---
_id: '11160'
abstract:
- lang: eng
text: Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent
cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses
macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency
affects neurodevelopmental is unclear. Here, employing human cerebral organoids,
we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories
with an accelerated and delayed generation of, respectively, inhibitory and excitatory
neurons that yields, at days 60 and 120, symmetrically opposite expansions in
their proportions. This imbalance is consistent with an enlargement of cerebral
organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic
design of patient-specific mutations and mosaic organoids, we define genotype-phenotype
relationships and uncover their cell-autonomous nature. Our results define cell-type-specific
CHD8-dependent molecular defects related to an abnormal program of proliferation
and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations,
our study uncovers reproducible developmental alterations that may be employed
for neurodevelopmental disease modeling.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: We thank Farnaz Freeman for technical assistance. This research was
supported by the Scientific Service Units (SSU) of IST Austria through resources
provided by the Bioimaging Facility (BIF) and the Life Science Facility (LSF). This
work supported by the European Union’s Horizon 2020 research and innovation program
(ERC) grant 715508 to G.N. (REVERSEAUTISM) and grant 825759 to G.T. (ENDpoiNTs);
the Fondazione Cariplo 2017-0886 to A.L.T.; E-Rare-3 JTC 2018 IMPACT to M. Gabriele;
and the Austrian Science Fund FWF I 4205-B to G.N. Graphical abstract and figures
were created using BioRender.com.
article_number: '110615'
article_processing_charge: Yes
article_type: original
author:
- first_name: Carlo Emanuele
full_name: Villa, Carlo Emanuele
last_name: Villa
- first_name: Cristina
full_name: Cheroni, Cristina
last_name: Cheroni
- first_name: Christoph
full_name: Dotter, Christoph
id: 4C66542E-F248-11E8-B48F-1D18A9856A87
last_name: Dotter
orcid: 0000-0002-9033-9096
- first_name: Alejandro
full_name: López-Tóbon, Alejandro
last_name: López-Tóbon
- first_name: Bárbara
full_name: Oliveira, Bárbara
id: 3B03AA1A-F248-11E8-B48F-1D18A9856A87
last_name: Oliveira
- first_name: Roberto
full_name: Sacco, Roberto
id: 42C9F57E-F248-11E8-B48F-1D18A9856A87
last_name: Sacco
- first_name: Aysan Çerağ
full_name: Yahya, Aysan Çerağ
id: 365A65F8-F248-11E8-B48F-1D18A9856A87
last_name: Yahya
- first_name: Jasmin
full_name: Morandell, Jasmin
id: 4739D480-F248-11E8-B48F-1D18A9856A87
last_name: Morandell
- first_name: Michele
full_name: Gabriele, Michele
last_name: Gabriele
- first_name: Mojtaba
full_name: Tavakoli, Mojtaba
id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
last_name: Tavakoli
orcid: 0000-0002-7667-6854
- first_name: Julia
full_name: Lyudchik, Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Mariano
full_name: Gabitto, Mariano
last_name: Gabitto
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
- first_name: Giuseppe
full_name: Testa, Giuseppe
last_name: Testa
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism
to transient alterations in excitatory and inhibitory trajectories. Cell Reports.
2022;39(1). doi:10.1016/j.celrep.2022.110615
apa: Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco,
R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations
in excitatory and inhibitory trajectories. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2022.110615
chicago: Villa, Carlo Emanuele, Cristina Cheroni, Christoph Dotter, Alejandro López-Tóbon,
Bárbara Oliveira, Roberto Sacco, Aysan Çerağ Yahya, et al. “CHD8 Haploinsufficiency
Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.”
Cell Reports. Elsevier, 2022. https://doi.org/10.1016/j.celrep.2022.110615.
ieee: C. E. Villa et al., “CHD8 haploinsufficiency links autism to transient
alterations in excitatory and inhibitory trajectories,” Cell Reports, vol.
39, no. 1. Elsevier, 2022.
ista: Villa CE, Cheroni C, Dotter C, López-Tóbon A, Oliveira B, Sacco R, Yahya AÇ,
Morandell J, Gabriele M, Tavakoli M, Lyudchik J, Sommer CM, Gabitto M, Danzl JG,
Testa G, Novarino G. 2022. CHD8 haploinsufficiency links autism to transient alterations
in excitatory and inhibitory trajectories. Cell Reports. 39(1), 110615.
mla: Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient
Alterations in Excitatory and Inhibitory Trajectories.” Cell Reports, vol.
39, no. 1, 110615, Elsevier, 2022, doi:10.1016/j.celrep.2022.110615.
short: C.E. Villa, C. Cheroni, C. Dotter, A. López-Tóbon, B. Oliveira, R. Sacco,
A.Ç. Yahya, J. Morandell, M. Gabriele, M. Tavakoli, J. Lyudchik, C.M. Sommer,
M. Gabitto, J.G. Danzl, G. Testa, G. Novarino, Cell Reports 39 (2022).
date_created: 2022-04-15T09:03:10Z
date_published: 2022-04-05T00:00:00Z
date_updated: 2024-03-27T23:30:44Z
day: '05'
ddc:
- '570'
department:
- _id: JoDa
- _id: GaNo
doi: 10.1016/j.celrep.2022.110615
ec_funded: 1
external_id:
isi:
- '000785983900003'
pmid:
- '35385734'
file:
- access_level: open_access
checksum: b4e8d68f0268dec499af333e6fd5d8e1
content_type: application/pdf
creator: dernst
date_created: 2022-04-15T09:06:25Z
date_updated: 2022-04-15T09:06:25Z
file_id: '11164'
file_name: 2022_CellReports_Villa.pdf
file_size: '7808644'
relation: main_file
success: 1
file_date_updated: 2022-04-15T09:06:25Z
has_accepted_license: '1'
intvolume: ' 39'
isi: 1
issue: '1'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 2690FEAC-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I04205
name: Identification of converging Molecular Pathways Across Chromatinopathies as
Targets for Therapy
publication: Cell Reports
publication_identifier:
issn:
- 2211-1247
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
record:
- id: '12364'
relation: dissertation_contains
status: public
status: public
title: CHD8 haploinsufficiency links autism to transient alterations in excitatory
and inhibitory trajectories
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 39
year: '2022'
...
---
_id: '12364'
abstract:
- lang: eng
text: "Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders
character\x02ized by behavioral symptoms such as problems in social communication
and interaction, as\r\nwell as repetitive, restricted behaviors and interests.
These disorders show a high degree\r\nof heritability and hundreds of risk genes
have been identifed using high throughput\r\nsequencing technologies. This genetic
heterogeneity has hampered eforts in understanding\r\nthe pathogenesis of ASD
but at the same time given rise to the concept of convergent\r\nmechanisms. Previous
studies have identifed that risk genes for ASD broadly converge\r\nonto specifc
functional categories with transcriptional regulation being one of the biggest\r\ngroups.
In this thesis, I focus on this subgroup of genes and investigate the gene regulatory\r\nconsequences
of some of them in the context of neurodevelopment.\r\nFirst, we showed that mutations
in the ASD and intellectual disability risk gene Setd5 lead\r\nto perturbations
of gene regulatory programs in early cell fate specifcation. In addition,\r\nadult
animals display abnormal learning behavior which is mirrored at the transcriptional\r\nlevel
by altered activity dependent regulation of postsynaptic gene expression. Lastly,\r\nwe
link the regulatory function of Setd5 to its interaction with the Paf1 and the
NCoR\r\ncomplex.\r\nSecond, by modeling the heterozygous loss of the top ASD gene
CHD8 in human cerebral\r\norganoids we demonstrate profound changes in the developmental
trajectories of both\r\ninhibitory and excitatory neurons using single cell RNA-sequencing.
