---
_id: '15016'
abstract:
- lang: eng
text: 'The development, evolution, and function of the vertebrate central nervous
system (CNS) can be best studied using diverse model organisms. Amphibians, with
their unique phylogenetic position at the transition between aquatic and terrestrial
lifestyles, are valuable for understanding the origin and evolution of the tetrapod
brain and spinal cord. Their metamorphic developmental transitions and unique
regenerative abilities also facilitate the discovery of mechanisms for neural
circuit remodeling and replacement. The genetic toolkit for amphibians, however,
remains limited, with only a few species having sequenced genomes and a small
number of transgenic lines available. In mammals, recombinant adeno-associated
viral vectors (AAVs) have become a powerful alternative to genome modification
for visualizing and perturbing the nervous system. AAVs are DNA viruses that enable
neuronal transduction in both developing and adult animals with low toxicity and
spatial, temporal, and cell-type specificity. However, AAVs have never been shown
to transduce amphibian cells efficiently. To bridge this gap, we established a
simple, scalable, and robust strategy to screen AAV serotypes in three distantly-related
amphibian species: the frogs Xenopus laevis and Pelophylax bedriagae, and the
salamander Pleurodeles waltl, in both developing larval tadpoles and post-metamorphic
animals. For each species, we successfully identified at least two AAV serotypes
capable of infecting the CNS; however, no pan-amphibian serotype was identified,
indicating rapid evolution of AAV tropism. In addition, we developed an AAV-based
strategy that targets isochronic cohorts of developing neurons – a critical tool
for parsing neural circuit assembly. Finally, to enable visualization and manipulation
of neural circuits, we identified AAV variants for retrograde tracing of neuronal
projections in adult animals. Our findings expand the toolkit for amphibians to
include AAVs, establish a generalizable workflow for AAV screening in non-canonical
research organisms, generate testable hypotheses for the evolution of AAV tropism,
and lay the foundation for modern cross-species comparisons of vertebrate CNS
development, function, and evolution. '
acknowledgement: "We would like to extend our thanks to members of the Sweeney, Tosches,
Shein-Idelson,\r\nYamaguchi, Kelley, and Cline Labs for their contributions to this
project, discussion and support.\r\nWe additionally thank the Beckman Institute
Clover Center and Viviana Gradinaru (Caltech),\r\nKimberly Ritola (UNC NeuroTools),
Flavia Gama Gomez Leite (ISTA Viral Core), and Hüseyin\r\nCihan Önal (Shigemoto
Group, ISTA) for their consultation and assistance regarding AAVs, as\r\nwell as
Andras Simon and Alberto Joven for feedback and discussions on AAVs in Pleurodeles.\r\nTo
do these experiments, we have also benefited from the tremendous support of our
animal care and imaging facilities at our respective institutions, as well as the
amphibian stock centers\r\n(National Xenopus Resource Center, European Xenopus Resource
Center, Xenopus Express)\r\nand our funding sources: U.S. National Science Foundation
(NSF) Grant Number IOS 2110086\r\n(D.B.K., L.B.S., M.A.T., A.Y., and H.T.C.); United
States-Israel Binational Science Foundation\r\n(BSF) Grant Number 2020702 (M.S.-I.);
NSF Award Number 1645105 (G.J.G., M.E.H.); FTI\r\nStrategy Lower Austria Dissertation
Grant Number FTI21-D-046 (D.V.); Horizon Europe ERC\r\nStarting Grant Number 101041551
(L.B.S.); NIH grant number R35GM146973 (M.A.T.); Rita Allen\r\nFoundation award
number GA_032522_FE (M.A.T.); European Molecular Biology Organization\r\nLong-Term
Fellowship ALTF 874-2021 (A.D.); National Science Foundation Graduate Research\r\nFellowship
DGE 2036197 (E.C.J.B.); NIH grant number P40OD010997 (M.E.H)."
article_processing_charge: No
author:
- first_name: Eliza C.B.
full_name: Jaeger, Eliza C.B.
last_name: Jaeger
- first_name: David
full_name: Vijatovic, David
id: cf391e77-ec3c-11ea-a124-d69323410b58
last_name: Vijatovic
- first_name: Astrid
full_name: Deryckere, Astrid
last_name: Deryckere
- first_name: Nikol
full_name: Zorin, Nikol
last_name: Zorin
- first_name: Akemi L.
full_name: Nguyen, Akemi L.
last_name: Nguyen
- first_name: Georgiy
full_name: Ivanian, Georgiy
id: eaf2b366-cfd1-11ee-bbdf-c8790f800a05
last_name: Ivanian
- first_name: Jamie
full_name: Woych, Jamie
last_name: Woych
- first_name: Rebecca C
full_name: Arnold, Rebecca C
id: d6cce458-14c9-11ed-a755-c1c8fc6fde6f
last_name: Arnold
- first_name: Alonso
full_name: Ortega Gurrola, Alonso
last_name: Ortega Gurrola
- first_name: Arik
full_name: Shvartsman, Arik
last_name: Shvartsman
- first_name: Francesca
full_name: Barbieri, Francesca
id: a9492887-8972-11ed-ae7b-bfae10998254
last_name: Barbieri
- first_name: Florina-Alexandra
full_name: Toma, Florina-Alexandra
id: 85dd99f2-15b2-11ec-abd3-d1ae4d57f3b5
last_name: Toma
- first_name: Gary J.
full_name: Gorbsky, Gary J.
last_name: Gorbsky
- first_name: Marko E.
full_name: Horb, Marko E.
last_name: Horb
- first_name: Hollis T.
full_name: Cline, Hollis T.
last_name: Cline
- first_name: Timothy F.
full_name: Shay, Timothy F.
last_name: Shay
- first_name: Darcy B.
full_name: Kelley, Darcy B.
last_name: Kelley
- first_name: Ayako
full_name: Yamaguchi, Ayako
last_name: Yamaguchi
- first_name: Mark
full_name: Shein-Idelson, Mark
last_name: Shein-Idelson
- first_name: Maria Antonietta
full_name: Tosches, Maria Antonietta
last_name: Tosches
- first_name: Lora Beatrice Jaeger
full_name: Sweeney, Lora Beatrice Jaeger
id: 56BE8254-C4F0-11E9-8E45-0B23E6697425
last_name: Sweeney
orcid: 0000-0001-9242-5601
citation:
ama: Jaeger ECB, Vijatovic D, Deryckere A, et al. Adeno-associated viral tools to
trace neural development and connectivity across amphibians. bioRxiv. doi:10.1101/2024.02.15.580289
apa: Jaeger, E. C. B., Vijatovic, D., Deryckere, A., Zorin, N., Nguyen, A. L., Ivanian,
G., … Sweeney, L. B. (n.d.). Adeno-associated viral tools to trace neural development
and connectivity across amphibians. bioRxiv. https://doi.org/10.1101/2024.02.15.580289
chicago: Jaeger, Eliza C.B., David Vijatovic, Astrid Deryckere, Nikol Zorin, Akemi
L. Nguyen, Georgiy Ivanian, Jamie Woych, et al. “Adeno-Associated Viral Tools
to Trace Neural Development and Connectivity across Amphibians.” BioRxiv,
n.d. https://doi.org/10.1101/2024.02.15.580289.
ieee: E. C. B. Jaeger et al., “Adeno-associated viral tools to trace neural
development and connectivity across amphibians,” bioRxiv. .
ista: Jaeger ECB, Vijatovic D, Deryckere A, Zorin N, Nguyen AL, Ivanian G, Woych
J, Arnold RC, Ortega Gurrola A, Shvartsman A, Barbieri F, Toma F-A, Gorbsky GJ,
Horb ME, Cline HT, Shay TF, Kelley DB, Yamaguchi A, Shein-Idelson M, Tosches MA,
Sweeney LB. Adeno-associated viral tools to trace neural development and connectivity
across amphibians. bioRxiv, 10.1101/2024.02.15.580289.
mla: Jaeger, Eliza C. B., et al. “Adeno-Associated Viral Tools to Trace Neural Development
and Connectivity across Amphibians.” BioRxiv, doi:10.1101/2024.02.15.580289.
short: E.C.B. Jaeger, D. Vijatovic, A. Deryckere, N. Zorin, A.L. Nguyen, G. Ivanian,
J. Woych, R.C. Arnold, A. Ortega Gurrola, A. Shvartsman, F. Barbieri, F.-A. Toma,
G.J. Gorbsky, M.E. Horb, H.T. Cline, T.F. Shay, D.B. Kelley, A. Yamaguchi, M.
Shein-Idelson, M.A. Tosches, L.B. Sweeney, BioRxiv (n.d.).
date_created: 2024-02-20T09:20:32Z
date_published: 2024-02-16T00:00:00Z
date_updated: 2024-02-20T09:34:25Z
day: '16'
department:
- _id: LoSw
- _id: MaDe
- _id: GaNo
doi: 10.1101/2024.02.15.580289
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2024.02.15.580289
month: '02'
oa: 1
oa_version: Preprint
project:
- _id: bd73af52-d553-11ed-ba76-912049f0ac7a
grant_number: FTI21-D-046
name: Entwicklung und Funktion der V1 Interneuronen vom Schwimmen zum Laufen während
der Metamorphose von Xenopus
- _id: ebb66355-77a9-11ec-83b8-b8ac210a4dae
grant_number: '101041551'
name: Development and Evolution of Tetrapod Motor Circuits
publication: bioRxiv
publication_status: submitted
status: public
title: Adeno-associated viral tools to trace neural development and connectivity across
amphibians
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2024'
...
---
_id: '14443'
abstract:
- lang: eng
text: "Importance Climate change, pollution, urbanization, socioeconomic inequality,
and psychosocial effects of the COVID-19 pandemic have caused massive changes
in environmental conditions that affect brain health during the life span, both
on a population level as well as on the level of the individual. How these environmental
factors influence the brain, behavior, and mental illness is not well known.\r\nObservations
\ A research strategy enabling population neuroscience to contribute to identify
brain mechanisms underlying environment-related mental illness by leveraging innovative
enrichment tools for data federation, geospatial observation, climate and pollution
measures, digital health, and novel data integration techniques is described.
This strategy can inform innovative treatments that target causal cognitive and
molecular mechanisms of mental illness related to the environment. An example
is presented of the environMENTAL Project that is leveraging federated cohort
data of over 1.5 million European citizens and patients enriched with deep phenotyping
data from large-scale behavioral neuroimaging cohorts to identify brain mechanisms
related to environmental adversity underlying symptoms of depression, anxiety,
stress, and substance misuse.\r\nConclusions and Relevance This research will
lead to the development of objective biomarkers and evidence-based interventions
that will significantly improve outcomes of environment-related mental illness."
article_processing_charge: No
article_type: review
author:
- first_name: Gunter
full_name: Schumann, Gunter
last_name: Schumann
- first_name: Ole A.
full_name: Andreassen, Ole A.
last_name: Andreassen
- first_name: Tobias
full_name: Banaschewski, Tobias
last_name: Banaschewski
- first_name: Vince D.
full_name: Calhoun, Vince D.
last_name: Calhoun
- first_name: Nicholas
full_name: Clinton, Nicholas
last_name: Clinton
- first_name: Sylvane
full_name: Desrivieres, Sylvane
last_name: Desrivieres
- first_name: Ragnhild Eek
full_name: Brandlistuen, Ragnhild Eek
last_name: Brandlistuen
- first_name: Jianfeng
full_name: Feng, Jianfeng
last_name: Feng
- first_name: Soeren
full_name: Hese, Soeren
last_name: Hese
- first_name: Esther
full_name: Hitchen, Esther
last_name: Hitchen
- first_name: Per
full_name: Hoffmann, Per
last_name: Hoffmann
- first_name: Tianye
full_name: Jia, Tianye
last_name: Jia
- first_name: Viktor
full_name: Jirsa, Viktor
last_name: Jirsa
- first_name: Andre F.
full_name: Marquand, Andre F.
last_name: Marquand
- first_name: Frauke
full_name: Nees, Frauke
last_name: Nees
- first_name: Markus M.
full_name: Nöthen, Markus M.
last_name: Nöthen
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Elli
full_name: Polemiti, Elli
last_name: Polemiti
- first_name: Markus
full_name: Ralser, Markus
last_name: Ralser
- first_name: Michael
full_name: Rapp, Michael
last_name: Rapp
- first_name: Kerstin
full_name: Schepanski, Kerstin
last_name: Schepanski
- first_name: Tamara
full_name: Schikowski, Tamara
last_name: Schikowski
- first_name: Mel
full_name: Slater, Mel
last_name: Slater
- first_name: Peter
full_name: Sommer, Peter
last_name: Sommer
- first_name: Bernd Carsten
full_name: Stahl, Bernd Carsten
last_name: Stahl
- first_name: Paul M.
full_name: Thompson, Paul M.
last_name: Thompson
- first_name: Sven
full_name: Twardziok, Sven
last_name: Twardziok
- first_name: Dennis
full_name: Van Der Meer, Dennis
last_name: Van Der Meer
- first_name: Henrik
full_name: Walter, Henrik
last_name: Walter
- first_name: Lars
full_name: Westlye, Lars
last_name: Westlye
citation:
ama: 'Schumann G, Andreassen OA, Banaschewski T, et al. Addressing global environmental
challenges to mental health using population neuroscience: A review. JAMA Psychiatry.
2023;80(10):1066-1074. doi:10.1001/jamapsychiatry.2023.2996'
apa: 'Schumann, G., Andreassen, O. A., Banaschewski, T., Calhoun, V. D., Clinton,
N., Desrivieres, S., … Westlye, L. (2023). Addressing global environmental challenges
to mental health using population neuroscience: A review. JAMA Psychiatry.
American Medical Association. https://doi.org/10.1001/jamapsychiatry.2023.2996'
chicago: 'Schumann, Gunter, Ole A. Andreassen, Tobias Banaschewski, Vince D. Calhoun,
Nicholas Clinton, Sylvane Desrivieres, Ragnhild Eek Brandlistuen, et al. “Addressing
Global Environmental Challenges to Mental Health Using Population Neuroscience:
A Review.” JAMA Psychiatry. American Medical Association, 2023. https://doi.org/10.1001/jamapsychiatry.2023.2996.'
ieee: 'G. Schumann et al., “Addressing global environmental challenges to
mental health using population neuroscience: A review,” JAMA Psychiatry,
vol. 80, no. 10. American Medical Association, pp. 1066–1074, 2023.'
ista: 'Schumann G, Andreassen OA, Banaschewski T, Calhoun VD, Clinton N, Desrivieres
S, Brandlistuen RE, Feng J, Hese S, Hitchen E, Hoffmann P, Jia T, Jirsa V, Marquand
AF, Nees F, Nöthen MM, Novarino G, Polemiti E, Ralser M, Rapp M, Schepanski K,
Schikowski T, Slater M, Sommer P, Stahl BC, Thompson PM, Twardziok S, Van Der
Meer D, Walter H, Westlye L. 2023. Addressing global environmental challenges
to mental health using population neuroscience: A review. JAMA Psychiatry. 80(10),
1066–1074.'
mla: 'Schumann, Gunter, et al. “Addressing Global Environmental Challenges to Mental
Health Using Population Neuroscience: A Review.” JAMA Psychiatry, vol.
80, no. 10, American Medical Association, 2023, pp. 1066–74, doi:10.1001/jamapsychiatry.2023.2996.'
short: G. Schumann, O.A. Andreassen, T. Banaschewski, V.D. Calhoun, N. Clinton,
S. Desrivieres, R.E. Brandlistuen, J. Feng, S. Hese, E. Hitchen, P. Hoffmann,
T. Jia, V. Jirsa, A.F. Marquand, F. Nees, M.M. Nöthen, G. Novarino, E. Polemiti,
M. Ralser, M. Rapp, K. Schepanski, T. Schikowski, M. Slater, P. Sommer, B.C. Stahl,
P.M. Thompson, S. Twardziok, D. Van Der Meer, H. Walter, L. Westlye, JAMA Psychiatry
80 (2023) 1066–1074.
date_created: 2023-10-22T22:01:14Z
date_published: 2023-10-01T00:00:00Z
date_updated: 2023-10-31T12:17:20Z
day: '01'
department:
- _id: GaNo
doi: 10.1001/jamapsychiatry.2023.2996
external_id:
pmid:
- '37610741'
intvolume: ' 80'
issue: '10'
language:
- iso: eng
month: '10'
oa_version: None
page: 1066-1074
pmid: 1
publication: JAMA Psychiatry
publication_identifier:
eissn:
- 2168-6238
publication_status: published
publisher: American Medical Association
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Addressing global environmental challenges to mental health using population
neuroscience: A review'
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 80
year: '2023'
...
---
_id: '14455'
acknowledgement: The author(s) declare that financial support was received for the
research, authorship, and/or publication of this article. This work has been partially
supported by Italian Ministry of Health Grant RC2023 (and the 5 × 1,000 voluntary
contributions). The authors thank the children and their families with whom they
work daily.
article_number: '1287879'
article_processing_charge: Yes
article_type: letter_note
author:
- first_name: Antonio
full_name: Narzisi, Antonio
last_name: Narzisi
- first_name: Alycia
full_name: Halladay, Alycia
last_name: Halladay
- first_name: Gabriele
full_name: Masi, Gabriele
last_name: Masi
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Catherine
full_name: Lord, Catherine
last_name: Lord
citation:
ama: 'Narzisi A, Halladay A, Masi G, Novarino G, Lord C. Tempering expectations:
Considerations on the current state of stem cells therapy for autism treatment.
Frontiers in Psychiatry. 2023;14. doi:10.3389/fpsyt.2023.1287879'
apa: 'Narzisi, A., Halladay, A., Masi, G., Novarino, G., & Lord, C. (2023).
Tempering expectations: Considerations on the current state of stem cells therapy
for autism treatment. Frontiers in Psychiatry. Frontiers. https://doi.org/10.3389/fpsyt.2023.1287879'
chicago: 'Narzisi, Antonio, Alycia Halladay, Gabriele Masi, Gaia Novarino, and Catherine
Lord. “Tempering Expectations: Considerations on the Current State of Stem Cells
Therapy for Autism Treatment.” Frontiers in Psychiatry. Frontiers, 2023.
https://doi.org/10.3389/fpsyt.2023.1287879.'
ieee: 'A. Narzisi, A. Halladay, G. Masi, G. Novarino, and C. Lord, “Tempering expectations:
Considerations on the current state of stem cells therapy for autism treatment,”
Frontiers in Psychiatry, vol. 14. Frontiers, 2023.'
ista: 'Narzisi A, Halladay A, Masi G, Novarino G, Lord C. 2023. Tempering expectations:
Considerations on the current state of stem cells therapy for autism treatment.
Frontiers in Psychiatry. 14, 1287879.'
mla: 'Narzisi, Antonio, et al. “Tempering Expectations: Considerations on the Current
State of Stem Cells Therapy for Autism Treatment.” Frontiers in Psychiatry,
vol. 14, 1287879, Frontiers, 2023, doi:10.3389/fpsyt.2023.1287879.'
short: A. Narzisi, A. Halladay, G. Masi, G. Novarino, C. Lord, Frontiers in Psychiatry
14 (2023).
date_created: 2023-10-29T23:01:16Z
date_published: 2023-10-03T00:00:00Z
date_updated: 2023-12-13T13:06:07Z
day: '03'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.3389/fpsyt.2023.1287879
external_id:
isi:
- '001084841700001'
pmid:
- '37854442'
file:
- access_level: open_access
checksum: 0a76373e9a4c0fc199f80380de257e86
content_type: application/pdf
creator: dernst
date_created: 2023-10-30T12:48:40Z
date_updated: 2023-10-30T12:48:40Z
file_id: '14468'
file_name: 2023_FrontiersPsychiatry_Narzisi.pdf
file_size: 147878
relation: main_file
success: 1
file_date_updated: 2023-10-30T12:48:40Z
has_accepted_license: '1'
intvolume: ' 14'
isi: 1
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
pmid: 1
publication: Frontiers in Psychiatry
publication_identifier:
eissn:
- 1664-0640
publication_status: published
publisher: Frontiers
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Tempering expectations: Considerations on the current state of stem cells
therapy for autism 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 14
year: '2023'
...
---
_id: '13107'
abstract:
- lang: eng
text: "Within the human body, the brain exhibits the highest rate of energy consumption
amongst all organs, with the majority of generated ATP being utilized to sustain
neuronal activity. Therefore, the metabolism of the mature cerebral cortex is
geared towards preserving metabolic homeostasis whilst generating significant
amounts of energy. This requires a precise interplay between diverse metabolic
pathways, spanning from a tissue-wide scale to the level of individual neurons.
Disturbances to this delicate metabolic equilibrium, such as those resulting from
maternal malnutrition\r\nor mutations affecting metabolic enzymes, often result
in neuropathological variants of neurodevelopment. For instance, mutations in
SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs),
have been associated with autism and microcephaly. However, despite recent progress
in the field, the extent of metabolic restructuring that occurs within the developing
brain and the corresponding alterations in nutrient demands during various critical
periods remain largely unknown. To investigate this, we performed metabolomic
profiling of the murine cerebral cortex to characterize the metabolic state of
the forebrain at different developmental stages. We found that the developing
cortex undergoes substantial metabolic reprogramming, with specific sets of metabolites
displaying stage-specific changes. According to our observations, we determined
a distinct temporal period in postnatal development during which the cortex displays
heightened reliance on LNAAs. Hence, using a conditional knock-out mouse model,
we deleted Slc7a5 in neural cells, allowing us to monitor the impact of a perturbed
neuronal metabolic state across multiple developmental stages of corticogenesis.
We found that manipulating the levels of essential LNAAs in cortical neurons in
vivo affects one particular perinatal developmental period critical for cortical
network refinement. Abnormally low intracellular LNAA levels result in cell-autonomous
alterations in neuronal lipid metabolism, excitability, and survival during this
particular time window. Although most of the effects of Slc7a5 deletion on neuronal
physiology are transient, derailment of these processes during this brief but
crucial window leads to long-term circuit dysfunction in mice. In conclusion,
out data indicate that the cerebral cortex undergoes significant metabolic reorganization
during development. This process involves the intricate integration of multiple
metabolic pathways to ensure optimal neuronal function throughout different developmental
stages. Our findings offer a paradigm for understanding how neurons synchronize
the expression of nutrient-related genes with their activity to allow proper brain
maturation. Further, our results demonstrate that disruptions in these precisely
calibrated metabolic processes during critical periods of brain development may
result in neuropathological outcomes in mice and in humans."
