RESEARCH - Science · Birch reductions The so-called Birch reduction is frequently used by chemists...

SCIENCE sciencemag.org

ELECTROCHEMISTRY

Scaled-up sodium-free Birch reductions The so-called Birch reduction

is frequently used by chemists

despite its daunting conditions:

Pyrophoric sodium is dissolved

in pure liquified ammonia

to achieve partial reduction

of aromatics. Peters et al.

surveyed and then optimized

small-scale electrochemical

alternatives to devise a safer

protocol that can work on a

larger scale with a broad range

of functionally complex sub-

strates. —JSY

Science, this issue p. 838

NEWS AND POLITICS

Concentrated news precedes legislationNews coverage can play a

crucial role in shaping or

reflecting public opinion and

legislation. Sheshadri and

Singh used machine-learning

techniques to analyze 25 years

of news articles from the New

York Times and the Guardian,

along with Google Trends data

and U.S. federal legislation

outcomes. Prolonged bursts of

similarly framed articles were

found to precede changes in

public perception and new

legislation. As an example, the

framing around “surveillance”

changed in conjunction with an

uptick in the word “Snowden,”

reflecting a shift in focus from

national security to individual

liberty. These findings illustrate

the critical interplay between

news, public attitudes, and new

laws. —AC

Sci. Adv. 10.1126/

sciadv.aat8296 (2019).

MESOSCOPIC PHYSICS

Probing the dynamics of anyons A two-dimensional electron gas

in the fractional quantum Hall

regime has unusual excitations

called anyons that carry only a

fraction of the electron’s charge.

Edited by Stella HurtleyI N SC IENCE J O U R NA L S

RESEARCH

This fractional charge can be

observed through a dynamical

response to irradiation by micro-

waves, but such experiments

require a combination of high

magnetic fields with sensitive

noise measurements and very

low temperatures. Kapfer et al.

observed this dynamical response

in a GaAs/AlGaAs heterostructure

hosting a high-mobility two-

dimensional electron gas with

fractional excitations of one-third

and one-fifth of the electron’s

charge. The method may be of

interest for use in topological

quantum computing. —JS


MASS EXTINCTION

Two timelines for extinction

The Cretaceous-Paleogene extinction that wiped out the nonavian dinosaurs 66 million years

ago was correlated with two extreme events: The Chicxulub impact occurred at roughly

the same time that massive amounts of lava were erupting from the Deccan Traps (see the

Perspective by Burgess). Sprain et al. used argon-argon dating of the volcanic ash from

the Deccan Traps to argue that a steady eruption of the flood basalts mostly occurred after

the Chicxulub impact. Schoene et al. used uranium-lead dating of zircons from ash beds and con-

cluded that four large magmatic pulses occurred during the flood basalt eruption, the first of

which preceded the Chicxulub impact. Whatever the correct ordering of events, better constraints on

the timing and rates of the eruption will help elucidate how volcanic gas influenced climate. —BG

Science, this issue p. 866, p. 862; see also p. 815

The Deccan Traps in India were a source

of large-scale volcanic activity that affected

the climate 66 million years ago.

Catalyst guides path to synthesize five-carbon rings Zhou and Uyeda, p. 857

22 FEBRUARY 2019 • VOL 363 ISSUE 6429 831

IMA

GE

S:

(TO

P T

O B

OT

TO

M)

ZH

OU

AN

D U

YE

DA

; G

ER

TA

KE

LL

ER

Published by AAAS

RESEARCH | IN OTHER JOURNALS

sciencemag.org SCIENCE

ION CHANNELS

A key to potassium channel activation Using drugs to activate

potassium channels has the

potential to treat conditions

like epilepsy, heart arrhyth-

mias, and pain. Schewe et al.

report a class of negatively

charged activators (NCAs)

with a defined pharmacore

that use a similar mechanism

to activate many types of

potassium channels. X-ray

crystallography, functional

analysis, and molecular

dynamics simulations showed

that the NCAs bind below the

selectivity filter to open the

filter gate and activate the

channels. Targeting this NCA

site might be exploited in ratio-

nal drug design. —VV


3D PRINTING

The key to keyhole formation The formation of keyholes,

or vapor-filled depressions,

during laser welding presents

a large problem for additive

manufacturing. Cunningham

et al. used high-speed x-ray

imaging to take a detailed

look at keyhole formation in

a titanium alloy. They found

a simplified relationship

between operational parame-

ters and keyhole shape, which

may allow for the prevention of

pore formation going forward.

