Science - USA (2022-05-27)

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CANCER GENOMICS

Grouping prostrate

cancers

Therapeutic interventions are
needed for prostate tumors
that exhibit a loss of andro-
gen receptor dependence in
castration-resistant prostate
cancer (CRPC). However, there is
a scarcity of prostate cancer cell
line models. Tang et al. performed
a molecular study on a number
of CRPC organoids, cell lines, and
patient-derived xenographs by
combining sequencing tech-
niques and transcriptomics to
identify four distinct genetic
subgroups of tumors. Dominant
transcription factors were identi-
fied for each subgroup, with a
deeper analysis of subgroup 4
leading to the identification of a
chromatin-opening positive-feed-
back loop. From these data, the
authors propose that inhibitors of
the transcriptional coactivators
YAP and TAZ may be used to treat
individuals with subgroup 4–like
tumors, the second most com-
mon type of CRPC observed in
this study. —LMZ
Science, abe1505, this issue p. 960

BIOMEDICINE

Better cardiac care
There is an unmet medical need
for minimally invasive devices
to aid patients with slow heart
rates, particularly after cardio-
vascular surgery. This is because
the lines required to connect
internal electrodes with battery
packs are a common cause of
infection and extended hospi-
talization. Choi et al. developed
a biodegradable, closed-loop,
wireless microelectrome-
chanical system (Bio-MEMS)
for heart rate monitoring and
control (see the Perspective by
Zimmermann). Because the
devices allow for both monitor-
ing and control of the heart rate,
they can be reprogrammed
on demand in response to
physiological conditions using
the onboard electronics.
Furthermore, the batteries in

the devices can be recharged

wirelessly through the skin, fully

eliminating the need for transcu-

taneous wires. —MSL

Science, abm1703, this issue p. 1006;

see also abq0605, p. 917

ADAPTATION

Rapid change

Human impacts are leading to

exceedingly rapid alteration of

our world, from land conver-

sion and habitat loss to climate

change. Some have proposed

that rapid adaptation could help

some species persist in the face

of these changes, but questions

remain about whether adapta-

tion could occur rapidly enough

to make a difference. Bonnet

et al. looked at additive genetic

variance, which determines

the contribution of selection to

genetic change that increases

fitness, in long-term data from 19

species and found it to be higher

than expected—often substan-

tially higher (see the Perspective

by Walsh). These results suggest

that many species may have

some capacity to adapt to our

changing world. —SNV

Science, abk0853, this issue p. 1012;

see also abo4624, p. 920

ENVIRONMENTAL TOXINS

Nutrient control must

include nitrogen

Lake Erie receives water from

important agricultural areas of

Canada and the United States

and is subject to high levels of

nitrogen and phosphorus in

runoff. These nutrients can lead

to rapid growth of photosyn-

thetic organisms, some of which

produce toxins that harm aquatic

animals and compromise drink-

ing water. Recent efforts have

focused on reducing phosphorus

loading. With support from a

large literature meta-analysis,

Hellweger et al. developed an

agent-based model of cyanobac-

terial metabolism to determine

how toxin production changed

under a range of nutrient and

environmental conditions and

defined the associated molecular

mechanisms (see the Perspective

by Ofiţ eru and Picioreanu). The

authors found that phosphorus

reduction alone was potentially

harmful, lowering total biomass

but increasing toxin produc-

tion. The proposed mechanism

involves response to hydrogen

peroxide stress and increased

light transmission. —MAF

Science, abm6791, this issue p. 1001;

see also abq0956, p. 914

ANTIBIOTIC DISCOVERY

Panning for antibiotics

that stand out

Despite their importance in

modern medicine, antibiotics are

under constant threat as patho-

gens adapt, acquire, or evolve

resistance with chilling regular-

ity. Finding new molecules and

mechanisms is one way that

we can keep ahead. Panning

genomes enriched in second-

ary metabolites, Wang et al.

used a computational approach

to predict the structure of a

cyclic nonribosomal lipopeptide

antibiotic, which they named

“cilagicin” (see the Perspective

by Seipke). Chemical synthesis

of the predicted peptide revealed

potent and broad antimicrobial

activity against Gram-positive

bacteria, including a number of

drug-resistant pathogens, and

a cilagicin derivative protected

mice in an acute infection model.

Mechanistic experiments sug-

gested that the peptide binds to

two closely related molecules

involved in lipid biosynthesis, an

ability that may help to prevent

the rapid development of resis-

tance. —MAF

Science, abn4213, this issue p. 991;

see also abq3206, p. 919

METABOLIC DISEASE

Mitigating

methylmalonylation

Methylmalonic acidemia (MMA)

is a genetic metabolic disorder

that results in a buildup of

methylmalonic acid in the body

and can lead to severe symp-

toms. Examining liver tissue

from patients and a mouse

model of MMA, Head et al. found

that the buildup of this metabo-

lite resulted in a widespread

posttranslational modification,

methylmalonylation, on a variety

of proteins. This included the

sirtuin (SIRT5) that reverses

methylmalonylation, dampen-

ing its ability to undo the protein

modification damage. A SIRT5

gene engineered to be resistant

to methylmalonylation reduced

symptoms in the MMA mice,

demonstrating a proof-of-

concept gene therapy strategy.

—CAC

Sci. Transl. Med. 14 , eabn4772 (2022).

GEOMORPHOLOGY

Abruptly changing course

River avulsions are places where

a river abandons its channel,

and are a common feature of

geomorphological structures

such as deltas. Brooke et al. used

50 years of satellite images to

look at the location and change in

river avulsions globally (see the

Perspective by Passalacqua and

Moodie) and found that avulsions

are often tied to changes in chan-

nel slope or sedimentation just

upstream of the river. However, in

some cases, the river avulsion is

farther upstream than expected,

likely due to erosional processes.

Understanding what controls

avulsion location in the context

of climate and land use changes

is vital because avulsions are

strongly tied to risks from flood-

ing. —BG

Science, abm1215, this issue p. 987;

see also abq1166, p. 916

IMMUNE REGULATION

A type 2 skew ages

neutrophils

Immune responses in patients

with atopy are skewed toward

type 2, with overproduction of

cytokines that drive allergic

Edited by Michael Funk

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