While the former\r\nwere generated earlier in CHD8+/- organoids, the generation
of the latter was shifted to\r\nlater times in favor of a prolonged progenitor
expansion phase and ultimately increased\r\norganoid size.\r\nFinally, by modeling
heterozygous mutations for four ASD associated chromatin modifers,\r\nASH1L, KDM6B,
KMT5B, and SETD5 in human cortical spheroids we show evidence of\r\nregulatory
convergence across three of those genes. We observe a shift from dorsal cortical\r\nexcitatory
neuron fates towards partially ventralized cell types resembling cells from the\r\nlateral
ganglionic eminence. As this project is still ongoing at the time of writing,
future\r\nexperiments will aim at elucidating the regulatory mechanisms underlying
this shift with\r\nthe aim of linking these three ASD risk genes through biological
convergence."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Christoph
full_name: Dotter, Christoph
id: 4C66542E-F248-11E8-B48F-1D18A9856A87
last_name: Dotter
orcid: 0000-0002-9033-9096
citation:
ama: Dotter C. Transcriptional consequences of mutations in genes associated with
Autism Spectrum Disorder. 2022. doi:10.15479/at:ista:12094
apa: Dotter, C. (2022). Transcriptional consequences of mutations in genes associated
with Autism Spectrum Disorder. Institute of Science and Technology Austria.
https://doi.org/10.15479/at:ista:12094
chicago: Dotter, Christoph. “Transcriptional Consequences of Mutations in Genes
Associated with Autism Spectrum Disorder.” Institute of Science and Technology
Austria, 2022. https://doi.org/10.15479/at:ista:12094.
ieee: C. Dotter, “Transcriptional consequences of mutations in genes associated
with Autism Spectrum Disorder,” Institute of Science and Technology Austria, 2022.
ista: Dotter C. 2022. Transcriptional consequences of mutations in genes associated
with Autism Spectrum Disorder. Institute of Science and Technology Austria.
mla: Dotter, Christoph. Transcriptional Consequences of Mutations in Genes Associated
with Autism Spectrum Disorder. Institute of Science and Technology Austria,
2022, doi:10.15479/at:ista:12094.
short: C. Dotter, Transcriptional Consequences of Mutations in Genes Associated
with Autism Spectrum Disorder, Institute of Science and Technology Austria, 2022.
date_created: 2023-01-24T13:09:57Z
date_published: 2022-09-19T00:00:00Z
date_updated: 2023-11-16T13:10:22Z
day: '19'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: GaNo
doi: 10.15479/at:ista:12094
ec_funded: 1
file:
- access_level: open_access
checksum: 896f4cac9adb6d3f26a6605772f4e1a3
content_type: application/pdf
creator: cchlebak
date_created: 2023-01-24T13:15:45Z
date_updated: 2023-09-20T22:30:03Z
embargo: 2023-09-19
file_id: '12365'
file_name: 220923_Thesis_CDotter_Final.pdf
file_size: 20457465
relation: main_file
- access_level: closed
checksum: ad01bb20da163be6893b7af832e58419
content_type: application/x-zip-compressed
creator: cchlebak
date_created: 2023-02-02T09:15:35Z
date_updated: 2023-09-20T22:30:03Z
embargo_to: open_access
file_id: '12482'
file_name: latex_source_CDotter_Thesis_2022.zip
file_size: 22433512
relation: source_file
file_date_updated: 2023-09-20T22:30:03Z
has_accepted_license: '1'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: '152'
project:
- _id: 254BA948-B435-11E9-9278-68D0E5697425
grant_number: '401299'
name: Probing development and reversibility of autism spectrum disorders
- _id: 9B91375C-BA93-11EA-9121-9846C619BF3A
grant_number: '707964'
name: Critical windows and reversibility of ASD associated with mutations in chromatin
remodelers
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 2690FEAC-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I04205
name: Identification of converging Molecular Pathways Across Chromatinopathies as
Targets for Therapy
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '3'
relation: part_of_dissertation
status: public
- id: '11160'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
title: Transcriptional consequences of mutations in genes associated with Autism Spectrum
Disorder
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2022'
...
---
_id: '10281'
abstract:
- lang: eng
text: Mutations affecting mTOR or RAS signaling underlie defined syndromes (the
so-called mTORopathies and RASopathies) with high risk for Autism Spectrum Disorder
(ASD). These syndromes show a broad variety of somatic phenotypes including cancers,
skin abnormalities, heart disease and facial dysmorphisms. Less well studied are
the neuropsychiatric symptoms such as ASD. Here, we assess the relevance of these
signalopathies in ASD reviewing genetic, human cell model, rodent studies and
clinical trials. We conclude that signalopathies have an increased liability for
ASD and that, in particular, ASD individuals with dysmorphic features and intellectual
disability (ID) have a higher chance for disruptive mutations in RAS- and mTOR-related
genes. Studies on rodent and human cell models confirm aberrant neuronal development
as the underlying pathology. Human studies further suggest that multiple hits
are necessary to induce the respective phenotypes. Recent clinical trials do only
report improvements for comorbid conditions such as epilepsy or cancer but not
for behavioral aspects. Animal models show that treatment during early development
can rescue behavioral phenotypes. Taken together, we suggest investigating the
differential roles of mTOR and RAS signaling in both human and rodent models,
and to test drug treatment both during and after neuronal development in the available
model systems
acknowledgement: 'This review was funded by the IMI2 Initiative under the grant AIMS-2-TRIALS
No 777394, by the Hessian Ministry for Science and Arts; State of Hesse Ministry
for Science and Arts: LOEWE-Grant to the CePTER-Consortium (www.uni-frankfurt.de/67689811);
Research (BMBF) under the grant RAISE-genic No 779282 all to AGC. This work was
also supported by the European Union’s Horizon 2020 research and innovation program
(ERC) grant 715508 (REVERSEAUTISM) and by the Austrian Science Fund (FWF) (DK W1232-B24)
both to G.N. and both BMBF GeNeRARe 01GM1519A and CRC 1080, project B10, of the
German Research Foundation (DFG) to M.J.S, respectively. We want to thank R. Waltes
for her support in preparing this manuscript.'
alternative_title:
- Special Issue "From Genes to Therapy in Autism Spectrum Disorder"
article_number: '1746'
article_processing_charge: No
article_type: original
author:
- first_name: Verica
full_name: Vasic, Verica
last_name: Vasic
- first_name: Mattson S.O.
full_name: Jones, Mattson S.O.
last_name: Jones
- first_name: Denise
full_name: Haslinger, Denise
id: 76922BDA-3D3B-11EA-90BD-A44F3DDC885E
last_name: Haslinger
- first_name: Lisa
full_name: Knaus, Lisa
id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87
last_name: Knaus
- first_name: Michael J.
full_name: Schmeisser, Michael J.
last_name: Schmeisser
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Andreas G.
full_name: Chiocchetti, Andreas G.
last_name: Chiocchetti
citation:
ama: 'Vasic V, Jones MSO, Haslinger D, et al. Translating the role of mtor-and ras-associated
signalopathies in autism spectrum disorder: Models, mechanisms and treatment.
Genes. 2021;12(11). doi:10.3390/genes12111746'
apa: 'Vasic, V., Jones, M. S. O., Haslinger, D., Knaus, L., Schmeisser, M. J., Novarino,
G., & Chiocchetti, A. G. (2021). Translating the role of mtor-and ras-associated
signalopathies in autism spectrum disorder: Models, mechanisms and treatment.