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: EM-Fac
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Lisa
full_name: Knaus, Lisa
id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87
last_name: Knaus
citation:
ama: 'Knaus L. The metabolism of the developing brain : How large neutral amino
acids modulate perinatal neuronal excitability and survival. 2023. doi:10.15479/at:ista:13107'
apa: 'Knaus, L. (2023). The metabolism of the developing brain : How large neutral
amino acids modulate perinatal neuronal excitability and survival. Institute
of Science and Technology Austria. https://doi.org/10.15479/at:ista:13107'
chicago: 'Knaus, Lisa. “The Metabolism of the Developing Brain : How Large Neutral
Amino Acids Modulate Perinatal Neuronal Excitability and Survival.” Institute
of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:13107.'
ieee: 'L. Knaus, “The metabolism of the developing brain : How large neutral amino
acids modulate perinatal neuronal excitability and survival,” Institute of Science
and Technology Austria, 2023.'
ista: 'Knaus L. 2023. The metabolism of the developing brain : How large neutral
amino acids modulate perinatal neuronal excitability and survival. Institute of
Science and Technology Austria.'
mla: 'Knaus, Lisa. The Metabolism of the Developing Brain : How Large Neutral
Amino Acids Modulate Perinatal Neuronal Excitability and Survival. Institute
of Science and Technology Austria, 2023, doi:10.15479/at:ista:13107.'
short: 'L. Knaus, The Metabolism of the Developing Brain : How Large Neutral Amino
Acids Modulate Perinatal Neuronal Excitability and Survival, Institute of Science
and Technology Austria, 2023.'
date_created: 2023-06-01T09:05:24Z
date_published: 2023-05-31T00:00:00Z
date_updated: 2024-02-07T08:03:33Z
day: '31'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: GaNo
doi: 10.15479/at:ista:13107
ec_funded: 1
file:
- access_level: closed
checksum: 4b69a4ac0bbf4163d59c0b58dcb4f2c3
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: lknaus
date_created: 2023-06-01T13:48:41Z
date_updated: 2023-06-01T13:48:41Z
file_id: '13112'
file_name: Thesis_Lisa Knaus_approved_final.docx
file_size: 12991551
relation: source_file
- access_level: open_access
checksum: 6903d152aa01181d87a696085af31c83
content_type: application/pdf
creator: lknaus
date_created: 2023-06-02T09:47:29Z
date_updated: 2023-06-07T08:41:49Z
file_id: '13114'
file_name: Thesis_Lisa Knaus_approved_final_pdfa2b.pdf
file_size: 9309015
relation: main_file
file_date_updated: 2023-06-07T08:41:49Z
has_accepted_license: '1'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: '147'
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_identifier:
issn:
- 2663 - 337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '12802'
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: 'The metabolism of the developing brain : How large neutral amino acids modulate
perinatal neuronal excitability and survival'
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2023'
...
---
_id: '13126'
abstract:
- lang: eng
text: Mapping the complex and dense arrangement of cells and their connectivity
in brain tissue demands nanoscale spatial resolution imaging. Super-resolution
optical microscopy excels at visualizing specific molecules and individual cells
but fails to provide tissue context. Here, we developed Comprehensive Analysis
of Tissues across Scales (CATS), a technology to densely map brain tissue architecture
from millimeter regional to nanometer synaptic scales in diverse chemically fixed
brain preparations, including rodent and human. CATS uses fixation-compatible
extracellular labeling and optical imaging, including stimulated emission depletion
or expansion microscopy, to comprehensively delineate cellular structures. It
enables three-dimensional reconstruction of single synapses and mapping of synaptic
connectivity by identification and analysis of putative synaptic cleft regions.
Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed
and quantified the synaptic input and output structure of identified neurons.
We furthermore demonstrate applicability to clinically derived human tissue samples,
including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing
the cellular architecture of brain tissue in health and disease.
acknowledged_ssus:
- _id: ScienComp
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: M-Shop
- _id: E-Lib
acknowledgement: "We thank Jakob Vorlaufer, Nathalie Agudelo-Dueñas, Wiebke Jahr,
Andreas Wartak for microscope maintenance and troubleshooting, Caroline Kreuzinger,
Anna Freeman, and Irene Erber for technical assistance and Matthias Tomschik for
support with obtaining human samples. We gratefully acknowledge Eder Miguel for
setting up webKnossos and Marek Šuplata for computational support and hardware control.
We are grateful to Ryuichi Shigemoto and Bernd Bickel for generous support, and
Michael Sixt and Scott Boyd (Stanford University) for discussions and critical reading
of the manuscript. PSD95-HaloTag mice were kindly provided by Seth Grant (University
of Edinburgh). We acknowledge expert support by IST Austria’s scientific computing,
imaging and optics, preclinical, and lab support facilities, and by the Library
and Miba machine shop.\r\nWe gratefully acknowledge funding by the following sources:
\r\nAustrian Science Fund (FWF) grant I3600-B27 (JGD)\r\nAustrian Science Fund (FWF)
grant DK W1232 (JGD, JMM)\r\nAustrian Science Fund (FWF) grant Z 312-B27, Wittgenstein
award (PJ)\r\nAustrian Science Funds (FWF) projects I4685-B, I6565-B (SYNABS) and
DOC 33-B27 (RH)\r\nGesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022
(JGD)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European
Research Council (ERC) grant 715508 – REVERSEAUTISM (GN)\r\nEuropean Union’s Horizon
2020 research and innovation programme, European Research Council (ERC) grant 692692
– GIANTSYN (PJ)\r\nMarie Skłodowska-Curie Actions Fellowship GA no. 665385 under
the EU Horizon 2020 program (JMM, JL)\r\nMarie Skłodowska-Curie Actions Individual
Fellowship 101026635 under the EU Horizon 2020 program (JFW)"
article_processing_charge: No
author:
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
citation:
ama: Danzl JG. Research data for the publication “Imaging brain tissue architecture
across millimeter to nanometer scales.” 2023. doi:10.15479/AT:ISTA:13126
apa: Danzl, J. G. (2023). Research data for the publication “Imaging brain tissue
architecture across millimeter to nanometer scales.” Institute of Science and
Technology Austria. https://doi.org/10.15479/AT:ISTA:13126
chicago: Danzl, Johann G. “Research Data for the Publication ‘Imaging Brain Tissue
Architecture across Millimeter to Nanometer Scales.’” Institute of Science and
Technology Austria, 2023. https://doi.org/10.15479/AT:ISTA:13126.
ieee: J. G. Danzl, “Research data for the publication ‘Imaging brain tissue architecture
across millimeter to nanometer scales.’” Institute of Science and Technology Austria,
2023.
ista: Danzl JG. 2023. Research data for the publication ‘Imaging brain tissue architecture
across millimeter to nanometer scales’, Institute of Science and Technology Austria,
10.15479/AT:ISTA:13126.
mla: Danzl, Johann G. Research Data for the Publication “Imaging Brain Tissue
Architecture across Millimeter to Nanometer Scales.” Institute of Science
and Technology Austria, 2023, doi:10.15479/AT:ISTA:13126.
short: J.G. Danzl, (2023).
contributor:
- first_name: Julia M
id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
last_name: Michalska
- first_name: Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
- first_name: Hana
id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed
last_name: Stefanickova
- first_name: Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Alban
id: 9ac8f577-2357-11eb-997a-e566c5550886
last_name: Cenameri
- first_name: Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Karl
last_name: Roessler
- first_name: Thomas
last_name: Czech
- first_name: Romana
last_name: Höftberger
- first_name: Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
- first_name: Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
date_created: 2023-06-07T07:15:12Z
date_published: 2023-08-04T00:00:00Z
date_updated: 2024-02-21T12:18:19Z
day: '04'
ddc:
- '610'
department:
- _id: JoDa
- _id: SaSi
- _id: GaNo
- _id: PeJo
- _id: Bio
- _id: RySh
doi: 10.15479/AT:ISTA:13126
ec_funded: 1
file:
- access_level: open_access
checksum: 6f18ce9b89b47ce5abeb379869ff5c49
content_type: text/plain
creator: jdanzl
date_created: 2023-08-04T13:19:47Z
date_updated: 2023-08-04T13:19:47Z
file_id: '13961'
file_name: Readme_Michalska_2023.txt
file_size: 541
relation: main_file
success: 1
- access_level: open_access
checksum: 2098e8c5285c5e86cb69075e1b5dcf39
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:29:29Z
date_updated: 2023-08-03T11:29:29Z
file_id: '13482'
file_name: Fig1_b_top-left.tif
file_size: 64582744
relation: main_file
success: 1
- access_level: open_access
checksum: 9affab3dacf847096cc8e8d5ff99467e
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:29:28Z
date_updated: 2023-08-03T11:29:28Z
file_id: '13483'
file_name: Fig1_b_top-right.tif
file_size: 1442113
relation: main_file
success: 1
- access_level: open_access
checksum: d7fec0296123a17f6bcdbfee17411424
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:29:29Z
date_updated: 2023-08-03T11:29:29Z
file_id: '13484'
file_name: Fig1_c_1.tif
file_size: 40078276
relation: main_file
success: 1
- access_level: open_access
checksum: 5195a180c4f26a7adc994bad0b3c53c7
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:29:29Z
date_updated: 2023-08-03T11:29:29Z
file_id: '13485'
file_name: Fig1_c_2.tif
file_size: 7984315
relation: main_file
success: 1
- access_level: open_access
checksum: df1105d8f41ebd5373cacc597ffa91f3
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:29:29Z
date_updated: 2023-08-03T11:29:29Z
file_id: '13486'
file_name: Fig1_c_3.tif
file_size: 8693320
relation: main_file
success: 1
- access_level: open_access
checksum: 00edbb0c9f42032c830d2291ec55c4c0
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:29:30Z
date_updated: 2023-08-03T11:29:30Z
file_id: '13487'
file_name: Fig1_c_4.tif
file_size: 6003063
relation: main_file
success: 1
- access_level: open_access
checksum: a58399e98ec4b6506a5dae13e387f391
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:29:30Z
date_updated: 2023-08-03T11:29:30Z
file_id: '13488'
file_name: Fig1_d.tif
file_size: 24003063
relation: main_file
success: 1
- access_level: open_access
checksum: 699df4bc104df14607359678963b3d2d
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:29:30Z
date_updated: 2023-08-03T11:29:30Z
file_id: '13489'
file_name: Fig1_e_zoom.tif
file_size: 18063
relation: main_file
success: 1
- access_level: open_access
checksum: ea7b1278da490d221fc7698fd6bc39a4
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:29:30Z
date_updated: 2023-08-03T11:29:30Z
file_id: '13490'
file_name: Fig1_e.tif
file_size: 186813
relation: main_file
success: 1
- access_level: open_access
checksum: 37b05ef3a36b9f6bf4ec46199230874a
content_type: application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
creator: jdanzl
date_created: 2023-08-03T11:29:30Z
date_updated: 2023-08-03T11:29:30Z
file_id: '13491'
file_name: Fig1_f.xlsx
file_size: 17494
relation: main_file
success: 1
- access_level: open_access
checksum: 872eb3dc1a94afb26947a365bfae581a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:40:43Z
date_updated: 2023-08-03T11:40:43Z
file_id: '13492'
file_name: Fig2_a_1.tif
file_size: 816786862
relation: main_file
success: 1
- access_level: open_access
checksum: cab6f72d7d546a81c105c229747949ef
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:40:13Z
date_updated: 2023-08-03T11:40:13Z
file_id: '13493'
file_name: Fig2_a_2.tif
file_size: 8654692
relation: main_file
success: 1
- access_level: open_access
checksum: c85bc3ffe7f6bdf16a81290761ed6253
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:40:14Z
date_updated: 2023-08-03T11:40:14Z
file_id: '13494'
file_name: Fig2_a_3.tif
file_size: 8654692
relation: main_file
success: 1
- access_level: open_access
checksum: 5a3fd5484e566c34e210a4acb2b97791
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:40:24Z
date_updated: 2023-08-03T11:40:24Z
file_id: '13495'
file_name: Fig2_a_4.tif
file_size: 272262438
relation: main_file
success: 1
- access_level: open_access
checksum: ae5cbacf56e3fdf934a6d6fd489f5fe0
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:40:37Z
date_updated: 2023-08-03T11:40:37Z
file_id: '13496'
file_name: Fig2_a_5.tif
file_size: 272262438
relation: main_file
success: 1
- access_level: open_access
checksum: e6da436b83bbe3a34138b52e5de49d69
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:40:44Z
date_updated: 2023-08-03T11:40:44Z
file_id: '13497'
file_name: Fig2_a_6.tif
file_size: 204301228
relation: main_file
success: 1
- access_level: open_access
checksum: 855f0a0bcf5b3d7cc7d50561f2c8f625
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:40:49Z
date_updated: 2023-08-03T11:40:49Z
file_id: '13498'
file_name: Fig2_a_7-8.tif
file_size: 68094350
relation: main_file
success: 1
- access_level: open_access
checksum: ff709f9f8ebaa8cf50a4b2fca5ce9813
content_type: application/octet-stream
creator: jdanzl
date_created: 2023-08-03T11:40:48Z
date_updated: 2023-08-03T11:40:48Z
file_id: '13499'
file_name: Fig2_a_roi.roi
file_size: 156
relation: main_file
success: 1
- access_level: open_access
checksum: ce9b774ff5163ebfa4e3fb162f4cfffe
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:41:37Z
date_updated: 2023-08-03T11:41:37Z
file_id: '13500'
file_name: Fig2_c-i_1_n2v.tif
file_size: 1036927887
relation: main_file
success: 1
- access_level: open_access
checksum: 21f1bb8d2a00c88bdd6febe6285acc2a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:41:25Z
date_updated: 2023-08-03T11:41:25Z
file_id: '13501'
file_name: Fig2_c-i_1.tif
file_size: 518519275
relation: main_file
success: 1
- access_level: open_access
checksum: 9af5b66b74c2ff4b2b99b0d94f2864e6
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:42:48Z
date_updated: 2023-08-03T11:42:48Z
file_id: '13502'
file_name: Fig2_c-i_3_n2v.tif
file_size: 1444202302
relation: main_file
success: 1
- access_level: open_access
checksum: c83261e88821747b301197314d92f2b2
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:42:57Z
date_updated: 2023-08-03T11:42:57Z
file_id: '13503'
file_name: Fig2_c-i_3.tif
file_size: 1075338708
relation: main_file
success: 1
- access_level: open_access
checksum: 5d1278ba4b7e085c0c186ea49fce535b
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:44:05Z
date_updated: 2023-08-03T11:44:05Z
file_id: '13504'
file_name: Fig2_c-i_2_n2v.tif
file_size: 851145493
relation: main_file
success: 1
- access_level: open_access
checksum: 5aaf1eba65582cf437ff3ce753eba4d7
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:43:47Z
date_updated: 2023-08-03T11:43:47Z
file_id: '13505'
file_name: Fig2_c-i_2.tif
file_size: 432099834
relation: main_file
success: 1
- access_level: open_access
checksum: ce9b774ff5163ebfa4e3fb162f4cfffe
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:44:41Z
date_updated: 2023-08-03T11:44:41Z
file_id: '13506'
file_name: Fig2_h_n2v.tif
file_size: 1036927887
relation: main_file
success: 1
- access_level: open_access
checksum: 21f1bb8d2a00c88bdd6febe6285acc2a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:44:36Z
date_updated: 2023-08-03T11:44:36Z
file_id: '13507'
file_name: Fig2_h.tif
file_size: 518519275
relation: main_file
success: 1
- access_level: open_access
checksum: b37f25a90ef42fa4358649fdd6b41f35
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:44:40Z
date_updated: 2023-08-03T11:44:40Z
file_id: '13508'
file_name: Fig2_j_1.tif
file_size: 19287397
relation: main_file
success: 1
- access_level: open_access
checksum: 50f0969c6c2c1209ff776bec4861030a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:44:41Z
date_updated: 2023-08-03T11:44:41Z
file_id: '13509'
file_name: Fig2_j_2.tif
file_size: 617552
relation: main_file
success: 1
- access_level: open_access
checksum: 2a8cc93471378ac4c3b640e4318d89eb
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:44:41Z
date_updated: 2023-08-03T11:44:41Z
file_id: '13510'
file_name: Fig2_j_3.tif
file_size: 19287392
relation: main_file
success: 1
- access_level: open_access
checksum: b90965d20133fea73c99050c32eb7695
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:44:42Z
date_updated: 2023-08-03T11:44:42Z
file_id: '13511'
file_name: Fig2_j_4.tif
file_size: 617552
relation: main_file
success: 1
- access_level: open_access
checksum: 568a1e0efaa62527b51e66a7aabfd05c
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:44:43Z
date_updated: 2023-08-03T11:44:43Z
file_id: '13512'
file_name: Fig2_j_coCATS_N2V.tif
file_size: 19287339
relation: main_file
success: 1
- access_level: open_access
checksum: c70447cebe073dd78e0ac34ecc36ad85
content_type: application/octet-stream
creator: jdanzl
date_created: 2023-08-03T11:44:44Z
date_updated: 2023-08-03T11:44:44Z
file_id: '13513'
file_name: Fig2_j_roi.roi
file_size: 148
relation: main_file
success: 1
- access_level: open_access
checksum: 505252cc4b443b76c2e41ecf5879a542
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:44:52Z
date_updated: 2023-08-03T11:44:52Z
file_id: '13514'
file_name: Fig3_a_n2v.tif
file_size: 316842690
relation: main_file
success: 1
- access_level: open_access
checksum: 35463183611e8ee4fba2025772c40eb2
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:45:01Z
date_updated: 2023-08-03T11:45:01Z
file_id: '13515'
file_name: Fig3_a.tif
file_size: 172839057
relation: main_file
success: 1
- access_level: open_access
checksum: e0469102a87332b46904b4ba35b8fb2f
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:45:05Z
date_updated: 2023-08-03T11:45:05Z
file_id: '13516'
file_name: Fig3_g_n2v.tif
file_size: 309407894
relation: main_file
success: 1
- access_level: open_access
checksum: 854c8fe02acd920f8e8f6a3173458e86
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:51:15Z
date_updated: 2023-08-03T11:51:15Z
file_id: '13517'
file_name: Fig4_a_MIP.tif
file_size: 11327792
relation: main_file
success: 1
- access_level: open_access
checksum: ab35811ffbe3f40733d0e054d9d6c4e6
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:51:18Z
date_updated: 2023-08-03T11:51:18Z
file_id: '13518'
file_name: Fig4_c_dghilus_bouton2_n2v.tif
file_size: 106696700
relation: main_file
success: 1
- access_level: open_access
checksum: e3b6410d68e42004ef3857967707aeb3
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:51:17Z
date_updated: 2023-08-03T11:51:17Z
file_id: '13519'
file_name: Fig4_c_dghilus_bouton2.tif
file_size: 53367287
relation: main_file
success: 1
- access_level: open_access
checksum: 9ef0e3f3ec6f0b7b2666e3a0d7e6f355
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:51:20Z
date_updated: 2023-08-03T11:51:20Z
file_id: '13520'
file_name: Fig4_c_dghilus_bouton5_n2v.tif
file_size: 103816699
relation: main_file
success: 1
- access_level: open_access
checksum: d5d846a4edaf0168ca6cc53d8cc39dde
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:51:21Z
date_updated: 2023-08-03T11:51:21Z
file_id: '13521'
file_name: Fig4_c_dghilus_bouton5.tif
file_size: 51927287
relation: main_file
success: 1
- access_level: open_access
checksum: 690a87182441c9742da2550189641e5a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:51:24Z
date_updated: 2023-08-03T11:51:24Z
file_id: '13522'
file_name: Fig4_c_stratum_bouton11_n2v.tif
file_size: 76391971
relation: main_file
success: 1
- access_level: open_access
checksum: 4dc575424729c5ba181bd9a3962d4781
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:51:23Z
date_updated: 2023-08-03T11:51:23Z
file_id: '13523'
file_name: Fig4_c_stratum_bouton11.tif
file_size: 38217920
relation: main_file
success: 1
- access_level: open_access
checksum: 9fdd51636928f45e8e534cc5a37a48ff
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:51:29Z
date_updated: 2023-08-03T11:51:29Z
file_id: '13524'
file_name: Fig4_c_stratum_bouton13_n2v.tif
file_size: 154149020
relation: main_file
success: 1
- access_level: open_access
checksum: 643169464252d67753ac6f8493668f34
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:51:28Z
date_updated: 2023-08-03T11:51:28Z
file_id: '13525'
file_name: Fig4_c_stratum_bouton13.tif
file_size: 77099447
relation: main_file
success: 1
- access_level: open_access
checksum: ab35811ffbe3f40733d0e054d9d6c4e6
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:51:32Z
date_updated: 2023-08-03T11:51:32Z
file_id: '13526'
file_name: Fig4_d.tif
file_size: 106696700
relation: main_file
success: 1
- access_level: open_access
checksum: 9fdd51636928f45e8e534cc5a37a48ff
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:51:35Z
date_updated: 2023-08-03T11:51:35Z
file_id: '13527'
file_name: Fig4_e.tif
file_size: 154149020
relation: main_file
success: 1
- access_level: open_access
checksum: 5380d0a98e97d7d8462b38bd0a96644c
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:51:32Z
date_updated: 2023-08-03T11:51:32Z
file_id: '13528'
file_name: Fig4_f_1_top.tif
file_size: 5986760
relation: main_file
success: 1
- access_level: open_access
checksum: 7d1309e806eb31588ebafcf40388e13f
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:51:33Z
date_updated: 2023-08-03T11:51:33Z
file_id: '13529'
file_name: Fig4_f_2_top.tif
file_size: 6001178
relation: main_file
success: 1
- access_level: open_access
checksum: a71c80207655d508cbc7626bc144d7a1
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:51:33Z
date_updated: 2023-08-03T11:51:33Z
file_id: '13530'
file_name: Fig4_f_3_top.tif
file_size: 6023318
relation: main_file
success: 1
- access_level: open_access
checksum: 5d76b2ad7d7acbb1afa27cf52194b1cb
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:51:34Z
date_updated: 2023-08-03T11:51:34Z
file_id: '13531'
file_name: Fig4_f_4_top.tif
file_size: 6038186
relation: main_file
success: 1
- access_level: open_access
checksum: 9cee6b3387bd880843f2c6cdfa0d4a8d
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:51:34Z
date_updated: 2023-08-03T11:51:34Z
file_id: '13532'
file_name: Fig4_f_5_top.tif
file_size: 2324158
relation: main_file
success: 1
- access_level: open_access
checksum: a48fc9e1bb2710cf28466ae6d2a20c19
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T11:51:34Z
date_updated: 2023-08-03T11:51:34Z
file_id: '13533'
file_name: Fig4_f_1_bottom.png
file_size: 1150264
relation: main_file
success: 1
- access_level: open_access
checksum: ff47ca30f814e17561974b73b0913a1a
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T11:51:34Z
