information Center

    Sebastian, Robert N.

    1989-01-01

    Explores problems encountered during attempts to translate French expressions occurring in English (such as concierge) into Spanish, particularly when the English interpretation of the expression is different from the standard French usage. Spanish translations are provided for about 200 French terms and expressions commonly used in English. (61…

  4. Syntheses of naturally occurring terphenyls and related compounds.

    PubMed

    Sawayama, Yusuke; Tsujimoto, Takashi; Sugino, Kumi; Nishikawa, Toshio; Isobe, Minoru; Kawagishi, Hirokazu

    2006-12-01

    Naturally occurring terphenyls and related compounds such as terferol and its corresponding quinone and phlebiarubrone were synthesized from 2,5-diphenyl-1,4-benzoquinone. According to the proposed biosynthetic pathway, chemical conversion of phlebiarubrone to ustalic acid, a toxic compound isolated from the poisonous mushroom, Tricholoma ustale, was examined to find a low-yield conversion to the ustalic acid dimethyl ester.

  5. Neutropenia occurring after starting gabapentin for neuropathic pain.

    PubMed

    Derbyshire, E; Martin, D

    2004-12-01

    We report a case of neutropenia occurring in a patient receiving gabapentin for neuropathic pain. Five weeks after treatment started, the patient was admitted to hospital with neutropenic sepsis. Gabapentin is widely used, and neutropenia is a rare adverse effect. This case highlights a serious and potential life-threatening complication.

  6. Temporal Sequencing of Brain Activations During Naturally Occurring Thermoregulatory Events

    PubMed Central

    Diwadkar, Vaibhav A.; Murphy, Eric R.; Freedman, Robert R.

    2014-01-01

    Thermoregulatory events are associated with activity in the constituents of the spinothalamic tract. Whereas studies have assessed activity within constituents of this pathway, in vivo functional magnetic resonance imaging (fMRI) studies have not determined if neuronal activity in the constituents of the tract is temporally ordered. Ordered activity would be expected in naturally occurring thermal events, such as menopausal hot flashes (HFs), which occur in physiological sequence. The origins of HFs may lie in brainstem structures where neuronal activity may occur earlier than in interoceptive centers, such as the insula and the prefrontal cortex. To study such time ordering, we conducted blood oxygen level-dependent-based fMRI in a group of postmenopausal women to measure neuronal activity in the brainstem, insula, and prefrontal cortex around the onset of an HF (detected using synchronously acquired skin conductance responses). Rise in brainstem activity occurred before the detectable onset of an HF. Activity in the insular and prefrontal trailed that in the brainstem, appearing following the onset of the HF. Additional activations associated with HF's were observed in the anterior cingulate cortex and the basal ganglia. Pre-HF brainstem responses may reflect the functional origins of internal thermoregulatory events. By comparison insular, prefrontal and striatal activity may be associated with the phenomenological correlates of HFs. PMID:23787950

  7. On properties of certain classical operators occurring in Fourier analysis

    NASA Astrophysics Data System (ADS)

    Zhizhiashvili, L. V.; Tkebuchava, G. E.

    2004-10-01

    Properties of conjugate functions, Hilbert transforms, and certain maximal operators occurring in Fourier analysis in weighted Lebesgue spaces are established. For functions of several variables in Orlicz spaces the divergence in measure of the Cesáro and the Abel means of the conjugate trigonometric series, and the question of the existence of conjugate functions are investigated.

  8. On properties of certain classical operators occurring in Fourier analysis

    SciTech Connect

    Zhizhiashvili, L V; Tkebuchava, G E

    2004-10-31

    Properties of conjugate functions, Hilbert transforms, and certain maximal operators occurring in Fourier analysis in weighted Lebesgue spaces are established. For functions of several variables in Orlicz spaces the divergence in measure of the Cesaro and the Abel means of the conjugate trigonometric series, and the question of the existence of conjugate functions are investigated.

  9. 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...

  10. The characteristics of gas hydrates occurring in natural environment

    NASA Astrophysics Data System (ADS)

    Lu, H.; Moudrakovski, I.; Udachin, K.; Enright, G.; Ratcliffe, C.; Ripmeester, J.

    2009-12-01

    In the past few years, extensive analyses have been carried out for characterizing the natural gas hydrate samples from Cascadia, offshore Vancouver Island; Mallik, Mackenzie Delta; Mount Elbert, Alaska North Slope; Nankai Trough, offshore Japan; Japan Sea and offshore India. With the results obtained, it is possible to give a general picture of the characteristics of gas hydrates occurring in natural environment. Gas hydrate can occur in sediments of various types, from sands to clay, although it is preferentially enriched in sediments of certain types, for example coarse sands and fine volcanic ash. Most of the gas hydrates in sediments are invisible, occurring in the pores of the sediments, while some hydrates are visible, appearing as massive, nodular, planar, vein-like forms and occurring around the seafloor, in the fractures related to fault systems, or any other large spaces available in sediments. Although methane is the main component of most of the natural gas hydrates, C2 to C7 hydrocarbons have been recognized in hydrates, sometimes even in significant amounts. Shallow marine gas hydrates have been found generally to contain minor amounts of hydrogen sulfide. Gas hydrate samples with complex gas compositions have been found to have heterogeneous distributions in composition, which might reflect changes in the composition of the available gas in the surrounding environment. Depending on the gas compositions, the structure type of a natural gas hydrate can be structure I, II or H. For structure I methane hydrate, the large cages are almost fully occupied by methane molecules, while the small cages are only partly occupied. Methane hydrates occurring in different environments have been identified with almost the same crystallographic parameters.

  11. 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.

  12. 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.

  13. Erythropoietin's inhibiting impact on hepcidin expression occurs indirectly.

    PubMed

    Gammella, Elena; Diaz, Victor; Recalcati, Stefania; Buratti, Paolo; Samaja, Michele; Dey, Soumyadeep; Noguchi, Constance Tom; Gassmann, Max; Cairo, Gaetano

    2015-02-15

    Under conditions of accelerated erythropoiesis, elevated erythropoietin (Epo) levels are associated with inhibition of hepcidin synthesis, a response that ultimately increases iron availability to meet the enhanced iron needs of erythropoietic cells. In the search for erythroid regulators of hepcidin, many candidates have been proposed, including Epo itself. We aimed to test whether direct interaction between Epo and the liver is required to regulate hepcidin. We found that prolonged administration of high doses of Epo in mice leads to great inhibition of liver hepcidin mRNA levels, and concomitant induction of the hepcidin inhibitor erythroferrone (ERFE). Epo treatment also resulted in liver iron mobilization, mediated by increased ferroportin activity and accompanied by reduced ferritin levels and increased TfR1 expression. The same inhibitory effect was observed in mice that do not express the homodimeric Epo receptor (EpoR) in liver cells because EpoR expression is restricted to erythroid cells. Similarly, liver signaling pathways involved in hepcidin regulation were not influenced by the presence or absence of hepatic EpoR. Moreover, Epo analogs, possibly interacting with the postulated heterodimeric β common EpoR, did not affect hepcidin expression. These findings were supported by the lack of inhibition on hepcidin found in hepatoma cells exposed to various concentrations of Epo for different periods of times. Our results demonstrate that hepcidin suppression does not require the direct binding of Epo to its liver receptors and rather suggest that the role of Epo is to stimulate the synthesis of the erythroid regulator ERFE in erythroblasts, which ultimately downregulates hepcidin.

  14. Cocaine disrupts histamine H3 receptor modulation of dopamine D1 receptor signaling: σ1-D1-H3 receptor complexes as key targets for reducing cocaine's effects.

    PubMed

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

    2014-03-05

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

  15. 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

  16. Serpentine ore microtextures occurring in the magnola magnesium process

    NASA Astrophysics Data System (ADS)

    Chen, T. T.; Dutrizac, J. E.; White, Carl

    2000-04-01

    Serpentine ore was leached at 95°C and 100°C in 7.0 M HCl media to study the reactions occurring in Noranda’s Magnola magnesium process. Magnesium leaches rapidly from the serpentine Mg3Si2O5(OH)4, and the silicon remains in-situ as an amorphous silica pseudomorph after the original serpentine particles. Negligible silica dissolution occurs, and silica gelation was never observed. The reaction interface extends over 300 400 µm; as a consequence, fine grinding does not significantly accelerate the rate of magnesium dissolution. Associated inclusions of brucite Mg(OH)2, awaruite Ni8Fe3, and magnetite Fe3O4 dissolve rapidly; whereas, chromite FeCr2O4 and a chromium-rich spinel (Cr,Fe,Al,Mg)3O4 remain largely unaffected.

  17. [Pathologic characteristics of malignant neoplasms occurring in the elderly].

    PubMed

    Arai, Tomio; Matsuda, Yoko; Aida, Junko; Takubo, Kaiyo

    2015-08-01

    Malignant neoplasm preferentially occurs in the elderly. Common cancers in the elderly are gastric, colorectal, lung and prostate cancers in men whereas colorectal, lung, gastric and pancreatic cancers in women. There are several characteristic features such as tumor location, histology, biological behavior and pathway of carcinogenesis in malignant neoplasms occurring in the elderly. Multiple cancers increase with aging. Although it is generally believed that carcinoma in the elderly shows well differentiation, slow growth, low incidence of metastasis and favorable prognosis, the tumor does not always show such features. Regarding biological behavior of malignant tumor in the elderly, age-related alterations of the host such as stromal weakness and decreased immune response against cancer cell invasion should be considered as well as characteristics of tumor cell itself. Thus, we need a specific strategy for treatment for malignant neoplasms in the elderly.

  18. Naturally Occurring Animal Models with Outer Retina Phenotypes

    PubMed Central

    Baehr, Wolfgang; Frederick, Jeanne M.

    2009-01-01

    Naturally occurring and laboratory generated animal models serve as powerful tools with which to investigate the etiology of human retinal degenerations, especially retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), cone dystrophies (CD) and macular degeneration (MD). Much progress has been made in elucidating gene defects underlying disease, in understanding mechanisms leading to disease, and in designing molecules for translational research and gene-based therapy to interfere with the progression of disease. Key to this progress has been study of naturally occurring murine and canine retinal degeneration mutants. This article will review the history, phenotypes and gene defects of select animal models with outer retina (photoreceptor and retinal pigment epithelium) degeneration phenotypes. PMID:19375447

  19. Nucleation processes occurring during dynamic recrystallization in ice

    NASA Astrophysics Data System (ADS)

    Chauve, T.; Montagnat, M.; Barou, F.; Hidas, K.; Tommasi, A.; Mainprice, D.; Piazolo, S.; Wheeler, J.

    2015-12-01

    The understanding of ice deformation mechanisms is a key point for ice flow modeling and interpretation of climatic signal extracted from ice cores. During deformation inside an ice sheet, recrystallization processes will impact texture and viscosity of ice. Recrystallization processes in ice are very similar to the ones observed in metals and rocks. Along ice cores, Continous (rotation) Dynamic Recrystallization (CDRX) and Discontinuous (migration) Dynamic Recrystallization (DDRX) occur, le later being observed mainly in the deeper part, where temperature and deviatoric stress are higher. The role of nucleation and grain boundary migration associated with DRX on texture development are still badly constrained. In this study, we associated ice creep experiments and high resolution EBSD observations (Electronic Microscopy) to better understand nucleation processes occurring during DRX. Ice is an hexagonal material in which deformation mainly occurs by dislocation glide along the basal plane conferring a strong viscoplastic anisotropy to the single crystal. Hence, during polycrystalline ice deformation the incompatibilty between grains lead to highly heterogeneous strain-field. DRX mechanisms arrise from these strong heterogeneities and induce a new microstructure and texture that relaxe the incompatibilites. The high resolution EBSD observations shown in this study are performed on selected samples of laboratory made polycrystalline columnar ice deformed until 3% macro strain (T=-7°C and σ=0.5 MPa). The analyse show that various kind of nucleation occur under these conditions such as polygonization (tilt bands, kink bands), bulge nucleation by SIGBM (strain Induced Grain Boundary Migration), and nucleation of grains with no obvious relationship with surrounding grains. All these nucleation processes are discussed regarding the associated dislocation fields using the Weigthed Burgers Vector analysis. These analyses highlight the strong heterogeneity of these fields

  20. Co-occurring depression and pain in multiple sclerosis.

    PubMed

    Alschuler, Kevin N; Ehde, Dawn M; Jensen, Mark P

    2013-11-01

    Depression and pain are highly prevalent among individuals with multiple sclerosis, and they often co-occur. The purpose of this article is to summarize the literature and theory related to the comorbidity of pain and depression and describe how their presence can impact individuals with multiple sclerosis. Additionally, the article discusses how existing treatments of pain and depression could be adapted to address shared mechanisms and overcome barriers to treatment utilization.

  1. 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.

  2. Sensory-motor transformations for speech occur bilaterally.

    PubMed

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

    2014-03-06

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

  3. [A solitary ganglioneuroma occurring in the sigmoid colon].

    PubMed

    Rabjerg, Maj; Kolodziejczyk, Adam

    2012-09-24

    We report a case of a rare solitary ganglioneuroma occurring in the sigmoid colon of a 70-year-old woman. She experienced sudden onset of abdominal pain and loss of old blood from the gastrointestinal tract. A colonoscopy disclosed a pedunculate polyp in the sigmoid colon 20 cm from the anus, and a histopathologic examination revealed a polypoid mucosa with abundant ganglionic cells and nerve fibres.

  4. Snapthrough occurring in the postbuckling of thin films

    NASA Astrophysics Data System (ADS)

    Parry, G.; Colin, J.; Coupeau, C.; Foucher, F.; Cimetière, A.; Grilhé, J.

    2005-02-01

    The postbuckling transition from an initially straight-sided wrinkle to a distribution of bubbles has been investigated by means of finite element simulations in the case of a thin film relying on a rigid substrate. The calculations show that a snapthrough occurs when the buckling wavelength exceeds a critical value. Experimental atomic force microscopy observations of this transition have been reported and found to be in good agreement with the calculations.

  5. Ticks of Medical Importance Occurring in the Western Hemisphere

    DTIC Science & Technology

    1987-10-01

    disease agents such as protozoa, viruses , bacteria, rickettsiae and toxins. Ticks may also cause Irritation and discomfnrt directly as a result of their...the virus . BabEsiosis Human babesiosis is a malaria-like disease of varying severity which becomes clinically apparent I to 4 weeks after exposure. The...Panama, Colombia , Venezuela, and Ecuador (8). Distribution: This species (Figs. 7, 8) occurs in Panama (10), Paraguay, Colombia (3), Venezuela ,11

  6. When can inverted water tables occur beneath streams?

    PubMed

    Xie, Yueqing; Cook, Peter G; Brunner, Philip; Irvine, Dylan J; Simmons, Craig T

    2014-01-01

    Decline in regional water tables (RWT) can cause losing streams to disconnect from underlying aquifers. When this occurs, an inverted water table (IWT) will develop beneath the stream, and an unsaturated zone will be present between the IWT and the RWT. The IWT marks the base of the saturated zone beneath the stream. Although a few prior studies have suggested the likelihood of an IWT without a clogging layer, most of them have assumed that a low-permeability streambed is required to reduce infiltration from surface water to groundwater, and that the IWT only occurs at the bottom of the low-permeability layer. In this study, we use numerical simulations to show that the development of an IWT beneath an unclogged stream is theoretically possible under steady-state conditions. For a stream width of 1 m above a homogeneous and isotropic sand aquifer with a 47 m deep RWT (measured in an observation point 20 m away from the center of the stream), an IWT will occur provided that the stream depth is less than a critical value of 4.1 m. This critical stream depth is the maximum water depth in the stream to maintain the occurrence of an IWT. The critical stream depth decreases with stream width. For a stream width of 6 m, the critical stream depth is only 1 mm. Thus while theoretically possible, an IWT is unlikely to occur at steady state without a clogging layer, unless a stream is very narrow or shallow and the RWT is very deep.

  7. 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

  8. Clinical experience of esophageal perforation occurring with endoscopic submucosal dissection.

    PubMed

    Sato, H; Inoue, H; Ikeda, H; Grace R Santi, E; Yoshida, A; Onimaru, M; Kudo, S

    2014-01-01

    Esophageal perforation occurring during or after endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) is a rare, but serious complication. However, reports of its characteristics, including endoscopic imaging and management, have not been fully detailed. To analyze and report the clinical presentation and management of esophageal perforations occurred during or after EMR/ESD. Four hundred seventy-two esophageal neoplasms in 368 patients were treated (171 EMR; ESD 306) at Northern Yokohama Hospital from 2003 to 2012. Esophageal perforation occurred in a total of seven (1.9%) patients, all of whom were male and had undergone ESD. The etiology of perforation was: three (42.9%) intraoperative; three (42.9%) balloon dilatation for stricture prevention; one (14.2%) due to food bolus impaction. All cases were managed non-operatively based on the comprehensive assessment of clinical severity, extent of the injury, and the time interval from perforation to treatment onset. Conservative management included (i) bed rest and continuous monitoring to determine the need for operative intervention; (ii) fasting and intravenous fluid infusion/ tube feeding; and (iii) intravenous antibiotics. All defects closed spontaneously, save one case where closure was achieved by endoscopic clipping. Surgery was not required. Conservative management for esophageal perforation during advanced endoscopic resection is may be possible when there is no delay in diagnosis or treatment. Decision-making should be governed purely by multidisciplinary discussion.

  9. A novel trauma model: naturally occurring canine trauma.

    PubMed

    Hall, Kelly E; Sharp, Claire R; Adams, Cynthia R; Beilman, Gregory

    2014-01-01

    In human trauma patients, most deaths result from hemorrhage and brain injury, whereas late deaths, although rare, are the result of multiple organ failure and sepsis. A variety of experimental animal models have been developed to investigate the pathophysiology of traumatic injury and evaluate novel interventions. Similar to other experimental models, these trauma models cannot recapitulate conditions of naturally occurring trauma, and therefore therapeutic interventions based on these models are often ineffective. Pet dogs with naturally occurring traumatic injury represent a promising translational model for human trauma that could be used to assess novel therapies. The purpose of this article was to review the naturally occurring canine trauma literature to highlight the similarities between canine and human trauma. The American College of Veterinary Emergency and Critical Care Veterinary Committee on Trauma has initiated the establishment of a national network of veterinary trauma centers to enhance uniform delivery of care to canine trauma patients. In addition, the Spontaneous Trauma in Animals Team, a multidisciplinary, multicenter group of researchers has created a clinical research infrastructure for carrying out large-scale clinical trials in canine trauma patients. Moving forward, these national resources can be utilized to facilitate multicenter prospective studies of canine trauma to evaluate therapies and interventions that have shown promise in experimental animal models, thus closing the critical gap in the translation of knowledge from experimental models to humans and increasing the likelihood of success in phases 1 and 2 human clinical trials.

  10. Naturally Occurring Anthraquinones: Chemistry and Therapeutic Potential in Autoimmune Diabetes

    PubMed Central

    Wu, Yueh-Chen

    2015-01-01

    Anthraquinones are a class of aromatic compounds with a 9,10-dioxoanthracene core. So far, 79 naturally occurring anthraquinones have been identified which include emodin, physcion, cascarin, catenarin, and rhein. A large body of literature has demonstrated that the naturally occurring anthraquinones possess a broad spectrum of bioactivities, such as cathartic, anticancer, anti-inflammatory, antimicrobial, diuretic, vasorelaxing, and phytoestrogen activities, suggesting their possible clinical application in many diseases. Despite the advances that have been made in understanding the chemistry and biology of the anthraquinones in recent years, research into their mechanisms of action and therapeutic potential in autoimmune disorders is still at an early stage. In this paper, we briefly introduce the etiology of autoimmune diabetes, an autoimmune disorder that affects as many as 10 million worldwide, and the role of chemotaxis in autoimmune diabetes. We then outline the chemical structure and biological properties of the naturally occurring anthraquinones and their derivatives with an emphasis on recent findings about their immune regulation. We discuss the structure and activity relationship, mode of action, and therapeutic potential of the anthraquinones in autoimmune diabetes, including a new strategy for the use of the anthraquinones in autoimmune diabetes. PMID:25866536

  11. Evolution of virulence when transmission occurs before disease.

    PubMed

    Osnas, Erik E; Dobson, Andrew P

    2010-08-23

    Most models of virulence evolution assume that transmission and virulence are constant during an infection. In many viral (HIV and influenza), bacterial (TB) and prion (BSE and CWD) systems, disease-induced mortality occurs long after the host becomes infectious. Therefore, we constructed a model with two infected classes that differ in transmission rate and virulence in order to understand how the evolutionarily stable strategy (ESS) depends on the relative difference in transmission and virulence between classes, on the transition rate between classes and on the recovery rate from the second class. We find that ESS virulence decreases when expressed early in the infection or when transmission occurs late in an infection. When virulence occurred relatively equally in each class and there was disease recovery, ESS virulence increased with increased transition rate. In contrast, ESS virulence first increased and then decreased with transition rate when there was little virulence early in the infection and a rapid recovery rate. This model predicts that ESS virulence is highly dependent on the timing of transmission and pathology after infection; thus, pathogen evolution may either increase or decrease virulence after emergence in a new host.