—BG


SYNTHETIC BIOLOGY

Expanding the genetic code DNA and RNA are naturally

composed of four nucleotide

bases that form hydrogen

bonds in order to pair. Hoshika

et al. added an additional

four synthetic nucleotides to

produce an eight-letter genetic

code and generate so-called

hachimoji DNA. Coupled with

an engineered T7 RNA poly-

merase, this expanded DNA

alphabet could be transcribed

into RNA. Thus, new forms of

DNA that add information den-

sity to genetic biopolymers

can be generated that may

be useful for future synthetic

biological applications. —LMZ


NEURODEGENERATION

Sleep may protect the brain from AD Two main proteins accumulate

in the brain in Alzheimer’s dis-

ease (AD), b-amyloid (Ab) and

tau. Ab appears to instigate

AD, but tau appears to drive

brain damage and cognitive

decline. Sleep deprivation is

known to increase Ab acutely

and chronically. Now, Holth

et al. show that chronic sleep

deprivation strongly increases

tau acutely over hours and also

drives tau pathology spread-

ing in the brains of mice and

humans (see the Perspective

by Noble and Spires-Jones).

Thus, sleep appears to have a

direct protective effect on a key

protein that drives AD pathol-

ogy. —SMH

Science, this issue p. 880;

see also p. 813

ALLERGY

Digging skin deepDisrupted epithelial barriers

are thought to be central to

the development of allergic

disorders such as atopic

dermatitis, which is com-

monly associated with food

allergy. Leung et al. performed

repeated skin tape stripping

on lesional and nonlesional

skin of pediatric atopic derma-

titis subjects, some of whom

also had food allergies. Among

other parameters, the authors

measured lipids, barrier

integrity, and the microbi-

ome. Nonlesional skin from

atopic dermatitis patients

had different characteristics

depending on whether the

patient also had a food allergy.

The findings could help in the

development of food allergy

biomarkers. —LP

Sci. Transl. Med. 11, aav2685 (2019).

MUSCLE REGENERATION

Making more youthful muscleAging reduces the body’s ability to

regenerate. The myogenic poten-

tial of muscle stem cells (MuSCs)

is a prime example. Recent work

shows that some factors that allow

us to bounce back after injury

include extracellular signals from

the stem cell niche. Lukjanenko et

al. show that MuSC dysfunction

with aging is a result of the loss of

matricellar WNT1 inducible signal-

ing pathway protein 1 (WISP1)

from fibro-adipogenic progenitors

(FAPs). When WISP1 is secreted

from FAPs, the Akt pathway is

activated along with asymmetric

MuSC cell division. Eliminating

mouse WISP1 results in defective

myogenesis with reduced MuSCs.

By contrast, injecting aged mice

with WISP1 rescues MuSC func-

tion. By identifying the cells and

cell-secreted factors that support

repair, it should be possible to gen-

erate more youthful muscle. —BAP

Cell Stem Cell 10.1016/

j.stem.2018.12.014 (2019).

Edited by Caroline Ash

and Jesse SmithIN OTHER JOURNALS

DIAGNOSIS

Next-generation prenatal screeningFetal DNA that is circulating in

the blood of pregnant women is

frequently extracted noninva-

sively and screened for common

chromosome aneuploidies that

cause disease such as trisomy

of chromosome 21, which may

result in Down syndrome. There

are numerous other syndromes

that are caused by single gene

mutations that cannot be

assessed like this. Zhang et al.

developed a next-generation

DNA sequencing approach for

circulating fetal DNA that can

detect alterations in 30 genes

that cause monogenic disorders.

Tests were performed on 422

pregnant women, and follow-up

studies confirmed 20 positive

results and 127 negative results,

with no reported false-negative

or false-positive results, sug-

gesting that the method is highly

specific and accurate. —GKA

Nat. Med. 10.1038/

s41591-018-0334-x (2019).

Color-enhanced scanning electron

micrograph of bifidobacteria, which predominate

in the fecal microbiota of infant mammals.

