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


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


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


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


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


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


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


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


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


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


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

Published by AAAS

RESEARCH

25 OCTOBER 2019 • VOL 366 ISSUE 6464 442-CSCIENCE sciencemag.org

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


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


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RESEARCH - Science · that ball milling of boehmite, g-AlOOH, created ~13-nano-meter-diameter...

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