  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. Transient asymptomatic pulmonary opacities occurring during osimertinib treatment

    PubMed Central

    Noonan, Sinead A.; Sachs, Peter B.; Camidge, D. Ross

    2017-01-01

    Introduction Osimertinib is an Epidermal Growth Factor Receptor (EGFR) Inhibitor licensed for the treatment of EGFR mutant, T790M positive, non-small cell lung cancer (NSCLC). Previously unreported, common, transient asymptomatic pulmonary opacities (TAPOs) were noted at the University of Colorado in patients during osimertinib therapy. Methods CT imaging and clinical notes of NSCLC patients treated at the University of Colorado with osimertinib were retrospectively reviewed. Results Seven of twenty patients (35%), developed TAPOs while on osimertinib. The radiological patterns seen included ground-glass opacities with/without nodular consolidation. The median time to first lesion development was 8.7 weeks (range: 1.6 – 43 weeks) and 6 weeks (range: 1 – 11 weeks) to resolution during continued osimertinib. Conclusions TAPOs may be a previously unrecognized, benign feature associated with osimertinib therapy, which may be mistaken for isolated pulmonary progression or the beginning of more severe pneumonitis. If new onset pulmonary lesions, especially those associated with ground-glass appearances, are asymptomatic, localized and there is no evidence of disease progression elsewhere it may be reasonable to continue treatment with osimertinib and monitor these lesions for resolution. PMID:27618759

  14. Designing occupancy studies when false-positive detections occur

    USGS Publications Warehouse

    Clement, Matthew

    2016-01-01

    1.Recently, estimators have been developed to estimate occupancy probabilities when false-positive detections occur during presence-absence surveys. Some of these estimators combine different types of survey data to improve estimates of occupancy. With these estimators, there is a tradeoff between the number of sample units surveyed, and the number and type of surveys at each sample unit. Guidance on efficient design of studies when false positives occur is unavailable. 2.For a range of scenarios, I identified survey designs that minimized the mean square error of the estimate of occupancy. I considered an approach that uses one survey method and two observation states and an approach that uses two survey methods. For each approach, I used numerical methods to identify optimal survey designs when model assumptions were met and parameter values were correctly anticipated, when parameter values were not correctly anticipated, and when the assumption of no unmodelled detection heterogeneity was violated. 3.Under the approach with two observation states, false positive detections increased the number of recommended surveys, relative to standard occupancy models. If parameter values could not be anticipated, pessimism about detection probabilities avoided poor designs. Detection heterogeneity could require more or fewer repeat surveys, depending on parameter values. If model assumptions were met, the approach with two survey methods was inefficient. However, with poor anticipation of parameter values, with detection heterogeneity, or with removal sampling schemes, combining two survey methods could improve estimates of occupancy. 4.Ignoring false positives can yield biased parameter estimates, yet false positives greatly complicate the design of occupancy studies. Specific guidance for major types of false-positive occupancy models, and for two assumption violations common in field data, can conserve survey resources. This guidance can be used to design efficient

  15. 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

  16. On incompressibility of a matrix in naturally occurring composites

    NASA Astrophysics Data System (ADS)

    Gorbatikh, Larissa; Pingle, Pawan

    2007-12-01

    The work illustrates that a soft matrix, which has the Poisson ratio close to 0.5 and is reinforced with a rigid-line inclusion, possesses an interesting behavior at the inclusion/matrix interface. It experiences a hydrostatic stress state and behaves as an incompressible fluid under longitudinal and transverse loads. The stress singularities are eliminated ahead of the inclusion tips, and when interface defects are formed, their effect on the composite compliance is minimal. These observations have far reaching applications when one is interested in mechanisms of multifunctional property improvement of composites (such as toughness and stiffness) learned from naturally occurring composites.

  17. 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.

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

    USGS Publications Warehouse

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

    1998-01-01

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

  19. An Update on Antitumor Activity of Naturally Occurring Chalcones

    PubMed 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

  20. Transmission of naturally occurring lymphoma in macaque monkeys.

    PubMed Central

    Hunt, R D; Blake, B J; Chalifoux, L V; Sehgal, P K; King, N W; Letvin, N L

    1983-01-01

    Spontaneously occurring rhesus monkey lymphomas were transmitted into healthy rhesus monkeys by using tumor cell suspensions. The naturally arising tumors included an immunoblastic sarcoma and an undifferentiated lymphoma. Recipient animals developed undifferentiated lymphomas, poorly differentiated lymphomas, or parenchymal lymphoproliferative abnormalities suggestive of early lesions of lymphoma. Some of these animals developed such opportunistic infections as cytomegalovirus hepatitis and cryptosporidiosis. They also showed evidence of an abnormal circulating peripheral blood mononuclear cell. These findings, all characteristic of the acquired immune deficiency syndrome (AIDS) of macaques, suggest a link between these transmissible lymphomas and AIDS in macaque monkeys. Images PMID:6576377

  1. Naturally occurring anti-tissue antibodies in rat sera

    PubMed Central

    Weir, D. M.; Pinckard, R. N.; Elson, C. J.; Suckling, Deirdre E.

    1966-01-01

    Seventy per cent of normal rat sera have been shown to contain heat labile serum component(s) active against various rat organ homogenates as demonstrated by haemolytic complement fixation and passive haemagglutination tests. The main antigenic activity in rat liver has been found in the mitochondrial fractions. It was also demonstrated by the indirect fluorescent antibody technique that both guinea-pig complement and high molecular weight rat globulins were fixed to rat organ sections. Chemotactic activity has also been observed with rat serum and rat liver mitochondria and it is suggested that these naturally occurring antibodies may be implicated in the removal of tissue breakdown products. PMID:5338951

  2. Dangerous bifurcation at border collision: when does it occur?

    PubMed

    Ganguli, Anindita; Banerjee, Soumitro

    2005-05-01

    It has been shown recently that border collision bifurcation in a piecewise smooth map can lead to a situation where a fixed point remains stable at both sides of the bifurcation point, and yet the orbit becomes unbounded at the point of bifurcation because the basin of attraction of the stable fixed point shrinks to zero size. Such bifurcations have been named "dangerous bifurcations." In this paper we provide explanation of this phenomenon, and develop the analytical conditions on the parameters under which such dangerous bifurcations will occur.

  3. Most deaths related to abortion occur in the developing world.

    PubMed

    Ciment, J

    1999-06-05

    A new publication of the World Health Organization, "Abortion in the Developing World," reports that 40% of the 50 million abortions performed each year are unsafe, and 90% of these medically perilous procedures occur in developing countries. Although the 30 million abortions performed annually in developing countries represent 60% of the global total, they account for 95% of abortion-related deaths. Abortion was illegal in 94% of the developing countries included in the WHO study. Unexpectedly, the proportion of women who were using contraception when they experienced an unintended pregnancy was similar in countries with strong family planning programs and those with weak or nonexistent programs.

  4. 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.

  5. Transmission of Naturally Occurring Lymphoma in Macaque Monkeys

    NASA Astrophysics Data System (ADS)

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

    1983-08-01

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

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

    PubMed

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

    2015-05-18

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

  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. 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

  9. Testosterone release and social context: when it occurs and why.

    PubMed

    Gleason, Erin D; Fuxjager, Matthew J; Oyegbile, Temitayo O; Marler, Catherine A

    2009-10-01

    The functions of rapid increases in testosterone seem paradoxical because they can occur in response to different social contexts, such as male-male aggressive encounters and male-female sexual encounters. This suggests that context may impact the functional consequences of changes in testosterone, whether transient or long term. Many studies, including those with California mice (Peromyscus californicus), have addressed these issues using manipulations and species comparisons, but many areas remain to be investigated. We report a study here that suggests transient increases in testosterone after social competition influence future competitive behavior, but social experience alone may also be critical in determining future behavior. In other rodents, a comparable testosterone surge occurs in response to sexual stimulation, but the function is not entirely understood. In addition to competitive and sexual behavior, testosterone impacts other systems instrumental to social behaviors, including paternal behavior and degree of monogamy. Thus, mechanisms regulated by testosterone, such as the vasopressin and aromatase systems, may also be influenced by rapid surges of testosterone in aggressive or sexual contexts. We discuss how the functions of testosterone may overlap in some contexts.

  10. 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.

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

    PubMed

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

    2015-05-01

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

  12. Interactome disassembly during apoptosis occurs independent of caspase cleavage.

    PubMed

    Scott, Nichollas E; Rogers, Lindsay D; Prudova, Anna; Brown, Nat F; Fortelny, Nikolaus; Overall, Christopher M; Foster, Leonard J

    2017-01-12

    Protein-protein interaction networks (interactomes) define the functionality of all biological systems. In apoptosis, proteolysis by caspases is thought to initiate disassembly of protein complexes and cell death. Here we used a quantitative proteomics approach, protein correlation profiling (PCP), to explore changes in cytoplasmic and mitochondrial interactomes in response to apoptosis initiation as a function of caspase activity. We measured the response to initiation of Fas-mediated apoptosis in 17,991 interactions among 2,779 proteins, comprising the largest dynamic interactome to date. The majority of interactions were unaffected early in apoptosis, but multiple complexes containing known caspase targets were disassembled. Nonetheless, proteome-wide analysis of proteolytic processing by terminal amine isotopic labeling of substrates (TAILS) revealed little correlation between proteolytic and interactome changes. Our findings show that, in apoptosis, significant interactome alterations occur before and independently of caspase activity. Thus, apoptosis initiation includes a tight program of interactome rearrangement, leading to disassembly of relatively few, select complexes. These early interactome alterations occur independently of cleavage of these protein by caspases.

  13. Severe droughts have occurred in the northeastern United States

    NASA Astrophysics Data System (ADS)

    Balcerak, Ernie

    2011-12-01

    People do not usually consider the northeastern United States to be a drought-prone region, but new evidence shows that mega-droughts have occurred there in the past. Dorothy Peteet of Columbia University and NASA's Goddard Institute for Space Studies reported at the AGU Fall Meeting in San Francisco, Calif., on her analysis of sediment cores in marshes in New York State. Different chemicals flow into a marsh from freshwater upriver and from saltwater from the ocean; higher concentrations of bromine and calcium, which are more common in saltwater, indicate a drier period. The data indicate that at least three mega-droughts occurred in the past 6000 years, the longest during what scientists term as the “Medieval warm period,” which lasted from about 850 C.E. to 1350 C.E. “People don't think of this area as threatened by droughts because we've been in a wet period,” Peteet said.

  14. Multifaceted ability of naturally occurring polyphenols against metastatic cancer.

    PubMed

    Zhou, Qingyu; Bennett, Lunawati L; Zhou, Shufeng

    2016-04-01

    Although cancer metastases are known to be the main cause of cancer-related deaths, truly effective antimetastatic therapeutics remain scarce in clinical practice. Naturally occurring polyphenols are the most abundant antioxidants in human diets. Many of them possess chemopreventive and chemotherapeutic properties against various types of cancer. Recent advances in understanding the molecular pathways that mediate cancer development and progression have led to an increase of interest in preclinical investigations on the mechanisms underlying anticancer activity of polyphenols. In particular, an increasing number of preclinical studies using cultured cells and animal models have demonstrated the inhibitory effects of polyphenols on tumour cell invasion and metastasis, thereby highlighting the potential of polyphenols against metastatic cancer. This review specifically addresses growing evidence of the capability of polyphenols to impair the invasion and migration of tumour cells through a diverse set of mechanisms, including downregulation of expression of matrix metalloproteinases, modulation of regulators of epithelial-mesenchymal transition, interference with Met signalling, inhibition of nuclear factor-kappa B mediated transcription, and so on. Given that metastasis occurs through a multistep process in which each step is regulated by a complex network of signalling pathways, the multi-function and multi-target characteristics of polyphenols render those promising candidates for effective adjuvant therapy against metastatic cancer.

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

    PubMed

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

    2008-08-01

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

  16. 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.

  17. 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.

  18. 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.

  19. A naturally-occurring 'cold earth' spot in Northern China.

    PubMed

    Niu, Fujun; Cheng, Guodong; Niu, Yonghong; Zhang, Mingyi; Luo, Jing; Lin, Zhanju

    2016-09-29

    Permafrost is determined to a large extent by the Earth's surface temperature, therefore it distributes mainly in high altitude and latitude regions. However, stable, warm (about -1 °C) permafrost occurs within a scree slope in northern China that is more than 600 km south of the southernmost limit of latitudinal permafrost on the Eurasian Continent. It is at an elevation of only 900 m above sea level (ASL). The area has a mean annual air temperature (MAAT) of 6 to 8 °C. Thermal processes of the scree slope, investigated through field monitoring and numerical simulation, showed that the permafrost is caused by winter air convection within the porous rock deposits and is stable as air convection does not occur in summer time. The deposit is covered by a 30-cm-thick peaty soil layer dated (carbon C-14) to between 1,000 to 1,600 years ago. The layer also contributes to the permafrost's existence due to the peat's thermal conductivity offset when frozen and thawed. The existence of permafrost under such warm climatic conditions confirms the effectiveness of using crushed rock layer as basement or slope cover to protect the warm permafrost subgrade of the recently-constructed Qinghai-Tibet Railway (QTR), even under the predicted climate warming conditions.

  20. 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.

  1. Co-occurring psychotic and addictive disorders: neurobiology and diagnosis.

    PubMed

    Ross, Stephen; Peselow, Eric

    2012-01-01

    Psychosis and substance abuse are intimately related. Psychotic spectrum illnesses commonly co-occur with substance use disorders (SUDs), and many substances of abuse can cause or exacerbate psychotic symptoms along a temporal spectrum from acute to chronic presentations. Despite the common co-occurrence between psychotic spectrum illnesses and SUDs, they are often under-recognized and undertreated, leading to poor treatment outcomes. Accurate detection and diagnosis of individuals with psychotic illness co-occurring with addictive disorders is key to properly treat such disorders. This article will review the nature of the relationship between psychosis and substance abuse by examining prevalence rates of each disorder alone and their rates of co-occurrence, the neurobiological basis for substance abuse comorbidity in schizophrenia spectrum disorders, key and salient aspects related to accurate diagnosis along a continuum from acute to subacute to chronic conditions, and pitfalls associated with diagnostic dilemmas. A case example will be used to highlight key points related to diagnostic challenges.

  2. 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

  3. 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'.

  4. Definition of target antigens for naturally occurring CD4(+) CD25(+) regulatory T cells.

    PubMed

    Nishikawa, Hiroyoshi; Kato, Takuma; Tawara, Isao; Saito, Kanako; Ikeda, Hiroaki; Kuribayashi, Kagemasa; Allen, Paul M; Schreiber, Robert D; Sakaguchi, Shimon; Old, Lloyd J; Shiku, Hiroshi

    2005-03-07

    The antigenic targets recognized by naturally occurring CD4(+) CD25(+) regulatory T cells (T reg cells) have been elusive. We have serologically defined a series of broadly expressed self-antigens derived from chemically induced mouse sarcomas by serological identification of antigens by recombinant expression cloning (SEREX). CD4(+) CD25(+) T cells from mice immunized with SEREX-defined self-antigens had strong suppressive activity on peptide-specific proliferation of CD4(+) CD25(-) T cells and CD8(+) T cells. The suppressive effect was observed without in vitro T cell stimulation. Foxp3 expression in these CD4(+) CD25(+) T cells from immunized mice was 5-10 times greater than CD4(+) CD25(+) T cells derived from naive mice. The suppressive effect required cellular contact and was blocked by anti-glucocorticoid-induced tumor necrosis factor receptor family-related gene antibody. In vitro suppressive activity essentially disappeared 8 wk after the last immunization. However, it was regained by in vitro restimulation with cognate self-antigen protein but not with control protein. We propose that SEREX-defined self-antigens such as those used in this study represent self-antigens that elicit naturally occurring CD4(+) CD25(+) T reg cells.

  5. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-10-10

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

  8. Dipicolinic Acid Release by Germinating Clostridium difficile Spores Occurs through a Mechanosensing Mechanism

    PubMed Central

    Francis, Michael B.

    2016-01-01

    ABSTRACT Classically, dormant endospores are defined by their resistance properties, particularly their resistance to heat. Much of the heat resistance is due to the large amount of dipicolinic acid (DPA) stored within the spore core. During spore germination, DPA is released and allows for rehydration of the otherwise-dehydrated core. In Bacillus subtilis, 7 proteins are encoded by the spoVA operon and are important for DPA release. These proteins receive a signal from the activated germinant receptor and release DPA. This DPA activates the cortex lytic enzyme CwlJ, and cortex degradation begins. In Clostridium difficile, spore germination is initiated in response to certain bile acids and amino acids. These bile acids interact with the CspC germinant receptor, which then transfers the signal to the CspB protease. Activated CspB cleaves the cortex lytic enzyme, pro-SleC, to its active form. Subsequently, DPA is released from the core. C. difficile encodes orthologues of spoVAC, spoVAD, and spoVAE. Of these, the B. subtilis SpoVAC protein was shown to be capable of mechanosensing. Because cortex degradation precedes DPA release during C. difficile spore germination (opposite of what occurs in B. subtilis), we hypothesized that cortex degradation would relieve the osmotic constraints placed on the inner spore membrane and permit DPA release. Here, we assayed germination in the presence of osmolytes, and we found that they can delay DPA release from germinating C. difficile spores while still permitting cortex degradation. Together, our results suggest that DPA release during C. difficile spore germination occurs though a mechanosensing mechanism. IMPORTANCE Clostridium difficile is transmitted between hosts in the form of a dormant spore, and germination by C. difficile spores is required to initiate infection, because the toxins that are necessary for disease are not deposited on the spore form. Importantly, the C. difficile spore germination pathway

  9. 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.

  10. 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.

  11. 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.

  12. How did the 1906 San Francisco earthquake occur?

    USGS Publications Warehouse

    Thatcher, W.

    1976-01-01

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

  13. Naturally occurring mercury contamination in a pristine environment?

    NASA Astrophysics Data System (ADS)

    Sidle, W. C.

    1993-04-01

    About 19 percent of sampled residential water wells situated in a pristine, granitic Maine (USA) coastal environment have elevated mercury concentrations according to USEPA standards. There are no identified anthropogenic sources for mercury but some local granitoids have anomalous mercury concentrations in the Waldoboro Pluton Complex (WPC). Site-specific hydrogeologic conditions appear to have aggravated what is otherwise only trace amounts of some naturally occurring toxic analytes in the groundwater in contact with the suspect granitoids of the WPC. The extent of mercury in this crystalline rock environment is examined here. It is prudent to exercise preventive measures and appropriately site water supply wells and not expect complete remediation of the affected homeowners' wells.

  14. Where will tropical cyclogenesis occur around a preexisting tropical cyclone?

    NASA Astrophysics Data System (ADS)

    Shi, Wenli; Fei, Jianfang; Huang, Xiaogang; Ma, Zhanhong

    2017-01-01

    An observational study focusing on the locations of tropical cyclogenesis induced by tropical cyclone energy dispersion (TCED) in the western North Pacific is conducted. Statistical results indicate that the cyclogenesis cases associated with TCED widely occur around preexisting tropical cyclones (TCs). In addition to the typical scenario of cyclogenesis to the southeast of a preexisting TC, new TCs can even form in the east or southwest directions at distances ranging from 1000 km to 3500 km. Further analyses reveal that the locations of cyclogenesis are mainly governed by large-scale environments via regulating the patterns of Rossby wave trains. The observational relationships between wave train regimes and the structures of environmental flows are revealed, which are broadly consistent with previous idealized numerical simulations. The results in this study provide a valuable reference for the prediction of cyclogenesis considering the TCED mechanism.

  15. Naturally occurring B-cell autoreactivity: a critical overview.

    PubMed

    Avrameas, Stratis; Ternynck, Therese; Tsonis, Ioannis A; Lymberi, Peggy

    2007-12-01

    In over one century of research in immunology marked progress in the scientific knowledge and the implications derived from it has been made. At the same time several contradictory and seemingly opposing results have been obtained. The term autoimmunity is still conceived by many as a term directly related to an immunopathological state. However, strong evidence exist that not only the immune system is able to recognize self-constituents, but it appears also that this property is essential for homeostasis. Direct or indirect alterations of such self-recognition properties of the immune system may contribute to pathology. In this review, the most recent advances in the field of naturally occurring B-cell autoreactivity in health as well as in disease are presented and discussed.

  16. Spontaneously occurring alimentary osteofluorosis associated with proliferative gastroduodenopathy in rabbits.

    PubMed

    Bock, P; Peters, M; Bagó, Z; Wolf, P; Thiele, A; Baumgärtner, W

    2007-09-01

    Growing rabbits from two rabbitries, fed with commercial concentrates and hay, developed painful thickenings of the extremities. Four rabbits from each farm were clinically examined and necropsied. All animals showed multiple moderate to severe osseous proliferations of extremities and mandibles and a mild to severe proliferative gastroduodenopathy. Histologically, periosteal and endosteal hyperostosis and a mild to severe proliferation of the gastric and duodenal mucosa were noted. Bone analyses revealed 12,700 and 15,000 microg fluoride per gram of bone ash in affected rabbits, compared with 550 microg fluoride in a control animal. A highly elevated fluoride content was found in concentrates. Vitamin A levels were moderately increased only in one concentrate, and copper levels were normal. Results indicate that alimentary fluoride intoxication caused prominent bony proliferations in the examined rabbits. Whether the proliferative gastroduodenopathy is related to the elevated fluoride intake or represents an incidentally occurring secondary disease remains to be determined.

  17. Processing and disposal of scales containing naturally occurring radioactive materials

    SciTech Connect

    Chambers, D.G.; Woods, S.E.; Abernathy, S.E.

    1994-12-31

    Since the discovery that many drill cuttings, scales, sludges, and platings contain elevated amounts of Naturally Occurring Radioactive Material (NORM), many companies and regulating authorities have wondered what is the best method for disposing of this material. This paper covers a process which grinds and slurries this material to a form acceptable for injection to a well. The process consists of (1) classification of material, (2) bulk breakdown, and (3) grinding and slurrying to a consistency which keeps the particles suspended in solution until time for well injection. Well injection takes the form of encapsulation by cementing the well casing below and above the injected NORM during a plug and abandonment operation. In conclusion, the philosophy of the process is to take the NORM generated through the exploration and production of oil and gas and place it back into the reservoir from which it came. This technique is one which protects the environment from the possible hazards associated with mismanaged NORM.

  18. 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.

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

    USGS Publications Warehouse

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

    2001-01-01

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

  20. 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

  1. Terrestrial structured radio emissions occurring close to the equatorial regions

    NASA Astrophysics Data System (ADS)

    Boudjada, Mohammed Y.; Galopeau, Patrick H. M.; Sawas, Sami; Berthelier, Jean-Jacques

    2015-04-01

    We study the occurrence of terrestrial radio emissions observed by the electric field experiment (ICE) onboard DEMETER micro-satellite. We principally consider the ICE observations recorded in the HF frequency range between 10 kHz and 3.175 MHz. A dynamic spectrum is recorded each half-orbit with a time and frequency resolutions, respectively, in the order of 3.25 kHz and 2.048 sec. The terrestrial structured radio emission is found to occur when the satellite is approaching the equatorial region of the Earth. It appears as a structured narrow band 'continuum' with a positive or negative low frequency drift rate, less than 1 kHz/s. The bandwidth is, on average, of about 30 kHz. We derive from our investigation the beam and the probable location of the emission source. We discuss the origin of this terrestrial radio emission and its dependence, or not, on the solar and geomagnetic activities.

