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  • 1
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    Nucleoside reverse transcriptase inhibitors possess intrinsic anti-inflammatory activity (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-11-22
    Description: Nucleoside reverse transcriptase inhibitors (NRTIs) are mainstay therapeutics for HIV that block retrovirus replication. Alu (an endogenous retroelement that also requires reverse transcriptase for its life cycle)-derived RNAs activate P2X7 and the NLRP3 inflammasome to cause cell death of the retinal pigment epithelium in geographic atrophy, a type of age-related macular degeneration. We found that NRTIs inhibit P2X7-mediated NLRP3 inflammasome activation independent of reverse transcriptase inhibition. Multiple approved and clinically relevant NRTIs prevented caspase-1 activation, the effector of the NLRP3 inflammasome, induced by Alu RNA. NRTIs were efficacious in mouse models of geographic atrophy, choroidal neovascularization, graft-versus-host disease, and sterile liver inflammation. Our findings suggest that NRTIs are ripe for drug repurposing in P2X7-driven diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4274127/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4274127/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fowler, Benjamin J -- Gelfand, Bradley D -- Kim, Younghee -- Kerur, Nagaraj -- Tarallo, Valeria -- Hirano, Yoshio -- Amarnath, Shoba -- Fowler, Daniel H -- Radwan, Marta -- Young, Mark T -- Pittman, Keir -- Kubes, Paul -- Agarwal, Hitesh K -- Parang, Keykavous -- Hinton, David R -- Bastos-Carvalho, Ana -- Li, Shengjian -- Yasuma, Tetsuhiro -- Mizutani, Takeshi -- Yasuma, Reo -- Wright, Charles -- Ambati, Jayakrishna -- BB/J017345/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- DP1 GM114862/GM/NIGMS NIH HHS/ -- DP1GM114862/DP/NCCDPHP CDC HHS/ -- K99 EY024336/EY/NEI NIH HHS/ -- K99EY024336/EY/NEI NIH HHS/ -- P30EY003040/EY/NEI NIH HHS/ -- R01 EY018350/EY/NEI NIH HHS/ -- R01 EY018836/EY/NEI NIH HHS/ -- R01 EY020672/EY/NEI NIH HHS/ -- R01 EY022238/EY/NEI NIH HHS/ -- R01 EY024068/EY/NEI NIH HHS/ -- R01EY001545/EY/NEI NIH HHS/ -- R01EY018350/EY/NEI NIH HHS/ -- R01EY018836/EY/NEI NIH HHS/ -- R01EY020672/EY/NEI NIH HHS/ -- R01EY022238/EY/NEI NIH HHS/ -- R01EY024068/EY/NEI NIH HHS/ -- T32HL091812/HL/NHLBI NIH HHS/ -- TL1 RR033172/RR/NCRR NIH HHS/ -- TL1 TR000115/TR/NCATS NIH HHS/ -- UL1 RR033173/RR/NCRR NIH HHS/ -- UL1 TR000117/TR/NCATS NIH HHS/ -- UL1RR033173/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2014 Nov 21;346(6212):1000-3. doi: 10.1126/science.1261754.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY 40536, USA. Department of Physiology, University of Kentucky, Lexington, KY 40536, USA. ; Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY 40536, USA. Department of Microbiology, Immunology, and Human Genetics, University of Kentucky, Lexington, KY 40536, USA. Department of Biomedical Engineering, University of Kentucky, Lexington, KY 40536, USA. ; Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY 40536, USA. ; Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY 40536, USA. Angiogenesis Lab, Institute of Genetics and Biophysics, CNR, Naples, Italy. ; Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. ; School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK. ; Immunology Research Group, University of Calgary, Calgary, Alberta T2N 4N1, Canada. ; Chapman University School of Pharmacy, 9401 Jeronimo Road, Harry and Diane Rinker Health Science Campus, Irvine, CA 92618, USA. ; Departments of Pathology and Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA. ; Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY 40536, USA. Department of Physiology, University of Kentucky, Lexington, KY 40536, USA. jamba2@email.uky.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25414314" target="_blank"〉PubMed〈/a〉
    Keywords: Alu Elements ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/*pharmacology/therapeutic use ; Apoptosis/drug effects ; Carrier Proteins/metabolism ; Caspase 1/metabolism ; Choroidal Neovascularization/drug therapy ; Disease Models, Animal ; Geographic Atrophy/drug therapy ; Graft vs Host Disease/drug therapy ; Hepatitis/drug therapy ; Inflammasomes/*drug effects ; Liver/drug effects ; Mice ; Receptors, Purinergic P2X7/metabolism ; Retinal Pigment Epithelium/drug effects/metabolism/physiology ; Reverse Transcriptase Inhibitors/*pharmacology/therapeutic use
    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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  • 2
    Electronic Resource
    Electronic Resource
    Polystyrene modifications. II. Ring-substituted polystyrenesCommunication No. 2260 from the Kodak Research Laboratories. (1963)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Applied Polymer Science 7 (1963), S. 897-908 
    Details
    ISSN: 0021-8995
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Ring-substituted styrenes were prepared and polymerized. They usually had higher glass transition temperatures than polystyrene. In some disubstituted systems the Tg was an additive function of the individual groups. Crystallinities of methyl-substituted polymers varied, depending upon the ring positions involved. Crazing tendencies were equivalent to those in polystyrene.
