research - science · cns therapeutics delivering therapeutics to the brain is complicated by the...

PH

OT

O:

QU

INC

Y F

LO

YD

/S

HU

TT

ER

ST

OC

K

29 MAY 2020 • VOL 368 ISSUE 6494 961SCIENCE sciencemag.org

SEPARATIONS

Zeolites that prefer alkynesAlkenes such as ethylene and

propene must be separated from

alkynes before they can be con-

verted in polymers. Drawbacks in

current methods, such as hydro-

genation of alkynes producing

unwanted alkanes, has spurred

interest in sorption separation

methods. Zeolites have gener-

ally been inefficient, given the

similar sizes and volatilities of the

molecules. Chai et al. incor-

porated atomically dispersed

divalent transition metal cations

into faujasite zeolite and found

that the nickel-containing analog

efficiently removed alkynes from

olefins through chemoselective

binding at open nickel(II) sites.

At ambient conditions in the

presence of water and carbon

dioxide, the zeolites retained

separation selectivities of 100

and 92, respectively, for acetylene

over ethylene and propyne over

propylene for 10 adsorption-

desorption cycles. —PDS

Science, this issue p. 1002

CORONAVIRUS

Alternative hosts and model animalsThe severe acute respira-

tory syndrome–coronavirus 2

(SARS-CoV-2) pandemic may

have originated in bats, but how

it made its way into humans is

unknown. Because of its zoonotic

origins, SARS-CoV-2 is unlikely

to exclusively infect humans, so

it would be valuable to have an

animal model for drug and vac-

cine development. Shi et al. tested

ferrets, as well as livestock and

companion animals of humans,

for their susceptibility to SARS-

CoV-2 ( see the Perspective by

Lakdawala and Menachery). The

authors found that SARS-CoV-2

infects the upper respiratory

tracts of ferrets but is poorly

transmissible between individu-

als. In cats, the virus replicated in

the nose and throat and caused

inflammatory pathology deeper in

the respiratory tract, and airborne

transmission did occur between

pairs of cats. Dogs appeared not

to support viral replication well

and had low susceptibility to the

virus, and pigs, chickens, and

ducks were not susceptible to

SARS-CoV-2. —CA

Science, this issue p. 1016;

see also p. 942

BLOOD-BRAIN BARRIER

Transport vehicle for CNS therapeuticsDelivering therapeutics to the

brain is complicated by the pres-

ence of the blood-brain barrier.

Kariolis et al. and Ullman et al.

developed a transport vehicle

(TV) for central nervous system

(CNS) delivery of therapeutics

RESEARCHI N SC IENCE J O U R NA L S

Edited by Michael Funk

EVOLUTIONARY BIOLOGY

Primate kin recognition

Kin selection, the selection of behaviors that benefit kin, is key

to social and cooperative behavior. Primates can recognize

kin through heritable facial traits. The question is whether

this behavior is incidental from shared genes or if it is instead

subject to selection. Charpentier et al. studied the behavior

of mandrills, nonhuman primates that live in enormous groups

composed of matrilines, in which daughters stay with the mother

and sons disperse. Using sophisticated artificial intelligence,

they graded facial resemblances and correlated them with the

social interactions of maternal and paternal half-siblings. The

authors found evidence of selection for kin recognition and discuss

differences between maternal and paternal half-siblings and the

intricacies resulting from different social settings and the selective

forces involved. —ABR Sci. Adv. 10.1126/sciadv.aba3274 (2020).

Recognition of kin inf uences the social interactions of mandrills (shown), social primates that form large groups.

Published by AAAS

962 29 MAY 2020 • VOL 368 ISSUE 6494 sciencemag.org SCIENCE

RESEARCH | IN SCIENCE JOURNALS

and tested it in mice and mon-

keys. The TV was obtained by

binding an antibody fragment

of the human immunoglobulin

G1 to the transferrin receptor

expressed in brain endothelial

cells. Fusing the TV to the anti–

b-secretase antibody resulted in

high expression of the antibody

in the CNS in mice and monkeys.

In a mouse model of lysosomal

storage disorder, peripheral

delivery of iduronate 2-sulfatase

fused to the TV had therapeutic

effects. The TV might be effective

for delivering therapeutics in

neurological disorders. —MM

Sci. Transl. Med. 12, eaay1359,

eaay1163 (2020).