  2. Babesia Species Occurring in Austrian Ixodes ricinus Ticks▿

    PubMed Central

    Blaschitz, Marion; Narodoslavsky-Gföller, Melanie; Kanzler, Michaela; Stanek, Gerold; Walochnik, Julia

    2008-01-01

    Babesiosis is a tick-transmitted disease of veterinary and medical importance. The first Austrian case of human babesiosis was recently recorded. In the current study, ticks at all life cycle stages (instars), including 853 Ixodes ricinus and 11 Haemaphysalis concinna ticks, from sampling sites throughout Austria were examined for the presence of Babesia spp. by using 18S rRNA gene PCR and sequencing, and the overall mean infection rate was 51.04%. The infection rates for sampling sites were highly variable, ranging from 0% to almost 100%. Different instars and different sexes were infected almost equally. Babesia isolates occurring in Austrian ticks were identified as Babesia divergens, Babesia divergens-like, and Babesia sp. strain DD by sequencing a fragment of the heat shock protein 70 gene and internal transcribed spacer regions 1 and 2. To our knowledge, this is the first investigation of Babesia spp. in Austrian ticks. PMID:18539787

  3. Second-Degree Atrioventricular Block Occurring After Tooth Extraction

    PubMed Central

    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

  4. 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.

  5. 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.

  6. Forecasting seizures in dogs with naturally occurring epilepsy.

    PubMed

    Howbert, J Jeffry; Patterson, Edward E; Stead, S Matt; Brinkmann, Ben; Vasoli, Vincent; Crepeau, Daniel; Vite, Charles H; Sturges, Beverly; Ruedebusch, Vanessa; Mavoori, Jaideep; Leyde, Kent; Sheffield, W Douglas; Litt, Brian; Worrell, Gregory A

    2014-01-01

    Seizure forecasting has the potential to create new therapeutic strategies for epilepsy, such as providing patient warnings and delivering preemptive therapy. Progress on seizure forecasting, however, has been hindered by lack of sufficient data to rigorously evaluate the hypothesis that seizures are preceded by physiological changes, and are not simply random events. We investigated seizure forecasting in three dogs with naturally occurring focal epilepsy implanted with a device recording continuous intracranial EEG (iEEG). The iEEG spectral power in six frequency bands: delta (0.1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), low-gamma (30-70 Hz), and high-gamma (70-180 Hz), were used as features. Logistic regression classifiers were trained to discriminate labeled pre-ictal and inter-ictal data segments using combinations of the band spectral power features. Performance was assessed on separate test data sets via 10-fold cross-validation. A total of 125 spontaneous seizures were detected in continuous iEEG recordings spanning 6.5 to 15 months from 3 dogs. When considering all seizures, the seizure forecasting algorithm performed significantly better than a Poisson-model chance predictor constrained to have the same time in warning for all 3 dogs over a range of total warning times. Seizure clusters were observed in all 3 dogs, and when the effect of seizure clusters was decreased by considering the subset of seizures separated by at least 4 hours, the forecasting performance remained better than chance for a subset of algorithm parameters. These results demonstrate that seizures in canine epilepsy are not randomly occurring events, and highlight the feasibility of long-term seizure forecasting using iEEG monitoring.

  7. 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.

  8. 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.

  9. 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.

  10. Glucagon receptors: effect of exercise and fasting.

    PubMed

    Lavoie, Carole

    2005-06-01

    One paradox of hormonal regulation during exercise is the maintenance of glucose homeostasis after endurance training despite a lower increase in plasma glucagon. One explanation could be that liver sensitivity to glucagon is increased by endurance training. Glucagon exerts its effect through a 62 KDa glycoprotein receptor, member of the G protein-coupled receptor. To determine whether changes with exercise in glucagon sensitivity occurred at the level of the glucagon receptor (GR), binding characteristics of hepatic glucagon receptors were ascertained in rat purified plasma membranes. Saturation kinetics indicated no difference in the dissociation constant or affinity of glucagon receptor, but a significantly higher glucagon receptor binding density in liver in endurance trained compared to untrained animals. Along with endurance training, it appears that fasting also changes GR binding characteristics. In animals fasting 24 hrs, a significant increase in glucagon receptor density was also reported. Although the exact mechanism remains unknown, there is no doubt that the liver can adapt to physiological stress through modulation of GR binding characteristics to enhance the hepatic glucose production responsiveness to glucagon.

  11. Cortical spreading depression occurs during elective neurosurgical procedures.

    PubMed

    Carlson, Andrew P; William Shuttleworth, C; Mead, Brittany; Burlbaw, Brittany; Krasberg, Mark; Yonas, Howard

    2017-01-01

    OBJECTIVE Cortical spreading depression (CSD) has been observed with relatively high frequency in the period following human brain injury, including traumatic brain injury and ischemic/hemorrhagic stroke. These events are characterized by loss of ionic gradients through massive cellular depolarization, neuronal dysfunction (depression of electrocorticographic [ECoG] activity) and slow spread (2-5 mm/min) across the cortical surface. Previous data obtained in animals have suggested that even in the absence of underlying injury, neurosurgical manipulation can induce CSD and could potentially be a modifiable factor in neurosurgical injury. The authors report their initial experience with direct intraoperative ECoG monitoring for CSD. METHODS The authors prospectively enrolled patients undergoing elective craniotomy for supratentorial lesions in cases in which the surgical procedure was expected to last > 2 hours. These patients were monitored for CSD from the time of dural opening through the time of dural closure, using a standard 1 × 6 platinum electrode coupled with an AC or full-spectrum DC amplifier. The data were processed using standard techniques to evaluate for slow potential changes coupled with suppression of high-frequency ECoG propagating across the electrodes. Data were compared with CSD validated in previous intensive care unit (ICU) studies, to evaluate recording conditions most likely to permit CSD detection, and identify likely events during the course of neurosurgical procedures using standard criteria. RESULTS Eleven patients underwent ECoG monitoring during elective neurosurgical procedures. During the periods of monitoring, 2 definite CSDs were observed to occur in 1 patient and 8 suspicious events were detected in 4 patients. In other patients, either no events were observed or artifact limited interpretation of the data. The DC-coupled amplifier system represented an improvement in stability of data compared with AC-coupled systems. Compared

  12. Intraprison HIV transmission: an assessment of whether it occurs, how it occurs, and who is at risk.

    PubMed

    Krebs, Christopher P; Simmons, Melanie

    2002-10-01

    The prevalence of AIDS infection is approximately five times higher in state and federal prisons than among the general U.S. population. It is also apparent that high-risk HIV transmission behaviors occur inside prison; however, data validly documenting instances of intraprison HIV transmission are rare. This study validly identifies 33 inmates in a large sample of state prison inmates who contracted HIV inside prison and presents data on how they likely contracted HIV. It further compares these inmates to inmates who did not contract HIV inside prison in terms of age, race, and level of education. Documenting the burden posed by HIV transmission inside prison, providing insight into how they contract HIV inside prison, and what types of inmates are at risk will help public and correctional health officials reform their current education and prevention practices and ultimately reduce or prevent HIV transmission both inside and outside prison.

  13. Scrap metal management issues associated with naturally occurring radioactive material

    SciTech Connect

    Smith, K.P.; Blunt, D.L.

    1995-08-01

    Certain industrial processes sometimes generate waste by-products that contain naturally occurring radioactive material (NORM) at elevated concentrations. Some industries, including the water treatment, geothermal energy, and petroleum industries, generate scrap metal that may be contaminated with NORM wastes. Of these three industries, the petroleum industry probably generates the largest quantity of NORM-contaminated equipment, conservatively estimated at 170,000 tons per year. Equipment may become contaminated when NORM-containing scale or sludge accumulates inside water-handling equipment. The primary radionuclides of concern in these NORM wastes are radium-226 and radium-228. NORM-contaminated equipment generated by the petroleum industry currently is managed several ways. Some equipment is routinely decontaminated for reuse; other equipment becomes scrap metal and may be disposed of by burial at a licensed landfill, encapsulation inside the wellbore of an abandoned well, or shipment overseas for smelting. In view of the increased regulatory activities addressing NORM, the economic burden of managing NORM-contaminated wastes, including radioactive scrap metal, is likely to continue to grow. Efforts to develop a cost-effective strategy for managing radioactive scrap metal should focus on identifying the least expensive disposition options that provide adequate protection of human health and the environment. Specifically, efforts should focus on better characterizing the quantity of radioactive scrap available for recycle or reuse, the radioactivity concentration levels, and the potential risks associated with different disposal options.

  14. Characteristics of schools in which fatal shootings occur.

    PubMed

    de Apodaca, Roberto Flores; Brighton, Lauren M; Perkins, Ashley N; Jackson, Kiana N; Steege, Jessica R

    2012-04-01

    School-based violence, and fatal school shootings in particular, have gained increased attention in the media and psychological literature. Most reports have focused on the characteristics of perpetrators, but there is a growing awareness that school-related factors may also influence the occurrence of fatal school shootings. The current study examined several key characteristics of all schools where random (38) and targeted (96) fatal shootings occurred in the United States between 1966 and 2009. These were compared with a group (138) of schools randomly selected to represent the population of all schools in the United States. The size of a school's enrollment, urban or suburban locale, public funding, and predominantly non-white enrollment were positively associated with fatal shootings. Universities and colleges were disproportionately associated with random shootings and high schools with targeted ones. It was proposed that characteristics of schools that allow feelings of anonymity or alienation among students may help create environmental conditions associated with fatal school shootings. Implications for future research and interventions are considered.

  15. 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.

  16. Franckeite as a naturally occurring van der Waals heterostructure.

    PubMed

    Molina-Mendoza, Aday J; Giovanelli, Emerson; Paz, Wendel S; Niño, Miguel Angel; Island, Joshua O; Evangeli, Charalambos; Aballe, Lucía; Foerster, Michael; van der Zant, Herre S J; Rubio-Bollinger, Gabino; Agraït, Nicolás; Palacios, J J; Pérez, Emilio M; Castellanos-Gomez, Andres

    2017-02-13

    The fabrication of van der Waals heterostructures, artificial materials assembled by individual stacking of 2D layers, is among the most promising directions in 2D materials research. Until now, the most widespread approach to stack 2D layers relies on deterministic placement methods, which are cumbersome and tend to suffer from poor control over the lattice orientations and the presence of unwanted interlayer adsorbates. Here, we present a different approach to fabricate ultrathin heterostructures by exfoliation of bulk franckeite which is a naturally occurring and air stable van der Waals heterostructure (composed of alternating SnS2-like and PbS-like layers stacked on top of each other). Presenting both an attractive narrow bandgap (<0.7 eV) and p-type doping, we find that the material can be exfoliated both mechanically and chemically down to few-layer thicknesses. We present extensive theoretical and experimental characterizations of the material's electronic properties and crystal structure, and explore applications for near-infrared photodetectors.

  17. Naturally occurring regulatory T cells: markers, mechanisms, and manipulation.

    PubMed

    Schmetterer, Klaus G; Neunkirchner, Alina; Pickl, Winfried F

    2012-06-01

    Naturally occurring CD4(+)CD25(high) forkhead box protein 3 (FOXP3)(+) regulatory T cells (nTregs) are key mediators of immunity, which orchestrate and maintain tolerance to self and foreign antigens. In the recent 1.5 decades, a multitude of studies have aimed to define the phenotype and function of nTregs and to assess their therapeutic potential for modulating immune mediated disorders such as autoimmunity, allergy, and episodes of transplant rejection. In this review, we summarize the current knowledge on the biology of nTregs. We address the exact definition of nTregs by specific markers and combinations thereof, which is a prerequisite for the state-of-the-art isolation of defined nTreg populations. Furthermore, we discuss the mechanism by which nTregs mediate immunosuppression and how this knowledge might translate into novel therapeutic modalities. With first clinical studies of nTreg-based therapies being finished, questions concerning the reliable sources of nTregs are becoming more and more eminent. Consequently, approaches allowing conversion of CD4(+) T cells into nTregs by coculture with antigen-presenting cells, cytokines, and/or pharmacological agents are discussed. In addition, genetic engineering approaches for the generation of antigen-specific nTregs are described.

  18. Two primes priming: does feature integration occur before response activation?

    PubMed

    Grainger, Julianne E; Scharnowski, Frank; Schmidt, Thomas; Herzog, Michael H

    2013-07-17

    Responses to a target can be sped up or slowed down by a congruent or incongruent prime, respectively. Even though presentations are rapid, the prime and the target are thought to activate motor responses in strict sequence, with prime activation preceding target activation. In feature fusion, the opposite seems to be the case. For example, a vernier offset to the left is immediately followed by a vernier offset to the right at the same location. The two verniers are not perceived as two elements in sequence but as a single, aligned vernier. Here, we ask the question as to how features are integrated: before or after motor activation? We presented two vernier primes with opposite offset directions preceding a single vernier target. No priming effect occurred when the vernier primes were presented at the same location, indicating that verniers integrate before motor activation. There was also no priming effect when the primes were presented simultaneously at different locations, indicating that there is an integration stage different from the perceptual fusion stage. When the second prime is delayed, it determines priming, even for very long delays. To explain these long integration times, we argue that there is a buffer preceding motor activation.

  19. 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.

  20. 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.

  1. Predictive model of squeal noise occurring on a laboratory brake

    NASA Astrophysics Data System (ADS)

    Giannini, Oliviero; Sestieri, Aldo

    2006-09-01

    This paper on brake squeal instability presents a reduced order model of a laboratory brake considered in a previous paper, and presents a description of the squeal mechanism occurring during experiments. The model uses the modal parameters of the laboratory brake components, the disc and the caliper, when they are not in contact between them. Successively, the caliper and the disc are put in contact through the pad that is modeled as a one degree of freedom system while the Coulomb law models the friction interaction between them. No stick slip motion of the pad is considered, because it was not observed in the experimental tests. As a result the model is linear and particularly suited for a parametric analysis. The stability of the model is studied by a complex eigenvalue analysis and the obtained results show a good agreement with the experimental data, provided that the key parameters of the model are consistent with the experimental set-up. The key role of the disc and the pad dynamics are discussed.

  2. 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.

  3. Individual and Co-occurring SNAP Risk Factors

    PubMed Central

    Balto, Julia M.; Ensari, Ipek; Hubbard, Elizabeth A.; Khan, Naiman; Barnes, Jennifer L.

    2016-01-01

    Background: Smoking, poor nutrition, excess alcohol consumption, and insufficient physical activity underlie most preventable causes of morbidity in the general population and may be associated with comorbidities and health outcomes in multiple sclerosis (MS). However, the frequency of co-occurrence of these risk factors in people with MS remains unclear. Methods: Sixty-nine individuals with MS completed self-report measures of smoking status, nutrition, alcohol use, physical activity levels, and sociodemographic and clinical characteristics. The data were analyzed using t tests and χ2 analyses. Results: Poor diet was the most common risk factor, with 85.5% of the sample not meeting dietary guidelines. Of participants with two risk factors, 90.3% were not meeting dietary and physical activity guidelines. Seventy-three percent of women were not meeting physical activity guidelines, compared with 38% of men (χ2 = 7.5, P < .01). There were also differential rates by sex of the most commonly co-occurring risk factors: 65% of women reported the co-occurrence of insufficient physical activity and poor diet, compared with 38% of men (χ2 = 4.2, P = .05). Conclusions: These results indicate that 85.5% of the sample was not meeting nutrition guidelines, 90.3% of participants with two risk factors reported the co-occurrence of poor diet and insufficient levels of physical activity, and physical activity levels and the total number of risk factors varied across sex. PMID:27999524

  4. 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

  5. Pioneer round of translation occurs during serum starvation

    SciTech Connect

    Oh, Nara; Kim, Kyoung Mi; Cho, Hana; Choe, Junho; Kim, Yoon Ki

    2007-10-12

    The pioneer round of translation plays a role in translation initiation of newly spliced and exon junction complex (EJC)-bound mRNAs. Nuclear cap-binding protein complex CBP80/20 binds to those mRNAs at the 5'-end, recruiting translation initiation complex. As a consequence of the pioneer round of translation, the bound EJCs are dissociated from mRNAs and CBP80/20 is replaced by the cytoplasmic cap-binding protein eIF4E. Steady-state translation directed by eIF4E allows for an immediate and rapid response to changes in physiological conditions. Here, we show that nonsense-mediated mRNA decay (NMD), which restricts only to the pioneer round of translation but not to steady-state translation, efficiently occurs even during serum starvation, in which steady-state translation is drastically abolished. Accordingly, CBP80 remains in the nucleus and processing bodies are unaffected in their abundance and number in serum-starved conditions. These results suggest that mRNAs enter the pioneer round of translation during serum starvation and are targeted for NMD if they contain premature termination codons.

  6. Franckeite as a naturally occurring van der Waals heterostructure

    NASA Astrophysics Data System (ADS)

    Molina-Mendoza, Aday J.; Giovanelli, Emerson; Paz, Wendel S.; Niño, Miguel Angel; Island, Joshua O.; Evangeli, Charalambos; Aballe, Lucía; Foerster, Michael; van der Zant, Herre S. J.; Rubio-Bollinger, Gabino; Agraït, Nicolás; Palacios, J. J.; Pérez, Emilio M.; Castellanos-Gomez, Andres

    2017-02-01

    The fabrication of van der Waals heterostructures, artificial materials assembled by individual stacking of 2D layers, is among the most promising directions in 2D materials research. Until now, the most widespread approach to stack 2D layers relies on deterministic placement methods, which are cumbersome and tend to suffer from poor control over the lattice orientations and the presence of unwanted interlayer adsorbates. Here, we present a different approach to fabricate ultrathin heterostructures by exfoliation of bulk franckeite which is a naturally occurring and air stable van der Waals heterostructure (composed of alternating SnS2-like and PbS-like layers stacked on top of each other). Presenting both an attractive narrow bandgap (<0.7 eV) and p-type doping, we find that the material can be exfoliated both mechanically and chemically down to few-layer thicknesses. We present extensive theoretical and experimental characterizations of the material's electronic properties and crystal structure, and explore applications for near-infrared photodetectors.

  7. 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.

  8. 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.

  9. 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.

  10. Franckeite as a naturally occurring van der Waals heterostructure

    PubMed Central

    Molina-Mendoza, Aday J.; Giovanelli, Emerson; Paz, Wendel S.; Niño, Miguel Angel; Island, Joshua O.; Evangeli, Charalambos; Aballe, Lucía; Foerster, Michael; van der Zant, Herre S. J.; Rubio-Bollinger, Gabino; Agraït, Nicolás; Palacios, J. J.; Pérez, Emilio M.; Castellanos-Gomez, Andres

    2017-01-01

    The fabrication of van der Waals heterostructures, artificial materials assembled by individual stacking of 2D layers, is among the most promising directions in 2D materials research. Until now, the most widespread approach to stack 2D layers relies on deterministic placement methods, which are cumbersome and tend to suffer from poor control over the lattice orientations and the presence of unwanted interlayer adsorbates. Here, we present a different approach to fabricate ultrathin heterostructures by exfoliation of bulk franckeite which is a naturally occurring and air stable van der Waals heterostructure (composed of alternating SnS2-like and PbS-like layers stacked on top of each other). Presenting both an attractive narrow bandgap (<0.7 eV) and p-type doping, we find that the material can be exfoliated both mechanically and chemically down to few-layer thicknesses. We present extensive theoretical and experimental characterizations of the material's electronic properties and crystal structure, and explore applications for near-infrared photodetectors. PMID:28194037

  11. Effects of a naturally occurring neurosteroid on GABAA IPSCs during development in rat hippocampal or cerebellar slices

    PubMed Central

    Cooper, Elizabeth J; Johnston, Graham A R; Edwards, Frances A

    1999-01-01

    The effects of the naturally occurring neurosteroid tetrahydrodeoxycorticosterone (THDOC) on GABAA receptor-mediated miniature, spontaneous and evoked IPSCs was tested using patch-clamp techniques in slices of hippocampus and cerebellum from rats at two developmental stages (≈10 and ≈20 days postnatal). The cells studied were hippocampal granule cells and cerebellar Purkinje and granule cells. Most miniature GABAergic currents (mIPSCs) decayed with two exponentials and neurosteroids caused a ≈4-fold increase in the decay time constant of the second exponential at the highest concentration used (2 μm). Similar effects were seen at high concentrations of THDOC (1-2 μm) in all cell groups tested. No effects were seen on amplitude or rise time of mIPSCs. The effects of THDOC (1 μm) were shown to be stereoselective and rapidly reversible, indicating that the neurosteroid binds to the GABAA receptor, rather than acting genomically. At concentrations of THDOC likely to occur physiologically (50–100 nm), the decay time of IPSCs was also enhanced (25–50 %) in all cerebellar cell groups tested. In contrast, at 100 nm THDOC, seven of 11 hippocampal granule cells were sensitive from the 10 day group but the 20 day hippocampal granule cells showed no significant enhancement in the presence of these lower concentrations of THDOC. The differences in sensitivity of hippocampal and cerebellar cells to THDOC are compared to data reported in the literature on regional development of expression of different receptor subunits in the brain and it is suggested that the progressive relative insensitivity of the 20 day hippocampal cells may depend on increasing expression of the δ subunit of the GABAA receptor and possibly an increase in the α4 subunit. PMID:10581314

  12. 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.

