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Myoung-Gyun Suh, Qi-Fan Yang, Ki Youl Yang, Xu Yi, Kerry J Vahala
Rapid characterization of optical and vibrational spectra with high resolution can identify species in cluttered environments and is important for assays and early alerts. Dual-comb spectroscopy has emerged as a powerful approach to acquire nearly instantaneous Raman and optical spectra with unprecedented resolution. Spectra are generated directly in the electrical domain and avoid bulky mechanical spectrometers. We demonstrate a miniature soliton-based dual-comb system that can potentially transfer the approach to a chip platform...
October 13, 2016: Science
B Roche, B Arcangioli, R A Martienssen
Quiescent cells play a predominant role in most organisms. Here, we identify RNA interference (RNAi) as a major requirement for quiescence (G0) in Schizosaccharomyces pombe RNAi mutants lose viability at G0-entry and are unable to maintain long-term quiescence. We obtained dcr1Δ G0 suppressors, which mapped to genes involved in chromosome segregation, RNA polymerase-associated factors, and heterochromatin formation. We propose a model in which RNAi promotes RNA polymerase release in cycling and quiescent cells: (i) RNA pol II release mediates heterochromatin formation at centromeres allowing proper chromosome segregation during mitotic growth and G0-entry, and (ii) RNA pol I release prevents heterochromatin formation at rDNA during quiescence maintenance...
October 13, 2016: Science
Yair Field, Evan A Boyle, Natalie Telis, Ziyue Gao, Kyle J Gaulton, David Golan, Loic Yengo, Ghislain Rocheleau, Philippe Froguel, Mark I McCarthy, Jonathan K Pritchard
Detection of recent natural selection is a challenging problem in population genetics. Here we introduce the Singleton Density Score (SDS), a method to infer very recent changes in allele frequencies from contemporary genome sequences. Applied to data from the UK10K Project, SDS reflects allele frequency changes in the ancestors of modern Britons during the past ~2,000-3,000 years. We see strong signals of selection at lactase and the MHC, and in favor of blond hair and blue eyes. For polygenic adaptation we find that recent selection for increased height has driven allele frequency shifts across most of the genome...
October 13, 2016: Science
A Sipahigil, R E Evans, D D Sukachev, M J Burek, J Borregaard, M K Bhaskar, C T Nguyen, J L Pacheco, H A Atikian, C Meuwly, R M Camacho, F Jelezko, E Bielejec, H Park, M Lončar, M D Lukin
Efficient interfaces between photons and quantum emitters form the basis for quantum networks and enable optical nonlinearities at the single-photon level. We demonstrate an integrated platform for scalable quantum nanophotonics based on silicon-vacancy (SiV) color centers coupled to diamond nanodevices. By placing SiV centers inside diamond photonic crystal cavities, we realize a quantum-optical switch controlled by a single color center. We control the switch using SiV metastable states and observe optical switching at the single-photon level...
October 13, 2016: Science
Lukas C Buelens, Vladimir V Galvita, Hilde Poelman, Christophe Detavernier, Guy B Marin
Efficient CO2 transformation from a waste product to carbon source for chemicals and fuels will require reaction conditions that effect its reduction. We develop a "super-dry" CH4 reforming reaction for enhanced CO production from CH4 and CO2 We used Ni/MgAl2O4 as a CH4 reforming catalyst, Fe2O3/MgAl2O4 as a solid oxygen carrier, and CaO/Al2O3 as a CO2 sorbent. The isothermal coupling of these three different processes resulted in higher CO production compared with conventional dry reforming by avoiding back reactions with water...
October 13, 2016: Science
Kyoko Ito, Raphaël Turcotte, Jinhua Cui, Samuel E Zimmerman, Sandra Pinho, Toshihide Mizoguchi, Fumio Arai, Judith M Runnels, Clemens Alt, Julie Teruya-Feldstein, Jessica C Mar, Rajat Singh, Toshio Suda, Charles P Lin, Paul S Frenette, Keisuke Ito
A single hematopoietic stem cell (HSC) is capable of reconstituting hematopoiesis and maintaining homeostasis by balancing self-renewal and cell differentiation. The mechanisms of HSC division balance, however, are not yet defined. Here we demonstrate, by characterizing at the single cell level a purified and minimally heterogeneous Tie2(+) HSC population, that these top hierarchical HSCs preferentially undergo symmetric divisions. The induction of mitophagy, a quality-control process in mitochondria, plays an essential role in self-renewing expansion of Tie2(+) HSCs...
October 13, 2016: Science
Charles P Fulco, Mathias Munschauer, Rockwell Anyoha, Glen Munson, Sharon R Grossman, Elizabeth M Perez, Michael Kane, Brian Cleary, Eric S Lander, Jesse M Engreitz
Gene expression in mammals is regulated by noncoding elements that can impact physiology and disease, yet the functions and target genes of most noncoding elements remain unknown. We present a high-throughput approach that uses CRISPR interference (CRISPRi) to discover regulatory elements and identify their target genes. We assess >1 megabase (Mb) of sequence in the vicinity of 2 essential transcription factors, MYC and GATA1, and identify 9 distal enhancers that control gene expression and cellular proliferation...
