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Science
Journal Prestige (SJR): 14.142
Citation Impact (citeScore): 16
Number of Followers: 4435  
 
  Full-text available via subscription Subscription journal
ISSN (Print) 0036-8075 - ISSN (Online) 1095-9203
Published by AAAS Homepage  [7 journals]
  • Reactivation of PTEN tumor suppressor for cancer treatment through
           inhibition of a MYC-WWP1 inhibitory pathway
    • Authors: Lee, Y.-R; Chen, M, Lee, J. D, Zhang, J, Lin, S.-Y, Fu, T.-M, Chen, H, Ishikawa, T, Chiang, S.-Y, Katon, J, Zhang, Y, Shulga, Y. V, Bester, A. C, Fung, J, Monteleone, E, Wan, L, Shen, C, Hsu, C.-H, Papa, A, Clohessy, J. G, Teruya-Feldstein, J, Jain, S, Wu, H, Matesic, L, Chen, R.-H, Wei, W, Pandolfi, P. P.
      Abstract: Activation of tumor suppressors for the treatment of human cancer has been a long sought, yet elusive, strategy. PTEN is a critical tumor suppressive phosphatase that is active in its dimer configuration at the plasma membrane. Polyubiquitination by the ubiquitin E3 ligase WWP1 (WW domain–containing ubiquitin E3 ligase 1) suppressed the dimerization, membrane recruitment, and function of PTEN. Either genetic ablation or pharmacological inhibition of WWP1 triggered PTEN reactivation and unleashed tumor suppressive activity. WWP1 appears to be a direct MYC (MYC proto-oncogene) target gene and was critical for MYC-driven tumorigenesis. We identified indole-3-carbinol, a compound found in cruciferous vegetables, as a natural and potent WWP1 inhibitor. Thus, our findings unravel a potential therapeutic strategy for cancer prevention and treatment through PTEN reactivation.
      Keywords: Genetics, Medicine, Diseases, Online Only
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aau0159
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Erratum for the Report "Conformationally supple glucose monomers enable
           synthesis of the smallest cyclodextrins" by D. Ikuta, Y. Hirata, S.
           Wakamori, H. Shimada, Y. Tomabechi, Y. Kawasaki, K. Ikeuchi, T. Hagimori,
           S. Matsumoto, H. Yamada
    • PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aay0378
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Recall responses by human NK cells
    • Authors: Williams I.
      Pages: 646
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.645-i
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Spatiotemporal light control with active metasurfaces
    • Authors: Shaltout, A. M; Shalaev, V. M, Brongersma, M. L.
      Abstract: Optical metasurfaces have provided us with extraordinary ways to control light by spatially structuring materials. The space-time duality in Maxwell’s equations suggests that additional structuring of metasurfaces in the time domain can even further expand their impact on the field of optics. Advances toward this goal critically rely on the development of new materials and nanostructures that exhibit very large and fast changes in their optical properties in response to external stimuli. New physics is also emerging as ultrafast tuning of metasurfaces is becoming possible, including wavelength shifts that emulate the Doppler effect, Lorentz nonreciprocity, time-reversed optical behavior, and negative refraction. The large-scale manufacturing of dynamic flat optics has the potential to revolutionize many emerging technologies that require active wavefront shaping with lightweight, compact, and power-efficient components.
      Keywords: Physics, Applied, Online Only, Physics
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aat3100
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Local protein synthesis is a ubiquitous feature of neuronal pre- and
           postsynaptic compartments
    • Authors: Hafner, A.-S; Donlin-Asp, P. G, Leitch, B, Herzog, E, Schuman, E. M.
      Abstract: There is ample evidence for localization of messenger RNAs (mRNAs) and protein synthesis in neuronal dendrites; however, demonstrations of these processes in presynaptic terminals are limited. We used expansion microscopy to resolve pre- and postsynaptic compartments in rodent neurons. Most presynaptic terminals in the hippocampus and forebrain contained mRNA and ribosomes. We sorted fluorescently labeled mouse brain synaptosomes and then sequenced hundreds of mRNA species present within excitatory boutons. After brief metabolic labeling, >30% of all presynaptic terminals exhibited a signal, providing evidence for ongoing protein synthesis. We tested different classic plasticity paradigms and observed distinct patterns of rapid pre- and/or postsynaptic translation. Thus, presynaptic terminals are translationally competent, and local protein synthesis is differentially recruited to drive compartment-specific phenotypes that underlie different forms of plasticity.
      Keywords: Cell Biology, Neuroscience, Online Only
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aau3644
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Hierarchical reasoning by neural circuits in the frontal cortex
    • Authors: Sarafyazd, M; Jazayeri, M.
