Physical Review Research,
Год журнала:
2025,
Номер
7(2)
Опубликована: Апрель 7, 2025
Relating
macroscopic
observables
to
microscopic
interactions
is
a
central
challenge
in
the
study
of
complex
systems.
While
current
approaches
often
focus
on
pairwise
interactions,
complete
understanding
requires
going
beyond
these
capture
full
range
possible
interactions.
We
present
unified
mathematical
formalism,
based
Möbius
inversion
theorem,
that
reveals
how
different
decompositions
system
into
parts
lead
different,
but
equally
valid,
theories.
By
providing
an
exact
bridge
between
and
descriptions,
this
framework
demonstrates
many
existing
notions
interaction,
from
epistasis
genetics
many-body
couplings
physics,
synergy
game
theory
artificial
intelligence,
naturally
uniquely
arise
particular
choices
decomposition,
or
.
revealing
common
structure
underlying
seemingly
disparate
phenomena,
our
paper
highlights
choice
decomposition
fundamentally
determines
nature
resulting
discuss
unifying
perspective
can
facilitate
transfer
insights
across
domains,
guide
selection
appropriate
decompositions,
enable
search
for
new
interaction.
To
illustrate
latter
practice,
we
decompose
Kullback-Leibler
divergence,
show
method
correctly
identifies
which
variables
are
responsible
divergence.
In
addition,
use
Rota's
Galois
connection
theorem
describe
coarse
grainings
mereologies,
efficiently
derive
renormalized
1D
Ising
model.
Our
results
suggest
provides
powerful
practical
lens
emergence
behavior
interplay
parts,
with
applications
wide
disciplines.
Published
by
American
Physical
Society
2025
Cell Research,
Год журнала:
2024,
Номер
34(2), С. 101 - 123
Опубликована: Янв. 24, 2024
Abstract
Transforming
growth
factor-βs
(TGF-βs)
and
bone
morphometric
proteins
(BMPs)
belong
to
the
TGF-β
superfamily
perform
essential
functions
during
osteoblast
chondrocyte
lineage
commitment
differentiation,
skeletal
development,
homeostasis.
TGF-βs
BMPs
transduce
signals
through
SMAD-dependent
-independent
pathways;
specifically,
they
recruit
different
receptor
heterotetramers
R-Smad
complexes,
resulting
in
unique
biological
readouts.
promote
osteogenesis,
osteoclastogenesis,
chondrogenesis
at
all
differentiation
stages,
while
play
roles
a
stage-dependent
manner.
have
opposite
articular
cartilage
Moreover,
has
specific
role
maintaining
osteocyte
network.
The
precise
activation
of
BMP
signaling
requires
regulatory
machinery
multiple
levels,
including
latency
control
matrix,
extracellular
antagonists,
ubiquitination
phosphorylation
cytoplasm,
nucleus-cytoplasm
transportation,
transcriptional
co-regulation
nuclei.
This
review
weaves
background
information
with
latest
advances
facilitated
by
BMPs,
advanced
understanding
their
diverse
physiological
regulations.
also
summarizes
human
diseases
mouse
models
associated
disordered
signaling.
A
more
could
facilitate
development
bona
fide
clinical
applications
treating
disorders.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Фев. 17, 2024
Abstract
How
paracrine
signals
are
interpreted
to
yield
multiple
cell
fate
decisions
in
a
dynamic
context
during
human
development
vivo
and
vitro
remains
poorly
understood.
Here
we
report
an
automated
tracking
method
follow
signaling
histories
linked
large
numbers
of
pluripotent
stem
cells
(hPSCs).
Using
unbiased
statistical
approach,
discover
that
measured
BMP
history
correlates
strongly
with
individual
cells.
We
find
response
hPSCs
varies
more
the
duration
than
level.
However,
both
level
activity
control
choices
only
by
changing
time
integral.
Therefore,
interchangeable
this
context.
In
model
for
patterning
embryo,
show
predict
pattern
integral
correctly
predicts
changes
domains
when
is
perturbed.
Our
data
suggest
mechanistically,
integrated
SOX2.
Nature,
Год журнала:
2024,
Номер
629(8011), С. 402 - 409
Опубликована: Апрель 17, 2024
Abstract
Throughout
life,
neuronal
networks
in
the
mammalian
neocortex
maintain
a
balance
of
excitation
and
inhibition,
which
is
essential
for
computation
1,2
.
Deviations
from
balanced
state
have
been
linked
to
neurodevelopmental
disorders,
severe
disruptions
result
epilepsy
3–5
To
balance,
microcircuits
composed
excitatory
inhibitory
neurons
sense
alterations
neural
activity
adjust
connectivity
function.
Here
we
identify
signalling
pathway
adult
mouse
that
activated
response
increased
network
activity.
Overactivation
signalled
through
an
increase
levels
BMP2,
growth
factor
well
known
its
role
as
morphogen
embryonic
development.
BMP2
acts
on
parvalbumin-expressing
(PV)
interneurons
transcription
SMAD1,
controls
array
glutamatergic
synapse
proteins
components
perineuronal
nets.
PV-interneuron-specific
disruption
BMP2–SMAD1
accompanied
by
loss
innervation
PV
cells,
underdeveloped
nets
decreased
excitability.
Ultimately,
this
impairment
functional
recruitment
disrupts
cortical
excitation–inhibition
with
mice
exhibiting
spontaneous
epileptic
seizures.
Our
findings
suggest
developmental
repurposed
stabilize
brain.
Cell Systems,
Год журнала:
2022,
Номер
13(5), С. 408 - 425.e12
Опубликована: Апрель 13, 2022
In
multicellular
organisms,
secreted
ligands
selectively
activate,
or
"address,"
specific
target
cell
populations
to
control
fate
decision-making
and
other
processes.
Key
cell-cell
communication
pathways
use
multiple
promiscuously
interacting
receptors,
provoking
the
question
of
how
addressing
specificity
can
emerge
from
molecular
promiscuity.
To
investigate
this
issue,
we
developed
a
general
mathematical
modeling
framework
based
on
bone
morphogenetic
protein
(BMP)
pathway
architecture.
We
find
that
ligand-receptor
systems
allow
small
number
ligands,
acting
in
combinations,
address
larger
individual
types,
defined
by
their
receptor
expression
profiles.
Promiscuous
outperform
seemingly
more
one-to-one
signaling
architectures
capability.
Combinatorial
extends
groups
is
robust
noise,
grows
powerful
with
increases
variants,
maximized
biochemical
parameter
relationships.
Together,
these
results
identify
design
principles
governing
cellular
ligand
combinations.
