932-C 21 AUGUST 2020 • VOL 369 ISSUE 6506 sciencemag.org SCIENCE
RESEARCH
parcellation, consider varia-
tions between individual brains,
rely on reproducible workflows,
and provide web-based links
to other resources and data-
bases. Amunts et al. created
such an atlas based on serial
histological sections of brain.
They developed a computational
framework and refined the cur-
rent boundaries of the human
brain based on cytoarchitectural
patterns. This technique can
easily be transferred to build
brain atlases for other species
or a spatial framework for other
organs, other modalities, or
multimodal maps for regions of
interest at higher spatial scales.
This research makes similar
future attempts simultaneously
reproducible and flexible. —PRS
Science, this issue p. 988
DRUG DEVELOPMENT
Targeting STING for
cancer therapy
Activation of the STING
(stimulator of interferon genes)
protein by cyclic dinucleotide
metabolites plays a critical
role in antitumor immunity.
The development of synthetic
STING agonists is therefore
being pursued as a strategy for
cancer therapy, but the inherent
instability of dinucleotides has
limited current efforts. Pan et al.
and Chin et al. identified stable
STING agonists that act in a
“closed” conformation similar to
the natural STING ligand, cyclic
guanosine monophosphate–
adenosine monophosphate (see
the Perspective by Gajewski and
Higgs). The small molecules can
be given orally—an advantage
over previously developed STING
agonists, which required intra-
tumoral administration. After
oral or systemic administration
in mice, the agonists activated
STING and diverse immune cell
types to promote antitumor
immunity. These studies repre-
sent progress toward clinically
viable STING agonists for cancer
immunotherapy. —PNK
Science, this issue p. 935, p. 993;
see also p. 921
CORONAVIRUS
An antibody cocktail
against SARS-CoV-2
There is an urgent focus on
antibodies that target the severe
acute respiratory syndrome
coronavirus 2 (SARS-CoV-2)
viral spike and prevent the virus
from entering host cells. Hansen
et al. generated a large panel
of antibodies against the spike
protein from humanized mice
and recovered patients. From
this panel, they identified several
neutralizing antibodies, including
pairs that do not compete for
binding to the receptor binding
domain. Baum et al. focused
in on four of these antibodies.
All four are effective against
known spike variants. However,
by growing a pseudovirus that
expresses the spike in the pres-
ence of individual antibodies, the
authors were able to select for
spike mutants resistant to that
antibody. In contrast, escape
mutants are not selected when
pseudovirus is grown in the pres-
ence of pairs of antibodies that
either do not compete or only
partially compete for binding to
the RBD. Such a pair might be
used in a therapeutic antibody
cocktail. —VV
Science, this issue p. 1010, p. 1014GLOBAL CLIMATE CHANGE
All together then
Many geographically dispersed
records from across the globe
reveal the occurrence of abrupt
climate changes, called inter-
stadial events, during the last
glacial period. These events
appear to have happened at
the same time, but the difficulty
of determining absolute dates
in many of the records have
made that proposition difficult
to prove. Corrick et al. present
results from 63 precisely dated
speleothems that confirm the
synchrony of those interstadial
events. Their results also provide
a tool with which to validate
model simulations of abrupt cli-
mate change and calibrate other
time series such as ice-core
chronologies. —HJS
Science, this issue p. 963DEVELOPMENTAL BIOLOGY
In utero treatment for
hypertension
Chronic hypoxia during fetal
development increases car-
diovascular risk in offspring. In
experiments in sheep, Botting
et al. found that inhibition of
hypoxia-induced mitochondrial
stress through in utero delivery
of mitochondria-targeted ubiqui-
none (MitoQ) prevented growth
restriction and cardiovascular
dysfunction. Offspring of the
treated sheep were protected
from adult-onset hyperten-
sion. In chick embryos, MitoQ
treatment precluded structural
and functional heart defects
due to hypoxia. Thus, in utero
therapy to mitigate fetal hypoxia
exposure may protect against
adult-onset cardiovascular dys-
function. —JP
Sci. Adv. 10.1126/
sciadv.abb1929 (2020).CYTOKINES
Delivering IL-2 to Tregs
Interleukin-2 (IL-2) not only
promotes activation and expan-
sion of conventional T cells
but also plays a crucial role in
regulating homeostasis and
functions of regulatory T cells
(Tregs). Because expression of
the high-affinity IL-2 recep-
tor is largely restricted to Tregs,
engineering IL-2 variants called
muteins that selectively bind to
the high-affinity IL-2 receptor
and potentiate Treg functions
can be used in the treatment of
autoimmune diseases. Khoryati
et al. engineered a mouse IL-2
mutein that selectively promotes
expansion of Tregs. They demon-
strate that administration of this
IL-2 mutein resolved ongoing
diabetes in nonobese diabetic
mice. This proof-of-principle
study raises the possibility that
engineered human IL-2 muteins
could be used in the treatment
of autoimmune diseases. —AB
Sci. Immunol. 5 , eaba5264 (2020).MICROROBOTS
Robots fuel up
Batteries are a convenient
source of energy for untetheredminiature robots. However, the
low specific energy of small-
scale batteries sets limits on
how long such a robot can
operate. Yang et al. report
an insect-scale robot called
RoBeetle that is powered by the
controlled catalytic combus-
tion of methanol, a fuel with
more than 10 times the specific
energy of a small-scale battery.
RoBeetle, with size and mass
comparable to a small insect,
can carry payloads of up to 2.6
times its body weight, crawl
on rough surfaces, and ascend
inclines of 15 degrees. —MML
Sci. Robot. 5 , eaba0015 (2020).Published by AAAS