      Abstract: Humans process information hierarchically. In the presence of hierarchies, sources of failures are ambiguous. Humans resolve this ambiguity by assessing their confidence after one or more attempts. To understand the neural basis of this reasoning strategy, we recorded from dorsomedial frontal cortex (DMFC) and anterior cingulate cortex (ACC) of monkeys in a task in which negative outcomes were caused either by misjudging the stimulus or by a covert switch between two stimulus-response contingency rules. We found that both areas harbored a representation of evidence supporting a rule switch. Additional perturbation experiments revealed that ACC functioned downstream of DMFC and was directly and specifically involved in inferring covert rule switches. These results‏ reveal the computational principles of hierarchical reasoning, as implemented by cortical circuits.
      Keywords: Neuroscience, Online Only
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aav8911
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Initial results from the New Horizons exploration of 2014 MU69, a small
           Kuiper Belt object
    • Authors: Stern, S. A; Weaver, H. A, Spencer, J. R, Olkin, C. B, Gladstone, G. R, Grundy, W. M, Moore, J. M, Cruikshank, D. P, Elliott, H. A, McKinnon, W. B, Parker, J. W, Verbiscer, A. J, Young, L. A, Aguilar, D. A, Albers, J. M, Andert, T, Andrews, J. P, Bagenal, F, Banks, M. E, Bauer, B. A, Bauman, J. A, Bechtold, K. E, Beddingfield, C. B, Behrooz, N, Beisser, K. B, Benecchi, S. D, Bernardoni, E, Beyer, R. A, Bhaskaran, S, Bierson, C. J, Binzel, R. P, Birath, E. M, Bird, M. K, Boone, D. R, Bowman, A. F, Bray, V. J, Britt, D. T, Brown, L. E, Buckley, M. R, Buie, M. W, Buratti, B. J, Burke, L. M, Bushman, S. S, Carcich, B, Chaikin, A. L, Chavez, C. L, Cheng, A. F, Colwell, E. J, Conard, S. J, Conner, M. P, Conrad, C. A, Cook, J. C, Cooper, S. B, Custodio, O. S, Dalle Ore, C. M, Deboy, C. C, Dharmavaram, P, Dhingra, R. D, Dunn, G. F, Earle, A. M, Egan, A. F, Eisig, J, El-Maarry, M. R, Engelbrecht, C, Enke, B. L, Ercol, C. J, Fattig, E. D, Ferrell, C. L, Finley, T. J, Firer, J, Fischetti, J, Folkner, W. M, Fosbury, M. N, Fountain, G. H, Freeze, J. M, Gabasova, L, Glaze, L. S, Green, J. L, Griffith, G. A, Guo, Y, Hahn, M, Hals, D. W, Hamilton, D. P, Hamilton, S. A, Hanley, J. J, Harch, A, Harmon, K. A, Hart, H. M, Hayes, J, Hersman, C. B, Hill, M. E, Hill, T. A, Hofgartner, J. D, Holdridge, M. E, Horanyi, M, Hosadurga, A, Howard, A. D, Howett, C. J. A, Jaskulek, S. E, Jennings, D. E, Jensen, J. R, Jones, M. R, Kang, H. K, Katz, D. J, Kaufmann, D. E, Kavelaars, J. J, Keane, J. T, Keleher, G. P, Kinczyk, M, Kochte, M. C, Kollmann, P, Krimigis, S. M, Kruizinga, G. L, Kusnierkiewicz, D. Y, Lahr, M. S, Lauer, T. R, Lawrence, G. B, Lee, J. E, Lessac-Chenen, E. J, Linscott, I. R, Lisse, C. M, Lunsford, A. W, Mages, D. M, Mallder, V. A, Martin, N. P, May, B. H, McComas, D. J, McNutt, R. L, Mehoke, D. S, Mehoke, T. S, Nelson, D. S, Nguyen, H. D, Nunez, J. I, Ocampo, A. C, Owen, W. M, Oxton, G. K, Parker, A. H, Pätzold, M, Pelgrift, J. Y, Pelletier, F. J, Pineau, J. P, Piquette, M. R, Porter, S. B, Protopapa, S, Quirico, E, Redfern, J. A, Regiec, A. L, Reitsema, H. J, Reuter, D. C, Richardson, D. C, Riedel, J. E, Ritterbush, M. A, Robbins, S. J, Rodgers, D. J, Rogers, G. D, Rose, D. M, Rosendall, P. E, Runyon, K. D, Ryschkewitsch, M. G, Saina, M. M, Salinas, M. J, Schenk, P. M, Scherrer, J. R, Schlei, W. R, Schmitt, B, Schultz, D. J, Schurr, D. C, Scipioni, F, Sepan, R. L, Shelton, R. G, Showalter, M. R, Simon, M, Singer, K. N, Stahlheber, E. W, Stanbridge, D. R, Stansberry, J. A, Steffl, A. J, Strobel, D. F, Stothoff, M. M, Stryk, T, Stuart, J. R, Summers, M. E, Tapley, M. B, Taylor, A, Taylor, H. W, Tedford, R. M, Throop, H. B, Turner, L. S, Umurhan, O. M, Van Eck, J, Velez, D, Versteeg, M. H, Vincent, M. A, Webbert, R. W, Weidner, S. E, Weigle, G. E, Wendel, J. R, White, O. L, Whittenburg, K. E, Williams, B. G, Williams, K. E, Williams, S. P, Winters, H. L, Zangari, A. M, Zurbuchen, T. H.
      Abstract: The Kuiper Belt is a distant region of the outer Solar System. On 1 January 2019, the New Horizons spacecraft flew close to (486958) 2014 MU69, a cold classical Kuiper Belt object approximately 30 kilometers in diameter. Such objects have never been substantially heated by the Sun and are therefore well preserved since their formation. We describe initial results from these encounter observations. MU69 is a bilobed contact binary with a flattened shape, discrete geological units, and noticeable albedo heterogeneity. However, there is little surface color or compositional heterogeneity. No evidence for satellites, rings or other dust structures, a gas coma, or solar wind interactions was detected. MU69’s origin appears consistent with pebble cloud collapse followed by a low-velocity merger of its two lobes.
      Keywords: Online Only, Planetary Science
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aaw9771
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Two threats to U.S. science
    • Authors: Alberts, B; Narayanamurti, V.
      Pages: 613 - 613
      Keywords: Editorials
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aax9846
      Issue No: Vol. 364, No. 6441 (2019)
       
