ILLUSTRATION: SIMON PRADES
SCIENCE sciencemag.org 2 OCTOBER 2020 • VOL 370 ISSUE 6512 7NEWS
IN BRIEF
14 News at a glanceIN DEPTH
16 Europe builds ‘digital twin’ of Earth
to hone climate forecasts
Ingesting more data than ever before,
exascale model will simulate the impact of
climate change on humans B y P. Vo o s e n2 OCTOBER 2020 • VOLUME 370 • ISSUE 6512CONTENTS
INTRODUCTION
48 A cruel end to too many livesREVIEWS
50 Glymphatic failure as a final common
pathway to dementia
M. Nedergaard and S. A. Goldman56 Beyond aggregation: Pathological
phase transitions in neurodegenerative
disease C. Mathieu et al.61 Translating genetic risk of
Alzheimer’s disease into mechanistic
insight and drug targets A. Sierksma et al.66 Microglia modulate
neurodegeneration in Alzheimer’s and
Parkinson’s diseases T. B a r t e l s et al.SPECIAL SECTIONNEURODEGENERATION
ON THE COVER
Neurodegeneration in later life robs
us of our abilities and our memories,
slowly and inexorably, like leaves
falling from a tree. A greater under-
standing of the pathophysiological
underpinnings within the brain
may provide
crucial hints that
will help us delay
and perhaps
even reverse
symptoms.
See page 48.
Illustration:
Simon PradesSEE ALSO PERSPECTIVE p. 3217 China’s bold climate pledge earns
praise—but is it feasible?
Plan to achieve carbon neutrality by 2060
would make China a global leader, but
abandoning coal will be hard
By D. Normile18 Record U.S. and Australian fires
raise fears for many species
Scientists say fires likely wiped out
some rare Australian organisms,
and worry U.S. blazes now threaten more
By J. Pickrell and E. Pennisi
EDITORIAL p. 13INSIGHTS
LETTERS
30 NextGen Voices:
Funding fix: Spend timePERSPECTIVES
32 Shifts and drifts in prion science
Important questions remain unanswered
since prions were discovered four
decades ago By A. Aguzzi and E. De Cecco
NEURODEGENERATION SECTION p. 4834 Mutational selection in
normal urothelium
Mutations in normal tissue point to causes
of DNA damage and set the stage for cancer
By S. G. Rozen
RESEARCH ARTICLES pp. 75 & 8236 Coaxing stem cells to repair
the spinal cord
Spinal cells in mice can be induced to
generate protective oligodendrocytes
after injury By C. G. Becker and T. Becker
RESEARCH ARTICLE p. 7337 A rival to superalloys at high
temperatures
Slip-pathway activation provides plasticity
in a multiprincipal element alloy with
high-temperature strength By J. Cairney
RESEARCH ARTICLE p. 9519 Stem cell studies probe origins
of the placenta
Lab models of organ will track how
it emerges—and what can go wrong
By K. Servick20 The ‘bat man’ tackles COVID-
After a career investigating why so many
viruses come from bats, Linfa Wang
eyes a new challenge By K. Kupferschmidt22 A call for diagnostic tests to
report viral load
Measure could help officials know
who is most contagious By R. F. ServiceFEATURES
24 Official inaction
A Science investigation shows that FDA
oversight of clinical trials is lax, slow moving,
and secretive—and that enforcement is
declining By C. Piller
27 Disgraced researchers can
still reap drug industry payouts
By C. Piller
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