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  • 1
    Publication Date: 2018-06-29
    Description: Chiral amines are widely used as catalysts in asymmetric synthesis to activate carbonyl groups for α-functionalization. Carbonyl catalysis reverses that strategy by using a carbonyl group to activate a primary amine. Inspired by biological carbonyl catalysis, which is exemplified by reactions of pyridoxal-dependent enzymes, we developed an N-quaternized pyridoxal catalyst for the asymmetric Mannich reaction of glycinate with aryl N -diphenylphosphinyl imines. The catalyst exhibits high activity and stereoselectivity, likely enabled by enzyme-like cooperative bifunctional activation of the substrates. Our work demonstrates the catalytic utility of the pyridoxal moiety in asymmetric catalysis.
    Keywords: Chemistry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2018-09-07
    Description: Galaxies grow inefficiently, with only a small percentage of the available gas converted into stars each free-fall time. Feedback processes, such as outflowing winds driven by radiation pressure, supernovae, or supermassive black hole accretion, can act to halt star formation if they heat or expel the gas supply. We report a molecular outflow launched from a dust-rich star-forming galaxy at redshift 5.3, 1 billion years after the Big Bang. The outflow reaches velocities up to 800 kilometers per second relative to the galaxy, is resolved into multiple clumps, and carries mass at a rate within a factor of 2 of the star formation rate. Our results show that molecular outflows can remove a large fraction of the gas available for star formation from galaxies at high redshift.
    Keywords: Astronomy
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2018-05-19
    Description: Multiferroic materials, which simultaneously have multiple orderings, hold promise for use in the next generation of memory devices. We report a novel self-assembled MnO double layer forming at the interface between a multiferroic YMnO 3 film and a c -Al 2 O 3 substrate. The crystal structures and the valence states of this MnO double layer were studied by atomically resolved scanning transmission electron microscopy and spectroscopy, as well as density functional theory (DFT) calculations. A new type of charge ordering has been identified within this MnO layer, which also contributes to a polarization along the [001] direction. DFT calculations further establish the occurrence of multiple couplings between charge and lattice in this novel double layer, in addition to the polarization in nearby YMnO 3 single layer. The interface reconstruction reported here creates a new playground for emergent physics, such as giant ferroelectricity and strong magnetoelectric coupling, in manganite systems.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 4
    Publication Date: 2018-04-19
    Description: Extensive effort is under way to survey the epigenomic landscape of primary ex vivo tissues to establish normal reference data and to discern variation associated with disease. The low abundance of some tissue types and the isolation procedure required to generate a homogenous cell population often yield a small quantity of cells for examination. This difficulty is further compounded by the need to profile a myriad of epigenetic marks. Thus, technologies that permit both ultralow input and high throughput are desired. We demonstrate a simple microfluidic technology, SurfaceChIP-seq, for profiling genome-wide histone modifications using as few as 30 to 100 cells per assay and with up to eight assays running in parallel. We applied the technology to profile epigenomes using nuclei isolated from prefrontal cortex and cerebellum of mouse brain. Our cell type–specific data revealed that neuronal and glial fractions exhibited profound epigenomic differences across the two functionally distinct brain regions.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 5
    Publication Date: 2018-03-09
    Description: The gut microbiota benefits humans via short-chain fatty acid (SCFA) production from carbohydrate fermentation, and deficiency in SCFA production is associated with type 2 diabetes mellitus (T2DM). We conducted a randomized clinical study of specifically designed isoenergetic diets, together with fecal shotgun metagenomics, to show that a select group of SCFA-producing strains was promoted by dietary fibers and that most other potential producers were either diminished or unchanged in patients with T2DM. When the fiber-promoted SCFA producers were present in greater diversity and abundance, participants had better improvement in hemoglobin A1c levels, partly via increased glucagon-like peptide-1 production. Promotion of these positive responders diminished producers of metabolically detrimental compounds such as indole and hydrogen sulfide. Targeted restoration of these SCFA producers may present a novel ecological approach for managing T2DM.
