ABSTRACT
Ion
homeostasis
is
critical
for
numerous
cellular
processes,
and
disturbances
in
ionic
balance
underlie
diverse
pathological
conditions,
including
cancer
progression.
Targeting
ion
even
considered
as
a
strategy
to
treat
cancer.
However,
very
little
known
about
how
may
influence
anticancer
drug
response.
In
genome-wide
CRISPR-Cas9
resistance
screen,
we
identified
validated
the
master
osmostress
regulator
WNK1
kinase
modulator
of
response
mitotic
rigosertib.
Osmotic
stress
inactivation
lead
an
altered
not
only
rigosertib
treatment
but
also
other
microtubule-related
drugs,
minimizing
prototypical
arrest
produced
by
these
drugs.
This
effect
due
alteration
microtubule
stability
polymerization
dynamics,
likely
maintained
fluctuations
intracellular
molecular
crowding
upon
inactivation.
promotes
depolymerizing
increased
sensitivity
stabilizing
summary,
our
data
proposes
osmoregulation
activity
biomarker
microtubule-associated
chemotherapy
mSphere,
Journal Year:
2021,
Volume and Issue:
6(5)
Published: Oct. 20, 2021
Horizontal
gene
transfer
(HGT)
is
a
driving
force
of
microbial
evolution.
The
gut
animals
acts
as
potent
reservoir
for
the
lateral
virulence,
fitness,
and
antimicrobial
resistance
genes
through
plasmids.
Reduced-complexity
models
examination
host-microbe
interactions
involved
in
plasmid
are
greatly
desired.
Thus,
this
study
identifies
use
Drosophila
melanogaster
model
organism
conjugation
plasmids
various
incompatibility
groups
gut.
Enterobacteriaceae
pairs
were
identified
vitro
used
oral
inoculation
Flies
enumerated
donor,
recipient,
transconjugant
populations.
Each
donor-recipient
pair
was
observed
to
persist
fly
guts
duration
experiment.
Gut
concentrations
donors
recipients
significantly
different
between
male
female
flies,
with
females
generally
demonstrating
increased
concentrations.
Furthermore,
host
genetics
altered
recipients.
However,
not
affected
by
sex
or
detected
only
IncPε
IncI1
groups.
This
demonstrates
gut-mediated
transfer.
IMPORTANCE
Microbial
evolution
due
horizontal
significant
interest
well
within
context
human
animal
health.
populations
evolve
host,
factors
from
bacteria
interact
regulate
little
currently
known
about
how
bacterial
plasmid-mediated
HGT
roles
sexual
dimorphism
Abstract
When
infected
by
intestinal
pathogenic
bacteria,
animals
initiate
both
local
and
systemic
defence
responses.
These
responses
are
required
to
reduce
pathogen
burden
also
alter
host
physiology
behavior
promote
infection
tolerance,
they
often
mediated
through
alterations
in
gene
expression.
Here,
we
have
used
transcriptome
profiling
examine
expression
changes
induced
enteric
with
the
Gram-negative
bacteria
Pseudomonas
entomophila
adult
female
Drosophila.
We
find
that
induces
a
strong
upregulation
of
metabolic
expression,
including
gut
fat
body-enriched
genes
involved
lipid
transport,
lipolysis,
beta-oxidation,
as
well
glucose
amino
acid
metabolism
genes.
Furthermore,
classic
innate
immune
deficiency
(Imd)/Relish/NF-KappaB
pathway
is
not
for,
some
cases
limits,
these
infection-mediated
increases
see
downregulates
many
transcription
factors
cell–cell
signaling
molecules,
particularly
those
previously
shown
be
gut-to-brain
neuronal
signaling.
Moreover,
genes,
occurred
largely
independent
Imd
pathway.
Together,
our
study
identifies
metabolic,
signaling,
factor
may
contribute
organismal
physiological
behavioral
infection.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2022,
Volume and Issue:
unknown
Published: Dec. 11, 2022
Summary
Risk
of
neurodegenerative
disease
such
as
late
onset
Alzheimer’s
is
linked
to
aberrant
ubiquitinylation
and
accumulation
non-degraded
proteins
in
brain
cells.
A
glial
network
innate
immune
genes
modulates
inflammatory
responses
protein
deposition.
However,
vulnerability
differs
between
the
sexes.
Here,
we
show
that
Drosophila
homologue
deubiquitylase
Trabid
can
align
sex-specific
aspects
phenotypes
with
changes
ubiquitylation
activity.
An
enzymatically
null
flies,
caused
locomotion,
sleep
patterns,
histology
ultimately,
lifespan.
These
were
underscored
by
altered
ubiquitin
proteome
enrichment
profiles
same
enzymatic
activity
its
human
counterpart.
When
sex-determination
gene
transformer
was
silenced
astrocytes
or
immunocompetent
tissues,
sex
differences
significantly
reduced.
Our
results
indicate
underscores
sex-specificity
neurology,
controlling
balance
inflammation.
ABSTRACT
Ion
homeostasis
is
critical
for
numerous
cellular
processes,
and
disturbances
in
ionic
balance
underlie
diverse
pathological
conditions,
including
cancer
progression.
Targeting
ion
even
considered
as
a
strategy
to
treat
cancer.
However,
very
little
known
about
how
may
influence
anticancer
drug
response.
In
genome-wide
CRISPR-Cas9
resistance
screen,
we
identified
validated
the
master
osmostress
regulator
WNK1
kinase
modulator
of
response
mitotic
rigosertib.
Osmotic
stress
inactivation
lead
an
altered
not
only
rigosertib
treatment
but
also
other
microtubule-related
drugs,
minimizing
prototypical
arrest
produced
by
these
drugs.
This
effect
due
alteration
microtubule
stability
polymerization
dynamics,
likely
maintained
fluctuations
intracellular
molecular
crowding
upon
inactivation.
promotes
depolymerizing
increased
sensitivity
stabilizing
summary,
our
data
proposes
osmoregulation
activity
biomarker
microtubule-associated
chemotherapy