Genes. MDPI. https://doi.org/10.3390/genes12111746'
chicago: 'Vasic, Verica, Mattson S.O. Jones, Denise Haslinger, Lisa Knaus, Michael
J. Schmeisser, Gaia Novarino, and Andreas G. Chiocchetti. “Translating the Role
of Mtor-and Ras-Associated Signalopathies in Autism Spectrum Disorder: Models,
Mechanisms and Treatment.” Genes. MDPI, 2021. https://doi.org/10.3390/genes12111746.'
ieee: 'V. Vasic et al., “Translating the role of mtor-and ras-associated
signalopathies in autism spectrum disorder: Models, mechanisms and treatment,”
Genes, vol. 12, no. 11. MDPI, 2021.'
ista: 'Vasic V, Jones MSO, Haslinger D, Knaus L, Schmeisser MJ, Novarino G, Chiocchetti
AG. 2021. Translating the role of mtor-and ras-associated signalopathies in autism
spectrum disorder: Models, mechanisms and treatment. Genes. 12(11), 1746.'
mla: 'Vasic, Verica, et al. “Translating the Role of Mtor-and Ras-Associated Signalopathies
in Autism Spectrum Disorder: Models, Mechanisms and Treatment.” Genes,
vol. 12, no. 11, 1746, MDPI, 2021, doi:10.3390/genes12111746.'
short: V. Vasic, M.S.O. Jones, D. Haslinger, L. Knaus, M.J. Schmeisser, G. Novarino,
A.G. Chiocchetti, Genes 12 (2021).
date_created: 2021-11-14T23:01:24Z
date_published: 2021-10-30T00:00:00Z
date_updated: 2023-08-14T11:46:12Z
day: '30'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.3390/genes12111746
ec_funded: 1
external_id:
isi:
- '000834044200002'
file:
- access_level: open_access
checksum: 256cb832a9c3051c7dc741f6423b8cbd
content_type: application/pdf
creator: dernst
date_created: 2022-05-16T07:02:27Z
date_updated: 2022-05-16T07:02:27Z
file_id: '11380'
file_name: 2021_Genes_Vasic.pdf
file_size: 1335308
relation: main_file
success: 1
file_date_updated: 2022-05-16T07:02:27Z
has_accepted_license: '1'
intvolume: ' 12'
isi: 1
issue: '11'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
project:
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
publication: Genes
publication_identifier:
eissn:
- 2073-4425
publication_status: published
publisher: MDPI
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Translating the role of mtor-and ras-associated signalopathies in autism spectrum
disorder: Models, mechanisms and treatment'
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 12
year: '2021'
...
---
_id: '10301'
abstract:
- lang: eng
text: De novo protein synthesis is required for synapse modifications underlying
stable memory encoding. Yet neurons are highly compartmentalized cells and how
protein synthesis can be regulated at the synapse level is unknown. Here, we characterize
neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic
target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to
mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A
subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR
complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR
activation and restricts the mTOR-dependent translation of specific activity-regulated
mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent
protein synthesis, and facilitates the consolidation of associative and spatial
memories in mice. The memory enhancement becomes evident with light or spaced
training, can be achieved by selectively deleting GluN3A from excitatory neurons
during adulthood, and does not compromise other aspects of cognition such as memory
flexibility or extinction. Our findings provide mechanistic insight into synaptic
translational control and reveal a potentially selective target for cognitive
enhancement.
acknowledgement: We thank Stuart Lipton and Nobuki Nakanishi for providing the Grin3a
knockout mice, Beverly Davidson for the AAV-caRheb, Jose Esteban for help with behavioral
and biochemical experiments, and Noelia Campillo, Rebeca Martínez-Turrillas, and
Ana Navarro for expert technical help. Work was funded by the UTE project CIMA;
fellowships from the Fundación Tatiana Pérez de Guzmán el Bueno, FEBS, and IBRO
(to M.J.C.D.), Generalitat Valenciana (to O.E.-Z.), Juan de la Cierva (to L.G.R.),
FPI-MINECO (to E.R.V., to S.N.) and Intertalentum postdoctoral program (to V.B.);
ANR (GluBrain3A) and ERC Advanced Grants (#693021) (to P.P.); Ramón y Cajal program
RYC2014-15784, RETOS-MINECO SAF2016-76565-R, ERANET-Neuron JTC 2019 ISCIII AC19/00077
FEDER funds (to R.A.); RETOS-MINECO SAF2017-87928-R (to A.B.); an NIH grant (NS76637)
and UTHSC College of Medicine funds (to S.J.T.); and NARSAD Independent Investigator
Award and grants from the MINECO (CSD2008-00005, SAF2013-48983R, SAF2016-80895-R),
Generalitat Valenciana (PROMETEO 2019/020)(to I.P.O.) and Severo-Ochoa Excellence
Awards (SEV-2013-0317, SEV-2017-0723).
article_number: e71575
article_processing_charge: No
article_type: original
author:
- first_name: María J
full_name: Conde-Dusman, María J
last_name: Conde-Dusman
- first_name: Partha N
full_name: Dey, Partha N
last_name: Dey
- first_name: Óscar
full_name: Elía-Zudaire, Óscar
last_name: Elía-Zudaire
- first_name: Luis E
full_name: Garcia Rabaneda, Luis E
id: 33D1B084-F248-11E8-B48F-1D18A9856A87
last_name: Garcia Rabaneda
- first_name: Carmen
full_name: García-Lira, Carmen
last_name: García-Lira
- first_name: Teddy
full_name: Grand, Teddy
last_name: Grand
- first_name: Victor
full_name: Briz, Victor
last_name: Briz
- first_name: Eric R
full_name: Velasco, Eric R
last_name: Velasco
- first_name: Raül
full_name: Andero Galí, Raül
last_name: Andero Galí
- first_name: Sergio
full_name: Niñerola, Sergio
last_name: Niñerola
- first_name: Angel
full_name: Barco, Angel
last_name: Barco
- first_name: Pierre
full_name: Paoletti, Pierre
last_name: Paoletti
- first_name: John F
full_name: Wesseling, John F
last_name: Wesseling
- first_name: Fabrizio
full_name: Gardoni, Fabrizio
last_name: Gardoni
- first_name: Steven J
full_name: Tavalin, Steven J
last_name: Tavalin
- first_name: Isabel
full_name: Perez-Otaño, Isabel
last_name: Perez-Otaño
citation:
ama: Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, et al. Control of protein synthesis
and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly.
eLife. 2021;10. doi:10.7554/elife.71575
apa: Conde-Dusman, M. J., Dey, P. N., Elía-Zudaire, Ó., Garcia Rabaneda, L. E.,
García-Lira, C., Grand, T., … Perez-Otaño, I. (2021). Control of protein synthesis
and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly.
ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.71575
chicago: Conde-Dusman, María J, Partha N Dey, Óscar Elía-Zudaire, Luis E Garcia
Rabaneda, Carmen García-Lira, Teddy Grand, Victor Briz, et al. “Control of Protein
Synthesis and Memory by GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1
Assembly.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/elife.71575.
ieee: M. J. Conde-Dusman et al., “Control of protein synthesis and memory
by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly,” eLife,
vol. 10. eLife Sciences Publications, 2021.
ista: Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, Garcia Rabaneda LE, García-Lira C,
Grand T, Briz V, Velasco ER, Andero Galí R, Niñerola S, Barco A, Paoletti P, Wesseling
JF, Gardoni F, Tavalin SJ, Perez-Otaño I. 2021. Control of protein synthesis and
memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. eLife.
10, e71575.
mla: Conde-Dusman, María J., et al. “Control of Protein Synthesis and Memory by
GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1 Assembly.” ELife,
vol. 10, e71575, eLife Sciences Publications, 2021, doi:10.7554/elife.71575.
short: M.J. Conde-Dusman, P.N. Dey, Ó. Elía-Zudaire, L.E. Garcia Rabaneda, C. García-Lira,
T. Grand, V. Briz, E.R. Velasco, R. Andero Galí, S. Niñerola, A. Barco, P. Paoletti,
J.F. Wesseling, F. Gardoni, S.J. Tavalin, I. Perez-Otaño, ELife 10 (2021).
date_created: 2021-11-18T06:59:45Z
date_published: 2021-11-17T00:00:00Z
date_updated: 2023-08-14T11:50:50Z
day: '17'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.7554/elife.71575
external_id:
isi:
- '000720945900001'
file:
- access_level: open_access
checksum: 59318e9e41507cec83c2f4070e6ad540
content_type: application/pdf
creator: lgarciar
date_created: 2021-11-18T07:02:02Z
date_updated: 2021-11-18T07:02:02Z
file_id: '10302'
file_name: elife-71575-v1.pdf
file_size: 2477302
relation: main_file
success: 1
file_date_updated: 2021-11-18T07:02:02Z
has_accepted_license: '1'
intvolume: ' 10'
isi: 1
keyword:
- general immunology and microbiology
- general biochemistry
- genetics and molecular biology
- general medicine
- general neuroscience
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
publication: eLife
publication_identifier:
issn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
status: public
title: Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition
of GIT1/mTORC1 assembly
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 10
year: '2021'
...