date_updated: 2023-08-03T11:51:34Z
file_id: '13534'
file_name: Fig4_f_2_bottom.png
file_size: 1157424
relation: main_file
success: 1
- access_level: open_access
checksum: 2ea3fb8d79cee8ae9de7ca31d003910f
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T11:51:34Z
date_updated: 2023-08-03T11:51:34Z
file_id: '13535'
file_name: Fig4_f_3_bottom.png
file_size: 1152715
relation: main_file
success: 1
- access_level: open_access
checksum: d25e5ecf2f0c3be7c20a7e25a7a334b8
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T11:51:34Z
date_updated: 2023-08-03T11:51:34Z
file_id: '13536'
file_name: Fig4_f_4_bottom.png
file_size: 1105240
relation: main_file
success: 1
- access_level: open_access
checksum: 76535f569a57b967e378df89b7d2982a
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T11:51:35Z
date_updated: 2023-08-03T11:51:35Z
file_id: '13537'
file_name: Fig4_f_5_bottom.png
file_size: 1228157
relation: main_file
success: 1
- access_level: open_access
checksum: d46fefe73daa3ec08b847631e9de6828
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:53:52Z
date_updated: 2023-08-03T11:53:52Z
file_id: '13538'
file_name: Fig5_a_1.tif
file_size: 91181184
relation: main_file
success: 1
- access_level: open_access
checksum: 354c0ba876a33672eca37cd61dac7073
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:53:54Z
date_updated: 2023-08-03T11:53:54Z
file_id: '13539'
file_name: Fig5_a_2.tif
file_size: 176024124
relation: main_file
success: 1
- access_level: open_access
checksum: d07925040ef0c3c51edbdca8cf3ec1fa
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:53:53Z
date_updated: 2023-08-03T11:53:53Z
file_id: '13540'
file_name: Fig5_a_3.tif
file_size: 15812494
relation: main_file
success: 1
- access_level: open_access
checksum: 7c34b19a1764e2f501f11dcabd442ce2
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:53:53Z
date_updated: 2023-08-03T11:53:53Z
file_id: '13541'
file_name: Fig5_a_4.tif
file_size: 11117689
relation: main_file
success: 1
- access_level: open_access
checksum: c49af4b96532e00b3a51574a2a94decb
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:53:53Z
date_updated: 2023-08-03T11:53:53Z
file_id: '13542'
file_name: Fig5_a_5.tif
file_size: 111665
relation: main_file
success: 1
- access_level: open_access
checksum: 1b42eadcdd71f2dc00d82784673aa577
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:53:54Z
date_updated: 2023-08-03T11:53:54Z
file_id: '13543'
file_name: Fig5_b_1.tif
file_size: 16676449
relation: main_file
success: 1
- access_level: open_access
checksum: 0d27266bf216f71fcb5496731ce76dd5
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:53:54Z
date_updated: 2023-08-03T11:53:54Z
file_id: '13544'
file_name: Fig5_b_2-4.tif
file_size: 427651
relation: main_file
success: 1
- access_level: open_access
checksum: c4232930068a0a8f7c8a70ce0ea48dc2
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:53:55Z
date_updated: 2023-08-03T11:53:55Z
file_id: '13545'
file_name: Fig5_c_1-3.tif
file_size: 11117705
relation: main_file
success: 1
- access_level: open_access
checksum: c9caad749be0ef04ef8013cfdb69f8fc
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:53:55Z
date_updated: 2023-08-03T11:53:55Z
file_id: '13546'
file_name: Fig5_c_2-4.tif
file_size: 254153
relation: main_file
success: 1
- access_level: open_access
checksum: 5c6d36b96bde1e090cc428b269aba6ec
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:54:14Z
date_updated: 2023-08-03T11:54:14Z
file_id: '13547'
file_name: Fig5_e_1.tif
file_size: 737290746
relation: main_file
success: 1
- access_level: open_access
checksum: f97632984b6a73e06cc0c8c947cdcc71
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:53:57Z
date_updated: 2023-08-03T11:53:57Z
file_id: '13548'
file_name: Fig5_e_2.tif
file_size: 31366288
relation: main_file
success: 1
- access_level: open_access
checksum: 8c471eeaa59008eed9e91afe5e1f1698
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:53:57Z
date_updated: 2023-08-03T11:53:57Z
file_id: '13549'
file_name: Fig5_e_3.tif
file_size: 1216304
relation: main_file
success: 1
- access_level: open_access
checksum: 31c10c3a1d874b5028e35e2dd8800a68
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:53:59Z
date_updated: 2023-08-03T11:53:59Z
file_id: '13550'
file_name: Fig5_g.tif
file_size: 35669193
relation: main_file
success: 1
- access_level: open_access
checksum: 0e9fe7b7ee06a630837e9d3c41b80e01
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:53:59Z
date_updated: 2023-08-03T11:53:59Z
file_id: '13551'
file_name: Fig5_h.tif
file_size: 7492349
relation: main_file
success: 1
- access_level: open_access
checksum: d25b3d04bb8364089cafdf8deb6846b6
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:59:18Z
date_updated: 2023-08-03T11:59:18Z
file_id: '13552'
file_name: Fig6_a_1.tif
file_size: 121446390
relation: main_file
success: 1
- access_level: open_access
checksum: 4361e10db6ec48c2d4579ac089ff3ca3
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:59:22Z
date_updated: 2023-08-03T11:59:22Z
file_id: '13553'
file_name: Fig6_a_2.tif
file_size: 264412158
relation: main_file
success: 1
- access_level: open_access
checksum: fe3a00ae75fb3388438e53ced92a9498
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:59:21Z
date_updated: 2023-08-03T11:59:21Z
file_id: '13554'
file_name: Fig6_a_3.tif
file_size: 57399051
relation: main_file
success: 1
- access_level: open_access
checksum: 4372c13d6dd2274aa749799b8e96bf06
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:59:21Z
date_updated: 2023-08-03T11:59:21Z
file_id: '13555'
file_name: Fig6_b_left.tif
file_size: 6003163
relation: main_file
success: 1
- access_level: open_access
checksum: f7ae4e50f2f4d414c598bddd691b722a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:59:21Z
date_updated: 2023-08-03T11:59:21Z
file_id: '13556'
file_name: Fig6_b_right.tif
file_size: 511265
relation: main_file
success: 1
- access_level: open_access
checksum: cde658a9ca666bdef1b29613ab72092d
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:59:39Z
date_updated: 2023-08-03T11:59:39Z
file_id: '13557'
file_name: Fig6_c_n2v.tif
file_size: 467125933
relation: main_file
success: 1
- access_level: open_access
checksum: 57e73c1fedcee4bd8ab62518baa0e0e5
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:59:36Z
date_updated: 2023-08-03T11:59:36Z
file_id: '13558'
file_name: Fig6_c.tif
file_size: 322251440
relation: main_file
success: 1
- access_level: open_access
checksum: 53175073b83ab569241ae64ef7f180b3
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:59:38Z
date_updated: 2023-08-03T11:59:38Z
file_id: '13559'
file_name: Fig6_d_1.tif
file_size: 37641738
relation: main_file
success: 1
- access_level: open_access
checksum: af97423e1077af85465a5e39fa25d1e4
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:59:40Z
date_updated: 2023-08-03T11:59:40Z
file_id: '13560'
file_name: Fig6_d_2.tif
file_size: 70596929
relation: main_file
success: 1
- access_level: open_access
checksum: f1fd7a9fa2a12a930fe35bdf53ba3ff7
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:59:42Z
date_updated: 2023-08-03T11:59:42Z
file_id: '13561'
file_name: Fig6_d_3.tif
file_size: 15303146
relation: main_file
success: 1
- access_level: open_access
checksum: 95655df5cdb05f09912298de9a3711b4
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:59:41Z
date_updated: 2023-08-03T11:59:41Z
file_id: '13562'
file_name: Fig6_d_4.tif
file_size: 893051
relation: main_file
success: 1
- access_level: open_access
checksum: 4d722b4e09ce617252d284f78ea2ee30
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:59:58Z
date_updated: 2023-08-03T11:59:58Z
file_id: '13563'
file_name: Fig6_e.tif
file_size: 381232200
relation: main_file
success: 1
- access_level: open_access
checksum: d1eda9599f422a614404dd112f0c3185
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T11:59:58Z
date_updated: 2023-08-03T11:59:58Z
file_id: '13564'
file_name: Fig6_f.tif
file_size: 345804470
relation: main_file
success: 1
- access_level: open_access
checksum: 1cd202570f964b78e1f55c987d5d5de1
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:00:08Z
date_updated: 2023-08-03T12:00:08Z
file_id: '13565'
file_name: Fig6_g.tif
file_size: 346119927
relation: main_file
success: 1
- access_level: open_access
checksum: 78cbf1906ff8746ed524c62f8f580f52
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:00:02Z
date_updated: 2023-08-03T12:00:02Z
file_id: '13566'
file_name: Fig6_h.tif
file_size: 7064977
relation: main_file
success: 1
- access_level: open_access
checksum: 21635ce59f1ae5a334aaad3f4c0b171c
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:00:03Z
date_updated: 2023-08-03T12:00:03Z
file_id: '13567'
file_name: Fig6_i.tif
file_size: 7110129
relation: main_file
success: 1
- access_level: open_access
checksum: 704962856f2a024ce1f321a1785556e3
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:00:07Z
date_updated: 2023-08-03T12:00:07Z
file_id: '13568'
file_name: Fig6_j.tif
file_size: 110297540
relation: main_file
success: 1
- access_level: open_access
checksum: 4b74ba5ae1e2bb2201bf51c74d733268
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:00:07Z
date_updated: 2023-08-03T12:00:07Z
file_id: '13569'
file_name: Fig6_k.tif
file_size: 11117689
relation: main_file
success: 1
- access_level: open_access
checksum: a8efa3007df4e9e0f80c7a2bbc451178
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:05:41Z
date_updated: 2023-08-03T12:05:41Z
file_id: '13570'
file_name: Extdata_01_a_1.tif
file_size: 1287107
relation: main_file
success: 1
- access_level: open_access
checksum: 7f24b6c84ce96a67347eb5ef4c43fac1
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:05:41Z
date_updated: 2023-08-03T12:05:41Z
file_id: '13571'
file_name: Extdata_01_a_2.tif
file_size: 58307
relation: main_file
success: 1
- access_level: open_access
checksum: fa7ae4eefc11b9b60c4ab80f6e839b73
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:05:41Z
date_updated: 2023-08-03T12:05:41Z
file_id: '13572'
file_name: Extdata_01_a_3.tif
file_size: 1283209
relation: main_file
success: 1
- access_level: open_access
checksum: cec9a5eb87f1b56e64626a00c6d0e53d
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:05:41Z
date_updated: 2023-08-03T12:05:41Z
file_id: '13573'
file_name: Extdata_01_a_4.tif
file_size: 54409
relation: main_file
success: 1
- access_level: open_access
checksum: 450e4786d66d5059028420153908a4dc
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T12:05:41Z
date_updated: 2023-08-03T12:05:41Z
file_id: '13574'
file_name: Extdata_01_c_1.png
file_size: 2431
relation: main_file
success: 1
- access_level: open_access
checksum: feb758609b399cf644dd3ae7cd75fb96
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T12:05:41Z
date_updated: 2023-08-03T12:05:41Z
file_id: '13575'
file_name: Extdata_01_c_2.png
file_size: 612
relation: main_file
success: 1
- access_level: open_access
checksum: 52f43300a50f83f9a6ff1409324086ee
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:05:41Z
date_updated: 2023-08-03T12:05:41Z
file_id: '13576'
file_name: Extdata_01_d_1.tif
file_size: 433981
relation: main_file
success: 1
- access_level: open_access
checksum: 28925dcf8792f524e286beb16b0c532c
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:05:41Z
date_updated: 2023-08-03T12:05:41Z
file_id: '13577'
file_name: Extdata_01_d_2.tif
file_size: 19649
relation: main_file
success: 1
- access_level: open_access
checksum: c93b2f0426c80d18e252435f1e146568
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:05:41Z
date_updated: 2023-08-03T12:05:41Z
file_id: '13578'
file_name: Extdata_01_d_3.tif
file_size: 433981
relation: main_file
success: 1
- access_level: open_access
checksum: c0ed722a768001431f47646ef98c44da
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:05:41Z
date_updated: 2023-08-03T12:05:41Z
file_id: '13579'
file_name: Extdata_01_d_4.tif
file_size: 19649
relation: main_file
success: 1
- access_level: open_access
checksum: db9d386276b985b8e702f797e910bd0b
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T12:05:41Z
date_updated: 2023-08-03T12:05:41Z
file_id: '13580'
file_name: Extdata_01_f_1.png
file_size: 4752
relation: main_file
success: 1
- access_level: open_access
checksum: 244f6645d191c50d997c0dc6a15535ec
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T12:05:41Z
date_updated: 2023-08-03T12:05:41Z
file_id: '13581'
file_name: Extdata_01_f_2.png
file_size: 2698
relation: main_file
success: 1
- access_level: open_access
checksum: 3d6100b836d850b38e66e0f5a7919495
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:07:27Z
date_updated: 2023-08-03T12:07:27Z
file_id: '13582'
file_name: Extdata_02_a.tif
file_size: 24003247
relation: main_file
success: 1
- access_level: open_access
checksum: 3cd6a3b7bf2061cf5c7810c0001236e5
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:07:27Z
date_updated: 2023-08-03T12:07:27Z
file_id: '13583'
file_name: Extdata_02_b.tif
file_size: 1164723
relation: main_file
success: 1
- access_level: open_access
checksum: d87c82d663ffea379cc86c56981e2e16
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:10:32Z
date_updated: 2023-08-03T12:10:32Z
file_id: '13584'
file_name: Extdata_03_SYPH1_xy_1.tif
file_size: 7109763
relation: main_file
success: 1
- access_level: open_access
checksum: a3703d0d26393578d4ba466681fc6be8
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:10:32Z
date_updated: 2023-08-03T12:10:32Z
file_id: '13585'
file_name: Extdata_03_SYPH1_xz_1-2.tif
file_size: 27791
relation: main_file
success: 1
- access_level: open_access
checksum: f653ac7d531cf9896cbd6a9edf2a7759
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:10:32Z
date_updated: 2023-08-03T12:10:32Z
file_id: '13586'
file_name: Extdata_03_SYPH1_xz_3-4.tif
file_size: 27721
relation: main_file
success: 1
- access_level: open_access
checksum: 04edbb337df4d5470e033a4f53c07300
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:10:33Z
date_updated: 2023-08-03T12:10:33Z
file_id: '13587'
file_name: Extdata_03_SYPH1_xz_n2v.tif
file_size: 57657482
relation: main_file
success: 1
- access_level: open_access
checksum: 09e1fe2dd3a1e8349693fda55d0985ca
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:10:34Z
date_updated: 2023-08-03T12:10:34Z
file_id: '13588'
file_name: Extdata_03_SYPH1_xz.tif
file_size: 57657527
relation: main_file
success: 1
- access_level: open_access
checksum: 458f8d486cb63876c6664cde4a9be27c
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:12:25Z
date_updated: 2023-08-03T12:12:25Z
file_id: '13589'
file_name: Extdata_03_SYP1_xy_1.tif
file_size: 7109763
relation: main_file
success: 1
- access_level: open_access
checksum: e2dfccc882d85b660d65a596e1a8cbac
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:12:25Z
date_updated: 2023-08-03T12:12:25Z
file_id: '13590'
file_name: Extdata_03_SYP1_xy_2-3.tif
file_size: 72963
relation: main_file
success: 1
- access_level: open_access
checksum: a331be6052c68cc027cdb79f15447d9a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:12:25Z
date_updated: 2023-08-03T12:12:25Z
file_id: '13591'
file_name: Extdata_03_SYP1_xz_1-2.tif
file_size: 27724
relation: main_file
success: 1
- access_level: open_access
checksum: 4de626b035b43feaacd923fca411e6a2
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:12:25Z
date_updated: 2023-08-03T12:12:25Z
file_id: '13592'
file_name: Extdata_03_SYP1_xz_3-4.tif
file_size: 27724
relation: main_file
success: 1
- access_level: open_access
checksum: d8076e927a074f024924d9bdb6fdd5e6
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:12:30Z
date_updated: 2023-08-03T12:12:30Z
file_id: '13593'
file_name: Extdata_03_SYP1_xz_n2v.tif
file_size: 214613644
relation: main_file
success: 1
- access_level: open_access
checksum: 79cf7d0f450c397caa877dd06b52f8df
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:12:30Z
date_updated: 2023-08-03T12:12:30Z
file_id: '13594'
file_name: Extdata_03_SYP1_xz.tif
file_size: 214613687
relation: main_file
success: 1
- access_level: open_access
checksum: 60ac6ea988d9b8bdaba2f09e0e1ef370
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:14:29Z
date_updated: 2023-08-03T12:14:29Z
file_id: '13595'
file_name: Extdata03_VAMP2_xy_1.tif
file_size: 7109747
relation: main_file
success: 1
- access_level: open_access
checksum: 92bf312da2dd356aa4fc9a0e7d811af2
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:14:29Z
date_updated: 2023-08-03T12:14:29Z
file_id: '13596'
file_name: Extdata03_VAMP2_xy_2-3.tif
file_size: 72947
relation: main_file
success: 1
- access_level: open_access
checksum: 9319e293092eeee24e3c658fc178af1a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:14:29Z
date_updated: 2023-08-03T12:14:29Z
file_id: '13597'
file_name: Extdata03_VAMP2_xz_1-2.tif
file_size: 27724
relation: main_file
success: 1
- access_level: open_access
checksum: a627d7fd9a89bdde968e6d9bff846254
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:14:29Z
date_updated: 2023-08-03T12:14:29Z
file_id: '13598'
file_name: Extdata03_VAMP2_xz_3-4.tif
file_size: 27708
relation: main_file
success: 1
- access_level: open_access
checksum: 7a5363a185edce59ce57535f7d855092
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:14:32Z
date_updated: 2023-08-03T12:14:32Z
file_id: '13599'
file_name: Extdata03_VAMP2_xz_n2v.tif
file_size: 102457485
relation: main_file
success: 1
- access_level: open_access
checksum: 8e7fc4d00fff8ec6d9340e969f37e176
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:14:32Z
date_updated: 2023-08-03T12:14:32Z
file_id: '13600'
file_name: Extdata03_VAMP2_xz.tif
file_size: 102457527
relation: main_file
success: 1
- access_level: open_access
checksum: be17472f73ed8cd02a700b861f1dbac0
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:16:08Z
date_updated: 2023-08-03T12:16:08Z
file_id: '13601'
file_name: Extdata04_VGLUT_xy_1.tif
file_size: 11117763
relation: main_file
success: 1
- access_level: open_access
checksum: dbc3ec477f491ce3e98ab40475bd90ca
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:16:08Z
date_updated: 2023-08-03T12:16:08Z
file_id: '13602'
file_name: Extdata04_VGLUT_xy_2-3.tif
file_size: 72947
relation: main_file
success: 1
- access_level: open_access
checksum: 8ee877e6b843bb0e38febb0481962d69
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:16:08Z
date_updated: 2023-08-03T12:16:08Z
file_id: '13603'
file_name: Extdata04_VGLUT_xz_1-2.tif
file_size: 53367
relation: main_file
success: 1
- access_level: open_access
checksum: 9873f54d50955a2c204d0559c87aa13d
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:16:08Z
date_updated: 2023-08-03T12:16:08Z
file_id: '13604'
file_name: Extdata04_VGLUT_xz_3-4.tif
file_size: 53358
relation: main_file
success: 1
- access_level: open_access
checksum: 8eda08ae5981fcfa3758d0320b1923af
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:16:11Z
date_updated: 2023-08-03T12:16:11Z
file_id: '13605'
file_name: Extdata04_VGLUT_xz_n2v.tif
file_size: 144076208
relation: main_file
success: 1
- access_level: open_access
checksum: bc0b10229d498f60996a5b05cb87c428
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:16:10Z
date_updated: 2023-08-03T12:16:10Z
file_id: '13606'
file_name: Extdata04_VGLUT_xz.tif
file_size: 72071440
relation: main_file
success: 1
- access_level: open_access
checksum: e8d093ce7d98ea5647d8a80e3084c40b
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:32:32Z
date_updated: 2023-08-03T12:32:32Z
file_id: '13607'
file_name: Extdata03_VGAT_xy_1.tif
file_size: 7109763
relation: main_file
success: 1
- access_level: open_access
checksum: 36590ca7a586de7ad76d3ad659c38995
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:32:32Z
date_updated: 2023-08-03T12:32:32Z
file_id: '13608'
file_name: Extdata03_VGAT_xy_2-3.tif
file_size: 72947
relation: main_file
success: 1
- access_level: open_access
checksum: 3914c7709f69d4d18f23a9fb6dc64572
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:32:32Z
date_updated: 2023-08-03T12:32:32Z
file_id: '13609'
file_name: Extdata03_VGAT_xz_1-2.tif
file_size: 53355
relation: main_file
success: 1
- access_level: open_access
checksum: fa98aa521adaefb9e4476fe519e88e59
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:32:32Z
date_updated: 2023-08-03T12:32:32Z
file_id: '13610'
file_name: Extdata03_VGAT_xz_3-4.tif
file_size: 53339
relation: main_file
success: 1
- access_level: open_access
checksum: cd6f384c51756977e37f45043c913252
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:32:36Z
date_updated: 2023-08-03T12:32:36Z
file_id: '13611'
file_name: Extdata03_VGAT_xz_n2v.tif
file_size: 204861338
relation: main_file
success: 1
- access_level: open_access
checksum: fb7e46feda5ac07877a91ad963da0e31
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:32:35Z
date_updated: 2023-08-03T12:32:35Z
file_id: '13612'
file_name: Extdata03_VGAT_xz.tif
file_size: 102457527
relation: main_file
success: 1
- access_level: open_access
checksum: fe033e0a377d391cd8e4af04987d9900
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T12:36:46Z
date_updated: 2023-08-03T12:36:46Z
file_id: '13613'
file_name: Extdata04_MUNC_xy_1.png
file_size: 4348932
relation: main_file
success: 1
- access_level: open_access
checksum: 771d8e2b9192b6620f54ab30e4fad594
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:35:58Z
date_updated: 2023-08-03T12:35:58Z
file_id: '13614'
file_name: Extdata04_MUNC_xy_2-3.tif
file_size: 72947
relation: main_file
success: 1
- access_level: open_access
checksum: 4256d8f06fa2077b352776cf76b46618
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:35:58Z
date_updated: 2023-08-03T12:35:58Z
file_id: '13615'
file_name: Extdata04_MUNC_xz_1-2.tif
file_size: 53435
relation: main_file
success: 1
- access_level: open_access
checksum: 0b9365638c81d545e773170cf04b04b8
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:35:58Z
date_updated: 2023-08-03T12:35:58Z
file_id: '13616'
file_name: Extdata04_MUNC_xz_3-4.tif
file_size: 55941
relation: main_file
success: 1
- access_level: open_access
checksum: 9fa62688dab03c592cec47bf5d1c304d
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:36:04Z
date_updated: 2023-08-03T12:36:04Z
file_id: '13617'
file_name: Extdata04_MUNC_xz_n2v.tif
file_size: 204861404
relation: main_file
success: 1
- access_level: open_access
checksum: 39f710080a26136dbbe4c8916b434c65
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:36:02Z
date_updated: 2023-08-03T12:36:02Z
file_id: '13618'
file_name: Extdata04_MUNC_xz.tif
file_size: 102457527
relation: main_file
success: 1
- access_level: open_access
checksum: eaabc8112645a73f4326e621b4e6ad0a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:38:39Z
date_updated: 2023-08-03T12:38:39Z
file_id: '13619'
file_name: Extdata04_BASSOON_xy_1.tif
