RESEARCH...SCIENCE sciencemag.org 11 DECEMBER 2020 • VOL 370 ISSUE 6522 1288-B RESEARCH DISEASE DYNAMICS Emergence to endemism The emergence of a devastat-ing transmissible facial

PH

OT

O:

SA

M P

AN

TH

AK

Y/

ST

RIN

GE

R/

GE

TT

Y I

MA

GE

S

1286 11 DECEMBER 2020 • VOL 370 ISSUE 6522 sciencemag.org SCIENCE

being applied to treat some

epithelial cancers. Krishna

et al. investigated why some

cancer patients respond to ACT,

whereas others do not. They

identified a population of CD8+ T

cells that had stem-like surface

markers that were associated

with effective tumor cell killing

and favorable response of

melanoma patients to ACT. Only

a small subset of T cells specific

against tumor mutations were

found in this stem-like state,

whereas most mutation-

reactive T cells were terminally

differentiated. These findings

could be of value in improving

cancer immunotherapy out-

comes. —PNK

Science, this issue p. 1328

CELL DEATH

Corals catch firePyroptosis is a form of inflam-

matory cell death that occurs in

response to pathogen infection

and results in the release of

intracellular contents mediated

by the pore-forming gasder-

min family proteins. Jiang

et al. identified a conserved

gasdermin E homolog in corals

that is cleaved by both coral

and human caspase 3 to form

two active N-terminal isoforms,

each capable of inducing

pyroptosis. After pathogen

infection, caspase-dependent

gasdermin E activation was

associated with mitochondrial

disruption and necrosis in

the reef-building coral spe-

cies Pocillopora damicornis.

Gasdermin-mediated cell

death is likely conserved in

some invertebrates and may

represent an immune defense

activated in corals during bac-

terial infection resulting from

environmental stress. —CO

Sci. Immunol.5, eabd2591 (2020).

CLIMATE CHANGE

A decline in the carbon fertilization effectOne source of uncertainty in

climate science is how the

carbon fertilization effect (CFE)

will contribute to mitigation

of anthropogenic climate

SOLAR CELLS

Efficiency from hole-selective contactsPerovskite/silicon tandem solar

cells must stabilize a perovskite

material with a wide bandgap

and also maintain efficient

charge carrier transport.

Al-Ashouri et al. stabilized a

perovskite with a 1.68–electron

volt bandgap with a self-assem-

bled monolayer that acted as an

efficient hole-selective contact

that minimizes nonradiative

carrier recombination. In air

without encapsulation, a tan-

dem silicon cell retained 95%

of its initial power conversion

efficiency of 29% after 300

hours of operation. —PDS


CANCER IMMUNOTHERAPY

Stem-like T cells mediate responseAdoptive cell transfer (ACT) is

a type of immunotherapy that

uses a patient’s own T lympho-

cytes to recognize and attack

cancer. ACT has been effective

in treating certain patients with

metastatic melanoma and is

INDIAN MONSOON

Season of the drought

The Indian monsoon is a critical source of water for hundreds of millions of people, and when

it fails to deliver its normal quantity of rain, enormous human, economic, and ecological

costs can be incurred. Monsoon droughts are not always seasonal, however. Borah et al.

found that nearly half of all monsoonal droughts were subseasonal and characterized by a

steep decline in late-season rainfall. Moreover, this type of subseasonal drought appears

to be related to a distinct cold anomaly in the North Atlantic Ocean, raising the possibility that

monsoon droughts may be more predictable. —HJS Science, this issue p. 1335

RESEARCHEdited by Michael Funk

I N SC IENCE J O U R NA L S

A woman carries water across a dry lakebed in India, where a late-season decline in the monsoon can lead to drought.

Published by AAAS

11 DECEMBER 2020 • VOL 370 ISSUE 6522 1287SCIENCE sciencemag.org

Edited by Caroline Ash

and Jesse SmithIN OTHER JOURNALS

CANCER

Alleviating side effectsPlatinum-based chemotherapy

drugs, such as cisplatin and

oxaliplatin, are commonly used

to treat diverse cancer types.

