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Lina Chong, Jianguo Wen, Joseph Kubal, Fatih G Sen, Jianxin Zou, Jeffery Greeley, Maria Chan, Heather Barkholtz, Wenjiang Ding, Di-Jia Liu
Achieving high catalytic performance with the lowest amount of platinum is critical in fuel cell cost reduction. We describe a method of preparing highly active yet stable electrocatalysts containing ultralow Pt content using Co or Co/Zn zeolitic imidazolate frameworks as precursors. Synergistic catalysis between strained Pt-Co core-shell nanoparticles over a platinum-group-metal-free (PGM-free) catalytic substrate led to excellent fuel cell performance under 1 atmosphere of O2 or air at both high voltage and high current domains...
November 8, 2018: Science
Jeong-Mok Kim, Ok-Hee Seok, Shinyeong Ju, Ji-Eun Heo, Jeonghun Yeom, Da-Som Kim, Joo-Yeon Yoo, Alexander Varshavsky, Cheolju Lee, Cheol-Sang Hwang
In bacteria, nascent proteins bear the pretranslationally generated N-terminal (Nt) formyl-methionine (fMet) residue. Nt-fMet of bacterial proteins is a degradation signal, termed fMet/N-degron. In contrast, proteins synthesized by cytosolic ribosomes of eukaryotes were presumed to bear unformylated Nt-Met. Here we found that the yeast formyltransferase Fmt1, although imported into mitochondria, could also produce Nt-formylated proteins in the cytosol. Nt-formylated proteins were strongly up-regulated in stationary phase or upon starvation for specific amino acids...
November 8, 2018: Science
J Víctor Moreno-Mayar, Lasse Vinner, Peter de Barros Damgaard, Constanza de la Fuente, Jeffrey Chan, Jeffrey P Spence, Morten E Allentoft, Tharsika Vimala, Fernando Racimo, Thomaz Pinotti, Simon Rasmussen, Ashot Margaryan, Miren Iraeta Orbegozo, Dorothea Mylopotamitaki, Matthew Wooller, Clement Bataille, Lorena Becerra-Valdivia, David Chivall, Daniel Comeskey, Thibaut Devièse, Donald K Grayson, Len George, Harold Harry, Verner Alexandersen, Charlotte Primeau, Jon Erlandson, Claudia Rodrigues-Carvalho, Silvia Reis, Murilo Q R Bastos, Jerome Cybulski, Carlos Vullo, Flavia Morello, Miguel Vilar, Spencer Wells, Kristian Gregersen, Kasper Lykke Hansen, Niels Lynnerup, Marta Mirazón Lahr, Kurt Kjær, André Strauss, Marta Alfonso-Durruty, Antonio Salas, Hannes Schroeder, Thomas Higham, Ripan S Malhi, Jeffrey T Rasic, Luiz Souza, Fabricio R Santos, Anna-Sapfo Malaspinas, Martin Sikora, Rasmus Nielsen, Yun S Song, David J Meltzer, Eske Willerslev
Studies of the peopling of the Americas have focused on the timing and number of initial migrations. Less attention has been paid to the subsequent spread of people within the Americas. We sequenced 15 ancient human genomes spanning Alaska to Patagonia; six are ≥10,000 years old (up to ~18× coverage). All are most closely related to Native Americans, including an Ancient Beringian individual, and two morphologically distinct "Paleoamericans." We find evidence of rapid dispersal and early diversification, including previously unknown groups, as people moved south...
November 8, 2018: Science
Hilary C Martin, Wendy D Jones, Rebecca McIntyre, Gabriela Sanchez-Andrade, Mark Sanderson, James D Stephenson, Carla P Jones, Juliet Handsaker, Giuseppe Gallone, Michaela Bruntraeger, Jeremy F McRae, Elena Prigmore, Patrick Short, Mari Niemi, Joanna Kaplanis, Elizabeth J Radford, Nadia Akawi, Meena Balasubramanian, John Dean, Rachel Horton, Alice Hulbert, Diana S Johnson, Katie Johnson, Dhavendra Kumar, Sally Ann Lynch, Sarju G Mehta, Jenny Morton, Michael J Parker, Miranda Splitt, Peter D Turnpenny, Pradeep C Vasudevan, Michael Wright, Andrew Bassett, Sebastian S Gerety, Caroline F Wright, David R FitzPatrick, Helen V Firth, Matthew E Hurles, Jeffrey C Barrett
We estimated the genome-wide contribution of recessive coding variation from 6,040 families from the Deciphering Developmental Disorders study. The proportion of cases attributable to recessive coding variants was 3.6% in patients of European ancestry, compared to 50% explained by de novo coding mutations. It was higher (31%) in patients with Pakistani ancestry, due to elevated autozygosity. Half of this recessive burden is attributable to known genes. We identified two genes not previously associated with recessive developmental disorders, KDM5B and EIF3F , and functionally validated them with mouse and cellular models...
