RESEARCH

Spin-bearing defects
in graphene
Lombardi et al., p. 1107

IN S CIENCE JOURNAL S Edited by Stella Hurtley

MOLECULAR BIOLOGY

The fitness landscape of AAV

A
deno-associated virus (AAV) is an
important gene therapy vector. Using

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tools from synthetic biology, Ogden
et al. provide a comprehensive view
of how sequence changes in capsid
proteins affect AAV properties. After satu-
ration mutagenesis of the AAV2 capsid
gene, the resulting library was subjected
to multiplexed phenotypic analyses,
including virus production, immunity,
thermostability, and biodistribution. The
mutant distribution to major organs in
mice revealed dominant trends affecting
in vivo delivery. Moreover, the findings
uncovered a viral accessory protein with
a role in viral production. Finally, a model
built from the capsid fitness landscape
enabled machine-guided design of useful
variants with much higher efficiency than
random mutagenesis. —SYM
Science, this issue p. 1139

Computer-generated image of the atomic

structure of adeno-associated virus

CREDITS: (TOP TO BOTTOM) LOMBARDI ET AL.; SCIENCE PICTURE CO/SCIENCE SOURCE

SUPERCONDUCTIVITY
A sharp boundary
in the cuprates
Many physicists working on
cuprate superconductors believe
that the so-called strange
metal phase in the cuprate
phase diagram is associated
with a quantum critical point.
Within this picture, the quan-
tum critical point gives rise to a
V-shaped region in the doping-
temperature phase diagram
of the cuprates: the strange
metal phase. Chen et al. used
angle-resolved photoemission
spectroscopy in the cuprate
family Bi2212 to challenge this
view. By taking comprehensive
measurements as a function of
doping and temperature—and
making sure that the signal was
not affected by environmental
conditions—they found an inco-
herent strange metal phase that
was sharply separated from a
conventional phase by a temper-
ature-independent vertical line in
the phase diagram. —JS
Science, this issue p. 1099
ELASTOCALORICS
A million times cooler
Elastocaloric materials can be
used for solid-state cooling
applications because they can
pump heat out of a system
using a reversible phase
transformation. However, many
such materials fail after a small
number of cycles. Hou et al.
found that laser melting of
elastocaloric metals can create
fatigue-resistant microstruc-
tures. A nickel-titanium–based
alloy could be cycled a million
times and still produce a
cooling of about 4 kelvin. This
processing method could
improve elastocaloric perfor-
mance and move us closer to
using these materials more
widely for solid-state cooling
applications. —BG
Science, this issue p. 1116
MATERIALS SCIENCE
Growing polymer brushes
from surfaces
Surface functionalization is
important in a broad range of
fields. One approach involves
polymer brushes, where poly-
mer chains are grafted onto
a surface. Cai et al. describe
the nanoscale functionaliza-
tion of surfaces by exploiting
the living crystallization-driven
self-assembly of polyferrocenyl-
based block copolymers (see
the Perspective by Presa Soto).
Small crystalline cylindrical
micelle seeds were attached
using noncovalent bonds to

1090 29 NOVEMBER 2019 • VOL 366 ISSUE 6469 sciencemag.org SCIENCE

Published by AAAS
 a variety of surfaces, includ-
ing silicon wafers, graphene
oxide nanosheets, and gold.
Addition of dissolved unimers
over the seed-coated surfaces
allowed micellar brushes to
grow. Protonation and post-
decoration with gold and silver
nanoparticles demonstrated the
applicability of such modified
surfaces in catalysis, as antibac-
terial agents, and in separation
processes. —MSL
Science, this issue p. 1095;
see also p. 1078
ENHANCER GENOMICS
Linking enhancers
growth, and patients with a
IN OTHER JOURNALS Edited by Caroline Ash
lactose-malabsorption genotype
and Jesse Smith
had a greater abundance of
Enterococcus. A lactose-free diet
limited Enterococcus growth,
reduced the severity of GVHD,
and improved survival in gnoto-
biotic mouse models. —PNK
Science, this issue p. 1143;
see also p. 1077
HIV
Early to treat, early
to thrive
Timing of antiretroviral therapy
(ART) initiation for HIV can
influence viral-reservoir seeding
and also the immune response.

