research - science · tóth et al. looked at the loss of large-bod-ied mammals in the pleistocene...

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1260 20 SEPTEMBER 2019 • VOL 365 ISSUE 6459 sciencemag.org SCIENCE

These magnetic WSM states

provide an ideal setting for exotic

transport effects. —JS

Science, this issue p. 1278, p. 1282,

p. 1286; see also p. 1248

TUMOR IMMUNOLOGY

Priming responses to checkpoint blockadeActivation of intracellular DNA

sensing has been proposed as

a means to promote antitumor

immunity, but molecules that

regulate sensing of intracellular

RNAs have received less atten-

tion. Heidegger et al. found that

PROTEIN FOLDING

Catch and releaseChaperones are essential for

proper protein folding inside cells,

but their interactions with client

proteins are difficult to study

because they are dynamic. Jiang

et al. used nuclear magnetic reso-

nance spectroscopy to look at

how the chaperones Hsp70 and

Hsp40 work together in the client

binding and release cycle. Hsp40

alters the folding properties of the

client protein, perhaps unfolding

a non-native state, by binding

dynamically through multiple

binding sites. Hsp70 binding to

Edited by Michael FunkI N SC IENCE J O U R NA L S

RESEARCHNodal lines in topological matter Wu et al., p. 1273

Hsp40 displaces the unfolded

client. The released protein may

either fold to its native state, or be

rebound for another chaperone

cycle. —VV

Science, this issue p. 1313

TOPOLOGICAL MATTER

Magnetic Weyl semimetalsWeyl semimetals (WSMs)—

materials that host exotic

quasiparticles called Weyl

fermions—must break either

spatial inversion or time-reversal

symmetry. A number of WSMs

that break inversion symmetry

have been identified, but showing

unambiguously that a material is

a time-reversal-breaking WSM is

tricky. Three groups now provide

spectroscopic evidence for this

latter state in magnetic materials

(see the Perspective by da Silva

Neto). Belopolski et al. probed

the material Co2MnGa using

angle-resolved photoemission

spectroscopy, revealing exotic

drumhead surface states. Using

the same technique, Liu et al.

studied the material Co3Sn

2S

2,

which was complemented by the

scanning tunneling spectroscopy

measurements of Morali et al.

Artist's rendering of a woolly

mammoth. Such animals shaped

Pleistocene ecosystems.

PALEONTOLOGY

Extinction leads to restructuring

By most accounts, human

activities are resulting in

Earth’s sixth major extinc-

tion event, and large-bodied

mammals are among those

at greatest risk. Loss of such vital

ecosystem components can have

substantial impacts on the struc-

ture and function of ecological

systems, yet fully understanding

these effects is challenging. Tóth et

al. looked at the loss of large-bod-

ied mammals in the Pleistocene

epoch to identify potential com-

munity assembly effects. They

found that the demise of large

mammals led to a restructuring

and a shift from biotic to abiotic

drivers of community structure.

Understanding past changes may

help predict the community-level

effects of the extinctions we are

currently driving. —SNV


er

Published by AAAS

20 SEPTEMBER 2019 • VOL 365 ISSUE 6459 1261SCIENCE sciencemag.org

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expression of the RNA sensor

RIG-I in tumor cells plays a vital

role in promoting responsiveness

to an immune checkpoint therapy

in mouse models of cancer. The

authors used engineered mela-

noma cell lines to map the relative

importance of various pathways

in regulating antitumor immunity

and responsiveness to check-

point blockade. Activation of RNA

sensing may be useful to increase

the immunogenicity of poorly

immunogenic tumors. —AB

Sci. Immunol. 4, eaau8943 (2019).

HIV

Taking RV144 beyond ThailandThe RV144 vaccine trial in

Thailand is based on the only HIV

vaccine to show efficacy against

HIV infection to date. Gray et al.

designed the HIV Vaccine Trials

Network 097 trial to test this

regimen in South Africa, where

clade C HIV circulates. Examining

immune protective responses

previously identified in the RV144

trial, the authors found the

vaccine to be even more immuno-

genic in South Africans, and the

magnitude of protective antibody

responses was greater compared

with RV144. The RV144 regimen

or others like it may therefore be

protective in areas where clade C

HIV is endemic. —LP

Sci. Transl. Med. 11, eaax1880 (2019).

NEUROSCIENCE

A brain pathway for active forgettingSleep affects memories via

several mechanisms. Izawa et

al. identified a possible new

pathway in the brain: REM

sleep–active hypothalamic

melanin-concentrating hormone

(MCH)–producing neurons,

which, among others, project to

the hippocampus. Surprisingly,

genetic ablation of MCH neurons

increased memory performance

in mice. Conversely, pharmacoge-

netic activation of MCH neurons

impaired memory. In vitro physi-

ological experiments showed that

activation of MCH fibers in hippo-

campal slices suppressed spiking

Edited by Caroline Ash

and Jesse SmithIN OTHER JOURNALS

IMMUNOLOGY

A haven for T cellsMemory T cells (MTCs) help

the host to respond quickly and

effectively to subsequent chal-

lenges by the same pathogen.