    Keywords: Medicine, Diseases, Microbiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2018-06-08
    Description: Plants regulate photosynthetic light harvesting to maintain balanced energy flux into photosystems I and II (PSI and PSII). Under light conditions favoring PSII excitation, the PSII antenna, light-harvesting complex II (LHCII), is phosphorylated and forms a supercomplex with PSI core and the PSI antenna, light-harvesting complex I (LHCI). Both LHCI and LHCII then transfer excitation energy to the PSI core. We report the structure of maize PSI-LHCI-LHCII solved by cryo–electron microscopy, revealing the recognition site between LHCII and PSI. The PSI subunits PsaN and PsaO are observed at the PSI-LHCI interface and the PSI-LHCII interface, respectively. Each subunit relays excitation to PSI core through a pair of chlorophyll molecules, thus revealing previously unseen paths for energy transfer between the antennas and the PSI core.
    Keywords: Biochemistry, Botany
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-07-03
    Description: In cells, RNA polymerase (RNAP) must transcribe supercoiled DNA, whose torsional state is constantly changing, but how RNAP deals with DNA supercoiling remains elusive. We report direct measurements of individual Escherichia coli RNAPs as they transcribed supercoiled DNA. We found that a resisting torque slowed RNAP and increased its pause frequency and duration. RNAP was able to generate 11 +/- 4 piconewton-nanometers (mean +/- standard deviation) of torque before stalling, an amount sufficient to melt DNA of arbitrary sequence and establish RNAP as a more potent torsional motor than previously known. A stalled RNAP was able to resume transcription upon torque relaxation, and transcribing RNAP was resilient to transient torque fluctuations. These results provide a quantitative framework for understanding how dynamic modification of DNA supercoiling regulates transcription.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ma, Jie -- Bai, Lu -- Wang, Michelle D -- GM059849/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Jun 28;340(6140):1580-3. doi: 10.1126/science.1235441.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics-Laboratory of Atomic and Solid State Physics, Cornell University, Ithaca, NY 14853, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23812716" target="_blank"〉PubMed〈/a〉
    Keywords: DNA, Superhelical/*chemistry/*genetics ; DNA-Directed RNA Polymerases/genetics/*metabolism ; Escherichia coli/*enzymology/genetics ; Nucleic Acid Conformation ; *Torque ; *Transcription, Genetic
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2014-01-11
    Description: It has been assumed that most, if not all, signals regulating early development have been identified. Contrary to this expectation, we identified 28 candidate signaling proteins expressed during zebrafish embryogenesis, including Toddler, a short, conserved, and secreted peptide. Both absence and overproduction of Toddler reduce the movement of mesendodermal cells during zebrafish gastrulation. Local and ubiquitous production of Toddler promote cell movement, suggesting that Toddler is neither an attractant nor a repellent but acts globally as a motogen. Toddler drives internalization of G protein-coupled APJ/Apelin receptors, and activation of APJ/Apelin signaling rescues toddler mutants. These results indicate that Toddler is an activator of APJ/Apelin receptor signaling, promotes gastrulation movements, and might be the first in a series of uncharacterized developmental signals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107353/" 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/PMC4107353/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pauli, Andrea -- Norris, Megan L -- Valen, Eivind -- Chew, Guo-Liang -- Gagnon, James A -- Zimmerman, Steven -- Mitchell, Andrew -- Ma, Jiao -- Dubrulle, Julien -- Reyon, Deepak -- Tsai, Shengdar Q -- Joung, J Keith -- Saghatelian, Alan -- Schier, Alexander