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Alexander B Rosenberg, Charles M Roco, Richard A Muscat, Anna Kuchina, Paul Sample, Zizhen Yao, Lucas Gray, David J Peeler, Sumit Mukherjee, Wei Chen, Suzie H Pun, Drew L Sellers, Bosiljka Tasic, Georg Seelig
To facilitate scalable profiling of single cells, we developed split-pool ligation-based transcriptome sequencing (SPLiT-seq), a single-cell RNA-seq (scRNA-seq) method that labels the cellular origin of RNA through combinatorial barcoding. SPLiT-seq is compatible with fixed cells or nuclei, allows efficient sample multiplexing and requires no customized equipment. We used SPLiT-seq to analyze 156,049 single-nucleus transcriptomes from postnatal day 2 and 11 mouse brains and spinal cords. Over 100 cell types were identified, with gene expression patterns corresponding to cellular function, regional specificity, and stage of differentiation...
March 15, 2018: Science
Alan L Deino, Anna K Behrensmeyer, Alison S Brooks, John E Yellen, Warren D Sharp, Richard Potts
The origin of the Middle Stone Age (MSA) denotes the transition from a highly persistent mode of stone toolmaking, the Acheulean, to a period of increasing technological innovation and cultural indicators associated with the evolution of Homo sapiens Here we use40 Ar/39 Ar and U-series dating to calibrate the chronology of Acheulean- and early MSA-rich sedimentary deposits in the Olorgesailie Basin, South Kenya Rift. We establish the age of late Acheulean tool assemblages from 615 to 499 ka, after which a large technological and faunal transition occurred, with definitive MSA lacking Acheulean elements beginning most likely by ~320 ka, but at least by 305 ka...
March 15, 2018: Science
Kutay Deniz Atabay, Samuel A LoCascio, Thom de Hoog, Peter W Reddien
During animal regeneration cells must organize into discrete and functional systems. We show that self-organization, along with patterning cues, govern progenitor behavior in planarian regeneration. Surgical paradigms allowed manipulation of planarian eye regeneration in predictable locations and numbers, generating alternative stable neuroanatomical states for wild-type animals with multiple functional ectopic eyes. We utilized animals with multiple ectopic eyes and eye transplantation to demonstrate that broad progenitor specification, combined with self-organization, allows anatomy maintenance during regeneration...
March 15, 2018: Science
Alison S Brooks, John E Yellen, Richard Potts, Anna K Behrensmeyer, Alan L Deino, David E Leslie, Stanley H Ambrose, Jeffrey R Ferguson, Francesco d'Errico, Andrew M Zipkin, Scott Whittaker, Jeffrey Post, Elizabeth G Veatch, Kimberly Foecke, Jennifer B Clark
Previous research suggests that the complex symbolic, technological, and socio-economic behaviors that typify Homo sapiens had roots in the middle Pleistocene <200 ka, but data bearing on human behavioral origins are limited. We present a series of excavated Middle Stone Age sites from the Olorgesailie Basin, southern Kenya, dated ≥295 to ~320 ka by40 Ar/39 Ar and U-Series methods. Hominins at these sites made prepared cores and points, exploited iron-rich rocks to obtain red pigment, and procured stone tool materials from ≥25-50 km distance...
March 15, 2018: Science
Marieke van de Loosdrecht, Abdeljalil Bouzouggar, Louise Humphrey, Cosimo Posth, Nick Barton, Ayinuer Aximu-Petri, Birgit Nickel, Sarah Nagel, El Hassan Talbi, Mohammed Abdeljalil El Hajraoui, Saaïd Amzazi, Jean-Jacques Hublin, Svante Pääbo, Stephan Schiffels, Matthias Meyer, Wolfgang Haak, Choongwon Jeong, Johannes Krause
North Africa is a key region for understanding human history, but the genetic history of its people is largely unknown. We present genomic data from seven 15,000-year-old modern humans from Morocco, attributed to the Iberomaurusian culture. We find a genetic affinity with early Holocene Near Easterners, best represented by Levantine Natufians, suggesting a pre-agricultural connection between Africa and the Near East. We do not find evidence for gene flow from Paleolithic Europeans into Late Pleistocene North Africans...
