RESEARCH - science.sciencemag.orgscience.sciencemag.org/content/sci/355/6321/twis.full.pdf · ory traces. The brain structures and neural mechanisms involved in metamemory are completely

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


A molecular knot with eight crossings Danon et al., p. 159

Research in macaques

reveals the seat

of metamemory.

CR

ED

ITS

(T

OP

TO

BO

TT

OM

): J

EA

N-F

RA

NC

OIS

LE

MO

NN

IER

/U

NIV

ER

SIT

Y O

F M

AN

CH

ES

TE

R;

AL

AIN

RO

LL

I/G

ET

TY

IM

AG

ES

DA_0113ISIO.indd 143 1/11/17 11:28 AM

Published by AAAS

sciencemag.org SCIENCE

CR

ED

ITS

(L

EF

T T

O R

IGH

T):

CH

AIK

EE

RA

TIS

AK

ET

AL

.; L

AR

RY

GE

DD

IS/A

LA

MY

ST

OC

K P

HO

TO

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


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


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


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

DA_0113ISIO.indd 144 1/11/17 11:28 AM

Published by AAAS

145-B 13 JANUARY 2017 • VOL 355 ISSUE 6321 sciencemag.org SCIENCE

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


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


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


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


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


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


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

DA_0113ISIO.indd 146 1/11/17 11:28 AM

Published by AAAS

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


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


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


DA_0113ISIO.indd 147 1/11/17 11:28 AM

Published by AAAS

Documents

RESEARCH - science.sciencemag.orgscience.sciencemag.org/content/sci/355/6321/twis.full.pdf · ory traces. The brain structures and neural mechanisms involved in metamemory are completely