F -- K99 HD076935/HD/NICHD NIH HHS/ -- R01 GM056211/GM/NIGMS NIH HHS/ -- R01 GM102491/GM/NIGMS NIH HHS/ -- R01 HG005111/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Feb 14;343(6172):1248636. doi: 10.1126/science.1248636. Epub 2014 Jan 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24407481" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Cell Movement ; Chemokine CXCL12/metabolism ; Frameshift Mutation ; Gastrulation/genetics/*physiology ; Molecular Sequence Data ; Receptors, G-Protein-Coupled/genetics/*metabolism ; Signal Transduction ; Zebrafish/*embryology/genetics/metabolism ; Zebrafish Proteins/genetics/*metabolism
    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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  • 9
    Publication Date: 2014-08-12
    Description: Spinal muscular atrophy (SMA) is a genetic disease caused by mutation or deletion of the survival of motor neuron 1 (SMN1) gene. A paralogous gene in humans, SMN2, produces low, insufficient levels of functional SMN protein due to alternative splicing that truncates the transcript. The decreased levels of SMN protein lead to progressive neuromuscular degeneration and high rates of mortality. Through chemical screening and optimization, we identified orally available small molecules that shift the balance of SMN2 splicing toward the production of full-length SMN2 messenger RNA with high selectivity. Administration of these compounds to Delta7 mice, a model of severe SMA, led to an increase in SMN protein levels, improvement of motor function, and protection of the neuromuscular circuit. These compounds also extended the life span of the mice. Selective SMN2 splicing modifiers may have therapeutic potential for patients with SMA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Naryshkin, Nikolai A -- Weetall, Marla -- Dakka, Amal -- Narasimhan, Jana -- Zhao, Xin -- Feng, Zhihua -- Ling, Karen K Y -- Karp, Gary M -- Qi, Hongyan -- Woll, Matthew G -- Chen, Guangming -- Zhang, Nanjing -- Gabbeta, Vijayalakshmi -- Vazirani, Priya -- Bhattacharyya, Anuradha -- Furia, Bansri -- Risher, Nicole -- Sheedy, Josephine -- Kong, Ronald -- Ma, Jiyuan -- Turpoff, Anthony -- Lee, Chang-Sun -- Zhang, Xiaoyan -- Moon, Young-Choon -- Trifillis, Panayiota -- Welch, Ellen M -- Colacino, Joseph M -- Babiak, John -- Almstead, Neil G -- Peltz, Stuart W -- Eng, Loren A -- Chen, Karen S -- Mull, Jesse L -- Lynes, Maureen S -- Rubin, Lee L -- Fontoura, Paulo -- Santarelli, Luca -- Haehnke, Daniel -- McCarthy, Kathleen D -- Schmucki, Roland -- Ebeling, Martin -- Sivaramakrishnan, Manaswini -- Ko, Chien-Ping -- Paushkin, Sergey V -- Ratni, Hasane -- Gerlach, Irene -- Ghosh, Anirvan -- Metzger, Friedrich -- New York, N.Y. -- Science. 2014 Aug 8;345(6197):688-93. doi: 10.1126/science.1250127.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉PTC Therapeutics, 100 Corporate Court, South Plainfield, NJ 07080, USA. ; Section of Neurobiology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA. ; PTC Therapeutics, 100 Corporate Court, South Plainfield, NJ 07080, USA. friedrich.metzger@roche.com speltz@ptcbio.com. ; SMA Foundation, 888 Seventh Avenue, Suite 400, New York, NY 10019, USA. ; Department of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. ; Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Grenzacherstrasse 124, 4070 Basel, Switzerland. ; Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Grenzacherstrasse 124, 4070 Basel, Switzerland. friedrich.metzger@roche.com speltz@ptcbio.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25104390" target="_blank"〉PubMed〈/a〉
    Keywords: Administration, Oral ; Alternative Splicing/*drug effects ; Animals ; Cells, Cultured ; Coumarins/*administration & dosage/chemistry ; Disease Models, Animal ; Drug Evaluation, Preclinical ; Humans ; Isocoumarins/*administration & dosage/chemistry ; Longevity/*drug effects ; Mice ; Muscular Atrophy, Spinal/*drug therapy/genetics/metabolism ; Pyrimidinones/*administration & dosage/chemistry ; RNA, Messenger/genetics ; Sequence Deletion ; Small Molecule Libraries/*administration & dosage/chemistry ; Survival of Motor Neuron 2 Protein/*genetics/metabolism