  • News at a glance
    • Pages: 614 - 615
      Keywords: Scientific Community
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.614
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Vanishing Bering Sea ice poses climate puzzle
    • Authors: Cornwall W.
      Pages: 616 - 617
      Keywords: Ecology, Oceanography
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.616
      Issue No: Vol. 364, No. 6441 (2019)
       
  • African swine fever marches across much of Asia
    • Authors: Normile D.
      Pages: 617 - 618
      Keywords: Animal Behavior, Asia/Pacific News
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.617
      Issue No: Vol. 364, No. 6441 (2019)
       
  • European Commission kills billion-euro flagship concept
    • Authors: Kupferschmidt K.
      Pages: 618 - 619
      Keywords: European News, Scientific Community
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.618
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Facing Plan S, publishers may set papers free
    • Authors: Brainard J.
      Pages: 620 - 620
      Keywords: Scientific Community
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.620
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Climate scientists say no to flying
    • Authors: Langin K.
      Pages: 621 - 621
      Keywords: Scientific Community
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.621
      Issue No: Vol. 364, No. 6441 (2019)
       
  • They persisted
    • Authors: Talpos S.
      Pages: 622 - 626
      Keywords: Ecology, Scientific Community
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.622
      Issue No: Vol. 364, No. 6441 (2019)
       