---
_id: '9953'
abstract:
- lang: eng
text: Chronic psychological stress is one of the most important triggers and environmental
risk factors for neuropsychiatric disorders. Chronic stress can influence all
organs via the secretion of stress hormones, including glucocorticoids by the
adrenal glands, which coordinate the stress response across the body. In the brain,
glucocorticoid receptors (GR) are expressed by various cell types including microglia,
which are its resident immune cells regulating stress-induced inflammatory processes.
To study the roles of microglial GR under normal homeostatic conditions and following
chronic stress, we generated a mouse model in which the GR gene is depleted in
microglia specifically at adulthood to prevent developmental confounds. We first
confirmed that microglia were depleted in GR in our model in males and females
among the cingulate cortex and the hippocampus, both stress-sensitive brain regions.
Then, cohorts of microglial-GR depleted and wild-type (WT) adult female mice were
housed for 3 weeks in a standard or stressful condition, using a chronic unpredictable
mild stress (CUMS) paradigm. CUMS induced stress-related behavior in both microglial-GR
depleted and WT animals as demonstrated by a decrease of both saccharine preference
and progressive ratio breakpoint. Nevertheless, the hippocampal microglial and
neural mechanisms underlying the adaptation to stress occurred differently between
the two genotypes. Upon CUMS exposure, microglial morphology was altered in the
WT controls, without any apparent effect in microglial-GR depleted mice. Furthermore,
in the standard environment condition, GR depleted-microglia showed increased
expression of pro-inflammatory genes, and genes involved in microglial homeostatic
functions (such as Trem2, Cx3cr1 and Mertk). On the contrary, in CUMS condition,
GR depleted-microglia showed reduced expression levels of pro-inflammatory genes
and increased neuroprotective as well as anti-inflammatory genes compared to WT-microglia.
Moreover, in microglial-GR depleted mice, but not in WT mice, CUMS led to a significant
reduction of CA1 long-term potentiation and paired-pulse ratio. Lastly, differences
in adult hippocampal neurogenesis were observed between the genotypes during normal
homeostatic conditions, with microglial-GR deficiency increasing the formation
of newborn neurons in the dentate gyrus subgranular zone independently from stress
exposure. Together, these findings indicate that, although the deletion of microglial
GR did not prevent the animal’s ability to respond to stress, it contributed to
modulating hippocampal functions in both standard and stressful conditions, notably
by shaping the microglial response to chronic stress.
acknowledgement: We acknowledge that Université Laval stands on the traditional and
unceded land of the Huron-Wendat peoples; and that the University of Victoria exists
on the territory of the Lekwungen peoples and that the Songhees, Esquimalt and WSÁNEÆ
peoples have relationships to this land. We thank Emmanuel Planel for the access
to the epifluorescence microscope and Julie-Christine Lévesque at the Bioimaging
Platform of CRCHU de Québec-Université Laval for technical assistance. We also thank
the Centre for Advanced Materials and Related Technology for the access to the confocal
microscope with Airyscan. K.P. was supported by a doctoral scholarship from Fonds
de Recherche du Québec – Santé (FRQS), an excellence award from Fondation du CHU
de Québec, as well as from Centre Thématique de Recherche en Neurosciences and from
Fondation Famille-Choquette. K.B. was supported by excellence scholarships from
Université Laval and Fondation du CHU de Québec. S.G. is supported by FIRC-AIRC
fellowship for Italy 22329/2018 and by Pilot ARISLA NKINALS 2019. C.W.H. and J.C.S.
were supported by postdoctoral fellowships from FRQS. This study was funded by a
Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery grant
(RGPIN-2014-05308) awarded to M.E.T., by ERANET neuron 2017 MicroSynDep to M.E.T.
and I.B., and by the Italian Ministry of Health, grant RF-2018-12367249 to I.B,
by PRIN 2017, AIRC 2019 and Ministero della Salute RF2018 to C.L. M.E.T. is a Tier
II Canada Research Chair in Neurobiology of Aging and Cognition.
article_processing_charge: No
article_type: original
author:
- first_name: Katherine
full_name: Picard, Katherine
last_name: Picard
- first_name: Kanchan
full_name: Bisht, Kanchan
last_name: Bisht
- first_name: Silvia
full_name: Poggini, Silvia
last_name: Poggini
- first_name: Stefano
full_name: Garofalo, Stefano
last_name: Garofalo
- first_name: Maria Teresa
full_name: Golia, Maria Teresa
last_name: Golia
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Fatima
full_name: Abdallah, Fatima
last_name: Abdallah
- first_name: Naomi
full_name: Ciano Albanese, Naomi
last_name: Ciano Albanese
- first_name: Irmgard
full_name: Amrein, Irmgard
last_name: Amrein
- first_name: Nathalie
full_name: Vernoux, Nathalie
last_name: Vernoux
- first_name: Kaushik
full_name: Sharma, Kaushik
last_name: Sharma
- first_name: Chin Wai
full_name: Hui, Chin Wai
last_name: Hui
- first_name: Julie
full_name: C. Savage, Julie
last_name: C. Savage
- first_name: Cristina
full_name: Limatola, Cristina
last_name: Limatola
- first_name: Davide
full_name: Ragozzino, Davide
last_name: Ragozzino
- first_name: Laura
full_name: Maggi, Laura
last_name: Maggi
- first_name: Igor
full_name: Branchi, Igor
last_name: Branchi
- first_name: Marie Ève
full_name: Tremblay, Marie Ève
last_name: Tremblay
citation:
ama: Picard K, Bisht K, Poggini S, et al. Microglial-glucocorticoid receptor depletion
alters the response of hippocampal microglia and neurons in a chronic unpredictable
mild stress paradigm in female mice. Brain, Behavior, and Immunity. 2021;97:423-439.
doi:10.1016/j.bbi.2021.07.022
apa: Picard, K., Bisht, K., Poggini, S., Garofalo, S., Golia, M. T., Basilico, B.,
… Tremblay, M. È. (2021). Microglial-glucocorticoid receptor depletion alters
the response of hippocampal microglia and neurons in a chronic unpredictable mild
stress paradigm in female mice. Brain, Behavior, and Immunity. Elsevier.
https://doi.org/10.1016/j.bbi.2021.07.022
chicago: Picard, Katherine, Kanchan Bisht, Silvia Poggini, Stefano Garofalo, Maria
Teresa Golia, Bernadette Basilico, Fatima Abdallah, et al. “Microglial-Glucocorticoid
Receptor Depletion Alters the Response of Hippocampal Microglia and Neurons in
a Chronic Unpredictable Mild Stress Paradigm in Female Mice.” Brain, Behavior,
and Immunity. Elsevier, 2021. https://doi.org/10.1016/j.bbi.2021.07.022.
ieee: K. Picard et al., “Microglial-glucocorticoid receptor depletion alters
the response of hippocampal microglia and neurons in a chronic unpredictable mild
stress paradigm in female mice,” Brain, Behavior, and Immunity, vol. 97.
