Dominguez-Medina et al., p. 918Rhabdomyosarcoma is a difficult-to-treat soft tissue pediatric tumor. In a particular subtype of this cancer, a fusion protein generated by a chro-mosomal

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23 NOVEMBER 2018 • VOL 362 ISSUE 6417 905SCIENCE sciencemag.org

RESEARCHA new approach can weigh individual virus particles Dominguez-Medina et al., p. 918

GENETICS

The mutational burden of aging As people age, they accumulate

somatic mutations in healthy

cells. About 25% of cells in

normal, sun-exposed skin harbor

cancer driver mutations. What

about tissues not exposed

to powerful mutagens like

ultraviolet light? Martincorena

et al. performed targeted gene

sequencing of normal esopha-

geal epithelium from nine human

donors of varying age (see the

Perspective by Chanock). The

mutation rate was lower in

esophagus than in skin, but there

was a strong positive selection

of clones carrying mutations in

14 cancer-associated genes. By

middle age, more than half of

the esophageal epithelium was

colonized by mutant clones.

Interestingly, mutations in the

cancer driver gene NOTCH1

were more common in normal

esophageal epithelium than in

esophageal cancer. —PAK

Science, this issue p. 911;

see also p. 893

SUPERCONDUCTIVITY

A monolayer of many talents Superconductors with a topolog-

ically nontrivial band structure

have been predicted to exhibit

exotic properties. However,

such materials are few and

far between. Now, two groups

show that the monolayer of the

material tungsten ditelluride

(WTe2)—already known to be

a two-dimensional topological

insulator—can also go supercon-

ducting. Fatemi et al. and Sajadi

et al. varied the carrier density

in the monolayer by applying

a gate voltage and observed a

transition from a topological to

a superconducting phase. The

findings may lead to the fabrica-

tion of devices in which local

gating enables topological and

superconducting phases to exist

in the same material. —JS

Science, this issue p. 926, p. 922

METALLURGY

Nanoparticle superalloy Improving the strength of a

metal alloy is hard to do without

sacrificing the ductility. Yang et

al. designed an iron-nickel-cobalt

(Fe-Ni-Co) alloy laced with

aluminum-titanium (Al-Ti)

nanoparticles with both high

strength and ductility. The key

was getting the composition

tuned correctly, because the

Fe-Ni-Co matrix reacts with the

Al-Ti nanoparticles. This was

vital for avoiding environmental

embrittlement, enhancing work

hardening, and improving ductil-

ity. —BG

Science, this issue p. 933

IMMUNOLOGY

Fine-tuning pyroptosis with ESCRT-III Pyroptosis is an inflammatory

form of cell death induced by

select caspases downstream

of inflammasome complexes.

PALEOECOLOGY

Megaherbivore extinctions in Africa

Human ancestors have

been proposed as drivers

of extinctions of Africa’s

diverse large mammal

communities. Faith et al.

challenge this view with an

analysis of eastern African her-

bivore communities spanning

the past ~7 million years (see

the Perspective by Bobe and

Carvalho). Megaherbivores (for

example, elephants, rhinos, and

hippos) began to decline about

4.6 million years ago, preceding

evidence for hominin consump-

tion of animal tissues by more

than 1 million years. Instead,

megaherbivore decline may

have been triggered by declining

atmospheric carbon dioxide and

expansion of grasslands. —AMS


see also p. 892

Artist’s rendering of a

prehistoric African landscape

I N SC IENCE J O U R NA L SEdited by Stella Hurtley

Published by AAAS

906 23 NOVEMBER 2018 • VOL 362 ISSUE 6417 sciencemag.org SCIENCE

These caspases cleave gas-

dermin D (GSDMD), whose

N-terminal fragments quickly

form large permeability pores

that induce cell death. However,

a large percentage of cells with

active inflammasomes are

resistant to pyroptosis. Rühl

et al. found that the mem-

brane-remodeling ESCRT-III

machinery was recruited to

the plasma membrane upon

GSDMD activation. ESCRT-III–

dependent membrane repair

limited proinflammatory cyto-

kine secretion and pyroptosis

after activation of inflamma-

somes. —STS


CANCER

Taking aim at a childhood cancerRhabdomyosarcoma is a

difficult-to-treat soft tissue

pediatric tumor. In a particular

subtype of this cancer, a fusion

protein generated by a chro-

mosomal abnormality drives

chemoresistance and aggres-

sive progression. Bharathy et

al. investigated why the histone

deacetylase inhibitor entinostat

shows promise in treating this

rhabdomyosarcoma subtype.