  • When science and politics collide: Enhancing the FDA
    • Authors: Adashi, E. Y; Rajan, R. S, Cohen, I. G.
      Pages: 628 - 631
      Keywords: Medicine, Diseases
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aaw8093
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Putting sugars under strain
    • Authors: Pohl N.
      Pages: 631 - 632
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aax3501
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Absolute structure, at the nanoscale
    • Authors: Xu, H; Zou, X.
      Pages: 632 - 633
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aax5385
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Restoring tumor suppression
    • Authors: Parsons R.
      Pages: 633 - 634
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aax5526
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Curbing the costs of chemical manufacturing
    • Authors: Caille S.
      Pages: 635 - 635
      Keywords: Chemistry
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aax2613
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Senolytic therapies for healthy longevity
    • Authors: van Deursen J. M.
      Pages: 636 - 637
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aaw1299
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Sydney Brenner (1927-2019)
    • Authors: Kenyon C.
      Pages: 638 - 638
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aax8563
      Issue No: Vol. 364, No. 6441 (2019)
       
  • An exhibition fit for a king
    • Authors: Black R.
      Pages: 639 - 639
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aax3716
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Exploitation and extraction
    • Authors: Hudson-Edwards K.
      Pages: 640 - 640
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aaw9397
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Fund U.S. veteran toxic exposure database
    • Authors: Small D. S.
      Pages: 642 - 642
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aax5077
      Issue No: Vol. 364, No. 6441 (2019)
       
  • NextGen Voices: Submit Now
    • Pages: 642 - 642
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.642-b
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Improving political deliberation
    • Authors: Castree N.
      Pages: 642 - 643
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aax4542
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Improving political deliberation--Response
    • Authors: Bächtiger, A; Dryzek, J.
      Pages: 643 - 643
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aax5038
      Issue No: Vol. 364, No. 6441 (2019)
       
  • A tale of tadpole tail regeneration
    • Authors: Purnell B. A.
      Pages: 645 - 645
      Keywords: Cell Biology, Development
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.645-a
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Visualizing superexchange interactions
    • Authors: Szuromi P.
      Pages: 645 - 645
      Keywords: Chemistry, Physics
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.645-b
      Issue No: Vol. 364, No. 6441 (2019)
       
  • The brain circuits of strategic decisions
    • Authors: Stern P.
      Pages: 645 - 645
      Keywords: Neuroscience
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.645-c
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Brain cell transcriptomes in autism
    • Authors: Hines P. J.
      Pages: 645 - 645
      Keywords: Development, Medicine, Diseases, Neuroscience
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.645-d
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Dynamical refinement spots a difference
    • Authors: Funk M. A.
      Pages: 645 - 646
      Keywords: Materials Science, Techniques
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.645-e
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Transport control
    • Authors: Vinson V.
      Pages: 645 - 646
      Keywords: Biochemistry
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.645-f
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Bonding's outer limit
    • Authors: Yeston J.
      Pages: 645 - 646
      Keywords: Physics
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.645-g
      Issue No: Vol. 364, No. 6441 (2019)
       
  • The secret life of cediranib
    • Authors: Nusinovich Y.
      Pages: 645 - 646
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.645-h
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Supporting tumor suppression
    • Authors: Ray L. B.
      Pages: 645 - 647
      Keywords: Genetics, Medicine, Diseases
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.645-j
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Dynamic metasurfaces
    • Authors: Osborne I. S.
      Pages: 645 - 647
      Keywords: Physics, Applied, Physics
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.645-k
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Local translation in presynaptic terminals
    • Authors: Hurtley S. M.
      Pages: 645 - 647
      Keywords: Cell Biology, Neuroscience
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.645-l
      Issue No: Vol. 364, No. 6441 (2019)
       
  • New Horizons flies past MU69
    • Authors: Smith K. T.
      Pages: 645 - 647
      Keywords: Planetary Science
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.645-m
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Sweet spot for making oligosaccharides
    • Authors: Funk M. A.
      Pages: 645 - 647
      Keywords: Chemistry
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.645-n
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Excising an olefin
    • Authors: Yeston J.
      Pages: 645 - 647
      Keywords: Chemistry
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.645-o
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Machine learning improves hearing aids
    • Authors: Clauset, A; Post, K.
      Pages: 645 - 647
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.645-p
      Issue No: Vol. 364, No. 6441 (2019)
       
  • BCAPing inflammasome activation
    • Authors: Williams E.
      Pages: 645 - 647
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.645-q
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Designed to respond
    • Authors: Vinson V.
      Pages: 645 - 647
      Keywords: Biochemistry, Molecular Biology
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.645-r
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Agents for healthful aging
    • Authors: Alderton G.
      Pages: 645 - 647
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.645-s
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Interferometry spots an exoplanet
    • Authors: Smith K. T.
      Pages: 646 - 647
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.646-a
      Issue No: Vol. 364, No. 6441 (2019)
       
