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Xuchu Que, Ming-Yow Hung, Calvin Yeang, Ayelet Gonen, Thomas A Prohaska, Xiaoli Sun, Cody Diehl, Antti Määttä, Dalia E Gaddis, Karen Bowden, Jennifer Pattison, Jeffrey G MacDonald, Seppo Ylä-Herttuala, Pamela L Mellon, Catherine C Hedrick, Klaus Ley, Yury I Miller, Christopher K Glass, Kirk L Peterson, Christoph J Binder, Sotirios Tsimikas, Joseph L Witztum
In this Letter, affiliation number 1 was originally missing from the HTML; the affiliations were missing for author Ming-Yow Hung in the HTML; and the Fig. 4 legend erroneously referred to panels a-h, instead of a-g. These errors have been corrected online.
July 16, 2018: Nature
Ysbrand M Nusse, Adam K Savage, Pauline Marangoni, Axel K M Rosendahl-Huber, Tyler A Landman, Frederic J de Sauvage, Richard M Locksley, Ophir D Klein
In this Letter, the received date should have been 23 March 2017 instead of 13 April 2018. Authors R.M.K. and O.D.K. were incorrectly denoted as 'equally contributing' authors. The labels for 'control' and 'IFNγ' in Extended Data Fig. 4g were reversed. These have been corrected online.
July 16, 2018: Nature
Xiaoguo Liu, Fei Zhang, Xinxin Jing, Muchen Pan, Pi Liu, Wei Li, Bowen Zhu, Jiang Li, Hong Chen, Lihua Wang, Jianping Lin, Yan Liu, Dongyuan Zhao, Hao Yan, Chunhai Fan
Genetically encoded protein scaffolds often serve as templates for the mineralization of biocomposite materials with complex yet highly controlled structural features that span from nanometres to the macroscopic scale1-4 . Methods developed to mimic these fabrication capabilities can produce synthetic materials with well defined micro- and macro-sized features, but extending control to the nanoscale remains challenging5,6 . DNA nanotechnology can deliver a wide range of customized nanoscale two- and three-dimensional assemblies with controlled sizes and shapes7-11 ...
July 16, 2018: Nature
Ben J Woodcroft, Caitlin M Singleton, Joel A Boyd, Paul N Evans, Joanne B Emerson, Ahmed A F Zayed, Robert D Hoelzle, Timothy O Lamberton, Carmody K McCalley, Suzanne B Hodgkins, Rachel M Wilson, Samuel O Purvine, Carrie D Nicora, Changsheng Li, Steve Frolking, Jeffrey P Chanton, Patrick M Crill, Scott R Saleska, Virginia I Rich, Gene W Tyson
As global temperatures rise, large amounts of carbon sequestered in permafrost are becoming available for microbial degradation. Accurate prediction of carbon gas emissions from thawing permafrost is limited by our understanding of these microbial communities. Here we use metagenomic sequencing of 214 samples from a permafrost thaw gradient to recover 1,529 metagenome-assembled genomes, including many from phyla with poor genomic representation. These genomes reflect the diversity of this complex ecosystem, with genus-level representatives for more than sixty per cent of the community...
