Deleterious coding variation associated with autism is consistent across populations, as exemplified by admixed Latin American populations
medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 6, 2025
The
past
decade
has
seen
remarkable
progress
in
identifying
genes
that,
when
impacted
by
deleterious
coding
variation,
confer
high
risk
for
autism
spectrum
disorder
(ASD),
intellectual
disability,
and
other
developmental
disorders.
However,
most
underlying
gene
discovery
efforts
have
focused
on
individuals
of
European
ancestry,
limiting
insights
into
genetic
risks
across
diverse
populations.
To
help
address
this,
the
Genomics
Autism
Latin
American
Ancestries
Consortium
(GALA)
was
formed,
presenting
here
largest
sequencing
study
ASD
(n>15,000).
We
identified
35
genome-wide
significant
(FDR
<
0.05)
genes,
with
substantial
overlap
findings
from
cohorts,
highly
constrained
showing
consistent
signal
results
provide
support
emerging
(e.g.,
MARK2
,
YWHAG
PACS1
RERE,
SPEN,
GSE1,
GLS,
TNPO3,
ANKRD17
)
established
utility
testing
approaches
variants
populations,
while
also
demonstrating
ongoing
need
more
inclusive
research
testing.
conclude
that
biology
is
universal
not
to
any
detectable
degree
ancestry.
Branko
Aleksic,
Mykyta
Artomov,
Mafalda
Barbosa,
Elisa
Benetti,
Catalina
Betancur,
Monica
Biscaldi-Schafer,
Anders
D.
Børglum,
Harrison
Brand,
Alfredo
Brusco,
Joseph
Buxbaum,
Gabriele
Campos,
Simona
Cardaropoli,
Diana
Carli,
Angel
Carracedo,
Marcus
C.
Y.
Chan,
Andreas
G.
Chiocchetti,
Brian
H.
Chung,
Brett
Collins,
Ryan
L.
Edwin
Cook,
Hilary
Coon,
Claudia
I.
S.
Costa,
Michael
Cuccaro,
David
J.
Cutler,
Mark
Daly,
Silvia
De
Rubeis,
Bernie
Devlin,
N.
Doan,
Enrico
Domenici,
Shan
Dong,
Chiara
Fallerini,
Magdalena
Fernandez,
Montserrat
Fernández-Prieto,
Giovanni
Battista
Ferrero,
Eugenio
Ferro,
Jennifer
Foss
Feig,
Christine
M.
Freitag,
Jack
Fu,
Liliana
Galeano,
Jay
Gargus,
Sherif
Gerges,
Giorgio,
Ana
Cristina
Girardi,
Stephen
Guter,
Emily
Hansen-Kiss,
Erina
Hara,
Danielle
Halpern,
Gail
E.
Herman,
Luis
Hernandez,
Irva
Hertz-Picciotto,
Hougaard,
Christina
Hultman,
Suma
Jacob,
Miia
Kaartinen,
Lambertus
Klei,
Alexander
Kolevzon,
Itaru
Kushima,
Maria
Lattig,
So
Lun
Lee,
Terho
Lehtimäki,
Lindsay
Liang,
Carla
Lintas,
Alicia
Ljungdahl,
Andrea
del
Pilar
Lopez,
Caterina
Lo
Rizzo,
Yunin
Ludena,
Patricia
Maciel,
Behrang
Mahjani,
Nell
Maltman,
Marianna
Manara,
Dara
Manoach,
Dalia
Marquez,
Gal
Meiri,
Idan
Menashe,
Judith
Miller,
Nancy
Minshew,
Matthew
Mosconi,
Marina
Natividad
Avila,
Rachel
Nguyen,
Norio
Ozaki,
Aarno
Palotie,
Mara
Parellada,
Rita
Passos-Bueno,
Lisa
Pavinato,
Katherine
P.
Peña,
Minshi
Peng,
Margaret
Pericak-Vance,
Antonio
Persico,
Isaac
Pessah,
Thariana
Pichardo,
Kaija
Puura,
Abraham
Reichenberg,
Alessandra
Renieri,
Kathryn
Roeder,
Catherine
Sancimino,
Stephan
Sanders,
Sven
Sandin,
F.
