The American Journal of Human Genetics,
Journal Year:
2023,
Volume and Issue:
111(1), P. 200 - 210
Published: Dec. 20, 2023
The
homologous
genes
GTPBP1
and
GTPBP2
encode
GTP-binding
proteins
1
2,
which
are
involved
in
ribosomal
homeostasis.
Pathogenic
variants
were
recently
shown
to
be
an
ultra-rare
cause
of
neurodegenerative
or
neurodevelopmental
disorders
(NDDs).
Until
now,
no
human
phenotype
has
been
linked
GTPBP1.
Here,
we
describe
individuals
carrying
bi-allelic
that
display
identical
with
characterize
the
overall
spectrum
protein
(1/2)-related
disorders.
In
this
study,
20
from
16
families
distinct
NDDs
syndromic
facial
features
investigated
by
whole-exome
(WES)
whole-genome
(WGS)
sequencing.
To
assess
functional
impact
identified
genetic
variants,
semi-quantitative
PCR,
western
blot,
ribosome
profiling
assays
performed
fibroblasts
affected
individuals.
We
also
effect
reducing
expression
CG2017,
ortholog
GTPBP1/2,
fruit
fly
Drosophila
melanogaster.
Individuals
presented
microcephaly,
profound
impairment,
pathognomonic
craniofacial
features,
ectodermal
defects.
Abnormal
vision
and/or
hearing,
progressive
spasticity,
choreoathetoid
movements,
refractory
epilepsy,
brain
atrophy
part
core
syndrome.
Cell
line
studies
a
loss-of-function
(LoF)
disease-associated
but
significant
abnormalities
on
profiling.
Reduced
CG2017
isoforms
was
associated
locomotor
impairment
Drosophila.
conclusion,
LoF
identical,
Mutant
knockout
flies
motor
highlighting
conserved
role
for
CNS
development
across
species.
Journal of Neuroscience,
Journal Year:
2023,
Volume and Issue:
43(14), P. 2537 - 2551
Published: March 3, 2023
General
anesthetics
cause
a
profound
loss
of
behavioral
responsiveness
in
all
animals.
In
mammals,
general
anesthesia
is
induced
part
by
the
potentiation
endogenous
sleep-promoting
circuits,
although
"deep"
understood
to
be
more
similar
coma
(Brown
et
al.,
2011).
Surgically
relevant
concentrations
anesthetics,
such
as
isoflurane
and
propofol,
have
been
shown
impair
neural
connectivity
across
mammalian
brain
(Mashour
Hudetz,
2017;
Yang
2021),
which
presents
one
explanation
why
animals
become
largely
unresponsive
when
exposed
these
drugs.
It
remains
unclear
whether
affect
dynamics
similarly
animal
brains,
or
simpler
animals,
insects,
even
display
levels
that
could
disrupted
Here,
we
used
whole-brain
calcium
imaging
behaving
female
Current Opinion in Neurobiology,
Journal Year:
2023,
Volume and Issue:
81, P. 102748 - 102748
Published: July 14, 2023
The
brain's
evolution
and
operation
are
inextricably
linked
to
animal
movement,
critical
functions,
such
as
motor
control,
spatial
perception,
navigation,
rely
on
precise
knowledge
of
body
movement.
Such
internal
estimates
self-motion
emerge
from
the
integration
mechanosensory
visual
feedback
with
motor-related
signals.
Thus,
this
representation
likely
depends
activity
circuits
distributed
across
central
nervous
system.
However,
responsible
for
estimation,
exact
mechanisms
by
which
motor-sensory
coordination
occurs
within
these
remain
poorly
understood.
Recent
technological
advances
have
positioned
Drosophila
melanogaster
an
advantageous
model
investigating
emergence,
maintenance,
utilization
representations
during
naturalistic
walking
behaviors.
In
review,
I
will
illustrate
how
adult
fly
is
providing
insights
into
fundamental
problems
computations
relevance
all
animals.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: June 11, 2023
Abstract
The
heterogeneity
of
brain
imaging
methods
in
neuroscience
provides
rich
data
that
cannot
be
captured
by
a
single
technique,
and
our
interpretations
benefit
from
approaches
enable
easy
comparison
both
within
across
different
types.