March 15, 2018: Science
Richard Potts, Anna K Behrensmeyer, J Tyler Faith, Christian A Tryon, Alison S Brooks, John E Yellen, Alan L Deino, Rahab Kinyanjui, Jennifer B Clark, Catherine Haradon, Naomi E Levin, Hanneke J M Meijer, Elizabeth G Veatch, R Bernhart Owen, Robin W Renaut
Development of the African Middle Stone Age (MSA) before 300 thousand years ago (ka) raises the question of how environmental change influenced the evolution of behaviors characteristic of early Homo sapiens We use temporally well-constrained sedimentological and paleoenvironmental data to investigate environmental dynamics before and after the appearance of the early MSA in the Olorgesailie Basin, Kenya. In contrast to the Acheulean archeological record in the same basin, MSA sites are associated with a dramatically different faunal community, more pronounced erosion-deposition cycles, tectonic activity, and enhanced wet-dry variability...
March 15, 2018: Science
S Tylewicz, A Petterle, S Marttila, P Miskolczi, A Azeez, R K Singh, J Immanen, N Mähler, T R Hvidsten, D M Eklund, J L Bowman, Y Helariutta, R P Bhalerao
In temperate and boreal ecosystems, seasonal cycles of growth and dormancy allow perennial plants to adapt to winter conditions. We show, in hybrid aspen trees, that photoperiodic regulation of dormancy is mechanistically distinct from autumnal growth cessation. Dormancy sets in when symplastic inter-cellular communication through plasmodesmata is blocked by a process dependent upon the phytohormone abscisic acid (ABA). The communication blockage prevents growth-promoting signals from accessing the meristem...
March 8, 2018: Science
Jianwei Wang, Stefano Paesani, Yunhong Ding, Raffaele Santagati, Paul Skrzypczyk, Alexia Salavrakos, Jordi Tura, Remigiusz Augusiak, Laura Mančinska, Davide Bacco, Damien Bonneau, Joshua W Silverstone, Qihuang Gong, Antonio Acín, Karsten Rottwitt, Leif K Oxenløwe, Jeremy L O'Brien, Anthony Laing, Mark G Thompson
The ability to control multidimensional quantum systems is key for the investigation of fundamental science and for the development of advanced quantum technologies. We demonstrate a multidimensional integrated quantum photonic platform able to generate, control and analyze high-dimensional entanglement. A programmable bipartite entangled system is realized with dimension up to 15 × 15 on a large-scale silicon-photonics quantum circuit. The device integrates more than 550 photonic components on a single chip, including 16 identical photon-pair sources...
March 8, 2018: Science
Peng Zhang, Koichiro Yaji, Takahiro Hashimoto, Yuichi Ota, Takeshi Kondo, Kozo Okazaki, Zhijun Wang, Jinsheng Wen, G D Gu, Hong Ding, Shik Shin
Topological superconductors are predicted to host exotic Majorana states that obey non-Abelian statistics and can be used to implement a topological quantum computer. Most of the proposed topological superconductors are realized in difficult-to-fabricate heterostructures at very low temperatures. Here by using high-resolution spin-resolved and angle-resolved photoelectron spectroscopy, we find that the iron-based superconductor FeTe1- x Se x ( x = 0.45, superconducting transition temperature T c = 14.5 K) hosts Dirac-cone type spin-helical surface states at Fermi level; the surface states exhibit an s -wave superconducting gap below T c Our study shows that the surface states of FeTe0...
March 8, 2018: Science
Christoph A Thaiss, Maayan Levy, Inna Grosheva, Danping Zheng, Eliran Soffer, Eran Blacher, Sofia Braverman, Anouk C Tengeler, Oren Barak, Maya Elazar, Rotem Ben-Zeev, Dana Lehavi-Regev, Meirav N Katz, Meirav Pevsner-Fischer, Arieh Gertler, Zamir Halpern, Alon Harmelin, Suhail Aamar, Patricia Serradas, Alexandra Grosfeld, Hagit Shapiro, Benjamin Geiger, Eran Elinav
Obesity, diabetes and related manifestations are associated with an enhanced, but poorly understood risk for mucosal infection and systemic inflammation. Here, we show in mouse models of obesity and diabetes that hyperglycemia drives intestinal barrier permeability, through GLUT2-dependent transcriptional reprogramming of intestinal epithelial cells and alteration of tight and adherence junction integrity. Consequently, hyperglycemia-mediated barrier disruption leads to systemic influx of microbial products and enhanced dissemination of enteric infection...