to disease
Enhancers are genomic regions
that regulate gene expression,
sometimes in a cell-dependent
manner. However, most of our
knowledge of human brain cell–
type enhancers derives from
studies of bulk human brain
tissue. Nott et al. examined chro-
matin and promoter activity in
cell nuclei isolated from human
brains. Genetic variants associ-
ated with brain traits and disease
showed cell-specific patterns
of enhancer enrichment. These
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However, this has not been
well characterized in neonatal
HIV infection. To discern how
ART affects neonates, Garcia-
Broncano et al. studied infants
from Botswana who were placed
on ART hours or months after
birth. Early initiation of therapy
reduced seeding of the viral
reservoir and also modulated
natural killer cell and T cell
responses to HIV. Thus, immedi- DRUG SOLVATION
ate ART initiation—earlier than
the current guidelines of a few A spoonful of sugar for your coffee
weeks—could provide real ben-

data indicate that Alzheimer’s
disease is regulated by genetic
variants within microglial cells,
whereas psychiatric diseases
tend to affect neurons. —LMZ
Science, this issue p. 1134
MICROBIOME
Lactose can fuel GVHD
Allogeneic hematopoietic cell
transplantation (allo-HCT) is
used to treat certain hema-
topoietic malignancies, but
patients have a risk of develop-
ing graft-versus-host disease
(GVHD). Stein-Thoeringer et
al. performed a large-scale
analysis of more than 1300
patients treated with allo-HCT
PHOTO: NEW AFRICA/SHUTTERSTOCK
efit to infants with HIV. —LP
Sci. Transl. Med. 11, eaax7350 (2019).
TUMOR IMMUNOTHERAPY
New cell therapy fights
brain tumors
An adoptive cellular therapy
that expands clonal T cells could
help fight deadly heterogeneous
brain tumors, medulloblastoma,
and glioblastoma. Working in
mice, Flores et al. used dendritic
cells expressing tumor RNA to
expand polyclonal T cells that
quickly react against a variety of
different antigens within different
brain tumors. Promising results
were also obtained in a patient
with recurrent medulloblastoma.
A
lthough we brew coffee and tea in water, the psychoac-
tive drug we crave, caffeine, is moderately hydrophobic
and becomes more so as the temperature of a beverage
decreases. Stacked aggregates of caffeine molecules,
which may have different properties, can form at satura-
tion. Shumilin et al. investigated the distribution of caffeine
aggregates and monomers in response to increasing concen-
tration of a common excipient: sugar. Although various sugars
decreased overall caffeine solubility, they had a preferential
effect on oligomers and resulted in a higher relative proportion
of caffeine in the monomer form. —MAF
J. Am. Chem. Soc. 141, 18056 (2019).
Adding sugar to coffee can change the solubility and aggregation
behavior of caffeine molecules.
HEART DISEASE by studying mice that volun-
tarily ran for long distances on
Exercise finds its niche exercise wheels. They found that
Regular physical activity is asso-
these physically active mice had

ciated with a lower rate of death

across four clinical centers (see
the Perspective by Zitvogel and
Kroemer). High levels of bacteria
from the Enterococcus genus
were associated with greater
incidence of GVHD and mortal-
ity. Lactose appears to provide
a substrate for Enterococcus
Although previous adoptive T cell
therapies have proven effective
against several advanced cancers,
the current method could provide
patients with effective T cell
therapy for brain tumors. —SMF
Sci. Adv. 10.1126/
sciadv.aav9879 (2019).
from heart disease, but the
underlying mechanisms are not
fully understood. Frodermann
et al. examined the effect of
exercise on cardiovascular
inflammation, a known risk
factor for atherosclerosis,
fewer inflammatory cells (leuko-
cytes) than sedentary mice, an
effect they traced to diminished
activity of hematopoietic stem
and progenitor cells (HSPCs).
The lower activity of HSPCs was
due at least in part to exercise-
induced reduction in the levels