OCEAN CIRCULATION

Changing forces in midstreamThe intensity and frequency

of the strongest cyclones east

of Taiwan have increased over

the past several decades as the

climate has warmed. Zhang et

al. found that one result of this

trend has been the strength-

ening of Kuroshio current

transport off the coast of Japan.

The Kuroshio, like its Atlantic

counterpart the Gulf Stream,

is a surface current that moves

huge volumes of warm water

from low latitudes to high ones.

As strong Pacific cyclones have

become stronger, they have

increased the amount of energy

contained in cyclonic mesoscale

ocean eddies and decreased

that of anticyclonic ones. This in

turn has increased the transfer

of energy to the Kuroshio as

eddies move into the current,

providing a feedback between

climate warming and ocean heat

transport. —HJS


ORGANIC CHEMISTRY

Stitching alkynes into bryostatin 3The bryostatin family of marine

natural products has been

explored for a wide variety of

pharmaceutical applications but

remains challenging to source.

The general structure comprises

a macrocycle that contains three

smaller, six-membered rings.

Bryostatin 3 is distinguished by

the added complexity of a fourth,

fused lactone ring. Trost et al.

report a convergent synthesis

of this complex molecule, taking

advantage of alkyne coupling

reactions to stitch together three

main fragments and asym-

metric dihydroxylation and

propargylation reactions to set

stereochemistry. —JSY


CANCER

Profiling tumor bacteriaBacteria are well-known residents

in human tumors, but whether

their presence is advantageous

to the tumors or to the bacteria

themselves has been unclear. As

an initial step toward addressing

this question, Nejman et al. pro-

duced an exhaustive catalog of

the bacteria present in more than

1500 human tumors representing

seven different tumor types (see

the Perspective by Atreya and

Turnbaugh). They found that the

bacteria within tumors were local-

ized within both cancer cells and

immune cells and that the bacte-

rial composition varied

according to tumor

type. Certain biologically

plausible associations

were identified. For

example, breast cancer

subtypes characterized

by increased oxidative

stress were enriched in

bacteria that produce

mycothiol, which can

detoxify reactive oxygen

species. —PAK


see also p. 938

MEDICAL GENETICS

Genetic variant takes the pressure offThe identification of rare genetic

variants that protect carriers

from a specific disease can pro-

vide a launch point for studies

of disease biology and therapy.

In a search for genes that affect

the risk of developing the com-

mon eye disease glaucoma,

Tanigawa et al. examined data

from more than 500,000 indi-

viduals represented in UK and

Finnish biobanks. They found

that missense and nonsense

variants in ANGPTL7, the gene

encoding angiopoietin-related

protein 7, which is a member of

IN OTHER JOURNALS Edited by Caroline Ash

and Jesse Smith

BIOLOGICAL MEMBRANES

Dissecting uneven complex distribution

Eukaryotic cells contain heterogeneous membranes that

vary in curvature, lipid and protein composition, and cel-

lular context. Filling in molecular details for such cellular

structures is a great challenge for structural biologists.

Wietrzynski et al. used in situ cryo–electron tomography

to capture views of the native thylakoid membranes of the

single-celled green alga Chlamydomonas reinhardtii. Advances

in data collection and processing permitted identification of

specific membrane-associated complexes such as pho-

tosystems I and II, adenosine triphosphate synthase, and

thylakoid-associated ribosomes. Two-dimensional projections

of the membrane surface revealed a sharp compositional

transition between appressed membranes (those that directly

face another membrane) and nonappressed membranes. This

technique should enable study of how these membranes are

organized at both the cellular and molecular levels and how

they react to different light conditions. —MAF

eLife 9, e53740 (2020).

IMA

GE

S (

FR

OM

LE

FT

): E

OS

DIS

WO

RL

DV

IEW

/N

AS

A;

BIO

PH

OT

O A

SS

OC

IAT

ES

/S

CIE

NC

E S

OU

RC

E

Color-enhanced

transmission

electron micrograph of a

single-celled green alga

Chlamydomonas reinhardtii

Tropical cyclones, such as Typhoon Maria in 2018,

seen in a satellite image, appear to be strengthening

the Kuroshio current in the North Pacif c.

