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  • Wiley-Blackwell  (955)
  • American Association for the Advancement of Science (AAAS)  (93)
  • The American Association for Cancer Research (AACR)  (75)
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  • 1
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    Structure-guided design affirms inhibitors of hepatitis C virus p7 as a viable class of antivirals targeting virion release (2013)
    Wiley-Blackwell
    Details
    Publication Date: 2013-08-13
    Description: Current interferon-based therapy for hepatitis C virus (HCV) infection is inadequate, prompting a shift towards combinations of direct-acting antivirals (DAA) with the first protease-targeted drugs licensed in 2012. Many compounds are in the pipeline yet primarily target only three viral proteins, namely NS3/4A protease, NS5B polymerase and NS5A. With concerns growing over resistance, broadening the repertoire for DAA targets is a major priority. Here we describe the complete structure of the HCV p7 protein as a monomeric hairpin, solved using a novel combination of chemical shift and NOE based methods. This represents atomic resolution information for a full-length virus-coded ion channel, or “viroporin”, whose essential functions represent a clinically proven class of antiviral target exploited previously for influenza A virus therapy. Specific drug-protein interactions validate an allosteric site on the channel periphery and its relevance is demonstrated by the selection of novel, structurally diverse inhibitory small molecules with nanomolar potency in culture. Hit compounds represent a 10,000-fold improvement over prototypes, suppress rimantadine resistance polymorphisms at sub-micromolar concentrations and show activity against other HCV genotypes. Conclusions : This proof-of-principle that structure-guided design can lead to drug-like molecules affirms p7 as a much needed new target in the burgeoning era of HCV DAA. (H epatology 2013;)
    Print ISSN: 0270-9139
    Electronic ISSN: 1527-3350
    Topics: Medicine
    Published by Wiley-Blackwell on behalf of The American Association for the Study of Liver Diseases.
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  • 2
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    An extensive reef system at the Amazon River mouth (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-04-28
    Description: Large rivers create major gaps in reef distribution along tropical shelves. The Amazon River represents 20% of the global riverine discharge to the ocean, generating up to a 1.3 x 10 6 –km 2 plume, and extensive muddy bottoms in the equatorial margin of South America. As a result, a wide area of the tropical North Atlantic is heavily affected in terms of salinity, pH, light penetration, and sedimentation. Such unfavorable conditions were thought to imprint a major gap in Western Atlantic reefs. We present an extensive carbonate system off the Amazon mouth, underneath the river plume. Significant carbonate sedimentation occurred during lowstand sea level, and still occurs in the outer shelf, resulting in complex hard-bottom topography. A permanent near-bottom wedge of ocean water, together with the seasonal nature of the plume’s eastward retroflection, conditions the existence of this extensive (~9500 km 2 ) hard-bottom mosaic. The Amazon reefs transition from accretive to erosional structures and encompass extensive rhodolith beds. Carbonate structures function as a connectivity corridor for wide depth–ranging reef-associated species, being heavily colonized by large sponges and other structure-forming filter feeders that dwell under low light and high levels of particulates. The oxycline between the plume and subplume is associated with chemoautotrophic and anaerobic microbial metabolisms. The system described here provides several insights about the responses of tropical reefs to suboptimal and marginal reef-building conditions, which are accelerating worldwide due to global changes.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Astronomy. ASASSN-15lh: A highly super-luminous supernova (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-01-28