    Additional Material: 9 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/app.1963.070070309
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  • 3
    Electronic Resource
    Electronic Resource
    Polystyrene modifications. I. Styrene copolymersCommunication No. 2235 from the Kodak Research Laboratories. (1963)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Applied Polymer Science 7 (1963), S. 143-152 
    Details
    ISSN: 0021-8995
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: The Tg of polystyrene was raised by copolymerization with acenaphthylene. Although physical properties of S20A polymer equaled or surpassed those of polystyrene, the addition of butadiene, mineral oil, or isoprene to poly(styrene-co-acenaphthylene) drastically reduced the Tg. The reduction of Tg of S20A by the addition of butadiene was less severe when butadiene was added several hours after the polymerization had begun. The incompatible terpolymers were flexible but showed no improvement in craze resistance. Crazing has been explained as being caused by forces concentrated in regions of irregularities.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/app.1963.070070113
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  • 4
    Electronic Resource
    Electronic Resource
    Polystyrene modifications. III. Copolymers and terpolymers of 2,5-dichlorostyrene and 3,4-dichlorostyreneCommunication No. 2284 from the Kodak Research Laboratories. (1963)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Applied Polymer Science 7 (1963), S. 1531-1541 
    Details
    ISSN: 0021-8995
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Thermal properties and resistance to crazing of copolymers and terpolymers of 2,5-dichlorostyrene and 3,4-dichlorostyrene have been studied. Copolymers based on 2,5-dichlorostyrene showed little or no improvement over polystyrene in craze resistance or glass transition temperature. Although copolymers of 3,4-dichlorostyrene were generally brittle and crazed readily, poly(3,4-dichlorostyrene-co-2-ethylhexyl methacrylate) and poly(3,4-dichlorostyrene-co-n-hexyl methacrylate) crazed less readily than polystyrene.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/app.1963.070070431
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  • 5
    Electronic Resource
    Electronic Resource
    Kinetic studies of C. pyrenoidosa using 94% 13C CO2 (1972)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 14 (1972), S. 819-829 
    Details
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The alga Chlorella pyrenoidosa has been grown in mass quantities on 94 at. % 13CO2. The algal cells have been labeled to the 90 at. % 13C level. Neither inhibition nor a requirement for adaptation was encountered; changes in morphology were not evident. A statistically significant increase in mass of cells produced in the presence of 13CO2 was observed.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260140511
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  • 6
    Electronic Resource
    Electronic Resource
    Some aspects of data processing for an optical absorption experiment in a pulsed 1000-Tesla magnet (1998)
    New York, NY : Wiley-Blackwell
    International Journal of Quantum Chemistry 70 (1998), S. 797-804 
    Details
    ISSN: 0020-7608
    Keywords: pulsed magnetic field ; Zeeman effect ; quadruple metal bonds ; octachlorodirhenate ; Chemistry ; Theoretical, Physical and Computational Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A procedure is given for the analysis of optical absorption data acquired in the hostile environment of a pulsed 1000-Tesla magnet.   © 1998 John Wiley & Sons, Inc. Int J Quant Chem 70: 797-804, 1998
    Additional Material: 9 Ill.
