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  • 1
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    Knockout rats via embryo microinjection of zinc-finger nucleases (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-07-25
    Description: The toolbox of rat genetics currently lacks the ability to introduce site-directed, heritable mutations into the genome to create knockout animals. By using engineered zinc-finger nucleases (ZFNs) designed to target an integrated reporter and two endogenous rat genes, Immunoglobulin M (IgM) and Rab38, we demonstrate that a single injection of DNA or messenger RNA encoding ZFNs into the one-cell rat embryo leads to a high frequency of animals carrying 25 to 100% disruption at the target locus. These mutations are faithfully and efficiently transmitted through the germline. Our data demonstrate the feasibility of targeted gene disruption in multiple rat strains within 4 months time, paving the way to a humanized monoclonal antibody platform and additional human disease models.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831805/" 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/PMC2831805/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Geurts, Aron M -- Cost, Gregory J -- Freyvert, Yevgeniy -- Zeitler, Bryan -- Miller, Jeffrey C -- Choi, Vivian M -- Jenkins, Shirin S -- Wood, Adam -- Cui, Xiaoxia -- Meng, Xiangdong -- Vincent, Anna -- Lam, Stephen -- Michalkiewicz, Mieczyslaw -- Schilling, Rebecca -- Foeckler, Jamie -- Kalloway, Shawn -- Weiler, Hartmut -- Menoret, Severine -- Anegon, Ignacio -- Davis, Gregory D -- Zhang, Lei -- Rebar, Edward J -- Gregory, Philip D -- Urnov, Fyodor D -- Jacob, Howard J -- Buelow, Roland -- 5P01HL082798-03/HL/NHLBI NIH HHS/ -- 5U01HL066579-08/HL/NHLBI NIH HHS/ -- P01 HL082798/HL/NHLBI NIH HHS/ -- P01 HL082798-03/HL/NHLBI NIH HHS/ -- U01 HL066579/HL/NHLBI NIH HHS/ -- U01 HL066579-08/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 24;325(5939):433. doi: 10.1126/science.1172447.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI 52336, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19628861" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Dna ; Embryo, Mammalian ; Endodeoxyribonucleases/genetics/*metabolism ; Feasibility Studies ; Female ; *Gene Knockout Techniques ; Green Fluorescent Proteins ; Immunoglobulin M/*genetics ; Male ; *Microinjections ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; RNA, Messenger ; Rats ; *Zinc Fingers/genetics ; rab GTP-Binding Proteins/*genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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    Synchronous x-ray and radio mode switches: a rapid global transformation of the pulsar magnetosphere (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-01-26
    Description: Pulsars emit from low-frequency radio waves up to high-energy gamma-rays, generated anywhere from the stellar surface out to the edge of the magnetosphere. Detecting correlated mode changes across the electromagnetic spectrum is therefore key to understanding the physical relationship among the emission sites. Through simultaneous observations, we detected synchronous switching in the radio and x-ray emission properties of PSR B0943+10. When the pulsar is in a sustained radio-"bright" mode, the x-rays show only an unpulsed, nonthermal component. Conversely, when the pulsar is in a radio-"quiet" mode, the x-ray luminosity more than doubles and a 100% pulsed thermal component is observed along with the nonthermal component. This indicates rapid, global changes to the conditions in the magnetosphere, which challenge all proposed pulsar emission theories.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hermsen, W -- Hessels, J W T -- Kuiper, L -- van Leeuwen, J -- Mitra, D -- de Plaa, J -- Rankin, J M -- Stappers, B W -- Wright, G A E -- Basu, R -- Alexov, A -- Coenen, T -- Griessmeier, J-M -- Hassall, T E -- Karastergiou, A -- Keane, E -- Kondratiev, V I -- Kramer, M -- Kuniyoshi, M -- Noutsos, A -- Serylak, M -- Pilia, M -- Sobey, C -- Weltevrede, P -- Zagkouris, K -- Asgekar, A -- Avruch, I M -- Batejat, F -- Bell, M E -- Bell, M R -- Bentum, M J -- Bernardi, G -- Best, P -- Birzan, L -- Bonafede, A -- Breitling, F -- Broderick, J -- Bruggen, M -- Butcher, H R -- Ciardi, B -- Duscha, S -- Eisloffel, J -- Falcke, H -- Fender, R -- Ferrari, C -- Frieswijk, W -- Garrett, M A -- de Gasperin, F -- de Geus, E -- Gunst, A W -- Heald, G -- Hoeft, M -- Horneffer, A -- Iacobelli, M -- Kuper, G -- Maat, P -- Macario, G -- Markoff, S -- McKean, J P -- Mevius, M -- Miller-Jones, J C A -- Morganti, R -- Munk, H -- Orru, E -- Paas, H -- Pandey-Pommier, M -- Pandey, V N -- Pizzo, R -- Polatidis, A G -- Rawlings, S -- Reich, W -- Rottgering, H -- Scaife, A M M -- Schoenmakers, A -- Shulevski, A -- Sluman, J -- Steinmetz, M -- Tagger, M -- Tang, Y -- Tasse, C -- ter Veen, S -- Vermeulen, R -- van de Brink, R H -- van Weeren, R J -- Wijers, R A M J -- Wise, M W -- Wucknitz, O -- Yatawatta, S -- Zarka, P -- New York, N.Y. -- Science. 