sciencemag.org SCIENCERESEARCH | IN OTHER JOURNALS
SIGNAL TRANSDUCTION
miRNAs mediate
mTORC1 effects
Too much signaling by the
mammalian target of rapamy-
cin complex 1 (mTORC1)
protein kinase complex is a
bad thing in part because it
enhances production of par-
ticular microRNAs (miRNAs).
Mouse cells engineered
to lack the mTORC1 inhibi-
tor component Tsc1 and thus
exhibit excessive mTORC1
signaling also showed altered
glucose metabolism. Liko et al.
traced this effect to enhanced
production of miRNAs from
an imprinted locus (that is,
expressed from the alleles from
one parent of origin only) on
chromosome 12. Expression
of these miRNAs increased
production of enzymes that
catalyze gluconeogenesis and
resulted in glucose intolerance.
Precisely how the miRNAs work
is unclear, but they may provide
a previously unrecognized
target for managing metabolic
diseases. —LBR
Proc. Natl. Acad. Sci. U.S.A.
117 , 1524 (2020).NUTRITION
High-protein diet
affects circulation
Diets that are high in protein
can be used to promote weight
loss. The downside is that recent
evidence suggests that high
dietary protein is associated
with increased incidence of
cardiovascular disease, particu-
larly atherosclerosis. Zhang et
al. fed pro-atherogenic mice a
high-protein diet and found that
more atherosclerotic plaques
formed. They observed that the
resulting high concentrations
of amino acids in the blood
activated mammalian target of
rapamycin (mTOR) signaling
in macrophages in atheroscle-
rotic plaques. mTOR integrates
numerous amino acid–sensing
pathways, and its activation
in macrophages leads to the
accumulation of dysfunctional
mitochondria and apoptosis.
This work provides importantmechanistic insight into how
dietary nutrients can influence
systemic homeostasis. —GKA
Nat. Metab. 2 , 110 (2020).ORGANIC SYNTHESIS
Closing rings with
porous templates
The closure of large rings from
linear substrates (macrocycliza-
tion) must avoid the competing
coupling between molecules
and the entropic penalty for
folding long chains. Hydrophobic
nanoscale cavities can assist in
both folding of chains and avoid-
ing intermolecular reactions.
Liu et al. used a self-assembling
molecule bearing bent chains
of aromatic groups to create
two-dimensional sheets with
~2-nanometer pores. A
palladium(0) catalyst performed
Suzuki couplings on linear
substrates bound in the pores
to create >30-mer macrocycles.
On formation, the macrocycles
released spontaneously to
enable subsequent rounds of
reaction. —PDS
J. Am. Chem. Soc. 142 , 1904 (2020).PSYCHOLOGY
Altruism reduces
physical pain
The physical sensation of pain
may depend on how people psy-
chologically construe it. Wang et
al. conducted a series of studies
to demonstrate that engaging in
painful activities to help others is
associated with reduced percep-
tions of pain. In follow-up studies,
they found that experimentally
manipulating people to donate to
charitable causes reduces pain
sensations. Brain areas related
to pain sensation demonstrated
reduced activation when
participants donated. In a final
study, cancer patients randomly
assigned to engage in helping
behaviors over the course of a
week reported less chronic pain.
These results suggest that engag-
ing in prosocial behaviors may
have alleviative properties for the
individual performer. —TSR
Proc. Acad. Natl. Sci. U.S.A.
117 , 950 (2020).INFECTIONTrouble brewing
in the gut
I
nvasive infections with
fungi likeCandida albicans
can be a serious complica-
tion of organ transplantation
and chemotherapy. One possible
explanation is that these procedures
alter the intestinal microbiota, which
may provide an opening for opportu-
nistic fungi. For better insight into this
relationship, Zhaiet al.investigated
patients receiving allogeneic hemato-
poietic stem cell transplants. They used
high-resolution mycobiota and micro-
biota sequencing of recipients’ blood
and feces to track the dynamics of
infection. A pronounced loss of bacterial
microbiota and diversity (especially of
anaerobes) was accompanied by expan-
sion of pathogenic Candidaspecies in
the intestine. This overgrowth in the gut
preceded bloodstreamCandida infec-
tions. In the future, similar monitoring
approaches may be used to better
target patients at risk for invasive fungal
infections. —STS
Nat. Med. 26 , 59 (2020).Candida albicans,
shown here, is a fungus
often found in the
gut, but it can become
pathogenic and
invasive after surgery.IMAGE: 3D4MEDICAL/SCIENCE SOURCE754 14 FEBRUARY 2020 • VOL 367 ISSUE 6479
Published by AAAS