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R E Evans, M K Bhaskar, D D Sukachev, C T Nguyen, A Sipahigil, M J Burek, B Machielse, G H Zhang, A S Zibrov, E Bielejec, H Park, M Lončar, M D Lukin
Photon-mediated interactions between quantum systems are essential for realizing quantum networks and scalable quantum information processing. We demonstrate such interactions between pairs of silicon-vacancy (SiV) color centers coupled to a diamond nanophotonic cavity. When the optical transitions of the two color centers are tuned into resonance, the coupling to the common cavity mode results in a coherent interaction between them, leading to spectrally-resolved superradiant and subradiant states. We use the electronic spin degrees of freedom of the SiV centers to control these optically-mediated interactions...
September 20, 2018: Science
Chika Yamashiro, Kotaro Sasaki, Yukihiro Yabuta, Yoji Kojima, Tomonori Nakamura, Ikuhiro Okamoto, Shihori Yokobayashi, Yusuke Murase, Yukiko Ishikura, Kenjiro Shirane, Hiroyuki Sasaki, Takuya Yamamoto, Mitinori Saitou
Human in vitro gametogenesis may transform reproductive medicine. Human pluripotent stem cells (hPSCs) have been induced into primordial germ cell-like cells (hPGCLCs); however, further differentiation to a mature germ cell has not been achieved. Here, we show that hPGCLCs differentiate progressively into oogonia-like cells during a long-term in vitro culture (~four months) in xenogeneic reconstituted ovaries with mouse embryonic ovarian somatic cells. The hPGCLC-derived oogonia display hallmarks of epigenetic reprogramming, i...
September 20, 2018: Science
Shibin Zhao, Tobias Gensch, Benjamin Murray, Zachary L Niemeyer, Matthew S Sigman, Mark R Biscoe
Despite the enormous potential for the use of stereospecific cross-coupling reactions to rationally manipulate the three-dimensional structure of organic molecules, the factors that control the transfer of stereochemistry in these reactions remain poorly understood. Herein we report a mechanistic and synthetic investigation into the use of enantioenriched alkylboron nucleophiles in stereospecific Pd-catalyzed Suzuki cross-coupling reactions. By developing a suite of molecular descriptors of phosphine ligands, we could apply predictive statistical models to select or design distinct ligands that respectively promoted stereoinvertive and stereoretentive cross-coupling reactions...
September 20, 2018: Science
David J F Ramrath, Moritz Niemann, Marc Leibundgut, Philipp Bieri, Céline Prange, Elke K Horn, Alexander Leitner, Daniel Boehringer, André Schneider, Nenad Ban
Ribosomal RNA (rRNA) plays key functional and architectural roles in ribosomes. Using electron microscopy, we determined the atomic structure of a highly divergent ribosome found in mitochondria of Trypanosoma brucei, a unicellular parasite that causes sleeping sickness in humans. The trypanosomal mitoribosome features the smallest rRNAs and contains more proteins than all known ribosomes. The structure shows how the proteins have taken over the role of architectural scaffold from the rRNA: they form an autonomous outer shell that surrounds the entire particle and stabilizes and positions the functionally important regions of the rRNA...
September 13, 2018: Science
Nako Nakatsuka, Kyung-Ae Yang, John M Abendroth, Kevin Cheung, Xiaobin Xu, Hongyan Yang, Chuanzhen Zhao, Bowen Zhu, You Seung Rim, Yang Yang, Paul S Weiss, Milan N Stojanović, Anne M Andrews
Detection of analytes with field-effect transistors bearing ligand-specific receptors is fundamentally limited by the shielding created by the electrical double layer (the "Debye length" limitation). We detected small molecules under physiological high ionic-strength conditions by modifying printed ultrathin metal-oxide field-effect transistor arrays with deoxyribonucleotide aptamers selected to bind their targets adaptively. Target-induced conformational changes of negatively charged aptamer phosphodiester backbones in close proximity to semiconductor channels gated conductance in physiological buffers, resulting in highly sensitive detection...
