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13 JANUARY 2017 • VOL 355 ISSUE 6321 143SCIENCE sciencemag.org
RESEARCHEdited by Stella Hurtley
I N SC IENCE J O U R NA L S
PROTEIN DESIGN
Designing proteins with cavitiesIn de novo protein design,
creating custom-tailored binding
sites is a particular challenge
because these sites often involve
nonideal backbone structures.
For example, curved b sheets
are a common ligand binding
motif. Marcos et al. investigated
the principles that drive b-sheet
curvature by studying the
geometry of b sheets in natural
proteins and folding simula-
tions. In a step toward custom
design of enzyme catalysts, they
used these principles to control
b-sheet geometry and design
proteins with differently shaped
cavities. —VV
Science, this issue p. 201
CANCER
Initiating an antitumor attackCancer is notorious for relapsing
after treatment. Such relapses are
driven by tumor-initiating cells, a
type of stem cell that gives rise to
tumors. Damelin et al. determined
that a protein called PTK7 is
frequently present on tumor-
initiating cells and developed an
antibody-drug conjugate target-
ing it. In mouse models of several
tumor types, the therapy reduced
tumor-initiating cells and outper-
formed standard chemotherapy.
The antibody-drug conjugate also
reduced tumor angiogenesis and
promoted antitumor immunity,
possibly contributing to its effec-
tiveness. —YN
Sci. Transl. Med. 9, eaag2611 (2017).
STRUCTURAL BIOLOGY
Poised for the second step of splicingIn eukaryotes, noncoding
sequences in transcribed
precursor mRNA are cut out
by a dynamic macromolecular
machine, the spliceosome. This
involves two sequential reactions.
BRAIN RESEARCH
Are you aware how well you remember?
Self-monitoring and evaluation of our
own memory is a mental process
called metamemory. For metamem-
ory, we need access to information
about the strength of our own mem-
ory traces. The brain structures and neural
mechanisms involved in metamemory
are completely unknown. Miyamoto et al.
devised a test paradigm for metamemory
in macaques, in which the monkeys judged
their own confidence in remembering past
experiences. The authors combined this
approach with functional brain imag-
ing to reveal the neural substrates of
metamemory for retrospection. A specific
region in the prefrontal brain was essen-
tial for meta mnemonic decision-making.
Inactivation of this region caused selective
impairment of metamemory, but not of
memory itself. —PRS Science, this issue p. 188
The first cuts one end of the non-
coding intron and loops it back on
itself to form an intron lariat, and
the next excises the intron and
ligates the coding mRNA. Insights
into the first step of splicing have
come from the structures of two
intermediates: the Bact complex,
which is primed for catalysis, and
the C complex, which is formed
after the first splicing reaction.
Yan et al. now report a high-
resolution structure of the step
II catalytically activated spliceo-
some (the C* complex). This
structure shows conformational
changes that position catalytic
motifs to accomplish the second
splicing reaction. —VV
Science, this issue p. 149
A molecular knot with eight crossings Danon et al., p. 159
Research in macaques
reveals the seat
of metamemory.
CR
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sciencemag.org SCIENCE
CR
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(L
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CH
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.; L
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QUANTUM ELECTRONICS
Inducing strong couplingQuantum dots, or artificial atoms,
are being pursued as prospec-
tive building blocks for quantum
information processing architec-
tures. Communication with other,
distant quantum dots requires
strong coupling between photons
and the electronic states of the
dots. Mi et al. used double quan-
tum dots defined in silicon and
embedded in a superconducting
cavity to achieve such coupling.
This demonstration in an indus-
try-relevant material bodes well
for the large-scale development of
semiconductor-based quantum
processors. —ISO
Science, this issue p. 156
CELL BIOLOGY
Phages build themselves a wallThe compartmentalization
of DNA replication away from
other cytoplasmic events is a
key feature of the cell nucleus.
Chaikeeratisak et al. studied
the replication of the very large
Pseudomonas bacteriophage
201f2-1 by using fluorescence
microscopy and cryo–elec-
tron tomography. They found
that the phage assembled a
nucleus-like compartment when
it infected a bacterial cell. The
phage genome was completely
enclosed by an apparently
contiguous protein shell, within
which DNA replication, recom-
bination, and transcription
occurred. Translation, precursor
biosynthesis, and viral assembly
occurred outside the structure.