Elsevier, pp. 423–439, 2021.
ista: Picard K, Bisht K, Poggini S, Garofalo S, Golia MT, Basilico B, Abdallah F,
Ciano Albanese N, Amrein I, Vernoux N, Sharma K, Hui CW, C. Savage J, Limatola
C, Ragozzino D, Maggi L, Branchi I, Tremblay MÈ. 2021. Microglial-glucocorticoid
receptor depletion alters the response of hippocampal microglia and neurons in
a chronic unpredictable mild stress paradigm in female mice. Brain, Behavior,
and Immunity. 97, 423–439.
mla: Picard, Katherine, et al. “Microglial-Glucocorticoid Receptor Depletion Alters
the Response of Hippocampal Microglia and Neurons in a Chronic Unpredictable Mild
Stress Paradigm in Female Mice.” Brain, Behavior, and Immunity, vol. 97,
Elsevier, 2021, pp. 423–39, doi:10.1016/j.bbi.2021.07.022.
short: K. Picard, K. Bisht, S. Poggini, S. Garofalo, M.T. Golia, B. Basilico, F.
Abdallah, N. Ciano Albanese, I. Amrein, N. Vernoux, K. Sharma, C.W. Hui, J. C.
Savage, C. Limatola, D. Ragozzino, L. Maggi, I. Branchi, M.È. Tremblay, Brain,
Behavior, and Immunity 97 (2021) 423–439.
date_created: 2021-08-22T22:01:21Z
date_published: 2021-10-01T00:00:00Z
date_updated: 2023-10-03T09:49:18Z
day: '01'
department:
- _id: GaNo
doi: 10.1016/j.bbi.2021.07.022
external_id:
isi:
- '000702878400007'
pmid:
- '34343616'
intvolume: ' 97'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.zora.uzh.ch/id/eprint/208855/1/ZORA208855.pdf
month: '10'
oa: 1
oa_version: Submitted Version
page: 423-439
pmid: 1
publication: Brain, Behavior, and Immunity
publication_identifier:
issn:
- 0889-1591
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Microglial-glucocorticoid receptor depletion alters the response of hippocampal
microglia and neurons in a chronic unpredictable mild stress paradigm in female
mice
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 97
year: '2021'
...
---
_id: '8730'
abstract:
- lang: eng
text: P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) restrict
at the blood–brain barrier (BBB) the brain distribution of the majority of currently
known molecularly targeted anticancer drugs. To improve brain delivery of dual
ABCB1/ABCG2 substrates, both ABCB1 and ABCG2 need to be inhibited simultaneously
at the BBB. We examined the feasibility of simultaneous ABCB1/ABCG2 inhibition
with i.v. co-infusion of erlotinib and tariquidar by studying brain distribution
of the model ABCB1/ABCG2 substrate [11C]erlotinib in mice and rhesus macaques
with PET. Tolerability of the erlotinib/tariquidar combination was assessed in
human embryonic stem cell-derived cerebral organoids. In mice and macaques, baseline
brain distribution of [11C]erlotinib was low (brain distribution volume, VT,brain < 0.3 mL/cm3).
Co-infusion of erlotinib and tariquidar increased VT,brain in mice by 3.0-fold
and in macaques by 3.4- to 5.0-fold, while infusion of erlotinib alone or tariquidar
alone led to less pronounced VT,brain increases in both species. Treatment of
cerebral organoids with erlotinib/tariquidar led to an induction of Caspase-3-dependent
apoptosis. Co-infusion of erlotinib/tariquidar may potentially allow for complete
ABCB1/ABCG2 inhibition at the BBB, while simultaneously achieving brain-targeted
EGFR inhibition. Our protocol may be applicable to enhance brain delivery of molecularly
targeted anticancer drugs for a more effective treatment of brain tumors.
article_processing_charge: No
article_type: original
author:
- first_name: N
full_name: Tournier, N
last_name: Tournier
- first_name: S
full_name: Goutal, S
last_name: Goutal
- first_name: S
full_name: Mairinger, S
last_name: Mairinger
- first_name: IH
full_name: Lozano, IH
last_name: Lozano
- first_name: T
full_name: Filip, T
last_name: Filip
- first_name: M
full_name: Sauberer, M
last_name: Sauberer
- first_name: F
full_name: Caillé, F
last_name: Caillé
- first_name: L
full_name: Breuil, L
last_name: Breuil
- first_name: J
full_name: Stanek, J
last_name: Stanek
- first_name: AF
full_name: Freeman, AF
last_name: Freeman
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: C
full_name: Truillet, C
last_name: Truillet
- first_name: T
full_name: Wanek, T
last_name: Wanek
- first_name: O
full_name: Langer, O
last_name: Langer
citation:
ama: Tournier N, Goutal S, Mairinger S, et al. Complete inhibition of ABCB1 and
ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to
improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. Journal
of Cerebral Blood Flow and Metabolism. 2021;41(7):1634-1646. doi:10.1177/0271678X20965500
apa: Tournier, N., Goutal, S., Mairinger, S., Lozano, I., Filip, T., Sauberer, M.,
… Langer, O. (2021). Complete inhibition of ABCB1 and ABCG2 at the blood-brain
barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of
the model ABCB1/ABCG2 substrate [11C]erlotinib. Journal of Cerebral Blood Flow
and Metabolism. SAGE Publications. https://doi.org/10.1177/0271678X20965500
chicago: Tournier, N, S Goutal, S Mairinger, IH Lozano, T Filip, M Sauberer, F Caillé,
et al. “Complete Inhibition of ABCB1 and ABCG2 at the Blood-Brain Barrier by Co-Infusion
of Erlotinib and Tariquidar to Improve Brain Delivery of the Model ABCB1/ABCG2
Substrate [11C]Erlotinib.” Journal of Cerebral Blood Flow and Metabolism.
SAGE Publications, 2021. https://doi.org/10.1177/0271678X20965500.
ieee: N. Tournier et al., “Complete inhibition of ABCB1 and ABCG2 at the
blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain
delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib,” Journal of Cerebral
Blood Flow and Metabolism, vol. 41, no. 7. SAGE Publications, pp. 1634–1646,
2021.
ista: Tournier N, Goutal S, Mairinger S, Lozano I, Filip T, Sauberer M, Caillé F,
Breuil L, Stanek J, Freeman A, Novarino G, Truillet C, Wanek T, Langer O. 2021.
Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion
of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2
substrate [11C]erlotinib. Journal of Cerebral Blood Flow and Metabolism. 41(7),
1634–1646.
mla: Tournier, N., et al. “Complete Inhibition of ABCB1 and ABCG2 at the Blood-Brain
Barrier by Co-Infusion of Erlotinib and Tariquidar to Improve Brain Delivery of
the Model ABCB1/ABCG2 Substrate [11C]Erlotinib.” Journal of Cerebral Blood
Flow and Metabolism, vol. 41, no. 7, SAGE Publications, 2021, pp. 1634–46,
doi:10.1177/0271678X20965500.
short: N. Tournier, S. Goutal, S. Mairinger, I. Lozano, T. Filip, M. Sauberer, F.
Caillé, L. Breuil, J. Stanek, A. Freeman, G. Novarino, C. Truillet, T. Wanek,
O. Langer, Journal of Cerebral Blood Flow and Metabolism 41 (2021) 1634–1646.
date_created: 2020-11-06T08:39:01Z
date_published: 2021-07-01T00:00:00Z
date_updated: 2023-10-18T06:45:30Z
day: '01'
department:
- _id: GaNo
doi: 10.1177/0271678X20965500
external_id:
isi:
- '000664214100012'
pmid:
- '33081568'
intvolume: ' 41'
isi: 1
issue: '7'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221757/
month: '07'
oa: 1
oa_version: Published Version
page: 1634-1646
pmid: 1
publication: Journal of Cerebral Blood Flow and Metabolism
publication_identifier:
eissn:
- 1559-7016
issn:
- 0271-678x
publication_status: published
publisher: SAGE Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion
of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate
[11C]erlotinib
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 41
year: '2021'
...
