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Ferdinand Huber, Julian Berwanger, Svitlana Polesya, Sergiy Mankovsky, Hubert Ebert, Franz J Giessibl
Surface molecules can transition from physisorption through weak van-der-Waals forces to a strongly bound chemisorption state by overcoming an energy barrier. We show that a CO molecule adsorbed to the tip of an atomic force microscope enables a controlled observation of bond formation, including its potential transition from physisorption to chemisorption. During imaging of Cu and Fe adatoms on a Cu(111) surface, the CO was not chemically inert but transited through a physisorbed local energy minimum into a chemisorbed global minimum, and an energy barrier was seen for the Fe adatom...
September 12, 2019: Science
#2
Matthew A Norcia, Aaron W Young, William J Eckner, Eric Oelker, Jun Ye, Adam M Kaufman
Coherent control of high-quality-factor optical transitions in atoms has revolutionized precision frequency metrology. Leading optical atomic clocks rely on the interrogation of such transitions in either single ions or ensembles of neutral atoms to stabilize a laser frequency at high precision and accuracy. Here, we demonstrate a platform that combines key strengths of these two leading approaches, based on arrays of individual strontium atoms held within optical tweezers. We report coherence times of 3.4 s, single-ensemble duty cycles up to 96% through repeated interrogation, and 4...
September 12, 2019: Science
#3
Jonathan S Packer, Qin Zhu, Chau Huynh, Priya Sivaramakrishnan, Elicia Preston, Hannah Dueck, Derek Stefanik, Kai Tan, Cole Trapnell, Junhyong Kim, Robert H Waterston, John I Murray
Caenorhabditis elegans is an animal with few cells, but a striking diversity of cell types. Here, we characterize the molecular basis for their specification by profiling the transcriptomes of 86,024 single embryonic cells. We identify 502 terminal and pre-terminal cell types, mapping most single-cell transcriptomes to their exact position in C. elegans ' invariant lineage. Using these annotations, we find that: 1) the correlation between a cell's lineage and its transcriptome increases from mid to late gastrulation, then falls dramatically as cells in the nervous system and pharynx adopt their terminal fates; 2) multilineage priming contributes to the differentiation of sister cells at dozens of lineage branches; and 3) most distinct lineages that produce the same anatomical cell type converge to a homogenous transcriptomic state...
September 5, 2019: Science
#4
M Agostini, A M Bakalyarov, M Balata, I Barabanov, L Baudis, C Bauer, E Bellotti, S Belogurov, A Bettini, L Bezrukov, D Borowicz, V Brudanin, R Brugnera, A Caldwell, C Cattadori, A Chernogorov, T Comellato, V D'Andrea, E V Demidova, N DiMarco, A Domula, E Doroshkevich, V Egorov, R Falkenstein, M Fomina, A Gangapshev, A Garfagnini, M Giordano, P Grabmayr, V Gurentsov, K Gusev, J Hakenmüller, A Hegai, M Heisel, S Hemmer, R Hiller, W Hofmann, M Hult, L V Inzhechik, J Janicskó Csáthy, J Jochum, M Junker, V Kazalov, Y Kermaïdic, T Kihm, I V Kirpichnikov, A Kirsch, A Kish, A Klimenko, R Kneißl, K T Knöpfle, O Kochetov, V N Kornoukhov, P Krause, V V Kuzminov, M Laubenstein, A Lazzaro, M Lindner, I Lippi, A Lubashevskiy, B Lubsandorzhiev, G Lutter, C Macolino, B Majorovits, W Maneschg, M Miloradovic, R Mingazheva, M Misiaszek, P Moseev, I Nemchenok, K Panas, L Pandola, K Pelczar, L Pertoldi, P Piseri, A Pullia, C Ransom, S Riboldi, N Rumyantseva, C Sada, E Sala, F Salamida, C Schmitt, B Schneider, S Schönert, A-K Schütz, O Schulz, M Schwarz, B Schwingenheuer, O Selivanenko, E Shevchik, M Shirchenko, H Simgen, A Smolnikov, L Stanco, D Stukov, L Vanhoefer, A A Vasenko, A Veresnikova, K von Sturm, V Wagner, A Wegmann, T Wester, C Wiesinger, M Wojcik, E Yanovich, I Zhitnikov, S V Zhukov, D Zinatulina, A Zschocke, A J Zsigmond, K Zuber, G Zuzel
A discovery that neutrinos are Majorana fermions would have profound implications for particle physics and cosmology. The Majorana character of neutrinos would make possible the neutrinoless double-β (0νββ) decay, a matter-creating process without the balancing emission of antimatter. The Gerda collaboration searches for the 0νββ decay of 76 Ge by operating bare germanium detectors in an active liquid argon shield. With a total exposure of 82.4 kg ⋅ yr, we observe no signal and derive a lower half-life limit of T 1/2 > 0...