Published by AAAS

963-B 29 MAY 2020 • VOL 368 ISSUE 6494 sciencemag.org SCIENCE

RESEARCH

MAGNETISM

A structurally ordered spin glassSpin glasses that form in

disordered materials such as

magnetic alloys have locally

varying magnetic patterns, and

their spin relaxation occurs

over time scales spanning many

orders of magnitude. Kamber et

al. used spin-polarized scan-

ning tunneling microscopy to

image the magnetism on the

(0001) surface of thick, single-

crystal films of neodymium as

a function of temperature and

magnetic field. Despite the lack

of structural disorder, they found

a spectral distribution of degen-

erate magnetic wave vectors, or

Q states, that exhibited spatio-

temporal variation. In this spin-Q

glass, pockets of nearly degener-

ate spin spiral states formed

with varying periodicity. Ab initio

electronic structure coupled to

atomistic spin dynamics calcula-

tions suggests that the double

hexagonal closed packed crystal

structure in neodymium drove

strongly frustrated magnetism

that created these pockets.

—PDS


FOREST ECOLOGY

Shifting forest dynamicsForest dynamics are the pro-

cesses of recruitment, growth,

death, and turnover of the con-

stituent tree species of the forest

community. These processes are

driven by disturbances both natu-

ral and anthropogenic. McDowell

et al. review recent progress in

understanding the drivers of for-

est dynamics and how these are

interacting and changing in the

context of global climate change.

The authors show that shifts

in forest dynamics are already

occurring, and the emerging

pattern is that global forests

are tending toward younger

stands with faster turnover as

old-growth forest with stable

dynamics are dwindling. —AMS


SYNTHETIC BIOLOGY

Electronic control of designer cellsThere is increasing interest in

using designer cells to pro-

duce or deliver therapeutics.

Achieving direct communica-

tion between such cells and

electronic devices would allow

precise control of therapies.

Krawczyk et al. describe a

bioelectronic interface that

uses wireless-powered elec-

trical stimulation of cells to

promote the release of insulin

(see the Perspective by Brier

and Dordick). The authors

engineered human b cells to

respond to membrane depo-

larization by rapidly releasing

insulin from intracellular storage

vesicles. A bioelectronic device

that incorporates the cells can

be wirelessly triggered by an

external field generator. When

subcutaneously implanted in

type 1 diabetic mice, the device

could be triggered to restore nor-

mal blood glucose levels. —VV


see also p. 936

CORONAVIRUS

Safe vaccine developmentThe coronavirus disease 2019

(COVID-19) pandemic has

prompted accelerated vaccine

development in the hope that

predicted mortality rates can

be reduced and population,

or herd, immunity achieved.

These measures could result in

eventual eradication of the dis-

ease. In a Perspective, Graham

discusses the need to ensure

that vaccines are safe and do not

aggravate coronavirus infection.

Based on lessons learned from

past vaccines, various steps

need to be taken to ensure that

expedited vaccine development

is accompanied in parallel by

safety assessments to prioritize

the most effective candidates.

—GKA


IMMUNOLOGY

Granzyme A lights a fire

Cytotoxic T cells and natural

killer cells use several strategies

to kill infected or transformed

cells. One such pathway entails

the delivery of a family of serine

proteases called granzymes to

target cells through perforin-

mediated pores to induce a form

of programmed cell death called

apoptosis. Zhou et al. show

that granzyme A cleaves and

activates gasdermin B (GSDMB),

a central player in the highly

inflammatory cell death process

known as pyroptosis (see the

Perspective by Nicolai and

Raulet). GSDMB expression was

highly expressed in some tissues

and could be up-regulated by

interferon-g. Enforced expres-

sion of GSDMB in cancer cells

enhanced tumor clearance in a

mouse model, suggesting that

this pathway may be a target for

future cancer immunotherapies.

—STS


see also p. 943

INVASIVE SPECIES

Exotic plants reduce carbon sequestrationInvasive exotic plants have

become a major problem

worldwide, with transformational

effects on the composition

and function of ecosystems.

In a multifactorial experiment

in New Zealand, Waller et al.