November 8, 2018: Science
Ang Guo, Yihui Wang, Biyi Chen, Yunhao Wang, Jinxiang Yuan, Liyang Zhang, Duane Hall, Jennifer Wu, Yun Shi, Qi Zhu, Cheng Chen, William H Thiel, Xin Zhan, Robert M Weiss, Fenghuang Zhan, Catherine A Musselman, Miles Pufall, Weizhong Zhu, Kin Fai Au, Jiang Hong, Mark E Anderson, Chad E Grueter, Long-Sheng Song
Junctophilin-2 (JP2) is a structural protein required for normal excitation-contraction (E-C) coupling. Following cardiac stress, JP2 is cleaved by Ca2+ -dependent protease calpain, which disrupts the E-C coupling ultrastructural machinery and drives heart failure progression. Here we demonstrate that stress-induced proteolysis of JP2 liberates an N-terminal fragment (JP2NT) that translocates to the nucleus, binds to genomic DNA and controls expression of a spectrum of genes in cardiomyocytes. Transgenic overexpression of JP2NT in mice modifies the transcriptional profile resulting in attenuated pathological remodeling in response to cardiac stress...
November 8, 2018: Science
Samuel P Fraiberger, Roberta Sinatra, Magnus Resch, Christoph Riedl, Albert-László Barabási
In areas of human activity where performance is difficult to quantify in an objective fashion, reputation and networks of influence play a key role in determining access to resources and rewards. To understand the role of these factors, we reconstructed the exhibition history of half a million artists, mapping out the coexhibition network that captures the movement of art between institutions. Centrality within this network captured institutional prestige, allowing us to explore the career trajectory of individual artists in terms of access to coveted institutions...
November 8, 2018: Science
Julien Ablain, Mengshu Xu, Harriet Rothschild, Richard C Jordan, Jeffrey K Mito, Brianne H Daniels, Caitlin F Bell, Nancy M Joseph, Hong Wu, Boris C Bastian, Leonard I Zon, Iwei Yeh
Melanomas originating from mucosal surfaces have low mutation burden, genomic instability, and poor prognosis. To identify potential driver genes, we sequenced hundreds of cancer-related genes in 43 human mucosal melanomas, cataloguing point mutations, amplifications and deletions. The SPRED1 gene, which encodes a negative regulator of MAPK signaling, was inactivated in 37% of the tumors. Four distinct genotypes were associated with SPRED1 loss. Using a rapid, tissue-specific CRISPR technique to model these genotypes in zebrafish, we found that SPRED1 functions as a tumor suppressor, particularly in the context of KIT mutations...
November 1, 2018: Science
Jeffrey R Moffitt, Dhananjay Bambah-Mukku, Stephen W Eichhorn, Eric Vaughn, Karthik Shekhar, Julio D Perez, Nimrod D Rubinstein, Junjie Hao, Aviv Regev, Catherine Dulac, Xiaowei Zhuang
The hypothalamus controls essential social behaviors and homeostatic functions. However, the cellular architecture of hypothalamic nuclei, including the molecular identity, spatial organization, and function of distinct cell types, is poorly understood. Here, we developed an imaging-based in situ cell type identification and mapping method and combined it with single-cell RNA-sequencing to create a molecularly annotated and spatially resolved cell atlas of the mouse hypothalamic preoptic region. We profiled ~1 million cells, identified ~70 neuronal populations characterized by distinct neuromodulatory signatures and spatial organizations, and defined specific neuronal populations activated during social behaviors in male and female mice, providing a high-resolution framework for mechanistic investigation of behavior circuits...
November 1, 2018: Science
Itay Budin, Tristan de Rond, Yan Chen, Leanne Jade G Chan, Christopher J Petzold, Jay D Keasling
Lipid composition determines the physical properties of biological membranes and can vary substantially between and within organisms. We describe a specific role for the viscosity of energy-transducing membranes in cellular respiration. Engineering of fatty acid biosynthesis in Escherichia coli allowed us to titrate inner membrane viscosity across a 10-fold range by controlling the abundance of unsaturated or branched lipids. These fluidizing lipids tightly controlled respiratory metabolism, an effect that can be explained with a quantitative model of the Electron Transport Chain (ETC) that features diffusion-coupled reactions between enzymes and electron carriers (quinones)...