September 5, 2019: Science
#5
REVIEW
Yuval Eshed, Zachary B Lippman
The dominance of the major crops that feed humans and their livestock arose from agricultural revolutions that increased productivity and adapted plants to large-scale farming practices. Two hormone systems that universally control flowering and plant architecture, florigen and gibberellin, were the source of multiple revolutions that modified reproductive transitions and proportional growth among plant parts. While step-changes based on serendipitous mutations in these hormone systems laid the foundation, genetic and agronomic tuning was required for broad agricultural benefits...
September 5, 2019: Science
#6
Haifeng Wang, Muneaki Nakamura, Timothy R Abbott, Dehua Zhao, Kaiwen Luo, Cordelia Yu, Cindy M Nguyen, Albert Lo, Timothy P Daley, Marie La Russa, Yanxia Liu, Lei S Qi
We report a robust, versatile approach named CRISPR Live-cell fluorescent in situ hybridization (LiveFISH) using fluorescent oligos for genome tracking in broad cell types including primary cells. An intrinsic stability switch of CRISPR guide RNAs enables LiveFISH to accurately detect chromosomal disorders such as Patau Syndrome in prenatal amniotic fluid cells and track multiple loci in human T lymphocytes. In addition, LiveFISH tracks the real-time movement of DNA double-strand breaks induced by CRISPR-Cas9-mediated editing and consequent chromosome translocations...
September 5, 2019: Science
#7
Melinda M Diver, Yifan Cheng, David Julius
TRPM8 is the primary detector of environmental cold and an important target for treating pathological cold hypersensitivity. Here, we present cryo-EM structures of TRPM8 in ligand-free, antagonist- or calcium-bound forms, revealing how robust conformational changes give rise to two non-conducting states, closed and desensitized. We describe a malleable ligand-binding pocket that accommodates drugs of diverse chemical structures, and delineate the ion permeation pathway, including the contribution of lipids to pore architecture...
September 5, 2019: Science
#8
François Legoux, Déborah Bellet, Celine Daviaud, Yara El Morr, Aurelie Darbois, Kristina Niort, Emanuele Procopio, Marion Salou, Jules Gilet, Bernhard Ryffel, Aurélie Balvay, Anne Foussier, Manal Sarkis, Ahmed El Marjou, Frederic Schmidt, Sylvie Rabot, Olivier Lantz
How the microbiota modulate immune functions remains poorly understood. Mucosal-associated invariant T (MAIT) cells are implicated in mucosal homeostasis and absent in germ-free mice. Here, we show that commensal bacteria govern murine MAIT intrathymic development, as MAIT cells did not recirculate to the thymus. MAIT development required RibD expression in bacteria, indicating that production of the MAIT antigen 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU) was necessary. 5-OP-RU rapidly traveled from mucosal surfaces to the thymus, where it was captured by the major histocompatibility complex class Ib molecule MR1...
August 29, 2019: Science
#9
Maleness-on-the-Y ( MoY ) orchestrates male sex determination in major agricultural fruit fly pests.
Angela Meccariello, Marco Salvemini, Pasquale Primo, Brantley Hall, Panagiota Koskinioti, Martina Dalíková, Andrea Gravina, Michela Anna Gucciardino, Federica Forlenza, Maria-Eleni Gregoriou, Domenica Ippolito, Simona Maria Monti, Valeria Petrella, Maryanna Martina Perrotta, Stephan Schmeing, Alessia Ruggiero, Francesca Scolari, Ennio Giordano, Konstantina T Tsoumani, František Marec, Nikolai Windbichler, Kallare P Arunkumar, Kostas Bourtzis, Kostas D Mathiopoulos, Jiannis Ragoussis, Luigi Vitagliano, Zhijian Tu, Philippos Aris Papathanos, Mark D Robinson, Giuseppe Saccone
In insects, rapidly evolving primary sex-determining signals are transduced by a conserved regulatory module controlling sexual differentiation. In the agricultural pest Ceratitis capitata (Mediterranean fruit fly, Medfly) we identified a Y-linked gene, Maleness-on the-Y ( MoY ), encoding a small protein that is necessary and sufficient for male development. Silencing or disruption of MoY in XY embryos causes feminization whereas overexpression of MoY in XX embryos induces masculinization. Crosses between transformed XY females and XX males give rise to males and females, indicating that a Y chromosome can be transmitted by XY females...