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  • 7
    Electronic Resource
    Electronic Resource
    A 1H-NMR Spectroscopic Investigation of the Conformation of the Acetamido Group in Some Derivatives of N-Acetyl-D-allosamine and -D-glucosamine (1996)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 79 (1996), S. 269-287 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The population of the conformations obtained by rotation around the C(2)—N and the N—C(O) bonds of AllNAc, GlcNAc, and GlcNMeAc derivatives was investigated by 1H-NMR spectroscopy. The AllNAc-derived α-D-and β-D-pyranosides 4-7, the AllNAc diazirine 16, and the GlcNAc-derived axial anomers α-D-8-10 prefer the (Z)-anti-conformation. A significant population of the (Z)-syn-conformer in the (Z)-syn/(Z)-anti-equilibrium for the equatorial anomers β-D-8-10 and the GlcNAc diazirine 17 was evidenced by an upfield shift of H—C(2), downfield shifts of H—C(1) and H—C(3), and by NOE measurements. The population of the (Z)-syn-conformation depends on the substituent at C(1) and is highest for the hexafluoroisopropyl glycoside. The population of the (Z)-syn-conformation of β-D-14 decreases with increasing polarity of the solvent, but a substantial population is still observed for solutions in D2O. Whereas the α-D-anomers of the hemiacetal 22 and the methyl glycoside 21 prefer the (Z)-anti-conformation in D2O solution, the corresponding β-D-anomers are mixtures of the (Z)-anti-and (Z)-syn-conformers. The diazirine 17 self-associates in CD2Cl2 solution at concentrations above 0.005M at low temperatures. The axial anomers of the GlcNMeAc derivatives α-D-26-28 are 2:1 to 3:1 mixtures of (Z)-anti-and (E)-anti-conformers, whereas the corresponding β-D-glycosides are ca. 1:3:6 mixtures of (Z)-syn-, (Z)-anti-, and (E)-anti-conformers.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19960790127
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  • 8
    Electronic Resource
    Electronic Resource
    An evaluation of DNA fingerprinting for forensic purposes (1987)
    Weinheim : Wiley-Blackwell
    Electrophoresis 8 (1987), S. 38-44 
    Details
    ISSN: 0173-0835
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Many highly polymorphic minisatellite loci can be detected simultaneously in the human genome by hybridisation to probes consisting of tandem repeats of the ‘core’ sequence. The resulting DNA fingerprints produced by Southern blot hybridisation are comprised of multiple hypervariable DNA fragments, show somatic and germline stability and are completely specific to an individual. DNA of high molecular weight can be isolated from blood and semen stains up to 4 years old. Sperm nuclei can be separated from vaginal debris and the sperm DNA examined in isolation, allowing the positive identification of rapists. Correspondingly, vaginal DNA can be isolated from extracts of penile swabs. DNA can also be isolated from extracts of buccal swabs. A blind trial involving 43 blood samples, 11 bloodstains and 11 semen stains has been successfully carried out. It is envisaged that genetic fingerprinting will shortly form an important part of casework procedure in forensic science laboratories.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/elps.1150080109
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  • 9
    Electronic Resource
    Electronic Resource
    Quantitative time-of-flight secondary ion mass spectrometry of a perfluorinated polyether (1991)
    Chichester [u.a.] : Wiley-Blackwell
    Surface and Interface Analysis 17 (1991), S. 125-136 
    Details
    ISSN: 0142-2421
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Physics
    Notes: Quantitative determination of the molecular weight and composition of submicrogram of a perfluorinated polyether (PFPE) supported on Ag and Si substrates was from empirical relationships derived from the intensities of specific high-mass (≥ 800 amu) fragmentation ions from time-of-flight secondary ion mass spectrometry (TOF-SIMS) measurements. These relationships are explained in terms of simple concepts regarding the process of volatilization, fragmentation and ionization in TOF-SIMS. The results for both negative and positive ions are nearly independent of the substrate materials used, demonstrating that the high-mass fragmentation ions in TOF-SIMS may be useful generally for in situ quantitative analysis of PEPEs on non-specific substrates. This is an important difference between the TOF-SIMS fragmentation spectrum and the complementary TOF-SIMS cationized molecular ion spectrum, which requires special sample preparation and/or substrates. In order to interpret the quantitative information available in the TOF-SIMS fragment spectrum, it was absolutely necessary to characterize extensively the PFPE samples using NMR and TOF-SIMS Ag+ -cationized molecular ion results. This characterization helped to demonstrate the power of TOF-SIMS to do quantitative analysis and led to additional insight concerning the SIMS ion-forming process for PFPE. This study represents one of the first attempts to make quantitative use of the high-mass fragment ion intensities in SIMS studies of polymers, and presents a method for confirming the origin of the mass peaks in the spectra.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/sia.740170303
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  • 10
    Electronic Resource
    Electronic Resource
    Altered protein synthesis in rat kidney cells exposed to semiconductor materials (1994)
    New York, NY [u.a.] : Wiley-Blackwell
    Applied Organometallic Chemistry 8 (1994), S. 253-258 
    Details
    ISSN: 0268-2605
    Keywords: Arsenite ; arsenic ; gallium ; indium ; kidney tubule epithelial cells ; primary culture ; heat-shock protein ; stress protein ; semiconductor ; rat ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: It is thought that the extensive industrial use of arsenic, gallium and indium, which have applications as the materials for III-V semiconductors, will increase human exposure to these compounds in the near future. We have undertaken the development of new biological indicators for assessing exposure to these elements. Element-specific alterations in protein synthesis patterns were expected to occur following exposure to arsenic compounds. We examined alterations in protein synthesis in primary cultures of rat kidney proximal tubule epithelial cells by sodium arsenite, gallium chloride and indium chloride, utilizing two-dimensional gel electrophoresis. After incubation with the chemicals for 20 h, newly synthesized proteins were labeled with [35S]methionine. A protein with a molecular weight (Mr) of 30 000 was markedly induced on exposure to 10 μM arsenite or 300 μM gallium chloride, and synthesis of proteins with Mr values of 85 000, 71 000, 65 000, 51 000, 38 000 and 28 000 were also increased by exposure to arsenite and gallium chloride. No significant changes were observed upon exposure to indium. Some of these increased proteins could be heat-shock proteins.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aoc.590080316
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