October 25, 2018: Science
Stéphanie Liénart, Romain Merceron, Christophe Vanderaa, Fanny Lambert, Didier Colau, Julie Stockis, Bas van der Woning, Hans De Haard, Michael Saunders, Pierre G Coulie, Savvas N Savvides, Sophie Lucas
Transforming growth factor-β1 (TGF-β1) is one of very few cytokines produced in a latent form, requiring activation to exert any of its vastly diverse effects on development, immunity, and cancer. Regulatory T cells (Tregs) suppress immune cells within close proximity by activating latent TGF-β1 presented by GARP to integrin αVβ8 on their surface. We solved the crystal structure of GARP:latent TGF-β1 bound to an antibody that stabilizes the complex and blocks release of active TGF-β1. This reveals how GARP exploits an unusual medley of interactions, including fold complementation by the N terminus of TGF-β1, to chaperone and orient the cytokine for binding and activation by αVβ8...
October 25, 2018: Science
Hongri Gong, Jun Li, Ao Xu, Yanting Tang, Wenxin Ji, Ruogu Gao, Shuhui Wang, Lu Yu, Changlin Tian, Jingwen Li, Hsin-Yung Yen, Sin Man Lam, Guanghou Shui, Xiuna Yang, Yuna Sun, Xuemei Li, Minze Jia, Cheng Yang, Biao Jiang, Zhiyong Lou, Carol V Robinson, Luet-Lok Wong, Luke W Guddat, Fei Sun, Quan Wang, Zihe Rao
We report a 3.5-Å resolution cryo-EM structure of a respiratory supercomplex isolated from Mycobacterium smegmatis. It comprises a complex III dimer flanked on either side by individual complex IV subunits. Complex III and IV associate such that electrons can be transferred from quinol in complex III to the oxygen reduction center in complex IV via a bridging cytochrome subunit. We observe a superoxide dismutase-like subunit at the periplasmic face, which may be responsible for detoxification of superoxide formed by complex III...
October 25, 2018: Science
Ebrahim Sajadi, Tauno Palomaki, Zaiyao Fei, Wenjin Zhao, Philip Bement, Christian Olsen, Silvia Luescher, Xiaodong Xu, Joshua A Folk, David H Cobden
The layered semimetal WTe2 has recently been found to be a two-dimensional topological insulator (2D TI) when thinned down to a single monolayer, with conducting helical edge channels. We report here that intrinsic superconductivity can be induced in this monolayer 2D TI by mild electrostatic doping, at temperatures below 1 K. The 2D TI-superconductor transition can be easily driven by applying a small gate voltage. This discovery offers possibilities for gate-controlled devices combining superconductivity and non-trivial topological properties, and could provide a basis for quantum information schemes based on topological protection...
October 25, 2018: Science
Valla Fatemi, Sanfeng Wu, Yuan Cao, Landry Bretheau, Quinn D Gibson, Kenji Watanabe, Takashi Taniguchi, Robert J Cava, Pablo Jarillo-Herrero
Turning on superconductivity in a topologically non-trivial insulator may provide a route to search for non-Abelian topological states. However, existing demonstrations of superconductor-insulator switches have involved only topologically trivial systems. Here we report reversible, in situ electrostatic on/off switching of superconductivity in the recently established quantum spin Hall insulator monolayer tungsten ditelluride (WTe2 ). Fabricated into a van der Waals field effect transistor, the monolayer's ground state can be continuously gate-tuned from the topological insulating to the superconducting state, with critical temperatures Tc up to ~ 1 Kelvin...
October 25, 2018: Science
Pontus Orning, Dan Weng, Kristian Starheim, Dmitry Ratner, Zachary Best, Bettina Lee, Alexandria Brooks, Shiyu Xia, Hao Wu, Michelle A Kelliher, Scott B Berger, Peter J Gough, John Bertin, Megan M Proulx, Jon D Goguen, Nobuhiko Kayagaki, Katherine A Fitzgerald, Egil Lien
Limited proteolysis of gasdermin D (GSDMD) generates an N-terminal pore-forming fragment, which controls pyroptosis in macrophages. GSDMD is processed via inflammasome-activated caspase-1 or -11. It is currently unknown whether macrophage GSDMD can be processed by other mechanisms. Here, we describe an additional pathway controlling GSDMD processing. The inhibition of TAK1 or IKK kinases by the Yersinia effector protein YopJ elicits RIPK1- and caspase-8-dependent cleavage of GSDMD, which subsequently results in cell death...