file_size: 11117757
relation: main_file
success: 1
- access_level: open_access
checksum: 15f624d29c473ce6e0ae7e466efc059a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:38:39Z
date_updated: 2023-08-03T12:38:39Z
file_id: '13620'
file_name: Extdata04_BASSOON_xy_2-3.tif
file_size: 74041
relation: main_file
success: 1
- access_level: open_access
checksum: 1cb4b4d219767a30072c804a07140240
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:38:39Z
date_updated: 2023-08-03T12:38:39Z
file_id: '13621'
file_name: Extdata04_BASSOON_xz_1-2.tif
file_size: 53435
relation: main_file
success: 1
- access_level: open_access
checksum: 1bac9c192da9375d81cb3747f48c9be4
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:38:39Z
date_updated: 2023-08-03T12:38:39Z
file_id: '13622'
file_name: Extdata04_BASSOON_xz_3-4.tif
file_size: 53362
relation: main_file
success: 1
- access_level: open_access
checksum: 57fa91bfb1e2937e3449e57096b6fc74
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:38:50Z
date_updated: 2023-08-03T12:38:50Z
file_id: '13623'
file_name: Extdata04_BASSOON_xz_n2v.tif
file_size: 576071410
relation: main_file
success: 1
- access_level: open_access
checksum: ac51a734dcf7d1b94afcd4a471f10626
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:38:46Z
date_updated: 2023-08-03T12:38:46Z
file_id: '13624'
file_name: Extdata04_BASSOON_xz.tif
file_size: 288066640
relation: main_file
success: 1
- access_level: open_access
checksum: 244043f7acba250d560e29123702dcd7
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:40:57Z
date_updated: 2023-08-03T12:40:57Z
file_id: '13625'
file_name: Extdata04_HOMER1_xy_1.tif
file_size: 7109763
relation: main_file
success: 1
- access_level: open_access
checksum: eff51ff97539f6491989bfc3d3f88860
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:40:57Z
date_updated: 2023-08-03T12:40:57Z
file_id: '13626'
file_name: Extdata04_HOMER1_xy_2-3.tif
file_size: 72963
relation: main_file
success: 1
- access_level: open_access
checksum: df35046d9bca4e97a5625c5a55218cfb
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:40:57Z
date_updated: 2023-08-03T12:40:57Z
file_id: '13627'
file_name: Extdata04_HOMER1_xz_1-2.tif
file_size: 53375
relation: main_file
success: 1
- access_level: open_access
checksum: 5dc7536f7aaea084dfc329537d8412ce
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:40:57Z
date_updated: 2023-08-03T12:40:57Z
file_id: '13628'
file_name: Extdata04_HOMER1_xz_3-4.tif
file_size: 53359
relation: main_file
success: 1
- access_level: open_access
checksum: 0b407669a26b9d7730a41361ceffda9a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:41:00Z
date_updated: 2023-08-03T12:41:00Z
file_id: '13629'
file_name: Extdata04_HOMER1_xz_n2v.tif
file_size: 204861339
relation: main_file
success: 1
- access_level: open_access
checksum: f95a0da9bea8b605fc2ed310190836b3
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:40:59Z
date_updated: 2023-08-03T12:40:59Z
file_id: '13630'
file_name: Extdata04_HOMER1_xz.tif
file_size: 102457527
relation: main_file
success: 1
- access_level: open_access
checksum: cf74307696548e7aa90e59a0935a74a1
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:45:08Z
date_updated: 2023-08-03T12:45:08Z
file_id: '13631'
file_name: Extdata04_SHANK2_xy_1.tif
file_size: 7120361
relation: main_file
success: 1
- access_level: open_access
checksum: 7b3490246df4f5bb68d0df682161820f
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:45:08Z
date_updated: 2023-08-03T12:45:08Z
file_id: '13632'
file_name: Extdata04_SHANK2_xy_2-3.tif
file_size: 72973
relation: main_file
success: 1
- access_level: open_access
checksum: c599d6830e61c386219e266f4717fe7c
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:45:08Z
date_updated: 2023-08-03T12:45:08Z
file_id: '13633'
file_name: Extdata04_SHANK2_xz_1-2.tif
file_size: 53443
relation: main_file
success: 1
- access_level: open_access
checksum: 5b9912b2a408d224ad669f39dc8d5bc6
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:45:08Z
date_updated: 2023-08-03T12:45:08Z
file_id: '13634'
file_name: Extdata04_SHANK2_xz_3-4.tif
file_size: 53362
relation: main_file
success: 1
- access_level: open_access
checksum: 17f2064ceeb99cbb51208c27b1961ed5
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:45:30Z
date_updated: 2023-08-03T12:45:30Z
file_id: '13635'
file_name: Extdata04_SHANK2_xz_n2v.tif
file_size: 691291157
relation: main_file
success: 1
- access_level: open_access
checksum: 21f1bb8d2a00c88bdd6febe6285acc2a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:45:26Z
date_updated: 2023-08-03T12:45:26Z
file_id: '13636'
file_name: Extdata04_SHANK2_xz.tif
file_size: 518519275
relation: main_file
success: 1
- access_level: open_access
checksum: 47597ca873f1ea81cd4f7e9bfbb34aa4
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:46:25Z
date_updated: 2023-08-03T12:46:25Z
file_id: '13637'
file_name: Extdata04_GEPHYRIN_xy_1.tif
file_size: 752109
relation: main_file
success: 1
- access_level: open_access
checksum: 14ed7ae64eb783e6b30f824f21959d0f
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:46:25Z
date_updated: 2023-08-03T12:46:25Z
file_id: '13638'
file_name: Extdata04_GEPHYRIN_xy_2-3.tif
file_size: 72909
relation: main_file
success: 1
- access_level: open_access
checksum: e361e226428d7b23618eed35b1cad080
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:46:25Z
date_updated: 2023-08-03T12:46:25Z
file_id: '13639'
file_name: Extdata04_GEPHYRIN_xz_1-2.tif
file_size: 53375
relation: main_file
success: 1
- access_level: open_access
checksum: abe7cee22f69fc2bf1a3ff9955ccf45a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:46:25Z
date_updated: 2023-08-03T12:46:25Z
file_id: '13640'
file_name: Extdata04_GEPHYRIN_xz_3-4.tif
file_size: 53360
relation: main_file
success: 1
- access_level: open_access
checksum: 59b49b451a63c5ac06fa31a17640c1a2
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:46:27Z
date_updated: 2023-08-03T12:46:27Z
file_id: '13641'
file_name: Extdata04_GEPHYRIN_xz_n2v.tif
file_size: 73174939
relation: main_file
success: 1
- access_level: open_access
checksum: 1ee1feea85c8319ebc6c49147502e412
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:46:26Z
date_updated: 2023-08-03T12:46:26Z
file_id: '13642'
file_name: Extdata04_GEPHYRIN_xz.tif
file_size: 36614327
relation: main_file
success: 1
- access_level: open_access
checksum: 64d9d868ef89c5cfc65cb199aff831b4
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:52:23Z
date_updated: 2023-08-03T12:52:23Z
file_id: '13643'
file_name: Extdata06_a-b_n2v.tif
file_size: 2195652677
relation: main_file
success: 1
- access_level: open_access
checksum: df41d97987798715b1f66e6e72be169b
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:51:41Z
date_updated: 2023-08-03T12:51:41Z
file_id: '13644'
file_name: Extdata06_a-b.tif
file_size: 1097875840
relation: main_file
success: 1
- access_level: open_access
checksum: 95a3eaa3b70e964f6871a5765a53659b
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:52:57Z
date_updated: 2023-08-03T12:52:57Z
file_id: '13645'
file_name: Extdata07_01_bottom.tif
file_size: 3564577
relation: main_file
success: 1
- access_level: open_access
checksum: 80b41ad0de73fd61eb67a35262627fac
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:52:57Z
date_updated: 2023-08-03T12:52:57Z
file_id: '13646'
file_name: Extdata07_01_top.tif
file_size: 11958844
relation: main_file
success: 1
- access_level: open_access
checksum: f694a0f11e2f782702cb4c411941873a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:54:27Z
date_updated: 2023-08-03T12:54:27Z
file_id: '13647'
file_name: Extdata07_2_bottom.tif
file_size: 3564581
relation: main_file
success: 1
- access_level: open_access
checksum: b8b1a1339a25806615c0aa7906a032ff
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:54:27Z
date_updated: 2023-08-03T12:54:27Z
file_id: '13648'
file_name: Extdata07_2_top.tif
file_size: 11973592
relation: main_file
success: 1
- access_level: open_access
checksum: 8a24eb623d65d809fe8afbd527528a77
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:54:27Z
date_updated: 2023-08-03T12:54:27Z
file_id: '13649'
file_name: Extdata07_3_bottom.tif
file_size: 1281901
relation: main_file
success: 1
- access_level: open_access
checksum: 816b35def703bc48d55b0293fcd8212f
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:54:27Z
date_updated: 2023-08-03T12:54:27Z
file_id: '13650'
file_name: Extdata07_3_top.tif
file_size: 16569776
relation: main_file
success: 1
- access_level: open_access
checksum: 7f1375ab8cf28cd136e2e44d1fdfd87d
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:54:27Z
date_updated: 2023-08-03T12:54:27Z
file_id: '13651'
file_name: Extdata07_04_bottom.tif
file_size: 3564595
relation: main_file
success: 1
- access_level: open_access
checksum: b1dbda28e2a010968716c0411568f139
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:54:27Z
date_updated: 2023-08-03T12:54:27Z
file_id: '13652'
file_name: Extdata07_04_top.tif
file_size: 5896404
relation: main_file
success: 1
- access_level: open_access
checksum: d6e96b7c8e6a7084c14eda83a4dd778a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:54:28Z
date_updated: 2023-08-03T12:54:28Z
file_id: '13653'
file_name: Extdata07_5_bottom.tif
file_size: 3564609
relation: main_file
success: 1
- access_level: open_access
checksum: a647f89a3048f71512cc58c9e53ec022
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:54:28Z
date_updated: 2023-08-03T12:54:28Z
file_id: '13654'
file_name: Extdata07_5_top.tif
file_size: 15555618
relation: main_file
success: 1
- access_level: open_access
checksum: 66becb046fe591914df572617d720202
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:54:28Z
date_updated: 2023-08-03T12:54:28Z
file_id: '13655'
file_name: Extdata07_6_bottom.tif
file_size: 3564577
relation: main_file
success: 1
- access_level: open_access
checksum: 5d76b2ad7d7acbb1afa27cf52194b1cb
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:54:28Z
date_updated: 2023-08-03T12:54:28Z
file_id: '13656'
file_name: Extdata07_6_top.tif
file_size: 6038186
relation: main_file
success: 1
- access_level: open_access
checksum: 7f137bdea0f0acb3db75c983ce44ab44
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:54:28Z
date_updated: 2023-08-03T12:54:28Z
file_id: '13657'
file_name: Extdata07_7_bottom.tif
file_size: 3560937
relation: main_file
success: 1
- access_level: open_access
checksum: 479e26106280eb61a2d74e29137a2e43
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:54:28Z
date_updated: 2023-08-03T12:54:28Z
file_id: '13658'
file_name: Extdata07_7_top.tif
file_size: 12031850
relation: main_file
success: 1
- access_level: open_access
checksum: 8426197ad283c1bc83e3193f323d5f5a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:54:28Z
date_updated: 2023-08-03T12:54:28Z
file_id: '13659'
file_name: Extdata07_8_bottom.tif
file_size: 3560937
relation: main_file
success: 1
- access_level: open_access
checksum: b9f75a82b564e1c5c363a495d078f6b7
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:54:28Z
date_updated: 2023-08-03T12:54:28Z
file_id: '13660'
file_name: Extdata07_8_top.tif
file_size: 22877176
relation: main_file
success: 1
- access_level: open_access
checksum: 7f1a9f3bb9611362995ae832b2607f4d
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:54:28Z
date_updated: 2023-08-03T12:54:28Z
file_id: '13661'
file_name: Extdata07_9_bottom.tif
file_size: 3564605
relation: main_file
success: 1
- access_level: open_access
checksum: 40286bcb876b655d7421534d0215e86b
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T12:54:28Z
date_updated: 2023-08-03T12:54:28Z
file_id: '13662'
file_name: Extdata07_9_top.tif
file_size: 2744190
relation: main_file
success: 1
- access_level: open_access
checksum: 4af220986cc94d412c2354aa7e6c8cce
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:00:03Z
date_updated: 2023-08-03T13:00:03Z
file_id: '13663'
file_name: Extdata08_6_left.png
file_size: 7243611
relation: main_file
success: 1
- access_level: open_access
checksum: af9c2299f1005a3ccc39f41082cea642
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:00:03Z
date_updated: 2023-08-03T13:00:03Z
file_id: '13664'
file_name: Extdata08_6_right.tif
file_size: 5562487
relation: main_file
success: 1
- access_level: open_access
checksum: 63ef28a174215c70e31d2cabf67d90fc
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:00:04Z
date_updated: 2023-08-03T13:00:04Z
file_id: '13665'
file_name: Extdata08_7_left.tif
file_size: 34745956
relation: main_file
success: 1
- access_level: open_access
checksum: 46de918dfe5f3c23e497ee3daa608dd9
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:00:03Z
date_updated: 2023-08-03T13:00:03Z
file_id: '13666'
file_name: Extdata08_7_right.tif
file_size: 5562483
relation: main_file
success: 1
- access_level: open_access
checksum: 8243a7985d2902446183adc35519a0c8
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:00:04Z
date_updated: 2023-08-03T13:00:04Z
file_id: '13667'
file_name: Extdata08_b_1_left.tif
file_size: 31506150
relation: main_file
success: 1
- access_level: open_access
checksum: 857cffa31569efcd5917f9802a106d58
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:00:04Z
date_updated: 2023-08-03T13:00:04Z
file_id: '13668'
file_name: Extdata08_b_1_right.tif
file_size: 11117705
relation: main_file
success: 1
- access_level: open_access
checksum: e34902de9119d2cd9f1910f610627c5f
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:00:04Z
date_updated: 2023-08-03T13:00:04Z
file_id: '13669'
file_name: Extdata08_b_2_left.png
file_size: 3540493
relation: main_file
success: 1
- access_level: open_access
checksum: 1247d636ac5af22e8950ffd2ff213fea
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:00:05Z
date_updated: 2023-08-03T13:00:05Z
file_id: '13670'
file_name: Extdata08_b_2_right.tif
file_size: 5562553
relation: main_file
success: 1
- access_level: open_access
checksum: f47c2d3f6824e08853ae2631f6ee7c5f
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:00:05Z
date_updated: 2023-08-03T13:00:05Z
file_id: '13671'
file_name: Extdata08_b_3_left.png
file_size: 3541547
relation: main_file
success: 1
- access_level: open_access
checksum: 1247d636ac5af22e8950ffd2ff213fea
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:00:05Z
date_updated: 2023-08-03T13:00:05Z
file_id: '13672'
file_name: Extdata08_b_3_right.tif
file_size: 5562553
relation: main_file
success: 1
- access_level: open_access
checksum: e90a95ec902a683678acd70336852fd9
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:00:05Z
date_updated: 2023-08-03T13:00:05Z
file_id: '13673'
file_name: Extdata08_b_4_left.tif
file_size: 25819844
relation: main_file
success: 1
- access_level: open_access
checksum: 94cd44cd1c8c7a87ffd5861bf88561a1
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:00:05Z
date_updated: 2023-08-03T13:00:05Z
file_id: '13674'
file_name: Extdata08_b_4_right.tif
file_size: 5561131
relation: main_file
success: 1
- access_level: open_access
checksum: fd4ca56dc5c48ad4546df22daef04efc
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:00:06Z
date_updated: 2023-08-03T13:00:06Z
file_id: '13675'
file_name: Extdata08_b_5_left.tif
file_size: 38786287
relation: main_file
success: 1
- access_level: open_access
checksum: 52c04890160c4e0f23d3fe2d3ed0c8e7
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:00:06Z
date_updated: 2023-08-03T13:00:06Z
file_id: '13676'
file_name: Extdata08_b_5_right.tif
file_size: 5562487
relation: main_file
success: 1
- access_level: open_access
checksum: 47ee6f4b083130d5bb720bcf8a832443
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:04:52Z
date_updated: 2023-08-03T13:04:52Z
file_id: '13677'
file_name: Extdata08_a_1-1.png
file_size: 2133527
relation: main_file
success: 1
- access_level: open_access
checksum: 5ca2279c372b3b7dbce3ea5658a68399
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:04:52Z
date_updated: 2023-08-03T13:04:52Z
file_id: '13678'
file_name: Extdata08_a_1-2.png
file_size: 1782607
relation: main_file
success: 1
- access_level: open_access
checksum: 34b7781e3e4abf9f30a0c85db156b6d5
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:04:52Z
date_updated: 2023-08-03T13:04:52Z
file_id: '13679'
file_name: Extdata08_a_2.png
file_size: 5117469
relation: main_file
success: 1
- access_level: open_access
checksum: 25717007393682098d2208bd0676a0f7
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:04:52Z
date_updated: 2023-08-03T13:04:52Z
file_id: '13680'
file_name: Extdata08_a_3.png
file_size: 6911658
relation: main_file
success: 1
- access_level: open_access
checksum: b4b003809acec33c71628066744c7ea9
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:04:53Z
date_updated: 2023-08-03T13:04:53Z
file_id: '13681'
file_name: Extdata08_a_4.png
file_size: 8579427
relation: main_file
success: 1
- access_level: open_access
checksum: 4410976cf867ecacf8f197dbd28cc5a0
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:04:53Z
date_updated: 2023-08-03T13:04:53Z
file_id: '13682'
file_name: Extdata08_a_5.png
file_size: 9675065
relation: main_file
success: 1
- access_level: open_access
checksum: a235dd204f28d3323883e044b031b984
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:04:53Z
date_updated: 2023-08-03T13:04:53Z
file_id: '13683'
file_name: Extdata08_a_6.png
file_size: 9769588
relation: main_file
success: 1
- access_level: open_access
checksum: 0e2b768e4eb7200cf6fe28ba511a5ef6
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:04:53Z
date_updated: 2023-08-03T13:04:53Z
file_id: '13684'
file_name: Extdata08_a_7.png
file_size: 9114791
relation: main_file
success: 1
- access_level: open_access
checksum: df4a01c62233ee8ed601c4b90d7780d0
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:04:57Z
date_updated: 2023-08-03T13:04:57Z
file_id: '13685'
file_name: Extdata08_a_8.png
file_size: 124540688
relation: main_file
success: 1
- access_level: open_access
checksum: 1f407c7915e2717a56fec258708e7b7a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:11:30Z
date_updated: 2023-08-03T13:11:30Z
file_id: '13686'
file_name: Exdata09_c_n2v.tif
file_size: 204861336
relation: main_file
success: 1
- access_level: open_access
checksum: 9089dc7c9914edf9750eebd65819708d
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:11:26Z
date_updated: 2023-08-03T13:11:26Z
file_id: '13687'
file_name: Extdata09_a_zoom.tif
file_size: 252149
relation: main_file
success: 1
- access_level: open_access
checksum: 62d295a62cb8dd36c268b28cf0251322
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:11:26Z
date_updated: 2023-08-03T13:11:26Z
file_id: '13688'
file_name: Extdata09_a.tif
file_size: 11117705
relation: main_file
success: 1
- access_level: open_access
checksum: e874d8ee287f924c1076134b5b06bdb2
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:11:31Z
date_updated: 2023-08-03T13:11:31Z
file_id: '13689'
file_name: Extdata09_b_n2v.tif
file_size: 256074660
relation: main_file
success: 1
- access_level: open_access
checksum: 488068fff7b42bcf5728739e2a06d742
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:12:53Z
date_updated: 2023-08-03T13:12:53Z
file_id: '13690'
file_name: Extdata10_n2v_CLAHE.tif
file_size: 127914854
relation: main_file
success: 1
- access_level: open_access
checksum: 35351f5af21ce854d41577813a7bdb57
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:21:35Z
date_updated: 2023-08-03T13:21:35Z
file_id: '13691'
file_name: Supplfig01_a_1.png
file_size: 430878
relation: main_file
success: 1
- access_level: open_access
checksum: 36204e9e604206366ffc6f61ec91915b
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:21:35Z
date_updated: 2023-08-03T13:21:35Z
file_id: '13692'
file_name: Supplfig01_a_2.png
file_size: 438843
relation: main_file
success: 1
- access_level: open_access
checksum: 92ccc934c4603b29f4f7a96573e49c83
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:21:35Z
date_updated: 2023-08-03T13:21:35Z
file_id: '13693'
file_name: Supplfig01_a_3.png
file_size: 426713
relation: main_file
success: 1
- access_level: open_access
checksum: e71faa54934bee8ac3e66ce692f542ab
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:21:35Z
date_updated: 2023-08-03T13:21:35Z
file_id: '13694'
file_name: Supplfig01_a_4.tif
file_size: 723221
relation: main_file
success: 1
- access_level: open_access
checksum: 95dc33563f48b650e5ac020bdfd10c48
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:21:35Z
date_updated: 2023-08-03T13:21:35Z
file_id: '13695'
file_name: Supplfig01_a_5.tif
file_size: 723235
relation: main_file
success: 1
- access_level: open_access
checksum: c62df0a9faf1c47af121d77eb1582edd
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:21:35Z
date_updated: 2023-08-03T13:21:35Z
file_id: '13696'
file_name: Supplfig01_b_1.tif
file_size: 1442129
relation: main_file
success: 1
- access_level: open_access
checksum: 8ae157c5a4a543da1193cb8ca12b1919
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:21:35Z
date_updated: 2023-08-03T13:21:35Z
file_id: '13697'
file_name: Supplfig01_b_2.tif
file_size: 725407
relation: main_file
success: 1
- access_level: open_access
checksum: 388370d954ce842781c0d62edfb448a7
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:21:35Z
date_updated: 2023-08-03T13:21:35Z
file_id: '13698'
file_name: Supplfig01_c_1.tif
file_size: 721641
relation: main_file
success: 1
- access_level: open_access
checksum: 6cae58ba3c98bc8253e1c769e93657a7
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:21:35Z
date_updated: 2023-08-03T13:21:35Z
file_id: '13699'
file_name: Supplfig01_c_2.tif
file_size: 6003079
relation: main_file
success: 1
- access_level: open_access
checksum: 85cf013232c72895aefc07f5411a765a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:21:35Z
date_updated: 2023-08-03T13:21:35Z
file_id: '13700'
file_name: Supplfig01_c_3.tif
file_size: 2003311
relation: main_file
success: 1
- access_level: open_access
checksum: dfb33b91066e3f34d3803f59a4105aba
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:21:35Z
date_updated: 2023-08-03T13:21:35Z
file_id: '13701'
file_name: Supplfig01_c_4.tif
file_size: 723271
relation: main_file
success: 1
- access_level: open_access
checksum: 8b899826fe48d7e7536b0b02a2645e87
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:21:35Z
date_updated: 2023-08-03T13:21:35Z
file_id: '13702'
file_name: Supplfig01_d_1.tif
file_size: 721901
relation: main_file
success: 1
- access_level: open_access
checksum: 67529fa6e0f12c272275e823f6045f6d
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:21:35Z
date_updated: 2023-08-03T13:21:35Z
file_id: '13703'
file_name: Supplfig01_d_2.tif
file_size: 721901
relation: main_file
success: 1
- access_level: open_access
checksum: 111a9231f63c775340d3356109715cb0