March 8, 2018: Science
Jan Michael Schuller, Sebastian Falk, Lisa Fromm, Ed Hurt, Elena Conti
The RNA exosome complex processes and degrades a wide range of transcripts, including ribosomal RNAs. We used cryo-EM to visualize the yeast nuclear exosome holo-complex captured on a precursor large ribosomal subunit (pre-60S) during 7S-to-5.8S rRNA processing. The cofactors of the nuclear exosome are sandwiched between the ribonuclease core complex (Exo-10) and the remodeled "foot" structure of the pre-60S particle, which harbors the 5.8S rRNA precursor. The exosome-associated helicase Mtr4 recognizes the preribosomal substrate by docking to specific sites on the 25S rRNA, captures the 3' extension of the 5...
March 8, 2018: Science
Katharina Braunger, Stefan Pfeffer, Shiteshu Shrimal, Reid Gilmore, Otto Berninghausen, Elisabet C Mandon, Thomas Becker, Friedrich Förster, Roland Beckmann
Protein synthesis, transport and N-glycosylation are coupled at the mammalian endoplasmic reticulum (ER) by complex formation between the ribosome, the Sec61 protein-conducting channel and the oligosaccharyltransferase (OST). Here, we used different cryo-electron microscopy approaches to determine structures of native and solubilized ribosome-Sec61-OST complexes. A molecular model for the catalytic OST subunit revealed how STT3A is integrated into the OST and how STT3 paralog specificity for translocon-associated OST is achieved...
March 8, 2018: Science
Eric M Spanton, Alexander A Zibrov, Haoxin Zhou, Takashi Taniguchi, Kenji Watanabe, Michael P Zaletel, Andrea F Young
Topologically ordered phases are characterized by long-range quantum entanglement and fractional statistics rather than by symmetry breaking. First observed in a fractionally filled continuum Landau level, topological order has since been proposed to arise more generally at fractional fillings of topologically non-trivial "Chern" bands. Here, we report the observation of gapped states at fractional fillings of Harper-Hofstadter bands arising from the interplay of a magnetic field and a superlattice potential in a bilayer graphene/hexagonal boron nitride heterostructure...
March 1, 2018: Science
Joanna Kaplanis, Assaf Gordon, Tal Shor, Omer Weissbrod, Dan Geiger, Mary Wahl, Michael Gershovits, Barak Markus, Mona Sheikh, Melissa Gymrek, Gaurav Bhatia, Daniel G MacArthur, Alkes L Price, Yaniv Erlich
Family trees have vast applications in multiple fields from genetics to anthropology and economics. However, the collection of extended family trees is tedious and usually relies on resources with limited geographical scope and complex data usage restrictions. Here, we collected 86 million profiles from publicly-available online data shared by genealogy enthusiasts. After extensive cleaning and validation, we obtained population-scale family trees, including a single pedigree of 13 million individuals. We leveraged the data to partition the genetic architecture of longevity by inspecting millions of relative pairs and to provide insights into the geographical dispersion of families...
March 1, 2018: Science
Mahipal Ganji, Indra A Shaltiel, Shveta Bisht, Eugene Kim, Ana Kalichava, Christian H Haering, Cees Dekker
It has been hypothesized that Structural Maintenance of Chromosomes (SMC) protein complexes such as condensin and cohesin spatially organize chromosomes by extruding DNA into large loops. Here, we provide unambiguous evidence for loop extrusion by directly visualizing the formation and processive extension of DNA loops by yeast condensin in real-time. We find that a single condensin complex is able to extrude tens of kilobase pairs of DNA at a force-dependent speed of up to 1,500 base pairs per second, using the energy of ATP hydrolysis...
