Science - USA (2021-11-12)

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837-B 12 NOVEMBER 2021 • VOL 374 ISSUE 6569 science.org SCIENCE


RESEARCH


NEURODEVELOPMENT


Insulation for circuit


regulation


Lipid-rich myelin, which wraps
around and insulates neuronal
axons, improves the speed and
efficiency of signal propagation.
Myelination is not universally
applied in the central nervous
system, and even axons within
the same circuit can vary in the
amount of myelination they
carry. Bonetto et al. reviewed
what is known about how such
variability can affect computa-
tional functions in brain circuits.
Myelin plasticity may be one
mechanism linking experien-
tial learning to modified brain
connections. Whether you are
learning to juggle or learning to
read, changes in myelination
may tune the circuits underlying
those skills. —PJH
Science, aba6905, this issue p. 838


DISEASE GENOMICS


Detangling gene-disease


connections


Many diseases are at least
partially due to genetic causes
that are not always understood
or targetable with specific treat-
ments. To provide insight into
the biology of various human
diseases as well as potential
leads for therapeutic develop-
ment, Pietzner et al. undertook
detailed, genome-wide pro-
teogenomic mapping. The
authors analyzed thousands of
connections between potential
disease-associated mutations,
specific proteins, and medical
conditions, thereby providing a
detailed map for use by future
researchers. They also sup-
plied some examples in which
they applied their approach to
medical contexts as varied as
connective tissue disorders,
gallstones, and COVID-19
infections, sometimes even
identifying single genes that
play roles in multiple clinical
scenarios. —YN
Science, abj1541, this issue p. 839


PLANT SCIENCE
A closer look at
centromeres
Centromeres are key for anchor-
ing chromosomes to the mitotic
spindle, but they have been
difficult to sequence because
they can contain many repeating
DNA elements. These repeats,
however, carry regularly spaced,
distinctive sequence markers
because of sequence heteroge-
neity between the mostly, but
not completely, identical DNA
sequence repeats. Such differ-
ences aid sequence assembly.
Naish et al. used ultra-long-read
DNA sequencing to establish a
reference assembly that resolves
all five centromeres in the small
mustard plant Arabidopsis. Their
view into the subtly homog-
enized world of centromeres
reveals retrotransposons that
interrupt centromere orga-
nization and repressive DNA
methylation that excludes
centromeres from meiotic cross-
over repair. Thus, Arabidopsis
centromeres evolve under the
opposing forces of sequence
homogenization and retrotrans-
poson disruption. —PJH
Science, abi7489, this issue p. 840

NEUROSCIENCE
Common basis for
language and tool use
Tool use and language are
hallmarks of human evolu-
tion. Because of the similarity
between the motor processes for
tool use and those supporting
language, it has been hypoth-
esized that syntax and tool use
may share brain resources.
Using functional magnetic reso-
nance imaging and multivariate
pattern analysis, Thibault et al.
found that small portions of
the basal ganglia in the human
brain act as common neural
substrates for both tool use and
syntax in language. In a behav-
ioral experiment, they showed
that learning a novel task that
involves the use of a tool also

improves performance in a com-
plex language task. These results
further support the hypothesis
of a co-evolution of tool use and
language. —PRS
Science, abe0874, this issue p. 841

NEURODEGENERATION
Autoimmunity in Lewy
body dementia
Lewy body dementia (LBD) is
a brain disease that leads to
progressive decline in thinking,
movement, and independent
function. It results from the
buildup of microscopic depos-
its called Lewy bodies, which
develop from the aggregation
of a misfolded protein called
a-synuclein. Gate et al. observed
immune cells known as T cells
in the brains of LBD patients
(see the Perspective by Krot
and Rolls). Genomics analysis
revealed that T cells traffic to the
LBD brain and are associated
with neuronal damage. When
stimulated with a-synuclein,
LBD patient T cells secrete an
inflammatory protein known
to damage neurons. These
findings suggest an unexpected
detrimental role of the immune
system in LBD. —SMH
Science, abf7266, this issue p. 868;
see also abm4739, p. 823

GENOMICS OF AGING
A fishy tale of long
and short life span
Fish have wide variations in life
span even within closely related
species. One such example
are the rockfish species found
along North Pacific coasts,
which have life spans ranging
from 11 to more than 200 years.
Kolora et al. sequenced and
performed a genomic analysis
of 88 rockfish species, includ-
ing long-read sequencing of the
genomes of six species (see
the Perspective by Lu et al.).
From this analysis, the authors
unmasked the genetic drivers
of longevity evolution, including

immunity and DNA repair–
related pathways. Copy number
expansion in the butyrophilin
gene family was shown to be
positively associated with life
span, and population histori-
cal dynamics and life histories
correlated differently between
long- and short-lived species.
These results support the idea
that inflammation may modulate
the aging process in these fish.
—LMZ
Science, abg5332, this issue p. 842;
see also abm3392, p. 824

DYNAMIC BIOSCAFFOLDS
Fibril motion improves
peptide signaling
Artificial scaffolds that bear the
peptide-signaling sequences of
proteins for tissue regeneration
often have limited effective-
ness. Álvarez et al. synthesized
supramolecular peptide fibril
scaffolds bearing two peptide
sequences that promote nerve
regeneration, one that reduces
glial scarring and another that
promotes blood vessel forma-
tion (see the Perspective by
Wojciechowski and Stevens).
In a mouse model of paralyzing
human spinal cord injury, muta-
tions in a tetrapeptide domain
outside of the signaling regions
improved recovery by promoting
intense supramolecular motion
within the fibrils. The mutation
with the most intense dynam-
ics resulted in corticospinal
axon regrowth and myelination,
functional revascularization, and
motor neuron survival. —PDS
Science, abh3602, this issue p. 848
see also abm3881, p. 825

MINERALOGY
Lower mantle
“garbage can”
Calcium silicate perovskite has
finally been identified in a natural
sample and now has the mineral
name davemaoite. Tschauner et
al. discovered the type mineral
trapped at high pressure and

Edited by Michael Funk

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