Table of Contents

Volume 546 Number 7658 pp327-446

15 June 2017

About the cover

Three papers in this issue provide a plethora of new genome sequences for the Zika virus and offer insights into its genetic epidemiology. On page 401, Kristian Andersen and his colleagues reveal 39 new genome sequences obtained from infected patients and Aedes aegypti mosquitoes. Using phylogenetic analysis they conclude that the virus has been introduced to Florida on multiple separate occasions and that most of these events were linked to travel from the Caribbean. Their work also suggests that Zika transmission chains in Florida are unlikely to persist, indicating that future outbreaks would depend on transmission dynamics in the Americas. On page 406, Nuno Faria and his colleagues provide 54 new virus genomes, mostly from northeast Brazil, several sequenced in real time using portable DNA sequencers and a mobile genomics laboratory. Using these and other available sequences they trace the spatial origins and spread of the virus in Brazil and the Americas, revealing that northeast Brazil played a crucial role in establishing the epidemic and the spread of the virus on the continent. And on page 411, Bronwyn MacInnis and her colleagues analyse 110 Zika virus genomes derived from clinical and mosquito samples from ten countries and territories. Their work affirms the rapid expansion of the epidemic within Brazil and multiple introductions to other geographical regions. They also describe the ongoing evolution of the virus and look at how the accumulation of mutations might affect the future performance of diagnostic tests. Cover image: Jasiek Krzysztofiak/Nature

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  • Plot your course

    A safe haven for career support unlocks a range of non-academic options, says Nathan L. Vanderford.

    • Nathan L. Vanderford

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Futures

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    How to live happily ever after.

    • Cassandra Khaw

Specials

spotlight: Patience for patients

Spotlight

  • Patience for patients

    Researchers find that perseverance and an altruistic streak keep them going along the long road to drug discovery.

    • Neil Savage

research

Perspectives

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  • Damming the rivers of the Amazon basin

    • Edgardo M. Latrubesse
    • Eugenio Y. Arima
    • Thomas Dunne
    • Edward Park
    • Victor R. Baker
    • Fernando M. d’Horta
    • Charles Wight
    • Florian Wittmann
    • Jansen Zuanon
    • Paul A. Baker
    • Camila C. Ribas
    • Richard B. Norgaard
    • Naziano Filizola
    • Atif Ansar
    • Bent Flyvbjerg
    • Jose C. Stevaux

    The current and expected environmental consequences of built dams and proposed dam constructions in the Amazon basin are explored with the help of a Dam Environmental Vulnerability Index.

Articles

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  • Common genetic variation drives molecular heterogeneity in human iPSCs

    • Helena Kilpinen
    • Angela Goncalves
    • Andreas Leha
    • Vackar Afzal
    • Kaur Alasoo
    • Sofie Ashford
    • Sendu Bala
    • Dalila Bensaddek
    • Francesco Paolo Casale
    • Oliver J. Culley
    • Petr Danecek
    • Adam Faulconbridge
    • Peter W. Harrison
    • Annie Kathuria
    • Davis McCarthy
    • Shane A. McCarthy
    • Ruta Meleckyte
    • Yasin Memari
    • Nathalie Moens
    • Filipa Soares
    • Alice Mann
    • Ian Streeter
    • Chukwuma A. Agu
    • Alex Alderton
    • Rachel Nelson
    • Sarah Harper
    • Minal Patel
    • Alistair White
    • Sharad R. Patel
    • Laura Clarke
    • Reena Halai
    • Christopher M. Kirton
    • Anja Kolb-Kokocinski
    • Philip Beales
    • Ewan Birney
    • Davide Danovi
    • Angus I. Lamond
    • Willem H. Ouwehand
    • Ludovic Vallier
    • Fiona M. Watt
    • Richard Durbin
    • Oliver Stegle
    • Daniel J. Gaffney

    Genetic and phenotypic analysis reveals expression quantitative trait loci in human induced pluripotent stem cell lines associated with cancer and disease.

