research - science · 2019. 10. 30. · 585-b 1 november 2019 • vol 366 issue 6465 sciencemag.org...

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1 NOVEMBER 2019 • VOL 366 ISSUE 6465 583SCIENCE sciencemag.org

VIRAL IMMUNOLOGY

The toll of measles on the immune systemMany of the deaths attributable

to measles virus are caused by

secondary infections because

the virus infects and functionally

impairs immune cells. Whether

measles infection causes

long-term damage to immune

memory has been unclear. This

question has become increas-

ingly important given the

resurgence in measles epidem-

ics worldwide. Using a blood

test called VirScan, Mina et al.

comprehensively analyzed the

antibody repertoire in children

before and after natural infection

with measles virus as well as in

children before and after mea-

sles vaccination. They found that

measles infection can greatly

diminish previously acquired

immune memory, potentially

leaving individuals at risk for

infection by other pathogens.

These adverse effects on the

immune system were not seen in

vaccinated children. —PAK

Science, this issue p. 599

CELL BIOLOGY

Order in the cytoplasmExtracts of the very large eggs of

the African clawed frog, Xenopus

laevis, have proven a valuable

model system for the study of

cell division. Cheng and Ferrell

found that after homogenization,

such cytoplasm can reorganize

back into cell-like structures

and undergo multiple rounds

of division (see the Perspective

by Mitchison and Field). This

reorganization apparently

occurs without the usual fac-

tors that are known to lead to

such structural changes during

cell division, such as F-actin,

myosin II, various individual

kinesins, aurora kinase A, or

DNA. What is required is energy

from adenosine triphosphate,

microtubule polymerization,

cytoplasmic dynein activity, and

a specific kinase-involved cell

cycle progression. Nongenetic

information in the cytoplasm is

apparently sufficient for basic

spatial organization of the cell.

—LBR

Science, this issue p. 631;

see also p. 569

STRUCTURAL VIROLOGY

Unveiling African swine fever virusAfrican swine fever virus (ASFV)

is highly contagious and often

lethal. With no vaccine or effec-

tive treatment, infections often

require large-scale culling of

pigs. Wang et al. apply cutting-

edge cryo–electron microscopy

techniques to determine the

structure of this very large

DNA virus. An 8.8-angstrom-

resolution reconstruction shows

the five layers of the virus, and

the fourth capsid layer could be

reconstructed at 4.8-angstrom

resolution. The structure reveals

epitopes in the major capsid pro-

tein that distinguish ASFV from

other nucleocytoplasmic large

DNA viruses and shows how the

minor capsid proteins stabilize

the capsid. —VV


ISOTOPIC SEPARATION

Quantum sieves for hydrogen isotopesOne method for improving

the efficiency of separation of

hydrogen from deuterium (D) is

to exploit kinetic quantum siev-

ing with nanoporous solids. This

method requires ultrafine pore

apertures (around 3 angstroms),

which usually leads to low pore

RESEARCHEdited by Michael Funk

I N SC IENCE J O U R NA L S

IMMUNE REGULATION

Pharmacological retraining for T cells

Regulatory T cells (Tregs) expressing the Foxp3

transcription factor play a critical role in

dampening overactive immune responses,

including autoimmune diseases. Akamatsu

et al. screened a library of small molecules

and identified a compound that promotes Treg

differentiation by inhibiting the cyclin-dependent

kinases CDK8 and CDK19. The Treg-promoting

activity of the CDK8/19 inhibitor reduced disease

activity in mouse models of autoimmune diabetes

and encephalomyelitis. CDK8/19 inhibitors are

thus a new class of immunomodulatory drugs

capable of generating Tregs with potential clinical

applications in promoting tolerance and reducing

autoimmunity. —IRW

Sci. Immunol. 4, eaaw2707 (2019).