During times of nutritional

stress, the host may have to

balance productive immune

responses with competing

claims on limited resources.

In mice subjected to dietary

restriction, Collins et al. found

that MTCs translocate to the

bone marrow where they enter

a quiescent, energy-conserving

state accompanied by reduced

mechanistic target of rapamy-

cin signaling. Glucocorticoid

hormones mediated accumula-

tion of several cell types, not

only other immune cells, but

also adipocytes in bone marrow.

Adipocytes were important

for recruitment and survival of

MTCs in this niche. This adaptive

response ensures that immune

responses can persist during

periods of caloric restriction.

—STS

Cell 178, 1088 (2019).

activity of pyramidal cells. These

findings indicate that the MCH

pathway may become a target for

memory modulation. —PRS


SIGNAL TRANSDUCTION

Worms yield opioid receptor insightThe µ-opioid receptor (MOR)

is the target of pain-reducing

drugs, including morphine and

the potent synthetic opioid

fentanyl. Better understand-

ing of the receptor system is

needed to suppress potentially

deadly side effects and manage

addiction potential. Wang et

al. used a screen in the worm

Caenorhabditis elegans to find

genes that influenced MOR

function (see the Perspective by

Mercer Lindsay and Scherrer).

They found another receptor

called GPR139, loss of which

enhanced effects of morphine

in mice but reduced withdrawal

effects. GPR139 could be a tar-

get to improve safety or efficacy

of opioid therapy. —LBR

Science, this issue p. 1627;

see also p. 1246

BIOTECHNOLOGY

Tracking nucleic acids in living cellsFluorescence in situ hybridization

(FISH) is a powerful molecular

technique for detecting nucleic

acids in cells. However, it requires

cell fixation and denaturation.

Wang et al. found that CRISPR-

Cas9 protects guide RNAs

from degradation in cells only

when bound to target DNA.

Taking advantage of this target-

dependent stability switch, they

developed a labeling technique,

named CRISPR LiveFISH, to

detect DNA and RNA using

fluorophore-conjugated guide

RNAs with Cas9 and Cas13,

respectively. CRISPR LiveFISH

improves the signal-to-noise

ratio, is compatible with liv-

ing cells, and allows tracking

real-time dynamics of genome

editing, chromosome transloca-

tion, and transcription. —SYM


REPRODUCTION

Reorganization to initiate ovulation

In mammalian reproduction, oocyte development begins

before birth. The germ cell is surrounded by granulosa cells

of the primordial follicle. As luteinizing hormone from the

pituitary gland triggers follicle ovulation, transcriptional

changes enable cellular differentiation and, ultimately,

oocyte release. Bianco et al. use the systems biology approach

called FAIRE-seq to map regulatory elements before and after

the ovulatory signal and identify the mechanisms control-

ling the mouse follicle. After hormone signaling, granulosa

cells display modifications in distal regulatory elements. The

orphan nuclear receptor, liver receptor homolog-1, is remod-

eled and reprogrammed in granulosa cells to direct global

transcription during early ovulation for processes including

cytoskeletal architecture and cell migration. —BAP

Cell Rep. 28, 2443 (2019).

Scanning electron micrograph (false color) of an ovarian follicle

Published by AAAS

1262-B 20 SEPTEMBER 2019 • VOL 365 ISSUE 6459 sciencemag.org SCIENCE

RESEARCH

CLIMATE CHANGE

The need to stabilize global climateClimate change will be the great-

est threat to humanity and global

ecosystems in the coming years,

and there is a pressing need

to understand and communi-

cate the impacts of warming,

across the perspectives of the

natural and social sciences.

Hoegh-Guldberg et al. review the

climate change–impact litera-

ture, expanding on the recent

report of the Intergovernmental

Panel on Climate Change. They

provide evidence of the impacts

of warming at 1°, 1.5°, and 2°C—

and higher—for the physical

system, ecosystems, agricul-

ture, and human livelihoods.

The benefits of limiting climate

change to no more than 1.5°C

above preindustrial levels would

outweigh the costs. —AMS


HYDROLOGY

River restoration guided by researchHuman activities have altered the

flow regimes of many of Earth’s

rivers, with negative impacts

on biodiversity, water quality,

and ecological processes. In a

Review, Palmer and Ruhi explain

how restoration designs now

attempt to mimic ecologically

important aspects of natural flow

regimes, guided by insights into

how variations in flow affect biota

and ecosystem processes. To be

successful, such efforts must

go beyond accounting for flood

pulses to restore natural flow vari-

ability and achieve hydrological

connectivity between a river and

its surroundings. —JFU


DEVELOPMENT

Identifying terminal nematode cellsSingle-cell RNA sequencing

provides the power to identify

the developmental trajectory of

an organism. However, identify-

ing the temporal lineage of cell

development can be difficult

without large-scale analyses.