—SMH
Science, this issue p. 194
BACTERIAL PRIONS
Prions enter another domain of lifePrions are self-propagating
protein aggregates, discov-
ered in connection with the
fatal transmissible spongiform
encephalopathies in mammals.
Prions have also been identi-
fied in fungi, where they act as
protein-based elements of inher-
itance. Although prions have
been uncovered in evolutionarily
diverse eukaryotic species, it is
not known whether prions exist
in bacteria. Yuan and Hochschild
report the identification of a
bacterial protein—the transcrip-
tion termination factor Rho from
Clostridium botulinum—that
exhibits the defining hallmarks of
a prion-forming protein. —SMH
Science, this issue p. 198
NEUROSCIENCE
Channeling pain through GPCRs Mutations in Na
v1.7 result in
the absence of sensitivity to
pain, but drugs targeting this
sodium channel are not effective
as pain relievers. Isensee et al.
found that the absence of Nav1.7
altered the signaling efficiency
of G protein–coupled receptors
(GPCRs) in pain-sensing neu-
rons of the spinal
cord. Normally,
pain-promoting
serotonin receptor
signaling is balanced
by pain-relieving
mu opioid receptor
signaling. In mice
lacking Nav1.7, the
balance was shifted
so that the opioid
arm dominated,
resulting in neurons
that were less active
and more respon-
sive to pain-relieving
signals. —NRG
Sci. Signal. 10,
eaah4874 (2017).
QUANTUM FLUIDS
Observing peculiar vorticesWhen a vessel filled with a
superfluid is rotated, the super-
fluid, instead of moving with
the vessel the way water would,
develops an array of whirlpools
called vortices. The flow around
a vortex is “quantized,” char-
acterized by discrete, integer
numbers. It has long been
suspected that in a particular
kind of superfluid—3He at very
low temperatures—it would be
possible to observe vortices that
are associated with half-integer
numbers. Autti et al. observed
the signature of these half-
quantum vortices (HQVs) in the
nuclear magnetic resonance
(NMR) spectra of superfluid 3He
confined in a porous medium.
Pairs of HQVs caused the
appearance of an additional
NMR peak, whose position and
dependence on the various
parameters were consistent with
theoretical expectations. —JS
Phys. Rev. Lett. 117, 255301 (2016).
MEDICAL DIAGNOSTICS
Fast point-of-care detection of biomarkersMany diseases can be diag-
nosed by detecting nucleic
acid or protein biomarkers,
but, with few exceptions, this
detection requires complex
and costly instruments. Du
et al. adapted commercially
available pregnancy kits for
affordable and fast point-of-care
diagnostics. In the detection
method, nucleic acid is first
amplified and then captured
by a DNA oligonucleotide–
human chorionic gonadotropin
conjugate. The latter is detected
by the commercial kits. The
method allowed detection of
just 20 copies of an Ebola virus
template and could distinguish
a melanoma-related biomarker
from the wild-type sequence. It
should be possible to adapt it
for low-cost detection of other
biomarkers in clinical settings.
—JFU
Angew. Chem. Int. Ed. Engl. 10.1002/
anie.201609108 2016).
IN OTHER JOURNALS Edited by Caroline Ash
and Jesse Smith
A nucleus-like compartment in phage-infected bacteria
RESEARCH | IN SCIENCE JOURNALS
Drought limits pinyon
pine growth, whereas high
temperatures have little effect.
144 13 JANUARY 2017 • VOL 355 ISSUE 6321
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RESEARCH
ELECTROCHEMISTRY
Better living through water-splitting Chemists have known how to
use electricity to split water into
hydrogen and oxygen for more
than 200 years. Nonetheless,
beca use the electrochemical
route is inefficient, most of
the hydrogen made nowadays
comes from natural gas. Seh
et al. review recent progress in
electrocatalyst development to
accelerate water-splitting, the
reverse reactions that underlie
fuel cells, and related oxygen,
nitrogen, and carbon dioxide
reductions. A unified theoretical
framework highlights the need
for catalyst design strategies
that selectively stabilize distinct
reaction intermediates relative
to each other. —JSY
Science, this issue p. 146
RIBOSOME ASSEMBLY
A machine for building ribosomes The ribosome is a very large
protein and RNA complex
responsible for the difficult
process of synthesizing proteins.
