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Arnaud Pommier, Naishitha Anaparthy, Nicoletta Memos, Z Larkin Kelley, Alizée Gouronnec, Ran Yan, Cédric Auffray, Jean Albrengues, Mikala Egeblad, Christine A Iacobuzio-Donahue, Scott K Lyons, Douglas T Fearon
The majority of patients with pancreatic ductal adenocarcinoma (PDA) develop metastatic disease after resection of their primary tumor. We found that livers from patients and mice with PDA harbor single, disseminated cancer cells (DCCs) lacking expression of cytokeratin-19 (CK19) and major histocompatibility complex class I (MHCI). We created a mouse model to determine how these DCCs develop. Intra-portal injection of immunogenic PDA cells into pre-immunized mice seeded livers only with single, non-replicating DCCs that were CK19- and MHCI- The DCCs exhibited an endoplasmic reticulum (ER) stress response but, paradoxically lacked both inositol-requiring enzyme 1α activation and expression of the spliced form of transcription factor XBP1 (XBP1s)...
May 17, 2018: Science
Qiang Cai, Lulu Qiao, Ming Wang, Baoye He, Feng-Mao Lin, Jared Palmquist, Hsien-Da Huang, Hailing Jin
Some pathogens and pests deliver small RNAs (sRNAs) into host cells to suppress host immunity. Conversely, hosts also transfer sRNAs into pathogens and pests to inhibit their virulence. Although sRNA trafficking has been observed in a wide variety of interactions, how sRNAs are transferred, especially from hosts to pathogens/pests, is still unknown. Here we show that host Arabidopsis cells secrete exosome-like extracellular vesicles to deliver sRNAs into fungal pathogen Botrytis cinerea These sRNA-containing vesicles accumulate at the infection sites and are taken up by the fungal cells...
May 17, 2018: Science
Rumela Chakrabarti, Toni Celià-Terrassa, Sushil Kumar, Xiang Hang, Yong Wei, Abrar Choudhury, Julie Hwang, Jia Peng, Briana Nixon, John J Grady, Christina DeCoste, Jie Gao, Johan H van Es, Ming O Li, Iannis Aifantis, Hans Clevers, Yibin Kang
The stem cell niche is a specialized environment that dictates stem cell function during development and homeostasis. Here, we show that Dll1, a Notch pathway ligand, is enriched in mammary gland stem cells (MaSCs) and mediates critical interactions with stromal macrophages in the surrounding niche. Conditional deletion of Dll1 reduced the number of MaSCs and impaired ductal morphogenesis in the mammary gland. Moreover, MaSC-expressed Dll1 activates Notch signaling in stromal macrophages, increasing their expression of Wnt family ligands such as Wnt3, Wnt10A, and Wnt16, thereby initiating a feed back loop that promotes the function of Dll1+ MaSCs...
May 17, 2018: Science
Mark Lipson, Olivia Cheronet, Swapan Mallick, Nadin Rohland, Marc Oxenham, Michael Pietrusewsky, Thomas Oliver Pryce, Anna Willis, Hirofumi Matsumura, Hallie Buckley, Kate Domett, Nguyen Giang Hai, Trinh Hoang Hiep, Aung Aung Kyaw, Tin Tin Win, Baptiste Pradier, Nasreen Broomandkhoshbacht, Francesca Candilio, Piya Changmai, Daniel Fernandes, Matthew Ferry, Beatriz Gamarra, Eadaoin Harney, Jatupol Kampuansai, Wibhu Kutanan, Megan Michel, Mario Novak, Jonas Oppenheimer, Kendra Sirak, Kristin Stewardson, Zhao Zhang, Pavel Flegontov, Ron Pinhasi, David Reich
Southeast Asia is home to rich human genetic and linguistic diversity, but the details of past population movements in the region are not well known. Here, we report genome-wide ancient DNA data from eighteen Southeast Asian individuals spanning from the Neolithic period through the Iron Age (4100-1700 years ago). Early farmers from Man Bac in Vietnam exhibit a mixture of East Asian (southern Chinese agriculturalist) and deeply diverged eastern Eurasian (hunter-gatherer) ancestry characteristic of Austroasiatic speakers, with similar ancestry as far south as Indonesia providing evidence for an expansive initial spread of Austroasiatic languages...
