RESEARCH - Science · that ball milling of boehmite, g-AlOOH, created ~13-nano-meter-diameter...
Transcript of RESEARCH - Science · that ball milling of boehmite, g-AlOOH, created ~13-nano-meter-diameter...
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440 25 OCTOBER 2019 • VOL 366 ISSUE 6464 sciencemag.org SCIENCE
generated antibodies with long
regions that insert into the
active site of the neuraminidase
enzyme. —CA
Science, this issue p. 499
SOCIAL SCIENCES
Measuring street protest eventsStreet protests and popular
marches are an important form
of political expression, and how
they are measured shapes our
ability to understand their social
significance. Fisher et al. review
the growing research on protest
events and crowd forming, with
a focus on events following the
2016 U.S. election. They describe
best-practice methods for mea-
suring protest size and protester
motivation and making such
protest data publicly available
in real time. Such methods help
us understand who protests and
why and enable better assess-
ments of the social and political
impact of protests. —AC
Sci. Adv. 10.1126/
sciadv.aaw5461 (2019).
CELL ENGINEERING
Tea for type 1 and type 2 diabetesCell therapy is a promis-
ing approach for treating
diabetes. Yin et al. developed
an elegant control system by
engineering cells to respond to
protocatechuic acid, a metabo-
lite in green tea. Orally ingested
protocatechuic acid regulated
blood glucose by triggering
secretion of insulin or a short
variant of human glucagon–like
peptide 1 from engineered
cells implanted in mouse and
INFLUENZA
Alternative influenza targetThere is a pressing need for a
broadly protective influenza
vaccine that can neutralize
this constantly varying, deadly
virus. Stadlbauer et al. turned
their attention away from the
Edited by Michael FunkI N SC IENCE J O U R NA L S
RESEARCHSingle-atom spin manipulation Yang et al., p. 509
current vaccine target—the
mutable hemagglutinin—and
investigated an alternative, less
variable virus-coat glycoprotein:
neuraminidase. The authors
extracted monoclonal anti-
bodies (mAbs) from a human
donor naturally infected with
the H3N2 virus subtype. In
mice, the mAbs were broadly
protective against influenza
virus A groups 1 and 2 (human,
avian, and swine origin) and
some influenza B viruses. These
mAbs were also therapeutically
effective as late as 72 hours
after infection. The wide range
of reactivity probably relates
to the infection history of the
donor, whose plasmablasts
NEURODEVELOPMENT
Close-up of human cerebellar development
Early on, cerebellar development shares similarities across humans, nonhuman primates,
and even mice. But differences emerge while development progresses, as cellular and
molecular analyses by Haldipur et al. now reveal. The rhombic lip persists longer during
cerebellar development in humans than in either the mouse or the macaque and generates
a pool of neuroprogenitor cells. Similarly, the ventricular zone of the human cerebellum
goes a step further than that of the mouse in developing an additional proliferative layer with
outer radial glia cells. Transcriptome analysis revealed detailed similarities and differences
between progenitor cells of the developing human cerebellum and neocortex. —PJH
Science, this issue p. 454
tion
Fluorescence
microscopy image
of a developing
human cerebellum
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nonhuman primate models
of type 1 and type 2 diabetes.
This study demonstrates the
versatility of synthetic biology
for developing remotely con-
trolled cell-based therapies for
diabetes. —CC
Sci. Transl. Med.
11, eaav8826 (2019).
ECONOMICS
Racial bias in health algorithms The U.S. health care system
uses commercial algorithms
to guide health decisions.