July 16, 2018: Nature
Theodore L Roth, Cristina Puig-Saus, Ruby Yu, Eric Shifrut, Julia Carnevale, P Jonathan Li, Joseph Hiatt, Justin Saco, Paige Krystofinski, Han Li, Victoria Tobin, David N Nguyen, Michael R Lee, Amy L Putnam, Andrea L Ferris, Jeff W Chen, Jean-Nicolas Schickel, Laurence Pellerin, David Carmody, Gorka Alkorta-Aranburu, Daniela Del Gaudio, Hiroyuki Matsumoto, Montse Morell, Ying Mao, Min Cho, Rolen M Quadros, Channabasavaiah B Gurumurthy, Baz Smith, Michael Haugwitz, Stephen H Hughes, Jonathan S Weissman, Kathrin Schumann, Jonathan H Esensten, Andrew P May, Alan Ashworth, Gary M Kupfer, Siri Atma W Greeley, Rosa Bacchetta, Eric Meffre, Maria Grazia Roncarolo, Neil Romberg, Kevan C Herold, Antoni Ribas, Manuel D Leonetti, Alexander Marson
Decades of work have aimed to genetically reprogram T cells for therapeutic purposes1,2 using recombinant viral vectors, which do not target transgenes to specific genomic sites3,4 . The need for viral vectors has slowed down research and clinical use as their manufacturing and testing is lengthy and expensive. Genome editing brought the promise of specific and efficient insertion of large transgenes into target cells using homology-directed repair5,6 . Here we developed a CRISPR-Cas9 genome-targeting system that does not require viral vectors, allowing rapid and efficient insertion of large DNA sequences (greater than one kilobase) at specific sites in the genomes of primary human T cells, while preserving cell viability and function...
July 11, 2018: Nature
Laura F Seeholzer, Max Seppo, David L Stern, Vanessa Ruta
Courtship rituals serve to reinforce reproductive barriers between closely related species. Drosophila melanogaster and Drosophila simulans exhibit reproductive isolation, owing in part to the fact that D. melanogaster females produce 7,11-heptacosadiene, a pheromone that promotes courtship in D. melanogaster males but suppresses courtship in D. simulans males. Here we compare pheromone-processing pathways in D. melanogaster and D. simulans males to define how these sister species endow 7,11-heptacosadiene with the opposite behavioural valence to underlie species discrimination...
July 11, 2018: Nature
Yan Yan, Qikun Liu, Xin Zang, Shuguang Yuan, Undramaa Bat-Erdene, Calvin Nguyen, Jianhua Gan, Jiahai Zhou, Steven E Jacobsen, Yi Tang
Bioactive natural products have evolved to inhibit specific cellular targets and have served as lead molecules for health and agricultural applications for the past century1-3 . The post-genomics era has brought a renaissance in the discovery of natural products using synthetic-biology tools4-6 . However, compared to traditional bioactivity-guided approaches, genome mining of natural products with specific and potent biological activities remains challenging4 . Here we present the discovery and validation of a potent herbicide that targets a critical metabolic enzyme that is required for plant survival...
July 11, 2018: Nature
Jérôme Balesdent, Isabelle Basile-Doelsch, Joël Chadoeuf, Sophie Cornu, Delphine Derrien, Zuzana Fekiacova, Christine Hatté
The exchange of carbon between soil organic carbon (SOC) and the atmosphere affects the climate1,2 and-because of the importance of organic matter to soil fertility-agricultural productivity3 . The dynamics of topsoil carbon has been relatively well quantified4 , but half of the soil carbon is located in deeper soil layers (below 30 centimetres)5-7 , and many questions remain regarding the exchange of this deep carbon with the atmosphere8 . This knowledge gap restricts soil carbon management policies and limits global carbon models1,9,10 ...
July 11, 2018: Nature
Rozbeh Baradaran, Chongyuan Wang, Andrew Francis Siliciano, Stephen Barstow Long
The mitochondrial calcium uniporter (MCU) is a highly selective calcium channel and a major route of calcium entry into mitochondria. How the channel catalyses ion permeation and achieves ion selectivity are not well understood, partly because MCU is thought to have a distinct architecture in comparison to other cellular channels. Here we report cryo-electron microscopy reconstructions of MCU channels from zebrafish and Cyphellophora europaea at 8.5 Å and 3.2 Å resolutions, respectively. In contrast to a previous report of pentameric stoichiometry for MCU, both channels are tetramers...