Packer et al. sequenced

more than 80,000 cells from

embryos of the roundworm

Caenorhabditis elegans to deter-

mine the expression of genes

directing the development of

terminal cell types. Because all

somatic cells in a C. elegans indi-

vidual have been mapped, the

authors are able to connect gene

expression with cell lineages

over time during development,

noting stark transitions in some

cases. —LMZ


ONE HEALTH

Livestock antibiotic resistanceMost antibiotic use is for

livestock, and it is growing with

the increase in global demand

for meat. It is unclear what the

increase in demand for antibiot-

ics means for the occurrence of

drug resistance in animals and

risk to humans. Van Boeckel et

al. describe the global burden of

antimicrobial resistance in ani-

mals on the basis of systematic

reviews over the past 20 years

(see the Perspective by Moore).

There is a clear increase in the

number of resistant bacterial

strains occurring in chickens and

pigs. The current study provides

a much-needed baseline model

for low- and middle-income

countries and provides a “one

health” perspective to which

future data can be added. —CA


see also p. 1251

TOPOLOGICAL MATTER

The topology of line nodesBand structure degeneracies

in topological materials can

take the form of lines or even

chains of interconnected loops.

Wu et al. study theoretically

these nodal lines and how they

evolve as the system param-

eters are varied. They focus on

a class of materials that have

weak spin-orbit coupling and

that respect a combination of

inversion- and time-reversal

symmetry. Noncommutative

topological charges are associ-

ated with nodal lines in such

materials that place constraints

on the configurations of these

lines. Calculations indicate that

elemental scandium under strain

may provide a test system for

this unconventional topology.

—JS


SURFACE CHEMISTRY

An 18-member carbon ringCarbon’s allotropes include

molecular species such as

C60

and C70

fullerenes.

Kaiser et al. now report the

assembly of a large carbon ring,

cyclo[18]carbon, from organic

precursors whose reactivity was

controlled by adsorbing them

on a sodium chloride surface

at 5 kelvin (see the Perspective

by Maier). Manipulation, with

an atomic force microscope tip,

of a cyclocarbon oxide mol-

ecule, C24

O6, led to elimination

of carbon monoxide molecules

and formation of the desired

all-carbon ring. High-resolution

imaging revealed alternating

single and triple bonds versus an

all-double-bond structure. —PDS


see also p. 1245

LIFE HISTORY

The decline of resistance in old ageInfection, immunity, and demog-

raphy are rarely measured

simultaneously, despite being

intertwined. Froy et al. measured

an immune marker of resistance

to infection by worm parasites

(helminths) in Soay sheep off

the remote Atlantic island of

St. Kilda (see the Perspective

by Gaillard and Lemaître). They

used a library of 2000 blood

samples from 800 known indi-

viduals that have been left to run

wild and unmanaged. Resistance

declines as the sheep age, which

reduces a sheep’s chances of

surviv ing the winter. Helminths

are an important component of

many natural systems, including

humans, and may thus become

an increasing burden on health

with age. —CA


see also p. 1244

PLANT SCIENCE

Flood-resistance from gene regulationSome plants tolerate flooding

better than others. Reynoso et

al. compared gene regulatory

networks activated by flood-

ing in rice, which is adapted to

flooding, with those in spe-

cies less adapted to flooding.

Flood-related gene regulation

was characterized according to

chromatin accessibility as well

as transcription. Although flood

response circuitry is evident

in dryland species as well, its

activation is greater in wetland

rice. —PJH


IMMUNOLOGY

Tumors metabolically paralyze T cellsThe cytokine transforming

growth factor–b (TGF-b) sup-

presses both immune and tumor

cells. Dimeloe et al. found that

TGF-b from tumor effusions

suppressed the antitumor activ-

ity of CD4+ T cells by inhibiting

their production of the inflam-

matory cytokine interferon-g

(IFN-g). The effects of TGF-b

were mediated by Smad proteins

in the mitochondria and led to

decreased mitochondrial respi-

ration. Indeed, IFN-g production

by CD4+ T cells was suppressed

by inhibiting a mitochondrial

electron transport chain

Edited by Michael FunkALSO IN SCIENCE JOURNALS

Published by AAAS

20 SEPTEMBER 2019 • VOL 365 ISSUE 6459 1262-CSCIENCE sciencemag.org

complex. These data suggest

that TGF-b suppresses antitu-

mor immunity by metabolically

paralyzing T cells. —JFF

Sci. Signal. 12, eaav3334 (2019).

NEUROSCIEN CE

How learning to read changes the bra inLearning to read requires

fine-tuning of perceptual and

cognitive abilities and is thought

to depend, in part, on an ortho-

graphically sensitive brain region

in the visual cort ex. Hervais-

Adelman et al. conducted a

large-scale functional magnetic

resonance imaging st udy with

individuals of varying degrees of

literacy to test whether this brain

region takes over cortical terri-

tory from neighboring areas of

the bra in. By examining cortical

responses to orthographic and

nonorthographic stimuli, they

found that literacy enhances

early visual responses rather

than contracting the extent of

tissue sensitive to other visual

categories. The brain areas

responsible for visual processing

thus develop a dual representa-

tional capacity. —KL

Sci. Adv. 10.1126/

sci adv.aax0262 (2019).

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