May 17, 2018: Science
Koyel Banerjee-Ghosh, Oren Ben Dor, Francesco Tassinari, Eyal Capua, Shira Yochelis, Amir Capua, See-Hun Yang, Stuart S P Parkin, Soumyajit Sarkar, Leeor Kronik, Lech Tomasz Baczewski, Ron Naaman, Yossi Paltiel
It is commonly assumed that recognition and discrimination of chirality, both in nature and in artificial systems, depend solely on spatial effects. However, recent studies have suggested that charge redistribution in chiral molecules manifests an enantiospecific preference in electron spin orientation. We therefore reasoned that the induced spin polarization may affect enantiorecognition through exchange interactions. Here, we show experimentally that the interaction of chiral molecules with a perpendicularly magnetized substrate is enantiospecific...
May 10, 2018: Science
Teng Wang, Qibin Shi, Mehdi Nikkhoo, Shengji Wei, Sylvain Barbot, Douglas Dreger, Roland Bürgmann, Mahdi Motagh, Qi-Fu Chen
Surveillance of clandestine nuclear tests relies on a global seismic network, but the potential of spaceborne monitoring has been underexploited. Here, we determined the complete surface displacement field of up to 3.5 m of divergent horizontal motion with 0.5 m of subsidence associated with North Korea's largest underground nuclear test using satellite radar imagery. Combining insight from geodetic and seismological remote sensing, we found that the aftermath of the initial explosive deformation involved subsidence associated with sub-surface collapse and aseismic compaction of the damaged rocks of the test site...
May 10, 2018: Science
Elizabeth H Kellogg, Nisreen M A Hejab, Simon Poepsel, Kenneth H Downing, Frank DiMaio, Eva Nogales
Tau is a developmentally regulated axonal protein that stabilizes and bundles microtubules (MTs). Its hyperphosphorylation is thought to cause detachment from MTs and subsequent aggregation into fibrils implicated in Alzheimer's disease. It is unclear which tau residues are crucial for tau-MT interactions, where tau binds on MTs, and how it stabilizes them. We used cryo-electron microscopy to visualize different tau constructs on MTs, and computational approaches to generate atomic models of tau-tubulin interactions...
May 10, 2018: Science
Peter de Barros Damgaard, Rui Martiniano, Jack Kamm, J Víctor Moreno-Mayar, Guus Kroonen, Michaël Peyrot, Gojko Barjamovic, Simon Rasmussen, Claus Zacho, Nurbol Baimukhanov, Victor Zaibert, Victor Merz, Arjun Biddanda, Ilja Merz, Valeriy Loman, Valeriy Evdokimov, Emma Usmanova, Brian Hemphill, Andaine Seguin-Orlando, Fulya Eylem Yediay, Inam Ullah, Karl-Göran Sjögren, Katrine Højholt Iversen, Jeremy Choin, Constanza de la Fuente, Melissa Ilardo, Hannes Schroeder, Vyacheslav Moiseyev, Andrey Gromov, Andrei Polyakov, Sachihiro Omura, Süleyman Yücel Senyurt, Habib Ahmad, Catriona McKenzie, Ashot Margaryan, Abdul Hameed, Abdul Samad, Nazish Gul, Muhammad Hassan Khokhar, O I Goriunova, Vladimir I Bazaliiskii, John Novembre, Andrzej W Weber, Ludovic Orlando, Morten E Allentoft, Rasmus Nielsen, Kristian Kristiansen, Martin Sikora, Alan K Outram, Richard Durbin, Eske Willerslev
The Yamnaya expansions from the western steppe into Europe and Asia during the Early Bronze Age (~3000 BCE) are believed to have brought with them Indo-European languages and possibly horse husbandry. We analyze 74 ancient whole-genome sequences from across Inner Asia and Anatolia and show that the Botai people associated with the earliest horse husbandry derived from a hunter-gatherer population deeply diverged from the Yamnaya. Our results also suggest distinct migrations bringing West Eurasian ancestry into South Asia before and after but not at the time of Yamnaya culture...
