RESEARCH

DASH/Dam1c makes
rings around microtubules
s
Jenni and Harrison, p. 552

IN S CIENCE JOURNAL S Edited by Caroline Ash

MALARIA

Saturating malaria
mutagenesis

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M
alaria is caused by eukaryotic
Plasmodium spp. parasites that classically
infect red blood cells. These are difficult
organisms to investigate genetically
because of their AT-rich genomes. Zhang
et al. have exploited this peculiarity by using
piggyBac transposon insertion sites to achieve
saturation-level mutagenesis for identifying and
ranking essential genes and drug targets (see
the Perspective by White and Rathod). Genes
that are current candidates for drug targets
were identified as essential, in contrast to many
vaccine target genes. Notably, the proteasome
degradation pathway was confirmed as a target
for developing therapeutic interventions because
of the several essential genes involved and the
link to the mechanism of action of the current
frontline drug, artemisinin. —CA
Science, this issue p. 506; see also p. 490

Red blood cells infected by malaria parasites

NANOMATERIALS symmetry of the synthons and motion of a slower-moving acti- virus. Lim et al. treated simian
CREDITS: (FROM TOP) S. JENNI AND S. C. HARRISON; LONDON SCHOOL OF HYGIENE & TROPICAL

Retrosynthesizing
complex nanostructures
The solution synthesis of complex
and asymmetric nanostructures
is still challenging. For many appli-
cations, it will be important to gain
simultaneous control over particle
size and morphology, constituent
materials, and internal interfaces.
Fenton et al. have developed a
strategy that mimics chemical
retrosynthesis, starting with
simple nanoparticle synthons—in
MEDICINE/SCIENCE SOURCE
assembles them into higher-order
structures. The nanostruc-
tures can thus be formed with
asymmetric, patchy, porous, or
sculpted regions. —PDS
Science, this issue p. 513
MEMBRANES
Turing structures
at the nanoscale
Turing structures arise when
imbalances in diffusion rates
vator. Tan et al. grew polyamide
membranes by using interfa-
cial polymerization, where the
reactions occur at the interface
between oil and water layers. The
addition of polyvinyl alcohol to
the aqueous phase reduced the
diffusion of the monomer. This
process generates membranes
with more bumps, voids, and
islands, which prove to be better
for water desalination. —MSL
Science, this issue p. 518
immunodeficiency virus (SIV)–
infected rhesus macaques on
antiretroviral therapy with up to
19 doses of the Toll-like receptor
7 agonists GS-986 or GS-9620.
By the third dose, all macaques
experienced transient SIV
plasma viremia within 48 hours.
Dosing was also associated with
activation of lymphocytes and
reductions in SIV DNA in cells
from the peripheral blood, lymph
nodes, and gastrointestinal tract.
When antiretroviral therapy

this case, Cu1.8S nanoparticles,
nanorods, and nanosheets.
Various types of interfaces and
junctions can be introduced, for
example, by cation substitution.
This intervention breaks the
make a stable steady-state
system sensitive to small het-
erogeneous perturbations. For
example, Turing patterns occur
in chemical reactions when a
fast-moving inhibitor controls the
SIV
Emptying the reservoir
Antiretroviral therapy can halt
HIV-1 replication but cannot clear
the hidden reservoirs of latent
ceased, two of nine treated
macaques did not suffer rebound
of virus and remained apparently
virus-free and disease-free for
more than 2 years. —OMS
Sci. Transl. Med. 10, eaao4521 (2018).

SCIENCE sciencemag.org 4 MAY 2018 • VOL 360 ISSUE 6388 503

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RESEA RCH | I N S C I E N C E J OU R N A L S

