473-B 29 APRIL 2022 • VOL 376 ISSUE 6592 science.org SCIENCE
RESEARCH
PAIN
Trk’ing mutations
for pain relief
The nerve growth factor receptor
tropomyosin receptor kinase A
(TrkA) is an attractive target for
alleviating pain, but it also medi-
ates other signaling pathways
that are critical to neuronal func-
tion and survival. To find targets
specifically within its pain-
mediating pathways, Moraes
et al. examined the structural
consequences of TrkA mutations
that cause a pain-insensitivity
disorder. They found mutations
that disrupted the interaction of
TrkA with one of its downstream
effectors, phospholipase Cg.
Treating mice with a peptide
designed to similarly disrupt the
interaction reduced sensitivity to
painful inflammation. —LKF
Sci. Signal. 15 , eabm6046 (2022).
DOG GENOMICS
What is your dog like?
Modern domestic dog breeds
are only ~160 years old and
are the result of selection for
specific cosmetic traits. To inves-
tigate how genetics align with
breed characteristics, Morrill et
al. sequenced the DNA of more
than 2000 purebred and mixed-
breed dogs. These data, coupled
with owner surveys, were used
to map genes associated with
behavioral and physical traits.
Although many physical traits
were associated with breeds,
behavior was much more vari-
able among individual dogs. In
general, physical trait heritability
was a greater predictor of breed
but was not necessarily a predic-
tor of breed ancestry in mutts.
Among behavioral traits, bidda-
bility—how well dogs respond to
human direction—was the most
heritable by breed but varied
significantly among individual
dogs. Thus, dog breed is gener-
ally a poor predictor of individual
behavior and should not be used
to inform decisions relating to
selection of a pet dog. —LMZ
Science, abk0639, this issue p. 475
Edited by Michael FunkALSO IN SCIENCE JOURNALS
PATHOGEN EVOLUTION
Immunity-induced
evolution
Population immunity is thought
to drive pathogen evolution-
ary dynamics, but this process
can be hard to measure.
Considering the switch from
whole-cell vaccines to acellular
vaccines (ACVs) as a natural
experiment, Lefrancq et al. ana-
lyzed the diversity of Bordetella
pertussis genome isolates
from five continents to infer
local changes in strain fitness
after ACV introduction. Their
analysis provides evidence that
ACVs have led to the increased
fitness of strains that lack
the virulence factor pertactin
and may have implications for
understanding asymptomatic
B. pertussis infection. —CAC
Sci. Transl. Med. 14 , eabn3253
(2022).BATTERIES
Observations
of cathode evolution
The loss of capacity in a
rechargeable battery can be
due to changes in the elec-
trode structure that occur with
cycling. Li et al. used hard x-ray
holotomography to visualize
the structure of a nickel-rich
LiNi0.8Mn0.1Co0.1O 2 composite
cathode (see the Perspective
by Xiao). They were able to
track the behavior of thousands
of individual particles with
time and thus determine the
relationship between structure
and performance as well as the
deterioration of the cathode at
a size scale that is not gener-
ally accessible. They found
that damage during cycling is
driven not only by each particle
but also by its surrounding
neighbors, although the con-
tributions shift over time. This
work suggests ways to better
design electrodes to maximize
their performance. —MSL
Science, abm8962, this issue p. 517;
see also abo7670, p. 455ZEOLITES
Benzene stretches
zeolite channels
The pores of zeolites allow
for selective adsorption of
molecules based on their size
and shape. The pore sizes that
are calculated based on their
structure are smaller than what
would be expected from their
absorption and chemical reac-
tion properties, which implies
that the frameworks must have
inherent flexibility. Xiong et al.
used environmental transmis-
sion electron microscopy to
image the straight channels of
ZSM-5 zeolite with adsorbed
benzene (see the Perspective
by Willhammar and Zou). The
pores stretched along the lon-
gest direction of the confined
benzene molecules by up to
15%. This large change was
compensated for by adjacent
channels so that the overall
deformation of the original unit
cells was less than 0.5%. —PDS
Science, abn7667, this issue p. 491;
see also abo5434, p. 457EXTINCTION
Rising temperatures,
rising risks
Climate change brings with it
the increasing risk of extinction
across species and systems.
Marine species face particular
risks related to water warming
and oxygen depletion. Penn and
Deutsch looked at extinction
risk for marine species across
climate warming and as related
to ecophysiological limits (see
the Perspective by Pinsky and
Fredston). They found that
under business-as-usual global
temperature increases, marine
systems are likely to experience
mass extinctions on par with
past great extinctions based
on ecophysiological limits
alone. Drastically reducing
global emissions, however,
offers substantial protection,
which emphasizes a need for
rapid action to prevent possiblyINFECTIOUS DISEASE
Another pandemic
threat?
Over the past year, a highly
pathogenic avian influenza virus
(HPAIv) lineage has caused
widespread outbreaks and
deaths in poultry and wild birds,
as well as some infections in
humans. Although there is no
evidence of human-to-human
transmission, there is concern
that the prevalence of these
viruses could result in adapta-
tion that allows transmission
between humans. In addition,
the unprecedented spread and
frequency in Europe, Asia, and
North America has had major
impacts on the poultry industry
and is a threat to wild birds,
especially those that are already
endangered. In a Perspective,
Wille and Barr discuss the fac-
tors that have led to outbreaks of
this HPAIv lineage, the conse-
quences, and what can be done.
—GKA
Science, abo1232, this issue p. 459CANCER
Building up to melanoma
Numerous cancer-causing muta-
tions have been identified over
the years, but they do not occur
in isolation, and it is difficult
to disentangle the effects of
individual genetic changes in a
tumor that contains hundreds
of mutations. To gain insight
into melanoma biology and
facilitate further study of this
cancer, Hodis et al. began with
healthy human melanocytes and
sequentially introduced mel-
anoma-associated mutations
using gene editing. The edited
cells were then grown in mouse
models, simulating human mela-
nomas with different mutation
patterns. The authors examined
the genomics, histology, and
biological behavior of the result-
ing tumors and compared them
with naturally occurring human
tumors, demonstrating the rel-
evance of their approach. —YN
Science, abi8175, this issue p. 474