  • A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis

    • Ujjini H. Manjunatha
    • Sumiti Vinayak
    • Jennifer A. Zambriski
    • Alexander T. Chao
    • Tracy Sy
    • Christian G. Noble
    • Ghislain M. C. Bonamy
    • Ravinder R. Kondreddi
    • Bin Zou
    • Peter Gedeck
    • Carrie F. Brooks
    • Gillian T. Herbert
    • Adam Sateriale
    • Jayesh Tandel
    • Susan Noh
    • Suresh B. Lakshminarayana
    • Siau H. Lim
    • Laura B. Goodman
    • Christophe Bodenreider
    • Gu Feng
    • Lijun Zhang
    • Francesca Blasco
    • Juergen Wagner
    • F. Joel Leong
    • Boris Striepen
    • Thierry T. Diagana

    The establishment of a drug-discovery screening pipeline for cryptosporidiosis, and identification of pyrazolopyridines as selective ATP-competitive inhibitors of the Cryptosporidium lipid kinase PI(4)K.

Letters

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  • Slush-like polar structures in single-crystal relaxors

    • Hiroyuki Takenaka
    • Ilya Grinberg
    • Shi Liu
    • Andrew M. Rappe

    Molecular dynamics simulations of the Pb(Mg1/3,Nb2/3)O3–PbTiO3 relaxor reveal a multi-domain state analogous to the slush state of water that provides an explanation for the unusual properties of relaxors.

  • Genomic epidemiology reveals multiple introductions of Zika virus into the United States

    • Nathan D. Grubaugh
    • Jason T. Ladner
    • Moritz U. G. Kraemer
    • Gytis Dudas
    • Amanda L. Tan
    • Karthik Gangavarapu
    • Michael R. Wiley
    • Stephen White
    • Julien Thézé
    • Diogo M. Magnani
    • Karla Prieto
    • Daniel Reyes
    • Andrea M. Bingham
    • Lauren M. Paul
    • Refugio Robles-Sikisaka
    • Glenn Oliveira
    • Darryl Pronty
    • Carolyn M. Barcellona
    • Hayden C. Metsky
    • Mary Lynn Baniecki
    • Kayla G. Barnes
    • Bridget Chak
    • Catherine A. Freije
    • Adrianne Gladden-Young
    • Andreas Gnirke
    • Cynthia Luo
    • Bronwyn MacInnis
    • Christian B. Matranga
    • Daniel J. Park
    • James Qu
    • Stephen F. Schaffner
    • Christopher Tomkins-Tinch
    • Kendra L. West
    • Sarah M. Winnicki
    • Shirlee Wohl
    • Nathan L. Yozwiak
    • Joshua Quick
    • Joseph R. Fauver
    • Kamran Khan
    • Shannon E. Brent
    • Robert C. Reiner Jr
    • Paola N. Lichtenberger
    • Michael J. Ricciardi
    • Varian K. Bailey
    • David I. Watkins
    • Marshall R. Cone
    • Edgar W. Kopp IV
    • Kelly N. Hogan
    • Andrew C. Cannons
    • Reynald Jean
    • Andrew J. Monaghan
    • Robert F. Garry
    • Nicholas J. Loman
    • Nuno R. Faria
    • Mario C. Porcelli
    • Chalmers Vasquez
    • Elyse R. Nagle
    • Derek A. T. Cummings
    • Danielle Stanek
    • Andrew Rambaut
    • Mariano Sanchez-Lockhart
    • Pardis C. Sabeti
    • Leah D. Gillis
    • Scott F. Michael
    • Trevor Bedford
    • Oliver G. Pybus
    • Sharon Isern
    • Gustavo Palacios
    • Kristian G. Andersen

    Genome sequencing of Zika virus samples from infected patients and Aedes aegypti mosquitoes in Florida shows that the virus was probably introduced into the United States on multiple occasions, and that the Caribbean is the most likely source.