For
example,
comparing
brain-wide
neural
dynamics
experiments
aligning
such
to
anatomical
resources,
as
gene
expression
patterns
or
connectomes,
requires
precise
alignment
common
set
coordinates.
However,
this
is
challenging
because
registering
vivo
functional
ex
reference
atlases
accommodating
differences
modality,
microscope
specification,
sample
preparation.
We
overcome
these
challenges
Drosophila
building
an
atlas
multiphoton-imaged
brains,
called
the
Functional
Atlas
(FDA).
then
develop
two-step
pipeline,
BrIdge
Registering
Over
Statistical
Templates
(BIFROST),
for
transforming
into
space
importing
resources
connectomes.
Using
genetically
labeled
cell
types
ground
truth,
we
demonstrate
registration
with
precision
less
than
10
microns.
Overall,
BIFROST
pipeline
datasets
fly,
experiments.
Significance
Large-scale
have
given
us
new
insights
activity
various
sensory
behavioral
contexts.
precisely
volumetric
images
studies
has
proven
challenging,
limiting
quantitative
comparisons
Here,
address
limitation
developing
BIFROST,
robust
experimental
setups
datasets.
benchmark
labeling
fly
sub-10
micron
precision,
specimens
laboratories.
further
accurate
between
in-vivo
volumes
ultrastructural
enabling
direct
structure-function
future
Proceedings of the National Academy of Sciences,
Journal Year:
2024,
Volume and Issue:
121(47)
Published: Nov. 14, 2024
Imaging
methods
that
span
both
functional
measures
in
living
tissue
and
anatomical
fixed
have
played
critical
roles
advancing
our
understanding
of
the
brain.
However,
making
direct
comparisons
between
different
imaging
modalities,
particularly
spanning
tissue,
has
remained
challenging.
For
example,
comparing
brain-wide
neural
dynamics
across
experiments
aligning
such
data
to
resources,
as
gene
expression
patterns
or
connectomes,
requires
precise
alignment
a
common
set
coordinates.
reaching
this
goal
is
difficult
because
registering
vivo
ex
reference
atlases
accommodating
differences
modality,
microscope
specification,
sample
preparation.
We
overcome
these
challenges
The American Journal of Human Genetics,
Journal Year:
2023,
Volume and Issue:
111(1), P. 200 - 210
Published: Dec. 20, 2023
The
homologous
genes
GTPBP1
and
GTPBP2
encode
GTP-binding
proteins
1
2,
which
are
involved
in
ribosomal
homeostasis.
Pathogenic
variants
were
recently
shown
to
be
an
ultra-rare
cause
of
neurodegenerative
or
neurodevelopmental
disorders
(NDDs).
Until
now,
no
human
phenotype
has
been
linked
GTPBP1.
Here,
we
describe
individuals
carrying
bi-allelic
that
display
identical
with
characterize
the
overall
spectrum
protein
(1/2)-related
disorders.
In
this
study,
20
from
16
families
distinct
NDDs
syndromic
facial
features
investigated
by
whole-exome
(WES)
whole-genome
(WGS)
sequencing.
To
assess
functional
impact
identified
genetic
variants,
semi-quantitative
PCR,
western
blot,
ribosome
profiling
assays
performed
fibroblasts
affected
individuals.
We
also
effect
reducing
expression
CG2017,
ortholog
GTPBP1/2,
fruit
fly
Drosophila
melanogaster.
Individuals
presented
microcephaly,
profound
impairment,
pathognomonic
craniofacial
features,
ectodermal
defects.
Abnormal
vision
and/or
hearing,
progressive
spasticity,
choreoathetoid
movements,
refractory
epilepsy,
brain
atrophy
part
core
syndrome.
Cell
line
studies
a
loss-of-function
(LoF)
disease-associated
but
significant
abnormalities
on
profiling.
Reduced
CG2017
isoforms
was
associated
locomotor
impairment
Drosophila.
conclusion,
LoF
identical,
Mutant
knockout
flies
motor
highlighting
conserved
role
for
CNS
development
across
species.