---
_id: '9429'
abstract:
- lang: eng
text: De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3
lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency
leads to motor coordination deficits as well as ASD-relevant social and cognitive
impairments. However, induction of Cul3 haploinsufficiency later in life does
not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during
a critical developmental window. Here we show that Cul3 is essential to regulate
neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice
display cortical lamination abnormalities. At the molecular level, we found that
Cul3 controls neuronal migration by tightly regulating the amount of Plastin3
(Pls3), a previously unrecognized player of neural migration. Furthermore, we
found that Pls3 cell-autonomously regulates cell migration by regulating actin
cytoskeleton organization, and its levels are inversely proportional to neural
migration speed. Finally, we provide evidence that cellular phenotypes associated
with autism-linked gene haploinsufficiency can be rescued by transcriptional activation
of the intact allele in vitro, offering a proof of concept for a potential therapeutic
approach for ASDs.
acknowledged_ssus:
- _id: PreCl
acknowledgement: We thank A. Coll Manzano, F. Freeman, M. Ladron de Guevara, and A.
Ç. Yahya for technical assistance, S. Deixler, A. Lepold, and A. Schlerka for the
management of our animal colony, as well as M. Schunn and the Preclinical Facility
team for technical assistance. We thank K. Heesom and her team at the University
of Bristol Proteomics Facility for the proteomics sample preparation, data generation,
and analysis support. We thank Y. B. Simon for kindly providing the plasmid for
lentiviral labeling. Further, we thank M. Sixt for his advice regarding cell migration
and the fruitful discussions. This work was supported by the ISTPlus postdoctoral
fellowship (Grant Agreement No. 754411) to B.B., by the European Union’s Horizon
2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM), and by
the Austrian Science Fund (FWF) to G.N. (DK W1232-B24 and SFB F7807-B) and to J.G.D
(I3600-B27).
article_number: '3058'
article_processing_charge: No
article_type: original
author:
- first_name: Jasmin
full_name: Morandell, Jasmin
id: 4739D480-F248-11E8-B48F-1D18A9856A87
last_name: Morandell
- first_name: Lena A
full_name: Schwarz, Lena A
id: 29A8453C-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Saren
full_name: Tasciyan, Saren
id: 4323B49C-F248-11E8-B48F-1D18A9856A87
last_name: Tasciyan
orcid: 0000-0003-1671-393X
- first_name: Georgi A
full_name: Dimchev, Georgi A
id: 38C393BE-F248-11E8-B48F-1D18A9856A87
last_name: Dimchev
orcid: 0000-0001-8370-6161
- first_name: Armel
full_name: Nicolas, Armel
id: 2A103192-F248-11E8-B48F-1D18A9856A87
last_name: Nicolas
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Caroline
full_name: Kreuzinger, Caroline
id: 382077BA-F248-11E8-B48F-1D18A9856A87
last_name: Kreuzinger
- first_name: Christoph
full_name: Dotter, Christoph
id: 4C66542E-F248-11E8-B48F-1D18A9856A87
last_name: Dotter
orcid: 0000-0002-9033-9096
- first_name: Lisa
full_name: Knaus, Lisa
id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87
last_name: Knaus
- first_name: Zoe
full_name: Dobler, Zoe
id: D23090A2-9057-11EA-883A-A8396FC7A38F
last_name: Dobler
- first_name: Emanuele
full_name: Cacci, Emanuele
last_name: Cacci
- first_name: Florian KM
full_name: Schur, Florian KM
id: 48AD8942-F248-11E8-B48F-1D18A9856A87
last_name: Schur
orcid: 0000-0003-4790-8078
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein
homeostasis and cell migration during a critical window of brain development.
Nature Communications. 2021;12(1). doi:10.1038/s41467-021-23123-x
apa: Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Dimchev, G. A.,
Nicolas, A., … Novarino, G. (2021). Cul3 regulates cytoskeleton protein homeostasis
and cell migration during a critical window of brain development. Nature Communications.
Springer Nature. https://doi.org/10.1038/s41467-021-23123-x
chicago: Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan,
Georgi A Dimchev, Armel Nicolas, Christoph M Sommer, et al. “Cul3 Regulates Cytoskeleton
Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.”
Nature Communications. Springer Nature, 2021. https://doi.org/10.1038/s41467-021-23123-x.
ieee: J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis
and cell migration during a critical window of brain development,” Nature Communications,
vol. 12, no. 1. Springer Nature, 2021.
ista: Morandell J, Schwarz LA, Basilico B, Tasciyan S, Dimchev GA, Nicolas A, Sommer
CM, Kreuzinger C, Dotter C, Knaus L, Dobler Z, Cacci E, Schur FK, Danzl JG, Novarino
G. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during
a critical window of brain development. Nature Communications. 12(1), 3058.
mla: Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis
and Cell Migration during a Critical Window of Brain Development.” Nature Communications,
vol. 12, no. 1, 3058, Springer Nature, 2021, doi:10.1038/s41467-021-23123-x.
short: J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, G.A. Dimchev, A. Nicolas,
C.M. Sommer, C. Kreuzinger, C. Dotter, L. Knaus, Z. Dobler, E. Cacci, F.K. Schur,
J.G. Danzl, G. Novarino, Nature Communications 12 (2021).
date_created: 2021-05-28T11:49:46Z
date_published: 2021-05-24T00:00:00Z
date_updated: 2024-03-27T23:30:23Z
day: '24'
ddc:
- '572'
department:
- _id: GaNo
- _id: JoDa
- _id: FlSc
- _id: MiSi
- _id: LifeSc
- _id: Bio
doi: 10.1038/s41467-021-23123-x
ec_funded: 1
external_id:
isi:
- '000658769900010'
file:
- access_level: open_access
checksum: 337e0f7959c35ec959984cacdcb472ba
content_type: application/pdf
creator: kschuh
date_created: 2021-05-28T12:39:43Z
date_updated: 2021-05-28T12:39:43Z
file_id: '9430'
file_name: 2021_NatureCommunications_Morandell.pdf
file_size: 9358599
relation: main_file
success: 1
file_date_updated: 2021-05-28T12:39:43Z
has_accepted_license: '1'
intvolume: ' 12'
isi: 1
issue: '1'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
- _id: 05A0D778-7A3F-11EA-A408-12923DDC885E
grant_number: F07807
name: Neural stem cells in autism and epilepsy
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
name: Optical control of synaptic function via adhesion molecules
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: press_release
url: https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/
record:
- id: '7800'
relation: earlier_version
status: public
- id: '12401'
relation: dissertation_contains
status: public
status: public
title: Cul3 regulates cytoskeleton protein homeostasis and cell migration during a
critical window of brain development
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 12
year: '2021'
...
---
_id: '7149'
abstract:
- lang: eng
text: In recent years, many genes have been associated with chromatinopathies classified
as “Cornelia de Lange Syndrome‐like.” It is known that the phenotype of these
patients becomes less recognizable, overlapping to features characteristic of
other syndromes caused by genetic variants affecting different regulators of chromatin
structure and function. Therefore, Cornelia de Lange syndrome diagnosis might
be arduous due to the seldom discordance between unexpected molecular diagnosis
and clinical evaluation. Here, we review the molecular features of Cornelia de
Lange syndrome, supporting the hypothesis that “CdLS‐like syndromes” are part
of a larger “rare disease family” sharing multiple clinical features and common
disrupted molecular pathways.
acknowledgement: ' Dipartimento DiSS, Università degli Studi di Milano, Grant/Award
Number: Linea 2; Fondazione Cariplo, Grant/Award Number: 2015-0783; German Federal
Ministry of Education and Research (BMBF), Grant/Award Number: CHROMATIN-Net; Medical
Faculty of the University of Lübeck, Grant/Award Number: J09-2017; Nickel & Co S.p.A.;
Università degli Studi di Milano, Grant/Award Numbers: Molecular & Translational
Medicine PhD Scholarship, Translational Medicine PhD Scholarship'
article_processing_charge: No
article_type: review
author:
- first_name: Laura
full_name: Avagliano, Laura
last_name: Avagliano
- first_name: Ilaria
full_name: Parenti, Ilaria
id: D93538B0-5B71-11E9-AC62-02EBE5697425
last_name: Parenti
- first_name: Paolo
full_name: Grazioli, Paolo
last_name: Grazioli
- first_name: Elisabetta
full_name: Di Fede, Elisabetta
last_name: Di Fede
- first_name: Chiara
full_name: Parodi, Chiara
last_name: Parodi
- first_name: Milena
full_name: Mariani, Milena
last_name: Mariani
- first_name: Frank J.
full_name: Kaiser, Frank J.
last_name: Kaiser
- first_name: Angelo
full_name: Selicorni, Angelo
last_name: Selicorni
- first_name: Cristina
full_name: Gervasini, Cristina
last_name: Gervasini
- first_name: Valentina
full_name: Massa, Valentina
last_name: Massa
citation:
ama: 'Avagliano L, Parenti I, Grazioli P, et al. Chromatinopathies: A focus on Cornelia
de Lange syndrome. Clinical Genetics. 2020;97(1):3-11. doi:10.1111/cge.13674'
apa: 'Avagliano, L., Parenti, I., Grazioli, P., Di Fede, E., Parodi, C., Mariani,
M., … Massa, V. (2020). Chromatinopathies: A focus on Cornelia de Lange syndrome.