    See also
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  • Establishment and cryptic transmission of Zika virus in Brazil and the Americas

    • N. R. Faria
    • J. Quick
    • I.M. Claro
    • J. Thézé
    • J. G. de Jesus
    • M. Giovanetti
    • M. U. G. Kraemer
    • S. C. Hill
    • A. Black
    • A. C. da Costa
    • L. C. Franco
    • S. P. Silva
    • C.-H. Wu
    • J. Raghwani
    • S. Cauchemez
    • L. du Plessis
    • M. P. Verotti
    • W. K. de Oliveira
    • E. H. Carmo
    • G. E. Coelho
    • A. C. F. S. Santelli
    • L. C. Vinhal
    • C. M. Henriques
    • J. T. Simpson
    • M. Loose
    • K. G. Andersen
    • N. D. Grubaugh
    • S. Somasekar
    • C. Y. Chiu
    • J. E. Muñoz-Medina
    • C. R. Gonzalez-Bonilla
    • C. F. Arias
    • L. L. Lewis-Ximenez
    • S. A. Baylis
    • A. O. Chieppe
    • S. F. Aguiar
    • C. A. Fernandes
    • P. S. Lemos
    • B. L. S. Nascimento
    • H. A. O. Monteiro
    • I. C. Siqueira
    • M. G. de Queiroz
    • T. R. de Souza
    • J. F. Bezerra
    • M. R. Lemos
    • G. F. Pereira
    • D. Loudal
    • L. C. Moura
    • R. Dhalia
    • R. F. França
    • T. Magalhães
    • E. T. Marques Jr
    • T. Jaenisch
    • G. L. Wallau
    • M. C. de Lima
    • V. Nascimento
    • E. M. de Cerqueira
    • M. M. de Lima
    • D. L. Mascarenhas
    • J. P. Moura Neto
    • A. S. Levin
    • T. R. Tozetto-Mendoza
    • S. N. Fonseca
    • M. C. Mendes-Correa
    • F. P. Milagres
    • A. Segurado
    • E. C. Holmes
    • A. Rambaut
    • T. Bedford
    • M. R. T. Nunes
    • E. C. Sabino
    • L. C. J. Alcantara
    • N. J. Loman
    • O. G. Pybus

    Virus genomes reveal the establishment of Zika virus in Brazil and the Americas, and provide an appropriate timeframe for baseline (pre-Zika) microcephaly in different regions.

    See also
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  • Zika virus evolution and spread in the Americas

    • Hayden C. Metsky
    • Christian B. Matranga
    • Shirlee Wohl
    • Stephen F. Schaffner
    • Catherine A. Freije
    • Sarah M. Winnicki
    • Kendra West
    • James Qu
    • Mary Lynn Baniecki
    • Adrianne Gladden-Young
    • Aaron E. Lin
    • Christopher H. Tomkins-Tinch
    • Simon H. Ye
    • Daniel J. Park
    • Cynthia Y. Luo
    • Kayla G. Barnes
    • Rickey R. Shah
    • Bridget Chak
    • Giselle Barbosa-Lima
    • Edson Delatorre
    • Yasmine R. Vieira
    • Lauren M. Paul
    • Amanda L. Tan
    • Carolyn M. Barcellona
    • Mario C. Porcelli
    • Chalmers Vasquez
    • Andrew C. Cannons
    • Marshall R. Cone
    • Kelly N. Hogan
    • Edgar W. Kopp
    • Joshua J. Anzinger
    • Kimberly F. Garcia
    • Leda A. Parham
    • Rosa M. Gélvez Ramírez
    • Maria C. Miranda Montoya
    • Diana P. Rojas
    • Catherine M. Brown
    • Scott Hennigan
    • Brandon Sabina
    • Sarah Scotland
    • Karthik Gangavarapu
    • Nathan D. Grubaugh
    • Glenn Oliveira
    • Refugio Robles-Sikisaka
    • Andrew Rambaut
    • Lee Gehrke
    • Sandra Smole
    • M. Elizabeth Halloran
    • Luis Villar
    • Salim Mattar
    • Ivette Lorenzana
    • Jose Cerbino-Neto
    • Clarissa Valim
    • Wim Degrave
    • Patricia T. Bozza
    • Andreas Gnirke
    • Kristian G. Andersen
    • Sharon Isern
    • Scott F. Michael
    • Fernando A. Bozza
    • Thiago M. L. Souza
    • Irene Bosch
    • Nathan L. Yozwiak
    • Bronwyn L. MacInnis
    • Pardis C. Sabeti