  13. Brain receptor imaging.

    PubMed

    Heiss, Wolf-Dieter; Herholz, Karl

    2006-02-01

    Receptors have a prominent role in brain function, as they are the effector sites of neurotransmission at the postsynaptic membrane, have a regulatory role on presynaptic sites for transmitter reuptake and feedback, and are modulating various functions on the cell membrane. Distribution, density, and activity of receptors in the brain can be visualized by radioligands labeled for SPECT and PET, and the receptor binding can be quantified by appropriate tracer kinetic models, which can be modified and simplified for particular application. Selective radioligands are available for the various transmitter systems, by which the distribution of these receptors in the normal brain and changes in receptor binding during various physiologic activities or resulting from pathologic conditions can be visualized. The quantitative imaging for several receptors has gained clinical importance-for example, dopamine (D2)) receptors for differential diagnosis of movement disorders and for assessment of receptor occupancy by neuroleptics drugs; serotonin (5-hydroxytryptamine, 5-HT) receptors and the 5-HT transporter in affective disorders and for assessment of activity of antidepressants; nicotinic receptors and acetylcholinesterase as markers of cognitive and memory impairment; central benzodiazepine-binding sites at the gamma-aminobutyric acid A (GABAA) receptor complex as markers of neuronal integrity in neurodegenerative disorders, epilepsy, and stroke and as the site of action of benzodiazepines; peripheral benzodiazepine receptors as indicators of inflammatory changes; opioid receptors detecting increased cortical excitability in focal epilepsy but also affected in perception of and emotional response to pain; and several receptor systems affected in drug abuse and craving. Further studies of the various transmitter/receptor systems and their balance and infraction will improve our understanding of complex brain functions and will provide more insight into the pathophysiology of

  14. Anti-NMDA Receptor Encephalitis in a Pregnant Woman.

    PubMed

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

    2015-06-01

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

  15. 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.

  16. Naturally Occurring Variants of the Dysglycemic Peptide Pancreastatin

    PubMed Central

    Allu, Prasanna K. R.; Chirasani, Venkat R.; Ghosh, Dhiman; Mani, Anitha; Bera, Amal K.; Maji, Samir K.; Senapati, Sanjib; Mullasari, Ajit S.; Mahapatra, Nitish R.

    2014-01-01

    Pancreastatin (PST), a chromogranin A-derived peptide, is a potent physiological inhibitor of glucose-induced insulin secretion. PST also triggers glycogenolysis in liver and reduces glucose uptake in adipocytes and hepatocytes. Here, we probed for genetic variations in PST sequence and identified two variants within its functionally important carboxyl terminus domain: E287K and G297S. To understand functional implications of these amino acid substitutions, we tested the effects of wild-type (PST-WT), PST-287K, and PST-297S peptides on various cellular processes/events. The rank order of efficacy to inhibit insulin-stimulated glucose uptake was: PST-297S > PST-287K > PST-WT. The PST peptides also displayed the same order of efficacy for enhancing intracellular nitric oxide and Ca2+ levels in various cell types. In addition, PST peptides activated gluconeogenic genes in the following order: PST-297S ≈ PST-287K > PST-WT. Consistent with these in vitro results, the common PST variant allele Ser-297 was associated with significantly higher (by ∼17 mg/dl, as compared with the wild-type Gly-297 allele) plasma glucose level in our study population (n = 410). Molecular modeling and molecular dynamics simulations predicted the following rank order of α-helical content: PST-297S > PST-287K > PST-WT. Corroboratively, circular dichroism analysis of PST peptides revealed significant differences in global structures (e.g. the order of propensity to form α-helix was: PST-297S ≈ PST-287K > PST-WT). This study provides a molecular basis for enhanced potencies/efficacies of human PST variants (likely to occur in ∼300 million people worldwide) and has quantitative implications for inter-individual variations in glucose/insulin homeostasis. PMID:24338022

  17. 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.

  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.

  19. Death in pediatric Cushing syndrome is uncommon but still occurs

    PubMed Central

    Gkourogianni, Alexandra; Lodish, Maya B.; Zilbermint, Mihail; Lyssikatos, Charalampos; Belyavskaya, Elena; Keil, Margaret F.; Stratakis, Constantine A.

    2014-01-01

    Cushing syndrome (CS) in children is rare. Delayed diagnosis and treatment of CS may be associated with increased morbidity and, unfortunately, mortality. We performed a retrospective review of all patients with CS under the age of 18 referred to the NIH from 1998 to 2013 in order to describe deceased patients among cases of pediatric CS referred to the National Institutes of Health (NIH). The deaths of 4 children (3 females and 1 male), aged 7.5–15.5 years (mean age 11.2 years) with length of disease 2–4 years were recorded among 160 (2.5%) children seen at, or referred to the NIH over the last 15 years. All died at different institutions, prior to coming to the NIH (two of them) or after leaving NIH (two of them). Presenting symptoms included increasing weight and decreasing height gain, facial plethora, dorsocervical fat pad (webbed neck), striae, headache, vision disturbances and depression and other mood or behavior changes; there were no differences between how these patients presented and the others in our cohort. The causes of CS in the deceased patients were also not different, in fact, they spanned the entire spectrum of CS: pituitary disease (on of them), ectopic corticotropin production (one of them), and primary adrenal hyperplasia (1). In one patient, the cause of CS could not be verified. Three died of sepsis and one due to residual disease and complications of the primary tumor. Conclusions Despite advances in early diagnosis and treatment of pediatric CS, a 2.5% mortality rate was identified in a large cohort of patients with this condition referred to an experienced, tertiary care referral center (although these deaths occurred elsewhere). Pediatricians need to recognize the possibility of death, primarily due to sepsis, in a patient with pediatric CS and act accordingly. PMID:25241829

  20. [Melatonin receptor agonist].

    PubMed

    Uchiyama, Makoto

    2015-06-01

    Melatonin is a hormone secreted by the pineal gland and is involved in the regulation of human sleep-wake cycle and circadian rhythms. The melatonin MT1 and MT2 receptors located in the suprachiasmatic nucleus in the hypothalamus play a pivotal role in the sleep-wake regulation. Based on the fact that MT1 receptors are involved in human sleep onset process, melatonin receptor agonists have been developed to treat insomnia. In this article, we first reviewed functions of melatonin receptors with special reference to MT1 and MT2, and properties and clinical application of melatonin receptor agonists as hypnotics.

  1. Standardizing scavenger receptor nomenclature.

    PubMed

    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

    2014-03-01

    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.

  2. 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

  3. 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

  4. 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.

  5. Catch-up growth occurs after diarrhea in early childhood.

    PubMed

    Richard, Stephanie A; Black, Robert E; Gilman, Robert H; Guerrant, Richard L; Kang, Gagandeep; Lanata, Claudio F; Mølbak, Kåre; Rasmussen, Zeba A; Sack, R Bradley; Valentiner-Branth, Palle; Checkley, William

    2014-06-01

    Diarrhea and linear growth faltering continue to burden low-income countries and are among the most important contributors to poor health during early childhood. Diarrhea is thought to adversely affect linear growth, but catch-up growth can occur if no additional insults are experienced. We sought to characterize catch-up growth in relation to diarrhea burden in a multisite dataset of 1007 children. Using longitudinal anthropometry and diarrheal surveillance data from 7 cohort studies in 4 countries, we examined the relation between diarrhea prevalence and growth in 3- to 6-mo periods using linear mixed-effect models. Growth during each period was calculated as a function of age using linear splines. We incorporated the longitudinal prevalence of diarrhea in both current and previous periods into the model. Diarrhea during the current period was associated with slower linear and ponderal growth. Faster (catch-up) growth in length was observed in children with no diarrhea in age groups immediately after an age group in which diarrhea was experienced [age group >6-12 mo: 0.03 mm/mo for each percentage diarrhea prevalence in the previous period (95% CI: 0.007, 0.06) relative to 11.3 mm/mo mean growth rate; age group >12-18 mo: 0.04 mm/mo (95% CI: 0.02, 0.06) relative to 8.9 mm/mo mean growth rate; age group >18-24 mo: 0.04 mm/mo (95% CI: 0.003, 0.09) relative to 7.9 mm/mo mean growth rate]. The associations were stronger in boys than in girls when separate models were run. Similar results were observed when weight was the outcome variable. When diarrheal episodes are followed by diarrhea-free periods in the first 2 y of life, catch-up growth is observed that may allow children to regain their original trajectories. The finding of a greater effect of diarrhea on linear growth in boys than in girls was unexpected and requires additional study. Diarrhea burdens are high throughout the first 2 y of life in these study sites, therefore reducing the likelihood of catch

  6. 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

  7. 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

  8. CB receptor ligands from plants.

    PubMed

    Woelkart, Karin; Salo-Ahen, Outi M H; Bauer, Rudolf

    2008-01-01

    Advances in understanding the physiology and pharmacology of the endogenous cannabinoid system have potentiated the interest of cannabinoid receptors as potential therapeutic targets. Cannabinoids have been shown to modulate a variety of immune cell functions and have therapeutic implications on central nervous system (CNS) inflammation, chronic inflammatory conditions such as arthritis, and may be therapeutically useful in treating autoimmune conditions such as multiple sclerosis. Many of these drug effects occur through cannabinoid receptor signalling mechanisms and the modulation of cytokines and other gene products. Further, endocannabinoids have been found to have many physiological and patho-physiological functions, including mood alteration and analgesia, control of energy balance, gut motility, motor and co-ordination activities, as well as alleviation of neurological, psychiatric and eating disorders. Plants offer a wide range of chemical diversity and have been a growing domain in the search for effective cannabinoid ligands. Cannabis sativa L. with the known plant cannabinoid, Delta(9-)tetrahydrocannabinol (THC) and Echinacea species with the cannabinoid (CB) receptor-binding lipophilic alkamides are the best known herbal cannabimimetics. This review focuses on the state of the art in CB ligands from plants, as well their possible therapeutic and immunomodulatory effects.

  9. [Diagnosis of osteoporosis occurring in autoimmune thyroid gland disease].

    PubMed

    Radojković, Ivan; Radojković, Jana; Djurica, Snezana

    2005-10-01

    Osteoporosis or porotic bone is a general, systemic bone disease, which is manifested by fracture as its consequence. The main characteristic of this disease is the loss of bone microarchitecture, bone mass reduction, and its increased fragility. The result, thereof, is susceptibility to fracture. Etiology of osteoporosis is polymorph. Its socio-medical importance is enormous, since there is one osteoporotic fracture every 20 sec. worldwide. Million and six hundred thousand osteoporotic fractures occur annualy throughout the world. Thyroid gland is susceptible to autoimmune reactions that lead to autoimmune diseases, just like many other organs. The autoimmune disorder is a final consequence of a failure, in some instance, within the crucial mechanism of regulation of self tissue tolerance. The main goal is to prove the presence of osteoporosis, its inexpensive and quick diagnostics; to make a distinction among the causes that lead to it. In addition, to indicate the importance of osteoporosis that is caused by normal, metabolic processes which are an inevitable part of ageing. Diagnosis of osteoporosis can be done through laboratory, which is a tiresome, time consuming task. Measurements of BMD could be also performed by using new devices. Osteometers could be constructed on the basis of X-ray photon energy or US. Utilization most contemporary one uses laser beam, and it approximates the distance of additional tissue that also absorbs part of energy changing absorption of the reception unit and thus making the measurement results accurate. In diagnosing BMD by osteometer, one faces with certain difficulties. When axial quantitative CT is used, the value may be falsely lower, because of the loss of energy absorbed by aorta which is often calcified in elderly people. In devices with transversal scanning, of the same nature and technology, a part of the energy is being absorbed by transversal and spinal vertebrals. After the research, one may conclude that the most

  10. 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

  11. 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

  12. Engineering death receptor ligands for cancer therapy.

    PubMed

    Wajant, Harald; Gerspach, Jeannette; Pfizenmaier, Klaus

    2013-05-28

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

  13. The origins of major platelet receptor nomenclature.

    PubMed

    Clemetson, Kenneth J

    2017-01-01

    The nomenclature of the major platelet receptors may appear complex, but in fact there are logical reasons why it developed in the way it did. In this short review, I describe the origins of this nomenclature, how it developed as more information became available and as relationships were established with receptors on other types of cells. Difficulties have also arisen with alternative nomenclature systems and the various equivalences with these are described and listed. There remain areas such as immunology and transfusion where the accepted nomenclature leaves something to be desired, but it is unlikely that major changes will occur.

  14. Anabolic and Antiresorptive Modulation of Bone Homeostasis by the Epigenetic Modulator Sulforaphane, a Naturally Occurring Isothiocyanate*

    PubMed Central

    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.

    2016-01-01

    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 via Tet1 and Tet2 and promotes preosteoblast differentiation by enhancing extracellular matrix mineralization and the expression of osteoblastic markers (Runx2, Col1a1, Bglap2, Sp7, Atf4, and Alpl). 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 the Tet1/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 resorption in 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

  15. Neurobiological perspective of spasticity as occurs after a spinal cord injury.

    PubMed

    Roy, Roland R; Edgerton, V Reggie

    2012-05-01

    In this review we use the term spasticity to mean the generation of abnormal patterns of forces that are generated involuntarily. It is clear that spasticity can have both detrimental and beneficial effects on the neuromuscular system of the affected individuals. Muscle spasticity routinely occurs after a spinal cord injury and other neurological disorders. Although often studied as if there was a single mechanism associated with this phenomenon, it is clear that there are multiple mechanisms having both neural and muscular components, particularly when such terms also are applied to other neuromotor disorders. The aims of this review are to describe the neural and muscular adaptations that are associated with spasticity, highlight the major possible mechanisms producing spasticity, and discuss the role of selected pharmacological interventions in controlling spasticity. Spasticity appears to be related to altered membrane channel and receptor properties that are primarily associated with an increase in the excitability of spinal neurons, resulting in abnormal (in the intensity and combination of muscles activated) contractions that are generated involuntarily. While most of the efforts to understand the etiology of spasticity have focused on motoneurons, it is likely that spinal interneurons play a central role as well as the mechanical properties of muscle fibers and associated connective tissues. A number of pharmacological interventions have been used in attempts to suppress spasticity with varying results, but concomitant with suppressed muscle activation, there can be significant side effects including a reduction in the control of movement.

  16. From naturally-occurring neurotoxic agents to CNS shuttles for drug delivery.

    PubMed

    Soddu, Elena; Rassu, Giovanna; Giunchedi, Paolo; Sarmento, Bruno; Gavini, Elisabetta

    2015-07-10

    Central nervous system (CNS) diseases are hard to diagnose and therapeutically target due to the blood brain barrier (BBB), which prevents most drugs from reaching their sites of action within the CNS. Brain drug delivery systems were conceived to bypass the BBB and were derived from anatomical and functional analysis of the BBB; this analysis led researchers to take advantage of brain endothelial membrane physiology to allow drug access across the BBB. Both receptors and carriers can be used to transport endogenous and exogenous substances into the CNS. Combining a drug with substances that take advantage of these internalization mechanisms is a widely exploited strategy for drug delivery because it is an indirect method that overcomes the BBB in a non-invasive way and is therefore less dangerous and costly than invasive methods. Neurotoxins, among other naturally-occurring substances, may be used as drug carriers to specifically target the CNS. This review covers the current delivery systems that take advantage of the non-toxic components of neurotoxins to overcome the BBB and reach the CNS. We hope to give insights to researchers toward developing new delivery systems that exploit the positive features of substances usually regarded as natural hazards.

  17. Acute Severe Thrombocytopenia Occurring After Administration of Eptifibatide Postpones Emergent Coronary Artery Surgery

    PubMed Central

    Boettcher, Brent T.; Olund, Timothy J.; Pagel, Paul S.

    2016-01-01

    Introduction Eptifibatide is a platelet glycoprotein IIb/IIIa (GP IIb/IIIa) receptor antagonist that inhibits fibrinogen binding to the activated GP IIb/IIIa site and prevents platelet-platelet interaction and clot formation. GP IIb/IIIa inhibitors improve outcome in patients undergoing percutaneous coronary intervention for acute coronary syndrome. Thrombocytopenia is a complication of GP IIb/IIIa inhibitors, but severe thrombocytopenia is unusual. Most reported cases of severe thrombocytopenia after eptifibatide occurred in patients with acute coronary syndrome. The authors describe a patient who developed acute profound thrombocytopenia after receiving eptifibatide before emergent coronary artery bypass graft surgery. Case Presentation A 67-year-old man with a normal platelet count (220 K/uL) developed atrial fibrillation, left bundle branch block, and respiratory insufficiency consistent with acute coronary syndrome two days after colectomy. He received eptifibatide during cardiac catheterization, where three-vessel coronary artery disease was encountered. Emergent coronary artery surgery was planned, but the platelet count before surgery was 2 K/uL. Eptifibatide was discontinued, surgery was postponed, and acute coronary syndrome was treated with intraaortic balloon counterpulsation. Conclusions The authors describe the second reported case of eptifibatide-induced severe thrombocytopenia associated with cardiac surgery. In this case, discontinuation of eptifibatide and transfusion of apheresis platelets increased the platelet count (137 K/uL) the following day, and the patient subsequently underwent successful coronary artery surgery using cardiopulmonary bypass. PMID:27843778

  18. 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

  19. Selective Glucocorticoid Receptor modulators.

    PubMed

    De Bosscher, Karolien

    2010-05-31

    The ancient two-faced Roman god Janus is often used as a metaphor to describe the characteristics of the Glucocorticoid Receptor (NR3C1), which exhibits both a beneficial side, that serves to halt inflammation, and a detrimental side responsible for undesirable effects. However, recent developments suggest that the Glucocorticoid Receptor has many more faces with the potential to express a range of different functionalities, depending on factors that include the tissue type, ligand type, receptor variants, cofactor surroundings and target gene promoters. This behavior of the receptor has made the development of safer ligands, that trigger the expression program of only a desirable subset of genes, a real challenge. Thus more knowledge-based fundamental research is needed to ensure the design and development of selective Glucocorticoid Receptor modulators capable of reaching the clinic. Recent advances in the characterization of novel selective Glucocorticoid Receptor modulators, specifically in the context of anti-inflammatory strategies, will be described in this review.

  20. Chicken NK cell receptors.

    PubMed

    Straub, Christian; Neulen, Marie-Luise; Sperling, Beatrice; Windau, Katharina; Zechmann, Maria; Jansen, Christine A; Viertlboeck, Birgit C; Göbel, Thomas W

    2013-11-01

    Natural killer cells are innate immune cells that destroy virally infected or transformed cells. They recognize these altered cells by a plethora of diverse receptors and thereby differ from other lymphocytes that use clonally distributed antigen receptors. To date, several receptor families that play a role in either activating or inhibiting NK cells have been identified in mammals. In the chicken, NK cells have been functionally and morphologically defined, however, a conclusive analysis of receptors involved in NK cell mediated functions has not been available. This is partly due to the low frequencies of NK cells in blood or spleen that has hampered their intensive characterization. Here we will review recent progress regarding the diverse NK cell receptor families, with special emphasis on novel families identified in the chicken genome with potential as chicken NK cell receptors.

  1. AMPA receptors as a molecular target in epilepsy therapy.

    PubMed

    Rogawski, M A

    2013-01-01

    Epileptic seizures occur as a result of episodic abnormal synchronous discharges in cerebral neuronal networks. Although a variety of non-conventional mechanisms may play a role in epileptic synchronization, cascading excitation within networks of synaptically connected excitatory glutamatergic neurons is a classical mechanism. As is the case throughout the central nervous system, fast synaptic excitation within and between brain regions relevant to epilepsy is mediated predominantly by AMPA receptors. By inhibiting glutamate-mediated excitation, AMPA receptor antagonists markedly reduce or abolish epileptiform activity in in vitro preparations and confer seizure protection in a broad range of animal seizure models. NMDA receptors may also contribute to epileptiform activity, but NMDA receptor blockade is not sufficient to eliminate epileptiform discharges. AMPA receptors move into and out of the synapse in a dynamic fashion in forms of synaptic plasticity, underlying learning and memory. Often, the trigger for these dynamic movements is the activation of NMDA receptors. While NMDA receptor antagonists inhibit these forms of synaptic plasticity, AMPA receptor antagonists do not impair synaptic plasticity and do not inhibit memory formation or retrieval. The demonstrated clinical efficacy of perampanel, a high-potency, orally active non-competitive AMPA receptor antagonist, supports the concept that AMPA receptors are critical to epileptic synchronization and the generation and spread of epileptic discharges in human epilepsy.

  2. Stronger Dopamine D1 Receptor-Mediated Neurotransmission in Dyskinesia.

    PubMed

    Farré, Daniel; Muñoz, Ana; Moreno, Estefanía; Reyes-Resina, Irene; Canet-Pons, Júlia; Dopeso-Reyes, Iria G; Rico, Alberto J; Lluís, Carme; Mallol, Josefa; Navarro, Gemma; Canela, Enric I; Cortés, Antonio; Labandeira-García, José L; Casadó, Vicent; Lanciego, José L; Franco, Rafael

    2015-12-01

    Radioligand binding assays to rat striatal dopamine D1 receptors showed that brain lateralization of the dopaminergic system were not due to changes in expression but in agonist affinity. D1 receptor-mediated striatal imbalance resulted from a significantly higher agonist affinity in the left striatum. D1 receptors heteromerize with dopamine D3 receptors, which are considered therapeutic targets for dyskinesia in parkinsonian patients. Expression of both D3 and D1-D3 receptor heteromers were increased in samples from 6-hydroxy-dopamine-hemilesioned rats rendered dyskinetic by treatment with 3, 4-dihydroxyphenyl-L-alanine (L-DOPA). Similar findings were obtained using striatal samples from primates. Radioligand binding studies in the presence of a D3 agonist led in dyskinetic, but not in lesioned or L-DOPA-treated rats, to a higher dopamine sensitivity. Upon D3-receptor activation, the affinity of agonists for binding to the right striatal D1 receptor increased. Excess dopamine coming from L-DOPA medication likely activates D3 receptors thus making right and left striatal D1 receptors equally responsive to dopamine. These results show that dyskinesia occurs concurrently with a right/left striatal balance in D1 receptor-mediated neurotransmission.

  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. AMPA Receptors as a Molecular Target in Epilepsy Therapy

    PubMed Central

    Rogawski, Michael A.