A T regulatory cell (red)

and an antigen-presenting

cell (blue), as seen by

scanning electron microscopy

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584 1 NOVEMBER 2019 • VOL 366 ISSUE 6465 sciencemag.org SCIENCE

CANCER

The ABCs of brain tumor prognosisMeningiomas are brain tumors that are typically benign and cur-able by surgery. In about 20% of cases, however, the tumors recur, and then patient prognosis is poor. Tumor histopathology is currently used to predict which patients might benefit from more aggressive treatment, but this method can be inaccurate. Patel et al. used clinical, gene expression, and sequencing data to classify meningiomas from 140 patients. Their analysis identified three distinct groups of tumors (A, B, and C), with type C being the most likely to recur. Type C tumors were characterized by altered activ-ity of a protein complex that controls cell cycle progression. Importantly, this molecular clas-sification system was a better

predictor of prognosis than the method currently used in clinics. —PAK

Proc. Natl. Acad. Sci. U.S.A.

116, 21715 (2019).

MOLECULAR BIOLOGY

Stepping on the condensationCondensin complexes are molecular motors that extrude DNA loops in a highly conserved and adenosine triphosphate–dependent manner, essential for eukaryotic chromosome condensation during mitosis. Elbatsh et al. mutated conden-sin at two motor sites (AS1 and AS2). They found that mutat-ing AS1 impairs the initiation of loop formation leading to hypocondensation, and mutat-ing AS2 speeds up contraction of DNA and diminishes the formation of high-order, stable

Edited by Caroline Ash

and Jesse SmithIN OTHER JOURNALS

for use as pendants. These find-ings address questions around the recurrent appearance of large raptor talons throughout the Middle Paleolithic time frame. —AC

Sci. Adv. 10.1126/sciadv.aax1984

(2019).

BLACK HOLES

A black hole hiding in a binary starAs material falls toward a black hole, it heats up and emits x-rays. Almost all black holes are discovered by this x-ray emission. Thompson et al. observed light from a giant star that is Doppler shifted, indicat-ing an orbit around a binary companion. The companion object must weigh more than 2.6 solar masses, but it emits no light, including x-rays. This indicates the presence of a black hole that is not currently consuming any material. There may be a population of similarly hidden black holes that have been missed by x-ray observa-tions. —KTS


BATTERIES

Controlling electrode growthBatteries with metal anodes can grow dendrites during cycling, which can cause short circuits in a battery or sub-sequently reduce the charge capacity. Zheng et al. developed a process to electrodeposit zinc on a graphene-coated stainless-steel electrode, such that the zinc forms plates with preferential orientation parallel to the electrode. This is achieved by depositing a graphene layer on stainless steel designed to epitaxially match the basal (002) plane of metallic zinc, minimizing lattice strain. During cycling, the zinc will redeposit in plate form rather than as a dendrite such that the batteries show excel-lent reversibility over thousands of cycles. —MSL


RESEARCH | IN SCIENCE JOURNALS

ECOLOGY

Nocturnal migration of night hunters

Bird migration is a vast global biannual phenomenon requir-

ing food as fuel on a similar scale. Superimposed on these

twice-yearly events are other regular occurrences, including

tightly predictable lunar cycles. Norevik et al. wondered

how the moon might influence migration of birds that hunt

at night, such as the European nightjar Caprimulgus europaeus.

These birds hunt insect prey by sight and are more active during

moonlit nights, giving a monthly boost to their food intake. Using

GPS-linked data loggers, the authors found that migration activ-

ity in these birds en route tends to peak after a full-moon feeding

binge. The lunar cycle strongly synchronizes migration responses

among individuals, which means a large proportion of a popula-

tion migrates simultaneously. Such synchronized responses

may make them vulnerable to climate change–related or other

adverse events along their migration route. —CA

PLOS Biol. 10.1371/journal.pbio.3000456 (2019).

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volumes and low D2 adsorption capacities. Liu et al. used organic synthesis to tune the pore size of the internal cavities of organic cage molecules. A hybrid cocrys-tal contained both a small-pore cage that imparted high selectiv-ity and a larger-pore cage that enabled high D2 uptake. —PDS


ANTHROPOLOGY

Symbolic behavior in NeanderthalsA new discovery provides rare evidence of symbolic behavior in Neanderthal communities and extends the record further geographically and temporally across Europe. Rodríguez-Hidalgo et al. analyzed recently unearthed Spanish impe-rial eagle phalanges, which were found along the Iberian Peninsula, and inferred that Neanderthal communities used these talons for symbolic purposes. Neanderthals most likely cut the eagle phalanges to extract the talon, presumably

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585-B 1 NOVEMBER 2019 • VOL 366 ISSUE 6465 sciencemag.org SCIENCE

RESEARCH

MEDICINE

Cryptic signs of aging in our bloodTime is not a friend to our DNA.