Obermeyer et al. find evidence
of racial bias in one widely
used algorithm, such that
Black patients assigned the
same level of risk by the algo-
rithm are sicker than White
patients (see the Perspective
by Benjamin). The authors
estimated that this racial bias
reduces the number of Black
patients identified for extra
care by more than half. Bias
occurs because the algorithm
uses health costs as a proxy
for health needs. Less money
is spent on Black patients who
have the same level of need,
and the algorithm thus falsely
concludes that Black patients
are healthier than equally sick
White patients. Reformulating
the algorithm so that it no
longer uses costs as a proxy
for needs eliminates the racial
bias in predicting who needs
extra care. —TSR
Science, this issue p. 447;
see also p. 421
NANOMATERIALS
Milling corundum nanoparticlesHigh-purity corundum
(a-Al2O
3) nanoparticles could
enable applications such as
more stable catalyst supports
or precursors for high-strength
ceramics. Milling of corundum
only produces micrometer-
scale particles, and direct
synthesis from other alumi-
num oxides that would be
likely starting materials, such
as g-Al2O
3, fails because of
Edited by Caroline Ash
and Jesse SmithIN OTHER JOURNALS
SIGNALING
Network rewiring in cancerCancer-causing mutations
are likely to modulate exist-
ing signaling networks rather
than generate newly rewired
networks. During tumor growth,
tyrosine phosphorylation offers
a candidate mechanism for
transient alteration of physi-
ological function because of
its pivotal role in cell signaling.
Working with mouse lung tissue
samples, Lundby et al. used
advances in mass spectrometry
and proteomics to examine
how oncogenic mutations in
the epidermal growth factor
the high activation barrier for
converting the lattice structure
of these cubic close-packed
oxides. Amrute et al. show
that ball milling of boehmite,
g-AlOOH, created ~13-nano-
meter-diameter corundum
nanoparticles of high purity
through a mechanically induced
dehydration reaction and by the
effect of milling impacts on the
surface energy of the particles.
—PDS
Science, this issue p. 485
BIOGEOGRAPHY
Earthworm distribution in global soilsEarthworms are key com-
ponents of soil ecological
communities, performing vital
functions in decomposition
and nutrient cycling through
ecosystems. Using data from
more than 7000 sites, Phillips
et al. developed global maps of
the distribution of earthworm
diversity, abundance, and
biomass (see the Perspective
by Fierer). The patterns differ
from those typically found
in aboveground taxa; there
are peaks of diversity and
abundance in the mid-latitude
regions and peaks of biomass
in the tropics. Climate variables
strongly influence these pat-
terns, and changes are likely
to have cascading effects on
other soil organisms and wider
ecosystem functions. —AMS
Science, this issue p. 480;
see also p. 425
FERROELECTRICS
Flexible ferroelectricsHigh-quality ferroelectric materi-
als, which polarize in response
to an electric field, are usually
oxides that crack when bent.
Dong et al. found that high-
quality membranes of barium
titanate are surprisingly flexible
and super-elastic. These films
accommodate large strains
through dynamic evolution of
nanodomains during deforma-
tion. This discovery is important
for developing more robust flex-
ible devices. —BG
Science, this issue p. 475
BEHAVIOR
Dogs’ brains and behaviors
Dogs have been bred for traits ranging from herding and
hunting to companionship. Attributes such as trainability
or highly tuned olfaction characterize different breeds.
Using magnetic resonance imaging, Hecht et al. scanned
the brains of dogs from 10 breed groups defined by
behavioral specializations. Although dogs showed diversity in
craniofacial shape and brain volume, brain size was not strictly
defined by body size. Brain networks were identified that
related to behavioral specializations roughly corresponding
to social bonding, taste and smell, physical movement, and
affective and instinctual functions. The results show that the
fingerprints of humans’ selective interest in particular types of
behaviors is evident in the evolution of dogs’ brains. —PJH
J. Neurosci. 39, 7748 (2019).
Signs of
human
selection for
behavioral
specializations
is evident in
dogs’ brains.
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RESEARCH
RENEWABLE ENERGY
A multifaceted future for wind powerModern wind turbines already
represent a tightly optimized
confluence of materials science
and aerodynamic engineering.
Veers et al. review the challenges
and opportunities for further
expanding this technology, with
an emphasis on the need for
interdisciplinary collaboration.
