733-B 18 FEBRUARY 2022 • VOL 375 ISSUE 6582 science.org SCIENCE
RESEARCH
ECOLOGY
Animal tracking
in a big-data world
So-called “big-data” approaches
have revolutionized fields of
research from astronomy to
genetics. Such approaches are
not limited to fields that seem
inherently technical, because the
combination of rapid data col-
lection and advanced analytical
techniques could be applied to
almost any scientific question.
Nathan et al. reviewed how these
modern approaches are being
applied to the very old field of
animal tracking and monitor-
ing. Large-scale data collection
can reveal details about how
animals use their environment
and interact with each other
that were impossible to explore
previously. Such methodological
shifts will open new avenues of
research—and conservation—
across species. —SNV
Science, abg1780, this issue p. 734
ENVIRONMENTAL TOXINS
Mixed chemicals’
potential risks
Exposure to endocrine-
disrupting chemicals in the
environment can cause a variety
of health problems in human
patients. Such exposures are not
isolated, however, and environ-
mental safety regulations that
only consider doses of individual
chemicals do not take multisub-
stance exposures into account.
Caporale et al. examined chemi-
cal exposure data in a large
cohort of human mother-child
pairs and identified a set of
common endocrine-disrupting
chemicals (see the Perspective
by Liew and Guo). The authors
then showed that a mixture of
these substances could cause
abnormalities in two model
organisms and may also be
associated with language delay
in humans. These findings sug-
gest a need for further research
into the effects of chemical
mixtures and regulations that
take such combinatorial effects
into account. —YN
Science, abe8244, this issue p. 735;
see also abn9080, p. 720BLOOD–BRAIN BARRIER
Endothelial-targeted
BBB therapeutics
The brain is protected not
only by the skull, but also by
the blood-brain barrier (BBB),
which restricts transmission
of substances from the blood
into the central nervous system
(CNS) extracellular fluid. If the
BBB is breached, neurological
disorders result. Therefore, it is
desirable to develop interven-
tion strategies that correct BBB
deficits by restoring its function.
Wnt signaling proteins have been
shown to regulate the BBB, and
Martin et al. developed a large,
single-residue mutational screen
covering more than half of the
exposed surface of Wnt7a (see
the Perspective by McMahon
and Ichida). The authors identi-
fied a class of variants that
exhibit strict specificity for
the BBB’s Gpr124/Reck Wnt
signaling module. Gpr124/Reck
agonists display “on-target” neu-
rovascular protective properties
in stroke and glioblastoma mod-
els in mice without “off-target”
Wnt activation in other tissues,
thereby defining a strategy
to alleviate CNS disorders by
repairing the BBB. —BAP
Science, abm4459, this issue p. 737;
see also abn7921, p. 715CELL BIOLOGY
Cystine as lysosomal
fasting signal
Communication between the
lysosome and mitochondria
appears to help maintain control
of metabolism in fruit flies
deprived of food for prolonged
periods. When food is limited,
the target of rapamycin complex
1 (TORC1) protein kinase com-
plex is inhibited, which promotes
catabolism and autophagyto provide nutrients. Newly
supplied amino acids could reac-
tivate TORC1, but Jouandin et al.
implicated cystine released from
lysosomes in allowing continued
catabolism during prolonged
fasting. Cystine, when reduced
to two molecules of cysteine,
may promote the transient stor-
age of remobilized amino acids
in the form of tricarboxylic acid
cycle intermediates in the mito-
chondria, thus limiting TORC1
reactivation during a prolonged
fast. —LBR
Science, abc4203, this issue p. 736IMMUNOLOGY
T cell proliferation
with Themis
The T cell–specific protein
Themis has been implicated in
the homeostasis and activa-
tion of mature T cells. Liu et al.
demonstrated that Themis is
required for cytokine-dependent
CD8+ T cell homeostasis in mice
and for T cell proliferation driven
by the cytokines interleukin-2
(IL-2) and IL-15 in vitro. Themis
stimulated cytokine signaling by
reducing the activity of the phos-
phatase Shp1 and promoted
cytokine-induced changes in
gene expression and metabolic
pathways that enabled T cell
proliferation. These results
identify Themis as an important
determinant of T cell prolifera-
tion. —AMV
Sci. Signal. 15 , eabi9983 (2022).INFLAMMATION
Stress leads to
IL-24 danger
It is unclear how protea-
some dysfunction leads to
inflammation in patients with
proteasome-associated autoin-
flammatory syndrome (PRAAS).
Davidson et al. used multiple
knockout cell lines, knockout
mice, and primary PRAAS
patient samples to show that
protein kinase R (PKR) activation
drives elevated innate immuneresponses. Activation of PKR
was induced by the cytoplas-
mic accumulation of misfolded
interleukin-24 (IL-24), acting as
a danger-associated molecular
pattern. Inhibiting PKR with a
targeted inhibitor ameliorated
the inflammation seen in PRAAS
primary cells. Thus, IL-24–driven
PKR activation induces innate
inflammation in the context of
PRAAS, and its inhibition may
present a therapeutic route for
these patients. —DAE
Sci. Immunol. 7 , eabi6763 (2022).STRUCTURAL BIOLOGY
Clearing up roles
of nebulin
Thin and thick actomyosin fila-
ments are the key components
of muscle. In skeletal muscle,
the protein nebulin is essential
for the length and strength of
the thin filaments, with muta-
tions of nebulin often leading to
muscle diseases called nemaline
myopathies. Wang et al. used
cryo–electron tomography
to identify nebulin integrated
within the thin filament of native
skeletal muscles. The authors
determined a near-atomic in situ
structure of nebulin and showed
how it stabilizes thin filaments
and functions as a “molecular
ruler.” The structure of nebulin
along thin filaments is key to
understanding the pathogenicity
of nemaline myopathies. —SMH
Science, abn1934, this issue p. 738RIVER ECOLOGY
Planning for
Amazonian hydropower
Hydropower projects are pro-
liferating in many parts of the
world, but the benefits they bring
in electricity supply are often
offset by environmental costs.
In an international collaboration,
Flecker et al. present a study
that aims to optimize the reten-
tion of ecosystem services in the
face of hydropower expansion
in the Amazon basin (see theEdited by Michael FunkALSO IN SCIENCE JOURNALS