IMA

GE

: E

YE

OF

SC

IEN

CE

/S

CIE

NC

E S

OU

RC

E

832 22 FEBRUARY 2019 • VOL 363 ISSUE 6429

Published by AAAS

sciencemag.org SCIENCE

TOPOLOGICAL MATTER

A topological paradigm shift The discovery of topological

phases of matter forced con-

densed matter physicists to

question and reexamine some of

the basic notions of their disci-

pline. Wen reviews the progress

of the field that took a sharp turn

from Landau’s broken symmetry

paradigm to arrive at the mod-

ern notions of topological order

and quantum entanglement in

many-body systems. This devel-

opment was made possible by

using increasingly sophisticated

mathematical formalisms. —JS


PLANT BIOLOGY

Chloroplast-associated protein degradation Protein degradation is vital for

cellular functions, and it operates

selectively with distinct mecha-

nisms in different organelles.

Some organellar proteins

are targeted by the ubiquitin-

proteasome system (UPS)—a

major proteolytic network in

the eukaryotic cytosol. In such

cases, the organelle membrane

presents a substantial barrier

to protein degradation. Working

in the model plant Arabidopsis,

Ling et al. identified mechanisms

underlying the UPS-mediated

degradation of proteins in the

outer membrane of chloroplasts

(the organelles responsible for

photosynthesis). They identified

an Omp85-type b-barrel outer

membrane channel and a cyto-

solic AAA+ chaperone that fulfill

conductance and motor func-

tions in the retrotranslocation of

target proteins from chloroplasts.

This process thus enabled outer

membrane protein processing

by the cytosolic proteasome.

Such chloroplast-associated

protein degradation was initiated

by ubiquitination of the targets

by the chloroplast-localized E3

ubiquitin ligase SP1. —SMH


STRUCTURAL BIOLOGY

Structures of the simplest replisome The DNA replisome performs

concerted parental-strand

separation and DNA synthe-

sis on both strands. Gao et

al. report the cryo–electron

microscopy structures of the

minimum set of bacteriophage

T7 proteins that can carry out

leading- and lagging-strand

synthesis at the replication fork

(see the Perspective by Li and

O’Donnell). Three key enzymes

involved in DNA replication—

DNA polymerase, helicase, and

primase—were visualized in

complex with substrate DNA,

demonstrating their highly

dynamic organizations on

both strands. Comparison of

prokaryotic and eukaryotic

replisomes reveals evolutionarily

conserved operating principles

and provides a structural basis

for understanding coordination

among DNA replication, recom-

bination, and repair. —SYM


see also p. 814

NEUROSCIENCE

Coincidence detection in synaptogenesis In the brain, synaptic connections

are formed with exquisite specific-

ity, but the underlying molecular

mechanisms remain largely

unexplored. Synapse formation

is thought to involve bidirectional

signaling by proteins that bind to

each other across the synaptic

cleft. Sando et al. used conditional

genetic tools and in vitro assays

to investigate the mechanisms of

synapse formation. They found

that synapse formation in the

mouse hippocampus requires

latrophilins. Latrophilins are G

protein–coupled receptors that

bind to cell-surface proteins

called teneurins and fibronectin

leucine-rich repeat transmem-

brane proteins (FLRTs). Two

different latrophilins mediated

formation of distinct synapses on

the same hippocampal neuron.

This function required binding of

both teneurins and FLRTs. Thus,

latrophilins may guide synapse

formation by coincidence signal-

ing, which could help to explain

the specificity of synaptic connec-

tions. —SMH


COLD MOLECULES

Coaxing quantumness in a molecular gas A dilute atomic gas cooled down

to very cold temperatures can

enter the so-called quantum

degenerate regime, where quan-

tum properties of the gas come

to the fore. This regime has been

achieved for both bosonic and

fermionic atoms, but molecules,

with their many internal states,

present a special challenge. De

Marco et al. cooled a bulk gas of

fermionic potassium-rubidium

molecules to quantum degen-

eracy (see the Perspective by

Zelevinsky). The authors first

cooled atomic potassium and

rubidium gases separately, then

bound them together into potas-

sium-rubidium molecules, and

finally brought the molecules

down to their ground state. The

density profile of the molecular

gas revealed the system’s quan-

tum nature, which in turn kept

the gas stable by suppressing

chemical reactions. —JS


see also p. 820

ELECTROCHEMISTRY

Harnessing self-tuned strain Strain can modify the electronic

properties of a metal and has

provided a method for enhancing

electrocatalytic activity. For prac-

tical catalysts, nanomaterials with

high surface areas are needed.