Entinostat altered epigenetic

regulation to inhibit translation

of the fusion protein. Without

Edited by Caroline Ash

and Jesse Smith

IN OTHER JOURNALS

PHYSIOLOGY

Could microbes be diabetogenic?Microbes that live in the gut

secrete metabolites that enter

the bloodstream and may

influence the health of the host

organism. Koh et al. found that

human gut microbes can pro-

duce the amino acid metabolite

imidazole propionate, which is

abundant in blood from human

patients with type 2 diabetes and

might contribute to their disease.

Germ-free mice injected with

imidazole propionate developed

glucose intolerance and disrupted

insulin signaling, like the diabetic

patients. Imidazole propionate

appeared to act, at least in part,

through the p38g mitogen-

activated protein kinase to

activate the mechanistic target of

rapamycin complex 1 (mTORC1)

protein kinase complex. —LBR

Cell 175, 947 (2018).

MICROFLUIDICS

Flexibility via fiber drawingTraditional microfluidic devices

are fabricated either by build-

ing up layers or by etching solid

the fusion protein, rhabdo-

myosarcoma growth in m ouse

models slowed, and tumors

were sensitized to the chemo-

therapeutic drug vincristine.

—LKF

Sci. Signal. 11, eaau7632 (2018).

ROBOTIC SENSING

A firm, but gentle, touchMany seemingly simple manual

tasks require the ability to

detect force direction as well

as magnitude. Boutry et al.

developed an electronic skin

inspired by human skin and

nature. Tiny pyramids, similar

to hill-like structures in human

skin, were arranged in spirals,

like the center of a sunflower.

These microstructures enabled

the sensor array to differentiate

pressure applied perpendicu-

larly from pressure applied at

an angle—a key feature for

dexterity. The pressure infor-

mation was used to interrupt

automatic movement of a

robotic arm. The robot was able

to touch a fresh raspberry and

reverse motion quickly enough

to avoid damaging the fruit.

—RLK

Sci. Robot. 3, eaau6914 (2018).

EMERGING INFECTIONS

Antibodies to abrogate Andes hantavirusAndes hantavirus circula tes

in rodent reservoirs and can

cause hantavirus cardiopulmo-

nary syndrome in humans. This

results in a potentially lethal

disease for which no vaccines

or targeted treatments exist.

Garrido et al. screened memory

B cells from people that had

been infected with Andes

hantavirus. Antibodies were

isolated from one individual

with a high viral neutralization

capacity. Two of these antibod-

ies were fully protective against

disease in a hamster model,

even when given several days

after infection. These antibod-

ies target distinct epitopes on

the viral glycoprotein and could

be developed for use alone or

as a combination therapy. —LP

Sci. Transl. Med. 10, eaat6420 (2018).

Normally cooperative ants change

their behavior toward sick individuals.

EPIDEMIOLOGY

Protecting the colony

When we get a cold and then stay home from work, we

are not only taking care of ourselves but also protect-

ing others. Such changes in behavior after infection

are predicted in social animals but are difficult to

quantify. Stroeymeyt et al. looked for such changes

in the black garden ant and found that infected workers did

alter their behavior—and healthy workers altered their behav-

ior toward the sick. The changed behavior was especially

valuable for protecting the most important and vulnerable

members of the colony. —SNV


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RESEARCH | IN SCIENCE JOURNALS

