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Volume 552 Number 7684 pp147-278

14 December 2017

About the cover

The cover shows a selection of fossilized pollen from sediment cores collected from East Antarctica's continental shelf. These ancient remains were used by Sean Gulick, Amelia Shevenell and their colleagues to help date sediments eroded from the Aurora Subglacial Basin and document the evolution of the East Antarctic Ice Sheet over the past 55 million years. The team's marine geological record indicates that before 7 million years ago, the ice sheet behaved dynamically and was characterized by substantial surface meltwater, much like today's Greenland Ice Sheet. This behaviour occurred when temperatures and atmospheric CO2 levels were similar to and higher than present — climate conditions expected to occur with continued global warming. Cover image: Sophie Warny, LSU

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outline

Outline

  • Repairing the neural highway

    At present, there is no way to reverse damage to the spinal cord or to restore lost function. But regenerative therapies in the initial stages of clinical testing are offering hope.

    • David Holmes

spotlight on chile

Spotlight

spotlight on anti-ageing

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Articles

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  • Enhancing mitochondrial proteostasis reduces amyloid-β proteotoxicity

    • Vincenzo Sorrentino
    • Mario Romani
    • Laurent Mouchiroud
    • John S. Beck
    • Hongbo Zhang
    • Davide D’Amico
    • Norman Moullan
    • Francesca Potenza
    • Adrien W. Schmid
    • Solène Rietsch
    • Scott E. Counts
    • Johan Auwerx

    Amyloid-β peptide proteopathies disrupt mitochondria, and restoring mitochondrial proteostasis reduces protein aggregation in animal models of amyloid-β disease.

  • Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4

    • Zdenek Skrott
    • Martin Mistrik
    • Klaus Kaae Andersen
    • Søren Friis
    • Dusana Majera
    • Jan Gursky
    • Tomas Ozdian
    • Jirina Bartkova
    • Zsofia Turi
    • Pavel Moudry
    • Marianne Kraus
    • Martina Michalova
    • Jana Vaclavkova
    • Petr Dzubak
    • Ivo Vrobel
    • Pavla Pouckova
    • Jindrich Sedlacek
    • Andrea Miklovicova
    • Anne Kutt
    • Jing Li
    • Jana Mattova
    • Christoph Driessen
    • Q. Ping Dou
    • Jørgen Olsen
    • Marian Hajduch
    • Boris Cvek
    • Raymond J. Deshaies
    • Jiri Bartek

    Disulfiram is metabolized into copper–diethyldithiocarbamate, which binds to NPL4 and induces its aggregation in cells, leading to blockade of the p97–NPL4–UFD1 pathway and induction of a complex cellular phenotype that results in cell death.

Letters

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  • Force loading explains spatial sensing of ligands by cells

    • Roger Oria
    • Tina Wiegand
    • Jorge Escribano
    • Alberto Elosegui-Artola
    • Juan Jose Uriarte
    • Cristian Moreno-Pulido
    • Ilia Platzman
    • Pietro Delcanale
    • Lorenzo Albertazzi
    • Daniel Navajas
    • Xavier Trepat
    • José Manuel García-Aznar
    • Elisabetta Ada Cavalcanti-Adam
    • Pere Roca-Cusachs

    The formation of cellular adhesion complexes is important in normal and pathological cell activity, and is determined by the force imposed by the combined effect of the distribution of extracellular matrix molecules and substrate rigidity.

  • Initiation and long-term instability of the East Antarctic Ice Sheet

    • Sean P. S. Gulick
    • Amelia E. Shevenell
    • Aleksandr Montelli
    • Rodrigo Fernandez
    • Catherine Smith
    • Sophie Warny
    • Steven M. Bohaty
    • Charlotte Sjunneskog
    • Amy Leventer
    • Bruce Frederick
    • Donald D. Blankenship

    Geophysical and geological data reveal increased ice-sheet variability and surface meltwater—possibly analogous to future conditions—offshore of the Aurora subglacial basin of East Antarctica during warm climate intervals of the past 50 million years.

    See also
  • Large emissions from floodplain trees close the Amazon methane budget

    • Sunitha R. Pangala
    • Alex Enrich-Prast
    • Luana S. Basso
    • Roberta Bittencourt Peixoto
    • David Bastviken
    • Edward R. C. Hornibrook
    • Luciana V. Gatti
    • Humberto Marotta
    • Luana Silva Braucks Calazans
    • Cassia Mônica Sakuragui
    • Wanderley Rodrigues Bastos
    • Olaf Malm
    • Emanuel Gloor
    • John Bharat Miller
    • Vincent Gauci

    Methane fluxes from the stems of Amazonian floodplain trees indicate that the escape of soil gas through wetland trees is the dominant source of methane emissions in the Amazon basin.

