Advancing long-read nanopore genome assembly and accurate variant calling for rare disease detection
The American Journal of Human Genetics,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 1, 2025
Language: Английский
Glutamine Synthetase: Diverse Regulation and Functions of an Ancient Enzyme
Markus C. B. Tecson,
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Cyrina Joy Geluz,
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Yolanda P. Cruz
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et al.
Biochemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 22, 2025
Glutamine
synthetase
(GS)
is
a
ubiquitous
enzyme
central
to
nitrogen
metabolism,
catalyzing
the
ATP-dependent
formation
of
glutamine
from
glutamate
and
ammonia.
Positioned
at
intersection
metabolism
with
carbon
activity
GS
subject
sophisticated
regulation.
While
intricate
regulatory
pathways
that
govern
Escherichia
coli
were
established
long
ago,
recent
work
has
demonstrated
homologues
are
controlled
by
multiple
distinct
patterns,
such
as
metabolite
induced
oligomeric
state
in
archaeal
2-oxoglutarate.
Such
was
enabled
large
part
advances
cryo-electron
microscopy
(cryoEM)
allowed
greater
structural
access
this
complex,
assessment
heterogeneous
states
protein-interactor-GS
complexes.
This
perspective
highlights
understanding
regulation,
focusing
on
dynamic
interplay
between
its
state,
binding,
protein
interactors.
These
interactions
modulate
activity,
influencing
cellular
processes
assimilation,
stress
responses.
Furthermore,
we
explore
emerging
concept
"moonlighting"
functions,
revealing
roles
palmitoylation,
cell
cycle
ion
channel
modulation.
diverse
functions
highlight
newfound
versatility
beyond
primary
catalytic
role
suggest
complex
health
disease
warrant
further
study.
Language: Английский
Epigenetic and metabolic regulation of developmental timing in neocortex evolution
Matilde Aquilino,
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Nora Ditzer,
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Takashi Namba
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et al.
Trends in Neurosciences,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 1, 2025
The
human
brain
is
characterized
by
impressive
cognitive
abilities.
neocortex
the
seat
of
higher
cognition,
and
expansion
a
hallmark
evolution.
While
developmental
programs
are
similar
in
different
species,
timing
transitions
capacity
neural
progenitor
cells
(NPCs)
to
proliferate
differ,
contributing
increased
production
neurons
during
cortical
development.
Here,
we
review
epigenetic
regulation
corticogenesis,
focusing
mostly
on
humans
while
building
knowledge
from
studies
mice.
We
discuss
metabolic-epigenetic
interplay
as
potential
mechanism
integrate
extracellular
signals
into
chromatin.
Moreover,
synthesize
current
understanding
how
metabolic
deregulation
can
cause
neurodevelopmental
disorders.
Finally,
outline
be
investigated
using
organoid
models.
Language: Английский
Advancing long-read nanopore genome assembly and accurate variant calling for rare disease detection
medRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Aug. 22, 2024
Abstract
More
than
50%
of
families
with
suspected
rare
monogenic
diseases
remain
unsolved
after
whole
genome
analysis
by
short
read
sequencing
(SRS).
Long-read
(LRS)
could
help
bridge
this
diagnostic
gap
capturing
variants
inaccessible
to
SRS,
facilitating
long-range
mapping
and
phasing,
providing
haplotype-resolved
methylation
profiling.
To
evaluate
LRS’s
additional
yield,
we
sequenced
a
disease
cohort
98
samples,
including
41
probands
some
family
members,
using
nanopore
sequencing,
achieving
per
sample
∼36x
average
coverage
32
kilobase
(kb)
N50
from
single
flow
cell.
Our
Napu
pipeline
generated
assemblies,
phased
variants,
calls.
LRS
covered,
on
average,
coding
exons
in
∼280
genes
∼5
known
Mendelian
that
were
not
covered
SRS.
In
comparison
detected
rare,
functionally
annotated
SVs
tandem
repeats,
completely
87%
protein-coding
genes.
de
novo
be
used
distinguish
postzygotic
mosaic
prezygotic
novos
.
Eleven
solved,
diverse
underlying
genetic
causes
compound
heterozygous
large-scale
SVs,
epigenetic
modifications.
study
demonstrates
potential
enhance
yield
for
diseases,
implying
utility
future
clinical
genomics
workflows.
Language: Английский
Role of cell metabolism in the pathophysiology of brain size-associated neurodevelopmental disorders
Neurobiology of Disease,
Journal Year:
2024,
Volume and Issue:
199, P. 106607 - 106607
Published: July 17, 2024
Cell
metabolism
is
a
key
regulator
of
human
neocortex
development
and
evolution.
Several
lines
evidence
indicate
that
alterations
in
neural
stem/progenitor
cell
(NPC)
lead
to
abnormal
brain
development,
particularly
size-associated
neurodevelopmental
disorders,
such
as
microcephaly.
Abnormal
NPC
causes
impaired
proliferation
thus
insufficient
expansion
NPCs
for
neurogenesis.
Therefore,
the
production
neurons,
which
major
determinant
size,
decreased
size
brain,
especially
neocortex,
significantly
reduced.
This
review
discusses
recent
progress
understanding
metabolism,
focusing
particular
on
glucose
fatty
acid
amino
(e.g.,
glutaminolysis
serine
metabolism).
We
provide
an
overview
contributions
these
metabolic
pathways
evolution,
well
etiology
disorders.
Furthermore,
we
discuss
advantages
disadvantages
various
experimental
models
study
developing
brain.
Language: Английский