Construction of the ribosome
itself involves several molecu-
lar machines and an army of
helper proteins and RNAs.
Chaker-Margot et al. deter-
mined the structure of one
of those machines, the yeast
small subunit processome.
The structure reveals how the
processome helps in the matura-
tion of individual domains of the
ribosome and suggests that the
mechanism involves a molecular
motor to drive conformational
changes. —GR
Science, this issue p. 147
SUPERCONDUCTIVITY
Squeezing out the oddnessThe material Sr
2RuO
4 has
long been thought to exhibit
an exotic, odd-parity kind of
superconductivity, not unlike
the superfluidity in 3He. How
would perturbing this material’s
electronic structure affect its
superconductivity? Steppke et
al. put the material under large
uniaxial pressure and found
that the critical temperature
more than doubled and then
fell as a function of strain (see
the Perspective by Shen). The
maximum critical temperature
roughly coincided with the point
at which the material’s Fermi
surface underwent a topological
change. One intriguing possibil-
ity is that squeezing changed the
parity of the superconducting
gap from odd to even. —JS
Science, this issue p. 148;
see also p. 133
ORGANIC CHEMISTRY
A cyclic catalyst to pair up sugarsLinking sugar molecules
together to make complex
carbohydrates is a geometrical
challenge. For a six-carbon sugar
such as glucose, there are six dif-
ferent possible linkage sites and
also two possible configurations
in which to anchor the incipient
bond. Park et al. developed a
ring-shaped, dimeric catalyst
that pairs sugars after one of
them has been modified with
a chloride. The thiourea-based
catalyst appears to pull away the
chloride while simultaneously
activating the incoming second
sugar. The resultant bond-form-
ing process reliably inverts the
initial C–Cl configuration. —JSY
Science, this issue p. 162
MATERIALS SCIENCE
Pin the tail on the hydrogensX-ray diffraction has been the
method of choice for determin-
ing the positions of atoms within
a crystal. However, the tech-
nique works better for atoms
with higher atomic numbers
and requires single crystals of
a minimum size. Palatinus et
al. used electron diffraction, a
technique of increasing impor-
tance for analyzing very small
crystals, to identify the positions
of hydrogen atoms in organic
and inorganic materials (see the
Perspective by McCusker). —MSL
Science, this issue p. 166;
see also p. 136
STRUCTURAL BIOLOGY
Redox metabolite role in biofilmsIn the microbial world, the
chemical diversity of secreted
metabolites is vast, and their
physiological roles are under-
explored. Costa et al. studied
the redox-active secondary
metabolite pyocyanin, which
is produced by the opportu-
nistic pathogen Pseudomonas
aeruginosa. Pyocyanin mediates
the generation of thick biofilms
containing extracellular DNA
that are important in pathogen-
esis. The authors characterized
the demethylase PodA, which
catalyzes the conversion of
pyocyanin to hydroxyphenazine
and deranges biofilm forma-
tion. PodA could represent a
therapeutic lead for intractable
bacterial infections. —CA
Science, this issue p. 170
PLANT ECOLOGY
Soil biota and plant diversitySoil biota, including symbionts
such as mycorrhizal fungi and
nitrogen-fixing bacteria, as well
as fungal and bacterial patho-
gens, affect terrestrial plant
diversity and growth patterns
(see the Perspective by van der
Putten). Teste et al. monitored
growth and survival in Australian
shrubland plant species paired
with soil biota from plants of
the same species and from
other plants that use different
nutrient acquisition strategies.
Plant-soil feedbacks appear
to drive local plant diversity
through interactions between
the different types of plants
and their associated soil biota.
