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  • 1
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    A conformational checkpoint between DNA binding and cleavage by CRISPR-Cas9 (2017)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2017-08-05
    Description: The Cas9 endonuclease is widely used for genome engineering applications by programming its single-guide RNA, and ongoing work is aimed at improving the accuracy and efficiency of DNA targeting. DNA cleavage of Cas9 is controlled by the conformational state of the HNH nuclease domain, but the mechanism that governs HNH activation at on-target DNA while reducing cleavage activity at off-target sites remains poorly understood. Using single-molecule Förster resonance energy transfer, we identified an intermediate state of Streptococcus pyogenes Cas9, representing a conformational checkpoint between DNA binding and cleavage. Upon DNA binding, the HNH domain transitions between multiple conformations before docking into its active state. HNH docking requires divalent cations, but not strand scission, and this docked conformation persists following DNA cleavage. Sequence mismatches between the DNA target and guide RNA prevent transitions from the checkpoint intermediate to the active conformation, providing selective avoidance of DNA cleavage at stably bound off-target sites.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    CO/H2, C/CO, OH/CO, and OH/O2 in dense interstellar gas: from high ionization to low metallicity (2015)
    Oxford University Press
    Details
    Publication Date: 2015-05-28
    Description: We present numerical computations and analytic scaling relations for interstellar ion-molecule gas-phase chemistry down to very low metallicities (10 –3  solar), and/or up to high driving ionization rates. Relevant environments include the cool interstellar medium (ISM) in low-metallicity dwarf galaxies, early enriched clouds at the reionization and Pop-II star formation era, and in dense cold gas exposed to intense X-ray or cosmic ray sources. We focus on the behaviour for H 2 , CO, CH, OH, H 2 O and O 2 , at gas temperatures ~100 K, characteristic of a cooled ISM at low metallicities. We consider shielded or partially shielded one-zone gas parcels, and solve the gas-phase chemical rate equations for the steady-state ‘metal-molecule abundances for a wide range of ionization parameters, / n , and metallicties, Z ' . We find that the OH abundances are always maximal near the H-to-H 2 conversion points, and that large OH abundances persist at very low metallicities even when the hydrogen is predominantly atomic. We study the OH/O 2 , C/CO and OH/CO abundance ratios, from large to small, as functions of / n and Z ' . Much of the cold dense ISM for the Pop-II generation may have been OH-dominated and atomic rather than CO-dominated and molecular.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 3
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    HIV comes in five family groups (1992)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1992-05-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sternberg, S -- New York, N.Y. -- Science. 1992 May 15;256(5059):966.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1589779" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/epidemiology/*microbiology ; Africa ; HIV/*classification/genetics/immunology ; HIV-1/classification/genetics ; Humans
    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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    The emerging fungal threat (1994)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1994-12-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sternberg, S -- New York, N.Y. -- Science. 1994 Dec 9;266(5191):1632-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7702654" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS-Related Opportunistic Infections/epidemiology ; Animals ; Antifungal Agents/adverse effects/*therapeutic use ; California/epidemiology ; Candidiasis/epidemiology ; Cross Infection/*epidemiology ; Drug Resistance, Microbial ; Fungi/drug effects ; Humans ; Immunocompromised Host ; Mycoses/drug therapy/*epidemiology/etiology ; Opportunistic Infections/*epidemiology ; Research
    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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  • 5
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    Plague epidemic. Bottleneck keeps existing vaccine off the market (1994)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1994-10-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sternberg, S -- New York, N.Y. -- Science. 1994 Oct 7;266(5182):22-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7864946" target="_blank"〉PubMed〈/a〉
    Keywords: Disease Outbreaks ; Drug Approval ; Humans ; India/epidemiology ; Plague/epidemiology/*prevention & control ; *Plague Vaccine ; Pneumonia, Bacterial/epidemiology/*prevention & control ; United States ; United States Food and Drug Administration ; Vaccines, Inactivated ; Vaccines, Synthetic
    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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  • 6
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    Support grows for NIH trust fund (1994)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1994-08-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sternberg, S -- New York, N.Y. -- Science. 1994 Aug 12;265(5174):862.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8052837" target="_blank"〉PubMed〈/a〉
    Keywords: Budgets ; Financing, Government ; National Institutes of Health (U.S.)/*economics ; *Research Support as Topic ; United States
    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
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    Is dioxin a human carcinogen? (continued) (1994)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1994-03-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sternberg, S S -- New York, N.Y. -- Science. 1994 Mar 18;263(5153):1545-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8128234" target="_blank"〉PubMed〈/a〉
    Keywords: Female ; Humans ; Neoplasms/*chemically induced/epidemiology ; Tetrachlorodibenzodioxin/*adverse effects
    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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  • 8
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    Crassulacean Acid Metabolism in the Strangler Clusia rosea Jacq (1985)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1985-09-06
    Description: Observations of malic acid fluctuation, leaf anatomy, and stable carbon isotopic composition showed that the epiphytic strangler Clusia rosea, growing on Saint John, U.S. Virgin Islands, has crassulacean acid metabolism. This hemiepiphyte may be the only woody dicotyledonous tree species among the many thousands of flowering species in the 30 or more plant families that shows this type of metabolism. The finding has implications with respect to water balance during the process whereby Clusia rosea establishes itself as a tree, since crassulacean acid metabolism is a photosynthetic adaptation to water-stressed environments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ting, I P -- Lord, E M -- Sternberg, L da S -- Deniro, M J -- New York, N.Y. -- Science. 1985 Sep 6;229(4717):969-71.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17782529" 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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  • 9
    Electronic Resource
    Electronic Resource
    Concentration cells with quartz membranes in molten salts: PbCl"2NaCl, PbBr"2NaBr, PbI"2NaI systems
    Amsterdam : Elsevier
    Electrochimica Acta 13 (1968), S. 863-871 
    Details
    ISSN: 0013-4686
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0013-4686(68)85019-4
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  • 10
    Electronic Resource
    Electronic Resource
    Behaviour of silicon electrodes in LiClKClPbCl"2 molten chlorides
    Amsterdam : Elsevier
    Electrochimica Acta 30 (1985), S. 283-289 
    Details
    ISSN: 0013-4686
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0013-4686(85)80185-7
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