    Description: We report the discovery of ASASSN-15lh (SN 2015L), which we interpret as the most luminous supernova yet found. At redshift z = 0.2326, ASASSN-15lh reached an absolute magnitude of Mu ,AB = -23.5 +/- 0.1 and bolometric luminosity Lbol = (2.2 +/- 0.2) x 10(45) ergs s(-1), which is more than twice as luminous as any previously known supernova. It has several major features characteristic of the hydrogen-poor super-luminous supernovae (SLSNe-I), whose energy sources and progenitors are currently poorly understood. In contrast to most previously known SLSNe-I that reside in star-forming dwarf galaxies, ASASSN-15lh appears to be hosted by a luminous galaxy (MK approximately -25.5) with little star formation. In the 4 months since first detection, ASASSN-15lh radiated (1.1 +/- 0.2) x 10(52) ergs, challenging the magnetar model for its engine.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dong, Subo -- Shappee, B J -- Prieto, J L -- Jha, S W -- Stanek, K Z -- Holoien, T W-S -- Kochanek, C S -- Thompson, T A -- Morrell, N -- Thompson, I B -- Basu, U -- Beacom, J F -- Bersier, D -- Brimacombe, J -- Brown, J S -- Bufano, F -- Chen, Ping -- Conseil, E -- Danilet, A B -- Falco, E -- Grupe, D -- Kiyota, S -- Masi, G -- Nicholls, B -- Olivares E, F -- Pignata, G -- Pojmanski, G -- Simonian, G V -- Szczygiel, D M -- Wozniak, P R -- New York, N.Y. -- Science. 2016 Jan 15;351(6270):257-60. doi: 10.1126/science.aac9613.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Kavli Institute for Astronomy and Astrophysics, Peking University, Yi He Yuan Road 5, Hai Dian District, Beijing 100871, China. dongsubo@pku.edu.cn. ; Carnegie Observatories, 813 Santa Barbara Street, Pasadena, CA 91101, USA. ; Nucleo de Astronomia de la Facultad de Ingenieria, Universidad Diego Portales, Av. Ejercito 441, Santiago, Chile. Millennium Institute of Astrophysics, Santiago, Chile. ; Department of Physics and Astronomy, Rutgers, The State University of New Jersey, 136 Frelinghuysen Road, Piscataway, NJ 08854, USA. ; Department of Astronomy, The Ohio State University, 140 W. 18th Avenue, Columbus, OH 43210, USA. Center for Cosmology and AstroParticle Physics (CCAPP), The Ohio State University, 191 W. Woodruff Avenue, Columbus, OH 43210, USA. ; Las Campanas Observatory, Carnegie Observatories, Casilla 601, La Serena, Chile. ; Department of Astronomy, The Ohio State University, 140 W. 18th Avenue, Columbus, OH 43210, USA. ; Department of Astronomy, The Ohio State University, 140 W. 18th Avenue, Columbus, OH 43210, USA. Center for Cosmology and AstroParticle Physics (CCAPP), The Ohio State University, 191 W. Woodruff Avenue, Columbus, OH 43210, USA. Department of Physics, The Ohio State University, 191 W. Woodruff Avenue, Columbus, OH 43210, USA. ; Astrophysics Research Institute, Liverpool John Moores University, 146 Brownlow Hill, Liverpool L3 5RF, UK. ; Coral Towers Observatory, Cairns, Queensland 4870, Australia. ; INAF-Osservatorio Astrofisico di Catania, Via S.Sofia 78, 95123, Catania, Italy. ; Department of Astronomy, Peking University, Yi He Yuan Road 5, Hai Dian District, 100871, P. R. China. ; Association Francaise des Observateurs d'Etoiles Variables (AFOEV), Observatoire de Strasbourg 11, rue de l'Universite, F-67000 Strasbourg, France. ; Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138, USA. ; Department of Earth and Space Science, Morehead State University, 235 Martindale Drive, Morehead, KY 40351, USA. ; Variable Star Observers League in Japan (VSOLJ), 7-1 Kitahatsutomi, Kamagaya, Chiba 273-0126, Japan. ; The Virtual Telescope Project, Via Madonna de Loco 47, 03023 Ceccano, Italy. ; Mt Vernon Observatory, 6 Mt Vernon pl, Nelson, New Zealand. ; Millennium Institute of Astrophysics, Santiago, Chile. Departamento Ciencias Fisicas, Universidad Andres Bello, Av. Republica 252, Santiago, Chile. ; Warsaw University Astronomical Observatory, Al. Ujazdowskie 4, 00-478 Warsaw, Poland. ; Los Alamos National Laboratory, Mail Stop B244, Los Alamos, NM 87545, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26816375" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    Impacts of recent warming and the 2015/16 El Niño on tropical Peruvian ice fields (2017)