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Published by AAAS
RESEARCH
ALSO IN SCIENCE JOURNALS
NEUROSCIENCE
Brain anatomy revealed
in startling detail
The mammalian cerebral cortex
is an enormously complex net-
work of neuronal processes that
are long and thin, branching, and
extremely densely packed. This
high packing density has made
the reconstruction of cortical
neuronal networks challeng-
ing. Motta et al. used advanced
automated imaging and analysis
tools to reconstruct with high
spatial resolution the morpho-
logical features of 89 neurons
and their connections in the
mouse barrel cortex. The recon-
struction covered an area more
than two orders of magnitude
larger than earlier neuroana-
tomical mapping attempts. This
approach revealed information
about the connectivity of inhibi-
tory and excitatory synapses
of corticocortical as well as
excitatory thalamocortical con-
nections. —PRS
Science, this issue p. 1093
SEISMOLOGY
Marine observations
with optics
Placing sensors on the seafloor
is difficult, but a sensor network
has huge potential for observ-
ing processes occurring both
below and above the seafloor.
Lindsey et al. measured acoustic
vibrations collected by attach-
ing a laser to the Monterey
Accelerated Research System’s
subsea optical fiber during
a maintenance period (see
the Perspective by Jousset).
Acoustic waves were monitored
by changes in laser light along
the cable. The observations from
just a few days allowed mapping
of an unknown fault system and
detection of several dynamic
processes in the water column
above. —BG
Science, this issue p. 1103;
see also p. 1076
1092-B 29 NOVEMBER 2019 • VOL 366 ISSUE 6469
Edited by Stella Hurtley
QUANTUM MATERIALS
Controlling quantum
defects in graphene
The development of quantum
technologies relies on the abil-
ity to fabricate and engineer
materials with robust quantum
properties. The controlled
introduction of defects in
semiconductors is one of the
most promising platforms under
development. With the capabil-
ity to precisely position point
defects (five-membered rings) in
the graphene honeycomb lattice,
Lombardi et al. explored recent
theoretical work suggesting that
such defects should display
enhanced quantum properties
(see the Perspective by von
Kugelgen and Freedman). The
spin-bearing properties of the
defects and the engineered
control of their interactions
open up exciting possibilities for
graphene-based spintronics and
quantum electronics. —ISO
Science, this issue p. 1107;
see also p. 1070
CHEMICAL PHYSICS
Glimpsing an exchange
of partners
When two diatomic molecules
collide, they can sometimes
swap partners. For instance,
two potassium-rubidium (KRb)
molecules can produce K2 and
Rb2. The four-atom intermediate
formed upon collision is typi-
cally too scarce and short-lived
to spot, even using ultrafast
techniques. Hu et al. circum-
vented this problem by studying
the reaction at temperatures
approaching 0 kelvin. Using a
combination of mass spectrom-
etry and velocity-map imaging,
the authors directly character-
ized the ionized K2Rb2 complex
as well as the reactant and
product populations. —JSY
Science, this issue p. 1111
Published by AAAS
NEUROSCIENCE
Keeping tabs on bad
experiences
Identifying the neural basis
underlying how we acquire,
process, and store negative
experiences could help the
search for effective treatments
for mood disorders. Szőnyi et al.
used a range of neuroscientific
tools to elucidate the role of a
specific neural circuit that origi-
nates in the median raphe region
of the murine brainstem (see the
Perspective by Ikemoto). A sub-
population of excitatory neurons
projected to aversive brain areas
and received recurrent feedback
from the lateral habenula and
convergent feedback from a
range of fear-related circuitry.
These neurons were activated
by aversive stimuli, and artificial
stimulation promoted aversion
or anxiety-related behavior. This
group of cells thus plays a pivotal
role in a network that helps to
mediate aversive motivation.
—PRS
Science, this issue p. 1094;
see also p. 1071
MAGNONICS
Toward magnonic devices
The field of magnonics aims
to use spin waves (SWs) and
their associated quasipar-
ticles—magnons—as carriers
of information. Compared with
the movement of charge in
conventional electronics, a major
advantage of SWs is reduced
Joule heating. However, SWs are
trickier to direct and control. Two
groups now go a step further
toward magnon-based devices.
Han et al. show that in multi-
layer films, domain walls can be
used to change the phase and
magnitude of a spin wave. Wang
et al. demonstrate how magnon
currents can be used to switch
the magnetization of an adjacent
layer. —JS
Science, this issue p. 1121, p. 1125
BIOCHEMISTRY
CTP hydrolysis organizes
chromosomes
The bacterial DNA parS centro-
mere recruits the ParB protein to
the bacterial chromosome. Soh
et al. found that the widespread
family of ParB proteins not only
bind DNA but also bind and
hydrolyze cytidine triphosphate
(CTP) (see the Perspective by
Funnell). ParB CTP hydrolysis is
stimulated by parS and regulates
the spreading of ParB protein
to the parS flanking regions,
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which is crucial for organizing
the bacterial chromosome. The
cytidine triphosphatase domain
is conserved in a large variety of
protein sequences, suggesting
its potential roles in other cel-
lular processes. —SYM
Science, this issue p. 1129;
see also p. 1072
PROTEIN FOLDING
A pathway for helical
membrane proteins
Membrane proteins are inserted
into cell membranes while they
are being translated and may
fold concurrently into their sec-
ondary and tertiary structures.
Choi et al. describe a single-
molecule force microscopy
technique that allowed them to
monitor folding of helical mem-
brane proteins in vesicles and
bicelles. Two helical membrane
proteins, the Escherichia coli
rhomboid protease GlpG and the
human b2-adrenergic receptor,
both folded from the N to the C
terminus, with structures form-
ing in units of helical hairpins. In
the cell, this would allow these
proteins to begin folding while
being translated. —VV
Science, this issue p. 1150
sciencemag.org SCIENCE
 RE S E ARC H