  • DNA damage and parental age
    • Authors: Zahn L. M.
      Pages: 646 - 646
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.646-b
      Issue No: Vol. 364, No. 6441 (2019)
       
  • A pharmacological hat trick
    • Authors: Kiberstis P. A.
      Pages: 646 - 646
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.646-c
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Superresolving atomic densities
    • Authors: Stajic J.
      Pages: 646 - 647
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.646-d
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Size matters
    • Authors: Vignieri S.
      Pages: 646 - 647
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.646-e
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Training for cognitive skills
    • Authors: Hines P. J.
      Pages: 646 - 647
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.646-f
      Issue No: Vol. 364, No. 6441 (2019)
       
  • UV light as your guide
    • Authors: Lavine M. S.
      Pages: 646 - 647
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.646-g
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Identification of a regeneration-organizing cell in the Xenopus tail
    • Authors: Aztekin, C; Hiscock, T. W, Marioni, J. C, Gurdon, J. B, Simons, B. D, Jullien, J.
      Pages: 653 - 658
      Abstract: Unlike mammals, Xenopus laevis tadpoles have a high regenerative potential. To characterize this regenerative response, we performed single-cell RNA sequencing after tail amputation. By comparing naturally occurring regeneration-competent and -incompetent tadpoles, we identified a previously unrecognized cell type, which we term the regeneration-organizing cell (ROC). ROCs are present in the epidermis during normal tail development and specifically relocalize to the amputation plane of regeneration-competent tadpoles, forming the wound epidermis. Genetic ablation or manual removal of ROCs blocks regeneration, whereas transplantation of ROC-containing grafts induces ectopic outgrowths in early embryos. Transcriptional profiling revealed that ROCs secrete ligands associated with key regenerative pathways, signaling to progenitors to reconstitute lost tissue. These findings reveal the cellular mechanism through which ROCs form the wound epidermis and ensure successful regeneration.
      Keywords: Cell Biology, Development
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aav9996
      Issue No: Vol. 364, No. 6441 (2019)
       