Kyle
Satterstrom,
W.
Scherer,
Sabine
Schlitt,
Rebecca
Schmidt,
Lauren
Schmitt,
Katja
Schneider-Momm,
Paige
Siper,
Laura
Sloofman,
Moyra
Smith,
Renee
Soufer,
R.
Stevens,
Pål
Suren,
James
Sutcliffe,
John
A.
Sweeney,
Talkowski,
Flora
Tassone,
Karoline
Teufel,
Elisabetta
Trabetti,
Slavica
Trajkova,
Trelles,
Brie
Wamsley,
Jaqueline
T.
Wang,
Weiss,
Mullin
Yu,
Yuen,
Jessica
Zweifach.
Язык: Английский
Current landscape of fecal microbiota transplantation in treating depression
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Июнь 25, 2024
Depression,
projected
to
be
the
predominant
contributor
global
disease
burden,
is
a
complex
condition
with
diverse
symptoms
including
mood
disturbances
and
cognitive
impairments.
Traditional
treatments
such
as
medication
psychotherapy
often
fall
short,
prompting
pursuit
of
alternative
interventions.
Recent
research
has
highlighted
significant
role
gut
microbiota
in
mental
health,
influencing
emotional
neural
regulation.
Fecal
transplantation
(FMT),
infusion
fecal
matter
from
healthy
donor
into
patient,
emerges
promising
strategy
ameliorate
depressive
by
restoring
microbial
balance.
The
microbial-gut-brain
(MGB)
axis
represents
critical
pathway
through
which
potentially
rectify
dysbiosis
modulate
neuropsychiatric
outcomes.
Preclinical
studies
reveal
that
FMT
can
enhance
neurochemicals
reduce
inflammatory
markers,
thereby
alleviating
behaviors.
Moreover,
shown
promise
clinical
settings,
improving
gastrointestinal
overall
quality
life
patients
depression.
review
highlights
gut-brain
depression
need
for
further
validate
long-term
safety
efficacy
FMT,
identify
specific
therapeutic
strains,
develop
targeted
modulation
strategies.
Advancing
our
understanding
could
revolutionize
treatment,
shifting
paradigm
toward
microbiome-targeting
therapies.
Язык: Английский
SARS‐CoV‐2‐derived protein Orf9b enhances MARK2 activity via interaction with the autoinhibitory KA1 domain
Daiki Homma,
Sophia Jobien M. Limlingan,
Taro Saito
и другие.
FEBS Letters,
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 5, 2024
Microtubule
affinity‐regulating
kinase
2
(MARK2)
is
a
Ser/Thr
protein
that
regulates
cell
polarity
and
immune
responses.
Here,
we
report
Orf9b,
one
of
the
accessory
proteins
encoded
in
SARS‐CoV‐2
genome,
increases
MARK2
activity
via
interaction
with
autoinhibitory
KAI
domain.
We
found
co‐expression
Orf9b
enhances
HEK293
cells.
does
not
bind
to
or
enhance
mutant
form
lacking
KA1
lowers
inhibitory
phosphorylation
at
T595
while
mutation
experiments
indicate
this
site
dispensable
for
Orf9b‐mediated
enhancement
activity.
Our
results
suggest
by
binding
domain,
which
closely
interacts
Язык: Английский
Innovative Drug Discovery: Targeting Cancer, Neurological Disorders, and Obesity
ACS Medicinal Chemistry Letters,
Год журнала:
2024,
Номер
15(9), С. 1440 - 1442
Опубликована: Авг. 21, 2024
The
landscape
of
therapeutic
innovation
is
rapidly
evolving,
with
significant
advances
in
cancer
treatment,
obesity
management,
and
the
modulation
protein
interactions
neurodegenerative
disorders.
This
Patent
Highlight
explores
scientific
breakthroughs
described
four
recent
patents
covering
novel
compounds,
advanced
methods
for
identifying
E3
ligase
substrates,
developing
new
strategies
combating
its
related
metabolic
These
innovations,
focusing
on
specific
molecular
targets
pathways,
promise
more
effective
personalized
treatment
options,
addressing
unmet
needs
oncology,
neurology,
health.
Язык: Английский