July 11, 2018: Nature
Chao Fan, Minrui Fan, Benjamin J Orlando, Nathan M Fastman, Jinru Zhang, Yan Xu, Melissa G Chambers, Xiaofang Xu, Kay Perry, Maofu Liao, Liang Feng
Mitochondrial calcium uptake is critical for regulating ATP production, intracellular calcium signalling, and cell death. This uptake is mediated by a highly selective calcium channel called the mitochondrial calcium uniporter (MCU). Here, we determined the structures of the pore-forming MCU proteins from two fungi by X-ray crystallography and single-particle cryo-electron microscopy. The stoichiometry, overall architecture, and individual subunit structure differed markedly from those described in the recent nuclear magnetic resonance structure of Caenorhabditis elegans MCU...
July 11, 2018: Nature
Nam X Nguyen, Jean-Paul Armache, Changkeun Lee, Yi Yang, Weizhong Zeng, Vamsi K Mootha, Yifan Cheng, Xiao-Chen Bai, Youxing Jiang
The mitochondrial calcium uniporter (MCU) is a highly selective calcium channel localized to the inner mitochondrial membrane. Here, we describe the structure of an MCU orthologue from the fungus Neosartorya fischeri (NfMCU) determined to 3.8 Å resolution by phase-plate cryo-electron microscopy. The channel is a homotetramer with two-fold symmetry in its amino-terminal domain (NTD) that adopts a similar structure to that of human MCU. The NTD assembles as a dimer of dimers to form a tetrameric ring that connects to the transmembrane domain through an elongated coiled-coil domain...
July 11, 2018: Nature
Po-Ru Loh, Giulio Genovese, Robert E Handsaker, Hilary K Finucane, Yakir A Reshef, Pier Francesco Palamara, Brenda M Birmann, Michael E Talkowski, Samuel F Bakhoum, Steven A McCarroll, Alkes L Price
The selective pressures that shape clonal evolution in healthy individuals are largely unknown. Here we investigate 8,342 mosaic chromosomal alterations, from 50 kb to 249 Mb long, that we uncovered in blood-derived DNA from 151,202 UK Biobank participants using phase-based computational techniques (estimated false discovery rate, 6-9%). We found six loci at which inherited variants associated strongly with the acquisition of deletions or loss of heterozygosity in cis. At three such loci (MPL, TM2D3-TARSL2, and FRA10B), we identified a likely causal variant that acted with high penetrance (5-50%)...
July 11, 2018: Nature
Hsin-Yung Yen, Kin Kuan Hoi, Idlir Liko, George Hedger, Michael R Horrell, Wanling Song, Di Wu, Philipp Heine, Tony Warne, Yang Lee, Byron Carpenter, Andreas Plückthun, Christopher G Tate, Mark S P Sansom, Carol V Robinson
G-protein-coupled receptors (GPCRs) are involved in many physiological processes and are therefore key drug targets1 . Although detailed structural information is available for GPCRs, the effects of lipids on the receptors, and on downstream coupling of GPCRs to G proteins are largely unknown. Here we use native mass spectrometry to identify endogenous lipids bound to three class A GPCRs. We observed preferential binding of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2 ) over related lipids and confirm that the intracellular surface of the receptors contain hotspots for PtdIns(4,5)P2 binding...
July 11, 2018: Nature
Naama Kanarek, Heather R Keys, Jason R Cantor, Caroline A Lewis, Sze Ham Chan, Tenzin Kunchok, Monther Abu-Remaileh, Elizaveta Freinkman, Lawrence D Schweitzer, David M Sabatini
The chemotherapeutic drug methotrexate inhibits the enzyme dihydrofolate reductase1 , which generates tetrahydrofolate, an essential cofactor in nucleotide synthesis2 . Depletion of tetrahydrofolate causes cell death by suppressing DNA and RNA production3 . Although methotrexate is widely used as an anticancer agent and is the subject of over a thousand ongoing clinical trials4 , its high toxicity often leads to the premature termination of its use, which reduces its potential efficacy5 . To identify genes that modulate the response of cancer cells to methotrexate, we performed a CRISPR-Cas9-based screen6,7 ...