    One hundred and ten Zika virus genomes from ten countries and territories involved in the Zika virus epidemic reveal rapid expansion of the epidemic within Brazil and multiple introductions to other regions.

    See also
    See also
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  • Principles of early human development and germ cell program from conserved model systems

    • Toshihiro Kobayashi
    • Haixin Zhang
    • Walfred W. C. Tang
    • Naoko Irie
    • Sarah Withey
    • Doris Klisch
    • Anastasiya Sybirna
    • Sabine Dietmann
    • David A. Contreras
    • Robert Webb
    • Cinzia Allegrucci
    • Ramiro Alberio
    • M. Azim Surani

    The authors trace the emergence of porcine primordial germ cells and develop in vitro models of primordial germ cell development from human and monkey pluripotent stem cells in order to provide insight into early human development.

  • Stability and function of regulatory T cells expressing the transcription factor T-bet

    • Andrew G. Levine
    • Alejandra Medoza
    • Saskia Hemmers
    • Bruno Moltedo
    • Rachel E. Niec
    • Michail Schizas
    • Beatrice E. Hoyos
    • Ekaterina V. Putintseva
    • Ashutosh Chaudhry
    • Stanislav Dikiy
    • Sho Fujisawa
    • Dmitriy M. Chudakov
    • Piper M. Treuting
    • Alexander Y. Rudensky

    Regulatory T cells expressing the transcription factor T-bet selectively suppress TH1 and CD8 T cells, but not TH2 or TH17 activation and associated autoimmunity.

  • The metabolic function of cyclin D3–CDK6 kinase in cancer cell survival

    • Haizhen Wang
    • Brandon N. Nicolay
    • Joel M. Chick
    • Xueliang Gao
    • Yan Geng
    • Hong Ren
    • Hui Gao
    • Guizhi Yang
    • Juliet A. Williams
    • Jan M. Suski
    • Mark A. Keibler
    • Ewa Sicinska
    • Ulrike Gerdemann
    • W. Nicholas Haining
    • Thomas M. Roberts
    • Kornelia Polyak
    • Steven P. Gygi
    • Nicholas J. Dyson
    • Piotr Sicinski

    The cyclin D3–CDK6 kinase complex, which is overactive in some cancers, inhibits two key glycolysis enzymes and thereby enhances the levels of antioxidants in cells, promoting tumour cell survival.

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  • Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance

    • Sydney M. Shaffer
    • Margaret C. Dunagin
    • Stefan R. Torborg
    • Eduardo A. Torre
    • Benjamin Emert
    • Clemens Krepler
    • Marilda Beqiri
    • Katrin Sproesser
    • Patricia A. Brafford
    • Min Xiao
    • Elliott Eggan
    • Ioannis N. Anastopoulos
    • Cesar A. Vargas-Garcia
    • Abhyudai Singh
    • Katherine L. Nathanson
    • Meenhard Herlyn
    • Arjun Raj

    Through drug exposure, a rare, transient transcriptional program characterized by high levels of expression of known resistance drivers can get ‘burned in’, leading to the selection of cells endowed with a transcriptional drug resistance and thus more chemoresistant cancers.

Corrigendum

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