2013 Jan 25;339(6118):436-9. doi: 10.1126/science.1230960.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉SRON, Netherlands Institute for Space Research, Sorbonnelaan 2, 3584 CA Utrecht, Netherlands. w.hermsen@sron.nl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23349288" 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
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  • 3
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    An accurate geometric distance to the compact binary SS Cygni vindicates accretion disc theory (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-05-25
    Description: Dwarf novae are white dwarfs accreting matter from a nearby red dwarf companion. Their regular outbursts are explained by a thermal-viscous instability in the accretion disc, described by the disc instability model that has since been successfully extended to other accreting systems. However, the prototypical dwarf nova, SS Cygni, presents a major challenge to our understanding of accretion disc theory. At the distance of 159 +/- 12 parsecs measured by the Hubble Space Telescope, it is too luminous to be undergoing the observed regular outbursts. Using very long baseline interferometric radio observations, we report an accurate, model-independent distance to SS Cygni that places the source substantially closer at 114 +/- 2 parsecs. This reconciles the source behavior with our understanding of accretion disc theory in accreting compact objects.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller-Jones, J C A -- Sivakoff, G R -- Knigge, C -- Kording, E G -- Templeton, M -- Waagen, E O -- New York, N.Y. -- Science. 2013 May 24;340(6135):950-2. doi: 10.1126/science.1237145.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉International Centre for Radio Astronomy Research, Curtin University, Perth, WA 6845, Australia. james.miller-jones@curtin.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23704566" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    Genome maps IV 1993. Wall chart (1993)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1993-10-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Copeland, N G -- Gilbert, D J -- Jenkins, N A -- Nadeau, J H -- Eppig, J T -- Maltais, L J -- Miller, J C -- Dietrich, W F -- Steen, R G -- Lincoln, S E -- New York, N.Y. -- Science. 1993 Oct 1;262(5130):67-82.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Cancer Institute, Frederick MD.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8211131" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Chromosome Mapping ; Genetic Markers ; *Genome ; Genome, Human ; Humans ; Mice/*genetics ; Mice, Inbred Strains/genetics ; Sequence Homology, Nucleic Acid
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
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  • 5
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    A genetic linkage map of the mouse: current applications and future prospects (1993)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1993-10-01
    Description: Technological advances have made possible the development of high-resolution genetic linkage maps for the mouse. These maps in turn offer exciting prospects for understanding mammalian genome evolution through comparative mapping, for developing mouse models of human disease, and for identifying the function of all genes in the organism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Copeland, N G -- Jenkins, N A -- Gilbert, D J -- Eppig, J T -- Maltais, L J -- Miller, J C -- Dietrich, W F -- Weaver, A -- Lincoln, S E -- Steen, R G -- HG00198/HG/NHGRI NIH HHS/ -- N01-CO-74101/CO/NCI NIH HHS/ -- New York, N.Y. -- Science. 1993 Oct 1;262(5130):57-66.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8211130" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; *Chromosome Mapping ; Cloning, Molecular ; Crosses, Genetic ; Female ; Genetic Markers ; *Genome ; Human Genome Project ; Humans ; Male ; Mice/*genetics ; Multigene Family ; Muridae/*genetics ; Mutation ; Neoplasms/genetics
