of function in the mouse brain.
Selective deletion of TDP-43
from oligodendrocyte precursor
cells resulted in their rapid death.
Deletion of TDP-43 at different
stages of oligodendrocyte matu-
ration led to different outcomes.
Early deletion caused degenera-
tion of mature oligodendrocytes,
seizures, and premature lethality,
whereas late deletion spared
oligodendrocytes and allowed
seizure-free survival. Both
manipulations led to thinner and
fewer myelin sheaths and to inap-
propriate wrapping of neuronal
cell bodies and blood vessels.
Conditional removal of TDP-43
from oligodendrocytes in adults
caused hindlimb weakness. Loss
of TDP-43 led to the missplicing
of RNAs that encode key genes
involved in oligodendrocyte mor-
phogenesis and myelination and
may underlie abnormal neuronal
activity and neurodegeneration
in diverse neurological diseases.
—SMH
eLife 11 , e75230 (2022).SCIENCE science.org 29 APRIL 2022 • VOL 376 ISSUE 6592 473
In the dark, the fluttering motion
is much slower than chain
elongation, but under irradiation,
fluttering is 11 times faster. This
motion inhibits both nucleation
and polymerization until the solu-
tion is returned to the dark state
and provides a photoswitch for
polymerization. —PDS
J. Am. Chem. Soc. 10.1021/
jacs.2c02176 (2022).
CANCER GENOMICS
Mind the genome gaps
The Cancer Genome Atlas
(TCGA) is a major resource in
cancer genomics, encompass-
ing sequencing data for 33
different human cancer types.
Unfortunately, ethnic minority
patients are underrepresented
in TCGA, even though they
often have a higher cancer
risk. Wickland et al. examined
TCGA data for self-reported
Black patients with seven tumor
types and discovered that for
six of these cancers, the tumor
genomes of these patients were
sequenced at a lower depth than
tumor genomes of those with
European ancestry. In some
cases, this happened because the
genomes of most patients with
African ancestry were sequenced
in later batches. Additionally, they
were more likely to have insuf-
ficient coverage in parts of the
exome, likely because the human
reference genome is biased
toward European ancestry. These
findings highlight important gaps
to address in future sequencing
e f f o r t s. —Y N
J. Natl. Cancer Inst. 10.1093/
jnci/djac054 (2022).NEUROSCIENCE
Unwrapping TDP-43
Oligodendrocytes continually
renew and mature to generate
myelin sheaths that enwrap
and insulate axons. TDP-43 is
a protein known to play a role
in neurodegenerative disease.
Heo et al. studied TDP-43 lossPOLARITONIC CHEMISTRY
Proton transfer inside
an optical cavity
There is considerable interest in
developing approaches to control-
ling proton transfer reactions,
which play a key role in a wide
range of practically important
energy conversion processes.
Using quantum electrodynam-
ics ab initio methods, Pavoš ević
et al. studied the effect of strong
light-matter interactions, which
can be created by an optical cavity,
on intramolecular proton transfer
in malonaldehyde and aminopro-
penal. The authors showed that
the optical cavity can increase
or decrease the rate of proton
transfer in these two prototypical
systems, depending on the cavity-
mode polarization. The present
work demonstrates that the effect
of an optical cavity could serve as
a practical route to controlling pro-
ton transfer reactions and should
trigger further experimental devel-
opments in this direction. —YS
J. Am. Chem. Soc. 144 , 4995 (2022).INNATE IMMUNITY
Don’t hold your breath!
Breathing does more than just
ensure the oxygenation of an
animal’s tissues. With its dynamic
and regular mechanical forces,
breathing has been implicated in
all sorts of processes, including
lung development and regulation
of immune responses. Bai et al.
used a human lung alveolus chip
microfluidic device that recapitu-
lates human airway physiology to
model H3N2 influenza infection.
They found that cyclical respira-
tory motion inhibits viral infection
by activating the mechanosensi-
tive ion channel TRPV4, which
then induces lung epithelium and
endothelium to produce S100
alarmin proteins. These media-
tors bind the pattern recognition
receptor RAGE, which triggers
several innate immune response
programs that help combat virus.
Intriguingly, a TRPV4 inhibitor was
able to reduce both inflammation
and viral loads, suggesting that
this may be a useful approach for
the treatment of viral pneumonia.
—STS
Nat. Commun. 13 , 1928 (2022).