    2013-01-01

    Epileptic seizures occur as a result of episodic abnormal synchronous discharges in cerebral neuronal networks. Although a variety of nonconventional mechanisms may play a role in epileptic synchronization, cascading excitation within networks of synaptically connected excitatory glutamatergic neurons is a classical mechanism. As is the case throughout the central nervous system, fast synaptic excitation within and between brain regions relevant to epilepsy is mediated predominantly by AMPA receptors. By inhibiting glutamate-mediated excitation, AMPA receptor antagonists markedly reduce or abolish epileptiform activity in in vitro preparations and confer seizure protection in a broad range of animal seizure models. NMDA receptors may also contribute to epileptiform activity, but NMDA receptor blockade is not sufficient to eliminate epileptiform discharges. AMPA receptors move into and out of the synapse in a dynamic fashion in forms of synaptic plasticity, underlying learning and memory. Often the trigger for these dynamic movements is activation of NMDA receptors. While NMDA receptor antagonists inhibit these forms of synaptic plasticity, AMPA receptor antagonists do not impair synaptic plasticity and do not inhibit memory formation or retrieval. The demonstrated clinical efficacy of perampanel, a high-potency, orally active noncompetitive AMPA receptor antagonist, supports the concept that AMPA receptors are critical to epileptic synchronization and the generation and spread of epileptic discharges in human epilepsy. PMID:23480151

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

    PubMed Central

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

    1996-01-01

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

  6. 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

  7. Transduction of skin-migrating dendritic cells by human adenovirus 5 occurs via an actin-dependent phagocytic pathway.

    PubMed

    Guzman, Efrain; Taylor, Geraldine; Hope, Jayne; Herbert, Rebecca; Cubillos-Zapata, Carolina; Charleston, Bryan

    2016-10-01

    Dendritic cells (DC) are central to the initiation of immune responses, and various approaches have been used to target vaccines to DC in order to improve immunogenicity. Cannulation of lymphatic vessels allows for the collection of DC that migrate from the skin. These migrating DC are involved in antigen uptake and presentation following vaccination. Human replication-deficient adenovirus (AdV) 5 is a promising vaccine vector for delivery of recombinant antigens. Although the mechanism of AdV attachment and penetration has been extensively studied in permissive cell lines, few studies have addressed the interaction of AdV with DC. In this study, we investigated the interaction of bovine skin-migrating DC and replication-deficient AdV-based vaccine vectors. We found that, despite lack of expression of Coxsackie B-Adenovirus Receptor and other known adenovirus receptors, AdV readily enters skin-draining DC via an actin-dependent endocytosis. Virus exit from endosomes was pH independent, and neutralizing antibodies did not prevent virus entry but did prevent virus translocation to the nucleus. We also show that combining adenovirus with adjuvant increases the absolute number of intracellular virus particles per DC but not the number of DC containing intracellular virus. This results in increased trans-gene expression and antigen presentation. We propose that, in the absence of Coxsackie B-Adenovirus Receptor and other known receptors, AdV5-based vectors enter skin-migrating DC using actin-dependent endocytosis which occurs in skin-migrating DC, and its relevance to vaccination strategies and vaccine vector targeting is discussed.

  8. Alcohol's actions on neuronal nicotinic acetylcholine receptors.

    PubMed

    Davis, Tiffany J; de Fiebre, Christopher M

    2006-01-01

    Although it has been known for many years that alcoholism and tobacco addiction often co-occur, relatively little information is available on the biological factors that regulate the co-use and abuse of nicotine and alcohol. In the brain, nicotine acts at several different types of receptors collectively known as nicotinic acetylcholine receptors (nAChRs). Alcohol also acts on at least some of these receptors, enhancing the function of some nAChR subtypes and inhibiting the activity of others. Chronic alcohol and nicotine administration also lead to changes in the numbers of nAChRs. Natural variations (i.e., polymorphisms) in the genes encoding different nAChR subunits may be associated with individual differences in the sensitivity to some of alcohol's and nicotine's effects. Finally, at least one subtype of nAChR may help protect cells against alcohol-induced neurotoxicity.

  9. 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.

  10. Molecular piracy of chemokine receptors by herpesviruses.

    PubMed

    Murphy, P M

    1994-01-01

    To succeed as a biological entity, viruses must exploit normal cellular functions and elude the host immune system; they often do so by molecular mimicry. One way that mimicry may occur is when viruses copy and modify host genes. The best studied examples of this are the oncogenes of RNA retroviruses, but a growing number of examples are also known for DNA viruses. So far they all come from just two groups of DNA viruses, the herpesviruses and poxviruses, and the majority of examples are for genes whose products regulate immune responses, such as cytokines, cytokine receptors, and complement control proteins. This review will focus on human and herpesvirus receptors for chemokines, a family of leukocyte chemoattractant and activating factors that are thought to be important mediators of inflammation. Although the biological roles of the viral chemokine receptor homologues are currently unknown, their connection to specific sets of chemokines has suggested a number of possible functions.

  11. 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.

  12. G protein-coupled receptor mutations and human genetic disease.

    PubMed

    Thompson, Miles D; Hendy, Geoffrey N; Percy, Maire E; Bichet, Daniel G; Cole, David E C

    2014-01-01

    Genetic variations in G protein-coupled receptor genes (GPCRs) disrupt GPCR function in a wide variety of human genetic diseases. In vitro strategies and animal models have been used to identify the molecular pathologies underlying naturally occurring GPCR mutations. Inactive, overactive, or constitutively active receptors have been identified that result in pathology. These receptor variants may alter ligand binding, G protein coupling, receptor desensitization and receptor recycling. Receptor systems discussed include rhodopsin, thyrotropin, parathyroid hormone, melanocortin, follicle-stimulating hormone (FSH), luteinizing hormone, gonadotropin-releasing hormone (GNRHR), adrenocorticotropic hormone, vasopressin, endothelin-β, purinergic, and the G protein associated with asthma (GPRA or neuropeptide S receptor 1 (NPSR1)). The role of activating and inactivating calcium-sensing receptor (CaSR) mutations is discussed in detail with respect to familial hypocalciuric hypercalcemia (FHH) and autosomal dominant hypocalemia (ADH). The CASR mutations have been associated with epilepsy. Diseases caused by the genetic disruption of GPCR functions are discussed in the context of their potential to be selectively targeted by drugs that rescue altered receptors. Examples of drugs developed as a result of targeting GPCRs mutated in disease include: calcimimetics and calcilytics, therapeutics targeting melanocortin receptors in obesity, interventions that alter GNRHR loss from the cell surface in idiopathic hypogonadotropic hypogonadism and novel drugs that might rescue the P2RY12 receptor congenital bleeding phenotype. De-orphanization projects have identified novel disease-associated receptors, such as NPSR1 and GPR35. The identification of variants in these receptors provides genetic reagents useful in drug screens. Discussion of the variety of GPCRs that are disrupted in monogenic Mendelian disorders provides the basis for examining the significance of common

  13. Conversion of epidermal growth factor receptor 2 and hormone receptor expression in breast cancer metastases to the brain

    PubMed Central

    2012-01-01

    Introduction We investigated the status of estrogen receptor alpha (ERα), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) in primary tumor and in the corresponding brain metastases in a consecutive series of breast cancer patients. Additionally, we studied factors potentially influencing conversion and evaluated its association with survival. Methods The study group included 120 breast cancer patients. ERα, PR, and HER2 status in primary tumors and in matched brain metastases was determined centrally by immunohistochemistry and/or fluorescence in situ hybridization. Results Using the Allred score of ≥ 3 as a threshold, conversion of ERα and PR in brain metastases occurred in 29% of cases for both receptors, mostly from positive to negative. Conversion of HER2 occurred in 14% of patients and was more balanced either way. Time to brain relapse and the use of chemotherapy or trastuzumab did not influence conversion, whereas endocrine therapy induced conversion of ERα (P = 0.021) and PR (P = 0.001), mainly towards their loss. Receptor conversion had no significant impact on survival. Conclusions Receptor conversion, particularly loss of hormone receptors, is a common event in brain metastases from breast cancer, and endocrine therapy may increase its incidence. Receptor conversion does not significantly affect survival. PMID:22898337

  14. 5-HT2 receptors facilitate JC polyomavirus entry.

    PubMed

    Assetta, Benedetta; Maginnis, Melissa S; Gracia Ahufinger, Irene; Haley, Sheila A; Gee, Gretchen V; Nelson, Christian D S; O'Hara, Bethany A; Allen Ramdial, Stacy-ann A; Atwood, Walter J

    2013-12-01

    The human JC polyomavirus (JCPyV) causes the rapidly progressing demyelinating disease progressive multifocal leukoencephalopathy (PML). The disease occurs most often in individuals with AIDS but also occurs in individuals receiving immunomodulatory therapies for immune-related diseases such as multiple sclerosis. JCPyV infection of host cells requires the pentasaccharide lactoseries tetrasaccharide c (LSTc) and the serotonin receptor 5-hydroxytryptamine (5-HT) receptor 5-HT2AR. While LSTc is involved in the initial attachment of virus to cells via interactions with VP1, the mechanism by which 5-HT2AR contributes to infection is not clear. To further define the roles of serotonin receptors in infection, HEK293A cells, which are poorly permissive to JCPyV, were transfected with 14 different isoforms of serotonin receptor. Only 5-HT2 receptors were found to support infection by JCPyV. None of the other 11 isoforms of serotonin receptor supported JCPyV infection. Expression of 5-HT2 receptors did not increase binding of JCPyV to cells, but this was not unexpected, given that the cells uniformly expressed the major attachment receptor, LSTc. Infection of these cells remained sensitive to inhibition with soluble LSTc, confirming that LSTc recognition is required for JCPyV infection. Virus internalization into HEK293A cells was significantly and specifically enhanced when 5HT2 receptors were expressed. Taken together, these data confirm that the carbohydrate LSTc is the attachment receptor for JCPyV and that the type 2 serotonin receptors contribute to JCPyV infection by facilitating entry.

  15. [The LDL receptor family].

    PubMed

    Meilinger, Melinda

    2002-12-29

    The members of the LDL receptor family are structurally related endocytic receptors. Our view on these receptors has considerably changed in recent years. Not only have new members of the family been identified, but also several interesting observations have been published concerning the biological function of these molecules. The LDL receptor family members are able to bind and internalize a plethora of ligands; as a consequence, they play important roles in diverse physiological processes. These receptors are key players in the lipoprotein metabolism, vitamin homeostasis, Ca2+ homeostasis, cell migration, and embryonic development. Until recently, LDL receptor family members were thought to be classic endocytic receptors that provide cells with metabolites on one hand, while regulating the concentration of their ligands in the extracellular fluids on the other hand. However, recent findings indicate that in addition to their cargo transport function, LDL receptor family members can act as signal transducers, playing important roles in the development of the central nervous system or the skeleton. Better understanding of physiological and pathophysiological functions of these molecules may open new avenues for the treatment or prevention of many disorders.

  16. Differential trafficking of AMPA receptors following activation of NMDA receptors and mGluRs.

    PubMed

    Sanderson, Thomas M; Collingridge, Graham L; Fitzjohn, Stephen M

    2011-07-27

    The removal of AMPA receptors from synapses is a major component of long-term depression (LTD). How this occurs, however, is still only partially understood. To investigate the trafficking of AMPA receptors in real-time we previously tagged the GluA2 subunit of AMPA receptors with ecliptic pHluorin and studied the effects of NMDA receptor activation. In the present study we have compared the effect of NMDA receptor and group I mGluR activation, using GluA2 tagged with super ecliptic pHluorin (SEP-GluA2) expressed in cultured hippocampal neurons. Surprisingly, agonists of the two receptors, which are both able to induce chemical forms of LTD, had clearly distinct effects on AMPA receptor trafficking. In agreement with our previous work we found that transient NMDA receptor activation results in an initial decrease in surface GluA2 from extrasynaptic sites followed by a delayed reduction in GluA2 from puncta (putative synapses). In contrast, transient activation of group I mGluRs, using DHPG, led to a pronounced but more delayed decrease in GluA2 from the dendritic shafts. Surprisingly, there was no average change in the fluorescence of the puncta. Examination of fluorescence at individual puncta, however, indicated that alterations did take place, with some puncta showing an increase and others a decrease in fluorescence. The effects of DHPG were, like DHPG-induced LTD, prevented by treatment with a protein tyrosine phosphatase (PTP) inhibitor. The electrophysiological correlate of the effects of DHPG in the SEP-GluA2 infected cultures was a reduction in mEPSC frequency with no change in amplitude. The implications of these findings for the initial mechanisms of expression of both NMDA receptor- and mGluR-induced LTD are discussed.

  17. Androgen receptor gene mutation, rearrangement, polymorphism

    PubMed Central

    Eisermann, Kurtis; Wang, Dan; Jing, Yifeng; Pascal, Laura E.

    2013-01-01

    Genetic aberrations of the androgen receptor (AR) caused by mutations, rearrangements, and polymorphisms result in a mutant receptor that has varied functions compared to wild type AR. To date, over 1,000 mutations have been reported in the AR with most of these being associated with androgen insensitivity syndrome (AIS). While mutations of AR associated with prostate cancer occur less often in early stage localized disease, mutations in castration-resistant prostate cancer (CRPC) patients treated with anti-androgens occur more frequently with 10-30% of these patients having some form of mutation in the AR. Resistance to anti-androgen therapy usually results from gain-of-function mutations in the LBD such as is seen with bicalutamide and more recently with enzalutamide (MDV3100). Thus, it is crucial to investigate these new AR mutations arising from drug resistance to anti-androgens and other small molecule pharmacological agents. PMID:25045626

  18. Genetic analysis of neuronal ionotropic glutamate receptor subunits.

    PubMed

    Granger, Adam J; Gray, John A; Lu, Wei; Nicoll, Roger A

    2011-09-01

    In the brain, fast, excitatory synaptic transmission occurs primarily through AMPA- and NMDA-type ionotropic glutamate receptors. These receptors are composed of subunit proteins that determine their biophysical properties and trafficking behaviour. Therefore, determining the function of these subunits and receptor subunit composition is essential for understanding the physiological properties of synaptic transmission. Here, we discuss and evaluate various genetic approaches that have been used to study AMPA and NMDA receptor subunits. These approaches have demonstrated that the GluA1 AMPA receptor subunit is required for activity-dependent trafficking and contributes to basal synaptic transmission, while the GluA2 subunit regulates Ca(2+) permeability, homeostasis and trafficking to the synapse under basal conditions. In contrast, the GluN2A and GluN2B NMDA receptor subunits regulate synaptic AMPA receptor content, both during synaptic development and plasticity. Ongoing research in this field is focusing on the molecular interactions and mechanisms that control these functions. To accomplish this, molecular replacement techniques are being used, where native subunits are replaced with receptors containing targeted mutations. In this review, we discuss a single-cell molecular replacement approach which should arguably advance our physiological understanding of ionotropic glutamate receptor subunits, but is generally applicable to study of any neuronal protein.

  19. Regulatory Features for Odorant Receptor Genes in the Mouse Genome

    PubMed Central

    Degl’Innocenti, Andrea; D’Errico, Anna

    2017-01-01

    The odorant receptor genes, seven transmembrane receptor genes constituting the vastest mammalian gene multifamily, are expressed monogenically and monoallelicaly in each sensory neuron in the olfactory epithelium. This characteristic, often referred to as the one neuron–one receptor rule, is driven by mostly uncharacterized molecular dynamics, generally named odorant receptor gene choice. Much attention has been paid by the scientific community to the identification of sequences regulating the expression of odorant receptor genes within their loci, where related genes are usually arranged in genomic clusters. A number of studies identified transcription factor binding sites on odorant receptor promoter sequences. Similar binding sites were also found on a number of enhancers that regulate in cis their transcription, but have been proposed to form interchromosomal networks. Odorant receptor gene choice seems to occur via the local removal of strongly repressive epigenetic markings, put in place during the maturation of the sensory neuron on each odorant receptor locus. Here we review the fast-changing state of art for the study of regulatory features for odorant receptor genes. PMID:28270833

  20. Regulatory Features for Odorant Receptor Genes in the Mouse Genome.

    PubMed

    Degl'Innocenti, Andrea; D'Errico, Anna

    2017-01-01

    The odorant receptor genes, seven transmembrane receptor genes constituting the vastest mammalian gene multifamily, are expressed monogenically and monoallelicaly in each sensory neuron in the olfactory epithelium. This characteristic, often referred to as the one neuron-one receptor rule, is driven by mostly uncharacterized molecular dynamics, generally named odorant receptor gene choice. Much attention has been paid by the scientific community to the identification of sequences regulating the expression of odorant receptor genes within their loci, where related genes are usually arranged in genomic clusters. A number of studies identified transcription factor binding sites on odorant receptor promoter sequences. Similar binding sites were also found on a number of enhancers that regulate in cis their transcription, but have been proposed to form interchromosomal networks. Odorant receptor gene choice seems to occur via the local removal of strongly repressive epigenetic markings, put in place during the maturation of the sensory neuron on each odorant receptor locus. Here we review the fast-changing state of art for the study of regulatory features for odorant receptor genes.

  1. Palmitoylation of the GluR6 kainate receptor.

    PubMed Central

    Pickering, D S; Taverna, F A; Salter, M W; Hampson, D R

    1995-01-01

    The G-protein-coupled metabotropic glutamate receptor mGluR1 alpha and the ionotropic glutamate receptor GluR6 were examined for posttranslational palmitoylation. Recombinant receptors were expressed in baculovirus-infected insect cells or in human embryonic kidney cells and were metabolically labeled with [3H]palmitic acid. The metabotropic mGluR1 alpha receptor was not labeled whereas the GluR6 kainate receptor was labeled after incubation with [3H]palmitate. The [3H]palmitate labeling of GluR6 was eliminated by treatment with hydroxylamine, indicating that the labeling was due to palmitoylation at a cysteine residue via a thioester bond. Site-directed mutagenesis was used to demonstrate that palmitoylation of GluR6 occurs at two cysteine residues, C827 and C840, located in the carboxyl-terminal domain of the molecule. A comparison of the electrophysiological properties of the wild-type and unpalmitoylated mutant receptor (C827A, C840A) showed that the kainate-gated currents produced by the unpalmitoylated mutant receptor were indistinguishable from those of the wild-type GluR6. The unpalmitoylated mutant was a better substrate for protein kinase C than the wild-type GluR6 receptor. These data indicate that palmitoylation may not modulate kainate channel function directly but instead affect function indirectly by regulating the phosphorylation state of the receptor. Images Fig. 1 Fig. 2 Fig. 3 Fig. 5 PMID:8618850

  2. CB1 Cannabinoid Receptors and their Associated Proteins

    PubMed Central

    Howlett, Allyn C.; Blume, Lawrence C.; Dalton, George D.

    2011-01-01

    CB1 receptors are G-protein coupled receptors (GPCRs) abundant in neurons, in which they modulate neurotransmission. The CB1 receptor influence on memory and learning is well recognized, and disease states associated with CB1 receptors are observed in addiction disorders, motor dysfunction, schizophrenia, and in bipolar, depression, and anxiety disorders. Beyond the brain, CB1 receptors also function in liver and adipose tissues, vascular as well as cardiac tissue, reproductive tissues and bone. Signal transduction by CB1 receptors occurs through interaction with Gi/o proteins to inhibit adenylyl cyclase, activate mitogen-activated protein kinases (MAPK), inhibit voltage-gated Ca2+ channels, activate K+ currents (Kir), and influence Nitric Oxide (NO) signaling. CB1 receptors are observed in internal organelles as well as plasma membrane. β-Arrestins, adaptor protein AP-3, and G-protein receptor-associated sorting protein 1 (GASP1) modulate cellular trafficking. Cannabinoid Receptor Interacting Protein 1a (CRIP1a) is an accessory protein whose function has not been delineated. Factor Associated with Neutral sphingomyelinase (FAN) regulates ceramide signaling. Such diversity in cellular signaling and modulation by interacting proteins suggests that agonists and allosteric modulators could be developed to specifically regulate unique, cell type-specific responses. PMID:20166926

  3. 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.

  4. Pharmacology and function of melatonin receptors

    SciTech Connect

    Dubocovich, M.L.

    1988-09-01

    The hormone melatonin is secreted primarily from the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone, through an action in the brain, appears to be involved in the regulation of various neural and endocrine processes that are cued by the daily change in photoperiod. This article reviews the pharmacological characteristics and function of melatonin receptors in the central nervous system, and the role of melatonin in mediating physiological functions in mammals. Melatonin and melatonin agonists, at picomolar concentrations, inhibit the release of dopamine from retina through activation of a site that is pharmacologically different from a serotonin receptor. These inhibitory effects are antagonized by the novel melatonin receptor antagonist luzindole (N-0774), which suggests that melatonin activates a presynaptic melatonin receptor. In chicken and rabbit retina, the pharmacological characteristics of the presynaptic melatonin receptor and the site labeled by 2-(125I)iodomelatonin are identical. It is proposed that 2-(125I)iodomelatonin binding sites (e.g., chicken brain) that possess the pharmacological characteristics of the retinal melatonin receptor site (order of affinities: 2-iodomelatonin greater than 6-chloromelatonin greater than or equal to melatonin greater than or equal to 6,7-di-chloro-2-methylmelatonin greater than 6-hydroxymelatonin greater than or equal to 6-methoxymelatonin greater than N-acetyltryptamine greater than or equal to luzindole greater than N-acetyl-5-hydroxytryptamine greater than 5-methoxytryptamine much greater than 5-hydroxytryptamine) be classified as ML-1 (melatonin 1). The 2-(125I)iodomelatonin binding site of hamster brain membranes possesses different binding and pharmacological characteristics from the retinal melatonin receptor site and should be classified as ML-2. 64 references.

  5. Nuclear transportation of exogenous epidermal growth factor receptor and androgen receptor via extracellular vesicles.