Published by AAAS

sciencemag.org SCIENCE

RESEARCH

AGRICULTURE

The future of farming In the mid-20th century, food

production from agriculture

sharply increased worldwide;

however, this was achieved

through heavy use of agro-

chemicals. Extensive collateral

damage from excessive use

of pesticides, herbicides, and

fertilizers has occurred to the

wider environment. This has led

to biodiversity loss, pesticide

resistance and the emergence of

new pests, pollution and decline

of freshwater supplies, and soil

degradation and erosion, as

well as direct harm to health. In

a Review, Pretty examines the

alternative approaches that can

achieve sustainable intensifi-

cation of farming systems by

integrating pest management

with agroecological systems to

minimize costs, maximize yields,

restore ecosystem services, and

ensure environmental enhance-

ment. —CA


SKIN REPAIR

Myofibroblast diversity with injury and aging Fibroblasts deposit extracel-

lular matrix (ECM) molecules

to regulate tissue strength and

function. However, if too much

ECM is deposited, fibrosis and

scarring results. Shook et al.

examined cells during mouse

skin wound healing, fibrosis,

and aging (see the Perspective

by Willenborg and Eming).

They identified distinct sub-

populations of myofibroblasts,

including cells identified as

adipocyte precursors (APs).

In cellular ablation mouse

models, CD301b-expressing

macrophages selectively

activated proliferation of APs,

but not other myofibroblasts.

Myofibroblast composition and

gene expression changed during

aging. Thus, macrophage-fibro-

blast interactions are important

during tissue repair and aging,

which may have therapeutic

implications for chronic wounds

and fibrotic disease. —BAP


see also p. 891

DEVELOPMENTAL BIOLOGY

Maternal factor sets axis The vertebrate body form

changes from the round shape of

the fertilized egg to a cylindri-

cal shape when the body plan

is established. However, it is

unknown whether a maternal

factor controls this body axis

formation. Yan et al. identified

such a maternal factor and

named it Huluwa. Loss of mater-

nal Huluwa, a transmembrane

protein, in zebrafish or frog eggs

resulted in embryos that lacked

the body axis and were miss-

ing the head and dorsoanterior

tissues. Huluwa promoted Axin

degradation, likely independent

of Wnt ligand–receptor signaling,

to protect b-catenin from deg-

radation and induce body axis

development during embryogen-

esis. —BAP


TOPOLOGICAL MATTER

A messy topological wire Adding irregularity to a system

can lead to a transition from a

more orderly to a less orderly

phase. Meier et al. demonstrated

a counterintuitive transi-

tion in the opposite direction:

Controlled fluctuations in the

system’s parameters caused

it to become topologically

nontrivial. The starting point

was a one-dimensional lattice

of ultracold rubidium atoms in

momentum space whose band

structure was topologically

trivial. The researchers then

introduced fluctuations in the

tunneling between the lattice

sites and monitored the atomic

“wires” as the amplitude of the

fluctuations increased. The

wires first became topologically

nontrivial and then went back

to trivial for sufficient disorder

strengths. —JS


NEUROSCIENCE

Egocentric representation of objects The lateral entorhinal cortex

(LEC) and medial entorhinal

cortex (MEC) are the two major

cortical projections to the hip-

pocampus. The discovery of a

variety of functional cell types in

MEC has greatly advanced our

understanding of the functional

anatomy of entorhinal-hippo-

campal circuits. However, the

function of LEC and the behav-

ioral correlates of LEC cells are

still not fully understood. Wang

et al. analyzed the firing proper-

ties of LEC and MEC neurons.

They found that LEC and MEC

used different reference frames,

with LEC encoding objects ego-

centrically. —PRS


DEVELOPMENTAL BIOLOGY

A single myosin sets chirality at all scales When viewed externally, most

organisms appear symmetric

between the left and right sides.

However, many organs are

left-right asymmetric. Whether

macroscopic asymmetries are

directly related to molecular-

level chirality remains an open

question. Working in Drosophila,

Lebreton et al. found that the

conserved molecular motor

myosin 1D induced stereotyped

chirality at all biological scales—

from F-actin turning in vitro to

the organ level and even organ-

ismal behavior. Thus, a single

conserved myosin can generate

de novo nano-to-macroscopic

changes in form and direction

through chiral interaction with

the actin cytoskeleton. —BAP


IMMUNOLOGY

Visualizing TGF-b1 regulation by GARP Regulatory T cells (T

regs) can

suppress immune responses

through a variety of mecha-

nisms. One such mechanism

involves the activation of a

surface-bound latent form of the

cytokine transforming growth

factor–b1 (TGF-b1). Within the

cell, newly synthesized pro-TGF-

b1 homodimers form disulfide

bonds with the transmembrane

protein GARP, which acts to chap-

erone and orient the cytokine

for activation at the cell surface.