Bennett et al. studied plant-soil
feedbacks in soil and seeds from
550 populations of 55 species of
North American trees. Feedbacks
ranged from positive to nega-
tive, depending on the type of
mycorrhizal association, and
were related to how densely the
same species occurred in natural
populations. —AMS
Science, this issue p. 134, p. 173;
see also p. 181
BRAIN RESEARCH
How to get to place BWe constantly navigate around
our environment. This means
moving from our current location,
place A, to a new goal, place B.
We have recently learned much
about spatial maps in the brain
in which place cells indicate
current location. However, it is
unclear how navigational goals
are represented in the brain.
Sarel et al. describe a group of
neurons in the brains of bats that
are tuned to goal direction and
distance relative to the bat’s cur-
rent position as it flies toward its
goal. The finding elucidates the
computations involved in spatial
navigation. —PRS
Science, this issue p. 176
MEMORY PROCESSING
Parallel computation in memory-makingThe hippocampus plays a central
role in the encoding, consolida-
tion, and recall of memories.
Consolidation and recall are
thought to be executed by the
replay of previously acquired
memory traces by hippocampal
cell assemblies. The hippocam-
pus is thus considered to be
the initiator of memory redis-
tribution processes. However,
O’Neill et al. now report that the
superficial layers of the medial
entorhinal cortex show replay
events that are independent
of hippocampal activity (see
Edited by Stella HurtleyALSO IN SCIENCE JOURNALS
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13 JANUARY 2017 • VOL 355 ISSUE 6321 145-CSCIENCE sciencemag.org
the Perspective by Moser and
Gardner). Computations in
memory systems may thus be
organized in a less hierarchical,
more parallel way than previ-
ously thought. —PRS
Science, this issue p. 184;
see also p. 131
CLIMATE CHANGE
Faster tree growth is no panaceaClimate warming, nitrogen depo-
sition, and (in fertile ecosystems)
elevated carbon dioxide may
cause plants to grow faster. Can
this growth stimulation lead to
higher carbon storage in exist-
ing forests and help to mitigate
climate change? In a Perspective,
Körner argues that the carbon
capital of a forest is set by the
residence time of carbon in
organic matter, not by the rate
of tree growth. Faster growth
commonly shortens the life span
of trees and so does not help to
store more carbon in the long
term. —JFU
Science, this issue p. 130
NEUROPHYSIOLOGY
More light on dopamine receptorsThe dopamine D4 receptor is
a G protein–coupled receptor
that has been linked to attention
deficit hyperactivity disorder
and substance use disorders.
Bonaventura et al. found that
mutations in a key portion of
this receptor had functional
consequences. The receptor
consists of seven transmem-
brane helices (TMs) connected
by loops. The third intracellular
loop between TM6 and TM7 is
longer in the polymorphic variant
D4.7R. Expression of this loop in
the D4 receptor reduced release
of corticostriatal glutamate. The
findings provide insight into the
role of D4 receptor variations in
some neuropsychiatric syn-
dromes and the effects of certain
psychostimulants. —PLY
Sci. Adv. 10.1126.sciadv.1601631
(2017).
IMMUNOTHERAPY
TAMpering with tumors Immunotherapeutic antibodies
are a promising cancer therapy,
but little is known about the
nontargeted effects of these
antibodies on immune cells
through Fc receptor binding.
Tumor-associated macrophages
(TAMs) and neutrophils (TANs),
which have been implicated in
both promoting and inhibiting
tumor growth, express abundant
Fcg receptors. Lehmann et al.
examined these cells in tumors
growing in different sites (skin
and lung). The organ environ-
ment determined which TAM and
TAN subpopulations contributed
to antibody-dependent tumor
immunotherapy. These data
may help fine-tune therapeutic
strategies to target only cells
that promote tumors. —ACC
Sci. Immunol. 2, eaah6413 (2017).
MOLECULAR KNOTS
Three strands ironed closely togetherIt is not uncommon when braiding
hair or bread to intertwine three
different strands. At the molecular
level, however, synthetic knots
have thus far been restricted to
architectures accessible from
two-strand braids. Danon et al.
used iron ion coordination to
guide three organic ligand strands
to form a knot geometry with
eight separate crossings. —JSY
Science, this issue p. 159
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