    PubMed

    Read, Jolene; Ingram, Alistair; Al Saleh, Hassan A; Platko, Khrystyna; Gabriel, Kathleen; Kapoor, Anil; Pinthus, Jehonathan; Majeed, Fadwa; Qureshi, Talha; Al-Nedawi, Khalid

    2017-01-01

    Epidermal growth factor receptor (EGFR) plays a central role in the progression of several human malignancies. Although EGFR is a membrane receptor, it undergoes nuclear translocation, where it has a distinct signalling pathway. Herein, we report a novel mechanism by which cancer cells can directly transport EGFR to the nucleus of other cells via extracellular vesicles (EVs). The transported receptor is active and stimulates the nuclear EGFR pathways. Interestingly, the translocation of EGFR via EVs occurs independently of the nuclear localisation sequence that is required for nuclear translocation of endogenous EGFR. Also, we found that the mutant receptor EGFRvIII could be transported to the nucleus of other cells via EVs. To assess the role of EVs in the regulation of an actual nuclear receptor, we studied the regulation of androgen receptor (AR). We found that full-length AR and mutant variant ARv7 are secreted in EVs derived from prostate cancer cell lines and could be transported to the nucleus of AR-null cells. The EV-derived AR was able to bind the androgen-responsive promoter region of prostate specific antigen, and recruit RNA Pol II, an indication of active transcription. The nuclear-translocated AR via EVs enhanced the proliferation of acceptor cells in the absence of androgen. Finally, we provide evidence that nuclear localisation of AR could occur in vivo via orthotopically-injected EVs in male SCID mice prostate glands. To our knowledge, this is the first study showing the nuclear translocation of nuclear receptors via EVs, which significantly extends the role of EVs as paracrine transcriptional regulators.

  6. 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.

  7. 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

  8. Computational studies of ligand-receptor interactions in bitter taste receptors.

    PubMed

    Miguet, Laurence; Zhang, Ziding; Grigorov, Martin G

    2006-01-01

    Phenylthiocarbamide tastes intensely bitter to some individuals, but others find it completely tasteless. Recently, it was suggested that phenylthiocarbamide elicits bitter taste by interacting with a human G protein-coupled receptor (hTAS2R38) encoded by the PTC gene. The phenylthiocarbamide nontaster trait was linked to three single nucleotide polymorphisms occurring in the PTC gene. Using the crystal structure of bovine rhodopsin as template, we generated the 3D structure of hTAS2R38 bitter taste receptor. We were able to map on the receptor structure the amino acids affected by the genetic polymorphisms and to propose molecular functions for two of them that explained the emergence of the nontaster trait. We used molecular docking simulations to find that phenylthiocarbamide exhibited a higher affinity for the target receptor than the structurally similar molecule 6-n-propylthiouracil, in line with recent experimental studies. A 3D model was constructed for the hTAS2R16 bitter taste receptor as well, by applying the same protocol. We found that the recently published experimental ligand binding affinity data for this receptor correlated well with the binding scores obtained from our molecular docking calculations.

  9. 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

  10. 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.

  11. Delta opioid receptor analgesia: recent contributions from pharmacology and molecular approaches

    PubMed Central

    Gavériaux-Ruff, Claire; Kieffer, Brigitte Lina

    2012-01-01

    Delta opioid receptors represent a promising target for the development of novel analgesics. A number of tools have been developed recently that have significantly improved our knowledge of delta receptor function in pain control. These include several novel delta agonists with potent analgesic properties, as well as genetic mouse models with targeted mutations in the delta opioid receptor gene. Also, recent findings have further documented the regulation of delta receptor function at cellular level, which impacts on the pain-reducing activity of the receptor. These regulatory mechanisms occur at transcriptional and post-translational levels, along agonist-induced receptor activation, signaling and trafficking, or in interaction with other receptors and neuromodulatory systems. All these tools for in vivo research, as well as proposed mechanisms at molecular level, have tremendously increased our understanding of delta receptor physiology, and contribute to designing innovative strategies for the treatment of chronic pain and other diseases such as mood disorders. PMID:21836459

  12. Serotonin Receptors in Hippocampus

    PubMed Central

    Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

    2012-01-01

    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system. PMID:22629209

  13. Role of adenosine A2b receptor overexpression in tumor progression.

    PubMed

    Sepúlveda, Cesar; Palomo, Iván; Fuentes, Eduardo

    2016-12-01

    The adenosine A2b receptor is a G-protein coupled receptor. Its activation occurs with high extracellular adenosine concentration, for example in inflammation or hypoxia. These conditions are generated in the tumor environment. Studies show that A2b receptor is overexpressed in various tumor lines and biopsies from patients with different cancers. This suggests that A2b receptor can be used by tumor cells to promote progression. Thus A2b participates in different events, such as angiogenesis and metastasis, besides exerting immunomodulatory effects that protect tumor cells. Therefore, adenosine A2b receptor appears as an interesting therapeutic target for cancer treatment.

  14. Kappa-opioid receptor-selective dicarboxylic ester-derived salvinorin A ligands.

    PubMed

    Polepally, Prabhakar R; White, Kate; Vardy, Eyal; Roth, Bryan L; Ferreira, Daneel; Zjawiony, Jordan K

    2013-05-15

    Salvinorin A, the active ingredient of the hallucinogenic plant Salvia divinorum is the most potent known naturally occurring hallucinogen and is a selective κ-opioid receptor agonist. To better understand the ligand-receptor interactions, a series of dicarboxylic ester-type of salvinorin A derivatives were synthesized and evaluated for their binding affinity at κ-, δ- and μ-opioid receptors. Most of the analogues show high affinity to the κ-opioid receptor. Methyl malonyl derivative 4 shows the highest binding affinity (Ki=2nM), analogues 5, 7, and 14 exhibit significant affinity for the κ-receptor (Ki=21, 36 and 39nM).

  15. Kappa-Opioid Receptor-Selective Dicarboxylic Ester-Derived Salvinorin A Ligands

    PubMed Central

    Polepally, Prabhakar R.; White, Kate; Vardy, Eyal; Roth, Bryan L.; Ferreira, Daneel; Zjawiony, Jordan K.

    2013-01-01

    Salvinorin A, the active ingredient of the hallucinogenic plant Salvia divinorum is the most potent known naturally occurring hallucinogen and is a selective κ-opioid receptor agonist. To better understand the ligand-receptor interactions, a series of dicarboxylic ester-type of salvinorin A derivatives were synthesized and evaluated for their binding affinity at κ, δ, and μ-opioid receptors. Most of the analogues show high affinity to the κ-opioid receptor. Methyl malonyl derivative 4 shows the highest binding affinity (Ki = 2 nM), analogues 5, 7, and 14 exhibit significant affinity for the κ-receptor (Ki = 21, 36 and 39 nM). PMID:23587424

  16. Pituitary Somatostatin Receptor Signaling

    PubMed Central

    Ben-Shlomo, Anat; Melmed, Shlomo

    2010-01-01

    Somatostatin (SRIF) is a major regulator of pituitary function, mostly inhibiting hormone secretion and to a lesser extent pituitary cell growth. Five SRIF receptor subtypes (SSTR1–5) are ubiquitously expressed G-protein coupled receptors. In the pituitary, SSTR1, SSTR2, SSTR3 and SSTR5 are expressed, with SSTR2 and SSTR5 predominating. As new SRIF-analogs have recently been introduced for treatment of pituitary disease, we evaluate the current knowledge of cell-specific pituitary SRIF receptor signaling and highlight areas of future research for comprehensive understanding of these mechanisms. Elucidating pituitary SRIF receptor signaling enables understanding of pituitary hormone secretion and cell growth, and also points to future therapeutic development for pituitary disorders. PMID:20149677

  17. Sigma Receptor Binding Assays.

    PubMed

    Chu, Uyen B; Ruoho, Arnold E

    2015-12-08

    Sigma receptors, both Sigma-1(S1R) and Sigma-2 (S2R), are small molecule-regulated, primarily endoplasmic reticulum (ER) membrane-associated sites. A number of drugs bind to sigma receptors, including the antipsychotic haloperidol and (+)-pentazocine, an opioid analgesic. Sigma receptors are implicated in many central nervous system disorders, in particular Alzheimer's disease and conditions associated with motor control, such as Amyotrophic Lateral Sclerosis (ALS). Described in this unit are radioligand binding assays used for the pharmacological characterization of S1R and S2R. Methods detailed include a radioligand saturation binding assay for defining receptor densities and a competitive inhibition binding assay employing [³H]-(+)-pentazocine for identifying and characterizing novel ligands that interact with S1R. Procedures using [³H]-1,3-di(2-tolyl)guanidine ([³H]-DTG), a nonselective sigma receptor ligand, are described for conducting a saturation binding and competitive inhibition assays for the S2R site. These protocols are of value in drug discovery in identifying new sigma ligands and in the characterization of these receptors.

  18. Muscarinic Receptor Antagonists.

    PubMed

    Matera, Maria Gabriella; Cazzola, Mario

    2017-01-01

    Parasympathetic activity is increased in patients with chronic obstructive pulmonary disease (COPD) and asthma and appears to be the major reversible component of airway obstruction. Therefore, treatment with muscarinic receptor antagonists is an effective bronchodilator therapy in COPD and also in asthmatic patients. In recent years, the accumulating evidence that the cholinergic system controls not only contraction by airway smooth muscle but also the functions of inflammatory cells and airway epithelial cells has suggested that muscarinic receptor antagonists could exert other effects that may be of clinical relevance when we must treat a patient suffering from COPD or asthma. There are currently six muscarinic receptor antagonists licenced for use in the treatment of COPD, the short-acting muscarinic receptor antagonists (SAMAs) ipratropium bromide and oxitropium bromide and the long-acting muscarinic receptor antagonists (LAMAs) aclidinium bromide, tiotropium bromide, glycopyrronium bromide and umeclidinium bromide. Concerns have been raised about possible associations of muscarinic receptor antagonists with cardiovascular safety, but the most advanced compounds seem to have an improved safety profile. Further beneficial effects of SAMAs and LAMAs are seen when added to existing treatments, including LABAs, inhaled corticosteroids and phosphodiesterase 4 inhibitors. The importance of tiotropium bromide in the maintenance treatment of COPD, and likely in asthma, has spurred further research to identify new LAMAs. There are a number of molecules that are being identified, but only few have reached the clinical development.

  19. 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

  20. SIGMA RECEPTOR BINDING ASSAYS

    PubMed Central

    CHU, UYEN B.; RUOHO, ARNOLD E.

    2016-01-01

    Sigma receptors belong to a class of small molecule-regulated, primarily endoplasmic reticulum (ER) membrane-associated receptors, of which there are two subtypes: the Sigma-1 receptor (S1R) and the Sigma-2 receptor (S2R). Both S1R and S2R bind to a number of drugs including antipsychotic, haloperidol, and the opioid analgesic, (+)-pentazocine. Sigma receptors are implicated in multiple disease pathologies associated with the nervous system including diseases affecting motor control such as Amyotrophic Lateral Sclerosis (ALS) and Alzeimher's disease. This unit describes methods for the pharmacological characterization of S1R and S2R using radioligand-binding assays. In the first section, radioligand saturation binding assay to determine receptor densities and competitive inhibition assays to characterize affinities of novel compounds are presented for S1R using the selective S1R ligand, [3H]-(+)-pentazocine. The second section describes radioligand saturation binding assay and competitive inhibition assays for the S2R using a non-selective S1R and S2R ligand, [3H]-1,3-di(2-tolyl)guanidine ([3H]-DTG). PMID:26646191

  1. pH-Dependent Inhibition of Kainate Receptors by Zinc

    PubMed Central

    Mott, David D.; Benveniste, Morris; Dingledine, Raymond J.

    2014-01-01

    Kainate receptors contribute to synaptic plasticity and rhythmic oscillatory firing of neurons in corticolimbic circuits including hippocampal area CA3. We use zinc chelators and mice deficient in zinc transporters to show that synaptically released zinc inhibits postsynaptic kainate receptors at mossy fiber synapses and limits frequency facilitation of kainate, but not AMPA EPSCs during thetapattern stimulation. Exogenous zinc also inhibits the facilitatory modulation of mossy fiber axon excitability by kainate but does not suppress the depressive effect of kainate on CA3 axons. Recombinant kainate receptors are inhibited in a subunit-dependent manner by physiologically relevant concentrations of zinc, with receptors containing the KA1 subunit being sensitive to submicromolar concentrations of zinc. Zinc inhibition does not alter receptor desensitization nor apparent agonist affinity and is only weakly voltage dependent, which points to an allosteric mechanism. Zinc inhibition is reduced at acidic pH. Thus, in the presence of zinc, a fall in pH potentiates kainate receptors by relieving zinc inhibition. Acidification of the extracellular space, as occurs during repetitive activity, may therefore serve to unmask kainate receptor neurotransmission. We conclude that zinc modulation of kainate receptors serves an important role in shaping kainate neurotransmission in the CA3 region. PMID:18272686

  2. Photoaffinity ligand for dopamine D2 receptors: azidoclebopride

    SciTech Connect

    Niznik, H.B.; Guan, J.H.; Neumeyer, J.L.; Seeman, P.

    1985-02-01

    In order to label D2 dopamine receptors selectively and covalently by means of a photosensitive compound, azidoclebopride was synthesized directly from clebopride. The dissociation constant (KD) of clebopride for the D2 dopamine receptor (canine brain striatum) was 1.5 nM, while that for azidoclebopride was 21 nM. The affinities of both clebopride and azidoclebopride were markedly reduced in the absence of sodium chloride. In the presence of ultraviolet light, azidoclebopride inactivated D2 dopamine receptors irreversibly, as indicated by the inability of the receptors to bind (/sup 3/H)spiperone. Maximal photoinactivation of about 60% of the D2 dopamine receptors occurred at 1 microM azidoclebopride; 30% of the receptors were inactivated at 80 nM azidoclebopride (pseudo-IC50). Dopamine agonists selectively protected the D2 receptors from being inactivated by azidoclebopride, the order of potency being (-)-N-n-propylnorapomorphine greater than apomorphine greater than (+/-)-6,7-dihydroxy-2-aminotetralin greater than (+)-N-n-propylnorapomorphine greater than dopamine greater than noradrenaline greater than serotonin. Similarly, dopaminergic antagonists prevented the photoinactivation of D2 receptors by azidoclebopride with the following order of potency: spiperone greater than (+)-butaclamol greater than haloperidol greater than clebopride greater than (-)-sulpiride greater than (-)-butaclamol.

  3. Pouncing on the chemokine receptor Chimera.

    PubMed

    Mascolini, M

    1997-08-01

    Scientists are seeking to unravel the mystery of chemokine receptors in an attempt to develop treatments for HIV infection; however, receptor experts are realizing that the picture is more complicated than they first imagined. Scientists want to know, among other things, what parts of each coreceptor are essential for viral fusion with target cells, what makes macrophage-tropic viruses switch their preference to T-lymphocytes, why HIV goes after chemokine receptors in the first place, and how fusion and entry occur. Other issues discussed include whether blocking coreceptors for HIV will actually curb this disease, virus turnover in monkey studies showing that SIV may go through the cycle as many as 100 times per day, and studies showing that the first days of infection may predict the course of disease. Final comments concern the use of ritonavir plus indinavir in treatment combinations for children with HIV and the latest progress toward vaccine development. Understanding these and other puzzles might help scientists to develop drugs to block receptors active in HIV infection and perhaps curb HIV. More than 14 biotechnology and pharmaceutical firms are working to design coreceptor blockers, despite the opinions of several leading researchers that the drugs are not terribly promising. Dr. Anthony Fauci, director of the National Institute for Allergy and Infectious Disease (NIAID), notes that a famous attempt to block HIV's primary receptor failed, and David Ho, the man who demonstrated why CD4 would not work as therapy, is similarly cautious. According to Ho, drug makers will have no trouble developing compounds that keep HIV off chemokine receptors, such as CCR5 or CXCR4, but whether those compounds will slow disease progression is another question.

  4. Heterodimeric interaction between retinoid X receptor alpha and orphan nuclear receptor OR1 reveals dimerization-induced activation as a novel mechanism of nuclear receptor activation.

    PubMed Central

    Wiebel, F F; Gustafsson, J A

    1997-01-01

    OR1 is a member of the steroid/thyroid hormone nuclear receptor superfamily which has been described to mediate transcriptional responses to retinoids and oxysterols. On a DR4 response element, an OR1 heterodimer with the nuclear receptor retinoid X receptor alpha (RXR alpha) has been described to convey transcriptional activation in both the absence and presence of the RXR ligand 9-cis retinoic acid, the mechanisms of which have remained unclear. Here, we dissect the effects of RXR alpha and OR1 ligand-binding domain interaction on transcriptional regulation and the role of the respective carboxy-terminal activation domains (AF-2s) in the absence and presence of the RXR ligand, employing chimeras of the nuclear receptors containing the heterologous GAL4 DNA-binding domain as well as natural receptors. The results show that the interaction of the RXR and OR1 ligand-binding domains unleashes a transcription activation potential that is mainly dependent on the AF-2 of OR1, indicating that interaction with RXR activates OR1. This defines dimerization-induced activation as a novel function of heterodimeric interaction and mechanism of receptor activation not previously described for nuclear receptors. Moreover, we present evidence that activation of OR1 occurs by a conformational change induced upon heterodimerization with RXR. PMID:9199332

  5. Adenosine A1 receptor: Functional receptor-receptor interactions in the brain

    PubMed Central

    Sichardt, Kathrin

    2007-01-01

    Over the past decade, many lines of investigation have shown that receptor-mediated signaling exhibits greater diversity than previously appreciated. Signal diversity arises from numerous factors, which include the formation of receptor dimers and interplay between different receptors. Using adenosine A1 receptors as a paradigm of G protein-coupled receptors, this review focuses on how receptor-receptor interactions may contribute to regulation of the synaptic transmission within the central nervous system. The interactions with metabotropic dopamine, adenosine A2A, A3, neuropeptide Y, and purinergic P2Y1 receptors will be described in the first part. The second part deals with interactions between A1Rs and ionotropic receptors, especially GABAA, NMDA, and P2X receptors as well as ATP-sensitive K+ channels. Finally, the review will discuss new approaches towards treating neurological disorders. PMID:18404442

  6. Modulation of M(2) muscarinic receptor-receptor interaction by immunoglobulin G antibodies from Chagas' disease patients.

    PubMed

    Beltrame, S P; Auger, S R; Bilder, C R; Waldner, C I; Goin, J C

    2011-05-01

    Circulating immunoglobulin (Ig)G antibodies against M(2) muscarinic acetylcholine receptors (M(2) mAChR) have been implicated in Chagas' disease (ChD) pathophysiology. These antibodies bind to and activate their target receptor, displaying agonist-like activity through an unclear mechanism. This study tested the ability of serum anti-M(2) mAChR antibodies from chronic ChD patients to modulate M(2) muscarinic receptor-receptor interaction by bioluminescence resonance energy transfer (BRET). Human embryonic kidney (HEK) 293 cells co-expressing fusion proteins M(2) mAChR-Renilla luciferase (RLuc) and M(2) mAChR-yellow fluorescent protein (YFP) were exposed to the serum IgG fraction from ChD patients, and BRET between RLuc and YFP was assessed by luminometry. Unlike serum IgG from healthy subjects and conventional muscarinic ligands, ChD IgG promoted a time- and concentration-dependent increase in the BRET signal. This effect neither required cellular integrity nor occurred as a consequence of receptor activation. Enhancement of M(2) receptor-receptor interaction by ChD IgG was receptor subtype-specific and mediated by the recognition of the second extracellular loop of the M(2) mAChR. The monovalent Fab fragment derived from ChD IgG was unable to reproduce the effect of the native immunoglobulin. However, addition of ChD Fab in the presence of anti-human Fab IgG restored BRET-enhancing activity. These data suggest that the modulatory effect of ChD IgG on M(2) receptor-receptor interaction results from receptor cross-linking by bivalent antibodies.

  7. 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.