February 22, 2018: Science
Charleen Gaunitz, Antoine Fages, Kristian Hanghøj, Anders Albrechtsen, Naveed Khan, Mikkel Schubert, Andaine Seguin-Orlando, Ivy J Owens, Sabine Felkel, Olivier Bignon-Lau, Peter de Barros Damgaard, Alissa Mittnik, Azadeh F Mohaseb, Hossein Davoudi, Saleh Alquraishi, Ahmed H Alfarhan, Khaled A S Al-Rasheid, Eric Crubézy, Norbert Benecke, Sandra Olsen, Dorcas Brown, David Anthony, Ken Massy, Vladimir Pitulko, Aleksei Kasparov, Gottfried Brem, Michael Hofreiter, Gulmira Mukhtarova, Nurbol Baimukhanov, Lembi Lõugas, Vedat Onar, Philipp W Stockhammer, Johannes Krause, Bazartseren Boldgiv, Sainbileg Undrakhbold, Diimaajav Erdenebaatar, Sébastien Lepetz, Marjan Mashkour, Arne Ludwig, Barbara Wallner, Victor Merz, Ilja Merz, Viktor Zaibert, Eske Willerslev, Pablo Librado, Alan K Outram, Ludovic Orlando
The Eneolithic Botai culture of the Central Asian steppes provides the earliest archaeological evidence for horse husbandry, ~5,500 ya, but the exact nature of early horse domestication remains controversial. We generated 42 ancient horse genomes, including 20 from Botai. Compared to 46 published ancient and modern horse genomes, our data indicate that Przewalski's horses are the feral descendants of horses herded at Botai and not truly wild horses. All domestic horses dated from ~4,000 ya to present only show ~2...
February 22, 2018: Science
Da Mi, Zhen Li, Lynette Lim, Mingfeng Li, Monika Moissidis, Yifei Yang, Tianliuyun Gao, Tim Xiaoming Hu, Thomas Pratt, David J Price, Nenad Sestan, Oscar Marín
GABAergic interneurons regulate neural circuit activity in the mammalian cerebral cortex. These cortical interneurons are structurally and functionally diverse. Here, we use single-cell transcriptomics to study the origins of this diversity in mouse. We identify distinct types of progenitor cells and newborn neurons in the ganglionic eminences, the embryonic proliferative regions that give rise to cortical interneurons. These embryonic precursors show temporally and spatially restricted transcriptional patterns that lead to different classes of interneurons in the adult cerebral cortex...
February 22, 2018: Science
Bernhard Rauer, Sebastian Erne, Thomas Schweigler, Federica Cataldini, Mohammadamin Tajik, Jörg Schmiedmayer
The complexity of interacting quantum many-body systems leads to exceedingly long recurrence times of the initial quantum state for all but the smallest systems. For large systems, one cannot probe the full quantum state in all its details. Thus, experimentally, recurrences can only be determined on the level of the accessible observables. Realizing a commensurate spectrum of collective excitations in one-dimensional superfluids, we demonstrate recurrences of coherence and long range order in an interacting quantum many-body system containing thousands of particles...
February 22, 2018: Science
Rohan R Merchant, Jacob T Edwards, Tian Qin, Monika M Kruszyk, Cheng Bi, Guanda Che, Deng-Hui Bao, Wenhua Qiao, Lijie Sun, Michael R Collins, Olugbeminiyi O Fadeyi, Gary M Gallego, James J Mousseau, Philippe Nuhant, Phil S Baran
Cross-coupling chemistry is widely applied to carbon-carbon bond formation in the synthesis of medicines, agrochemicals, and other functional materials. Recently single-electron-induced variants of this reaction class have proven particularly useful in the formation of C(sp2 )-C(sp3 ) linkages, though certain compound classes have remained a challenge. Here we report the use of sulfones to activate the alkyl coupling partner in nickel-catalyzed radical cross-coupling with aryl zinc reagents. This method's tolerance of fluoroalkyl substituents proved particularly advantageous for the streamlined preparation of pharmaceutically-oriented fluorinated scaffolds that previously required multiple steps, toxic reagents, and non-modular retrosynthetic blueprints...
February 18, 2018: Science
Janice S Chen, Enbo Ma, Lucas B Harrington, Maria Da Costa, Xinran Tian, Joel M Palefsky, Jennifer A Doudna
CRISPR-Cas12a (Cpf1) proteins are RNA-guided enzymes that bind and cut DNA as components of bacterial adaptive immune systems. Like CRISPR-Cas9, Cas12a has been harnessed for genome editing based on its ability to generate targeted, double-stranded DNA (dsDNA) breaks. Here we show that RNA-guided DNA binding unleashes indiscriminate single-stranded DNA (ssDNA) cleavage activity by Cas12a that completely degrades ssDNA molecules. We find that target-activated, non-specific ssDNase cleavage is also a property of other type V CRISPR-Cas12 enzymes...
February 15, 2018: Science
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