Aging is associated with an accu-

mulation of somatic mutations

in normal dividing cells, including

the hematopoietic stem cells

(HSCs) that give rise to all blood

cells. Certain mutations in HSCs

confer a fitness advantage that

results in clonal expansions of

mutant blood cells that some-

times—but not always—forecast

the development of cancer and

other age-related diseases.

Jaiswal and Ebert review this

process of “clonal hematopoi-

esis,” including the mechanisms

by which it arises and the current

state of knowledge regarding its

effects on human health. —PAK


MICROBIOLOGY

Animal sociability through microbesAccumulating evidence suggests

that the microbiota living in and

on animals has important func-

tions in the social architecture

of those animals. Sherwin et al.

review how the microbiota might

facilitate neurodevelopment,

help program social behaviors,

and facilitate communication in

various animal species, including

humans. Understanding the

complex relationship between

microbiota and animal sociabil-

ity may also identify avenues

for treating social disorders in

humans. —GKA


COMBUSTION PHYSICS

Achieving unconfined supersonic explosionsIn some forms of supernovae

and chemical explosions, a flame

moving at subsonic speeds (def-

lagration) spontaneously evolves

into one driven by a supersonic

shock (detonation), vastly

increasing the power output. The

mechanism of this deflagration-

to-detonation transition (DDT) is

poorly understood. Poludnenko

et al. developed an analytical

model to describe DDTs, then

tested it with lab experiments

and numerical simulations. Their

model successfully reproduced

the DDT seen in the experiments

and predicted a DDT in type Ia

supernovae, which is consistent

with observational constraints.

The same mechanism may apply

to DDTs in any unconfined explo-

sion. —KTS


BUTTERFLY GENOMICS

Following gene flow in butterfly genomesThe role of hybridization in evo-

lution and species radiations has

long been debated. In Heliconius

butterflies, introgression was

a major factor in their radia-

tion, and the genetic variation it

imparted into species is variable

across the genome. Edelman et

al. developed a new sequenc-

ing strategy and produced 20

Heliconius genomes (see the

Perspective by Rieseberg).

They also developed a means

by which to identify genetic

variation that originates from

incomplete lineage sorting ver-

sus hybridization. Applying this

model to their newly developed

genomes, they investigated the

evolutionary history of the genus

and, in particular, the impact of

introgression. —LMZ


see also p. 570

RADICAL ENZYMES

Itaconate brings metalloenzyme to a haltControlled radicals enable

unusual enzymatic transforma-

tions, but radical generation and

management require dedicated

systems. Ruetz et al. investigated

how the immunometabolite

itaconate might undermine

these intricate systems to inhibit

propionate metabolism, a crucial

metabolic pathway in pathogenic

Mycobacterium tuberculosis

(Mtb) (see the Perspective

by Boal). They found that the

coenzyme A (CoA) derivative of

itaconate can irreversibly inhibit

the enzyme methylmalonyl-CoA

mutase (MCM), which uses

the radical-generating cofactor

adenosylcobalamin, or coen-

zyme B12

. Itaconyl-CoA derails

the normal radical reaction

catalyzed by MCM, forming a

long-lived, biradical species,

which is incapable of completing

the catalytic cycle and cannot

be recycled by the endogenous

coenzyme B12

regeneration

machinery. Itaconate blocks Mtb

growth on propionate, and this

inhibition mechanism may be

relevant to how macrophages

resist Mtb infection. —MAF


see also p. 574

PLANT MICROBIOTA

Protecting plants from the inside outSome soils show a remark-

able ability to suppress disease

caused by plant pathogens,

an ability that is attributed to

plant-associated microbiota.