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:21:35Z
date_updated: 2023-08-03T13:21:35Z
file_id: '13704'
file_name: Supplfig01_e_1.tif
file_size: 723223
relation: main_file
success: 1
- access_level: open_access
checksum: 7685bf02408dcb095a00854ff22763ed
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:21:35Z
date_updated: 2023-08-03T13:21:35Z
file_id: '13705'
file_name: Supplfig01_e_2.tif
file_size: 723223
relation: main_file
success: 1
- access_level: open_access
checksum: 455f5cb9aa8a87b91586a27aca122610
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:26:00Z
date_updated: 2023-08-03T13:26:00Z
file_id: '13706'
file_name: Supplfig02_b_01.tif
file_size: 34821298
relation: main_file
success: 1
- access_level: open_access
checksum: 311545b39aaa2c72755fd8ae190803a5
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:26:00Z
date_updated: 2023-08-03T13:26:00Z
file_id: '13707'
file_name: Supplfig02_b_02.tif
file_size: 32131123
relation: main_file
success: 1
- access_level: open_access
checksum: 682deb61f57d9ca54716160ddd52a6cf
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:26:01Z
date_updated: 2023-08-03T13:26:01Z
file_id: '13708'
file_name: Supplfig02_b_03.tif
file_size: 36872674
relation: main_file
success: 1
- access_level: open_access
checksum: 4f9579c91b2a3f36ff6e66b592907973
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:26:01Z
date_updated: 2023-08-03T13:26:01Z
file_id: '13709'
file_name: Supplfig02_b_04.tif
file_size: 39964115
relation: main_file
success: 1
- access_level: open_access
checksum: 7ae7053673b53dbed59ffb92618f969a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:26:02Z
date_updated: 2023-08-03T13:26:02Z
file_id: '13710'
file_name: Supplfig02_b_05.tif
file_size: 43053091
relation: main_file
success: 1
- access_level: open_access
checksum: 827b26d3d2b6ddc9bced9d6113023ced
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:26:02Z
date_updated: 2023-08-03T13:26:02Z
file_id: '13711'
file_name: Supplfig02_b_06.tif
file_size: 46998147
relation: main_file
success: 1
- access_level: open_access
checksum: bc2e7e8badb42f8e1facc8b7bc96fdda
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:26:03Z
date_updated: 2023-08-03T13:26:03Z
file_id: '13712'
file_name: Supplfig02_b_07.tif
file_size: 45179219
relation: main_file
success: 1
- access_level: open_access
checksum: c2b78aa0f433928afa10a743c5fb73b8
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:26:03Z
date_updated: 2023-08-03T13:26:03Z
file_id: '13713'
file_name: Supplfig02_b_08.tif
file_size: 46978802
relation: main_file
success: 1
- access_level: open_access
checksum: 9cd1ab61cced2c0981e813aeae930855
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:26:04Z
date_updated: 2023-08-03T13:26:04Z
file_id: '13714'
file_name: Supplfig02_b_09.tif
file_size: 48840915
relation: main_file
success: 1
- access_level: open_access
checksum: 3086126338aee6ec4ebc1d3350551197
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:26:04Z
date_updated: 2023-08-03T13:26:04Z
file_id: '13715'
file_name: Supplfig02_b_10.tif
file_size: 45907059
relation: main_file
success: 1
- access_level: open_access
checksum: 69f52c2b3bb5b5f9fef057860b3386fa
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:26:05Z
date_updated: 2023-08-03T13:26:05Z
file_id: '13716'
file_name: Supplfig02_b_11.tif
file_size: 32231538
relation: main_file
success: 1
- access_level: open_access
checksum: defdbeab1e672456bfeafdd1983e779e
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:26:05Z
date_updated: 2023-08-03T13:26:05Z
file_id: '13717'
file_name: Supplfig02_b_12.tif
file_size: 35264963
relation: main_file
success: 1
- access_level: open_access
checksum: 02c566f781b9ad44f04ce0088a1fa27a
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:28:40Z
date_updated: 2023-08-03T13:28:40Z
file_id: '13718'
file_name: Supplfig03_a_std_xy.png
file_size: 63326
relation: main_file
success: 1
- access_level: open_access
checksum: c6c3630ee9a6ed5d207cb68e330da566
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:28:40Z
date_updated: 2023-08-03T13:28:40Z
file_id: '13719'
file_name: Supplfig03_a_std_xz.png
file_size: 50211
relation: main_file
success: 1
- access_level: open_access
checksum: 0dcd4d19e83a7ff259d6aa04d746cd90
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:28:41Z
date_updated: 2023-08-03T13:28:41Z
file_id: '13720'
file_name: Supplfig03_b_std_xy.png
file_size: 52629
relation: main_file
success: 1
- access_level: open_access
checksum: 4785de4a6dcb23b25a06b0da29df5bb5
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:28:41Z
date_updated: 2023-08-03T13:28:41Z
file_id: '13721'
file_name: Supplfig03_b_std_xz.png
file_size: 72245
relation: main_file
success: 1
- access_level: open_access
checksum: 19d0f198bd8a25073e45e7950d7a78c2
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:28:45Z
date_updated: 2023-08-03T13:28:45Z
file_id: '13722'
file_name: Supplfig03_model1.tif
file_size: 98570368
relation: main_file
success: 1
- access_level: open_access
checksum: 51ff687df4a0867f39b69c2c7a4ee3ca
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:28:45Z
date_updated: 2023-08-03T13:28:45Z
file_id: '13723'
file_name: Supplfig03_model2.tif
file_size: 98570367
relation: main_file
success: 1
- access_level: open_access
checksum: ec9d9a041ca85fe632c612baf981fcc5
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:28:49Z
date_updated: 2023-08-03T13:28:49Z
file_id: '13724'
file_name: Supplfig03_model3.tif
file_size: 98570365
relation: main_file
success: 1
- access_level: open_access
checksum: a988b15a9529094f1b5519a72871e98e
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:28:49Z
date_updated: 2023-08-03T13:28:49Z
file_id: '13725'
file_name: Supplfig03_model4.tif
file_size: 98570365
relation: main_file
success: 1
- access_level: open_access
checksum: 4a4fe88fcfd87fcfe118a5a73d81d6b0
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:28:52Z
date_updated: 2023-08-03T13:28:52Z
file_id: '13726'
file_name: Supplfig03_model5.tif
file_size: 98570369
relation: main_file
success: 1
- access_level: open_access
checksum: ce9b774ff5163ebfa4e3fb162f4cfffe
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:34:27Z
date_updated: 2023-08-03T13:34:27Z
file_id: '13727'
file_name: Supplfig04_a_n2v.tif
file_size: 1036927887
relation: main_file
success: 1
- access_level: open_access
checksum: 21f1bb8d2a00c88bdd6febe6285acc2a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:34:13Z
date_updated: 2023-08-03T13:34:13Z
file_id: '13728'
file_name: Supplfig04_a.tif
file_size: 518519275
relation: main_file
success: 1
- access_level: open_access
checksum: 503820214ab994c01b18a241f3b62434
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:34:22Z
date_updated: 2023-08-03T13:34:22Z
file_id: '13729'
file_name: Supplfig04_b.tif
file_size: 158440069
relation: main_file
success: 1
- access_level: open_access
checksum: e0469102a87332b46904b4ba35b8fb2f
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:34:37Z
date_updated: 2023-08-03T13:34:37Z
file_id: '13730'
file_name: Supplfig04_c_n2v.tif
file_size: 309407894
relation: main_file
success: 1
- access_level: open_access
checksum: c30a0d18c43045a8fbc5501a37061bd2
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:34:38Z
date_updated: 2023-08-03T13:34:38Z
file_id: '13731'
file_name: Supplfig04_c.tif
file_size: 154728887
relation: main_file
success: 1
- access_level: open_access
checksum: 69c706710d642b30cda6951494702139
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:34:43Z
date_updated: 2023-08-03T13:34:43Z
file_id: '13732'
file_name: Supplfig04_d_n2v.tif
file_size: 106696749
relation: main_file
success: 1
- access_level: open_access
checksum: 7dbd2e881ebf049352913188fa10224a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:34:41Z
date_updated: 2023-08-03T13:34:41Z
file_id: '13733'
file_name: Supplfig04_d.tif
file_size: 53367343
relation: main_file
success: 1
- access_level: open_access
checksum: fd0d1ec674dabbb499fab383b7eb4d58
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:34:46Z
date_updated: 2023-08-03T13:34:46Z
file_id: '13734'
file_name: Supplfig04_e_n2v.tiff
file_size: 127917734
relation: main_file
success: 1
- access_level: open_access
checksum: 86de309d9cd434afbe371da283d8adb6
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:34:46Z
date_updated: 2023-08-03T13:34:46Z
file_id: '13735'
file_name: Supplfig04_e.tif
file_size: 63974204
relation: main_file
success: 1
- access_level: open_access
checksum: ada99b2b5900cb198d1de3cc9e37ebd1
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:37Z
date_updated: 2023-08-03T13:35:37Z
file_id: '13736'
file_name: Supplfig05_a_xy_1.png
file_size: 8403
relation: main_file
success: 1
- access_level: open_access
checksum: f2e382925a972b98560614016ae3bc55
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:37Z
date_updated: 2023-08-03T13:35:37Z
file_id: '13737'
file_name: Supplfig05_a_xy_2.png
file_size: 10087
relation: main_file
success: 1
- access_level: open_access
checksum: ef22b640f33d677add1a7b5153f95420
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:37Z
date_updated: 2023-08-03T13:35:37Z
file_id: '13738'
file_name: Supplfig05_a_xy_3.png
file_size: 24561
relation: main_file
success: 1
- access_level: open_access
checksum: b854cc4a5224b8a6f5d59c74f5740ccd
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:37Z
date_updated: 2023-08-03T13:35:37Z
file_id: '13739'
file_name: Supplfig05_a_xy_4.png
file_size: 8353
relation: main_file
success: 1
- access_level: open_access
checksum: 446b0362c5ea6e2a5f0e1f8359422358
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:37Z
date_updated: 2023-08-03T13:35:37Z
file_id: '13740'
file_name: Supplfig05_a_xy_5.png
file_size: 8337
relation: main_file
success: 1
- access_level: open_access
checksum: 5585f7b62fa09ed5a63090b679383601
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:37Z
date_updated: 2023-08-03T13:35:37Z
file_id: '13741'
file_name: Supplfig05_a_xz_1.png
file_size: 7399
relation: main_file
success: 1
- access_level: open_access
checksum: 190d88bcacbd11d41f4a0e2bbd140862
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:37Z
date_updated: 2023-08-03T13:35:37Z
file_id: '13742'
file_name: Supplfig05_a_xz_2.png
file_size: 10887
relation: main_file
success: 1
- access_level: open_access
checksum: 0c89010651862f21032a303e159b7a1c
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:37Z
date_updated: 2023-08-03T13:35:37Z
file_id: '13743'
file_name: Supplfig05_a_xz_3.png
file_size: 21654
relation: main_file
success: 1
- access_level: open_access
checksum: 94e61e553aa2280721acce7d407ff24a
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:37Z
date_updated: 2023-08-03T13:35:37Z
file_id: '13744'
file_name: Supplfig05_a_xz_4.png
file_size: 7248
relation: main_file
success: 1
- access_level: open_access
checksum: ef9157274686ff5d7056f5a519d413dd
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:37Z
date_updated: 2023-08-03T13:35:37Z
file_id: '13745'
file_name: Supplfig05_a_xz_5.png
file_size: 7214
relation: main_file
success: 1
- access_level: open_access
checksum: 4b389473cbf769e6e34670dae2224af1
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:37Z
date_updated: 2023-08-03T13:35:37Z
file_id: '13746'
file_name: Supplfig05_b_xy_1.png
file_size: 8544
relation: main_file
success: 1
- access_level: open_access
checksum: b05aa1e201758a5d55e35d719452fafc
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:37Z
date_updated: 2023-08-03T13:35:37Z
file_id: '13747'
file_name: Supplfig05_b_xy_2.png
file_size: 11135
relation: main_file
success: 1
- access_level: open_access
checksum: 890f3516930251a367066c049141d6bb
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:37Z
date_updated: 2023-08-03T13:35:37Z
file_id: '13748'
file_name: Supplfig05_b_xy_3.png
file_size: 26762
relation: main_file
success: 1
- access_level: open_access
checksum: 36345c1d582758ff463072fd04578c0c
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:37Z
date_updated: 2023-08-03T13:35:37Z
file_id: '13749'
file_name: Supplfig05_b_xy_4.png
file_size: 8438
relation: main_file
success: 1
- access_level: open_access
checksum: c9499ad8914c405a07fc4469b19e8987
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:37Z
date_updated: 2023-08-03T13:35:37Z
file_id: '13750'
file_name: Supplfig05_b_xy_5.png
file_size: 8434
relation: main_file
success: 1
- access_level: open_access
checksum: 7e7a7c900ce1fc3187ab648f207f9425
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:37Z
date_updated: 2023-08-03T13:35:37Z
file_id: '13751'
file_name: Supplfig05_b_xz_1.png
file_size: 8269
relation: main_file
success: 1
- access_level: open_access
checksum: b645d1e2422ef3f05344ccd3f955468d
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:37Z
date_updated: 2023-08-03T13:35:37Z
file_id: '13752'
file_name: Supplfig05_b_xz_2.png
file_size: 12762
relation: main_file
success: 1
- access_level: open_access
checksum: ef0b83b49cf47ca7d8ffe3bdc609fe38
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:37Z
date_updated: 2023-08-03T13:35:37Z
file_id: '13753'
file_name: Supplfig05_b_xz_3.png
file_size: 24819
relation: main_file
success: 1
- access_level: open_access
checksum: 68719d4d464a2ffc198cb6ad070c4579
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:37Z
date_updated: 2023-08-03T13:35:37Z
file_id: '13754'
file_name: Supplfig05_b_xz_4.png
file_size: 8126
relation: main_file
success: 1
- access_level: open_access
checksum: 18370f47177ef37a477c6fd7bda3fea0
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:38Z
date_updated: 2023-08-03T13:35:38Z
file_id: '13755'
file_name: Supplfig05_b_xz_5.png
file_size: 8114
relation: main_file
success: 1
- access_level: open_access
checksum: 013d4bd9704ace490810b9ef21b12454
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:38Z
date_updated: 2023-08-03T13:35:38Z
file_id: '13756'
file_name: Supplfig05_c_xy_1.png
file_size: 8273
relation: main_file
success: 1
- access_level: open_access
checksum: bb431f827386e79c54452d6284f501b9
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:38Z
date_updated: 2023-08-03T13:35:38Z
file_id: '13757'
file_name: Supplfig05_c_xy_2.png
file_size: 12639
relation: main_file
success: 1
- access_level: open_access
checksum: 4cd54f58c5afff88832a508655f913bb
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:38Z
date_updated: 2023-08-03T13:35:38Z
file_id: '13758'
file_name: Supplfig05_c_xy_3.png
file_size: 25288
relation: main_file
success: 1
- access_level: open_access
checksum: 07f86f98f6a65eac8608cec8c567309e
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:38Z
date_updated: 2023-08-03T13:35:38Z
file_id: '13759'
file_name: Supplfig05_c_xz_1.png
file_size: 6786
relation: main_file
success: 1
- access_level: open_access
checksum: 492f699b71761214272b17432e3a54fa
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:38Z
date_updated: 2023-08-03T13:35:38Z
file_id: '13760'
file_name: Supplfig05_c_xz_2.png
file_size: 9781
relation: main_file
success: 1
- access_level: open_access
checksum: af617da5638db849bea6ff51a08227c6
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:38Z
date_updated: 2023-08-03T13:35:38Z
file_id: '13761'
file_name: Supplfig05_c_xz_3.png
file_size: 20728
relation: main_file
success: 1
- access_level: open_access
checksum: 5e5d5694af4a22297046d697a01fa4d6
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:38Z
date_updated: 2023-08-03T13:35:38Z
file_id: '13762'
file_name: Supplfig05_d_xy_1.png
file_size: 8428
relation: main_file
success: 1
- access_level: open_access
checksum: 38bf7b75f3dedd0a3722faae05aa0233
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:38Z
date_updated: 2023-08-03T13:35:38Z
file_id: '13763'
file_name: Supplfig05_d_xy_2.png
file_size: 10813
relation: main_file
success: 1
- access_level: open_access
checksum: e4ea966553f158ec2cfbdc696780390e
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:38Z
date_updated: 2023-08-03T13:35:38Z
file_id: '13764'
file_name: Supplfig05_d_xy_3.png
file_size: 26552
relation: main_file
success: 1
- access_level: open_access
checksum: 356f424d9f5f608e9aea962bb63672f1
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:38Z
date_updated: 2023-08-03T13:35:38Z
file_id: '13765'
file_name: Supplfig05_d_xz_1.png
file_size: 7876
relation: main_file
success: 1
- access_level: open_access
checksum: 05068476beee0f394e28b98209686394
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:38Z
date_updated: 2023-08-03T13:35:38Z
file_id: '13766'
file_name: Supplfig05_d_xz_2.png
file_size: 11634
relation: main_file
success: 1
- access_level: open_access
checksum: 78b3a0d93df22383a384a2f3acc80401
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:38Z
date_updated: 2023-08-03T13:35:38Z
file_id: '13767'
file_name: Supplfig05_d_xz_3.png
file_size: 25006
relation: main_file
success: 1
- access_level: open_access
checksum: f5ee6a817f11a42c9db82ad6325f58b9
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:38Z
date_updated: 2023-08-03T13:35:38Z
file_id: '13768'
file_name: Supplfig05_e_xy_1.png
file_size: 7895
relation: main_file
success: 1
- access_level: open_access
checksum: 019ca89e892d6e19589609bc99eab331
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:38Z
date_updated: 2023-08-03T13:35:38Z
file_id: '13769'
file_name: Supplfig05_e_xy_2.png
file_size: 6180
relation: main_file
success: 1
- access_level: open_access
checksum: 0e1a5cbbd70dc245edaecaca70d974cb
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:38Z
date_updated: 2023-08-03T13:35:38Z
file_id: '13770'
file_name: Supplfig05_e_xy_3.png
file_size: 18326
relation: main_file
success: 1
- access_level: open_access
checksum: 4d4d64a5bb7b096aaf8130ece4512bc2
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:38Z
date_updated: 2023-08-03T13:35:38Z
file_id: '13771'
file_name: Supplfig05_e_xz_1.png
file_size: 6295
relation: main_file
success: 1
- access_level: open_access
checksum: 607302aec5ec2a14a271dbffd3465261
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:38Z
date_updated: 2023-08-03T13:35:38Z
file_id: '13772'
file_name: Supplfig05_e_xz_2.png
file_size: 4335
relation: main_file
success: 1
- access_level: open_access
checksum: a673e17ead1fd2e776b9a5f560a289ab
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T13:35:38Z
date_updated: 2023-08-03T13:35:38Z
file_id: '13773'
file_name: Supplfig05_e_xz_3.png
file_size: 23243
relation: main_file
success: 1
- access_level: open_access
checksum: 4349e511fc86a8bddb790a7be7175c75
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:46:13Z
date_updated: 2023-08-03T13:46:13Z
file_id: '13774'
file_name: Supplfig06_a_1.tif
file_size: 4002153
relation: main_file
success: 1
- access_level: open_access
checksum: cd12977e4c1a472d80193be01f69a895
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:46:13Z
date_updated: 2023-08-03T13:46:13Z
file_id: '13775'
file_name: Supplfig06_a_2.tif
file_size: 2252137
relation: main_file
success: 1
- access_level: open_access
checksum: 575e32b8c25ce658e20f0c86a5f1b9b7
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:46:13Z
date_updated: 2023-08-03T13:46:13Z
file_id: '13776'
file_name: Supplfig06_a_3.tif
file_size: 2252137
relation: main_file
success: 1
- access_level: open_access
checksum: b06f775e0210e7a16cb4b58aed32118c
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:46:13Z
date_updated: 2023-08-03T13:46:13Z
file_id: '13777'
file_name: Supplfig06_a_i.tif
file_size: 78329
relation: main_file
success: 1
- access_level: open_access
checksum: 56854c1a05c721c36877fe7c7454b7d7
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:46:13Z
date_updated: 2023-08-03T13:46:13Z
file_id: '13778'
file_name: Supplfig06_a_ii.tif
file_size: 78329
relation: main_file
success: 1
- access_level: open_access
checksum: 9aff42ea5138931fedb5a00643ae7a22
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:46:13Z
date_updated: 2023-08-03T13:46:13Z
file_id: '13779'
file_name: Supplfig06_a_iii.tif
file_size: 78329
relation: main_file
success: 1
- access_level: open_access
checksum: 9474b7d00d4dee46659afedef75dc095
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:46:13Z
date_updated: 2023-08-03T13:46:13Z
file_id: '13780'
file_name: Supplfig06_d_1.tif
file_size: 501149
relation: main_file
success: 1
- access_level: open_access
checksum: 53df41dd968b04b4657cd2b91870d636
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:46:13Z
date_updated: 2023-08-03T13:46:13Z
file_id: '13781'
file_name: Supplfig06_d_2.tif
file_size: 500153
relation: main_file
success: 1
- access_level: open_access
checksum: 1a39b8310598dd25d97f848b682b8de0
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:46:14Z
date_updated: 2023-08-03T13:46:14Z
file_id: '13782'
file_name: Supplfig06_d_3.tif
file_size: 500153
relation: main_file
success: 1
- access_level: open_access
checksum: 6d9b496be6aecedbb2cb4cbf68f02872
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:46:14Z
date_updated: 2023-08-03T13:46:14Z
file_id: '13783'
file_name: Supplfig06_d_i.tif
file_size: 78329
relation: main_file
success: 1
- access_level: open_access
checksum: bc034b1636c2db8b9d9e7bd131b9780a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:46:14Z
date_updated: 2023-08-03T13:46:14Z
file_id: '13784'
file_name: Supplfig06_d_ii.tif
file_size: 78329
relation: main_file
success: 1
- access_level: open_access
checksum: 54f6e55e30a2aeea6c82eb6dbd376240
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:46:14Z
date_updated: 2023-08-03T13:46:14Z
file_id: '13785'
file_name: Supplfig06_d_iii.tif
file_size: 78329
relation: main_file
success: 1
- access_level: open_access
checksum: 446da3cc16897277890f23f966c2bf52
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:46:14Z
date_updated: 2023-08-03T13:46:14Z
file_id: '13786'
file_name: Supplfig06_g_1.tif
file_size: 960011
relation: main_file
success: 1
- access_level: open_access
checksum: 71192d0ec592a33195f2386a5f95aa86
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:46:14Z
date_updated: 2023-08-03T13:46:14Z
file_id: '13787'
file_name: Supplfig06_g_2.tif
file_size: 960011
relation: main_file
success: 1
- access_level: open_access
checksum: 246782dbe8ff525aea360efc72e65f07
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:46:14Z
date_updated: 2023-08-03T13:46:14Z
file_id: '13788'
file_name: Supplfig06_g_3.tif
file_size: 960041
relation: main_file
success: 1
- access_level: open_access
checksum: d49b12fec5508aa8d72587757cccc0a4
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:46:14Z
date_updated: 2023-08-03T13:46:14Z
file_id: '13789'
file_name: Supplfig06_g_4.tif
file_size: 960041
relation: main_file
success: 1
