SCIENCE science.org 15 APRIL 2022 • VOL 376 ISSUE 6590 259IMAGE: STEVE GSCHMEISSNER/SCIENCE SOURCE
as protonated salts, but the
products can steadily deproton-
ate them a few at a time as the
reaction progresses. —JSY
Science, abn8382, this issue p. 276CELL BIOLOGY
Monitoring epithelial
integrity
Epithelia provide protective
interfaces between various
tissues and their surround-
ing environment. To function
as barriers, epithelia must
surveil themselves to prevent
breaches that can be caused by
either physical damage or the
formation of aberrant cells. The
mechanism by which an epithe-
lium monitors and maintains its
integrity is largely unknown. De
Vreede et al. describe a signal-
ing system in fruit fly organs
in which an apically polarized
receptor is spatially compart-
mentalized away from its ligand
that circulates in the basal
milieu. Polarity defects common
to neoplastic cells or wounds
mislocalize the receptor, allow-
ing ligand binding and signal
transduction. This work shows
how an elegant mechanism that
detects and repairs breaches
to the epithelial barrier has
also been adopted to eliminate
oncogenic clones and explains
how epithelial defects can be
recognized as a damage-associ-
ated molecular pattern. —BAP
Science, abl4213, this issue p. 297NEUROSCIENCE
Independent computations
within dendrites
Cortical pyramidal neurons typi-
cally have an elaborate dendritic
tree that receives and integrates
the many synaptic inputs target-
ing the neuron. An open question
is how information is represented
in dendrites in vivo. Otor et al.
investigated synaptic computa-
tions in the apical tuft of layer 5
pyramidal neurons in the mouse
motor cortex using two-photon
calcium imaging, behavioral
analysis, and cable modeling.
Early-branching layer 5 pyra-
midal neurons showed markedEdited by Caroline Ash
and Jesse SmithIN OTHER JOURNALS
MEDICINE
Gene therapy
promotes healing
The rare skin disease reces-
sive dystrophic epidermolysis
bullosa (RDEB) is caused by
mutations in the COL7A1 (col-
lagen type VII a1 chain) gene.
This gene normally encodes
an important component of
the basement membrane that
connects the epidermis and
dermis. RDEB is thus char-
acterized by skin blistering,
fibrosis, and susceptibility to
infection and cancer. Gurevich
et al. developed a topical
gene therapy, beremagenegeperpavec (B-VEC), for
RDEB in which COL7A1 coding
sequences are delivered by
inactivated herpes simplex
virus type 1 (HSV-1) to the
skin. Having established that
B-VEC restored COL7A1 pro-
tein expression in preclinical
models, the authors carried out
a phase 1/2 trial in nine RDEB
patients. B-VEC or placebo was
repeatedly applied to matched
wounds, and B-VEC promoted
COL7A1 expression and
wound closure. There was also
evidence of correct epidermis-
dermis organization. —GKA
Nat. Med. 10.1038/
s41591-022-01737-y (2022).compartmentalization of den-
dritic calcium signaling, whereas
late-branching pyramidal neurons
had synchronous tuft activation.
N-methyl- -aspartate spikes and
cable properties could explain the
varying compartmentalization
patterns. Compartmentalized
activity between hemi-trees
was correlated with behavioral
outcome. These results indicate
a cell-type-dependent dynamic
combinatorial code for motor
representation. —PRS
Science, abn1421, this issue p. 267CANCER
OVs and CARs team up
against solid tumors
Chimeric antigen receptor (CAR)
T cell therapies have limited
efficacy against solid tumors,
in part because of the lack of
tumor-specific antigens. One way
to circumvent this problem is
through combination treatment
with oncolytic viruses (OVs). Egvin
et al. loaded dual-specific CAR
T cells with vesicular stomatitis
virus or reovirus to treat mouse
models of solid tumors. Systemic
treatment with CAR T cells and
OVs extended overall survival by
restimulating memory CAR T cells
with viral T cell receptor specific-
ity. This strategy warrants further
investigation for treating patients
with solid tumors. —DLH
Sci. Transl. Med. 14 , eabn2231 (2022).AEROSOL OPTICS
Higher intensity
Light amplification inside atmo-
spheric aerosol particles could
affect their photochemical prop-
erties. Corral Arroyo et al. report
that optical confinement can
create spatial structuring of the
light intensity inside the particle
and thereby cause correspond-
ing variations of photochemical
rates. Using a combination of
x-ray spectromicroscopic imag-
ing and modeling of single ferric
citrate particles, the authors
predict that photochemical
reactions could be sped up in
this way by a factor of two to
three in atmospheric aerosol
particles. —HJS
Science, abm7915, this issue p. 293MICROBIOLOGYA musky warning signal for nematodes
T
he earthy smell that comes after a rain shower on a warm
day is the product of microbes in soil, a terpene called
geosmin. Zaroubi et al. show that geosmin serves as a
deterrent signal to the model nemotode Caenorhabditis
elegans, which lives in soil and consumes bacteria.
Geosmin and related terpenes are not themselves toxic but
may be a signal to the worms not to eat certain actinobacteria
that do produce other toxic compounds. —MAF
Appl. Environ. Microbiol. 10.1128/aem.00093-22 (2022).Scanning electron
micrograph of a
C. elegans nematode