September 6, 2018: Science
Elijah L Mena, Rachel A S Kjolby, Robert A Saxton, Achim Werner, Brandon G Lew, John M Boyle, Richard Harland, Michael Rape
Aberrant complex formation by recurrent interaction modules, such as BTB domains, leucine zippers, or coiled coils, can disrupt signal transduction, yet whether cells detect and eliminate complexes of irregular composition is unknown. By searching for regulators of the BTB family, we discovered a quality control pathway that ensures functional dimerization ( d imerization q uality c ontrol, DQC). Key to this network is the E3 ligase SCFFBXL17 , which selectively binds and ubiquitylates BTB dimers of aberrant composition to trigger their clearance by proteasomal degradation...
September 6, 2018: Science
Xiaojing Pan, Zhangqiang Li, Qiang Zhou, Huaizong Shen, Kun Wu, Xiaoshuang Huang, Jiaofeng Chen, Juanrong Zhang, Xuechen Zhu, Jianlin Lei, Wei Xiong, Haipeng Gong, Bailong Xiao, Nieng Yan
Voltage-gated sodium channels, which are responsible for action potential generation, are implicated in many human diseases. Despite decades of rigorous characterization, the lack of a structure of any human Nav channel has hampered mechanistic understanding. Here we report the cryo-EM structure of human Nav 1.4-β1 complex at 3.2 Å resolution. Accurate model building was made for the pore domain, the voltage-sensing domains, and the β1 subunit, giving insight into the molecular basis for Na+ permeation and kinetic asymmetry of the four repeats...
September 6, 2018: Science
Nicole D Marino, Jenny Y Zhang, Adair L Borges, Alexander A Sousa, Lina M Leon, Benjamin J Rauch, Russell T Walton, Joel D Berry, J Keith Joung, Benjamin P Kleinstiver, Joseph Bondy-Denomy
Bacterial CRISPR-Cas systems protect their host from bacteriophages and other mobile genetic elements. Mobile elements, in turn, encode various anti-CRISPR (Acr) proteins to inhibit the immune function of CRISPR-Cas. To date, Acr proteins have been discovered for type I (subtypes I-D, I-E, and I-F) and type II (II-A and II-C) but not other CRISPR systems. Here we report the discovery of 12 acr genes, including inhibitors of type V-A and I-C CRISPR systems. Notably, AcrVA1 inhibits a broad spectrum of Cas12a (Cpf1) orthologs including MbCas12a, Mb3Cas12a, AsCas12a, and LbCas12a when assayed in human cells...
September 6, 2018: Science
Kyle E Watters, Christof Fellmann, Hua B Bai, Shawn M Ren, Jennifer A Doudna
Cas12a (Cpf1) is a CRISPR-associated nuclease with broad utility for synthetic genome engineering, agricultural genomics, and biomedical applications. While bacteria harboring CRISPR-Cas9 or CRISPR-Cas3 adaptive immune systems sometimes acquire mobile genetic elements encoding anti-CRISPR proteins that inhibit Cas9, Cas3, or the DNA-binding Cascade complex, no such inhibitors have been found for CRISPR-Cas12a. Here we employ a comprehensive bioinformatic and experimental screening approach to identify three different inhibitors that block or diminish CRISPR-Cas12a-mediated genome editing in human cells...
September 6, 2018: Science
Junyue Cao, Darren A Cusanovich, Vijay Ramani, Delasa Aghamirzaie, Hannah A Pliner, Andrew J Hill, Riza M Daza, Jose L McFaline-Figueroa, Jonathan S Packer, Lena Christiansen, Frank J Steemers, Andrew C Adey, Cole Trapnell, Jay Shendure
Although we can increasingly measure transcription, chromatin, methylation, etc. at single cell resolution, most assays survey only one aspect of cellular biology. Here we describe sci-CAR, a combinatorial indexing-based co-assay that jointly profiles <u>c</u>hromatin <u>a</u>ccessibility and m<u>R</u>NA in each of thousands of single cells. As a proof-of-concept, we apply sci-CAR to 4,825 cells comprising a time-series of dexamethasone treatment, as well as to 11,296 cells from the adult mouse kidney...