PALEOGENOMICS SYSTEMS BIOLOGY

Relationships among
North Africans
The general view is that
Eurasians mostly descend from
a single group of humans that
dispersed outside of sub-Saha-
ran Africa around 50,000 to
100,000 years ago. Present-day
North Africans share a majority
of their ancestry with present-
day Near Easterners, but not
with sub-Saharan Africans. To
investigate this conundrum, Van
de Loosdrecht et al. sequenced
high-quality DNA obtained from
bone samples of seven indi-
viduals from Taforalt in eastern
Morocco dating from the Later
How to build a better IN OTHER JOURNALS Edited by Sacha Vignieri
and Jesse Smith
morphogen gradient
To translate insights in devel-
opmental biology into medical
applications, techniques are
needed to ensure correct cell
localization. Morphogen gradi-
ents allow precise and highly
reproducible pattern formation
during development. Through
in vitro experiments and
modeling, Li et al. tested the
effects of unusual properties
of Hedgehog (HH) signaling.
The HH morphogen’s recep-
tor, Patched (PTCH), sends an
inhibitory signal when no ligand
is bound, which is relieved by

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Stone Age, about 15,000 years
ago. The Taforalt individuals
were found to be most closely
related to populations from the
Near East (Natufians), with a
third of their ancestry from sub-
Saharan Africa. No evidence
was found for introgression
with western Europeans,
despite attribution to the
Iberomaurusian culture. None
of the present-day or ancient
Holocene African groups are a
good proxy for the sub-Saharan
genetic component. —LMZ
Science, this issue p. 548
IMMUNOLOGY
PTEN prevents the
cytokine storm
An uncontrolled infection leads
to sepsis, in which excessive
production of proinflamma-
tory cytokines, or a “cytokine
storm,” can cause potentially
fatal tissue damage and organ
failure. Sisti et al. found that
septic mice had increased
expression of the mRNA
encoding the lipid and pro-
tein phosphatase PTEN. Mice
lacking PTEN in myeloid cells
showed greater inflammation,
ligand binding. PTCH also regu-
lates spatial distribution of the
signal by sequestering the HH
ligand. Furthermore, signaling
through the receptor promotes
synthesis of more inhibitory
receptor. These characteristics
help speed gradient formation
and explain the robustness of
the system to changes in the
rate of morphogen production.
—LBR
Science, this issue p. 543
PLANT SCIENCE
Multiple, diverse,
and complex
Calcium currents character-
ize the developing pollen tube
in the small mustard plant
Arabidopsis and correlate with
growth at the tip of the pollen
tube. This system constitutes
a practical model for screening
for Ca2+-signaling mechanisms
in plants. Wudick et al. analyzed
multiple variants of glutamate
receptor–like (GLR) channels
and discovered that some work
alone and others work in pairs
or trios. Subcellular localization
of GLRs is a complex response
to CORNICHON sorting pro-
IMMUNOLOGY
Watching the
clock in asthma
Asthma symptoms often show
variations based on circadian
rhythms. Ehlers et al. report
that mice missing a functional
circadian clock (Bmal1−/−) are
more susceptible to acute bron-
chiolitis and chronic asthma-like
inflammation after infection
with Sendai virus. Similar,
though less potent, effects were
observed when wild-type mice
were subjected to a chronic jet
lag model. Concordantly, airway
cells from human asthmatics
show altered clock gene expres-
sion patterns. The disruption
of circadian rhythms alters
interferon-related antiviral
responses and enhances the M2
macrophage phenotype. Thus,
NEUROSCIENCE
Synaptic downscaling
during “up” states
During slow-wave sleep, corti-
cal networks oscillate between
periods of high activity, known as
“up” states, and quieter peri-
ods, known as “down” states.
González-Rueda et al. compared
synaptic plasticity during up and
down states in the mouse barrel
cortex during slow-wave sleep–
like cortical dynamics. They
studied connections between
cortical layers 4 and 2/3 in young
animals at postnatal days 16
to 21. This age corresponds to
the end of the critical period of
development of these synapses.
Plasticity rules were modulated
by up states: Spike timing–
dependent synaptic potentiation
was absent, and active synapses
PHOTO: NICK PECKER/SHUTTERSTOCK.COM