Clinical Genetics. Wiley. https://doi.org/10.1111/cge.13674'
chicago: 'Avagliano, Laura, Ilaria Parenti, Paolo Grazioli, Elisabetta Di Fede,
Chiara Parodi, Milena Mariani, Frank J. Kaiser, Angelo Selicorni, Cristina Gervasini,
and Valentina Massa. “Chromatinopathies: A Focus on Cornelia de Lange Syndrome.”
Clinical Genetics. Wiley, 2020. https://doi.org/10.1111/cge.13674.'
ieee: 'L. Avagliano et al., “Chromatinopathies: A focus on Cornelia de Lange
syndrome,” Clinical Genetics, vol. 97, no. 1. Wiley, pp. 3–11, 2020.'
ista: 'Avagliano L, Parenti I, Grazioli P, Di Fede E, Parodi C, Mariani M, Kaiser
FJ, Selicorni A, Gervasini C, Massa V. 2020. Chromatinopathies: A focus on Cornelia
de Lange syndrome. Clinical Genetics. 97(1), 3–11.'
mla: 'Avagliano, Laura, et al. “Chromatinopathies: A Focus on Cornelia de Lange
Syndrome.” Clinical Genetics, vol. 97, no. 1, Wiley, 2020, pp. 3–11, doi:10.1111/cge.13674.'
short: L. Avagliano, I. Parenti, P. Grazioli, E. Di Fede, C. Parodi, M. Mariani,
F.J. Kaiser, A. Selicorni, C. Gervasini, V. Massa, Clinical Genetics 97 (2020)
3–11.
date_created: 2019-12-04T16:10:59Z
date_published: 2020-01-01T00:00:00Z
date_updated: 2023-08-17T14:06:20Z
day: '01'
department:
- _id: GaNo
doi: 10.1111/cge.13674
external_id:
isi:
- '000562561800001'
pmid:
- '31721174'
intvolume: ' 97'
isi: 1
issue: '1'
language:
- iso: eng
month: '01'
oa_version: None
page: 3-11
pmid: 1
publication: Clinical Genetics
publication_identifier:
eissn:
- 1399-0004
issn:
- 0009-9163
publication_status: published
publisher: Wiley
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Chromatinopathies: A focus on Cornelia de Lange syndrome'
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 97
year: '2020'
...
---
_id: '7488'
abstract:
- lang: eng
text: Characteristic or classic phenotype of Cornelia de Lange syndrome (CdLS) is
associated with a recognisable facial pattern. However, the heterogeneity in causal
genes and the presence of overlapping syndromes have made it increasingly difficult
to diagnose only by clinical features. DeepGestalt technology, and its app Face2Gene,
is having a growing impact on the diagnosis and management of genetic diseases
by analysing the features of affected individuals. Here, we performed a phenotypic
study on a cohort of 49 individuals harbouring causative variants in known CdLS
genes in order to evaluate Face2Gene utility and sensitivity in the clinical diagnosis
of CdLS. Based on the profile images of patients, a diagnosis of CdLS was within
the top five predicted syndromes for 97.9% of our cases and even listed as first
prediction for 83.7%. The age of patients did not seem to affect the prediction
accuracy, whereas our results indicate a correlation between the clinical score
and affected genes. Furthermore, each gene presents a different pattern recognition
that may be used to develop new neural networks with the goal of separating different
genetic subtypes in CdLS. Overall, we conclude that computer-assisted image analysis
based on deep learning could support the clinical diagnosis of CdLS.
article_number: '1042'
article_processing_charge: No
article_type: original
author:
- first_name: Ana
full_name: Latorre-Pellicer, Ana
last_name: Latorre-Pellicer
- first_name: Ángela
full_name: Ascaso, Ángela
last_name: Ascaso
- first_name: Laura
full_name: Trujillano, Laura
last_name: Trujillano
- first_name: Marta
full_name: Gil-Salvador, Marta
last_name: Gil-Salvador
- first_name: Maria
full_name: Arnedo, Maria
last_name: Arnedo
- first_name: Cristina
full_name: Lucia-Campos, Cristina
last_name: Lucia-Campos
- first_name: Rebeca
full_name: Antoñanzas-Pérez, Rebeca
last_name: Antoñanzas-Pérez
- first_name: Iñigo
full_name: Marcos-Alcalde, Iñigo
last_name: Marcos-Alcalde
- first_name: Ilaria
full_name: Parenti, Ilaria
id: D93538B0-5B71-11E9-AC62-02EBE5697425
last_name: Parenti
- first_name: Gloria
full_name: Bueno-Lozano, Gloria
last_name: Bueno-Lozano
- first_name: Antonio
full_name: Musio, Antonio
last_name: Musio
- first_name: Beatriz
full_name: Puisac, Beatriz
last_name: Puisac
- first_name: Frank J.
full_name: Kaiser, Frank J.
last_name: Kaiser
- first_name: Feliciano J.
full_name: Ramos, Feliciano J.
last_name: Ramos
- first_name: Paulino
full_name: Gómez-Puertas, Paulino
last_name: Gómez-Puertas
- first_name: Juan
full_name: Pié, Juan
last_name: Pié
citation:
ama: Latorre-Pellicer A, Ascaso Á, Trujillano L, et al. Evaluating Face2Gene as
a tool to identify Cornelia de Lange syndrome by facial phenotypes. International
Journal of Molecular Sciences. 2020;21(3). doi:10.3390/ijms21031042
apa: Latorre-Pellicer, A., Ascaso, Á., Trujillano, L., Gil-Salvador, M., Arnedo,
M., Lucia-Campos, C., … Pié, J. (2020). Evaluating Face2Gene as a tool to identify
Cornelia de Lange syndrome by facial phenotypes. International Journal of Molecular
Sciences. MDPI. https://doi.org/10.3390/ijms21031042
chicago: Latorre-Pellicer, Ana, Ángela Ascaso, Laura Trujillano, Marta Gil-Salvador,
Maria Arnedo, Cristina Lucia-Campos, Rebeca Antoñanzas-Pérez, et al. “Evaluating
Face2Gene as a Tool to Identify Cornelia de Lange Syndrome by Facial Phenotypes.”
