SCIENCE science.org 25 FEBRUARY 2022 • VOL 375 ISSUE 6583 834-BNEUROSCIENCE
Aging and sleep
disruption
In humans, the deterioration of
sleep quality during aging is one
of the most prevalent com-
plaints. In an animal model, Li et
al. found that aging correlated
with enhanced spontaneous
activity of wake-promoting brain
areas during sleep (see the
Perspective by Jacobson and
Hoyer). Hypocretin-expressing
neurons were more active during
sleep, raising the chances of
brief arousals and thus causing
sleep to be more fragmented.
The excitability of hypocretin
neurons in aged brain tissue was
heightened, possibly because
of decreased expression of a
subpopulation of potassium
channels. Aging-related sleep
fragmentation may therefore be
due to altered intrinsic excit-
ability of arousal-promoting
neurons. —PRS
Science, abh3021, this issue p. 838;
see also abo1822, p. 816IMMUNOLOGY
Trained ILC3: Better,
faster, stronger!
Type 3 innate lymphoid cells
(ILC3s) are enriched in the intes-
tinal tract and play important
roles in mucosal homeostasis,
host defense, and the orga-
nization of lymphoid tissues.
Although certain innate immune
cell populations can adopt
new long-term phenotypes
in response to inflammatory
signals (“trained immunity”),
whether this is also true of ILC3s
is unclear. Serafini et al. report
that after mice were infected
with Citrobacter rodentium,
a subset of activated ILC3s
persisted for months. These
“trained” ILC3s (Tr-ILC3s)
showed superior activation and
controlled infection better than
“naïve” ILC3s after pathogen
rechallenge. The initial encoun-
ter with C. rodentium durably
rewired the metabolic pathwaysof Tr-ILC3s, endowing them with
an enhanced capacity to prolifer-
ate and secrete cytokines such
as interleukin-22. —STS
Science, aaz8777, this issue p. 859CORONAVIRUS
Ongoing adaptation
of SARS-CoV-2
Two years into the COVID-19
pandemic, several variants
of severe acute respiratory
syndrome coronavirus 2 (SARS-
CoV-2) have arisen that show
increased infectivity or evade
immunity. The Omicron variant
of concern has 37 mutations
in the spike protein, which is
responsible for host cell entry.
Most of these mutations are
in two domains targeted by
neutralizing antibodies, the
receptor-binding domain (RBD),
and the N-terminal domain
(NTD). McCallum et al. pre-
sent structures of the viral spike
bound to S309, a therapeutic
antibody that maintains neutral-
izing activity against Omicron,
and structures of the RBD bound
to S309 and the human ACE2
receptor. The structures show
how Omicron retains high-
affinity binding to ACE2 while
greatly reducing binding to other
therapeutic antibodies. —VV
Science, abn8652, this issue p. 864ORGANIC CHEMISTRY
Twisting enamines
through the mirror
Separating enantiomers, or mir-
ror-image molecules, is essential
to pharmaceutical synthesis.
Enriching an equal mixture of
them by selectively converting
one to the other is not possible
using catalysis alone. Recently,
however, an approach pairing
catalysis with energy injection
from light absorption has proven
feasible. Huang et al. report a
variant of this strategy whereby
a chiral amine catalytically
cycles chiral aldehydes through
enamine derivatives. Selectiveactivation by a light-absorbing
sensitizer then tilts the equi-
librium of enamine isomers to
favor net conversion of a single
aldehyde enantiomer into its
counterpart. —JSY
Science, abl4922, this issue p. 869BLACK HOLES
Misaligned spin in
an x-ray binary
If a black hole is in a close
enough binary system with
a star, it rips material off the
companion. As that material falls
into the black hole, it forms an
accretion disk that is hot enough
to emit optical and x-ray radia-
tion. Poutanen et al. used optical
polarimetry to determine the
orbital axis of a black hole x-ray
binary (see the Perspective by
Patat and Mapelli). Combining
these observations with previ-
ous measurements of the black
hole spin showed that the two
are misaligned by at least 40
degrees. This high misalignment
must have been generated dur-
ing the formation of the black
hole, because accretion always
brings the two axes closer
together. —KTS
Science, abl4679, this issue p. 874; see
also abn5290, p. 821ANTIBIOTIC RESISTANCE
Personal histories
of past resistance
A serious infection may initially
be diagnosed as antibiotic
susceptible but subsequently
become drug resistant—and life
threatening. Rather than de novo
resistance mutation occurring,
it is more likely that a resistant
strain or species persisting in
the patient’s gut or skin replaces
the susceptible strain. From this
starting point, Stracy et al. built
machine-learning models that
predict individual risks of gaining
resistance to specific antibiotics
using 8 years of records on more
than 200,000 patients’ microbi-
ome profiles (see the Perspectiveby Lugagne and Dunlop). Data on
antibiotic use for urinary tract
and wound infections were used
to train the algorithms and to
develop personalized antibiotic
treatment strategies. For most
patients, there was an alternative
susceptibility-matched antibiotic
that had a lower predicted risk of
resistance emerging compared
with the antibiotic prescribed by
the physician. —CA
Science, abg9868, this issue p. 889;
see also abn9969, p. 818ORGANIC CHEMISTRY
A late coupling for
himastatin
Himastatin is a bacterial natural
product that has been studied
over the past several decades
for its antibiotic properties
and intriguing structure. The
compound is a dimer of peptide
macrocycles linked through a
bond between the aryl rings of
two cyclotryptophan residues.
D’Angelo et al. report a com-
paratively efficient synthesis of
himastatin as well as its unnatu-
ral enantiomer and several other
derivatives (see the Perspective
by Smith). The key step is a late-
stage dimerization relying on
oxidation of the monomers by a
copper salt. Fluorescent tagging
sheds light on the compound’s
cell membrane–disrupting
mechanism of action. —JSY
Science, abm6509, this issue p. 894;
see also abn8327, p. 820INTERFERON SIGNALING
From bone marrow
to hemorrhage
Hemorrhaging is a potentially
fatal outcome of arenaviral infec-
tions and is related to increased
interferon-a (IFN-a) production.
Aiolfi et al. found that bleeding
from arenaviral infection in mice
resulted from IFN-a trigger-
ing the formation of defective
platelets through a pathway that
did not act directly on plate-
lets, which lack IFN receptors.Edited by Michael FunkALSO IN SCIENCE JOURNALS
RESEARCH0225ISIO_15096744.indd 835 2/18/22 5:51 PM