However, their use is limited

by side effects, particularly

vomiting, anorexia, muscle

wasting, and weight loss. Breen

et al. show that the amounts

of the cytokine growth dif-

ferentiation factor 15 (GDF15)

increase in the circulation of

patients with colorectal cancer,

non–small cell lung cancer

(NSCLC), and ovarian cancer

who were treated with platinum

chemotherapy. Moreover, the

amount of circulating GDF15

was correlated with weight loss

in metastatic colorectal cancer

patients receiving oxaliplatin.

Neutralization of GDF15 using

monoclonal antibodies in

nonhuman primates treated

with cisplatin attenuated vomit-

ing and anorexia. GDF15 also

reversed weight loss in mice with

NSCLC treated with cisplatin.

This work shows that GDF15 has

False-colored scanning electron microscope image of a coating for

cooling buildings, containing hollow glass microspheres (red) and

fluorescent pigment (green)

CR

ED

ITS

(F

RO

M L

EF

T T

O R

IGH

T):

WH

ITE

ET

AL

.; X

IAO

XU

E A

T T

HE

HO

NG

KO

NG

PO

LYT

EC

HN

IC U

NIV

ER

SIT

Y

RADIATIVE COOLING

A smarter radiative cooler

Passive daytime radiative cooling materials allow heat

to be transported into outer space through Earth’s

atmospheric infrared transparency window. Xue et al.

focus on engineering inexpensive coating materials for

buildings, which take advantage of daytime radiative

cooling but suppress it in the night when cooling no longer

is needed. This is accomplished by widening the emissivity

spectrum over the entire mid-infrared range. The strategy

also uses common materials for the coatings that are more

likely to withstand long-term weathering. —BG

Adv. Mater. 32, e1906751 (2020).

change. Wang et al. explored

the temporal dynamics of CFE

on vegetation photosynthesis at

the global scale. There has been

a decline over recent decades in

the contribution of CFE to vege-

tation photosynthesis, perhaps

owing to the limiting effects of

plant nutrients such as nitrogen

and phosphorus. This declining

trend has not been adequately

accounted for in carbon cycle

models. CFE thus has limita-

tions for long-term mitigation

of climate change, and future

warming might currently be

underestimated. —AMS


INTRACELLULAR IMAGING

Subcellular map of vesicle maturationInsulin-containing vesicles in

pancreatic b cells must migrate

from the cell interior to the cell

surface after stimulation by

glucose. Two studies now use

related whole-cell imaging tech-

niques, soft x-ray tomography,

and cryo–electron tomography

to resolve the distribution,

size, density, and location of

insulin-containing vesicles as

a function of time. White et al. visualized a mesoscale map

of whole cells, and Zhang et

al. provided higher-resolution

structural information in

specific “neighborhoods” of the

cell. Understanding insulin reg-

ulation of circulating glucose by

b cells will be advanced by this

global picture of intracellular

A colored soft x-ray tomogram shows

insulin vesicles (yellow spheres)

distributed within a pancreatic b cell

dynamics along the insulin

secretion pathway. —PLY

Sci. Adv. 10.1126/sciadv.abc8262,

10.1126/sciadv.abc8258 (2020).

QUANTUM INFORMATION

Molecular qubits that respond to lightSpins in solid-state systems such

as quantum dots and defect

centers in diamond can easily

be controlled by light for use in

quantum information process-

ing. More challenging is tuning

their properties and making

large arrays, something that

can be done more easily with

spins in molecules. Bayliss et al.