They highlight the need to better
understand atmospheric physics
in the regions where taller tur-
bines will operate as well as the
materials constraints associated
with the scale-up. The mutual
interaction of turbine sites
with one another and with the
evolving features of the overall
electricity grid will furthermore
necessitate a systems approach
to future development. —JSY
Science, this issue p. 443
MICROBIOTA
One world, one healthAs people increasingly move to
cities, their lifestyles profoundly
change. Sonnenburg and
Sonnenburg review how the shift
of recent generations from rural,
outdoor environments to urban-
ized and industrialized settings
has profoundly affected our biol-
ogy and health. The signals of
change are seen most strikingly
in the reduction of commensal
microbial taxa and loss of their
metabolic functions. The extir-
pation of human commensals is
a result of bombardment by new
chemicals, foodstuffs, sanita-
tion, and medical practices. For
most people, sanitation and
readily available food have been
beneficial, but have we now
reached a tipping point? How
do we “conserve” our beneficial
symbionts and keep the patho-
gens at bay? —CA
Science, this issue p. 444
IMMUNOLOGY
Commensals rule the MAITrixMucosal-associated invariant T
(MAIT) cells play an important
role in mucosal homeostasis.
MAIT cells recognize microbial
small molecules presented by
the major histocompatibility
complex class Ib molecule MR1.
MAIT cells are absent in germ-
free mice, and the mechanisms
by which microbiota control
MAIT cell development are
unknown (see the Perspective
by Oh and Unutmaz). Legoux
et al. show that, in mice,
development of MAIT cells
within the thymus is gov-
erned by the bacterial product
5-(2-oxopropylideneamino)-6-D-
ribitylaminouracil, which rapidly
traffics from the mucosa to the
thymus, where it is captured by
MR1 and presented to develop-
ing MAIT cells. Constantinides et
al. report that MAIT cell induc-
tion only occurs during a limited,
early-life window and requires
exposure to defined microbes
that produce riboflavin deriva-
tives. Continual interactions
between MAIT cells and com-
mensals in the skin modulates
tissue repair functions. Together,
these papers highlight how the
microbiota can direct immune
cell development and subse-
quent function at mucosal sites
by secreting compounds that act
like self-antigens. —STS
Science, this issue p. 494, p. 445;
see also p. 419
PLANT BIOLOGY
Plant thirst quenched without waterDrought causes many billions
of dollars of annual losses to
farmers worldwide. Central to a
plant’s water use efficiency are
signaling pathways regulated
by the hormone abscisic acid
and its receptors. Vaidya et al.
screened a pool of candidate
small molecules and used struc-
ture-guided design to optimize
the function of an abscisic
acid receptor agonist (see the
Perspective by Phillips and
Sussman). Application of the
agonist protected Arabidopsis,
wheat, and tomato from under-
watering. —PJH
Science, this issue p. 446;
see also p. 416
INNATE IMMUNITY
NODs require S-palmitoylation to signalThe compartmentalization
of proteins within the cell is
essential for their function.
The addition of lipid molecules
redistributes proteins to the
cell surface or to membrane-
bound organelles. Working in
transgenic mice and in tissue
cultured cells, Lu et al. found
that nucleotide oligomerization
domain–like receptors 1 and 2
(NOD1 and NOD2), two pro-
teins responsible for detecting
bacterial products, required
lipid modifications for their
recruitment to the cell mem-
brane and function. The specific
modification, palmitoylation
at a cysteine thiol, was medi-
ated by the enzyme ZDHHC5.
Loss of ZDHHC5 or removal
of key modification residues
in NOD1 and NOD2 abolished
their function, compromising
antibacterial responses. Human
variants of NOD2 display altered
palmitoylation, which could help
to explain many inflammatory
conditions, such as irritable
bowel syndrome. —SMH
Science, this issue p. 460
STRUCTURAL BIOLOGY
Complex regulationThe protein kinase mTORC1
controls cellular growth in
response to external signals.
In the presence of nutrients, it
localizes on the surface of the
lysosome, where it is activated.