May 9, 2018: Science
R W Pattie, N B Callahan, C Cude-Woods, E R Adamek, L J Broussard, S M Clayton, S A Currie, E B Dees, X Ding, E M Engel, D E Fellers, W Fox, P Geltenbort, K P Hickerson, M A Hoffbauer, A T Holley, A Komives, C-Y Liu, S W T MacDonald, M Makela, C L Morris, J D Ortiz, J Ramsey, D J Salvat, A Saunders, S J Seestrom, E I Sharapov, S K Sjue, Z Tang, J Vanderwerp, B Vogelaar, P L Walstrom, Z Wang, W Wei, H L Weaver, J W Wexler, T L Womack, A R Young, B A Zeck
The precise value of the mean neutron lifetime, τn , plays an important role in nuclear and particle physics and cosmology. It is used to predict the ratio of protons to helium atoms in the primordial universe and to search for physics beyond the Standard Model of particle physics. We eliminated loss mechanisms present in previous trap experiments by levitating polarized ultracold neutrons above the surface of an asymmetric storage trap using a repulsive magnetic field gradient so that the stored neutrons do not interact with material trap walls...
May 6, 2018: Science
Lorenzo Caputi, Jakob Franke, Scott C Farrow, Khoa Chung, Richard M E Payne, Trinh-Don Nguyen, Thu-Thuy T Dang, Inês Soares Teto Carqueijeiro, Konstantinos Koudounas, Thomas Dugé de Bernonville, Belinda Ameyaw, D Marc Jones, Ivo Jose Curcino Vieira, Vincent Courdavault, Sarah E O'Connor
Vinblastine, a potent anticancer drug, is produced by Madagascar periwinkle in small quantities: heterologous reconstitution of vinblastine biosynthesis could provide an additional source of this drug. The chemistry underlying vinblastine synthesis makes identification of the biosynthetic genes challenging. Here we identify the two missing steps of vinblastine biosynthesis in this plant, namely an oxidase and a reductase that isomerize stemmadenine acetate into dihydroprecondylocarpine acetate, which is then deacetoxylated and cyclized to either catharanthine or tabersonine via two herein characterized hydrolases...
May 3, 2018: Science
Tiancheng Song, Xinghan Cai, Matisse Wei-Yuan Tu, Xiaoou Zhang, Bevin Huang, Nathan P Wilson, Kyle L Seyler, Lin Zhu, Takashi Taniguchi, Kenji Watanabe, Michael A McGuire, David H Cobden, Di Xiao, Wang Yao, Xiaodong Xu
Magnetic multilayer devices that exploit magnetoresistance are the backbone of magnetic sensing and data storage technologies. Here, we report multiple-spin-filter magnetic tunnel junctions (sf-MTJs) based on van der Waals (vdW) heterostructures in which atomically thin chromium triiodide (CrI3 ) acts as a spin-filter tunnel barrier sandwiched between graphene contacts. We demonstrate tunneling magnetoresistance which is drastically enhanced with increasing CrI3 layer thickness, reaching a record 19,000% for magnetic multilayer structures using four-layer sf-MTJs at low temperatures...
May 3, 2018: Science
Maria Antonietta Tosches, Tracy M Yamawaki, Robert K Naumann, Ariel A Jacobi, Georgi Tushev, Gilles Laurent
Computations in the mammalian cortex are carried out by glutamatergic and GABAergic neurons forming specialized circuits and areas. Here we asked how these neurons and areas evolved in amniotes. We built a gene expression atlas of the pallium of two reptilian species using large-scale single-cell mRNA sequencing. The transcriptomic signature of glutamatergic neurons in reptilian cortex suggests that mammalian neocortical layers are made of new cell types generated by diversification of ancestral gene regulatory programs...
May 3, 2018: Science
Z Iftikhar, A Anthore, A K Mitchell, F D Parmentier, U Gennser, A Ouerghi, A Cavanna, C Mora, P Simon, F Pierre
Quantum phase transitions (QPTs) are ubiquitous in strongly-correlated materials. However the microscopic complexity of these systems impedes the quantitative understanding of QPTs. Here, we observe and thoroughly analyze the rich strongly-correlated physics in two profoundly dissimilar regimes of quantum criticality. With a circuit implementing a quantum simulator for the three-channel Kondo model, we reveal the universal scalings toward different low-temperature fixed points and along the multiple crossovers from quantum criticality...