September 29, 2016: Science
Min Peng, Na Yin, Sagar Chhangawala, Ke Xu, Christina S Leslie, Ming O Li
Aerobic glycolysis (the Warburg effect) is a metabolic hallmark of activated T cells, and has been implicated in augmenting effector T cell responses including expression of the proinflammatory cytokine interferon-γ (IFN-γ) via 3' untranslated region (3'UTR)-mediated mechanisms. Here, we show that lactate dehydrogenase A (LDHA) is induced in activated T cells to support aerobic glycolysis but promotes IFN-γ expression independently of its 3'UTR. Instead, LDHA maintains high levels of acetyl-coenzyme A to enhance histone acetylation and transcription of Ifng Ablation of LDHA in T cells protects mice from immunopathology triggered by excessive IFN-γ expression or deficiency of regulatory T cells...
September 29, 2016: Science
Aerin Yang, Sura Ha, Jihye Ahn, Rira Kim, Sungyoon Kim, Younghoon Lee, Jaehoon Kim, Dieter Söll, Hee-Yoon Lee, Hee-Sung Park
Many essential biological processes are controlled by post-translational protein modifications. The inability to synthetically attain the diversity enabled by these modifications limits functional studies of many proteins. We designed a three-step approach for installing authentic post-translational modifications into recombinant proteins. We first used the established O-phosphoserine (Sep) orthogonal translation system to create a Sep-containing recombinant protein. The Sep residue is then dephosphorylated to dehydroalanine (Dha)...
September 29, 2016: Science
Tom H Wright, Ben J Bower, Justin M Chalker, Gonçalo J L Bernardes, Rafal Wiewiora, Wai-Lung Ng, Ritu Raj, Sarah Faulkner, M Robert J Vallée, Anuchit Phanumartwiwath, Oliver D Coleman, Marie-Laëtitia Thézénas, Maola Khan, Sébastien R G Galan, Lukas Lercher, Matthew W Schombs, Stefanie Gerstberger, Maria E Palm-Espling, Andrew J Baldwin, Benedikt M Kessler, Timothy D W Claridge, Shabaz Mohammed, Benjamin G Davis
Posttranslational modification of proteins expands their structural and functional capabilities beyond those directly specified by the genetic code. However, the vast diversity of chemically-plausible (including unnatural but functionally relevant) side-chains is not readily accessible. We describe C (sp(3))-C (sp(3)) bond-forming reactions on proteins under biocompatible conditions, which exploit unusual carbon free radical chemistry, and use them to form Cβ-Cγ bonds with altered side chains. We demonstrate how these transformations enable a wide-diversity of natural, unnatural, posttranslationally-modified (methylated, glycosylated, phosphorylated, hydroxylated) and labeled (fluorinated, isotopically-labeled) side-chains to be added to a common, readily-accessible dehydroalanine precursor in a range of representative protein types and scaffolds...
September 22, 2016: Science
Wei Peng, Huaizong Shen, Jianping Wu, Wenting Guo, Xiaojing Pan, Ruiwu Wang, S R Wayne Chen, Nieng Yan
RyR2 is a high-conductance intracellular Ca(2+) channel that controls the release of Ca(2+) from the sarco(endo)plasmic reticulum of a variety of cells. Here, we report the structures of RyR2 from porcine heart in both the open and closed states at near atomic resolutions determined using single-particle electron cryomicroscopy. Structural comparison reveals breathing motion of the overall cytoplasmic region resulted from the interdomain movements of amino-terminal domains (NTDs), Helical domains, and Handle domains, whereas little intradomain shifts are observed in these armadillo repeats-containing domains...
September 22, 2016: Science
Ute Schellenberger, Jarred Oral, Barbara A Rosen, Jun-Zhi Wei, Genhai Zhu, Weiping Xie, Mark J McDonald, David C Cerf, Scott H Diehn, Virginia C Crane, Gary A Sandahl, Jian-Zhou Zhao, Timothy M Nowatzki, Amit Sethi, Lu Liu, Zaiqi Pan, Yiwei Wang, Albert L Lu, Gusui Wu, Lu Liu
The coleopteran insect western corn rootworm (WCR, Diabrotica virgifera virgifera LeConte) is a devastating crop pest in North America and Europe. Although crop plants that produce Bacillus thuringiensis (Bt) proteins can limit insect infestation, some insect populations have evolved to be resistance to Bt proteins. Here we describe an insecticidal protein, designated IPD072Aa, that is isolated from Pseudomonas chlororaphis. Transgenic corn plants expressing IPD072Aa show protection from WCR insect injury under field conditions...
September 22, 2016: Science
I Schwartz, D Cogan, E R Schmidgall, Y Don, L Gantz, O Kenneth, N H Lindner, D Gershoni
Photonic cluster states are a resource for quantum computation based solely on single photon measurements. We use semiconductor quantum dots to deterministically generate long strings of polarization entangled photons in a cluster state by periodic timed excitation of a precessing matter qubit. In each period, an entangled photon is added to the cluster state formed by the matter qubit and the previously emitted photons. In our prototype device, the qubit is the confined dark exciton, and it produces strings of hundreds of photons in which the entanglement persists over five sequential photons...