The Raptor domain of mTORC1
binds to a complex comprising
the protein Ragulator and a het-
erodimer of the Rag guanosine
triphosphatase, which can
adopt four different nucleotide
conformations depending on
nutrient availability. Rogala et al.
determined the structure of the
Raptor-Rag-Ragulator complex
at 3.2-angstrom resolution by
cryo–electron microscopy. The
structure shows why Raptor
binds only to a specific nucleo-
tide conformation of the Rag
heterodimer and suggests a
model for how mTORC1 would
dock onto the lysosomal surface,
which is a key step in its activa-
tion. —VV
Science, this issue p. 468
MUTATION
Genetic background affects variationRobustness, or the effect of
mutations on fitness, can affect
the evolutionary trajectory of a
species. By introducing a large
number of deleterious mutations
into many different genetic back-
grounds of yeast, Johnson et al.
found that, for many mutations,
the more fit the background,
the larger the deleterious
effect of the mutation (see the
Perspective by Miller). A more-fit
lineage is thus less tolerant to
deleterious mutations, whereas
less-fit lineages can tolerate
more mutations. This observa-
tion supports a tendency toward
diminishing returns for benefi-
cial mutations, which has been
shown to influence patterns of
adaptation. —LMZ
Science, this issue p. 490;
see also p. 418
STRUCTURAL BIOLOGY
Coupled transportCation-chloride cotransport-
ers move chloride and cations
across the cell membrane and
are important in regulating cell
volume and setting the chlo-
ride concentration inside the
cell. Mutations lead to serious
diseases, such as epilepsy. Liu
et al. present the structure of
the human potassium-chloride
Edited by Michael FunkALSO IN SCIENCE JOURNALS
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RESEARCH
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cotransporter KCC1, as deter-
mined by cryo–electron
microscopy. Based on the
structure, functional studies, and
molecular dynamics simulations,
they propose an ion transport
model. The structure provides
a framework for interpreting
disease-related mutations in
potassium-chloride cotransport-
ers. —VV
Science, this issue p. 505
TUMOR IMMUNOLOGY
Interior tumor viewsPrevious studies indicate that a
high frequency of intratumoral
neutrophils is associated with
a poor clinical prognosis. Si
et al. used microscopy and
imaging techniques to examine
how intratumoral interactions
between tumor-associated
neutrophils (TANs) and tumor-
infiltrating lymphocytes (TILs)
can affect TIL function. They
localized functional cell subsets,
which were then used to identify
hotspots of TAN-TIL interactions
within tumors. Some of these
TANs had a distinct phenotype,
and their physical association
with TILs reduced antitumor
functions of those TILs. —CNF
Sci. Immunol. 4, eaaw9159 (2019).
IMMUNOMETABOLISM
Metabolic quiescence for B cell maturityTransitional B cell precursors
mature into follicular B cells,
which are involved in antibody
responses. Farmer et al. discov-
ered a metabolic checkpoint
in this developmental process.
Compared with transitional
B cells, mouse and human fol-
licular B cells were metabolically
quiescent and had increased
activation of the kinase AMPK
and increased levels of the cell
surface ectoenzymes CD39 and
CD73, which generate extracel-
lular adenosine. Transitional
human B cells that expressed
CD73 or were exposed to an
AMPK agonist preferentially
acquired a follicular B cell
phenotype. —ERW
Sci. Signal. 12, eaaw5573 (2019).
SPIN PHYSICS
Coherent surface spin manipulationSpin-based quantum infor-
mation processing requires
coherent spin manipulation.
Yang et al. demonstrate coher-
ent control of surface titanium
and iron atom spins on a
magnesium oxide surface with
a magnetic scanning tunnel-
ing microscope tip. Arbitrary
sequences of fast electrical
pulses delivered to the top
induced large electric fields.
These fields drove metal-atom
movement, which then modu-
lated the tip-atom exchange
interaction to create an oscil-
lating effective magnetic field.
Advanced spin-control proto-
cols such as Ramsey fringes
and Hahn spin echoes revealed
quantum dynamics, such as
coherent oscillations in a tita-
nium atom dimer assembled on
the surface with the tip. —PDS
Science, this issue p. 509
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