  • Pluripotent state transitions coordinate morphogenesis in mouse and human embryos

    • Marta N. Shahbazi
    • Antonio Scialdone
    • Natalia Skorupska
    • Antonia Weberling
    • Gaelle Recher
    • Meng Zhu
    • Agnieszka Jedrusik
    • Liani G. Devito
    • Laila Noli
    • Iain C. Macaulay
    • Christa Buecker
    • Yakoub Khalaf
    • Dusko Ilic
    • Thierry Voet
    • John C. Marioni
    • Magdalena Zernicka-Goetz

    Exit of epiblasts from an unrestricted naive pluripotent state is required for epithelialization and generation of the pro-amniotic cavity in mouse embryos and for amniotic cavity formation in human embryos and human embryonic stem cells.

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  • Inhibition of soluble epoxide hydrolase prevents diabetic retinopathy

    • Jiong Hu
    • Sarah Dziumbla
    • Jihong Lin
    • Sofia-Iris Bibli
    • Sven Zukunft
    • Julian de Mos
    • Khader Awwad
    • Timo Frömel
    • Andreas Jungmann
    • Kavi Devraj
    • Zhixing Cheng
    • Liya Wang
    • Sascha Fauser
    • Charles G. Eberhart
    • Akrit Sodhi
    • Bruce D. Hammock
    • Stefan Liebner
    • Oliver J. Müller
    • Clemens Glaubitz
    • Hans-Peter Hammes
    • Rüdiger Popp
    • Ingrid Fleming

    A product of the soluble epoxide hydrolase enzyme, 19,20-dihydroxydocosapentaenoic acid (19,20-DHDP), is implicated in the pathogenesis of diabetic retinopathy; levels of 19,20-DHDP increase in the retinas of mice and humans with diabetes, and inhibition of its production can rescue vascular abnormalities in a mouse model of the disease.

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  • Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumours

    • J. Justin Milner
    • Clara Toma
    • Bingfei Yu
    • Kai Zhang
    • Kyla Omilusik
    • Anthony T. Phan
    • Dapeng Wang
    • Adam J. Getzler
    • Toan Nguyen
    • Shane Crotty
    • Wei Wang
    • Matthew E. Pipkin
    • Ananda W. Goldrath

    The transcription factor Runx3 is identified as a central regulator of the development of tissue-resident memory CD8+ T cells, providing insights into the signals that promote T cell residency in non-lymphoid tissues and tumours.

  • A non-canonical Notch complex regulates adherens junctions and vascular barrier function

    • William J. Polacheck
    • Matthew L. Kutys
    • Jinling Yang
    • Jeroen Eyckmans
    • Yinyu Wu
    • Hema Vasavada
    • Karen K. Hirschi
    • Christopher S. Chen

    The transmembrane domain of NOTCH1 plays a key role in the assembly of adherens junctions and the non-transcriptional regulation of vascular permeability that links transcriptional programs with adhesive and cytoskeletal remodelling.

  • RNA polymerase III limits longevity downstream of TORC1

    • Danny Filer
    • Maximillian A. Thompson
    • Vakil Takhaveev
    • Adam J. Dobson
    • Ilektra Kotronaki
    • James W. M. Green
    • Matthias Heinemann
    • Jennifer M. A. Tullet
    • Nazif Alic

    RNA polymerase III is a key evolutionarily conserved regulator of longevity that may have potential as a therapeutic target for age-related conditions.

    See also
  • KAT2A coupled with the α-KGDH complex acts as a histone H3 succinyltransferase

    • Yugang Wang
    • Yusong R. Guo
    • Ke Liu
    • Zheng Yin
    • Rui Liu
    • Yan Xia
    • Lin Tan
    • Peiying Yang
    • Jong-Ho Lee
    • Xin-jian Li
    • David Hawke
    • Yanhua Zheng
    • Xu Qian
    • Jianxin Lyu
    • Jie He
    • Dongming Xing
    • Yizhi Jane Tao
    • Zhimin Lu

    The histone acetyl transferase KAT2A (also known as GCN5) can also catalyse histone succinylation, with the α-KGDH complex providing a local source of succinyl-CoA.

Corrigendum

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  • Corrigendum: The 4D nucleome project

    • Job Dekker
    • Andrew S. Belmont
    • Mitchell Guttman
    • Victor O. Leshyk
    • John T. Lis
    • Stavros Lomvardas
    • Leonid A. Mirny
    • Clodagh C. O’Shea
    • Peter J. Park
    • Bing Ren
    • Joan C. Ritland Politz
    • Jay Shendure
    • Sheng Zhong
    • the 4D Nucleome Network

Errata

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