May 3, 2018: Science
G P Donaldson, M S Ladinsky, K B Yu, J G Sanders, B B Yoo, W C Chou, M E Conner, A M Earl, R Knight, P J Bjorkman, S K Mazmanian
The immune system responds vigorously to microbial infection, while permitting life-long colonization by the microbiome. Mechanisms that facilitate the establishment and stability of the gut microbiota remain poorly described. We discovered that a sensor/regulatory system in the prominent human commensal Bacteroides fragilis modulates its surface architecture to invite binding of immunoglobulin A (IgA). Specific immune recognition facilitated bacterial adherence to cultured intestinal epithelial cells and intimate association with the gut mucosal surface in vivo...
May 3, 2018: Science
D R Klein, D MacNeill, J L Lado, D Soriano, E Navarro-Moratalla, K Watanabe, T Taniguchi, S Manni, P Canfield, J Fernández-Rossier, P Jarillo-Herrero
Magnetic insulators are a key resource for next-generation spintronic and topological devices. The family of layered metal halides promises varied magnetic states including ultrathin insulating multiferroics, spin liquids, and ferromagnets, but device-oriented characterization methods are needed to unlock their potential. Here, we report tunneling through the layered magnetic insulator CrI3 as a function of temperature and applied magnetic field. We electrically detect the magnetic ground state and inter-layer coupling and observe a field-induced metamagnetic transition...
May 3, 2018: Science
Jeremy Berg, Philip Campbell, Veronique Kiermer, Natasha Raikhel, Deborah Sweet
No abstract text is available yet for this article.
April 30, 2018: Science
Daniel E Wagner, Caleb Weinreb, Zach M Collins, James A Briggs, Sean G Megason, Allon M Klein
High-throughput mapping of cellular differentiation hierarchies from single-cell data promises to empower systematic interrogations of vertebrate development and disease. Here, we applied single-cell RNA sequencing to >92,000 cells from zebrafish embryos during the first day of development. Using a graph-based approach, we mapped a cell state landscape that describes axis patterning, germ layer formation, and organogenesis. We tested how clonally related cells traverse this landscape by developing a transposon-based barcoding approach ("TracerSeq") for reconstructing single-cell lineage histories...
April 26, 2018: Science
Gregory A Wyant, Monther Abu-Remaileh, Evgeni M Frenkel, Nouf N Laqtom, Vimisha Dharamdasani, Caroline A Lewis, Sze Ham Chan, Ivonne Heinze, Alessandro Ori, David M Sabatini
The lysosome degrades and recycles macromolecules, signals to the master growth regulator mTORC1, and is associated with human disease. Here, we performed quantitative proteomic analyses of lysosomes rapidly isolated using the LysoIP method and find that nutrient levels and mTOR dynamically modulate the lysosomal proteome. We focus on NUFIP1, a protein that upon mTORC1 inhibition redistributes from the nucleus to autophagosomes and lysosomes. Upon these conditions, NUFIP1 interacts with ribosomes and delivers them to autophagosomes by directly binding to LC3B...
April 26, 2018: Science
James A Briggs, Caleb Weinreb, Daniel E Wagner, Sean Megason, Leonid Peshkin, Marc W Kirschner, Allon M Klein
Time series of single-cell transcriptome measurements can reveal dynamic features of cell differentiation pathways. From measurements of whole frog embryos spanning zygotic genome activation through early organogenesis, we derived a detailed catalog of cell states in vertebrate development and a map of differentiation across all lineages over time. The inferred map recapitulates most if not all developmental relationships and associates new regulators and marker genes with each cell state. We find that many embryonic cell states appear earlier than previously appreciated...
April 26, 2018: Science
F Grigoli, S Cesca, A P Rinaldi, A Manconi, J A López-Comino, J F Clinton, R Westaway, C Cauzzi, T Dahm, S Wiemer
The M w 5.5 earthquake that struck South Korea in November 2017 was one of the largest and most damaging events in this country over the last century. Its proximity to an Enhanced Geothermal Systems site, where high pressure hydraulic injection had been performed during the previous two years, raises the possibility that this earthquake was anthropogenic. We have combined seismological and geodetic analyses to characterize the mainshock and its largest aftershocks, constrain the geometry of this seismic sequence and shed light on its casual factors...
April 26, 2018: Science
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