1064 3 JUNE 2022 • VOL 376 ISSUE 6597 science.org SCIENCE
IMAGE: THE SIMULATING EXTREME SPACETIMES (SXS PROJECT/SCIENCE SOURCERESEARCH | IN SCIENCE JOURNALS
magnetic resonance imaging
brain scans to look for differ-
ences that can be attributed to
ASD and not to other causes of
individual variation. The authors
found evidence for continuous
variation and identified two
axes of variation in brain struc-
ture. Such clarity about ASD
variation may help to fine-tune
interventions for individual
patients. —PJH
Science, abm2461, this issue p. 1070
CHEMISTRY
A new cluster on the
p-block: P 3 N
Like carbon, both phospho-
rus and nitrogen are building
blocks of molecules important
for life, and clusters of these
elements provide fundamental
understanding of bonding and
electronic structure. A tetra-
hedral cluster is one of the
smallest and an important pro-
totype of spherical aromaticity
structures. Guided by com-
puted ionization energies, Zang
et al. demonstrate the synthesis
and gas-phase characterization
of the P 3 N tetrahedral cluster
by means of isomer-selective,
tunable soft photoionization
reflectron time-of-flight mass
spectrometry. Insight into the
electronic structure and the
computed strain energy is pro-
vided, laying the groundwork for
accessing this molecule under
less extreme conditions. — SMK
S c i. Ad v. 10.1126/
sciadv.abo5792 (2022).
TOPOLOGICAL OPTICS
Fractal topology
Topological insulators are
formed with insulating bulk
states surrounded by conduct-
ing surfaces. The insulating
bulk states were thought to
be crucial, stemming from the
theoretical framework of the
bulk-boundary correspondence;
however, Biesenthal et al. found
that need not be the case. Using
a fractal structure in which there
is no “bulk” as such, and thus no
bulk insulating states, they show
nonetheless that there are chiral
conducting states confined to
MEDICINE
Masking a toxic
therapeutic protein
Cytokines such as interleukin
12 (IL-12) have diverse roles
in immune regulation, and
although they may have thera-
peutic potential, they can cause
toxic immune cell activation.
Mansurov et al. masked the
pleiotropic effects of IL-12 by
linking it to a fragment of the
IL-12 receptor and engineered
the linker to be cleavable by
tumor-associated proteases.
This meant that the masked
IL-12 could be administered
intravenously to tumor-bearing
mice and was only activated in
the tumor microenvironment.
Upon delivery, masked IL-12
recruited immune cells, the
tumors subsequently became
responsive to immune check-
point therapy, and systemictoxicity was not observed.
This strategy could be viable
to develop more cytokines as
therapeutic agents for a broad
range of diseases that are asso-
ciated with immune dysfunction.
—GKA
Nat. Biomed. Eng. 10.1038/
s41551-022-00888-0 (2022).GENOMICS
Dependence of traits on
phosphorylation
Genome-wide studies defin-
ing mutations that influence
measured biological traits,
quantitative trait loci (QTL),
tend to focus on how the muta-
tions affect the abundance of
RNA transcripts or proteins.
Grossbach et al. extended a
QTL analysis of yeast cells to
measure posttranslational
modification of proteins bythe edge. The results provide a
possible new route to manipu-
lating the topological transport
of light with engineered struc-
tures. —ISO
Science, abm2842, this issue p. 1114PARTHENOGENESIS
It’s the start that counts
Parthenogenetic organisms,
those that have females
that produce asexually, are
relatively rare. The rarity of
these organisms has long
been attributed to the lack of
sex, which facilitates recom-
bination leading to increased
variation and, presumably,
fitness. Kearney et al. studied
a parthenogenetic grasshop-
per with a hybrid origin and
found no decrease in fitness,
across many traits, relative to
its sexual congeners (see the
Perspective by Normark). They
conclude that the rarity of this
type of asexual reproduction is
not due to a lack of fitness but
rather to the difficulty of their
origin. —SNV
Science, abm1072, this issue p. 1110;
see also abq3024, p. 1052ALZHEIMER’S DISEASE
A silent treatment for AD
The microglia-mediated loss of
synapses observed in patients
with Alzheimer’s disease
(AD) contributes to progres-
sive cognitive impairments.
Spurrier et al. evaluated the
role of the metabotropic glu-
tamate receptor 5 (mGluR5)
on synaptic loss and showed
that oral administration of
an mGluR5 silent allosteric
modulator (SAM) restored
synaptic density and reduced
phosphorylated TAU accu-
mulation in mouse models
of AD. Mechanistically, the
treatment reversed gene
expression changes induced
in AD mice and prevented the
synaptic localization of the
complement protein C1q. The
results suggest that SAMs
targeting mGluR5 could be an
effective approach for limiting
AD-related synaptic loss. —MM
Sci. Transl. Med. 14 ,
eabi8593 (2022).IN OTHER JOURNALS
Edited by Caroline Ash
and Jesse Smith