- access_level: open_access
checksum: 27b11b1d4fc784a49ffd7660624d00b6
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:46:14Z
date_updated: 2023-08-03T13:46:14Z
file_id: '13790'
file_name: Supplfig06_g_5.tif
file_size: 963241
relation: main_file
success: 1
- access_level: open_access
checksum: 9ce944049c1b88fadbf43609385f9e2f
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:38Z
date_updated: 2023-08-03T13:51:38Z
file_id: '13791'
file_name: Suppl08_a_1.tiff
file_size: 19286002
relation: main_file
success: 1
- access_level: open_access
checksum: 06265515f06688843a415362f7b2c485
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:38Z
date_updated: 2023-08-03T13:51:38Z
file_id: '13792'
file_name: Suppl08_a_2.tiff
file_size: 19286002
relation: main_file
success: 1
- access_level: open_access
checksum: 50f0969c6c2c1209ff776bec4861030a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:38Z
date_updated: 2023-08-03T13:51:38Z
file_id: '13793'
file_name: Suppl08_a_3.tif
file_size: 617552
relation: main_file
success: 1
- access_level: open_access
checksum: b90965d20133fea73c99050c32eb7695
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:38Z
date_updated: 2023-08-03T13:51:38Z
file_id: '13794'
file_name: Suppl08_a_4.tif
file_size: 617552
relation: main_file
success: 1
- access_level: open_access
checksum: 568a1e0efaa62527b51e66a7aabfd05c
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:40Z
date_updated: 2023-08-03T13:51:40Z
file_id: '13795'
file_name: Suppl08_a_coCATS_N2V.tif
file_size: 19287339
relation: main_file
success: 1
- access_level: open_access
checksum: 06265515f06688843a415362f7b2c485
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:40Z
date_updated: 2023-08-03T13:51:40Z
file_id: '13796'
file_name: Suppl08_c_1_4_predictedBASSOON.tiff
file_size: 19286002
relation: main_file
success: 1
- access_level: open_access
checksum: 568a1e0efaa62527b51e66a7aabfd05c
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:43Z
date_updated: 2023-08-03T13:51:43Z
file_id: '13797'
file_name: Suppl08_c_1_coCATS.tif
file_size: 19287339
relation: main_file
success: 1
- access_level: open_access
checksum: feae08c38b1d9c540b697977cd7f2666
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T15:36:47Z
date_updated: 2023-08-03T15:36:47Z
file_id: '13798'
file_name: Suppl08_c_2_coCATS.tif
file_size: 19287340
relation: main_file
success: 1
- access_level: open_access
checksum: af2c1199fdcaecfec76189dae86cc12e
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:44Z
date_updated: 2023-08-03T13:51:44Z
file_id: '13799'
file_name: Suppl08_c_2-3_predictedBASSOON.tiff
file_size: 19286002
relation: main_file
success: 1
- access_level: open_access
checksum: 1f92db47605959d0db01f612f7c9c034
content_type: application/octet-stream
creator: jdanzl
date_created: 2023-08-03T13:51:43Z
date_updated: 2023-08-03T13:51:43Z
file_id: '13800'
file_name: Suppl08_c_3-6_roi.roi
file_size: 156
relation: main_file
success: 1
- access_level: open_access
checksum: 4fc4f8803adcfacd53a41b91f4699dc5
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:45Z
date_updated: 2023-08-03T13:51:45Z
file_id: '13801'
file_name: Suppl08_e_1_3.tiff
file_size: 19286002
relation: main_file
success: 1
- access_level: open_access
checksum: 459551aae114daa4f5ca5d06fcd6b203
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:45Z
date_updated: 2023-08-03T13:51:45Z
file_id: '13802'
file_name: Suppl08_e_1-2.tiff
file_size: 19286002
relation: main_file
success: 1
- access_level: open_access
checksum: 032cbace7ec436f7b62478c0ffd35e5e
content_type: application/octet-stream
creator: jdanzl
date_created: 2023-08-03T13:51:45Z
date_updated: 2023-08-03T13:51:45Z
file_id: '13803'
file_name: Suppl08_e_2-5_roi.roi
file_size: 152
relation: main_file
success: 1
- access_level: open_access
checksum: 7379168be281ef618b8cecd8efd31ed5
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:46Z
date_updated: 2023-08-03T13:51:46Z
file_id: '13804'
file_name: Suppl08_e_4-5_coCATS.tiff
file_size: 19286002
relation: main_file
success: 1
- access_level: open_access
checksum: 5c4c092f608f4c10bb422c9e08b5955b
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:46Z
date_updated: 2023-08-03T13:51:46Z
file_id: '13805'
file_name: Suppl08_e_4.tif
file_size: 617552
relation: main_file
success: 1
- access_level: open_access
checksum: 903e31be124f6e4ec1c2e7ab7db80e6b
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:46Z
date_updated: 2023-08-03T13:51:46Z
file_id: '13806'
file_name: Suppl08_e_5.tif
file_size: 617552
relation: main_file
success: 1
- access_level: open_access
checksum: 173d956392d67b0a7e544629b51881e4
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:48Z
date_updated: 2023-08-03T13:51:48Z
file_id: '13807'
file_name: Suppl08_e_6_8.tiff
file_size: 19286002
relation: main_file
success: 1
- access_level: open_access
checksum: 2a4cea867a253a6af7e9b0d2e100de14
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:48Z
date_updated: 2023-08-03T13:51:48Z
file_id: '13808'
file_name: Suppl08_e_6-7.tiff
file_size: 19286002
relation: main_file
success: 1
- access_level: open_access
checksum: 6b40f99fddfa26f0a9713000769741b7
content_type: application/octet-stream
creator: jdanzl
date_created: 2023-08-03T13:51:48Z
date_updated: 2023-08-03T13:51:48Z
file_id: '13809'
file_name: Suppl08_e_7-10_roi.roi
file_size: 174
relation: main_file
success: 1
- access_level: open_access
checksum: 82f7013959df99c27366886de9b38ba2
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:49Z
date_updated: 2023-08-03T13:51:49Z
file_id: '13810'
file_name: Suppl08_e_9-10_coCATS.tiff
file_size: 19286002
relation: main_file
success: 1
- access_level: open_access
checksum: 50f0969c6c2c1209ff776bec4861030a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:48Z
date_updated: 2023-08-03T13:51:48Z
file_id: '13811'
file_name: Suppl08_e_9.tif
file_size: 617552
relation: main_file
success: 1
- access_level: open_access
checksum: 569f599d7f2be49d4dcf7cb385f428c4
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:49Z
date_updated: 2023-08-03T13:51:49Z
file_id: '13812'
file_name: Suppl08_e_10.tif
file_size: 617552
relation: main_file
success: 1
- access_level: open_access
checksum: 50f0969c6c2c1209ff776bec4861030a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:49Z
date_updated: 2023-08-03T13:51:49Z
file_id: '13813'
file_name: Suppl08_g_1.tif
file_size: 617552
relation: main_file
success: 1
- access_level: open_access
checksum: 62797fc860176197142a47e831eaf1f6
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:49Z
date_updated: 2023-08-03T13:51:49Z
file_id: '13814'
file_name: Suppl08_g_2.tif
file_size: 617552
relation: main_file
success: 1
- access_level: open_access
checksum: b90965d20133fea73c99050c32eb7695
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:49Z
date_updated: 2023-08-03T13:51:49Z
file_id: '13815'
file_name: Suppl08_g_3.tif
file_size: 617552
relation: main_file
success: 1
- access_level: open_access
checksum: a96dc9f38c6a1d3c959771a649a42748
content_type: application/octet-stream
creator: jdanzl
date_created: 2023-08-03T13:51:49Z
date_updated: 2023-08-03T13:51:49Z
file_id: '13816'
file_name: Suppl08_i_add_roi.roi
file_size: 160
relation: main_file
success: 1
- access_level: open_access
checksum: f2135207ebbc4bdc014763ba852a5cf0
content_type: application/octet-stream
creator: jdanzl
date_created: 2023-08-03T13:51:50Z
date_updated: 2023-08-03T13:51:50Z
file_id: '13817'
file_name: Suppl08_i_shape_roi.roi
file_size: 160
relation: main_file
success: 1
- access_level: open_access
checksum: f6f31fe2d87cf7208387f98ce1e37b04
content_type: application/octet-stream
creator: jdanzl
date_created: 2023-08-03T13:51:50Z
date_updated: 2023-08-03T13:51:50Z
file_id: '13818'
file_name: Suppl08_i_split_roi.roi
file_size: 158
relation: main_file
success: 1
- access_level: open_access
checksum: 71590db0ad391e0c5baf03024981b1d9
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:51Z
date_updated: 2023-08-03T13:51:51Z
file_id: '13819'
file_name: Suppl08_i_1.tiff
file_size: 19286002
relation: main_file
success: 1
- access_level: open_access
checksum: 9ce944049c1b88fadbf43609385f9e2f
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:51Z
date_updated: 2023-08-03T13:51:51Z
file_id: '13820'
file_name: Suppl08_i_2.tiff
file_size: 19286002
relation: main_file
success: 1
- access_level: open_access
checksum: 06265515f06688843a415362f7b2c485
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:52Z
date_updated: 2023-08-03T13:51:52Z
file_id: '13821'
file_name: Suppl08_i_3.tiff
file_size: 19286002
relation: main_file
success: 1
- access_level: open_access
checksum: 16c628c160fb81e40df0ad1eb134e92b
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:52Z
date_updated: 2023-08-03T13:51:52Z
file_id: '13822'
file_name: Suppl08_i_4.tif
file_size: 19284766
relation: main_file
success: 1
- access_level: open_access
checksum: b06e62c3a9834a40002d7aad3eaacc3f
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:53Z
date_updated: 2023-08-03T13:51:53Z
file_id: '13823'
file_name: Suppl08_i_5.tif
file_size: 9649818
relation: main_file
success: 1
- access_level: open_access
checksum: 41ef98c7f01755b43cf6e77fff287732
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:51:53Z
date_updated: 2023-08-03T13:51:53Z
file_id: '13824'
file_name: Suppl08_i_6.tif
file_size: 19284766
relation: main_file
success: 1
- access_level: open_access
checksum: feae08c38b1d9c540b697977cd7f2666
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:53:29Z
date_updated: 2023-08-03T13:53:29Z
file_id: '13825'
file_name: Suppl08_c_2_coCATS.tif
file_size: 19287340
relation: main_file
success: 1
- access_level: open_access
checksum: c01509a1c657fbbbfdbbd484c298b6e3
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:58:08Z
date_updated: 2023-08-03T13:58:08Z
file_id: '13826'
file_name: Supplfig09_b_1_n2v.tiff
file_size: 179788642
relation: main_file
success: 1
- access_level: open_access
checksum: 64a7f270274ff3480b18d690087016e2
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:58:20Z
date_updated: 2023-08-03T13:58:20Z
file_id: '13827'
file_name: Supplfig09_b_2_n2v.tif
file_size: 742420240
relation: main_file
success: 1
- access_level: open_access
checksum: b34a6beaaf13698f421df961e009efeb
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:58:20Z
date_updated: 2023-08-03T13:58:20Z
file_id: '13828'
file_name: Supplfig09_b_3_n2v.tif
file_size: 478900363
relation: main_file
success: 1
- access_level: open_access
checksum: ec04501f234b5e4fd91f9eac0e585395
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:58:25Z
date_updated: 2023-08-03T13:58:25Z
file_id: '13829'
file_name: Supplfig09_b_4_n2v.tif
file_size: 191873159
relation: main_file
success: 1
- access_level: open_access
checksum: 3a1b313298da35c97550abf0d245b4a7
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:59:27Z
date_updated: 2023-08-03T13:59:27Z
file_id: '13830'
file_name: Supplfig11_i.tif
file_size: 55286
relation: main_file
success: 1
- access_level: open_access
checksum: 9cf00c0252f0a2efe1994c83c224389a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:59:27Z
date_updated: 2023-08-03T13:59:27Z
file_id: '13831'
file_name: Supplfig11_ii.tif
file_size: 55286
relation: main_file
success: 1
- access_level: open_access
checksum: 9a6e83acdf6d70bb9a6e76fa7d41a372
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:59:27Z
date_updated: 2023-08-03T13:59:27Z
file_id: '13832'
file_name: Supplfig11_iii.tif
file_size: 55257
relation: main_file
success: 1
- access_level: open_access
checksum: 709fdd13b7e090846a4d8edd2425f675
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T13:59:32Z
date_updated: 2023-08-03T13:59:32Z
file_id: '13833'
file_name: Supplfig11_n2v+prediction.tif
file_size: 309457551
relation: main_file
success: 1
- access_level: open_access
checksum: e60ea3e6bb1bf380460d0d8ccdbd1f07
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:14:32Z
date_updated: 2023-08-03T14:14:32Z
file_id: '13834'
file_name: Supplfig12_a_01_n2v.tif
file_size: 119323629
relation: main_file
success: 1
- access_level: open_access
checksum: 2a4e1771e2f06383894361ba2a8155b4
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:14:29Z
date_updated: 2023-08-03T14:14:29Z
file_id: '13835'
file_name: Supplfig12_a_01.tif
file_size: 59680727
relation: main_file
success: 1
- access_level: open_access
checksum: 993c434069b9d1bcb09bfe70628f5bbe
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:14:34Z
date_updated: 2023-08-03T14:14:34Z
file_id: '13836'
file_name: Supplfig12_a_02_n2v.tif
file_size: 106696749
relation: main_file
success: 1
- access_level: open_access
checksum: e3b6410d68e42004ef3857967707aeb3
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:14:34Z
date_updated: 2023-08-03T14:14:34Z
file_id: '13837'
file_name: Supplfig12_a_02.tif
file_size: 53367287
relation: main_file
success: 1
- access_level: open_access
checksum: 0156e99806fe1539d5f48ea16c78e8c8
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:14:41Z
date_updated: 2023-08-03T14:14:41Z
file_id: '13838'
file_name: Supplfig12_a_03_n2v.tif
file_size: 149937979
relation: main_file
success: 1
- access_level: open_access
checksum: 6cc1533a221526a072a0b09fb44bcf50
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:14:39Z
date_updated: 2023-08-03T14:14:39Z
file_id: '13839'
file_name: Supplfig12_a_03.tif
file_size: 74987927
relation: main_file
success: 1
- access_level: open_access
checksum: f134834bd0d5e8c22e5a35aadf592007
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:14:53Z
date_updated: 2023-08-03T14:14:53Z
file_id: '13840'
file_name: Supplfig12_a_04_n2v.tif
file_size: 305581862
relation: main_file
success: 1
- access_level: open_access
checksum: 212ec76c02552fa1eef91e7bca9f07f7
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:14:50Z
date_updated: 2023-08-03T14:14:50Z
file_id: '13841'
file_name: Supplfig12_a_04.tif
file_size: 152821840
relation: main_file
success: 1
- access_level: open_access
checksum: 7d99807d5b4313b04b4b5e0fbc08ba78
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:14:52Z
date_updated: 2023-08-03T14:14:52Z
file_id: '13842'
file_name: Supplfig12_a_05_n2v.tif
file_size: 48082029
relation: main_file
success: 1
- access_level: open_access
checksum: a6d4024a8c6fa073a532cc0c78323df7
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:14:53Z
date_updated: 2023-08-03T14:14:53Z
file_id: '13843'
file_name: Supplfig12_a_05.tif
file_size: 24059983
relation: main_file
success: 1
- access_level: open_access
checksum: 1c42ad5423636478fe57495a3b506746
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:15:09Z
date_updated: 2023-08-03T14:15:09Z
file_id: '13844'
file_name: Supplfig12_a_06_n2v.tif
file_size: 305581860
relation: main_file
success: 1
- access_level: open_access
checksum: 821f1d31c6dbe68eb2513fb7520b5272
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:15:04Z
date_updated: 2023-08-03T14:15:04Z
file_id: '13845'
file_name: Supplfig12_a_06.tif
file_size: 152821840
relation: main_file
success: 1
- access_level: open_access
checksum: 86a4dc1e4948c4bc9c71e6d55b4fd104
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:15:08Z
date_updated: 2023-08-03T14:15:08Z
file_id: '13846'
file_name: Supplfig12_a_07_n2v.tif
file_size: 66855793
relation: main_file
success: 1
- access_level: open_access
checksum: fd5d45b1135800124fec635c4667dafe
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:15:09Z
date_updated: 2023-08-03T14:15:09Z
file_id: '13847'
file_name: Supplfig12_a_07.tif
file_size: 33446807
relation: main_file
success: 1
- access_level: open_access
checksum: 5683760cc119a09f0b7de8fea98cda9c
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:15:19Z
date_updated: 2023-08-03T14:15:19Z
file_id: '13848'
file_name: Supplfig12_a_08_n2v.tif
file_size: 231476260
relation: main_file
success: 1
- access_level: open_access
checksum: 0c336d554bcd8524f11bd25c2188b56f
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:15:15Z
date_updated: 2023-08-03T14:15:15Z
file_id: '13849'
file_name: Supplfig12_a_08.tif
file_size: 115769040
relation: main_file
success: 1
- access_level: open_access
checksum: fcaea6c95c363bd864a524fca8ed8e9b
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:15:31Z
date_updated: 2023-08-03T14:15:31Z
file_id: '13850'
file_name: Supplfig12_a_09_n2v.tif
file_size: 305581869
relation: main_file
success: 1
- access_level: open_access
checksum: f401f1875f072c345d106a1e419f9d13
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:15:28Z
date_updated: 2023-08-03T14:15:28Z
file_id: '13851'
file_name: Supplfig12_a_09.tif
file_size: 152821840
relation: main_file
success: 1
- access_level: open_access
checksum: 7ad7d5b1ac81da1ec3d5003d00ee870a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:15:42Z
date_updated: 2023-08-03T14:15:42Z
file_id: '13852'
file_name: Supplfig12_a_10_n2v.tif
file_size: 266386255
relation: main_file
success: 1
- access_level: open_access
checksum: 77b93d082debd5248348c0a1e886eab9
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:15:40Z
date_updated: 2023-08-03T14:15:40Z
file_id: '13853'
file_name: Supplfig12_a_10.tif
file_size: 133239040
relation: main_file
success: 1
- access_level: open_access
checksum: 5ece1d503f05133d07d5b867f666d7a8
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:15:49Z
date_updated: 2023-08-03T14:15:49Z
file_id: '13854'
file_name: Supplfig12_a_11_n2v.tif
file_size: 191866269
relation: main_file
success: 1
- access_level: open_access
checksum: a72ee7ab433097752ff00a63421d4b61
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:15:48Z
date_updated: 2023-08-03T14:15:48Z
file_id: '13855'
file_name: Supplfig12_a_11.tif
file_size: 95955040
relation: main_file
success: 1
- access_level: open_access
checksum: c9c6e4692e0e7f305a43058b201b50d3
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:16:49Z
date_updated: 2023-08-03T14:16:49Z
file_id: '13856'
file_name: Supplfig13_i.tif
file_size: 55281
relation: main_file
success: 1
- access_level: open_access
checksum: 345d11dbd70123d9d2723b547cbfc4fc
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:16:49Z
date_updated: 2023-08-03T14:16:49Z
file_id: '13857'
file_name: Supplfig13_ii.tif
file_size: 55193
relation: main_file
success: 1
- access_level: open_access
checksum: b4c74c08077cfd3e11bfd6ea9ee1c5b2
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:16:49Z
date_updated: 2023-08-03T14:16:49Z
file_id: '13858'
file_name: Supplfig13_n2v+predict.tif
file_size: 539037
relation: main_file
success: 1
- access_level: open_access
checksum: 15f5b44257d075f9e45811304dfd5f85
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:18:10Z
date_updated: 2023-08-03T14:18:10Z
file_id: '13859'
file_name: Supplfig14_a_n2v.tif
file_size: 854898609
relation: main_file
success: 1
- access_level: open_access
checksum: a9ca03e3e5696988d06fc6ab1c103440
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T14:19:58Z
date_updated: 2023-08-03T14:19:58Z
file_id: '13860'
file_name: Supplfig15_a_1.png
file_size: 7514502
relation: main_file
success: 1
- access_level: open_access
checksum: 4be3451e203a0fc5d9eb14279ff68a7a
content_type: image/png
creator: jdanzl
date_created: 2023-08-03T14:19:58Z
date_updated: 2023-08-03T14:19:58Z
file_id: '13861'
file_name: Supplfig15_a_2.png
file_size: 1784041
relation: main_file
success: 1
- access_level: open_access
checksum: 43068c31eecddb798dbf2f51bda9b6c9
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:19:58Z
date_updated: 2023-08-03T14:19:58Z
file_id: '13862'
file_name: Supplfig15_b_1.tif
file_size: 6030878
relation: main_file
success: 1
- access_level: open_access
checksum: ded4c0797f1a9152dc3128f1bb8c32a5
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:19:58Z
date_updated: 2023-08-03T14:19:58Z
file_id: '13863'
file_name: Supplfig15_b_2.tif
file_size: 723293
relation: main_file
success: 1
- access_level: open_access
checksum: 705394732d94bd8463479aee83c2d36e
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:19:58Z
date_updated: 2023-08-03T14:19:58Z
file_id: '13864'
file_name: Supplfig15_c_i.tif
file_size: 723409
relation: main_file
success: 1
- access_level: open_access
checksum: e08efe220bec6a93d583cab17754dd19
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:19:58Z
date_updated: 2023-08-03T14:19:58Z
file_id: '13865'
file_name: Supplfig15_c_ii.tif
file_size: 723409
relation: main_file
success: 1
- access_level: open_access
checksum: 0e08e5d965815240b0a8195e0f899aab
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:19:59Z
date_updated: 2023-08-03T14:19:59Z
file_id: '13866'
file_name: Supplfig15_c.tif
file_size: 31572914
relation: main_file
success: 1
- access_level: open_access
checksum: 594696a77d4a9be512046be5e2d602f0
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:19:59Z
date_updated: 2023-08-03T14:19:59Z
file_id: '13867'
file_name: Supplfig15_d_1.tif
file_size: 6030752
relation: main_file
success: 1
- access_level: open_access
checksum: ffe6733eb77858008c4ca07b5f8c432b
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:19:59Z
date_updated: 2023-08-03T14:19:59Z
file_id: '13868'
file_name: Supplfig15_d_2.tif
file_size: 8005495
relation: main_file
success: 1
- access_level: open_access
checksum: 663bf013cf1e5019e1e7ddd2d12fa492
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:20:56Z
date_updated: 2023-08-03T14:20:56Z
file_id: '13869'
file_name: Supplfig16_a.tif
file_size: 11117709
relation: main_file
success: 1
- access_level: open_access
checksum: 80aee233dc2a1f26ed8cc323270cf3a9
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:20:56Z
date_updated: 2023-08-03T14:20:56Z
file_id: '13870'
file_name: Supplfig16_b.tif
file_size: 113709
relation: main_file
success: 1
- access_level: open_access
checksum: 3b408e9345df2f16a942ad4ea61739b7
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:20:56Z
date_updated: 2023-08-03T14:20:56Z
file_id: '13871'
file_name: Supplfig16_c.tif
file_size: 113709
relation: main_file
success: 1
- access_level: open_access
checksum: fbf688ef1f907149f92e9e936d02df72
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:25:47Z
date_updated: 2023-08-03T14:25:47Z
file_id: '13872'
file_name: Supplfig17_a_1.tif
file_size: 6003131
relation: main_file
success: 1
- access_level: open_access
checksum: 9a56470f251f14b43903036fab338f76
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:25:47Z
date_updated: 2023-08-03T14:25:47Z
file_id: '13873'
file_name: Supplfig17_a_2.tif
file_size: 8004085
relation: main_file
success: 1
- access_level: open_access
checksum: 4578c020ba5d0a6ffe2a8a1c22e52c75
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:25:47Z
date_updated: 2023-08-03T14:25:47Z