International Journal of Molecular Sciences. MDPI, 2020. https://doi.org/10.3390/ijms21031042.
ieee: A. Latorre-Pellicer et al., “Evaluating Face2Gene as a tool to identify
Cornelia de Lange syndrome by facial phenotypes,” International Journal of
Molecular Sciences, vol. 21, no. 3. MDPI, 2020.
ista: Latorre-Pellicer A, Ascaso Á, Trujillano L, Gil-Salvador M, Arnedo M, Lucia-Campos
C, Antoñanzas-Pérez R, Marcos-Alcalde I, Parenti I, Bueno-Lozano G, Musio A, Puisac
B, Kaiser FJ, Ramos FJ, Gómez-Puertas P, Pié J. 2020. Evaluating Face2Gene as
a tool to identify Cornelia de Lange syndrome by facial phenotypes. International
Journal of Molecular Sciences. 21(3), 1042.
mla: Latorre-Pellicer, Ana, et al. “Evaluating Face2Gene as a Tool to Identify Cornelia
de Lange Syndrome by Facial Phenotypes.” International Journal of Molecular
Sciences, vol. 21, no. 3, 1042, MDPI, 2020, doi:10.3390/ijms21031042.
short: A. Latorre-Pellicer, Á. Ascaso, L. Trujillano, M. Gil-Salvador, M. Arnedo,
C. Lucia-Campos, R. Antoñanzas-Pérez, I. Marcos-Alcalde, I. Parenti, G. Bueno-Lozano,
A. Musio, B. Puisac, F.J. Kaiser, F.J. Ramos, P. Gómez-Puertas, J. Pié, International
Journal of Molecular Sciences 21 (2020).
date_created: 2020-02-16T23:00:49Z
date_published: 2020-02-04T00:00:00Z
date_updated: 2023-08-18T06:35:41Z
day: '04'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.3390/ijms21031042
external_id:
isi:
- '000522551606028'
file:
- access_level: open_access
checksum: 0e6658c4fe329d55d4d9bef01c5b15d0
content_type: application/pdf
creator: dernst
date_created: 2020-02-18T07:49:22Z
date_updated: 2020-07-14T12:47:59Z
file_id: '7496'
file_name: 2020_IntMolecSciences_Latorre.pdf
file_size: 4271234
relation: main_file
file_date_updated: 2020-07-14T12:47:59Z
has_accepted_license: '1'
intvolume: ' 21'
isi: 1
issue: '3'
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
publication: International Journal of Molecular Sciences
publication_identifier:
eissn:
- '14220067'
issn:
- '16616596'
publication_status: published
publisher: MDPI
quality_controlled: '1'
scopus_import: '1'
status: public
title: Evaluating Face2Gene as a tool to identify Cornelia de Lange syndrome by facial
phenotypes
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 21
year: '2020'
...
---
_id: '7586'
abstract:
- lang: eng
text: CLC chloride/proton exchangers may support acidification of endolysosomes
and raise their luminal Cl− concentration. Disruption of endosomal ClC‐3 causes
severe neurodegeneration. To assess the importance of ClC‐3 Cl−/H+ exchange, we
now generate Clcn3unc/unc mice in which ClC‐3 is converted into a Cl− channel.
Unlike Clcn3−/− mice, Clcn3unc/unc mice appear normal owing to compensation by
ClC‐4 with which ClC‐3 forms heteromers. ClC‐4 protein levels are strongly reduced
in Clcn3−/−, but not in Clcn3unc/unc mice because ClC‐3unc binds and stabilizes
ClC‐4 like wild‐type ClC‐3. Although mice lacking ClC‐4 appear healthy, its absence
in Clcn3unc/unc/Clcn4−/− mice entails even stronger neurodegeneration than observed
in Clcn3−/− mice. A fraction of ClC‐3 is found on synaptic vesicles, but miniature
postsynaptic currents and synaptic vesicle acidification are not affected in Clcn3unc/unc
or Clcn3−/− mice before neurodegeneration sets in. Both, Cl−/H+‐exchange activity
and the stabilizing effect on ClC‐4, are central to the biological function of
ClC‐3.
acknowledgement: "We thank T. Stauber and T. Breiderhoff for cloning expression constructs;
K. Räbel, S. Hohensee, and C. Backhaus for technical assistance; R. Jahn (MPIbpc,
Göttingen) for providing the equipment required for SV purification; and A\r\nWoehler
(MDC, Berlin) for assistance with SV imaging. Supported, in part, by grants from
the Deutsche Forschungsgemeinschaft (JE164/9-2, SFB740 TP C5, FOR 2625 (JE164/14-1),
NeuroCure Cluster of Excellence), the European Research Council Advanced Grant CYTOVOLION
(ERC 294435) and the Prix Louis-Jeantet de Médecine to TJJ, and Peter and Traudl
Engelhorn fellowship to ZF."
article_number: e103358
article_processing_charge: No
article_type: original
author:
- first_name: Stefanie
full_name: Weinert, Stefanie
last_name: Weinert
- first_name: Niclas
full_name: Gimber, Niclas
last_name: Gimber
- first_name: Dorothea
full_name: Deuschel, Dorothea
last_name: Deuschel
- first_name: Till
full_name: Stuhlmann, Till
last_name: Stuhlmann
- first_name: Dmytro
full_name: Puchkov, Dmytro
last_name: Puchkov
- first_name: Zohreh
full_name: Farsi, Zohreh
last_name: Farsi
- first_name: Carmen F.
full_name: Ludwig, Carmen F.
last_name: Ludwig
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Karen I.
full_name: López-Cayuqueo, Karen I.
last_name: López-Cayuqueo
- first_name: Rosa
full_name: Planells-Cases, Rosa
last_name: Planells-Cases
- first_name: Thomas J.
full_name: Jentsch, Thomas J.
last_name: Jentsch
citation:
ama: Weinert S, Gimber N, Deuschel D, et al. Uncoupling endosomal CLC chloride/proton
exchange causes severe neurodegeneration. EMBO Journal. 2020;39. doi:10.15252/embj.2019103358
apa: Weinert, S., Gimber, N., Deuschel, D., Stuhlmann, T., Puchkov, D., Farsi, Z.,
… Jentsch, T. J. (2020). Uncoupling endosomal CLC chloride/proton exchange causes
severe neurodegeneration. EMBO Journal. EMBO Press. https://doi.org/10.15252/embj.2019103358
chicago: Weinert, Stefanie, Niclas Gimber, Dorothea Deuschel, Till Stuhlmann, Dmytro
Puchkov, Zohreh Farsi, Carmen F. Ludwig, et al. “Uncoupling Endosomal CLC Chloride/Proton
Exchange Causes Severe Neurodegeneration.” EMBO Journal. EMBO Press, 2020.
https://doi.org/10.15252/embj.2019103358.
ieee: S. Weinert et al., “Uncoupling endosomal CLC chloride/proton exchange
causes severe neurodegeneration,” EMBO Journal, vol. 39. EMBO Press, 2020.
ista: Weinert S, Gimber N, Deuschel D, Stuhlmann T, Puchkov D, Farsi Z, Ludwig CF,
Novarino G, López-Cayuqueo KI, Planells-Cases R, Jentsch TJ. 2020. Uncoupling
endosomal CLC chloride/proton exchange causes severe neurodegeneration. EMBO Journal.
39, e103358.
mla: Weinert, Stefanie, et al. “Uncoupling Endosomal CLC Chloride/Proton Exchange
Causes Severe Neurodegeneration.” EMBO Journal, vol. 39, e103358, EMBO
Press, 2020, doi:10.15252/embj.2019103358.
short: S. Weinert, N. Gimber, D. Deuschel, T. Stuhlmann, D. Puchkov, Z. Farsi, C.F.
Ludwig, G. Novarino, K.I. López-Cayuqueo, R. Planells-Cases, T.J. Jentsch, EMBO
Journal 39 (2020).
date_created: 2020-03-15T23:00:55Z
date_published: 2020-03-02T00:00:00Z
date_updated: 2023-08-18T07:07:36Z
day: '02'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.15252/embj.2019103358
external_id:
isi:
- '000517335000001'
pmid:
- '32118314'
file:
- access_level: open_access
checksum: 82750a7a93e3740decbce8474004111a
content_type: application/pdf
creator: dernst
date_created: 2020-03-23T13:51:11Z
date_updated: 2020-07-14T12:48:00Z
file_id: '7615'
file_name: 2020_EMBO_Weinert.pdf
file_size: 12243278
relation: main_file
file_date_updated: 2020-07-14T12:48:00Z
has_accepted_license: '1'
intvolume: ' 39'
isi: 1
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
publication: EMBO Journal
publication_identifier:
eissn:
- '14602075'
issn:
- '02614189'
publication_status: published
publisher: EMBO Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 39
year: '2020'
...