August 30, 2018: Science
Leonela Amoasii, John C W Hildyard, Hui Li, Efrain Sanchez-Ortiz, Alex Mireault, Daniel Caballero, Rachel Harron, Thaleia-Rengina Stathopoulou, Claire Massey, John M Shelton, Rhonda Bassel-Duby, Richard J Piercy, Eric N Olson
Mutations in the gene encoding dystrophin, a protein that maintains muscle integrity and function, cause Duchenne muscular dystrophy (DMD). The deltaE50-MD dog model of DMD harbors a mutation corresponding to a mutational "hot spot" in the human DMD gene. We used adeno-associated viruses to deliver CRISPR gene editing components to four dogs and examined dystrophin protein expression 6 weeks after intramuscular delivery (n=2) or 8 weeks after systemic delivery (n=2). After systemic delivery in skeletal muscle, dystrophin was restored to levels ranging from 3 to 90% of normal, depending on muscle type...
August 30, 2018: Science
Z Xiang, Y Kasahara, T Asaba, B Lawson, C Tinsman, Lu Chen, K Sugimoto, S Kawaguchi, Y Sato, G Li, S Yao, Y L Chen, F Iga, John Singleton, Y Matsuda, Lu Li
In metals, orbital motions of conduction electrons on the Fermi surface are quantized in magnetic fields, which is manifested by quantum oscillations in electrical resistivity. This Landau quantization is generally absent in insulators. Here we report a notable exception in an insulator - ytterbium dodecaboride (YbB12 ). The resistivity of YbB12 , which is of a much larger magnitude than the resistivity in metals, exhibits distinct quantum oscillations. These unconventional oscillations arise from the insulating bulk, even though the temperature dependence of the oscillation amplitude follows the conventional Fermi liquid theory of metals with a large effective mass...
August 30, 2018: Science
Daniela Tsikou, Zhe Yan, Dennis B Holt, Nikolaj B Abel, Dugald E Reid, Lene H Madsen, Hemal Bhasin, Moritz Sexauer, Jens Stougaard, Katharina Markmann
Nitrogen-fixing root nodules on legumes result from two developmental processes, bacterial infection and nodule organogenesis. To balance symbiosis and plant growth, legume hosts restrict nodule numbers through an inducible autoregulatory process. Here, we present a mechanism where repression of a negative regulator ensures symbiotic susceptibility of uninfected roots of the host Lotus japonicus We show that microRNA miR2111 undergoes shoot-to-root translocation to control rhizobial infection through posttranscriptional regulation of the symbiosis suppressor TOO MUCH LOVE in roots...
August 30, 2018: Science
Li Guo, Thilo Winzer, Xiaofei Yang, Yi Li, Zemin Ning, Zhesi He, Roxana Teodor, Ying Lu, Tim A Bowser, Ian A Graham, Kai Ye
Morphinan-based painkillers are derived from opium poppy. We report a draft of the opium poppy genome, with 2.72 Gb assembled into 11 chromosomes with contig N50 and scaffold N50 of 1.77 Mb and 204 Mb, respectively. Synteny analysis suggests a whole genome duplication at approximately 7.8 million years ago (MYA) and ancient segmental or whole genome duplication(s) that occurred before the Papaveraceae-Ranunculaceae divergence 110 MYA. Syntenic blocks representative of phthalideisoquinoline and morphinan components of a benzylisoquinoline alkaloid cluster of 15 genes provides insight into how it evolved...
August 30, 2018: Science
Vitor Onuchic, Eugene Lurie, Ivenise Carrero, Piotr Pawliczek, Ronak Y Patel, Joel Rozowsky, Timur Galeev, Zhuoyi Huang, Robert C Altshuler, Zhizhuo Zhang, R Alan Harris, Cristian Coarfa, Lillian Ashmore, Jessica W Bertol, Walid D Fakhouri, Fuli Yu, Manolis Kellis, Mark Gerstein, Aleksandar Milosavljevic
To assess the impact of genetic variation in regulatory loci on human health, we construct a high-resolution map of allelic imbalances in DNA methylation, histone marks, and gene transcription in 71 epigenomes from 36 distinct cell and tissue types from 13 donors. Deep whole-genome bisulfite sequencing of 49 methylomes reveals sequence-dependent CpG methylation imbalances at thousands of heterozygous regulatory loci. Such loci are enriched for stochastic switching, defined as random transitions between fully methylated and unmethylated states of DNA...