October 25, 2018: Science
Iñigo Martincorena, Joanna C Fowler, Agnieszka Wabik, Andrew R J Lawson, Federico Abascal, Michael W J Hall, Alex Cagan, Kasumi Murai, Krishnaa Mahbubani, Michael R Stratton, Rebecca C Fitzgerald, Penny A Handford, Peter J Campbell, Kourosh Saeb-Parsy, Philip H Jones
The extent to which cells in normal tissues accumulate mutations throughout life is poorly understood. Some mutant cells expand into clones that can be detected by genome sequencing. We mapped mutant clones in normal esophageal epithelium from nine donors (age range, 20 to 75 years). Somatic mutations accumulated with age and were caused mainly by intrinsic mutational processes. We found strong positive selection of clones carrying mutations in 14 cancer genes, with tens to hundreds of clones per square centimeter...
October 18, 2018: Science
Fu-Sheng Guo, Benjamin M Day, Yan-Cong Chen, Ming-Liang Tong, Akseli Mansikkamäki, Richard A Layfield
Single-molecule magnets (SMMs) containing only one metal center may represent the lower size limit for molecule-based magnetic information storage materials. Their current drawback is that all SMMs require liquid-helium cooling to show magnetic memory effects. We now report a chemical strategy to access the dysprosium metallocene cation [(Cp i Pr5 )Dy(Cp*)]+ (Cp i Pr5 = penta-iso-propylcyclopentadienyl, Cp * = pentamethylcyclopentadienyl), which displays magnetic hysteresis above liquid-nitrogen temperatures...
October 18, 2018: Science
Lucas B Harrington, David Burstein, Janice S Chen, David Paez-Espino, Enbo Ma, Isaac P Witte, Joshua C Cofsky, Nikos C Kyrpides, Jillian F Banfield, Jennifer A Doudna
CRISPR-Cas systems provide microbes with adaptive immunity to infectious nucleic acids and are widely employed as genome editing tools. These tools utilize RNA-guided Cas proteins whose large size (950-1400 amino acids) has been considered essential to their specific DNA- or RNA-targeting activities. Here we present a set of CRISPR-Cas systems from uncultivated archaea that contain Cas14, a family of exceptionally compact RNA-guided nucleases (400-700 amino acids). Despite their small size, Cas14 proteins are capable of targeted single-stranded DNA (ssDNA) cleavage without restrictive sequence requirements...
October 18, 2018: Science
Sunghwan Jin, Ming Huang, Youngwoo Kwon, Leining Zhang, Bao-Wen Li, Sangjun Oh, Jichen Dong, Da Luo, Mandakini Biswal, Benjamin V Cunning, Pavel V Bakharev, Inyong Moon, Won Jong Yoo, Dulce C Camacho-Mojica, Yong-Jin Kim, Sun Hwa Lee, Bin Wang, Won Kyung Seong, Manav Saxena, Feng Ding, Hyung-Joon Shin, Rodney S Ruoff
Single-crystal metals have unique properties due to the absence of grain boundaries and strong anisotropy. Commercial single-crystal metals are usually synthesized by bulk crystal growth or by deposition of thin films onto substrates, and they are expensive and small. We prepare extremely large single-crystal metal foils by 'contact-free annealing' from commercial polycrystalline foils. The colossal grain growth (up to 32 cm2 ) is achieved by minimizing contact stresses, resulting in a preferred in-plane and out-of-plane crystal orientation, and is driven by surface energy minimization during the rotation of the crystal lattice followed by 'consumption' of neighboring grains...
October 18, 2018: Science
Eric J Meier, Fangzhao Alex An, Alexandre Dauphin, Maria Maffei, Pietro Massignan, Taylor L Hughes, Bryce Gadway
Topology and disorder have a rich combined influence on quantum transport. In order to probe their interplay, we synthesized one-dimensional chiral symmetric wires with controllable disorder via spectroscopic Hamiltonian engineering, based on the laser-driven coupling of discrete momentum states of ultracold atoms. Measuring the bulk evolution of a topological indicator following a sudden quench, we observed the topological Anderson insulator phase, in which added disorder drives the band structure of a wire from topologically trivial to non-trivial...
October 11, 2018: Science
Andres H de la Peña, Ellen A Goodall, Stephanie N Gates, Gabriel C Lander, A Martin
The 26 S proteasome is the primary eukaryotic degradation machine and thus critically involved in numerous cellular processes. The hetero-hexameric ATPase motor of the proteasome unfolds and translocates targeted protein substrates into the open gate of a proteolytic core, while a proteasomal deubiquitinase concomitantly removes substrate-attached ubiquitin chains. However, the mechanisms by which ATP hydrolysis drives the conformational changes responsible for these processes have remained elusive. Here we present the cryo-EM structures of four distinct conformational states of the actively ATP-hydrolyzing, substrate-engaged 26 S proteasome...
October 11, 2018: Science
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