combined the advantages of the

two approaches by designing

and characterizing three related

molecular species that are opti-

cally addressable. The molecules

consist of a central chromium ion

surrounded by organic ligands,

and their spin and optical proper-

ties can be tailored by simply

changing the positions of methyl

groups on the ligands. —JS


ULTRACOLD CHEMISTRY

Electric field shielding of ultracold moleculesBecause reactive collisions

limit the lifetime of ultracold

molecular ensembles, con-

trolling chemical reactivity at

ultralow temperatures has been

a long-standing goal. Using

large electric fields that trigger

resonant dipolar interactions

between potassium-rubidium

molecules trapped in a quasi–

two-dimensional geometry,

Matsuda et al. report suppres-

sion of the reactive loss rate

in the vicinity of the dipolar-

mediated resonances by up to

an order of magnitude below

the background value. The

proposed shielding mechanism

is general and is expected to be

effective in three-dimensional

geometry. It could also be used

for creating long-lived quantum

molecular gases of other polar

molecules under strong electric

fields. —YS


Published by AAAS

11 DECEMBER 2020 • VOL 370 ISSUE 6522 1288-BSCIENCE sciencemag.org

RESEARCH

DISEASE DYNAMICS

Emergence to endemismThe emergence of a devastat-

ing transmissible facial cancer

among Tasmanian devils over

the past few decades has caused

substantial concern for their

future because these animals

are already threatened by a

regional distribution and other

stressors. Little is known about

the overall history and trajec-

tory of this disease. Patton et

al. used an epidemiological

phylodynamic approach to

reveal the pattern of disease

emergence and spread. They

found that low Tasmanian devil

densities appear to be contribut-

ing to slower disease growth and

spread, which is good news for

Tasmanian devil persistence and

suggests that care should be

taken when considering options

for increasing devil populations.

—SNV


SYSTEMS BIOLOGY

From phenotype to structureMuch insight has come from

structures of macromolecular

complexes determined by meth-

ods such as crystallography

or cryo–electron microscopy.

However, looking at transient

complexes remains challenging,

as does determining structures

in the context of the cellular

environment. Braberg et al. used

an integrative approach in which

they mapped the phenotypic

profiles of a comprehensive set

of mutants in a protein complex

in the context of gene deletions

or environmental perturbations

(see the Perspective by Wang).

By associating the similarity

between phenotypic profiles with

the distance between residues,

they determined structures

for the yeast histone H3-H4

complex, subunits Rpb1-Rpb2

of yeast RNA polymerase II, and

subunits RpoB-RpoC of bacterial

RNA polymerase. Comparison

with known structures shows

that the accuracy is comparable

to structures determined based

on chemical cross-links. —VV

Science, this issue p. 1294;

see also p. 1269

BIOPHYSICS

Rheology of aging protein condensatesProtein condensates that form

by undergoing liquid-liquid

phase separation will show

changes in their rheological

properties with time, a process

known as aging. Jawerth et

al. used laser tweezer–based

active and microbead-based

passive rheology to characterize

the time-dependent material

properties of protein conden-

sates (see the Perspective

by Zhang). They found that

condensate aging is not gela-

tion of the condensates, but

rather a changing viscoelastic

Maxwell liquid with a viscosity

that strongly increases with age,

whereas the elastic modulus

stays the same. —MSL


see also p. 1271

BATTERIES

Cracking the problem of cracking cathodesPolycrystalline cathode materi-

als that contain a combination

of nickel, manganese, and

cobalt have been used for

advanced lithium batteries.

These materials fracture at

high voltage, which increases

surface area and leads to more

side reactions and shorter cycle

life. Using single-crystalline

samples as model materials,

Bi et al. observed changes in

nickel-rich cathodes to study

the fracture behavior under well-

characterized conditions. As the

material is charged and lithium

is removed, specific planes glide

over one another and micro-

cracks are observed. However,

this process is reversed on

discharge, removing all traces of

the microcracking. The authors

developed a diffusion-induced

stress model to understand the

origin of the planar gliding and

propose ways to stabilize these

nickel-rich cathodes in working

batteries. —MSL


PALEOCLIMATE

Controlling atmospheric carbon dioxideThe atmospheric concentra-

tion of carbon dioxide (CO2) has

varied substantially over the

past million years in tandem with

the glacial cycle. Although it is

widely agreed that upwelling of

Southern Ocean water is a key

factor, the finer details about

what caused these CO2 varia-

tions are of great importance for

understanding climate. Ai et al.