  • De novo design of tunable, pH-driven conformational changes
    • Authors: Boyken, S. E; Benhaim, M. A, Busch, F, Jia, M, Bick, M. J, Choi, H, Klima, J. C, Chen, Z, Walkey, C, Mileant, A, Sahasrabuddhe, A, Wei, K. Y, Hodge, E. A, Byron, S, Quijano-Rubio, A, Sankaran, B, King, N. P, Lippincott-Schwartz, J, Wysocki, V. H, Lee, K. K, Baker, D.
      Pages: 658 - 664
      Abstract: The ability of naturally occurring proteins to change conformation in response to environmental changes is critical to biological function. Although there have been advances in the de novo design of stable proteins with a single, deep free-energy minimum, the design of conformational switches remains challenging. We present a general strategy to design pH-responsive protein conformational changes by precisely preorganizing histidine residues in buried hydrogen-bond networks. We design homotrimers and heterodimers that are stable above pH 6.5 but undergo cooperative, large-scale conformational changes when the pH is lowered and electrostatic and steric repulsion builds up as the network histidine residues become protonated. The transition pH and cooperativity can be controlled through the number of histidine-containing networks and the strength of the surrounding hydrophobic interactions. Upon disassembly, the designed proteins disrupt lipid membranes both in vitro and after being endocytosed in mammalian cells. Our results demonstrate that environmentally triggered conformational changes can now be programmed by de novo protein design.
      Keywords: Biochemistry, Molecular Biology
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aav7897
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Quantum gas microscopy of Rydberg macrodimers
    • Authors: Hollerith, S; Zeiher, J, Rui, J, Rubio-Abadal, A, Walther, V, Pohl, T, Stamper-Kurn, D. M, Bloch, I, Gross, C.
      Pages: 664 - 667
      Abstract: The subnanoscale size of typical diatomic molecules hinders direct optical access to their constituents. Rydberg macrodimers—bound states of two highly excited Rydberg atoms—feature interatomic distances easily exceeding optical wavelengths. We report the direct microscopic observation and detailed characterization of such molecules in a gas of ultracold rubidium atoms in an optical lattice. The bond length of about 0.7 micrometers, comparable to the size of small bacteria, matches the diagonal distance of the lattice. By exciting pairs in the initial two-dimensional atom array, we resolved more than 50 vibrational resonances. Using our spatially resolved detection, we observed the macrodimers by correlated atom loss and demonstrated control of the molecular alignment by the choice of the vibrational state. Our results allow for rigorous testing of Rydberg interaction potentials and highlight the potential of quantum gas microscopy for molecular physics.
      Keywords: Physics
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aaw4150
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Electron diffraction determines molecular absolute configuration in a
           pharmaceutical nanocrystal
    • Authors: Brazda, P; Palatinus, L, Babor, M.
      Pages: 667 - 669
      Abstract: Determination of the absolute configuration of organic molecules is essential in drug development and the subsequent approval process. We show that this determination is possible through electron diffraction using nanocrystalline material. Ab initio structure determination by electron diffraction has so far been limited to compounds that maintain their crystallinity after a dose of one electron per square angstrom or more. We present a complete structure analysis of a pharmaceutical cocrystal of sofosbuvir and l-proline, which is about one order of magnitude less stable. Data collection on multiple positions of a crystal and an advanced-intensity extraction procedure enabled us to solve the structure ab initio. We further show that dynamical diffraction effects are strong enough to permit unambiguous determination of the absolute structure of material composed of light scatterers.
      Keywords: Materials Science, Techniques
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aaw2560
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Probing and imaging spin interactions with a magnetic single-molecule
           sensor
    • Authors: Czap, G; Wagner, P. J, Xue, F, Gu, L, Li, J, Yao, J, Wu, R, Ho, W.
      Pages: 670 - 673
      Abstract: Magnetic single atoms and molecules are receiving intensifying research focus because of their potential as the smallest possible memory, spintronic, and qubit elements. Scanning probe microscopes used to study these systems have benefited greatly from new techniques that use molecule-functionalized tips to enhance spatial and spectroscopic resolutions and enable new sensing capabilities. We demonstrate a microscopy technique that uses a magnetic molecule, Ni(cyclopentadienyl)2, adsorbed at the apex of a scanning probe tip, to sense exchange interactions with another molecule adsorbed on a Ag(110) surface in a continuously tunable fashion in all three spatial directions. We further used the probe to image contours of exchange interaction strength, revealing angstrom-scale regions where the quantum states of two magnetic molecules strongly mix. Our results pave the way for new nanoscale imaging capabilities based on magnetic single-molecule sensors.
      Keywords: Chemistry, Physics
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aaw7505
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Conformationally supple glucose monomers enable synthesis of the smallest
           cyclodextrins
    • Authors: Ikuta, D; Hirata, Y, Wakamori, S, Shimada, H, Tomabechi, Y, Kawasaki, Y, Ikeuchi, K, Hagimori, T, Matsumoto, S, Yamada, H.
      Pages: 674 - 677