However, for nanoparticles, strain

is often induced with overlayers

(adsorbates or heteroatoms)

that can undergo reconstruction

during operation that releases

the induced strain. Wang et al.

show that freestanding palla-

dium nanosheets (three to five

monolayers thick) form with an

internal compressive strain of 1 to

2% and can be much more active

for both the oxygen and hydrogen

evolution reactions under alkaline

conditions compared with

nanoparticles. —PDS


MICROBIOLOGY

Tiny modulators of parasite infection Extracellular vesicles are pro-

duced by diverse cell types, but

what are they? Do they have a

function, or are they cellular rub-

bish? In a Perspective, Ofir-Birin

and Regev-Rudzki discuss the

increasing evidence that extra-

cellular vesicles are secreted

by parasites to improve their

chances of survival in host cells

by modulating host immune

responses. It is possible that

parasite-derived extracellular

vesicles could be manipulated

to produce vaccines and/or be

used in diagnostics. —GKA


THYMIC SELECTION

Instructional signals for nascent T cellsSignals relayed through the

T cell receptor (TCR)–CD3

complex are critical to deter-

mining whether immature T

cells in the thymus undergo

positive or negative selection.

Positive selection enables T cell

survival and subsequent export

to the periphery, whereas

negative selection leads to T cell

death. Neier et al. developed

a proteomics-based approach

to profile proteins bound to

the TCR–CD3 complex and

compared differences between

signaling associated with

thymocyte survival and signal-

ing associated with death. The

full range of cellular outcomes

after thymic selection could be

Edited by Stella HurtleyALSO IN SCIENCE JOURNALS

833-B 22 FEBRUARY 2019 • VOL 363 ISSUE 6429

RESEARCH

Published by AAAS

SCIENCE sciencemag.org

attributed to quantitative dif-

ferences in a shared core set of

biochemical signals. Thus, dif-

ferences in the affinity of TCRs

for peptide–major histocompat-

ibility complex complexes are

transduced into downstream

signals that are quantitatively

variable, but qualitatively simi-

lar. —IRW

Sci. Immunol. 4, eaal2201 (2019).

BIOCHEMISTRY

Tumorigenic trioRho guanine nucleotide

exchange factors (RhoGEFs)

activate the Rho family of small

guanosine triphosphatases

that regulate cell migration

and gene expression in normal

development and disease,

including some cancers. In many

uveal (eye) melanomas, the

RhoGEF module of Trio medi-

ates signaling from oncogenic

Gaq/11

proteins, which drives

tumor progression. Bandekar

et al. investigated the struc-

tural regulation of Trio and

show that mutations found in

patients relieve its autoinhibitory

conformation, thereby enabling

sustained Gaq/11

-Trio-Rho signal-

ing in cells. —LKF

Sci. Signal. 12, eaav2449 (2019).

ORGANIC CHEMISTRY

Five-membered rings for two nickels The Diels-Alder reaction is widely

used to make six-membered

rings by adding four-carbon

dienes to two-carbon alkenes. It

would seem straightforward to

likewise access five-membered

rings from dienes and one-

carbon sources, or carbenes,

but that does not tend to work.

Instead, the carbene adds to

just half of the diene to form a

cyclopropane. Zhou and Uyeda

now show that a catalyst with

two nickel centers can steer this

reaction toward the cyclopentyl

products (see the Perspective

by Johnson and Weix). A chiral

version of the catalyst rendered

the reaction enantioselective in

intramolecular cases. —JSY


see also p. 819

22 FEBRUARY 2019 • VOL 363 ISSUE 6429 833-C

Published by AAAS

RESEARCH - Science · Birch reductions The so-called Birch reduction is frequently used by chemists...

Documents

Transcript of RESEARCH - Science · Birch reductions The so-called Birch reduction is frequently used by chemists...