identified three modes of change

in Southern Ocean upwelling,

adding a third to two previously

recognized ones. This new mode

can help explain better the rela-

tive timing of the glacial and CO2

cycles. —HJS


EVOLUTION

Diversity does not drive speciationThe role of the environment in

the origin of new species has

long been debated. Harvey et al.

examined the evolutionary history

and species diversity of subos-

cine birds in the tropics (see the

Perspective by Morlon). Contrary

to expectations that the tropics

have higher rates of speciation,

the authors observed that higher

and more constant speciation

rates occur in harsh environments

relative to the tropics. Thus, for

this group of birds, diversification

in temperate to Arctic regions

followed by the movement and

retention of species in the tropics

results in their higher local levels

of species diversity. —LMZ


see also p. 1268

CORONAVIRUS

Antibodies predating infectionImmunological memory after

infection with seasonal human

coronaviruses (hCoVs) may

potentially contribute to cross-

protection against severe acute

respiratory syndrome coro-

navirus 2 (SARS-CoV-2). Ng

et al. report that in a cohort of

350 SARS-CoV-2–uninfected

individuals, a small proportion

had circulating immunoglobulin

G (IgG) antibodies that could

cross-react with the S2 subunit

of the SARS-CoV-2 spike

protein (see the Perspective

by Guthmiller and Wilson). By

contrast, COVID-19 patients

generated IgA, IgG, and IgM anti-

bodies that recognized both the

S1 and S2 subunits. The anti-S2

antibodies from SARS-CoV-2–

uninfected patients showed

specific neutralizing activity

against both SARS-CoV-2 and

SARS-CoV-2 S pseudotypes.

A much higher percentage

of SARS-CoV-2–uninfected

children and adolescents were

positive for these antibodies

compared with adults. This pat-

tern may be due to the fact that

children and adolescents gener-

ally have higher hCoV infection

rates and a more diverse

antibody repertoire, which may

explain the age distribution of

COVID-19 susceptibility. —STS


see also p. 1272

IMMUNOLOGY

Small NOD to big changesThe innate pathogen-sensing

protein NOD1 mediates

proinflammatory responses

to molecular signals from

pathogens, but certain genetic

variants in the NOD1 gene are

associated with an increased

risk for developing gastric

cancer. Rommereim et al. found

that small increases in NOD1

abundance resulted in dispro-

portionately large increases in

the expression of inflammatory

Edited by Michael FunkALSO IN SCIENCE JOURNALS

Published by AAAS

1288-C 11 DECEMBER 2020 • VOL 370 ISSUE 6522 sciencemag.org SCIENCE

RESEARCH

genes and oncogenes. A 1.2-

to 1.3-fold increase in NOD1

abundance reduced the amount

of ligand required to activate

NOD1 in a monocytic cell line.

NOD1-mediated transcriptional

responses became ligand

independent upon a 1.5-fold

increase in NOD1 abundance.

—WW

Sci. Signal. 13, eaba3244 (2020).

INFLUENZA

Influencing influenza immunityHumans are exposed to influ-

enza virus throughout their

lifetimes through a combination

of infections and vaccinations.

It remains unclear whether dif-

ferent exposure routes induce

distinct influenza-specific

immunological memory. Dugan

et al. found that infection-

induced antibodies reacted

to non-neutralizing epitopes

of influenza virus, whereas

vaccination-induced antibodies

reacted to neutralizing epitopes.

Infection-induced antibodies

also preferentially responded

to influenza strains present

during an individual’s childhood.

Passive transfer of vaccination-

induced antibodies, but not

infection-induced antibodies,

protected mice in a model of

influenza infection. These find-

ings demonstrate that existing

influenza-specific memory and

route of exposure influence

influenza immunity. —CM

Sci. Transl. Med. 12, eabd3601 (2020).