    Wiley-Blackwell
    Details
    Publication Date: 2017-09-19
    Description: Data collected between 1974 and 2016 from snow pits and core samples from two Peruvian ice fields demonstrate the effect of the recent warming over the tropical Andes, augmented by El Niño, on the preservation of the climate record. As the 0 o C isotherm is approaching the summit of the Quelccaya ice cap in the Andes of southern Peru (5670 masl), the distinctive seasonal δ 18 O oscillations in the fresh snow deposited within each thermal year are attenuated at depth due to melting and percolation through the firn. This has become increasingly pronounced over 43 years. In the Andes of northern Peru, the ice field on the col of Nevado Huascarán (6050 masl) has retained its seasonal δ 18 O variations at depth due to its higher elevation. During the 2015/16 El Niño, snow on Quelccaya and Huascarán was isotopically (δ 18 O) enriched and the net sum of accumulation over the previous year (NSA) was below the mean for non-El Niño years, particularly on Quelccaya (up to 64% below the mean) which was more pronounced than the NSA decrease during the comparable 1982/83 El Niño. Interannual large-scale oceanic and middle to upper level atmospheric temperatures influence δ 18 O in precipitation on both ice fields, although the influences are variably affected by strong El Niño-Southern Oscillation events, especially on Quelccaya. The rate of ice wastage along Quelccaya's margin was dramatically higher during 2015/16 compared with that of the previous 15 years, suggesting that warming from future El Niños may accelerate mass loss on Peruvian glaciers.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley-Blackwell on behalf of American Geophysical Union (AGU).
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  • 5
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    Investigating the preservation of nitrate isotopic composition in a tropical ice core from the Quelccaya Ice Cap, Peru (2014)
    Wiley-Blackwell
    Details
    Publication Date: 2014-01-31
    Description: [1]  The nitrogen and oxygen isotopic composition of nitrate in ice cores offers unique potential for examining reactive nitrogen oxide (NO x ) budgets and oxidation chemistry of past atmospheres. A low-latitude record is of particular interest given that the dominant natural sources of NO x and production of hydroxyl radical are most prevalent in the Tropics. Any interpretation of nitrate in ice cores, however, must first consider that nitrate in snow is vulnerable to post-depositional loss and isotopic alteration. We report and assess the integrity of nitrate–δ 15 N, –δ 18 O and –Δ 17 O in a 30 m ice core from a high-elevation site in the central Andes. Clear seasonality in δ 15 N, δ 18 O and nitrate concentration exists throughout most of the record and cannot be explained by photolysis or evaporation based on our current understanding of these processes. In contrast, nitrate in the upper ~12 m of the core and in a snowpit shows very different behavior. This may reflect alteration facilitated by recent melting at the surface. The relationships between δ 15 N, δ 18 O, Δ 17 O and concentration in the unaltered sections can be interpreted in terms of mixing of nitrate from discrete sources. Transport effects and an englacial contribution from nitrification cannot be ruled out at this time, but the observed isotopic compositions are consistent with expected signatures of known NO x sources and atmospheric oxidation pathways. Specifically, nitrate deposited during the wet season reflects biogenic soil emissions and hydroxyl/peroxy radical chemistry in the Amazon while dry season deposition reflects a lightning source and ozone chemistry at higher levels in the Troposphere.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley-Blackwell on behalf of American Geophysical Union (AGU).