file_id: '13874'
file_name: Supplfig17_a_3.tif
file_size: 6003123
relation: main_file
success: 1
- access_level: open_access
checksum: a681d32f515da3bff8e803946f1d8b50
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:25:47Z
date_updated: 2023-08-03T14:25:47Z
file_id: '13875'
file_name: Supplfig17_a_4.tif
file_size: 6003131
relation: main_file
success: 1
- access_level: open_access
checksum: b89d366c39e25d17dc5d8ceee9145c8b
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:25:47Z
date_updated: 2023-08-03T14:25:47Z
file_id: '13876'
file_name: Supplfig17_a_5.tif
file_size: 6003131
relation: main_file
success: 1
- access_level: open_access
checksum: 0b9d60f0aba79525a97c122d972f0b22
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:25:47Z
date_updated: 2023-08-03T14:25:47Z
file_id: '13877'
file_name: Supplfig17_a_6.tif
file_size: 6003079
relation: main_file
success: 1
- access_level: open_access
checksum: 169aad3cea521cc2a0ce4c3e41473e0c
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:25:47Z
date_updated: 2023-08-03T14:25:47Z
file_id: '13878'
file_name: Supplfig17_a_7.tif
file_size: 6003115
relation: main_file
success: 1
- access_level: open_access
checksum: 39a44d77d9047bfa10da8d9c9bd7b391
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:25:47Z
date_updated: 2023-08-03T14:25:47Z
file_id: '13879'
file_name: Supplfig17_a_8.tif
file_size: 4002129
relation: main_file
success: 1
- access_level: open_access
checksum: f4ecb2bd44f2cea3d71587670344ac40
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:25:48Z
date_updated: 2023-08-03T14:25:48Z
file_id: '13880'
file_name: Supplfig17_b.tif
file_size: 8214335
relation: main_file
success: 1
- access_level: open_access
checksum: 44a20d2621680c90227416bf32b5a566
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:27:06Z
date_updated: 2023-08-03T14:27:06Z
file_id: '13881'
file_name: Supplfig18_a.tif
file_size: 7471479
relation: main_file
success: 1
- access_level: open_access
checksum: 5a5f7b616785f9213064e8c77f9d38c4
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:27:06Z
date_updated: 2023-08-03T14:27:06Z
file_id: '13882'
file_name: Supplfig18_b.tif
file_size: 290625
relation: main_file
success: 1
- access_level: open_access
checksum: 8f621722a636e808a03d85f9597ad1a2
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:27:07Z
date_updated: 2023-08-03T14:27:07Z
file_id: '13883'
file_name: Supplfig18_c.tif
file_size: 411767
relation: main_file
success: 1
- access_level: open_access
checksum: 3c8356f9170fe345e2ef725cd7d1b167
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:27:07Z
date_updated: 2023-08-03T14:27:07Z
file_id: '13884'
file_name: Supplfig18_d.tif
file_size: 11117685
relation: main_file
success: 1
- access_level: open_access
checksum: 5c8443e97724b54f359f7355483b890e
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:27:10Z
date_updated: 2023-08-03T14:27:10Z
file_id: '13885'
file_name: Supplfig18_e_n2v.tif
file_size: 259509773
relation: main_file
success: 1
- access_level: open_access
checksum: 413e3105c1bcd2ac2c569fa2b06253f2
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:29:25Z
date_updated: 2023-08-03T14:29:25Z
file_id: '13886'
file_name: Supplfig19_n2v.tif
file_size: 1430939360
relation: main_file
success: 1
- access_level: open_access
checksum: a864dc5b54f469c723e86286d538bb52
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:29:16Z
date_updated: 2023-08-03T14:29:16Z
file_id: '13887'
file_name: Supplfig19.tif
file_size: 715524468
relation: main_file
success: 1
- access_level: open_access
checksum: 8a78ce49446d207c0bf31196b788fa93
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:32:54Z
date_updated: 2023-08-03T14:32:54Z
file_id: '13888'
file_name: Supplfig20_a_left.tif
file_size: 8004743
relation: main_file
success: 1
- access_level: open_access
checksum: 48fa3abfd16a00c7a3757d6452a482ec
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:32:54Z
date_updated: 2023-08-03T14:32:54Z
file_id: '13889'
file_name: Supplfig20_a_right.tif
file_size: 5561081
relation: main_file
success: 1
- access_level: open_access
checksum: 85d82cd94dd3202f04b5987bc4466573
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:32:54Z
date_updated: 2023-08-03T14:32:54Z
file_id: '13890'
file_name: Supplfig20_b_1.tif
file_size: 8456797
relation: main_file
success: 1
- access_level: open_access
checksum: e16f04d5d4d40f6ec33456d0cf02e1eb
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:32:54Z
date_updated: 2023-08-03T14:32:54Z
file_id: '13891'
file_name: Supplfig20_b_2.tif
file_size: 8456795
relation: main_file
success: 1
- access_level: open_access
checksum: ff190edb269c28b25d27bffaeb7d25cf
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:32:54Z
date_updated: 2023-08-03T14:32:54Z
file_id: '13892'
file_name: Supplfig20_b_3.tif
file_size: 8456796
relation: main_file
success: 1
- access_level: open_access
checksum: deb10b81bae62d9e20e681411fb75fcc
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:32:54Z
date_updated: 2023-08-03T14:32:54Z
file_id: '13893'
file_name: Supplfig20_b_4.tif
file_size: 8538887
relation: main_file
success: 1
- access_level: open_access
checksum: 5c64bb94e76030d7a9d8624bac4b0f57
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:32:54Z
date_updated: 2023-08-03T14:32:54Z
file_id: '13894'
file_name: Supplfig20_b_5.tif
file_size: 8538851
relation: main_file
success: 1
- access_level: open_access
checksum: d6c20232c4bd36e213b4c456c5009644
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:32:54Z
date_updated: 2023-08-03T14:32:54Z
file_id: '13895'
file_name: Supplfig20_c_1.tif
file_size: 11077737
relation: main_file
success: 1
- access_level: open_access
checksum: 49c3396b8960af3f6fd8f6b078971d51
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:32:54Z
date_updated: 2023-08-03T14:32:54Z
file_id: '13896'
file_name: Supplfig20_c_2.tif
file_size: 11077737
relation: main_file
success: 1
- access_level: open_access
checksum: 73471528f691fb337839b84c31014da4
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:32:55Z
date_updated: 2023-08-03T14:32:55Z
file_id: '13897'
file_name: Supplfig20_c_3.tif
file_size: 11077737
relation: main_file
success: 1
- access_level: open_access
checksum: 47a0fd1a36d7e7907ce18007bdaaa145
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:32:55Z
date_updated: 2023-08-03T14:32:55Z
file_id: '13898'
file_name: Supplfig20_c_4.tif
file_size: 11077737
relation: main_file
success: 1
- access_level: open_access
checksum: 0c74b07f13fb08a91e61669368f38c9a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:32:55Z
date_updated: 2023-08-03T14:32:55Z
file_id: '13899'
file_name: Supplfig20_c_5.tif
file_size: 11077737
relation: main_file
success: 1
- access_level: open_access
checksum: fe3b76446ec8bd0d5cdba94a128a84b8
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:32:55Z
date_updated: 2023-08-03T14:32:55Z
file_id: '13900'
file_name: Supplfig20_d_1.tif
file_size: 4002133
relation: main_file
success: 1
- access_level: open_access
checksum: 0570bab9a471af3d0d1d8bf9a3cb17e7
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:32:55Z
date_updated: 2023-08-03T14:32:55Z
file_id: '13901'
file_name: Supplfig20_d_2.tif
file_size: 4002133
relation: main_file
success: 1
- access_level: open_access
checksum: 59f330990b5c95f98a768761a009940c
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:32:55Z
date_updated: 2023-08-03T14:32:55Z
file_id: '13902'
file_name: Supplfig20_d_3.tif
file_size: 4002199
relation: main_file
success: 1
- access_level: open_access
checksum: f0da06f2a278dff4bbd1aeace11700bf
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:32:55Z
date_updated: 2023-08-03T14:32:55Z
file_id: '13903'
file_name: Supplfig20_d_4.tif
file_size: 4002133
relation: main_file
success: 1
- access_level: open_access
checksum: e61d49dcc0952af3623cc26a78cc6495
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:32:55Z
date_updated: 2023-08-03T14:32:55Z
file_id: '13904'
file_name: Supplfig20_d_5.tif
file_size: 4002133
relation: main_file
success: 1
- access_level: open_access
checksum: bcf8294487abaf1a75033f388fba06ec
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:42:01Z
date_updated: 2023-08-03T14:42:01Z
file_id: '13905'
file_name: Supplfig22_b_1.tif
file_size: 12627576
relation: main_file
success: 1
- access_level: open_access
checksum: 14097feb4a73e7bb1e1694cef0115cab
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:42:01Z
date_updated: 2023-08-03T14:42:01Z
file_id: '13906'
file_name: Supplfig22_b_2.tif
file_size: 8543366
relation: main_file
success: 1
- access_level: open_access
checksum: 7e74b8cff2ada56d47d135a6a9e71e76
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:42:04Z
date_updated: 2023-08-03T14:42:04Z
file_id: '13907'
file_name: Supplfig22_b_3.tif
file_size: 8394010
relation: main_file
success: 1
- access_level: open_access
checksum: f6e6e0f0e3854fedd201ab8ff08a7651
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T15:35:39Z
date_updated: 2023-08-03T15:35:39Z
file_id: '13908'
file_name: Supplfig22_b_4.tif
file_size: 8682992
relation: main_file
success: 1
- access_level: open_access
checksum: 6ddeb84249768b46b9c2072bf85bdc8b
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:42:04Z
date_updated: 2023-08-03T14:42:04Z
file_id: '13909'
file_name: Supplfig22_b_5.tif
file_size: 8503466
relation: main_file
success: 1
- access_level: open_access
checksum: 40648b8a4ef375b8352f11a6772ea1a6
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:42:04Z
date_updated: 2023-08-03T14:42:04Z
file_id: '13910'
file_name: Supplfig22_b_6.tif
file_size: 8543342
relation: main_file
success: 1
- access_level: open_access
checksum: 78f601de4d88f6ccb97861eaf4a995f8
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:42:06Z
date_updated: 2023-08-03T14:42:06Z
file_id: '13911'
file_name: Supplfig22_b_7.tif
file_size: 33588990
relation: main_file
success: 1
- access_level: open_access
checksum: 2873c488b7c8ad4d111726025086e9ea
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:42:41Z
date_updated: 2023-08-03T14:42:41Z
file_id: '13912'
file_name: Supplfig22_c.tif
file_size: 1453171518
relation: main_file
success: 1
- access_level: open_access
checksum: c1d0e5e61ac0d0ddf08704769f80ac78
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:47:43Z
date_updated: 2023-08-03T14:47:43Z
file_id: '13913'
file_name: Supplfig23_a.tif
file_size: 1325919782
relation: main_file
success: 1
- access_level: open_access
checksum: f97632984b6a73e06cc0c8c947cdcc71
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:47:25Z
date_updated: 2023-08-03T14:47:25Z
file_id: '13914'
file_name: Supplfig23_b.tif
file_size: 31366288
relation: main_file
success: 1
- access_level: open_access
checksum: 16f4c17835a79d7c06e2a97b1603baf1
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:47:26Z
date_updated: 2023-08-03T14:47:26Z
file_id: '13915'
file_name: Supplfig23_c.tif
file_size: 31366288
relation: main_file
success: 1
- access_level: open_access
checksum: 00f35ca77165642ca9b3bc3608bd04c1
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:47:27Z
date_updated: 2023-08-03T14:47:27Z
file_id: '13916'
file_name: Supplfig23_d.tif
file_size: 31366428
relation: main_file
success: 1
- access_level: open_access
checksum: 1aff850f47ae8c8f05ca48ff9faa38b1
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:47:27Z
date_updated: 2023-08-03T14:47:27Z
file_id: '13917'
file_name: Supplfig23_e.tif
file_size: 31500832
relation: main_file
success: 1
- access_level: open_access
checksum: f644de697d142c83461ed5ad1d72a043
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:48:38Z
date_updated: 2023-08-03T14:48:38Z
file_id: '13918'
file_name: Supplfig24_a_i.tif
file_size: 44179078
relation: main_file
success: 1
- access_level: open_access
checksum: eccb84925a6699b396d4b07efcbc7349
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:48:38Z
date_updated: 2023-08-03T14:48:38Z
file_id: '13919'
file_name: Supplfig24_a_ii.tif
file_size: 44125924
relation: main_file
success: 1
- access_level: open_access
checksum: afe7253e70ec79144e59b28c3c66703a
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:48:54Z
date_updated: 2023-08-03T14:48:54Z
file_id: '13920'
file_name: Supplfig24_a.tif
file_size: 1061835435
relation: main_file
success: 1
- access_level: open_access
checksum: 94a03b022aa84ea6e8515450a481ad82
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:48:39Z
date_updated: 2023-08-03T14:48:39Z
file_id: '13921'
file_name: Supplfig24_b_iii.tif
file_size: 3977824
relation: main_file
success: 1
- access_level: open_access
checksum: 166832c173fcda88ec6e35decdf0d197
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:48:39Z
date_updated: 2023-08-03T14:48:39Z
file_id: '13922'
file_name: Supplfig24_b_iv.tif
file_size: 3977825
relation: main_file
success: 1
- access_level: open_access
checksum: 53175073b83ab569241ae64ef7f180b3
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:51:27Z
date_updated: 2023-08-03T14:51:27Z
file_id: '13923'
file_name: Supplfig25_a_1.tif
file_size: 37641738
relation: main_file
success: 1
- access_level: open_access
checksum: 70e6a1780daeae6a5bef2c27c996c442
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:51:26Z
date_updated: 2023-08-03T14:51:26Z
file_id: '13924'
file_name: Supplfig25_a_2.tif
file_size: 4932897
relation: main_file
success: 1
- access_level: open_access
checksum: 1748266d7b8a2ae1f6292b9c265c2068
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:51:31Z
date_updated: 2023-08-03T14:51:31Z
file_id: '13925'
file_name: Supplfig25_b_1.tif
file_size: 357433570
relation: main_file
success: 1
- access_level: open_access
checksum: 8490f44160a482ea06d858eb3bc25a11
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:51:27Z
date_updated: 2023-08-03T14:51:27Z
file_id: '13926'
file_name: Supplfig25_b_2.tif
file_size: 27734506
relation: main_file
success: 1
- access_level: open_access
checksum: e5e9c550cc934a7725dc209c79951847
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:53:43Z
date_updated: 2023-08-03T14:53:43Z
file_id: '13927'
file_name: Suppfig26_h.tif
file_size: 35082394
relation: main_file
success: 1
- access_level: open_access
checksum: 39ae411d1e950e78bdc12937fb36f661
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:53:42Z
date_updated: 2023-08-03T14:53:42Z
file_id: '13928'
file_name: Supplfig26_a_1.tif
file_size: 16676477
relation: main_file
success: 1
- access_level: open_access
checksum: 450f5d0e8091639e27eb7a7991524e88
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:53:42Z
date_updated: 2023-08-03T14:53:42Z
file_id: '13929'
file_name: Supplfig26_a_2.tif
file_size: 170493
relation: main_file
success: 1
- access_level: open_access
checksum: 8e5a71801fa1fcb7f679d1af23344662
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:53:43Z
date_updated: 2023-08-03T14:53:43Z
file_id: '13930'
file_name: Supplfig26_b_1.tif
file_size: 11117737
relation: main_file
success: 1
- access_level: open_access
checksum: 519fb0326a0f0774b3edc1dafffcdd08
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:53:43Z
date_updated: 2023-08-03T14:53:43Z
file_id: '13931'
file_name: Supplfig26_b_2.tif
file_size: 113753
relation: main_file
success: 1
- access_level: open_access
checksum: d051c7d717eeb6f2ca59d8727ea62200
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:53:52Z
date_updated: 2023-08-03T14:53:52Z
file_id: '13932'
file_name: Supplfig26_c.tif
file_size: 495452386
relation: main_file
success: 1
- access_level: open_access
checksum: 5437b53e708572e2e9ad1432c260a04f
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:53:46Z
date_updated: 2023-08-03T14:53:46Z
file_id: '13933'
file_name: Supplfig26_d.tif
file_size: 132167170
relation: main_file
success: 1
- access_level: open_access
checksum: 0baab38829a8587ded5e39f85068124b
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:53:46Z
date_updated: 2023-08-03T14:53:46Z
file_id: '13934'
file_name: Supplfig26_e.tif
file_size: 11431214
relation: main_file
success: 1
- access_level: open_access
checksum: afa57f254c9dd987d90d5e43db3fb9e6
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:53:48Z
date_updated: 2023-08-03T14:53:48Z
file_id: '13935'
file_name: Supplfig26_f.tif
file_size: 64005702
relation: main_file
success: 1
- access_level: open_access
checksum: c35ba67ab92c410cb4370f91f3dea819
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:53:52Z
date_updated: 2023-08-03T14:53:52Z
file_id: '13936'
file_name: Supplfig26_g.tif
file_size: 246421054
relation: main_file
success: 1
- access_level: open_access
checksum: 3fd6186d73cbce1be79cf14a94a7f3bd
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:56:43Z
date_updated: 2023-08-03T14:56:43Z
file_id: '13937'
file_name: Supplfig27_a.tif
file_size: 166614932
relation: main_file
success: 1
- access_level: open_access
checksum: d1fc4c88e8e258e4e536a26e196d09b0
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:56:42Z
date_updated: 2023-08-03T14:56:42Z
file_id: '13938'
file_name: Supplfig27_b.tif
file_size: 143583446
relation: main_file
success: 1
- access_level: open_access
checksum: 8d6985530e86f38548e89e6380d73771
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:56:47Z
date_updated: 2023-08-03T14:56:47Z
file_id: '13939'
file_name: Supplfig27_c.tif
file_size: 172528188
relation: main_file
success: 1
- access_level: open_access
checksum: d0b1309d2120892ede84e04fdf0dbfbf
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:56:46Z
date_updated: 2023-08-03T14:56:46Z
file_id: '13940'
file_name: Supplfig27_d.tif
file_size: 113699256
relation: main_file
success: 1
- access_level: open_access
checksum: 4789b5254d0415ce314fc9e39cc52121
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:56:47Z
date_updated: 2023-08-03T14:56:47Z
file_id: '13941'
file_name: Supplfig27_e.tif
file_size: 88664548
relation: main_file
success: 1
- access_level: open_access
checksum: 7ff2d06534f062b0f17dab181f6c1f4e
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:56:47Z
date_updated: 2023-08-03T14:56:47Z
file_id: '13942'
file_name: Supplfig27_f.tif
file_size: 2298356
relation: main_file
success: 1
- access_level: open_access
checksum: 46de66d457b0def90f753c11927536b7
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:56:47Z
date_updated: 2023-08-03T14:56:47Z
file_id: '13943'
file_name: Supplfig27_g_1.tif
file_size: 499618
relation: main_file
success: 1
- access_level: open_access
checksum: 9ef5fba064a73a79dbc74b5e166d08ec
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:56:50Z
date_updated: 2023-08-03T14:56:50Z
file_id: '13944'
file_name: Supplfig27_g_2.tif
file_size: 202079026
relation: main_file
success: 1
- access_level: open_access
checksum: bf956c2b58d3da2baa869db5206d8d49
content_type: image/tiff
creator: jdanzl
date_created: 2023-08-03T14:56:48Z
date_updated: 2023-08-03T14:56:48Z
file_id: '13945'
file_name: Supplfig27_g_3.tif
file_size: 14639269
relation: main_file
success: 1
- access_level: open_access
checksum: 327dca11f42d5375d7f47f4cbd5b36c0
content_type: application/octet-stream
creator: jdanzl
date_created: 2023-08-03T15:21:01Z
date_updated: 2023-08-03T15:21:01Z
file_id: '13946'
file_name: model.p
file_size: 279467712
relation: main_file
success: 1
file_date_updated: 2023-08-04T13:19:47Z
has_accepted_license: '1'
month: '08'
oa: 1
oa_version: Published Version
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
name: Optical control of synaptic function via adhesion molecules
- _id: 26AA4EF2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
- _id: 23889792-32DE-11EA-91FC-C7463DDC885E
name: High content imaging to decode human immune cell interactions in health and
allergic disease
- _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: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
publisher: Institute of Science and Technology Austria
related_material:
link:
- description: 'Original data for Fig. 5d, Fig. 5d (N2V) and Fig. 5f-i, provided
via an external link due to the large size (>10GB) of the datasets. '
relation: research_data
url: https://pub.ista.ac.at/group_danzl/data/CATS/
record:
- id: '14257'
relation: used_in_publication
status: public
status: public
title: Research data for the publication "Imaging brain tissue architecture across
millimeter to nanometer scales"
tmp:
image: /images/cc_by_nc_sa.png
legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC
BY-NC-SA 4.0)
short: CC BY-NC-SA (4.0)
type: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2023'
...
---
_id: '13168'
abstract:
- lang: eng
text: Urban-living individuals are exposed to many environmental factors that may
combine and interact to influence mental health. While individual factors of an
urban environment have been investigated in isolation, no attempt has been made
to model how complex, real-life exposure to living in the city relates to brain
and mental health, and how this is moderated by genetic factors. Using the data
of 156,075 participants from the UK Biobank, we carried out sparse canonical correlation
analyses to investigate the relationships between urban environments and psychiatric
symptoms. We found an environmental profile of social deprivation, air pollution,
street network and urban land-use density that was positively correlated with
an affective symptom group (r = 0.22, Pperm < 0.001), mediated by brain volume
differences consistent with reward processing, and moderated by genes enriched
for stress response, including CRHR1, explaining 2.01% of the variance in brain
volume differences. Protective factors such as greenness and generous destination
accessibility were negatively correlated with an anxiety symptom group (r = 0.10,
Pperm < 0.001), mediated by brain regions necessary for emotion regulation and
moderated by EXD3, explaining 1.65% of the variance. The third urban environmental
profile was correlated with an emotional instability symptom group (r = 0.03,
Pperm < 0.001). Our findings suggest that different environmental profiles of
urban living may influence specific psychiatric symptom groups through distinct
neurobiological pathways.
acknowledgement: This work received support from the European Union-funded Horizon
Europe project ‘environMENTAL’ (no. 101057429 to G.S., A.M. and M.M.N.) and cofunding
by UK Research and Innovation under the UK Government’s Horizon Europe funding guarantee
(nos. 10041392 and 10038599) for study design and data analysis; the Horizon 2020-funded
European Research Council Advanced Grant ‘STRATIFY’ (no. 695313 to G.S. for study
design and data analysis); the Human Brain Project (HBP SGA3, no. 945539 to G.S.
for study design and data analysis); the National Institutes of Health (grant no.
