bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Май 10, 2023
ABSTRACT
Cells
live
and
interact
in
three-dimensional
(3D)
cellular
neighborhoods.
However,
histology
spatial
omics
methods
mostly
focus
on
2D
tissue
sections.
Here
we
present
a
3D
atlas
of
routine
clinical
sample,
an
aggressive
human
lung
carcinoma,
by
combining
situ
quantification
960
cancer-related
genes
across
∼340,000
cells
with
measurements
tissue-mechanical
components.
neighborhoods
subdivided
the
tumor
microenvironment
into
tumor,
stromal,
immune
multicellular
niches.
Interestingly,
pseudotime
analysis
suggested
that
pro-invasive
epithelial-to-mesenchymal
transition
(EMT),
detected
stroma-infiltrating
cells,
already
occurred
one
region
at
surface.
There,
myofibroblasts
macrophages
specifically
co-localized
pre-invasive
their
molecular
signature
identified
patients
shorter
survival.
Moreover,
cytotoxic
T-cells
did
not
infiltrate
this
niche
but
colocalized
inhibitory
dendritic
regulatory
T
cells.
Importantly,
systematic
scoring
cell-cell
interactions
highlighted
niche-specific
signaling
networks
accompanying
invasion
escape.
Compared
to
2D,
improved
characterization
niches
identifying
niches,
capturing
extension
T-cell
boosting
interactions,
including
druggable
checkpoints.
We
believe
communication
analyses
can
improve
design
studies
investigating
personalized,
combination
immuno-oncology
therapies.
Cell,
Год журнала:
2023,
Номер
186(17), С. 3706 - 3725.e29
Опубликована: Авг. 1, 2023
The
bone
marrow
in
the
skull
is
important
for
shaping
immune
responses
brain
and
meninges,
but
its
molecular
makeup
among
bones
relevance
human
diseases
remain
unclear.
Here,
we
show
that
mouse
has
most
distinct
transcriptomic
profile
compared
with
other
states
of
health
injury,
characterized
by
a
late-stage
neutrophil
phenotype.
In
humans,
proteome
analysis
reveals
distinct,
differentially
expressed
neutrophil-related
pathways
unique
synaptic
protein
signature.
3D
imaging
demonstrates
structural
cellular
details
skull-meninges
connections
(SMCs)
veins.
Last,
using
translocator
positron
emission
tomography
(TSPO-PET)
imaging,
reflects
inflammatory
disease-specific
spatial
distribution
patients
various
neurological
disorders.
anatomical
functional
potential
as
site
diagnosing,
monitoring,
treating
diseases.
Translational Neurodegeneration,
Год журнала:
2024,
Номер
13(1)
Опубликована: Янв. 23, 2024
Abstract
Ageing
is
a
crucial
risk
factor
for
Alzheimer’s
disease
(AD)
and
characterised
by
systemic
changes
in
both
intracellular
extracellular
microenvironments
that
affect
the
entire
body
instead
of
single
organ.
Understanding
specific
mechanisms
underlying
role
ageing
development
can
facilitate
treatment
ageing-related
diseases,
such
as
AD.
Signs
brain
have
been
observed
AD
patients
animal
models.
Alleviating
pathological
caused
dramatically
ameliorate
amyloid
beta-
tau-induced
neuropathological
memory
impairments,
indicating
plays
pathophysiological
process
In
this
review,
we
summarize
impact
several
age-related
factors
on
propose
preventing
promising
strategy
improving
cognitive
health.
Computational and Structural Biotechnology Journal,
Год журнала:
2023,
Номер
21, С. 940 - 955
Опубликована: Янв. 1, 2023
Advances
in
transcriptomic
technologies
have
deepened
our
understanding
of
the
cellular
gene
expression
programs
multicellular
organisms
and
provided
a
theoretical
basis
for
disease
diagnosis
therapy.
However,
both
bulk
single-cell
RNA
sequencing
approaches
lose
spatial
context
cells
within
tissue
microenvironment,
development
transcriptomics
has
made
overall
bias-free
access
to
transcriptional
information
possible.
Here,
we
elaborate
help
researchers
select
best-suited
technology
their
goals
integrate
vast
amounts
data
facilitate
accessibility
availability.
Then,
marshal
various
computational
analyze
purposes
describe
multimodal
omics
its
potential
application
tumor
tissue.
Finally,
provide
detailed
discussion
outlook
technologies,
resources
analysis
guide
current
future
research
on
transcriptomics.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Апрель 5, 2023
ABSTRACT
Coronavirus
disease
2019
(COVID-19),
caused
by
the
severe
acute
respiratory
syndrome
coronavirus
type
2
(SARS-CoV-2),
has
been
associated
mainly
with
a
range
of
neurological
symptoms,
including
brain
fog
and
tissue
loss,
raising
concerns
about
virus’s
potential
chronic
impact
on
central
nervous
system.
In
this
study,
we
utilized
mouse
models
human
post-mortem
tissues
to
investigate
presence
distribution
SARS-CoV-2
spike
protein
in
skull-meninges-brain
axis.
Our
results
revealed
accumulation
skull
marrow,
meninges,
parenchyma.
The
injection
alone
cell
death
brain,
highlighting
direct
effect
tissue.
Furthermore,
observed
deceased
long
after
their
COVID-19
infection,
suggesting
that
spike’s
persistence
may
contribute
long-term
symptoms.
was
neutrophil-related
pathways
dysregulation
proteins
involved
PI3K-AKT
as
well
complement
coagulation
pathway.