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  • 6
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    Annually resolved ice core records of tropical climate variability over the past ~1800 years (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-04-06
    Description: Ice cores from low latitudes can provide a wealth of unique information about past climate in the tropics, but they are difficult to recover and few exist. Here, we report annually resolved ice core records from the Quelccaya ice cap (5670 meters above sea level) in Peru that extend back ~1800 years and provide a high-resolution record of climate variability there. Oxygen isotopic ratios (delta(18)O) are linked to sea surface temperatures in the tropical eastern Pacific, whereas concentrations of ammonium and nitrate document the dominant role played by the migration of the Intertropical Convergence Zone in the region of the tropical Andes. Quelccaya continues to retreat and thin. Radiocarbon dates on wetland plants exposed along its retreating margins indicate that it has not been smaller for at least six millennia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thompson, L G -- Mosley-Thompson, E -- Davis, M E -- Zagorodnov, V S -- Howat, I M -- Mikhalenko, V N -- Lin, P-N -- New York, N.Y. -- Science. 2013 May 24;340(6135):945-50. doi: 10.1126/science.1234210. Epub 2013 Apr 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Byrd Polar Research Center, The Ohio State University, Columbus, OH 43210, USA. thompson.3@osu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23558172" target="_blank"〉PubMed〈/a〉
    Keywords: *Climate Change ; *Ice Cover ; Nitrates/analysis ; Oxygen Isotopes/analysis ; Peru ; Plants ; Quaternary Ammonium Compounds/analysis ; *Tropical Climate ; Wetlands
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 7
    Electronic Resource
    Electronic Resource
    Models for hemoglobin and allosteric enzymes (1968)
    New York : Wiley-Blackwell
    Biopolymers 6 (1968), S. 1101-1118 
    Details
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A model for hemoglobin is proposed and its application to allosteric enzymes is discussed with particular reference to asparate transcarbamylase. The main assumptions made are that the molecule is composed of subunits and that occupation of a sub-unit produces a conformational change which affects the occupational probability of neighboring subunits. The results compare favorably with experiment and a number of specific predictions are made for aspartate transcarbamylase.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bip.1968.360060806
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  • 8
    Electronic Resource
    Electronic Resource
    Time dependent model for hemoglobin and allosteric enzymes. II. (1971)
    New York : Wiley-Blackwell
    Biopolymers 10 (1971), S. 1331-1349 
    Details
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The time-dependent theory developed in Part I is specialized to treat tetrameric hemoglobin, and the results of the theory for dimeric-and tetrameric hemoglobin are compared with data on the kinetics of the reactions of hemoglobin with carbon monoxide and oxygen at various salt concentrations for the case of large concentration of ligand relative to that of hemoglobin. The fit of the theoretical results to the data suggests that hemoglobin at a 2 M salt concentration is predominantly dimeric and that the tetramer should be taken as the functional unit to explain the kinetics of the reactions of normal hemoglobin. A relationship is established between the time-dependent theory arid Adair's Intermediate Compound Hypothesis (I.C.H.) for hemoglobin, as brought to its present state by Gibson and Roughton. A generalization (G.I.C.H.) of the I.C.H. is presented and is shown to be equivalent to the time-dependent theory in the limit of infinite ligand concentration. The I.C.H. is shown to be an excellent approximation to the centralized theory (G.I.C.H.) in this limit.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bip.360100807
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  • 9
    Electronic Resource
    Electronic Resource
    Time-dependent model for hemoglobin and allosteric enzymes. I. General formulation (1971)
    New York : Wiley-Blackwell
    Biopolymers 10 (1971), S. 961-972 
    Details
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A previous equilibrium model is generalized to study time-dependent behavior of hemoglobin and allosteric enzymes. An exact solution for two interacting subunits (e.g., diheme) is given, and a general method for solving the resulting set of differential equations is outlined. At half saturation (equilibrium) concentration, the model takes a particularly simple form which suggests an experiment to determine the number of subunits of an allosteric enzyme, or in particular to distinguish diheme from ordinary hemoglobin. The relation between the present model and other kinetic models is also discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bip.360100603
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  • 10
    Electronic Resource
    Electronic Resource
    A circular dichroic investigation of the secondary structure of lectins (1978)
    New York : Wiley-Blackwell
    Biopolymers 17 (1978), S. 2107-2120 
    Details
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The far-uv CD spectra of eight lectins are presented. These eight lectins, as well as others previously studied, are grouped into three classes according to their particular CD spectra. The eight lectins studied appeared to have secondary structure dominated by β-pleated sheet, which so far has been true of all lectins. An attempt was made to quantitate the three structural components (α-helix, β-pleated sheet, and aperiodic) in the lectins using the data for reference proteins given by Chen et al. [Biochemistry 13,3350 (1974)]. For lectins in two of the classes, this method proved excellent and values for the three components are given. However, for the third class of lectins, which includes most of the lectins as well as Concanavalin A, this method of analysis proved to be unsatisfactory. This inadequacy was due to two factors: (1) the reference proteins used by Chen and (2) the unusual CD spectra of these lectins manifested by considerable ellipticity above 225 nm in a region where there are no known peptide electronic transitions.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bip.1978.360170906
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