tissue injury, and mortality
from sepsis. PTEN activity in
the nucleus of macrophages
induced the production of
microRNAs that targeted
Myd88 mRNA, which encodes
an adaptor protein required for
cytokine production. —JFF
Sci. Signal. 11, eaai9085 (2018).
teins, which leave some GLRs
at the plasma membrane and
ferry others to internal calcium
reservoirs. The calcium current
at the tip of the growing pollen
tube apparently integrates
multiple intracellular currents.
—PJH
Science, this issue p. 533
one way that the circadian clock
may play a role in some forms of
asthma is by regulating immune
responses to respiratory viral
infections. Still uncertain is the
role of these genes in other
forms of the disease, including
atopic asthma. —STS
Mucosal Immunol. 11, 97 (2018).
failing to contribute to postsyn-
aptic spiking were selectively
depressed. This synaptic down-
scaling mechanism promotes
the elimination of weak and the
preservation of strong synapses,
thus enhancing the signal-to-
noise ratio. —PRS
Neuron 97, 1244 (2018).

504 4 MAY 2018 • VOL 360 ISSUE 6388 sciencemag.org SCIENCE

Published by AAAS
RESEARCH
ALSO IN SCIENCE JOURNALS
STRUCTURAL BIOLOGY
How calcium gates a
potassium channel
Small-conductance Ca2+-
activated K+ (SK) channels are
expressed throughout the ner-
vous system and affect both the
intrinsic excitability of neurons
and synaptic transmission. An
increase in the concentration of
intracellular calcium opens the
channels to conduct potassium
across the cell membrane. Lee
and MacKinnon report cryo–
electron microscopy structures
of human SK4-calmodulin
channel complexes. Activation
occurs when calcium binds
to calmodulin, a protein with
two lobes, known as C and N,
separated by a flexible region.
Each monomer in the channel
tetramer binds constitutively to
the C-lobe of calmodulin. The
N-lobe of calmodulin is reason-
ably unconstrained until it binds
calcium. With calcium bound, it
then binds to the channel and
induces conformational changes
that open the pore. —VV
Science, this issue p. 508
METALLURGY
Smaller but more
thermally stable
Synthesizing metals with
extremely small (nanoscale)
grain sizes makes for much
stronger materials. However,
very small–grained materials
start to coarsen at relatively low
temperatures, wiping out their
most desirable properties. Zhou
et al. discovered a way to avoid
this problem by mechanically
grinding copper and nickel at liq-
uid nitrogen temperatures. The
processing method creates low-
angle grain boundaries between
the nanograins, which promotes
thermal stability. —BG
Science, this issue p. 526
505-B 4 MAY 2018 • VOL 360 ISSUE 6388
Edited by Caroline Ash
NEUROSCIENCE
Loss of touch receptors
leads to itch
Itch in response to light touch of
the skin is an aging-associated
problem. This phenomenon
is called alloknesis and can
become a major medical condi-
tion associated with dry skin.
Feng et al. discovered that loss
or dysfunction of Merkel cells
causes scratching in mice (see
the Perspective by Lewis and
Grandl). Reduction of Merkel cell
numbers results in reduced firing
patterns and frequencies and
changes the activation thresh-
olds of slowly adapting afferent
nerve fibers. Like hair cells,
Merkel cells are lost with age. A
painful scratch will temporarily
alleviate itch because it induces
enough activity through the
remaining Merkel cells. —PRS
Science, this issue p. 530;
see also p. 492
NEUROSCIENCE
Setting conscious
perception alight
What are the neuronal mecha-
nisms that enable conscious
perception? Why do some
images remain subliminal? Van
Vugt et al. trained monkeys to
detect low-contrast images and
compared neuronal activity in
brain areas V1, V4, and the dor-
solateral prefrontal cortex. Some
stimuli made it into conscious-
ness, and others were subliminal
depending on their propagation,
which can be variable for weak
stimuli (see the Perspective by
Mashour). Strongly propagated
stimuli initiated a state in the
higher brain areas called “igni-
tion” that caused information
about a brief stimulus to become
sustained and broadcasted back
through recurrent interactions
between many brain areas.
—PRS
Science, this issue p. 537;
see also p. 493
Published by AAAS
IMMUNOLOGY
+
Complement is a CD8 T
cell metabolic rheostat
Systemic lupus erythemato-