CORONAVIRUS

A history of vaccine safetyVaccines are safe and effective

and save millions of lives each

year. Vaccine development has

led to rigorous safety protocols

to ensure that lessons from

history are not repeated. In a

Perspective, Knipe et al. discuss

the history of vaccine safety

issues that have led to cur-

rent regulations and protocols,

including pausing trials when

any adverse event arises and

ensuring safety monitoring

after regulatory approval. The

need for a COVID-19 vaccine

and possible early regulatory

approval before the completion

of phase 3 trials could risk our

ability to collect comprehensive

safety data. It is important that

safety, as well as efficacy, is

evaluated before deployment.

—GKA


ECONOMICS

Taxing mental healthMental equilibrium is essential

for an economically produc-

tive life in both industrialized

and developing countries.

Accumulating evidence shows

that mental ill-health and poverty

tend to be traveling partners,

but which is the cause? Ridley

et al. reviewed the literature on

natural and controlled economic

experiments involving individu-

als living in poverty. The authors

sought to resolve the mecha-

nisms whereby poverty triggers

mental illness and how mental

illness compounds poverty.

Their results reveal the benefits

of cash support and of low-cost

therapeutic interventions for

those suffering from mental ill-

ness under poverty. —CA


MOLECULAR BIOLOGY

CiBER-seq dissects genetic networksCells integrate environmental

signals and internal states

to dynamically control gene

expression. Muller et al. devel-

oped a technique to dissect this

cellular logic by linking targeted,

genome-wide genetic perturba-

tions with a deep-sequencing

readout that quantitatively mea-

sured the expression phenotype

induced by each perturbation.

The method, dubbed CiBER-

seq, was able to recapitulate

known regulatory pathways

linking protein synthesis with

nutrient availability in budding

yeast cells. Unexpectedly, the

authors found that the cellular

logic also appears to consider

protein production machinery

in this decision. By uncovering

additional facets of this deeply

conserved pathway, the findings

demonstrate the utility of

comprehensive and quantitative

CiBER-seq profiling in mapping

the gene networks underlying

cellular decisions. —SMH


DEVELOPMENTAL BIOLOGY

Trunk formation in a dishBuilding mammalian embryos

from self-organizing stem cells

in culture would accelerate the

investigation of morphogenetic

and differentiation processes

that shape the body plan.

Veenvliet et al. report a method

for generating embryonic trunk-

like structures (TLSs) with a

neural tube, somites, and gut

by embedding mouse embry-

onic stem cell aggregates in an

extracellular matrix surrogate.

Live imaging and comparative

single-cell transcriptomics

indicate that TLS formation is

analogous to mouse develop-

ment. TLSs therefore provide a

scalable, tractable, and acces-

sible high-throughput platform

for decoding mammalian

embryogenesis at a high level of

resolution. —BAP


DEVELOPMENTAL BIOLOGY

Timing and trigger of cell polarizationDuring mammalian embryo

development, the first cell fate

decision separates the pro-

genitors of the trophectoderm

(destined to form the placenta)

from the inner cell mass (which

forms all tissues of the embry-

onic and yolk sac). A key event for

this first lineage segregation is

the establishment of apicobasal

cell polarity. This event is set to

occur at a fixed developmental

stage. The factors that trigger the

establishment of cell polarity as

well as its temporal regulation

have remained unknown. Zhu et

al. show in mouse embryos that

three molecular regulators—

Tfap2c, Tead4, and RhoA—are

sufficient to advance the timing

of cell polarization with subse-

quent cell fate specification and

morphogenesis. —BAP


Published by AAAS

Documents

RESEARCH...SCIENCE sciencemag.org 11 DECEMBER 2020 • VOL 370 ISSUE 6522 1288-B RESEARCH DISEASE DYNAMICS Emergence to endemism The emergence of a devastat-ing transmissible facial