IMMUNOLOGY stress-granule formation. After

Microbiota influence
vaccine responses
Responses to vaccines can be
variable, and recent findings
suggest a potential explanation
may lie in the influence of gut
microbiota. In a Perspective,
Pulendran discusses how
systematic analyses of vaccina-
tion responses—for example,
to the influenza vaccine—are
revealing insights into vaccine
responses and the importance
of the gut microbiota in forming
immunogenicity to infectious
disease. This has implications for
vaccine design and for stratify-
ing individuals according to likely
DNA stimulation of human cells,
cGAS associated in an RNA-
dependent manner with G3BP1
and was found in cytoplasmic
foci that also contained messen-
ger RNA and the RNA-dependent
kinase PKR. Formation of
cytoplasmic cGAS condensates
necessary for DNA-stimulated
type I interferon production
required G3BP1 and PKR activity.
—ERW
Sci. Signal. 12, eaav7934 (2019).

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vaccine response. —GKA
Science, this issue p. 1074

T CELLS
Charting MAIT cell
development
Mucosal-associated invariant
T (MAIT) cells are a distinct
subset of T cells that recognize
vitamin B metabolites presented
by major histocompatibility
complex class I–related protein
(MR1). Koay et al. used bulk
and single-cell RNA sequencing
and flow cytometric analysis to
characterize the development of
murine and human MAIT cells.
In addition to providing a clearer
picture of MAIT cell development
in the thymus, the studies uncov-
ered several molecules that
play key roles in regulating this
process. Genetic inactivation
experiments in mice confirmed
the functions some of these mol-
ecules—including SAP, SATB1,
CXCR6, and CCR7—in regulating
MAIT cell development. —IW
Sci. Immunol. 4, eaay6039 (2019).

INNATE IMMUNITY
A convergence for RNA
and DNA sensing
In response to cytosolic DNA,
cyclic GMP-AMP synthase
(cGAS) initiates a type I inter-
feron response. Hu et al. found
that endogenous cGAS bound
to the nucleotide helicase
G3BP1, which is involved in

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