  8. Antitumor effects of naturally occurring cardiac glycosides convallatoxin and peruvoside on human ER+ and triple-negative breast cancers

    PubMed Central

    Kaushik, Vivek; Azad, Neelam; Yakisich, Juan Sebastian; Iyer, Anand Krishnan V

    2017-01-01

    Breast cancer is second most prevalent cancer in women, and the second only to lung cancer in cancer-related deaths. It is a heterogeneous disease and has several subtypes based on the presence or absence of hormone receptors and/or human epidermal growth factor receptor 2 (HER2). Hormone receptor-positive and HER2-enriched cancers can be targeted using hormone and HER2-targeting therapies such as trastuzumab or lapatinib. However, triple-negative breast cancers (TNBCs) do not express any of the receptors and therefore are resistant to most targeted therapies, and cytotoxic chemotherapies are the only viable option available for the treatment of TNBCs. Recently, cardiac glycosides (CGs) have emerged as potential anticancer agents that impart their antiproliferative effect by targeting multiple pathways. In this study our aim was to evaluate anticancer effects of two naturally occurring CGs, Convallatoxin (CT) and Peruvoside (PS), on ER+ and TNBCs cells. CT and PS demonstrated dose- and time-dependent cytotoxic effect on MCF-7 cells, which was further supported by loss of colony formation on drug treatment. CT and PS arrested MCF-7 cells in the G0/G1 phase and reduced the viability of MCF-7-derived mammospheres (MMs). Interestingly, while CT and PS imparted cell death in TNBCs cells from both Caucasians (MDA-MB-231 cells) and African Americans (MDA-MB-468 cells) in a dose- and time-dependent manner, the drugs were much more potent in MDA-MB-468 as compared with TNBC MDA-MB-231 cells. Both drugs significantly inhibited migration and invasion of both MCF-7 and MDA-MB-468 cells. An assessment of intracellular pathways indicated that both drugs were able to modulate several key cellular pathways such as EMT, cell cycle, proliferation and cell death in both cell types. Our data suggest a promising role for CGs in breast cancer treatment specifically in targeting TNBCs derived from African Americans, and provides impetus for further investigation of the anticancer

  9. Enhancement of GABAA-current run-down in the hippocampus occurs at the first spontaneous seizure in a model of temporal lobe epilepsy

    PubMed Central

    Mazzuferi, Manuela; Palma, Eleonora; Martinello, Katiuscia; Maiolino, Francesca; Roseti, Cristina; Fucile, Sergio; Fabene, Paolo F.; Schio, Federica; Pellitteri, Michele; Sperk, Guenther; Miledi, Ricardo; Eusebi, Fabrizio; Simonato, Michele

    2010-01-01

    Refractory temporal lobe epilepsy (TLE) is associated with a dysfunction of inhibitory signaling mediated by GABAA receptors. In particular, the use-dependent decrease (run-down) of the currents (IGABA) evoked by the repetitive activation of GABAA receptors is markedly enhanced in hippocampal and cortical neurons of TLE patients. Understanding the role of IGABA run-down in the disease, and its mechanisms, may allow development of medical alternatives to surgical resection, but such mechanistic insights are difficult to pursue in surgical human tissue. Therefore, we have used an animal model (pilocarpine-treated rats) to identify when and where the increase in IGABA run-down occurs in the natural history of epilepsy. We found: (i) that the increased run-down occurs in the hippocampus at the time of the first spontaneous seizure (i.e., when the diagnosis of epilepsy is made), and then extends to the neocortex and remains constant in the course of the disease; (ii) that the phenomenon is strictly correlated with the occurrence of spontaneous seizures, because it is not observed in animals that do not become epileptic. Furthermore, initial exploration of the molecular mechanism disclosed a relative increase in α4-, relative to α1-containing GABAA receptors, occurring at the same time when the increased run-down appears, suggesting that alterations in the molecular composition of the GABA receptors may be responsible for the occurrence of the increased run-down. These observations disclose research opportunities in the field of epileptogenesis that may lead to a better understanding of the mechanism whereby a previously normal tissue becomes epileptic. PMID:20133704

  10. Contribution of Schwann Cells to Remyelination in a Naturally Occurring Canine Model of CNS Neuroinflammation.

    PubMed

    Kegler, Kristel; Spitzbarth, Ingo; Imbschweiler, Ilka; Wewetzer, Konstantin; Baumgärtner, Wolfgang; Seehusen, Frauke

    2015-01-01

    Gliogenesis under pathophysiological conditions is of particular clinical relevance since it may provide evidence for regeneration promoting cells recruitable for therapeutic purposes. There is evidence that neurotrophin receptor p75 (p75NTR)-expressing cells emerge in the lesioned CNS. However, the phenotype and identity of these cells, and signals triggering their in situ generation under normal conditions and certain pathological situations has remained enigmatic. In the present study, we used a spontaneous, idiopathic and inflammatory CNS condition in dogs with prominent lympho-histiocytic infiltration as a model to study the phenotype of Schwann cells and their relation to Schwann cell remyelination within the CNS. Furthermore, the phenotype of p75NTR-expressing cells within the injured CNS was compared to their counter-part in control sciatic nerve and after peripheral nerve injury. In addition, organotypic slice cultures were used to further elucidate the origin of p75NTR-positive cells. In cerebral and cerebellar white and grey matter lesions as well as in the brain stem, p75NTR-positive cells co-expressed the transcription factor Sox2, but not GAP-43, GFAP, Egr2/Krox20, periaxin and PDGFR-α. Interestingly, and contrary to the findings in control sciatic nerves, p75NTR-expressing cells only co-localized with Sox2 in degenerative neuropathy, thus suggesting that such cells might represent dedifferentiated Schwann cells both in the injured CNS and PNS. Moreover, effective Schwann cell remyelination represented by periaxin- and P0-positive mature myelinating Schwann cells, was strikingly associated with the presence of p75NTR/Sox2-expressing Schwann cells. Intriguingly, the emergence of dedifferentiated Schwann cells was not affected by astrocytes, and a macrophage-dominated inflammatory response provided an adequate environment for Schwann cells plasticity within the injured CNS. Furthermore, axonal damage was reduced in brain stem areas with p75NTR/Sox2

  11. Contribution of Schwann Cells to Remyelination in a Naturally Occurring Canine Model of CNS Neuroinflammation

    PubMed Central

    Imbschweiler, Ilka; Wewetzer, Konstantin; Baumgärtner, Wolfgang; Seehusen, Frauke

    2015-01-01

    Gliogenesis under pathophysiological conditions is of particular clinical relevance since it may provide evidence for regeneration promoting cells recruitable for therapeutic purposes. There is evidence that neurotrophin receptor p75 (p75NTR)-expressing cells emerge in the lesioned CNS. However, the phenotype and identity of these cells, and signals triggering their in situ generation under normal conditions and certain pathological situations has remained enigmatic. In the present study, we used a spontaneous, idiopathic and inflammatory CNS condition in dogs with prominent lympho-histiocytic infiltration as a model to study the phenotype of Schwann cells and their relation to Schwann cell remyelination within the CNS. Furthermore, the phenotype of p75NTR-expressing cells within the injured CNS was compared to their counter-part in control sciatic nerve and after peripheral nerve injury. In addition, organotypic slice cultures were used to further elucidate the origin of p75NTR-positive cells. In cerebral and cerebellar white and grey matter lesions as well as in the brain stem, p75NTR-positive cells co-expressed the transcription factor Sox2, but not GAP-43, GFAP, Egr2/Krox20, periaxin and PDGFR-α. Interestingly, and contrary to the findings in control sciatic nerves, p75NTR-expressing cells only co-localized with Sox2 in degenerative neuropathy, thus suggesting that such cells might represent dedifferentiated Schwann cells both in the injured CNS and PNS. Moreover, effective Schwann cell remyelination represented by periaxin- and P0-positive mature myelinating Schwann cells, was strikingly associated with the presence of p75NTR/Sox2-expressing Schwann cells. Intriguingly, the emergence of dedifferentiated Schwann cells was not affected by astrocytes, and a macrophage-dominated inflammatory response provided an adequate environment for Schwann cells plasticity within the injured CNS. Furthermore, axonal damage was reduced in brain stem areas with p75NTR/Sox2

  12. 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

  13. Chemoprevention of Prostate Cancer by Naturally Occurring and Synthetic Organoselenium Compounds

    DTIC Science & Technology

    2010-12-01

    Suppression versus induction of androgen receptor functions by the phosphatidylinositol 3-kinase/Akt pathway in prostate cancer LNCaP cells with... prostate cancer , androgen receptor, Akt, mTOR 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF... androgen independent human prostate cancer cells and 2. to determine the in vivo effects of SM and p-XSC on tumorigenesis and biomarkers of cancer ]. The

  14. Inhibitory neurosteroids and the GABAA receptor.

    PubMed

    Seljeset, Sandra; Laverty, Duncan; Smart, Trevor G

    2015-01-01

    γ-Aminobutyric acid type A receptors (GABAARs) are vital proteins that are engaged in regulating neural circuit activity in the central nervous system. Their effectiveness in this task is dependent on the extent of receptor modulation by naturally occurring ligands that are released in the brain. One of the foremost examples of such ligands is the neurosteroids that can either potentiate GABAAR function or cause direct inhibition. To fully understand the underlying mechanisms by which neurosteroids modulate GABAARs, it is necessary to identify their binding sites on the receptors. For potentiating neurosteroids, recent work has made substantive progress in identifying a binding site located in the transmembrane domains of GABAAR α subunits. However, for the inhibitory neurosteroids, several possibilities exist including an ion channel site as well as potential sites in the transmembrane domain. This review systematically analyzes the evidence behind possible binding sites for the inhibitory neurosteroids. We consider the chemical structure-function properties of such inhibitory neurosteroids, their physiological effects on synaptic inhibition, and whether a binding site exists in the GABA ion channel or in other areas of the transmembrane domain. Finally, we discuss how structural homology modeling and Cys-loop receptor homologues may help to locate the inhibitory neurosteroid-binding site on GABAARs.

  15. Anti-NMDA Receptor Encephalitis and Vaccination

    PubMed Central

    Wang, Hsiuying

    2017-01-01

    Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is an acute autoimmune neurological disorder. The cause of this disease is often unknown, and previous studies revealed that it might be caused by a virus, vaccine or tumor. It occurs more often in females than in males. Several cases were reported to be related to vaccination such as the H1N1 vaccine and tetanus/diphtheria/pertussis and polio vaccines. In this study, we reported an anti-NMDA receptor encephalitis case that may be caused by Japanese encephalitis vaccination. To investigate the association between anti-NMDA receptor encephalitis and vaccination, we analyzed the phylogenetic relationship of the microRNAs, which significantly regulate these vaccine viruses or bacteria, and the phylogenetic relationship of these viruses and bacteria. This reveals that anti-NMDA receptor encephalitis may be caused by Japanese encephalitis vaccination, as well as H1N1 vaccination or tetanus/diphtheria/pertussis and polio vaccinations, from the phylogenetic viewpoint. PMID:28106787

  16. Anti-NMDA Receptor Encephalitis and Vaccination.

    PubMed

    Wang, Hsiuying

    2017-01-18

    Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is an acute autoimmune neurological disorder. The cause of this disease is often unknown, and previous studies revealed that it might be caused by a virus, vaccine or tumor. It occurs more often in females than in males. Several cases were reported to be related to vaccination such as the H1N1 vaccine and tetanus/diphtheria/pertussis and polio vaccines. In this study, we reported an anti-NMDA receptor encephalitis case that may be caused by Japanese encephalitis vaccination. To investigate the association between anti-NMDA receptor encephalitis and vaccination, we analyzed the phylogenetic relationship of the microRNAs, which significantly regulate these vaccine viruses or bacteria, and the phylogenetic relationship of these viruses and bacteria. This reveals that anti-NMDA receptor encephalitis may be caused by Japanese encephalitis vaccination, as well as H1N1 vaccination or tetanus/diphtheria/pertussis and polio vaccinations, from the phylogenetic viewpoint.

  17. 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.

  18. 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

  19. Epidermal Growth Factor Receptor Overexpression as a Target for Auger Electron Radiotherapy of Breast Cancer

    DTIC Science & Technology

    1999-08-01

    proportion of estrogen receptor-negative and hormone-resistant breast cancers. Our objective is to construct a human epidermal growth factor (hEGF...61 5 INTRODUCTION Overexpression of the epidermal growth factor receptor (EGFR) occurs in a high proportion of estrogen receptor-negative and...Lac Iq promotor induced by isopropyl-b- D -thiogalactopyranoside (IPTG). The DNA sequence of the final hEGF-CH1 construct was confirmed (FUi. 2). BamHJ

  20. Biomembrane and receptor mechanisms

    SciTech Connect

    Chapman, D.; Bertoli, E.

    1987-01-01

    This book cover the reviews on biomembrane dynamics; recent spectroscopic studies. Topics covered are freeze fracture: Seeing and thinking biological membranes, membrane proteins and receptors: structure and organisation; techniques to determine the transbilayer distribution and mobility of phospholipids in biological membranes, transbilayer organisation of phospholipids in the plasma membranes of pro-erythroblasts and normal and abnormal red cells, aminophospholipid translocation in the erythroctye membrane is mediated by a specific AIP-dependent enzyme; membrane protein interactions, lipid-protein interactions: selectively and receptor binding, membrane fluidity in the regulation of membrane-linked enzymes, the lipid regulation of receptor functions, microheterogencity of biological membrane: structural and functional implications, fusion-fission reactions in biological membranes and in phospholpid bilayers, methods for studying the structure and function of the mitochondrial uncoupling protein, methods for studying metabolite transport in mitochondria, transport of metabolites in mitochondria, membrane gangliosides and allied glycosphingolipids: Biochemical features and physicochemical properties, the use of merocyanine 540 for monitoring aggregation properties of sialogangliosides in solution, hormone reception at the cell surface - an overview, double role for GIP in the stimulus secretion sequence of mast cells and neurophils, tumor promoters and hormone receptor coupling mechanisms in the anterior pituitary. The regulation of hormone-dependent adenylate cyclase in native membranes and systems reconstituted from purified components.- Immunological tools for the study of plasma membrane receptors.

  1. The cannabinoid receptors.

    PubMed

    Howlett, Allyn C

    2002-08-01

    Cannabinoid receptors were named because they have affinity for the agonist delta9-tetrahydrocannabinol (delta9-THC), a ligand found in organic extracts from Cannabis sativa. The two types of cannabinoid receptors, CB1 and CB2. are G protein coupled receptors that are coupled through the Gi/o family of proteins to signal transduction mechanisms that include inhibition of adenylyl cyclase, activation of mitogen-activated protein kinase, regulation of calcium and potassium channels (CB1 only), and other signal transduction pathways. A class of the eicosanoid ligands are relevant to lipid-mediated cellular signaling because they serve as endogenous agonists for cannabinoid receptors, and are thus referred to as endocannabinoids. Those compounds identified to date include the eicosanoids arachidonoylethanolamide (anandamide), 2-arachidonoylglycerol and 2-arachidonylglyceryl ether (noladin ether). Several excellent reviews on endocannabinoids and their synthesis, metabolism and function have appeared in recent years. This paper will describe the biological activities, pharmacology, and signal transduction mechanisms for the cannabinoid receptors, with particular emphasis on the responses to the eicosanoid ligands.

  2. 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

  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. Functional ET(A)-ET(B) Receptor Cross-talk in Basilar Artery In Situ From ET(B) Receptor Deficient Rats.

    PubMed

    Yoon, SeongHun; Gariepy, Cheryl E; Yanagisawa, Masashi; Zuccarello, Mario; Rapoport, Robert M

    2016-03-01

    The role of endothelin (ET)(A)-ET(B) receptor cross-talk in limiting the ET(A) receptor antagonist inhibition of ET-1 constriction is revealed by the partial or complete dependency of the ET(A) receptor antagonist inhibition on functional removal of the ET(B) receptor. Although functional removal of the ET(B) receptor is generally accomplished with ET(B) receptor antagonist, a novel approach using rats containing a naturally occurring deletion mutation in the ET(B) receptor [rescued "spotting lethal" (sl) rats; ET(B)(sl/sl)] demonstrated increased ET(A) receptor antagonist inhibition of ET-1 constriction in vena cava. We investigated whether this deletion mutation was also sufficient to remove the ET(B) receptor dependency of the ET(A) receptor antagonist inhibition of ET-1 constriction in the basilar artery. Consistent with previous reports, ET-1 plasma levels were elevated in ET(B)(sl/sl) as compared with ET(B)(+/+) rats. ET(B) receptor antagonist failed to relax the ET-1 constricted basilar artery from ET(B)(+/+) and ET(B)(sl/sl) rats. Relaxation to combined ET(A) and ET(B) receptor antagonist was greater than relaxation to ET(A) receptor antagonist in the basilar artery from ET(B)(+/+) and, unexpectedly, ET(B)(sl/sl) rats. These findings confirm the presence of ET(A)-ET(B) receptor cross-talk in the basilar artery. We speculate that mutant ET(B) receptor expression produced by alternative splicing may be sufficient to allow cross-talk.

  5. The lipid habitats of neurotransmitter receptors in brain.

    PubMed

    Borroni, María Virginia; Vallés, Ana Sofía; Barrantes, Francisco J

    2016-11-01

    Neurotransmitter receptors, the macromolecules specialized in decoding the chemical signals encrypted in the chemical signaling mechanism in the nervous system, occur either at the somatic cell surface of chemically excitable cells or at specialized subcellular structures, the synapses. Synapses have lipid compositions distinct from the rest of the cell membrane, suggesting that neurotransmitter receptors and their scaffolding and adaptor protein partners require specific lipid habitats for optimal operation. In this review we discuss some paradigmatic cases of neurotransmitter receptor-lipid interactions, highlighting the chemical nature of the intervening lipid species and providing examples of the receptor mechanisms affected by interaction with lipids. The focus is on the effects of cholesterol, glycerophospholipids and covalent fatty acid acylation on neurotransmitter receptors. We also briefly discuss the role of lipid phase states involving lateral heterogeneities of the host membrane known to modulate membrane transport, protein sorting and signaling. Modulation of neurotransmitter receptors by lipids occurs at multiple levels, affecting a wide span of activities including their trafficking, sorting, stability, residence lifetime at the cell surface, endocytosis, and recycling, among other important functional properties at the synapse.

  6. 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…

  7. 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

  8. Husbands’ SUD is Associated with Higher Levels of Co-occurring but not Non-co-occurring Psychiatric Disorders among Their Wives

    PubMed Central

    Cornelius, Jack R.; Kirisci, Levent; Reynolds, Maureen; Homish, Gregory G.; Clark, Duncan B.

    2008-01-01

    Objective Substance use among husbands has been shown to be associated with an higher rates of substance use and of psychiatric symptoms among their wives. However, substance use disorders (SUD) and psychiatric disorders (as opposed to substance use or psychiatric symptoms) are rarely rigorously assessed among large samples of couples, so it is unclear whether SUD among husbands are associated with SUD among their wives, and whether the wives also display a higher prevalence of co-occurring or non-co-occurring psychiatric disorders. We compared the level of SUD, of co-occurring (with SUD) psychiatric disorders, and of non-co-occurring psychiatric diagnoses among the wives of males with SUDs vs among the wives of males without SUDs. We hypothesized that the presence of SUDs among males would be associated with a higher level of SUDs, of co-occurring psychiatric disorders, and of non-co-occurring psychiatric disorders in their wives. Method The subjects in this study were the spouses of adult men with a lifetime history of a SUD (SUD+ husbands, N=342) versus those with no lifetime history of a SUD (SUD- husbands, N=350). These subjects were recruited for participation in a longitudinal project designed to elucidate the etiology of substance use disorders. Results Co-occurring SUDs were five times more common among the spouses of SUD+ husbands than among the spouses of SUD- husbands (10.2% vs 2.0%, chi-square=19.7, p=0.000). SUD/depressive disorder and SUD/anxiety disorder were both seven times more common among the spouses of SUD+ husbands than among the spouses of SUD- husbands (19.4% vs 4.7%, chi-square=45.8, p=0.000; 14.3% vs 2.0%, chi-square=34.5, p=0.000). In contrast, non-co-occurring depressive disorders and non-co-occurring anxiety disorders were not more common among the wives of the SUD+ husbands than among the SUD- husbands. Conclusions These findings demonstrate that SUD and co-occurring psychiatric disorders (with SUD) are more common among the spouses

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

    PubMed

    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

    2002-04-30

    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.

  10. A restricted population of CB1 cannabinoid receptors with neuroprotective activity.

    PubMed

    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

    2014-06-03

    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.

  11. CONTAMINANT INTERACTIONS WITH STEROID RECEPTORS: EVIDENCE FOR RECEPTOR BINDING.

    EPA Science Inventory

    Steroid receptors are important determinants of endocrine disrupter consequences. As the most frequently proposed mechanism of endocrine-disrupting contaminant (EDC) action, steroid receptors are not only targets of natural steroids but are also commonly sites of nonsteroidal com...

  12. Rabies virus receptors.

    PubMed

    Lafon, Monique

    2005-02-01

    There is convincing in vitro evidence that the muscular form of the nicotinic acetylcholine receptor (nAChR), the neuronal cell adhesion molecule (NCAM), and the p75 neurotrophin receptor (p75NTR) bind rabies virus and/or facilitate rabies virus entry into cells. Other components of the cell membrane, such as gangliosides, may also participate in the entry of rabies virus. However, little is known of the role of these molecules in vivo. This review proposes a speculative model that accounts for the role of these different molecules in entry and trafficking of rabies virus into the nervous system.

  13. 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

  14. Assays for calcitonin receptors

    SciTech Connect

    Teitelbaum, A.P.; Nissenson, R.A.; Arnaud, C.D.

    1985-01-01

    The assays for calcitonin receptors described focus on their use in the study of the well-established target organs for calcitonin, bone and kidney. The radioligand used in virtually all calcitonin binding studies is /sup 125/I-labelled salmon calcitonin. The lack of methionine residues in this peptide permits the use of chloramine-T for the iodination reaction. Binding assays are described for intact bone, skeletal plasma membranes, renal plasma membranes, and primary kidney cell cultures of rats. Studies on calcitonin metabolism in laboratory animals and regulation of calcitonin receptors are reviewed.

  15. Biomimetic receptors and sensors.

    PubMed

    Dickert, Franz L

    2014-11-27

    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.

  16. 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.

  17. Correlating Structural and Energetic Changes in Glycine Receptor Activation*

    PubMed Central

    Scott, Suzanne; Lynch, Joseph W.; Keramidas, Angelo

    2015-01-01

    Pentameric ligand-gated ion channels (pLGICs) mediate fast chemoelectrical transduction in the nervous system. The mechanism by which the energy of ligand binding leads to current-conducting receptors is poorly understood and may vary among family members. We addressed these questions by correlating the structural and energetic mechanisms by which a naturally occurring M1 domain mutation (α1Q−26′E) enhances receptor activation in homo- and heteromeric glycine receptors. We systematically altered the charge of spatially clustered residues at positions 19′ and 24′, in the M2 and M2-M3 linker domains, respectively, which are known to be critical to efficient receptor activation, on a background of α1Q−26′E. Changes in the durations of single receptor activations (clusters) and conductance were used to determine interaction coupling energies, which we correlated with conformational displacements as measured in pLGIC crystal structures. Presence of the α1Q−26′E enhanced cluster durations and reduced channel conductance in homo- and heteromeric receptors. Strong coupling between α1−26′ and α119′ across the subunit interface suggests an important role in receptor activation. A lack of coupling between α1−26′ and α124′ implies that 24′ mutations disrupt activation via other interactions. A similar lack of energetic coupling between α1−26′ and reciprocal mutations in the β subunit suggests that this subunit remains relatively static during receptor activation. However, the channel effects of α1Q−26′E on α1β receptors suggests at least one α1-α1 interface per pentamer. The coupling-energy change between α1−26′ and α119′ correlates with a local structural rearrangement essential for pLGIC activation, implying it comprises a key energetic pathway in activating glycine receptors and other pLGICs. PMID:25572390

  18. Adenosine receptor targets for pain.

    PubMed

    Sawynok, J

    2016-12-03

    The main focus for the development of adenosine targets as analgesics to date has been A1Rs due to its antinociceptive profile in various preclinical pain models. The usefulness of systemic A1R agonists may be limited by other effects (cardiovascular, motor), but enhanced selectivity for pain might occur with partial agonists, potent and highly selective agonists, or allosteric modulators. A2AR agonists exhibit some peripheral pronociceptive effects, but also act on immune cells to suppress inflammation and on spinal glia to suppress pain signaling and may be useful for inflammatory and neuropathic pain. A2BR agonists exhibit peripheral proinflammatory effects on immune cells, but also spinal antinociceptive effects similar to A2AR agonists. A3Rs are now demonstrated to produce antinociception in several preclinical neuropathic pain models, with mechanistic actions on glial cells, and may be useful for neuropathic pain. Endogenous adenosine levels can be augmented by inhibition of metabolism (via adenosine kinase) or increased generation (via nucleotidases), and these approaches have implications for pain. Endogenous adenosine contributes to antinociception by several pharmacological agents, herbal remedies, acupuncture, transcutaneous electrical nerve stimulation, exercise, joint mobilization, and water immersion via spinal and/or peripheral effects, such that this system appears to constitute a major pain regulatory system. Finally, caffeine inhibits A1-, A2A- and A3Rs with similar potency, and dietary caffeine intake will need attention in trials of: (a) agonists and/or modulators acting at these receptors, (b) some pharmacological and herbal analgesics, and (c) manipulations that enhance endogenous adenosine levels, all of which are inhibited by caffeine and/or A1R antagonists in preclinical studies. All adenosine receptors have effects on spinal glial cells in regulating nociception, and gender differences in the involvement of such cells in chronic

  19. From anion receptors to transporters.

    PubMed

    Gale, Philip A

    2011-03-15

    Cystic fibrosis is the most well-known of a variety of diseases termed channelopathies, in which the regulation of ion transport across cell membranes is so disrupted that the threshold of a pathology is passed. The human toll exacted by these diseases has led a number of research groups, including our own, to create compounds that mediate ion transport across lipid bilayers. In this Account, we discuss three classes of synthetic compounds that were refined to bind and transport anions across lipid bilayer membranes. All of the compounds were originally designed as anion receptors, that is, species that would simply create stable complexes with anions, but were then further developed as transporters. By studying structurally simple systems and varying their properties to change the degree of preorganization, the affinity for anions, or the lipophilicity, we have begun to rationalize why particular anion transport mechanisms (cotransport or antiport processes) occur in particular cases. For example, we have studied the chloride transport properties of receptors based on the closely related structures of isophthalamide and pyridine-2,6-dicarboxamide: the central ring in each case was augmented with pendant methylimidazole groups designed to cotransport H(+) and Cl(-). We observed that the more preorganized pyridine-based receptor was the more efficient transporter, a finding replicated with a series of isophthalamides in which one contained hydroxyl groups designed to preorganize the receptor. This latter class of compound, together with the natural product prodigiosin, can transport bicarbonate (as part of a chloride/bicarbonate antiport process) across lipid bilayer membranes. We have also studied the membrane transport properties of calix[4]pyrroles. Although the parent meso-octamethylcalix[4]pyrrole functions solely as a Cs(+)/Cl(-) cotransporter, other compounds with increased anion affinities can function through an antiport process. One example is octafluoro

  20. 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.