Carrión et al. investigated the

role of endophytes, the inti-

mate microbial community

found within roots, in fungal

disease suppression (see the

Perspective by Tringe). The

wilt fungus Rhizoctonia solani

infects sugar beets, whereupon

transcriptional analysis shows

that several bacterial endophyte

species activate biosynthetic

gene clusters to cause disease

suppression. These organisms

produce antifungal effectors,

including enzymes that can

digest fungal cell walls, and

secondary metabolites, includ-

ing phenazines, polyketides,

and siderophores, which may

contribute to the antifungal

phenotype. —CA


see also p. 568

NEUROSCIENCE

Fluid dynamics during sleepDuring non–rapid eye movement

sleep, low-frequency oscilla-

tions in neural activity support

memory consolidation and

neuronal computation. Sleep is

also associated with increased

interstitial fluid volume and

clearance of metabolic waste

products. It is unknown why

these processes co-occur and

how they are related. Fultz et al.

simultaneously measured elec-

trophysiological, hemodynamic,

and flow signals in the human

brain (see the Perspective by

Grubb and Lauritzen). Large

oscillations of fluid inflow to the

brain appeared during sleep

and were tightly coupled to

functional magnetic resonance

imaging signals and entrained

to electroencephalogram slow

waves. Slow oscillatory neuronal

activity thus leads to oscillations

in blood volume, drawing cere-

brospinal fluid into and out of the

brain. —PRS


see also p. 572

NEONICOTINOIDS

Cascading effects of pesticide useIt is now well known that

neonicotinoids negatively

affect pollinators. As research

has expanded, it has become

clear that these globally used

insecticides directly affect other

ecosystem components, includ-

ing vertebrates. Yamamuro et al.

now show that these compounds

are indirectly affecting species

through trophic cascades (see

the Perspective by Jensen).

Since the application of neonic-

otinoids to agricultural fields

began in the 1990s, zooplankton

biomass has plummeted in a

Japanese lake surrounded by

these fields. This decline has led

to shifts in food web structure

and a collapse of two commer-

cially harvested freshwater fish

Edited by Michael FunkALSO IN SCIENCE JOURNALS

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RESEARCH

1 NOVEMBER 2019 • VOL 366 ISSUE 6465 585-CSCIENCE sciencemag.org

species. The authors argue that

such dynamics are likely occur-

ring widely. —SNV


see also p. 566

SURFACE MAGNETISM

Single molecules sense spinImaging surface magnetism,

and, in particular, spin excita-

tions of adsorbed molecules or

films, is challenging. Verlhac et

al. demonstrate spin-sensing

capability by using the magnetic

exchange interaction between

a surface sample and the spin-

excited states of a nickelocene

molecule attached to a scan-

ning tunneling microscope

tip. The spatial dependence

of the exchange field at the

atomic scale enabled imaging

of magnetic corrugation with

atomic-scale lateral resolution

for iron atoms and small islands

of cobalt atoms absorbed on

nonmagnetic copper surfaces.

—PDS


REGENERATIVE MEDICINE

Secreting healing factorsOne of the main complications

associated with the use of

nonsteroidal anti-inflammatory

drugs (NSAIDs) is the devel-

opment of gastric ulcers.

Proton-pump inhibitors are used

to alleviate this condition; how-

ever, they are also associated

with serious adverse events. Xia

et al. developed a porcine model

of NSAID-induced gastric ul cers

and showed that intragastric

administration of adipose tis-

sue–derived mesenchymal stem

cells rapidly promoted healing

and reduced gastric inflamma-

tion. The therapeutic effect was

mediated by activation of signal-

ing pathways in ulcer tissue

induced by stem cell–secreted

factors. Mesenchymal stem

cells or their secretome could be

useful in treating NSAID-induced

gastric ulcers. —MM

Sci. Transl. Med. 11, eaat7455 (2019).

FIBROSIS

Protecting against liver fibrosisChronic liver disease stimu-

lates hepatic stellate cells and

ultimately leads to fibrosis.

Sundaram et al. found that mice lacking the pseudopro-

tease iRhom2, which activates

the metalloprotease ADAM17,

showed increased stellate cell

activation and susceptibility

to liver fibrosis induced by bile

duct ligation (see the Focus by

Badenes and Adrain). iRhom2-

activated ADAM17 promoted the

shedding of tumor necrosis fac-

tor (TNF) receptors from stellate

cells. Treating iRhom2-deficient

mice with the TNF-a inhibitor

etanercept reduced liver fibrosis

induced by bile duct ligation.

—AMV

Sci. Signal. 12, eaax1194, eaaz0444 (2019).

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