sus (SLE) is associated with
deficiencies in the complement
protein C1q. Although C1q
plays a role in the clearance
of apoptotic cells, there are
several redundant clearance
pathways. Disruption of one
pathway does not lead to an
autoimmune defect. In a chronic
graft-versus-host disease
model of SLE, Ling et al. show
that C1q dampens CD8+ T cell
responses to self-antigens. C1q
modulates metabolism through
the mitochondrial cell-surface
protein p32/gC1qR. The lack of
C1q during a viral infection also
enhances CD8+ T cell responses.
Thus, C1q plays a role as a
“metabolic rheostat” for effector
CD8+ T cells. —STS
Science, this issue p. 558
BIODIVERSITY
Financing biodiversity
conservation
Global funds for protecting biodi-
versity are too low to prevent
wildlife populations from falling
and species extinctions from
increasing. In a Perspective,
Barbier et al. call for a Global
Agreement for Biodiversity
modeled on the Paris Climate
Agreement, with national
targets, policies, and timelines.
The overall goal is ambitious: to
conserve at least 50% of terres-
trial, inland water, coastal, and
marine habitats by 2050. Formal
involvement of the private sec-
tor, particularly in areas such as
seafood, forestry, agriculture,
and insurance, will be crucial to
raise the necessary funds. —JFU
Science, this issue p. 486
IMMUNOGENOMICS
Establishing NK cell
identity
The transcription factor ID2 is
required for normal differentia-
tion of all innate lymphoid cells.
ID2 supports full maturation of
natural killer (NK) cells into cyto-
toxic effectors. To investigate
the transcriptional program-
ming steps that underpin NK
cell differentiation, Zook et al.
characterized ID2-deficient
NK cells. ID2 limited chroma-
tin accessibility at multiple
Downloaded from http://science.sciencemag.org/ on December 2, 2020
lymphocyte-associated genes to
enable an effector-gene program
to take hold. —IW
Sci. Immunol. 3, eaao2139 (2018).
SURFACE CHEMISTRY
Direct plasmon chemistry
Light can excite plasmons at a
metal surface, which can then
decay and create hot electrons
that induce chemical reactions
of adsorbed molecules. Kazuma
et al. used a scanning tunneling
microscope (STM) to induce and
map out the surface dissociation
of a dimethyl disulfide molecule
on silver and copper surfaces. A
silver STM tip created localized
plasmons at different distances
from the molecule. The plas-
mons drove the reaction directly
by exciting the valence electrons
of the molecule into unoccupied
states and cleaving the sulfur-
sulfur bond. —PDS
Science, this issue p. 521
BIOMATERIALS
Curving bones
On larger length scales, bone
is known to have a hierarchical
structure in which small crystals
of calcium phosphates arrange
themselves around helices of
collagen. These make up larger
structures, such as the osteons
found in compact bone. However,
at smaller lengths, does the
hierarchical structure persist?
By combining three-dimensional
electron tomography with
two-dimensional electron
sciencemag.org SCIENCE
microscopy, Reznikov et al.
observed structural ordering
from the nanoscale upward.
At the smallest scale, needle-
shaped mineral units form
platelets that organize into
stacks bridging multiple collagen
units. —MSL
Science, this issue p. 507

STRUCTURAL BIOLOGY

Staying attached through

division
When a cell prepares to divide, it
copies its DNA into pairs of each
chromosome, called chromatids.
Microtubules attach to the chro-
mosome pairs through protein

Downloaded from http://science.sciencemag.org/ on December 2, 2020

complexes called kinetochores.
During cell division, microtu-
bule depolymerization pulls the
chromatids apart. Jenni and
Harrison describe the structure
of an essential component of the
yeast kinetochore, the DASH/
Dam1c complex, that forms a
ring around a microtubule. The
structure shows how the DASH/
Dam1c ring interacts with the
microtubule and kinetochore
components so that the kineto-
chore can track to the end of the
microtubule through cycles of
growth and shrinkage. —VV
Science, this issue p. 552

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Published by AAAS
Saturating malaria mutagenesis
Caroline Ash

Science 360 (6388), 503.

DOI: 10.1126/science.360.6388.503-a

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