August 29, 2019: Science
#10
QuanSheng Wu, Alexey A Soluyanov, Tomáš Bzdušek
ELECTRON ENERGY BANDS OF CRYSTALLINE SOLIDS GENERICALLY EXHIBIT DEGENERACIES CALLED BAND-STRUCTURE NODES HERE, WE INTRODUCE NON-ABELIAN TOPOLOGICAL CHARGES THAT CHARACTERIZE LINE NODES INSIDE THE MOMENTUM SPACE OF:
August 29, 2019: Science
#11
Yang Liu, Yuling You, Zhike Lu, Jiang Yang, Panpan Li, Lun Liu, Henan Xu, Yamei Niu, Xuetao Cao
Host cell metabolism can be modulated by viral infection, affecting viral survival or clearance. The cellular metabolism rewiring mediated by N 6 -methyladenosine (m6 A) modification in virus-host interaction remains largely unknown. Here we report that in response to viral infection, host cells impair the enzymatic activity of RNA m6 A demethylase ALKBH5. This increases the m6 A methylation on α-ketoglutarate dehydrogenase (OGDH) mRNA to reduce its mRNA stability and protein expression. Reduced OGDH decreases the production of metabolite itaconate that is required for viral replication...
August 22, 2019: Science
#12
Keyuan Ding, Jiangjing Wang, Yuxing Zhou, He Tian, Lu Lu, Riccardo Mazzarello, Chunlin Jia, Wei Zhang, Feng Rao, Evan Ma
Artificial intelligence and other data-intensive applications have escalated the demand for data storage and processing. New computing devices, e.g., phase-change random access memory (PCRAM) based neuro-inspired devices, are promising options for breaking the von Neumann barrier by unifying storage with computing in memory cells. However, current PCRAM devices have considerable noise and drift in electrical resistance that erodes the precision and consistency of these devices. We designed a phase-change heterostructure (PCH) consisting of alternately stacked phase-change and confinement nanolayers to suppress the noise and drift, allowing reliable iterative RESET and cumulative SET operations for high-performance neuro-inspired computing...
August 22, 2019: Science
#13
Katharina Kaiser, Lorel M Scriven, Fabian Schulz, Przemyslaw Gawel, Leo Gross, Harry L Anderson
Carbon allotropes built from rings of two-coordinate atoms, known as cyclo[ n ]carbons, have fascinated chemists for many years, but until now they could not be isolated or structurally characterized, due to their high reactivity. We generated cyclo[18]carbon (C18 ) using atom manipulation on bilayer NaCl on Cu(111) at 5 Kelvin by eliminating carbon monoxide from a cyclocarbon oxide molecule C24 O6 Characterization of cyclo[18]carbon by high-resolution atomic force microscopy revealed a polyynic structure with defined positions of alternating triple and single bonds...
August 15, 2019: Science
#14
Dandan Wang, Hannah M Stoveken, Stefano Zucca, Maria Dao, Cesare Orlandi, Chenghui Song, Ikuo Masuho, Caitlin Johnston, Karla J Opperman, Andrew C Giles, Matthew S Gill, Erik A Lundquist, Brock Grill, Kirill A Martemyanov
Opioids target the μ-opioid receptor (MOR) to produce unrivaled pain management but their addictive properties can lead to severe abuse. We developed a whole animal behavioral platform for unbiased discovery of genes influencing opioid responsiveness. Using forward genetics in C. elegans, we identified a conserved orphan receptor, GPR139, with anti-opioid activity. GPR139 is coexpressed with MOR in opioid-sensitive brain circuits, binds to MOR and inhibits signaling to G proteins. Deletion of GPR139 in mice enhanced opioid-induced inhibition of neuronal firing to modulate morphine-induced analgesia, reward, and withdrawal...
August 15, 2019: Science
#15
Masahiro Hiraizumi, Keitaro Yamashita, Tomohiro Nishizawa, Osamu Nureki
In eukaryotic membranes, P4-ATPases mediate the translocation of phospholipids from the outer to inner leaflet and maintain lipid asymmetry, which is critical for membrane trafficking and signaling pathways. Here we report the cryo-EM structures of six distinct intermediates of the human ATP8A1-CDC50a hetero-complex, at 2.6-3.3 Å resolutions, elucidating lipid translocation cycle of this P4-ATPase. ATP-dependent phosphorylation induces a large rotational movement of the actuator domain around the phosphorylation site in the phosphorylation domain, accompanied by lateral shifts of the first and second transmembrane helices, thereby allowing phosphatidylserine binding...