  1. 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.

  2. Bi-Directional Heterologous Desensitization Between the Major HIV-1 Co-Receptor CXCR4 and the κ-Opioid Receptor1

    PubMed Central

    Finley, Matthew J.; Chen, Xiaohong; Bardi, Guiseppe; Davey, Penny; Geller, Ellen B.; Zhang, Lily; Adler, Martin W.; Rogers, Thomas J.

    2008-01-01

    We previously characterized multiple interactions between chemokine and opioid G-protein coupled receptors (GPCR), and we found both µ and δ-opioid receptors cross-desensitize CCR1, CCR2, CCR5, but not CXCR4. Here we report that the κ-opioid receptor (KOR) is able to cross-desensitize CXCR4, and this phenomenon is bi-directional. Chemotactic responses by KOR activation are diminished with prior activation of CXCR4. Additionally, calcium mobilization assays show these cross-desensitization processes occur within seconds of receptor activation, and target receptor internalization is not responsible for desensitization between these receptors. These results have implications for several essential processes including neuronal and lymphocyte development, inflammatory responses, and pain/sensitivity. PMID:18533278

  3. 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.

  4. Multifactorial Regulation of G Protein-Coupled Receptor Endocytosis

    PubMed Central

    Zhang, Xiaohan; Kim, Kyeong-Man

    2017-01-01

    Endocytosis is a process by which cells absorb extracellular materials via the inward budding of vesicles formed from the plasma membrane. Receptor-mediated endocytosis is a highly selective process where receptors with specific binding sites for extracellular molecules internalize via vesicles. G protein-coupled receptors (GPCRs) are the largest single family of plasma-membrane receptors with more than 1000 family members. But the molecular mechanisms involved in the regulation of GPCRs are believed to be highly conserved. For example, receptor phosphorylation in collaboration with β-arrestins plays major roles in desensitization and endocytosis of most GPCRs. Nevertheless, a number of subsequent studies showed that GPCR regulation, such as that by endocytosis, occurs through various pathways with a multitude of cellular components and processes. This review focused on i) functional interactions between homologous and heterologous pathways, ii) methodologies applied for determining receptor endocytosis, iii) experimental tools to determine specific endocytic routes, iv) roles of small guanosine triphosphate-binding proteins in GPCR endocytosis, and v) role of post-translational modification of the receptors in endocytosis. PMID:28035080

  5. Why do cannabinoid receptors have more than one endogenous ligand?

    PubMed Central

    Di Marzo, Vincenzo; De Petrocellis, Luciano

    2012-01-01

    The endocannabinoid system was revealed following the understanding of the mechanism of action of marijuana's major psychotropic principle, Δ9-tetrahydrocannabinol, and includes two G-protein-coupled receptors (GPCRs; the cannabinoid CB1 and CB2 receptors), their endogenous ligands (the endocannabinoids, the best studied of which are anandamide and 2-arachidonoylglycerol (2-AG)), and the proteins that regulate the levels and activity of these receptors and ligands. However, other minor lipid metabolites different from, but chemically similar to, anandamide and 2-AG have also been suggested to act as endocannabinoids. Thus, unlike most other GPCRs, cannabinoid receptors appear to have more than one endogenous agonist, and it has been often wondered what could be the physiological meaning of this peculiarity. In 1999, it was proposed that anandamide might also activate other targets, and in particular the transient receptor potential of vanilloid type-1 (TRPV1) channels. Over the last decade, this interaction has been shown to occur both in peripheral tissues and brain, during both physiological and pathological conditions. TRPV1 channels can be activated also by another less abundant endocannabinoid, N-arachidonoyldopamine, but not by 2-AG, and have been proposed by some authors to act as ionotropic endocannabinoid receptors. This article will discuss the latest discoveries on this subject, and discuss, among others, how anandamide and 2-AG differential actions at TRPV1 and cannabinoid receptors contribute to making this signalling system a versatile tool available to organisms to fine-tune homeostasis. PMID:23108541

  6. 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. PMID:27635169

  7. The cardiac glycoside-receptor system in the human heart.

    PubMed

    Erdmann, E; Brown, L

    1983-01-01

    Specific binding sites have been demonstrated to exist in the heart for several drugs and hormones such as beta-blocking agents, cardiac glycosides, catecholamines, insulin, glucagon and acetylcholine. The specific binding sites for cardiac glycosides in the human heart have certain properties which make it likely that they are the pharmacological receptors for the therapeutic and toxic actions of digitalis glycosides: they are located in the cell membrane and bind cardioactive steroids reversibly with high affinity: half-maximal receptor binding occurs at approximately 2 nM (approximately 1.5 ng/ml) for digoxin; potassium decreases receptor affinity, calcium increases it; specific binding of ouabain, digoxin or digitoxin is related to inhibition of (Na+ + K+)-ATPase activity--which is supposed to be the receptor enzyme for cardiac glycosides. Human left ventricle contains approximately 1.5 x 10(14) binding sites/g wet weight, right ventricle approximately 0.9 x 10(14). In disease the number of receptors may decrease (hypothyroid states, myocardial infarction) or increase (hyperthyroidism, chronic hypokalaemia). Certain drugs (such as phenytoin) or different temperatures or pH changes cause a change in digitalis-receptor affinity. Thus, the number of receptors and possibly their properties are subject to regulation in clinically relevant situations. Further investigations will probably reveal those pathophysiological states, which allow the explanation of toxicity or digitalis refractoriness.

  8. Pharmacology of mammalian olfactory receptors.

    PubMed

    Smith, Richard S; Peterlin, Zita; Araneda, Ricardo C

    2013-01-01

    Mammalian species have evolved a large and diverse number of odorant receptors (ORs). These proteins comprise the largest family of G-protein-coupled receptors (GPCRs) known, amounting to ~1,000-different receptors in the rodent. From the perspective of olfactory coding, the availability of such a vast number of chemosensory receptors poses several fascinating questions; in addition, such a large repertoire provides an attractive biological model to study ligand-receptor interactions. The limited functional expression of these receptors in heterologous systems, however, has greatly hampered attempts to deorphanize them. We have employed a successful approach that combines electrophysiological and imaging techniques to analyze the response profiles of single sensory neurons. Our approach has enabled us to characterize the "odor space" of a population of native aldehyde receptors and the molecular range of a genetically engineered receptor, OR-I7.

  9. Adenosine receptors and the central nervous system.

    PubMed

    Sebastião, Ana M; Ribeiro, Joaquim A

    2009-01-01

    The adenosine receptors (ARs) in the nervous system act as a kind of "go-between" to regulate the release of neurotransmitters (this includes all known neurotransmitters) and the action of neuromodulators (e.g., neuropeptides, neurotrophic factors). Receptor-receptor interactions and AR-transporter interplay occur as part of the adenosine's attempt to control synaptic transmission. A(2A)ARs are more abundant in the striatum and A(1)ARs in the hippocampus, but both receptors interfere with the efficiency and plasticity-regulated synaptic transmission in most brain areas. The omnipresence of adenosine and A(2A) and A(1) ARs in all nervous system cells (neurons and glia), together with the intensive release of adenosine following insults, makes adenosine a kind of "maestro" of the tripartite synapse in the homeostatic coordination of the brain function. Under physiological conditions, both A(2A) and A(1) ARs play an important role in sleep and arousal, cognition, memory and learning, whereas under pathological conditions (e.g., Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, stroke, epilepsy, drug addiction, pain, schizophrenia, depression), ARs operate a time/circumstance window where in some circumstances A(1)AR agonists may predominate as early neuroprotectors, and in other circumstances A(2A)AR antagonists may alter the outcomes of some of the pathological deficiencies. In some circumstances, and depending on the therapeutic window, the use of A(2A)AR agonists may be initially beneficial; however, at later time points, the use of A(2A)AR antagonists proved beneficial in several pathologies. Since selective ligands for A(1) and A(2A) ARs are now entering clinical trials, the time has come to determine the role of these receptors in neurological and psychiatric diseases and identify therapies that will alter the outcomes of these diseases, therefore providing a hopeful future for the patients who suffer from these diseases.

  10. Calcitonin and calcitonin receptors

    PubMed Central

    Masi, Laura; Brandi, Maria Luisa

    2007-01-01

    Calcitonin (CT) is a polypeptide hormone with 32 aminoacids syntetized primarily by the thyroid. Several evidences support the existence of nonthyroidal CT like peptide. The CT gene transcript also encodes a distinct peptide known as calcitonin gene related peptide (CGRP) which is a potent vasodilator and responsible for the stimulation of the glomerular filtration rate. In addition, a 37 aminoacid peptide amylin has been originally isolated by pancreatic β-cells. Amylin is able to inhibit insulin secretion, glucose transport into the skeletal musculature and gluconeogenesis. It is also able to inhibit gastric emptying. In the kidney it is able to modulate Calcium (Ca2+) excretion and increases renin activity. Finally, high affinity amylin receptors have been identified in the brain of the rat. The calcitonin receptor (CTR) is a member of a subfamily of the seven-transmembrane domain G-protein coupled receptor super family that includes several peptides. Members of this family have a similar structure with other seven-membrane-spanning domain G-protein coupled receptors. The genetic contribution to osteoporosis susceptibility is well documented and many studies demonstrated that genetic factors play important roles in the regulation of bone metabolism. Restriction Fragment Length Polymorphisms (RFLPs) for the CTR gene have been described in the literature with a positive association with the lumbar bone mineral density (BMD), femoral neck BMD and with a lower incidence of vertebral fractures. PMID:22461211

  11. Characterization of melanocortin receptors.

    PubMed

    Goetz, Aaron S; Ignar, Diane M

    2003-11-01

    This unit describes a Scintillation Proximity Assay (SPA) for the measurement of ligand binding to melanocortin receptors (MCRs) using membranes prepared from cell lines stably expressing recombinant MCRs. It provides a facile method for determining the affinity of compounds at MC1R, MC3R, MC4R, or MC5R.

  12. Functional Characterization of Odorant Receptors

    DTIC Science & Technology

    1994-02-07

    94 IFINAL REPORT 9/1/92-11/30/93 4. TITLE AND SUBTITLE S. FUNDING NUMBERS Functional Characterization of Odorant Receptors DAAL03-92-G-0390 6. AUTHOR(S...characterization of odorant receptors have developed in two directions. One direction is concerned with the characterization of the ligand specificity of... receptor have been replaced by the equivalent regions of odorant receptor 1-15 (Buck and Axel, 1991), thus forming a chimaeric seven transmembrane domain

  13. P2 receptors and immunity

    PubMed Central

    Rayah, Amel; Kanellopoulos, Jean M.; Di Virgilio, Francesco

    2012-01-01

    Immune cells express receptors for extracellular nucleotides named P2 receptors. P2 receptors transduce signals delivered by nucleotides present in the extracellular environment. Accruing evidence shows that purinergic signalling has a profound effect on multiple immune cell responses such as T lymphocyte proliferation, chemotaxis, cytokine release, phagocytosis, Ag presentation and cytotoxicity. This makes P2 receptors an attractive target for the therapy of immuno-mediated disease and cancer. PMID:22909902

  14. Universality of receptor channel responses.

    PubMed

    Kardos, J; Nyikos, L

    2001-12-01

    Rate parameters estimated for neurotransmitter-gated receptor channel opening and receptor desensitization are classified according to their dependence on the temporal resolution of the techniques applied in the measurements. Because allosteric proteins constituting receptor channels impose restrictions on the types of model suitable to describe the dynamic response of channels to neurotransmitters, Markovian, non-linear or fractal dynamic models and their possible extension to receptor channel response in excitable membranes are discussed.

  15. Secretin-receptor and secretin-receptor-variant expression in gastrinomas: Correlation with clinical and tumoral features and secretin and calcium provocative test results.

    PubMed Central

    Long, Scott H.; Berna, Marc J.; Thill, Michelle; Pace, Andrea; Pradhan, Tapas K.; Hoffmann, K. Martin; Serrano, Jose; Jensen, Robert T.

    2008-01-01

    Context/Objectives The diagnosis of Zollinger-Ellison syndrome (ZES) requires secretin testing in 60%. Even with secretin the diagnosis may be difficult because variable responses occur and 6–30% have negative testing. The basis for variability or negative responses is unclear. It is unknown if the tumor density of secretin receptors or the presence of a secretin-receptor-variant, which can act as a dominant-negative, are important. The aim of this study was to investigate these possibilities. Patients/Methods Secretin-receptor and variant mRNA expression was determined in gastrinomas using real-time-PCR from 54 ZES patients. Results were correlated with Western blotting, secretin-receptor immunohistochemistry, with gastrin-provocative-test results and tumoral/clinical/laboratory features. Results Secretin-receptor mRNA was detectible in all gastrinomas but varied 132-fold with a mean of 0.89±0.12 molecules/β-actin. Secretin-receptor PCR results correlated closely with Western blotting (r=0.95,p<0.0001) and receptor-immunohistochemistry (p=0.0015, r=0.71). The variant was detected in all gastrinomas but levels varied 102-fold and were 72-fold lower than the total. Secretin-receptor levels correlated with variant levels, Δsecretin, but not Δcalcium and with tumor location, but not growth, extent or clinical responses. Variant levels did not correlate with the Δsecretin. Detailed analysis provides no evidence variant expression modified the secretin-receptor response or accounted for negative tests. Conclusions Secretin-receptor and secretin-receptor-variant expression occur in all gastrinomas. Because the expression of the total but not variant correlated with the secretin results and no evidence for dominant negative activity of the variant was found, our results suggest the total-secretin-receptor density is an important determinant of the secretin test response. PMID:17711922

  16. Inhibition of Hedgehog-dependent tumors and cancer stem cells by a newly identified naturally occurring chemotype

    PubMed Central

    Infante, Paola; Alfonsi, Romina; Ingallina, Cinzia; Quaglio, Deborah; Ghirga, Francesca; D'Acquarica, Ilaria; Bernardi, Flavia; Di Magno, Laura; Canettieri, Gianluca; Screpanti, Isabella; Gulino, Alberto; Botta, Bruno; Mori, Mattia; Di Marcotullio, Lucia

    2016-01-01

    Hedgehog (Hh) inhibitors have emerged as valid tools in the treatment of a wide range of cancers. Indeed, aberrant activation of the Hh pathway occurring either by ligand-dependent or -independent mechanisms is a key driver in tumorigenesis. The smoothened (Smo) receptor is one of the main upstream transducers of the Hh signaling and is a validated target for the development of anticancer compounds, as underlined by the FDA-approved Smo antagonist Vismodegib (GDC-0449/Erivedge) for the treatment of basal cell carcinoma. However, Smo mutations that confer constitutive activity and drug resistance have emerged during treatment with Vismodegib. For this reason, the development of new effective Hh inhibitors represents a major challenge for cancer therapy. Natural products have always represented a unique source of lead structures in drug discovery, and in recent years have been used to modulate the Hh pathway at multiple levels. Here, starting from an in house library of natural compounds and their derivatives, we discovered novel chemotypes of Hh inhibitors by mean of virtual screening against the crystallographic structure of Smo. Hh functional based assay identified the chalcone derivative 12 as the most effective Hh inhibitor within the test set. The chalcone 12 binds the Smo receptor and promotes the displacement of Bodipy-Cyclopamine in both Smo WT and drug-resistant Smo mutant. Our molecule stands as a promising Smo antagonist able to specifically impair the growth of Hh-dependent tumor cells in vitro and in vivo and medulloblastoma stem-like cells and potentially overcome the associated drug resistance. PMID:27899820

  17. A naturally occurring substitution in the E2 protein of Salmonid alphavirus subtype 3 changes viral fitness.

    PubMed

    Karlsen, Marius; Andersen, Linda; Blindheim, Steffen H; Rimstad, Espen; Nylund, Are

    2015-01-22

    Phylogenetic analyses of the Salmonid alphavirus subtype 3 (SAV3) epizootic have suggested that a substitution from proline to serine in the receptor binding protein E2 position 206 has occurred after the introduction of virus from a wild reservoir to farmed salmonid fish in Norway. We modelled the 3D structure of P62, the uncleaved E3-E2 precursor, of SAVH20/03 based on its sequence homology to the Chikungunya virus (CHIKV), and studied in vitro and in vivo effects of the mutation using reverse genetics. E2(206) is located on the surface of the B-domain of E2, which is associated with receptor attachment in alphaviruses. Recombinant virus expressing the E2(206S) codon replicated slower and produced significantly less genomic copies than virus expressing the ancestral E2(206P) codon in vitro in Bluegill Fry (BF2) cells. The E2(206S) mutant was out-competed by the E2(206P) mutant after 5 passages in an in vitro competition assay, confirming that the substitution negatively affects the efficacy of virus multiplication in cell culture. Both mutants were highly infectious to Atlantic salmon (Salmo salar), produced similar viral RNA loads in gills, heart, kidney and brain, and induced similar histopathologic changes in these organs. The E2(206S) mutant produced a less persistent infection in salmon and was shed more rapidly to water than the E2(206P) mutant. Reduced generation time through more rapid shedding could therefore explain why a serine in this position became dominant in the viral population after SAV3 was introduced to farmed salmon from the wild reservoir.

  18. Escape from Cbl-mediated downregulation: a recurrent theme for oncogenic deregulation of receptor tyrosine kinases.

    PubMed

    Peschard, Pascal; Park, Morag

    2003-06-01

    Deregulation of growth factor receptor tyrosine kinases (RTKs) is linked to a large number of malignancies. This occurs through a variety of mechanisms that result in enhanced activity of the receptor. Considerable evidence now supports the idea that loss of negative regulation plays an important role in receptor deregulation. RTKs are removed from the cell surface via endocytosis and many are subsequently degraded in the lysosome. Lysosomal targeting has recently been linked with receptor ubiquitination. We review here molecular alterations that uncouple RTKs from ubiquitination and implicate loss of ubiquitination as a process that plays a significant role in the pathogenesis of cancer.

  19. Neurokinin-1 receptor: a new promising target in the treatment of cancer.

    PubMed

    Muñoz, Miguel; Coveñas, Rafael

    2010-10-01

    Substance P (SP) has a widespread distribution in the whole body. After binding to the neurokinin-1 (NK-1) receptor, SP regulates biological functions related to cancer: tumor cell proliferation (favoring tumor growth), angiogenesis, and migration of the tumor cells for invasion and metastasis. SP also exerts an antiapoptotic effect. The peptide is secreted from primary tumors and from peripheral nerves, and reaches the whole body through the blood stream. NK-1 receptors are overexpressed in tumors (cancer cells express more NK-1 receptors than normal cells). By contrast, after binding to NK-1 receptors, the NK-1 receptor antagonists specifically inhibit tumor cell proliferation (tumor cells die by apoptosis), angiogenesis and the migration of the tumor cells. Thus, 1) the SP/NK-1 receptor system plays an important role in the development of cancer, angiogenesis, and metastasis; 2) a common mechanism for cancer cell proliferation mediated by the SP/NK-1 receptor system occurs; 3) NK-1 receptor antagonists act as a broad-spectrum antitumoral agent; 4) the NK-1 receptor could be a new promising target in the treatment of cancer; 5) NK-1 receptor antagonists could improve cancer treatment--the development of antagonist molecules of the NK-1 receptor represents an important opportunity for exploiting these molecules as novel therapeutic agents.

  20. In situ distinction between steroid receptor binding and transactivation at a target gene.

    PubMed Central

    McDonnell, D P; Nawaz, Z; O'Malley, B W

    1991-01-01

    We have developed a DNA interference assay in the yeast Saccharomyces cerevisiae that is designed to indicate the intracellular DNA-binding status of the estrogen receptor. The assay utilizes a promoter containing multiple copies of a GAL4-estrogen receptor binding