    Print ISSN: 0036-8075
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  • 6
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    Targeted genome editing across species using ZFNs and TALENs (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-06-28
    Description: Evolutionary studies necessary to dissect diverse biological processes have been limited by the lack of reverse genetic approaches in most organisms with sequenced genomes. We established a broadly applicable strategy using zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) for targeted disruption of endogenous genes and cis-acting regulatory elements in diverged nematode species.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3489282/" 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/PMC3489282/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wood, Andrew J -- Lo, Te-Wen -- Zeitler, Bryan -- Pickle, Catherine S -- Ralston, Edward J -- Lee, Andrew H -- Amora, Rainier -- Miller, Jeffrey C -- Leung, Elo -- Meng, Xiangdong -- Zhang, Lei -- Rebar, Edward J -- Gregory, Philip D -- Urnov, Fyodor D -- Meyer, Barbara J -- GM30702/GM/NIGMS NIH HHS/ -- R01 GM030702/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Jul 15;333(6040):307. doi: 10.1126/science.1207773. Epub 2011 Jun 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute (HHMI), Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3204, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21700836" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis/*genetics ; Caenorhabditis elegans/*genetics ; Deoxyribonucleases, Type II Site-Specific/genetics/*metabolism ; Gene Targeting ; Genes, Helminth ; *Genetic Techniques ; *Genome, Helminth ; INDEL Mutation ; Mutagenesis ; Regulatory Elements, Transcriptional/*genetics ; Transcription Factors/chemistry ; Transgenes ; *Zinc Fingers
    Print ISSN: 0036-8075
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  • 7
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    A radio jet from the optical and x-ray bright stellar tidal disruption flare ASASSN-14li (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-11-28
    Description: The tidal disruption of a star by a supermassive black hole leads to a short-lived thermal flare. Despite extensive searches, radio follow-up observations of known thermal stellar tidal disruption flares (TDFs) have not yet produced a conclusive detection. We present a detection of variable radio emission from a thermal TDF, which we interpret as originating from a newly launched jet. The multiwavelength properties of the source present a natural analogy with accretion-state changes of stellar mass black holes, which suggests that all TDFs could be accompanied by a jet. In the rest frame of the TDF, our radio observations are an order of magnitude more sensitive than nearly all previous upper limits, explaining how these jets, if common, could thus far have escaped detection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉van Velzen, S -- Anderson, G E -- Stone, N C -- Fraser, M -- Wevers, T -- Metzger, B D -- Jonker, P G -- van der Horst, A J -- Staley, T D -- Mendez, A J -- Miller-Jones, J C A -- Hodgkin, S T -- Campbell, H C -- Fender, R P -- New York, N.Y. -- Science. 2016 Jan 1;351(6268):62-5. doi: 10.1126/science.aad1182. Epub 2015 Nov 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics and Astronomy, The Johns Hopkins University, Baltimore, MD 21218, USA. sjoert@jhu.edu. ; Department of Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford OX1 3RH, UK. International Centre for Radio Astronomy Research, Curtin University, GPO Box U1987, Perth WA 6845, Australia. ; Columbia Astrophysics Laboratory, Columbia University, New York, NY 10027, USA. ; Institute of Astronomy, University of Cambridge, Madingley Road, Cambridge CB3 0HA, UK. ; Department of Astrophysics, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, Netherlands. ; Department of Astrophysics, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, Netherlands. SRON, Netherlands Institute for Space Research, Sorbonnelaan 2, 3584 CA Utrecht, Netherlands. ; Department of Physics, The George Washington University, 725 21st Street NW, Washington, DC 20052, USA. ; Department of Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford OX1 3RH, UK. ; Department of Physics and Astronomy, The Johns Hopkins University, Baltimore, MD 21218, USA. ; International Centre for Radio Astronomy Research, Curtin University, GPO Box U1987, Perth WA 6845, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26612833" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
