Science - 31 January 2020

(Marcin) #1
sciencemag.org SCIENCE

RESEARCH


NEUROSCIENCE


A learning mechanism in


the striatum


An intriguing characteristic of the
striatum is the random spatial
distribution and high degree of
intermingling between expression
of dopamine receptor types 1
(D1) and 2 (D2) within striatal
projection neurons (SPNs). The
resulting highly entropic mosaic
extends through a homogeneous
space and is mostly devoid of
histological boundaries. The rules
established locally by D1- and
D2-expressing SPNs (D1-SPNs
and D2-SPNs) are thus likely
critical in defining how functional
territories develop throughout
the striatum. Matamales et al.
found that activated D2-SPNs
access and modify developing
behavioral programs encoded by
regionally defined ensembles of
transcriptionally active D1-SPNs.
This process is slow because
it depends on the molecular
integration of additive neuro-
modulatory signals. However,
with time, it creates the regional
functional boundaries that are
necessary to identify and shape
specific learning in the striatum.
—PRS
Science, this issue p. 549


SYSTEMS BIOLOGY


Single-cell protein profiling
Single-cell DNA and RNA
sequencing can describe
numerous aspects of cell state,
but such techniques cannot
assess the functional effec-
tors of cells: proteins. In a
Perspective, Slavlov discusses
the advances in single-cell mass
spectrometry techniques that
allow protein profiling, includ-
ing characterization of protein
modifications and potentially
complex composition and sub-
cellular localization. Although
there are limitations to this
emerging technology, single-
cell proteomics may add to the
characterization of cellular com-
ponents and provide functional
information about signaling


networks in homeostasis and
disease. —GKA
Science, this issue p. 512

CANCER IMMUNOTHERAPY
Presurgical immune
checkpoint blockade
Checkpoint blockade immu-
notherapy using antibodies
that inhibit the programmed
cell death 1 (PD-1) or cytotoxic
T lymphocyte–associated
protein 4 (CTLA-4) pathways
has resulted in unprecedented
clinical outcomes for certain
cancers such as melanoma.
Topalian et al. review advances in
neoadjuvant (presurgical) immu-
notherapy as an important next
step for enhancing the response
of early-stage tumors to immune
checkpoint blockade. They high-
light the mechanistic rationale
for neoadjuvant immunotherapy
and recent neoadjuvant clinical
trials based on anti–PD-1 or
anti–PD-1 ligand 1 (anti–PD-L1)
therapy. Pathological assess-
ment criteria that may provide
early on-treatment biomarkers
to predict patient response are
also discussed. —PNK
Science, this issue p. 525

NEUROSCIENCE
Monosomes translate
proteins in neurons
Like all other cells, neurons use
different proteins to process infor-
mation and respond to stimuli. To
meet the huge demands for new
proteins in their large and com-
plex cell volume, neurons have
moved the protein templates—
messenger RNAs (mRNAs)—and
the protein synthesis machines—
ribosomes—out to synapses to
make proteins locally. During
protein synthesis, multiple
ribosomes can form a structure
known as a polysome, which
produces multiple protein
copies from a single mRNA.
Working in rodent preparations,
Biever et al. found that solitary,
mRNA-associated ribosomes, or

monosomes, are a substantial
source of proteins in neuro-
nal processes. Many synaptic
proteins are made on single
ribosomes, which may solve the
problem of limited space in tiny
synaptic compartments. —SMH
Science, this issue p. 526

CELL BIOLOGY
ER regulates stress
granule fission
A hallmark of eukaryotic cells is
the ability to compartmentalize
essential reactions into mem-
brane-bound and membraneless
organelles. Membrane-bound
organelles form networks
through transport vesicles and
interorganellar contact sites. The
endoplasmic reticulum (ER) has
emerged as a network hub and
forms physical connections with
nearly every membrane-bound
organelle. Lee et al. now identify
another class of ER contact sites
that appear to help regulate
the biogenesis and fission of
membraneless ribonucleopro-
tein (RNP) granules (see the
Perspective by Kornmann and
Weis). Live-cell fluorescence
microscopy of human cells
revealed that ER tubule dynam-
ics are spatially and temporally
coupled to the fission site of two
types of RNP granules, process-
ing bodies (P-bodies) and stress
granules. —SMH
Science, this issue p. 527;
see also p. 507

CATA LYS I S
Charging up cobalt for
hydroformylation
Hydroformylation reactions are
applied at massive scale in the
chemical industry to transform
olefins into aldehydes. The
original catalysts were neutral
cobalt complexes. Hood et
al. now report that positively
charged cobalt complexes,
stabilized by chelating phos-
phine ligands, show higher
activities at lower pressures

than their neutral counterparts,
approaching the activities of
precious rhodium catalysts.
These charged catalysts are
particularly adept at accelerating
the reactions of internal olefins
while avoiding decomposition.
Spectroscopic studies implicate
the involvement of 19-electron
intermediates in the catalytic
cycle. —JSY
Science, this issue p. 542

NANOMATERIALS
Growing coaxial
nanotubes
Heterostructures of highly
crystalline two-dimensional
materials such as graphene,
hexagonal boron nitride (hBN),
and molybdenum disulfide
(MoS 2 ) are now routinely
assembled from films or grown
as layers. Xiang et al. report
the growth of one-dimensional
analogs of these heterostruc-
tures on single-walled carbon
nanotubes (SWCNTs) through a
chemical vapor deposition (see
the Perspective by Gogotsi and
Yakobson). Single-crystalline
monolayers or multilayers
of hBN or MoS 2 were grown
that maintained the electrical
conductivity of the SWCNT. A
monolayer of MoS 2 was grown
on a trilayer of hBN that encap-
sulated a SWCNT. —PDS
Science, this issue p. 537;
see also p. 506

BEE HEALTH
Inducing immune
bee genes
Honey bees are prone to
parasitism by the Va r ro a mite,
which is a vector for several bee
pathogens. However, honey bees
are also host to the symbiotic
gut bacterium Snodgrasella alvi.
Leonard et al. engineered S. alvi
to produce double-stranded
RNA (dsRNA)—a stimulus for
insect RNA interference defense
responses—from a plasmid con-
taining two inverted promoters

Edited by Michael Funk

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524-B 31 JANUARY 2020 • VOL 367 ISSUE 6477


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