August 15, 2019: Science
#16
Thomas M Norman, Max A Horlbeck, Joseph M Replogle, Alex Y Ge, Albert Xu, Marco Jost, Luke A Gilbert, Jonathan S Weissman
How cellular and organismal complexity emerges from combinatorial expression of genes is a central question in biology. High-content phenotyping approaches such as Perturb-seq (single-cell RNA-seq pooled CRISPR screens) present an opportunity for exploring such genetic interactions (GIs) at scale. Here, we present an analytical framework for interpreting high-dimensional landscapes of cell states (manifolds) constructed from transcriptional phenotypes. We applied this approach to Perturb-seq profiling of strong GIs mined from a growth-based, gain-of-function GI map...
August 8, 2019: Science
#17
Takashi Kurumaji, Taro Nakajima, Max Hirschberger, Akiko Kikkawa, Yuichi Yamasaki, Hajime Sagayama, Hironori Nakao, Yasujiro Taguchi, Taka-Hisa Arima, Yoshinori Tokura
Geometrically frustrated magnets can host complex spin textures, leading to unconventional electromagnetic responses. Magnetic frustration may also promote topologically nontrivial spin states such as magnetic skyrmions. Experimentally, however, skyrmions have largely been observed in noncentrosymmetric lattice structures or interfacial symmetry-breaking heterostructures. Here, we report the emergence of a Bloch-type skyrmion state in a frustrated centrosymmetric triangular-lattice magnet Gd2 PdSi3 We observed a giant topological Hall response, indicating a field-induced skyrmion phase, which is further corroborated by the observation of in-plane spin modulation probed by resonant x-ray scattering...
August 8, 2019: Science
#18
Mengzhao Xue, Chung Sub Kim, Alan R Healy, Kevin M Wernke, Zhixun Wang, Madeline C Frischling, Emilee E Shine, Weiwei Wang, Seth B Herzon, Jason M Crawford
Colibactin is a complex secondary metabolite produced by some genotoxic gut Escherichia coli strains. The presence of colibactin-producing bacteria correlates with the frequency and severity of colorectal cancer in humans. However, because colibactin has not been isolated or structurally characterized, it has been difficult to study physiological effects of colibactin-producing bacteria in the human gut. We use a combination of genetics, isotope labeling, tandem mass spectrometry, and chemical synthesis to deduce the structure of colibactin...
August 8, 2019: Science
#19
Sylvain de Léséleuc, Vincent Lienhard, Pascal Scholl, Daniel Barredo, Sebastian Weber, Nicolai Lang, Hans Peter Büchler, Thierry Lahaye, Antoine Browaeys
The concept of topological phases is a powerful framework to characterize ground states of quantum many-body systems that goes beyond the paradigm of symmetry breaking. Topological phases can appear in condensed matter systems naturally, whereas the implementation and study of such quantum many-body ground states in artificial matter requires careful engineering. Here, we report the experimental realization of a symmetry-protected topological phase of interacting bosons in a one-dimensional lattice, and demonstrate a robust ground state degeneracy attributed to protected zero-energy edge states...
August 1, 2019: Science
#20
Ahmed S Abdelfattah, Takashi Kawashima, Amrita Singh, Ondrej Novak, Hui Liu, Yichun Shuai, Yi-Chieh Huang, Luke Campagnola, Stephanie C Seeman, Jianing Yu, Jihong Zheng, Jonathan B Grimm, Ronak Patel, Johannes Friedrich, Brett D Mensh, Liam Paninski, John J Macklin, Gabe J Murphy, Kaspar Podgorski, Bei-Jung Lin, Tsai-Wen Chen, Glenn C Turner, Zhe Liu, Minoru Koyama, Karel Svoboda, Misha B Ahrens, Luke D Lavis, Eric R Schreiter
Imaging changes in membrane potential using genetically encoded fluorescent voltage indicators (GEVIs) has great potential for monitoring neuronal activity with high spatial and temporal resolution. Brightness and photostability of fluorescent proteins and rhodopsins have limited the utility of existing GEVIs. We engineered a novel GEVI, "Voltron", that utilizes bright and photostable synthetic dyes instead of protein-based fluorophores, extending the combined duration of imaging and number of neurons imaged simultaneously by more than tenfold relative to existing GEVIs...
August 1, 2019: Science
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