Overall,
our
findings
suggest
trafficking
from
CNS
borders
into
parenchyma
identified
differentially
regulated
present
insights
mechanisms
underlying
immediate
consequences
diagnostic
therapeutic
opportunities.
Graphical
Summary
Short
axis
presents
molecular
targets
for
complications
long-COVID-19
patients
.
Nature Methods,
Год журнала:
2024,
Номер
21(7), С. 1306 - 1315
Опубликована: Апрель 22, 2024
Abstract
Automated
detection
of
specific
cells
in
three-dimensional
datasets
such
as
whole-brain
light-sheet
image
stacks
is
challenging.
Here,
we
present
DELiVR,
a
virtual
reality-trained
deep-learning
pipeline
for
detecting
c-Fos
+
markers
neuronal
activity
cleared
mouse
brains.
Virtual
reality
annotation
substantially
accelerated
training
data
generation,
enabling
DELiVR
to
outperform
state-of-the-art
cell-segmenting
approaches.
Our
available
user-friendly
Docker
container
that
runs
with
standalone
Fiji
plugin.
features
comprehensive
toolkit
visualization
and
can
be
customized
other
cell
types
interest,
did
here
microglia
somata,
using
dataset-specific
training.
We
applied
investigate
cancer-related
brain
activity,
unveiling
an
activation
pattern
distinguishes
weight-stable
cancer
from
cancers
associated
weight
loss.
Overall,
robust
tool
does
not
require
advanced
coding
skills
analyze
imaging
health
disease.
Physiological Reviews,
Год журнала:
2024,
Номер
104(3), С. 931 - 982
Опубликована: Фев. 1, 2024
Mass
spectrometry-based
proteomics
is
a
sophisticated
identification
tool
specializing
in
portraying
protein
dynamics
at
molecular
level.
Proteomics
provides
biologists
with
snapshot
of
context-dependent
and
proteoform
expression,
structural
conformations,
dynamic
turnover,
protein-protein
interactions.
Cardiac
can
offer
broader
deeper
understanding
the
mechanisms
that
underscore
cardiovascular
disease,
it
foundational
to
development
future
therapeutic
interventions.
This
review
encapsulates
evolution,
current
technologies,
perspectives
proteomic-based
mass
spectrometry
as
applies
study
heart.
Key
technological
advancements
have
allowed
researchers
proteomes
single-cell
level
employ
robot-assisted
automation
systems
for
enhanced
sample
preparation
techniques,
increase
fidelity
spectrometers
has
unambiguous
numerous
posttranslational
modifications.
Animal
models
ranging
from
early
animal
experiments
heart
failure
preserved
ejection
fraction,
provided
tools
challenging
organ
laboratory.
Further
will
pave
way
implementation
even
closer
within
clinical
setting,
allowing
not
only
scientists
but
also
patients
benefit
an
interplay
relates
cardiac
disease
physiology.
The Plant Journal,
Год журнала:
2024,
Номер
119(5), С. 2168 - 2180
Опубликована: Июль 11, 2024
SUMMARY
Mass
spectrometry
imaging
(MSI)
has
become
increasingly
popular
in
plant
science
due
to
its
ability
characterize
complex
chemical,
spatial,
and
temporal
aspects
of
metabolism.
Over
the
past
decade,
as
emerging
unique
features
various
MSI
techniques
have
continued
support
new
discoveries
studies
metabolism
closely
associated
with
function
physiology,
spatial
metabolomics
based
on
positioned
it
at
forefront
metabolic
studies,
providing
opportunity
for
far
higher
resolution
than
was
previously
available.
Despite
these
efforts,
profound
challenges
levels
resolution,
sensitivity,
quantitative
ability,
chemical
confidence,
isomer
discrimination,
multi‐omics
integration,
undoubtedly
remain.
In
this
Perspective,
we
provide
a
contemporary
overview
emergent
widely
used
sciences,
particular
emphasis
recent
advances
methodological
breakthroughs.
Having
established
detailed
context
MSI,
outline
both
golden
opportunities
key
currently
facing
metabolomics,
presenting
our
vision
how
enormous
potential
technologies
will
contribute
progress
coming
years.
Cell Host & Microbe,
Год журнала:
2024,
Номер
32(12), С. 2112 - 2130.e10
Опубликована: Ноя. 29, 2024
SARS-CoV-2
infection
is
associated
with
long-lasting
neurological
symptoms,
although
the
underlying
mechanisms
remain
unclear.
Using
optical
clearing
and
imaging,
we
observed
accumulation
of
spike
protein
in
skull-meninges-brain
axis
human
COVID-19
patients,
persisting
long
after
viral
clearance.
Further,
biomarkers
neurodegeneration
were
elevated
cerebrospinal
fluid
from
COVID
proteomic
analysis
skull,
meninges,
brain
samples
revealed
dysregulated
inflammatory
pathways
neurodegeneration-associated
changes.
Similar
distribution
patterns
SARS-CoV-2-infected
mice.
Injection
alone
was
sufficient
to
induce
neuroinflammation,
proteome
changes
axis,
anxiety-like
behavior,
exacerbated
outcomes
mouse
models
stroke
traumatic
injury.
Vaccination
reduced
but
did
not
eliminate
Our
findings
suggest
persistent
at
borders
may
contribute
lasting
sequelae
COVID-19.