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  • 8
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    Multichannel detection in high-performance liquid chromatography (1982)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1982-10-15
    Description: A linear photodiode array has been used as the photodetector element in a new ultraviolet-visible detection system for high-performance liquid chromatography. This array allows simultaneous acquisition of light intensity data at all wavelengths between 190 and 600 nanometers. By use of a computer network concept in the electronics, this detection system can process eight different chromatographic signals simultaneously in real time and acquire spectra manually or automatically. Detector response times are variable and can be as low as 0.040 second, and bandwidth selection is variable from 4 to 400 nanometers. These characteristics permit fast chromatographic techniques and user-selectable signal-to-noise ratio enhancement. Spectra can be acquired in 10 milliseconds, permitting qualitative characterization at several different points on a single peak without destroying chromatographic signal integrity. Examples illustrate applications in fast high-performance liquid chromatography peak purity determination, and postanalysis data reduction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, J C -- George, S A -- Willis, B G -- New York, N.Y. -- Science. 1982 Oct 15;218(4569):241-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17838610" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
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  • 9
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    Structure of the nucleotide exchange factor eIF2B reveals mechanism of memory-enhancing molecule (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018-03-30
    Description: Regulation by the integrated stress response (ISR) converges on the phosphorylation of translation initiation factor eIF2 in response to a variety of stresses. Phosphorylation converts eIF2 from a substrate to a competitive inhibitor of its dedicated guanine nucleotide exchange factor, eIF2B, thereby inhibiting translation. ISRIB, a drug-like eIF2B activator, reverses the effects of eIF2 phosphorylation, and in rodents it enhances cognition and corrects cognitive deficits after brain injury. To determine its mechanism of action, we solved an atomic-resolution structure of ISRIB bound in a deep cleft within decameric human eIF2B by cryo–electron microscopy. Formation of fully active, decameric eIF2B holoenzyme depended on the assembly of two identical tetrameric subcomplexes, and ISRIB promoted this step by cross-bridging a central symmetry interface. Thus, regulation of eIF2B assembly emerges as a rheostat for eIF2B activity that tunes translation during the ISR and that can be further modulated by ISRIB.
    Keywords: Biochemistry, Online Only
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    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
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    eIF2B-catalyzed nucleotide exchange and phosphoregulation by the integrated stress response (2019)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2019
    Description: 〈p〉The integrated stress response (ISR) tunes the rate of protein synthesis. Control is exerted by phosphorylation of the general translation initiation factor eIF2. eIF2 is a guanosine triphosphatase that becomes activated by eIF2B, a two-fold symmetric and heterodecameric complex that functions as eIF2’s dedicated nucleotide exchange factor. Phosphorylation converts eIF2 from a substrate into an inhibitor of eIF2B. We report cryo–electron microscopy structures of eIF2 bound to eIF2B in the dephosphorylated state. The structures reveal that the eIF2B decamer is a static platform upon which one or two flexible eIF2 trimers bind and align with eIF2B’s bipartite catalytic centers to catalyze nucleotide exchange. Phosphorylation refolds eIF2α, allowing it to contact eIF2B at a different interface and, we surmise, thereby sequestering it into a nonproductive complex.〈/p〉
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