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RESEARCH

SIGNAL TRANSDUCTION

Activated by interaction
Cytokines trigger immune
responses when they bind to
their cognate receptors. Class I
cytokine receptors rely on the
associated Janus kinase 2
(JAK2) to initiate signal trans-
duction. There has been debate
over whether activation involves
ligand-induced dimerization
of these receptors or ligand-
induced conformational change
of preformed dimers. Wilmes et
al. imaged cytokine receptors in
the plasma membranes of live
human cells by single-molecule
fluorescence microscopy
and observed ligand-induced
dimerization. They found
that the JAK2 pseudokinase
domains contribute to dimeriza-
tion and that hyperactive JAK2
mutants promote dimerization,
consistent with the model that
dimerization triggers activa-
tion. —VV
Science, this issue p. 643

MEDICINE

Clinical uses of cellular

communication

Exosomes are a type of extra-
cellular vesicle that contain
constituents (protein, DNA, and
RNA) of the cells that secrete
them. They are taken up by
distant cells, where they can
affect cell function and behavior.
Intercellular communication
through exosomes seems to be
involved in the pathogenesis
of various disorders, including
cancer, neurodegeneration,
and inflammatory diseases. In
a Review, Kalluri and LeBleu
discuss the biogenesis and
function of exosomes in disease,
highlighting areas where more
research is needed. They
also discuss the potential
clinical applications of exosome
profiling for diagnostics and
exosome-mediated delivery of
therapeutics to target disease
cells. —GKA
Science, this issue p. 640

INFECTIOUS DISEASE

Concern about swine

fever vaccines

African swine fever (ASF) is a

lethal hemorrhagic disease that

affects swine, including wild boar

and domestic pigs. Beginning in

mid-2018 with the introduction

of the ASF virus to China, an out-

break of ASF has devastated pig

farming in Asia. The disease is

spreading into Europe and may

soon become a global threat to

the pig population. Efforts to

prevent the spread of ASF virus

are challenged by residual infec-

tion in the wild boar population

and difficulties in preventing

the movement of pig products.

In a Perspective, Gavier-Widén

et al. discuss strategies to

develop a vaccine that can be

used in bait for wild boar and be

administered to farmed animals

to effectively overcome ASF.

However, in the rush to generate

a vaccine, there are concerns

that the existing options under

development may make matters

worse. —GKA

Science, this issue p. 622

PLANT SCIENCE

Decoupling tillering and

fertilization

For rice as an agricultural crop,

more tillers, or branches that

carry grains, are desired, as

is less demand for nitrogen

fertilization. Unfortunately, for

many rice varieties, the number

of tillers depends on the amount

of nitrogen fertilization. Wu

et al. now show that nitrogen

status affects chromatin func-

tion through modification of

histones, a process in which

the transcription factor NGR5

recruits polycomb repressive

complex 2 to target genes.

Some of these genes regulate

tillering, such that with more

nitrogen, the plants develop

more tillers. NGR5 is regulated

by proteasomal destruction and

mediates hormone signaling. An

increase in NGR5 levels can drive

increases in rice tillering and

yield without requiring increases

in nitrogen-rich fertilizer. —PJH

Science, this issue p. 641

IMMUNOLOGY

A weird way to recognize

phosphoantigens

In contrast to the well-studied

ab T cells, which recognize

peptide antigens presented

by major histocompatibility

complex (MHC) and MHC-like

molecules, how gd T cells recog-

nize antigens remains largely a

mystery. One major class of gd

T cells, designated Vg9Vd 2 +, is

activated by small, phosphoryl-

ated nonpeptide antigens, or

phosphoantigens, produced

by microbes and cancer cells.

Rigau et al. found that these

cells needed the combination

of two immunoglobulin super-

family members, butyrophilin

2A1 (BTN2A1) and BTN3A1, on

their cell surface to recognize

these phosphoantigens. BTN2A1

directly binds the Vg 9 + domain

of the T cell receptor (TCR),

whereas a second ligand, poten-

tially BTN3A1, binds the Vd2 and

g-chain regions on the opposite

side of the TCR. A better under-

standing of this unexpected

form of T cell antigen recogni-

tion should inform and enhance

future gd T cell–mediated immu-

notherapies. —STS

Science, this issue p. 642

CATA LYS I S

Water-selective zeolite

membranes

The yield of many gas-phase

industrial reactions is limited

by the formation of water as a

by-product. Li et al. harnessed

the water-sieving properties of

NaA zeolite crystals by forming

them into continuous defect-

free membranes within tube

reactors (see the Perspective

by Carreon). These membranes

can let water pass but reject

gases such as hydrogen, carbon

monoxide, and carbon dioxide

(CO 2 ). When these membranes

were used in CO 2 hydrogenation

to form methanol with water

as a by-product, substantial

increases were observed in both

the CO 2 conversion and metha-

nol yield. —PDS

Science, this issue p. 667;

see also p. 624

NEUROSCIENCE

Microglia modulate

memories

Synaptic reorganization and

circuit rewiring leads to loss

or weakening of connections

between neurons and may result

in the erasure of previously

formed memories. Microglia

eliminate excessive synapses in

the developing brain and regu-

late the dynamics of synaptic

connections between neurons

throughout life. However, it is

still unclear whether forgetting is

related to microglia activity and

how microglia regulate memory

erasure in the adult brain. Wang

et al. discovered that microglia

eliminated synaptic compo-

nents in the adult hippocampus

and that depleting microglia

or inhibiting phagocytosis of

microglia prevented forgetting.

Synapse elimination by microglia

may thus lead to degradation of

memory engrams and forgetting

of previously learned contextual

fear memory. —PRS

Science, this issue p. 688

PHASE SEPARATION

Not too sticky

There is increasing evidence for

a role of liquid-liquid phase sepa-

ration (LLPS) in many cellular

processes. Many proteins that

undergo LLPS include prion-

like domains (PLDs), which are

enriched in polar amino acids

and often interspersed with

aromatic residues. Combining

experimental data with simula-

tions, Martin et al. quantified

concentrations of PLDs in coex-

isting dilute and dense phases as

Edited by Michael Funk

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639-B 7 FEBRUARY 2020 • VOL 367 ISSUE 6478

Published by AAAS