September 8, 2016: Science
Anna Z Wec, Elisabeth K Nyakatura, Andrew S Herbert, Katie A Howell, Frederick W Holtsberg, Russell R Bakken, Eva Mittler, John R Christin, Sergey Shulenin, Rohit K Jangra, Sushma Bharrhan, Ana I Kuehne, Zachary A Bornholdt, Andrew I Flyak, Erica Ollmann Saphire, James E Crowe, M Javad Aman, John M Dye, Jonathan R Lai, Kartik Chandran
There is an urgent need for monoclonal antibody (mAb) therapies that broadly protect against Ebola virus and other filoviruses. The conserved, essential interaction between the filovirus glycoprotein, GP, and its entry receptor Niemann-Pick C1 (NPC1) provides an attractive target for such mAbs, but is shielded by multiple mechanisms, including physical sequestration in late endosomes. Here, we describe a bispecific antibody strategy to target this interaction, in which mAbs specific for NPC1 or the GP receptor-binding site are coupled to a mAb against a conserved, surface-exposed GP epitope...
September 8, 2016: Science
Li-Bo Mao, Huai-Ling Gao, Hong-Bin Yao, Lei Liu, Helmut Cölfen, Gang Liu, Si-Ming Chen, Shi-Kuo Li, You-Xian Yan, Yang-Yi Liu, Shu-Hong Yu
Although biomimetic designs are expected to play a key role in exploring future structural materials, facile fabrication of bulk biomimetic materials under ambient conditions remains a major challenge. Here, we describe a mesoscale "assembly-and-mineralization" approach inspired by the natural process in mollusks to fabricate bulk synthetic nacre that highly resembles both the chemical composition and the hierarchical structure of natural nacre. The millimeter-thick synthetic nacre consists of alternating organic layers and aragonite platelet layers (91 weight %) and exhibits good ultimate strength and fracture toughness...
August 18, 2016: Science
Chun-Kan Chen, Mario Blanco, Constanza Jackson, Erik Aznauryan, Noah Ollikainen, Christine Surka, Amy Chow, Andrea Cerase, Patrick McDonel, Mitchell Guttman
The Xist lncRNA orchestrates X chromosome inactivation, a process that entails chromosome-wide silencing and remodeling of the three-dimensional structure of the X chromosome. Yet, it remains unclear whether these changes in nuclear structure are mediated by Xist and whether they are required for silencing. Here, we show that Xist directly interacts with the Lamin B Receptor (LBR), an integral component of the nuclear lamina, and that this interaction is required for Xist-mediated silencing by recruiting the inactive X to the nuclear lamina and by doing so enables Xist to spread to actively transcribed genes across the X...
August 4, 2016: Science
Fatma Kaplan
No abstract text is available yet for this article.
October 14, 2016: Science
Anastasia Mylona, Francois-Xavier Theillet, Charles Foster, Tammy M Cheng, Francesc Miralles, Paul A Bates, Philipp Selenko, Richard Treisman
Multisite phosphorylation regulates many transcription factors, including the serum response factor partner Elk-1. Phosphorylation of the transcriptional activation domain (TAD) of Elk-1 by the protein kinase ERK at multiple sites potentiates recruitment of the Mediator transcriptional coactivator complex and transcriptional activation, but the roles of individual phosphorylation events had remained unclear. Using time-resolved nuclear magnetic resonance spectroscopy, we found that ERK2 phosphorylation proceeds at markedly different rates at eight TAD sites in vitro, which we classified as fast, intermediate, and slow...
October 14, 2016: Science
Romain A Studer, Ricard A Rodriguez-Mias, Kelsey M Haas, Joanne I Hsu, Cristina Viéitez, Carme Solé, Danielle L Swaney, Lindsay B Stanford, Ivan Liachko, René Böttcher, Maitreya J Dunham, Eulàlia de Nadal, Francesc Posas, Pedro Beltrao, Judit Villén
Living organisms have evolved protein phosphorylation, a rapid and versatile mechanism that drives signaling and regulates protein function. We report the phosphoproteomes of 18 fungal species and a phylogenetic-based approach to study phosphosite evolution. We observe rapid divergence, with only a small fraction of phosphosites conserved over hundreds of millions of years. Relative to recently acquired phosphosites, ancient sites are enriched at protein interfaces and are more likely to be functionally important, as we show for sites on H2A1 and eIF4E...
October 14, 2016: Science
Morgan F Schaller, Megan K Fung, James D Wright, Miriam E Katz, Dennis V Kent
Extraterrestrial impacts have left a substantial imprint on the climate and evolutionary history of Earth. A rapid carbon cycle perturbation and global warming event about 56 million years ago at the Paleocene-Eocene (P-E) boundary (the Paleocene-Eocene Thermal Maximum) was accompanied by rapid expansions of mammals and terrestrial plants and extinctions of deep-sea benthic organisms. Here, we report the discovery of silicate glass spherules in a discrete stratigraphic layer from three marine P-E boundary sections on the Atlantic margin...
October 14, 2016: Science
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