August 23, 2018: Science
Xiaofeng Qi, Philip Schmiege, Elias Coutavas, Xiaochun Li
Aberrant Hedgehog (HH) signaling leads to various types of cancer and birth defects. N-terminally palmitoylated HH initiates signaling by binding its receptor Patched-1 (PTCH1). A recent 1:1 PTCH1-HH complex structure visualized a palmitate-mediated binding site on HH, which was inconsistent with previous studies that implied a distinct, calcium-mediated binding site for PTCH1 and HH co-receptors. Here, our 3.5-Å resolution cryo-EM structure of native Sonic Hedgehog (SHH-N) in complex with PTCH1 at a physiological calcium concentration reconciles these disparate findings and demonstrates that one SHH-N molecule engages both epitopes to bind two PTCH1 receptors in an asymmetric manner...
August 23, 2018: Science
Nataliya Petryk, Maria Dalby, Alice Wenger, Caroline B Stromme, Anne Strandsby, Robin Andersson, Anja Groth
During genome replication, parental histones are recycled to newly replicated DNA with their posttranslational modifications (PTMs). It remains unknown whether sister chromatids inherit modified histones evenly. Here, we measured histone PTM partition to sister chromatids in embryonic stem cells. We found that parental histones H3-H4 segregate to both daughter DNA strands with a weak leading strand bias, skewing partition at topologically associating domain (TAD) borders and enhancers proximal to replication initiation zones...
August 16, 2018: Science
Chuanhe Yu, Haiyun Gan, Albert Serra-Cardona, Lin Zhang, Songlin Gan, Sushma Sharma, Erik Johansson, Andrei Chabes, Rui-Ming Xu, Zhiguo Zhang
How parental histone (H3-H4)2 tetramers, the primary carriers of epigenetic modifications, are transferred onto leading and lagging strands of DNA replication forks for epigenetic inheritance remains elusive. Here we show that parental (H3-H4)2 tetramers are assembled into nucleosomes onto both leading and lagging strands, with a slight preference for lagging strands. The lagging strand preference increases markedly in cells lacking Dpb3 and Dpb4, two subunits of the leading strand DNA polymerase, Pol ε, due to the impairment of parental (H3-H4)2 transfer to leading strands...
August 16, 2018: Science
Dongfei Wang, Lingyuan Kong, Peng Fan, Hui Chen, Shiyu Zhu, Wenyao Liu, Lu Cao, Yujie Sun, Shixuan Du, John Schneeloch, Ruidan Zhong, Genda Gu, Liang Fu, Hong Ding, Hong-Jun Gao
The search for Majorana bound states (MBSs) has been fueled by the prospect of using their non-Abelian statistics for robust quantum computation. Two-dimensional superconducting topological materials have been predicted to host MBSs as zero-energy modes in vortex cores. By using scanning tunneling spectroscopy on the superconducting Dirac surface state of the iron-based superconductor FeTe0.55 Se0.45 , we observe a sharp zero-bias peak inside a vortex core that does not split when moving away from the vortex center...
August 16, 2018: Science
Gavin P Hayes, Ginevra L Moore, Daniel E Portner, Mike Hearne, Hanna Flamme, Maria Furtney, Gregory M Smoczyk
Subduction zones are home to the most seismically active faults on the planet. The shallow megathrust interfaces of subduction zones host our largest earthquakes and are likely the only faults capable of magnitude 9+ ruptures. Despite these facts, our knowledge of subduction zone geometry-which likely plays a key role in determining the spatial extent and ultimately the size of subduction zone earthquakes-is incomplete. We calculated the three-dimensional geometries of all seismically active global subduction zones...
August 9, 2018: Science
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