      Abstract: Cyclodextrins (CDs) are cyclic oligomers of α-1,4-d-glucopyranoside and are known mainly as hexamers to octamers. The central cavities of CDs can retain small molecules, enabling diverse applications. The smallest members, CD3 and CD4, have ring sizes too small to permit the most stable conformations of glucopyranose and have not been accessible synthetically. In this study, we present methods to chemically synthesize both CD3 and CD4. The main factor in the successful synthesis is the creation of a glucopyranose ring conformationally counterbalanced between equatorial- and axial-rich forms. This suppleness is imparted by a bridge between O-3 and O-6 of glucose, which enables the generation of desirable, albeit deformed, conformers when synthesizing the cyclic trimer and tetramer.
      Keywords: Chemistry
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aaw3053
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Constrained sialic acid donors enable selective synthesis of
           {alpha}-glycosides
    • Authors: Komura, N; Kato, K, Udagawa, T, Asano, S, Tanaka, H.-N, Imamura, A, Ishida, H, Kiso, M, Ando, H.
      Pages: 677 - 680
      Abstract: Sialic acid is a sugar residue present in many biologically significant glycans of mammals, commonly as a terminal α-glycoside. The chemical structure of sialic acid, which features an anomeric center with carboxyl and methylene substituents, poses a challenge for synthesis of the α-glycoside, thus impeding biological and therapeutic studies on sialic acid–containing glycans. We present a robust method for the selective α-glycosidation of sialic acid using macrobicyclized sialic acid donors as synthetic equivalents of structurally constrained oxocarbenium ions to impart stereoselectivity. We demonstrate the power of our method by showcasing broad substrate scope and applicability in the preparation of diverse sialic acid–containing architectures.
      Keywords: Chemistry
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aaw4866
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Hydrodealkenylative C(sp3)-C(sp2) bond fragmentation
    • Authors: Smaligo, A. J; Swain, M, Quintana, J. C, Tan, M. F, Kim, D. A, Kwon, O.
      Pages: 681 - 685
      Abstract: Chemical synthesis typically relies on reactions that generate complexity through elaboration of simple starting materials. Less common are deconstructive strategies toward complexity—particularly those involving carbon-carbon bond scission. Here, we introduce one such transformation: the hydrodealkenylative cleavage of C(sp3)–C(sp2) bonds, conducted below room temperature, using ozone, an iron salt, and a hydrogen atom donor. These reactions are performed in nonanhydrous solvents and open to the air; reach completion within 30 minutes; and deliver their products in high yields, even on decagram scales. We have used this broadly functionality tolerant transformation to produce desirable synthetic intermediates, many of which are optically active, from abundantly available terpenes and terpenoid-derived precursors. We have also applied it in the formal total syntheses of complex molecules.
      Keywords: Chemistry
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aaw4212
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Single-cell genomics identifies cell type-specific molecular changes in
           autism
    • Authors: Velmeshev, D; Schirmer, L, Jung, D, Haeussler, M, Perez, Y, Mayer, S, Bhaduri, A, Goyal, N, Rowitch, D. H, Kriegstein, A. R.
      Pages: 685 - 689
      Abstract: Despite the clinical and genetic heterogeneity of autism, bulk gene expression studies show that changes in the neocortex of autism patients converge on common genes and pathways. However, direct assessment of specific cell types in the brain affected by autism has not been feasible until recently. We used single-nucleus RNA sequencing of cortical tissue from patients with autism to identify autism-associated transcriptomic changes in specific cell types. We found that synaptic signaling of upper-layer excitatory neurons and the molecular state of microglia are preferentially affected in autism. Moreover, our results show that dysregulation of specific groups of genes in cortico-cortical projection neurons correlates with clinical severity of autism. These findings suggest that molecular changes in upper-layer cortical circuits are linked to behavioral manifestations of autism.
      Keywords: Development, Medicine, Diseases, Neuroscience
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aav8130
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Mechanism of allosteric modulation of P-glycoprotein by transport
           substrates and inhibitors
    • Authors: Dastvan, R; Mishra, S, Peskova, Y. B, Nakamoto, R. K, Mchaourab, H. S.
      Pages: 689 - 692
      Abstract: The ATP-binding cassette subfamily B member 1 (ABCB1) multidrug transporter P-glycoprotein plays a central role in clearance of xenobiotics in humans and is implicated in cancer resistance to chemotherapy. We used double electron electron resonance spectroscopy to uncover the basis of stimulation of P-glycoprotein adenosine 5'-triphosphate (ATP) hydrolysis by multiple substrates and illuminate how substrates and inhibitors differentially affect its transport function. Our results reveal that substrate-induced acceleration of ATP hydrolysis correlates with stabilization of a high-energy, post-ATP hydrolysis state characterized by structurally asymmetric nucleotide-binding sites. By contrast, this state is destabilized in the substrate-free cycle and by high-affinity inhibitors in favor of structurally symmetric nucleotide binding sites. Together with previous data, our findings lead to a general model of substrate and inhibitor coupling to P-glycoprotein.
      Keywords: Biochemistry
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.aav9406
      Issue No: Vol. 364, No. 6441 (2019)
       
  • New Products
    • Pages: 696 - 696
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.696-a
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Technology Feature Epitranscriptomics: RNA revisited
    • Authors: Schubert C.
      Pages: 696 - 696
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.696-b
      Issue No: Vol. 364, No. 6441 (2019)
       
  • Uncovering the hidden curriculum
    • Authors: Hariharan J.
      Pages: 702 - 702
      PubDate: 2019-05-16T10:43:48-07:00
      DOI: 10.1126/science.364.6441.702
      Issue No: Vol. 364, No. 6441 (2019)
       
 
 
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