July 11, 2018: Nature
Xiaofeng Qi, Philip Schmiege, Elias Coutavas, Jiawei Wang, Xiaochun Li
Hedgehog (HH) signalling governs embryogenesis and adult tissue homeostasis in mammals and other multicellular organisms1-3 . Whereas deficient HH signalling leads to birth defects, unrestrained HH signalling is implicated in human cancers2,4-6 . N-terminally palmitoylated HH releases the repression of Patched to the oncoprotein smoothened (SMO); however, the mechanism by which HH recognizes Patched is unclear. Here we report cryo-electron microscopy structures of human patched 1 (PTCH1) alone and in complex with the N-terminal domain of 'native' sonic hedgehog (native SHH-N has both a C-terminal cholesterol and an N-terminal fatty-acid modification), at resolutions of 3...
July 11, 2018: Nature
Lu Liu, Yang Wang, Roberta Sinatra, C Lee Giles, Chaoming Song, Dashun Wang
The hot streak-loosely defined as 'winning begets more winnings'-highlights a specific period during which an individual's performance is substantially better than his or her typical performance. Although hot streaks have been widely debated in sports1,2 , gambling3-5 and financial markets6,7 over the past several decades, little is known about whether they apply to individual careers. Here, building on rich literature on the lifecycle of creativity8-22 , we collected large-scale career histories of individual artists, film directors and scientists, tracing the artworks, films and scientific publications they produced...
July 11, 2018: Nature
Clemens Plaschka, Pei-Chun Lin, Clément Charenton, Kiyoshi Nagai
The spliceosome catalyses the excision of introns from pre-mRNA in two steps, branching and exon ligation, and is assembled from five small nuclear ribonucleoprotein particles (snRNPs; U1, U2, U4, U5, U6) and numerous non-snRNP factors1 . For branching, the intron 5' splice site and the branch point sequence are selected and brought by the U1 and U2 snRNPs into the prespliceosome1 , which is a focal point for regulation by alternative splicing factors2 . The U4/U6.U5 tri-snRNP subsequently joins the prespliceosome to form the complete pre-catalytic spliceosome...
July 11, 2018: Nature
Zhaoyu Zhu, Robin Dennell, Weiwen Huang, Yi Wu, Shifan Qiu, Shixia Yang, Zhiguo Rao, Yamei Hou, Jiubing Xie, Jiangwei Han, Tingping Ouyang
Considerable attention has been paid to dating the earliest appearance of hominins outside Africa. The earliest skeletal and artefactual evidence for the genus Homo in Asia currently comes from Dmanisi, Georgia, and is dated to approximately 1.77-1.85 million years ago (Ma)1 . Two incisors that may belong to Homo erectus come from Yuanmou, south China, and are dated to 1.7 Ma2 ; the next-oldest evidence is an H. erectus cranium from Lantian (Gongwangling)-which has recently been dated to 1.63 Ma3 -and the earliest hominin fossils from the Sangiran dome in Java, which are dated to about 1...
July 11, 2018: Nature
Neelroop N Parikshak, Vivek Swarup, T Grant Belgard, Manuel Irimia, Gokul Ramaswami, Michael J Gandal, Christopher Hartl, Virpi Leppa, Luis de la Torre Ubieta, Jerry Huang, Jennifer K Lowe, Benjamin J Blencowe, Steve Horvath, Daniel H Geschwind
Change history: In this Letter, the labels for splicing events A3SS and A5SS were swapped in column D of Supplementary Table 3a and b. This has been corrected online.
July 11, 2018: Nature
Kai Ma, Yunye Gong, Tangi Aubert, Melik Z Turker, Teresa Kao, Peter C Doerschuk, Ulrich Wiesner
Change history: In Fig. 3b of this Letter, the labels for the outer (11.8 nm) and inner (7.4 nm) diameters of the structure were inadvertently omitted. Fig. 3 has been corrected online.
July 10, 2018: Nature
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