Liénart et al. reveal how GARP

interacts with TGF-b1, using a

crystal structure in which the

complex was stabilized using a

Fab fragment from a monoclonal

antibody (MHG-8) that binds to

the complex. In so doing, they

also demonstrate how MHG-8

prevents membrane-associated

TGF-b1 release. These structural

and mechanistic insights may

inform treatments of diseases

with altered TGF-b1 functionality

and dysfunctional Treg

activity,

including cancer immunotherapy.

—STS


BEHAVIOR

From behavior change to conservation successBetween 1970 and 2014, wild

vertebrate populations have

declined by 60%, and natural

systems worldwide are under

increasing pressure from

human actions. Changes in

human behavior will be key to

addressing these conservation

challenges. In a Perspective,

Cinner discusses a range of

cognitive biases and social

perceptions that can be lever-

aged in conservation programs.

For example, losses tend to

hurt more than gains feel good.

Conservation efforts can take

account of this loss aversion

bias by stressing the potential

losses from not pursuing them.

However, integration of this and

other behavioral insights into

conservation is not straight-

forward. It is crucial that behav-

ior change interventions are not

seen as coercive and that they

Edited by Stella HurtleyALSO IN SCIENCE JOURNALS

907-B 23 NOVEMBER 2018 • VOL 362 ISSUE 6417

Published by AAAS

SCIENCE sciencemag.org

are carefully tailored to the situ-

ation to which they are applied.

—JFU and SNV


STEM CELLS

Rethinking stemness Stem cells are defined by their

ability to produce multiple cell

lineages and to self-renew.

New technology has allowed

the investigation of lineage

relationships in hematopoiesis,

the process that maintains the

cellular constituents of blood.

In a Perspective, Yamamoto et

al. discuss the recent changes

in our definitions of what a

stem cell is, as well as in our

understanding of the lineage

hierarchy in hematopoiesis.

They also discuss how this might

have consequences for patients

receiving stem cell transplants.

Such changes in concepts may

apply to other systems, such as

neurogenesis in the brain, for

which stem cell lineages are also

being questioned. —GKA


INNATE LYMPHOID CELLS

Fishing for ILCs in zebrafishMost studies on innate lymphoid

cells (ILCs) have focused on

their functions in mammals.

Both lymphoid cells and adap-

tive immunity are not unique

to mammals but are shared

by all vertebrates. Hernández

et al. studied lymphoid cells in

rag1-deficient zebrafish that lack

both B and T cells to elucidate the

functions of ILC-like cells. They

used single-cell RNA sequenc-

ing to profile gene expression

in gut-resident lymphocytes of

rag1-deficient zebrafish after

immune challenge. They identi-

fied lymphocytes in zebrafish that

correspond to mammalian ILC1,

ILC2, and ILC3 lineages. —AB

Sci. Immunol. 3, eaau5265 (2018).

MASS SPECTROMETRY

Bridging the mass gap Viruses and many large bio-

molecule complexes are in a

mass range that is challenging

to measure with conventional

mass spectrometry methods.

Nanomechanical resona-

tors can determine masses

of impacting molecules, but

separation methods often lose

too much of the sample to be

efficient. Dominguez-Medina et

al. used an aerodynamic lens

that improved separation and

focusing of nebulized molecules

with increasing mass. The mass

of both filled and empty viral

capsids was determined with

an array of 20 nanoresonators.

—PDS


23 NOVEMBER 2018 • VOL 362 ISSUE 6417 907-C

Published by AAAS

Documents

Dominguez-Medina et al., p. 918Rhabdomyosarcoma is a difficult-to-treat soft tissue pediatric tumor. In a particular subtype of this cancer, a fusion protein generated by a chro-mosomal