show that exotic plants accel-

erate carbon loss from soils

through their interactions with

invertebrate herbivores and

soil biota (see the Perspective

by Urcelay and Austin). They

built 160 mini-ecosystems in

the field, manipulating interac-

tions among plants, invertebrate

herbivores, and soil biota. Key

biological and abiotic responses

were measured to quantify

the relative contribution and

interactions of the components

of each community, revealing

the potential of invasive plants to

influence and suppress carbon

sequestration through biotic

interactions. —AMS


see also p. 934

PEPTIDE SYNTHESIS

Fully synthetic whole proteins in reachSolid-phase peptide synthesis of

homogeneous peptides longer

than about 50 amino acids has

been a long-standing challenge

because of inefficient coupling

and side reactions. Hartrampf et

al. used an automated chemistry

platform to optimize fast-flow

peptide synthesis and were

able to produce fully synthetic

single-domain proteins (see

the Perspective by Proulx). The

targets included proinsulin and

enzymes such as barnase and

a version of HIV-1 protease con-

taining multiple noncanonical

amino acids. Refolded peptides

were nearly indistinguishable

from recombinant proteins,

and the synthesized enzymes

had activity close to that of

their ribosomally synthesized

counterparts. This method will

enable fast, on-demand synthe-

sis of small proteins with a vastly

expanded pool of precursor

amino acids. —MAF


see also p. 941

CORONAVIRUS

Coronavirus in nonhuman primatesWe urgently need vaccines and

drug treatments for coronavirus

disease 2019 (COVID-19). Even

under these extreme circum-

stances, we must have animal

models for rigorous testing of

new strategies. Rockx et al. have

undertaken a comparative study

of three human coronaviruses in

cynomolgus macaques: severe

acute respiratory syndrome–

coronavirus (SARS-CoV)

(2002), Middle East respira-

tory syndrome (MERS)–CoV

Edited by Michael FunkALSO IN SCIENCE JOURNALS

Published by AAAS

29 MAY 2020 • VOL 368 ISSUE 6494 963-CSCIENCE sciencemag.org

RESEARCH

(2012), and SARS-CoV-2 (2019),

which causes COVID-19 (see

the Perspective by Lakdawala

and Menachery). The most

recent coronavirus has a distinct

tropism for the nasal mucosa

but is also found in the intestinal

tract. Although none of the older

macaques showed the severe

symptoms that humans do, the

lung pathology observed was

similar. Like humans, the animals

shed virus for prolonged periods

from their upper respiratory

tracts, and like influenza but

unlike the 2002 SARS-CoV,

this shedding peaked early in

infection. It is this cryptic virus

shedding that makes case detec-

tion difficult and can jeopardize

the effectiveness of isolation.

—CA


see also p. 942

ICE SHEETS

A rapid retreatAre the rates at which we

observe ice shelves shrink-

ing today representative of

how fast they shrank in the

past? Dowdeswell et al. report

observations of the Antarctic

seafloor that reveal the presence

of submarine grounding-zone

wedges on the Larsen continen-

tal shelf (see the Perspective

by Jakobsson). The authors

interpret these ridges as being

caused by the tidal rise and fall

of the ice shelf at the grounding

line, which squeezes the underly-

ing sediments when it rests on

the seafloor. From this, they cal-

culated that ice shelf retreat at

this location about 14,000 years

ago was at times as much as 100

times as fast as the average over

the past 10,000 years. —HJS


see also p. 939

CELL BIOLOGY

Promoting cancer from the GolgiSignaling through insulin-like

growth factor 1 receptor (IGF-1R)

promotes cancer progression,

but therapies targeting IGF-1R

signaling have performed

poorly. Rieger et al. found that

phosphorylation-dependent

trafficking of IGF-1R promotes

aggressive cancer cell behav-

iors (see the Focus by Crudden

and Girnita). Ligand stimula-

tion induced the translocation

of IGF-1R to the Golgi, where it

enhanced cell migration before

being recycled to the plasma

membrane. These findings may

explain why targeting plasma

membrane–localized IGF-1R

has not been clinically effective.

—AMV

Sci. Signal. 13, eaba3176, eabb7887

(2020).

MACROPHAGES

Targeting overzealous macrophagesIntestinal homeostasis relies on

the maintenance of a complex

set of interactions between

intestinal microbiota and the

intestinal immune system.

Pathogens that colonize the gut

disrupt these interactions and

promote intestinal inflammation.

Corbin et al. used the mouse

pathobiont Helicobacter hepati-

cus, which causes inflammation

akin to human inflammatory

bowel disease, to study the role

of intestinal macrophages in

driving inflammation. Using this

model, the authors found that

the transcription factor inter-

feron regulatory factor 5 (IRF5)

was a critical regulator of mac-

rophage inflammatory potential.

Deletion of IRF5 rendered mice

resistant to H. hepaticus–driven

intestinal inflammation. IRF5 and

molecules upstream of IRF5 may

be potential drug targets in the

treatment of human inflamma-

tory bowel disease. —AB

Sci. Immunol. 5, eaax6085 (2020).

Published by AAAS

research - science · cns therapeutics delivering therapeutics to the brain is complicated by the...

Documents