    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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  • 10
    Publication Date: 2015-11-07
    Description: Coupling between the lower and upper atmosphere, combined with loss of gas from the upper atmosphere to space, likely contributed to the thin, cold, dry atmosphere of modern Mars. To help understand ongoing ion loss to space, the Mars Atmosphere and Volatile Evolution (MAVEN) spacecraft made comprehensive measurements of the Mars upper atmosphere, ionosphere, and interactions with the Sun and solar wind during an interplanetary coronal mass ejection impact in March 2015. Responses include changes in the bow shock and magnetosheath, formation of widespread diffuse aurora, and enhancement of pick-up ions. Observations and models both show an enhancement in escape rate of ions to space during the event. Ion loss during solar events early in Mars history may have been a major contributor to the long-term evolution of the Mars atmosphere.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jakosky, B M -- Grebowsky, J M -- Luhmann, J G -- Connerney, J -- Eparvier, F -- Ergun, R -- Halekas, J -- Larson, D -- Mahaffy, P -- McFadden, J -- Mitchell, D F -- Schneider, N -- Zurek, R -- Bougher, S -- Brain, D -- Ma, Y J -- Mazelle, C -- Andersson, L -- Andrews, D -- Baird, D -- Baker, D -- Bell, J M -- Benna, M -- Chaffin, M -- Chamberlin, P -- Chaufray, Y-Y -- Clarke, J -- Collinson, G -- Combi, M -- Crary, F -- Cravens, T -- Crismani, M -- Curry, S -- Curtis, D -- Deighan, J -- Delory, G -- Dewey, R -- DiBraccio, G -- Dong, C -- Dong, Y -- Dunn, P -- Elrod, M -- England, S -- Eriksson, A -- Espley, J -- Evans, S -- Fang, X -- Fillingim, M -- Fortier, K -- Fowler, C M -- Fox, J -- Groller, H -- Guzewich, S -- Hara, T -- Harada, Y -- Holsclaw, G -- Jain, S K -- Jolitz, R -- Leblanc, F -- Lee, C O -- Lee, Y -- Lefevre, F -- Lillis, R -- Livi, R -- Lo, D -- Mayyasi, M -- McClintock, W -- McEnulty, T -- Modolo, R -- Montmessin, F -- Morooka, M -- Nagy, A -- Olsen, K -- Peterson, W -- Rahmati, A -- Ruhunusiri, S -- Russell, C T -- Sakai, S -- Sauvaud, J-A -- Seki, K -- Steckiewicz, M -- Stevens, M -- Stewart, A I F -- Stiepen, A -- Stone, S -- Tenishev, V -- Thiemann, E -- Tolson, R -- Toublanc, D -- Vogt, M -- Weber, T -- Withers, P -- Woods, T -- Yelle, R -- New York, N.Y. -- Science. 2015 Nov 6;350(6261):aad0210. doi: 10.1126/science.aad0210.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Colorado, Boulder, CO, USA. bruce.jakosky@lasp.colorado.edu. ; NASA/Goddard Space Flight Center, Greenbelt, MD, USA. ; University of California at Berkeley, Berkeley, CA, USA. ; University of Colorado, Boulder, CO, USA. ; University of Iowa, Iowa City, IA, USA. ; Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA, USA. ; University of Michigan, Ann Arbor, MI, USA. ; University of California at Los Angeles, Los Angeles, CA, USA. ; CNRS-Institut de Recherche en Astrophysique et Planetologie (IRAP), Toulouse, France. University Paul Sabatier, Toulouse, France. ; Swedish Institute of Space Physics, Uppsala, Sweden. ; NASA/Johnson Space Center, Houston, TX, USA. ; National Institute of Aerospace, Hampton, VA, USA. ; Laboratoire atmospheres, milieux et observations spatiales (LATMOS)-CNRS, Paris, France. ; Boston University, Boston, MA, USA. ; University of Kansas, Lawrence, KS, USA. ; Computational Physics, Inc., Boulder, CO, USA. ; Wright State University, Dayton, OH, USA. ; University of Arizona, Tucson, AZ, USA. ; Nagoya University, Nagoya, Japan. ; Naval Research Laboratory, Washington, DC, USA. ; North Carolina State University, Raleigh, NC, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26542576" target="_blank"〉PubMed〈/a〉
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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