R01DA049238 to G.S. for study design and data analysis); the German Research Foundation
(COPE; grant no. 675346 to G.S. for study design and data analysis); the National
Natural Science Foundation of China (grant no. 82001797 to J.X., grant no. 82030053
to C.Y., grant no. 82202093 to J.T. and grant no. 82150710554 to G.S. for study
design, data analysis and preparation of the manuscript); National Key Research
and Development Program of China (grant no. 2018YFC1314301 to C.Y. for study design
and data analysis); Tianjin Applied Basic Research Diversified Investment Foundation
(grant no. 21JCYBJC01360 to J.X. for study design and data analysis); Tianjin Health
Technology Project (grant no. TJWJ2021QN002 to J.X. for preparation of the manuscript);
Science & Technology Development Fund of the Tianjin Education Commission for Higher
Education (grant no. 2019KJ195 to J.X. for preparation of the manuscript); the Tianjin
Medical University ‘Clinical Talent Training 123 Climbing Plan’ to J.X. for the
preparation of the manuscript; Tianjin Key Medical Discipline (Specialty) Construction
Project (grant no. TJYXZDXK-001A to C.Y. for preparation of the manuscript); the
National Key R&D Program of China (grant no. 2022YFE0209400 to L.Y. for study design
and data analysis); the Tsinghua University Initiative Scientific Research Program
(grant no. 2021Z11GHX002 to L.Y. for study design and data analysis); the National
Key Scientific and Technological Infrastructure Project ‘Earth System Science Numerical
Simulator Facility’ (EarthLab to L.Y. for study design and data analysis); the Chinese
National High-end Foreign Expert Recruitment Plan to G.S.; and the Alexander von
Humboldt Foundation to G.S. for study design and data analysis.
article_processing_charge: No
article_type: original
author:
- first_name: Jiayuan
full_name: Xu, Jiayuan
last_name: Xu
- first_name: Nana
full_name: Liu, Nana
last_name: Liu
- first_name: Elli
full_name: Polemiti, Elli
last_name: Polemiti
- first_name: Liliana
full_name: Garcia-Mondragon, Liliana
last_name: Garcia-Mondragon
- first_name: Jie
full_name: Tang, Jie
last_name: Tang
- first_name: Xiaoxuan
full_name: Liu, Xiaoxuan
last_name: Liu
- first_name: Tristram
full_name: Lett, Tristram
last_name: Lett
- first_name: Le
full_name: Yu, Le
last_name: Yu
- first_name: Markus M.
full_name: Nöthen, Markus M.
last_name: Nöthen
- first_name: Jianfeng
full_name: Feng, Jianfeng
last_name: Feng
- first_name: Chunshui
full_name: Yu, Chunshui
last_name: Yu
- first_name: Andre
full_name: Marquand, Andre
last_name: Marquand
- first_name: Gunter
full_name: Schumann, Gunter
last_name: Schumann
- first_name: Henrik
full_name: Walter, Henrik
last_name: Walter
- first_name: Andreas
full_name: Heinz, Andreas
last_name: Heinz
- first_name: Markus
full_name: Ralser, Markus
last_name: Ralser
- first_name: Sven
full_name: Twardziok, Sven
last_name: Twardziok
- first_name: Nilakshi
full_name: Vaidya, Nilakshi
last_name: Vaidya
- first_name: Emin
full_name: Serin, Emin
last_name: Serin
- first_name: Marcel
full_name: Jentsch, Marcel
last_name: Jentsch
- first_name: Esther
full_name: Hitchen, Esther
last_name: Hitchen
- first_name: Roland
full_name: Eils, Roland
last_name: Eils
- first_name: Ulrike Helene
full_name: Taron, Ulrike Helene
last_name: Taron
- first_name: Tatjana
full_name: Schütz, Tatjana
last_name: Schütz
- first_name: Kerstin
full_name: Schepanski, Kerstin
last_name: Schepanski
- first_name: Jamie
full_name: Banks, Jamie
last_name: Banks
- first_name: Tobias
full_name: Banaschewski, Tobias
last_name: Banaschewski
- first_name: Karina
full_name: Jansone, Karina
last_name: Jansone
- first_name: Nina
full_name: Christmann, Nina
last_name: Christmann
- first_name: Andreas
full_name: Meyer-Lindenberg, Andreas
last_name: Meyer-Lindenberg
- first_name: Heike
full_name: Tost, Heike
last_name: Tost
- first_name: Nathalie
full_name: Holz, Nathalie
last_name: Holz
- first_name: Emanuel
full_name: Schwarz, Emanuel
last_name: Schwarz
- first_name: Argyris
full_name: Stringaris, Argyris
last_name: Stringaris
- first_name: Maja
full_name: Neidhart, Maja
last_name: Neidhart
- first_name: Frauke
full_name: Nees, Frauke
last_name: Nees
- first_name: Sebastian
full_name: Siehl, Sebastian
last_name: Siehl
- first_name: Ole
full_name: A. Andreassen, Ole
last_name: A. Andreassen
- first_name: Lars
full_name: T. Westlye, Lars
last_name: T. Westlye
- first_name: Dennis
full_name: Van Der Meer, Dennis
last_name: Van Der Meer
- first_name: Sara
full_name: Fernandez, Sara
last_name: Fernandez
- first_name: Rikka
full_name: Kjelkenes, Rikka
last_name: Kjelkenes
- first_name: Helga
full_name: Ask, Helga
last_name: Ask
- first_name: Michael
full_name: Rapp, Michael
last_name: Rapp
- first_name: Mira
full_name: Tschorn, Mira
last_name: Tschorn
- first_name: Sarah Jane
full_name: Böttger, Sarah Jane
last_name: Böttger
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Lena
full_name: Marr, Lena
id: 4406F586-F248-11E8-B48F-1D18A9856A87
last_name: Marr
- first_name: Mel
full_name: Slater, Mel
last_name: Slater
- first_name: Guillem Feixas
full_name: Viapiana, Guillem Feixas
last_name: Viapiana
- first_name: Francisco Eiroa
full_name: Orosa, Francisco Eiroa
last_name: Orosa
- first_name: Jaime
full_name: Gallego, Jaime
last_name: Gallego
- first_name: Alvaro
full_name: Pastor, Alvaro
last_name: Pastor
- first_name: Andreas
full_name: Forstner, Andreas
last_name: Forstner
- first_name: Per
full_name: Hoffmann, Per
last_name: Hoffmann
- first_name: Markus
full_name: M. Nöthen, Markus
last_name: M. Nöthen
- first_name: Andreas
full_name: J. Forstner, Andreas
last_name: J. Forstner
- first_name: Isabelle
full_name: Claus, Isabelle
last_name: Claus
- first_name: Abbi
full_name: Miller, Abbi
last_name: Miller
- first_name: Stefanie
full_name: Heilmann-Heimbach, Stefanie
last_name: Heilmann-Heimbach
- first_name: Peter
full_name: Sommer, Peter
last_name: Sommer
- first_name: Mona
full_name: Boye, Mona
last_name: Boye
- first_name: Johannes
full_name: Wilbertz, Johannes
last_name: Wilbertz
- first_name: Karen
full_name: Schmitt, Karen
last_name: Schmitt
- first_name: Viktor
full_name: Jirsa, Viktor
last_name: Jirsa
- first_name: Spase
full_name: Petkoski, Spase
last_name: Petkoski
- first_name: Séverine
full_name: Pitel, Séverine
last_name: Pitel
- first_name: Lisa
full_name: Otten, Lisa
last_name: Otten
- first_name: Anastasios Polykarpos
full_name: Athanasiadis, Anastasios Polykarpos
last_name: Athanasiadis
- first_name: Charlie
full_name: Pearmund, Charlie
last_name: Pearmund
- first_name: Bernhard
full_name: Spanlang, Bernhard
last_name: Spanlang
- first_name: Elena
full_name: Alvarez, Elena
last_name: Alvarez
- first_name: Mavi
full_name: Sanchez, Mavi
last_name: Sanchez
- first_name: Arantxa
full_name: Giner, Arantxa
last_name: Giner
- first_name: Sören
full_name: Hese, Sören
last_name: Hese
- first_name: Paul
full_name: Renner, Paul
last_name: Renner
- first_name: Tianye
full_name: Jia, Tianye
last_name: Jia
- first_name: Yanting
full_name: Gong, Yanting
last_name: Gong
- first_name: Yunman
full_name: Xia, Yunman
last_name: Xia
- first_name: Xiao
full_name: Chang, Xiao
last_name: Chang
- first_name: Vince
full_name: Calhoun, Vince
last_name: Calhoun
- first_name: Jingyu
full_name: Liu, Jingyu
last_name: Liu
- first_name: Paul
full_name: Thompson, Paul
last_name: Thompson
- first_name: Nicholas
full_name: Clinton, Nicholas
last_name: Clinton
- first_name: Sylvane
full_name: Desrivieres, Sylvane
last_name: Desrivieres
- first_name: Allan
full_name: H. Young, Allan
last_name: H. Young
- first_name: Bernd
full_name: Stahl, Bernd
last_name: Stahl
- first_name: George
full_name: Ogoh, George
last_name: Ogoh
citation:
ama: Xu J, Liu N, Polemiti E, et al. Effects of urban living environments on mental
health in adults. Nature Medicine. 2023;29:1456-1467. doi:10.1038/s41591-023-02365-w
apa: Xu, J., Liu, N., Polemiti, E., Garcia-Mondragon, L., Tang, J., Liu, X., … Ogoh,
G. (2023). Effects of urban living environments on mental health in adults. Nature
Medicine. Springer Nature. https://doi.org/10.1038/s41591-023-02365-w
chicago: Xu, Jiayuan, Nana Liu, Elli Polemiti, Liliana Garcia-Mondragon, Jie Tang,
Xiaoxuan Liu, Tristram Lett, et al. “Effects of Urban Living Environments on Mental
Health in Adults.” Nature Medicine. Springer Nature, 2023. https://doi.org/10.1038/s41591-023-02365-w.
ieee: J. Xu et al., “Effects of urban living environments on mental health
in adults,” Nature Medicine, vol. 29. Springer Nature, pp. 1456–1467, 2023.
ista: Xu J, Liu N, Polemiti E, Garcia-Mondragon L, Tang J, Liu X, Lett T, Yu L,
Nöthen MM, Feng J, Yu C, Marquand A, Schumann G, Walter H, Heinz A, Ralser M,
Twardziok S, Vaidya N, Serin E, Jentsch M, Hitchen E, Eils R, Taron UH, Schütz
T, Schepanski K, Banks J, Banaschewski T, Jansone K, Christmann N, Meyer-Lindenberg
A, Tost H, Holz N, Schwarz E, Stringaris A, Neidhart M, Nees F, Siehl S, A. Andreassen
O, T. Westlye L, Van Der Meer D, Fernandez S, Kjelkenes R, Ask H, Rapp M, Tschorn
M, Böttger SJ, Novarino G, Marr L, Slater M, Viapiana GF, Orosa FE, Gallego J,
Pastor A, Forstner A, Hoffmann P, M. Nöthen M, J. Forstner A, Claus I, Miller
A, Heilmann-Heimbach S, Sommer P, Boye M, Wilbertz J, Schmitt K, Jirsa V, Petkoski
S, Pitel S, Otten L, Athanasiadis AP, Pearmund C, Spanlang B, Alvarez E, Sanchez
M, Giner A, Hese S, Renner P, Jia T, Gong Y, Xia Y, Chang X, Calhoun V, Liu J,
Thompson P, Clinton N, Desrivieres S, H. Young A, Stahl B, Ogoh G. 2023. Effects
of urban living environments on mental health in adults. Nature Medicine. 29,
1456–1467.
mla: Xu, Jiayuan, et al. “Effects of Urban Living Environments on Mental Health
in Adults.” Nature Medicine, vol. 29, Springer Nature, 2023, pp. 1456–67,
doi:10.1038/s41591-023-02365-w.
short: J. Xu, N. Liu, E. Polemiti, L. Garcia-Mondragon, J. Tang, X. Liu, T. Lett,
L. Yu, M.M. Nöthen, J. Feng, C. Yu, A. Marquand, G. Schumann, H. Walter, A. Heinz,
M. Ralser, S. Twardziok, N. Vaidya, E. Serin, M. Jentsch, E. Hitchen, R. Eils,
U.H. Taron, T. Schütz, K. Schepanski, J. Banks, T. Banaschewski, K. Jansone, N.
Christmann, A. Meyer-Lindenberg, H. Tost, N. Holz, E. Schwarz, A. Stringaris,
M. Neidhart, F. Nees, S. Siehl, O. A. Andreassen, L. T. Westlye, D. Van Der Meer,
S. Fernandez, R. Kjelkenes, H. Ask, M. Rapp, M. Tschorn, S.J. Böttger, G. Novarino,
L. Marr, M. Slater, G.F. Viapiana, F.E. Orosa, J. Gallego, A. Pastor, A. Forstner,
P. Hoffmann, M. M. Nöthen, A. J. Forstner, I. Claus, A. Miller, S. Heilmann-Heimbach,
P. Sommer, M. Boye, J. Wilbertz, K. Schmitt, V. Jirsa, S. Petkoski, S. Pitel,
L. Otten, A.P. Athanasiadis, C. Pearmund, B. Spanlang, E. Alvarez, M. Sanchez,
A. Giner, S. Hese, P. Renner, T. Jia, Y. Gong, Y. Xia, X. Chang, V. Calhoun, J.
Liu, P. Thompson, N. Clinton, S. Desrivieres, A. H. Young, B. Stahl, G. Ogoh,
Nature Medicine 29 (2023) 1456–1467.
date_created: 2023-06-25T22:00:46Z
date_published: 2023-06-15T00:00:00Z
date_updated: 2023-12-13T11:25:55Z
day: '15'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.1038/s41591-023-02365-w
external_id:
isi:
- '001013172700001'
file:
- access_level: open_access
checksum: bcd3225b2731c3442fa98987fd3bd46d
content_type: application/pdf
creator: dernst
date_created: 2023-06-26T10:15:44Z
date_updated: 2023-06-26T10:15:44Z
file_id: '13171'
file_name: 2023_NatureMedicine_Xu.pdf
file_size: 7365360
relation: main_file
success: 1
file_date_updated: 2023-06-26T10:15:44Z
has_accepted_license: '1'
intvolume: ' 29'
isi: 1
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: 1456-1467
publication: Nature Medicine
publication_identifier:
eissn:
- 1546-170X
issn:
- 1078-8956
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Effects of urban living environments on mental health in adults
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 29
year: '2023'
...
---
_id: '13267'
abstract:
- lang: eng
text: Three-dimensional (3D) reconstruction of living brain tissue down to an individual
synapse level would create opportunities for decoding the dynamics and structure–function
relationships of the brain’s complex and dense information processing network;
however, this has been hindered by insufficient 3D resolution, inadequate signal-to-noise
ratio and prohibitive light burden in optical imaging, whereas electron microscopy
is inherently static. Here we solved these challenges by developing an integrated
optical/machine-learning technology, LIONESS (live information-optimized nanoscopy
enabling saturated segmentation). This leverages optical modifications to stimulated
emission depletion microscopy in comprehensively, extracellularly labeled tissue
and previous information on sample structure via machine learning to simultaneously
achieve isotropic super-resolution, high signal-to-noise ratio and compatibility
with living tissue. This allows dense deep-learning-based instance segmentation
and 3D reconstruction at a synapse level, incorporating molecular, activity and
morphodynamic information. LIONESS opens up avenues for studying the dynamic functional
(nano-)architecture of living brain tissue.
acknowledged_ssus:
- _id: ScienComp
- _id: Bio
- _id: PreCl
- _id: E-Lib
- _id: LifeSc
- _id: M-Shop
acknowledgement: "We thank J. Vorlaufer, N. Agudelo and A. Wartak for microscope maintenance
and troubleshooting, C. Kreuzinger and A. Freeman for technical assistance, M. Šuplata
for hardware control support and M. Cunha dos Santos for initial exploration of
software. We\r\nthank P. Henderson for advice on deep-learning training and M. Sixt,
S. Boyd and T. Weiss for discussions and critical reading of the manuscript. L.
Lavis (Janelia Research Campus) generously provided the JF585-HaloTag ligand. We
acknowledge expert support by IST\r\nAustria’s scientific computing, imaging and
optics, preclinical, library and laboratory support facilities and by the Miba machine
shop. We gratefully acknowledge funding by the following sources: Austrian Science
Fund (F.W.F.) grant no. I3600-B27 (J.G.D.), grant no. DK W1232\r\n(J.G.D. and J.M.M.)
and grant no. Z 312-B27, Wittgenstein award (P.J.); the Gesellschaft für Forschungsförderung
NÖ grant no. LSC18-022 (J.G.D.); an ISTA Interdisciplinary project grant (J.G.D.
and B.B.); the European Union’s Horizon 2020 research and innovation programme,\r\nMarie-Skłodowska
Curie grant 665385 (J.M.M. and J.L.); the European Union’s Horizon 2020 research
and innovation programme, European Research Council grant no. 715767, MATERIALIZABLE
(B.B.); grant no. 715508, REVERSEAUTISM (G.N.); grant no. 695568, SYNNOVATE (S.G.N.G.);
and grant no. 692692, GIANTSYN (P.J.); the Simons\r\nFoundation Autism Research
Initiative grant no. 529085 (S.G.N.G.); the Wellcome Trust Technology Development
grant no. 202932 (S.G.N.G.); the Marie Skłodowska-Curie Actions Individual Fellowship
no. 101026635 under the EU Horizon 2020 program (J.F.W.);\r\nthe Human Frontier
Science Program postdoctoral fellowship LT000557/2018 (W.J.); and the National Science
Foundation grant no. IIS-1835231 (H.P.) and NCS-FO-2124179 (H.P.)."
article_processing_charge: Yes
article_type: original
author:
- first_name: Philipp
full_name: Velicky, Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
- first_name: Eder
full_name: Miguel Villalba, Eder
id: 3FB91342-F248-11E8-B48F-1D18A9856A87
last_name: Miguel Villalba
orcid: 0000-0001-5665-0430
- first_name: Julia M
full_name: Michalska, Julia M
id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
last_name: Michalska
orcid: 0000-0003-3862-1235
- first_name: Julia
full_name: Lyudchik, Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Donglai
full_name: Wei, Donglai
last_name: Wei
- first_name: Zudi
full_name: Lin, Zudi
last_name: Lin
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Jakob
full_name: Troidl, Jakob
last_name: Troidl
- first_name: Johanna
full_name: Beyer, Johanna
last_name: Beyer
- first_name: Yoav
full_name: Ben Simon, Yoav
id: 43DF3136-F248-11E8-B48F-1D18A9856A87
last_name: Ben Simon
- 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: Wiebke
full_name: Jahr, Wiebke
id: 425C1CE8-F248-11E8-B48F-1D18A9856A87
last_name: Jahr
- first_name: Alban
full_name: Cenameri, Alban
id: 9ac8f577-2357-11eb-997a-e566c5550886
last_name: Cenameri
- first_name: Johannes
full_name: Broichhagen, Johannes
last_name: Broichhagen
- first_name: Seth G.N.
full_name: Grant, Seth G.N.
last_name: Grant
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Hanspeter
full_name: Pfister, Hanspeter
last_name: Pfister
- first_name: Bernd
full_name: Bickel, Bernd
id: 49876194-F248-11E8-B48F-1D18A9856A87
last_name: Bickel
orcid: 0000-0001-6511-9385
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
citation:
ama: Velicky P, Miguel Villalba E, Michalska JM, et al. Dense 4D nanoscale reconstruction
of living brain tissue. Nature Methods. 2023;20:1256-1265. doi:10.1038/s41592-023-01936-6
apa: Velicky, P., Miguel Villalba, E., Michalska, J. M., Lyudchik, J., Wei, D.,
Lin, Z., … Danzl, J. G. (2023). Dense 4D nanoscale reconstruction of living brain
tissue. Nature Methods. Springer Nature. https://doi.org/10.1038/s41592-023-01936-6
chicago: Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Julia Lyudchik,
Donglai Wei, Zudi Lin, Jake Watson, et al. “Dense 4D Nanoscale Reconstruction
of Living Brain Tissue.” Nature Methods. Springer Nature, 2023. https://doi.org/10.1038/s41592-023-01936-6.
ieee: P. Velicky et al., “Dense 4D nanoscale reconstruction of living brain
tissue,” Nature Methods, vol. 20. Springer Nature, pp. 1256–1265, 2023.
ista: Velicky P, Miguel Villalba E, Michalska JM, Lyudchik J, Wei D, Lin Z, Watson
J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen
J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. 2023. Dense
4D nanoscale reconstruction of living brain tissue. Nature Methods. 20, 1256–1265.
mla: Velicky, Philipp, et al. “Dense 4D Nanoscale Reconstruction of Living Brain
Tissue.” Nature Methods, vol. 20, Springer Nature, 2023, pp. 1256–65, doi:10.1038/s41592-023-01936-6.
short: P. Velicky, E. Miguel Villalba, J.M. Michalska, J. Lyudchik, D. Wei, Z. Lin,
J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri,
J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel,
J.G. Danzl, Nature Methods 20 (2023) 1256–1265.
date_created: 2023-07-23T22:01:13Z
date_published: 2023-08-01T00:00:00Z
date_updated: 2024-01-10T08:37:48Z
day: '01'
department:
- _id: PeJo
- _id: GaNo
- _id: BeBi
- _id: JoDa
- _id: Bio
doi: 10.1038/s41592-023-01936-6
ec_funded: 1
external_id:
isi:
- '001025621500001'
pmid:
- '37429995'
intvolume: ' 20'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1038/s41592-023-01936-6
month: '08'
oa: 1
oa_version: Published Version
page: 1256-1265
pmid: 1
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
name: Optical control of synaptic function via adhesion molecules
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
- _id: 23889792-32DE-11EA-91FC-C7463DDC885E
name: High content imaging to decode human immune cell interactions in health and
allergic disease
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
- _id: 24F9549A-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715767'
name: 'MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and
Modeling'
- _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: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
- _id: 2668BFA0-B435-11E9-9278-68D0E5697425
grant_number: LT00057
name: High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration
publication: Nature Methods
publication_identifier:
eissn:
- 1548-7105
issn:
- 1548-7091
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://github.com/danzllab/LIONESS
record:
- id: '12817'
relation: research_data
status: public
- id: '14770'
relation: shorter_version
status: public
scopus_import: '1'
status: public
title: Dense 4D nanoscale reconstruction of living brain tissue
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 20
year: '2023'
...
---
_id: '14257'
abstract:
- lang: eng
text: Mapping the complex and dense arrangement of cells and their connectivity
in brain tissue demands nanoscale spatial resolution imaging. Super-resolution
optical microscopy excels at visualizing specific molecules and individual cells
but fails to provide tissue context. Here we developed Comprehensive Analysis
of Tissues across Scales (CATS), a technology to densely map brain tissue architecture
from millimeter regional to nanometer synaptic scales in diverse chemically fixed
brain preparations, including rodent and human. CATS uses fixation-compatible
extracellular labeling and optical imaging, including stimulated emission depletion
or expansion microscopy, to comprehensively delineate cellular structures. It
enables three-dimensional reconstruction of single synapses and mapping of synaptic
connectivity by identification and analysis of putative synaptic cleft regions.
Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed
and quantified the synaptic input and output structure of identified neurons.
We furthermore demonstrate applicability to clinically derived human tissue samples,
including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing
the cellular architecture of brain tissue in health and disease.
acknowledged_ssus:
- _id: ScienComp
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: M-Shop
- _id: E-Lib
acknowledgement: 'We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak
for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I.
Erber for technical assistance; and M. Tomschik for support with obtaining human
samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata
for computational support and hardware control. We are grateful to R. Shigemoto
and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University)
for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly
provided by S. Grant (University of Edinburgh). We acknowledge expert support by
Institute of Science and Technology Austria’s scientific computing, imaging and
optics, preclinical and lab support facilities and by the Miba machine shop and
library. We gratefully acknowledge funding by the following sources: Austrian Science
Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232
(J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award
(P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27
(R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.);
European Union’s Horizon 2020 research and innovation programme, European Research
Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020
research and innovation programme, European Research Council (ERC) grant 692692
– GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under
the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions
Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).'
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Julia M
full_name: Michalska, Julia M
id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
last_name: Michalska
orcid: 0000-0003-3862-1235
- first_name: Julia
full_name: Lyudchik, Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Philipp
full_name: Velicky, Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
- first_name: Hana
full_name: Korinkova, Hana
id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed
last_name: Korinkova
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Alban
full_name: Cenameri, Alban
id: 9ac8f577-2357-11eb-997a-e566c5550886
last_name: Cenameri
- 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: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Karl
full_name: Roessler, Karl
last_name: Roessler
- first_name: Thomas
full_name: Czech, Thomas
last_name: Czech
- first_name: Romana
full_name: Höftberger, Romana
last_name: Höftberger
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
citation:
ama: Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture
across millimeter to nanometer scales. Nature Biotechnology. 2023. doi:10.1038/s41587-023-01911-8
apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri,
A., … Danzl, J. G. (2023). Imaging brain tissue architecture across millimeter
to nanometer scales. Nature Biotechnology. Springer Nature. https://doi.org/10.1038/s41587-023-01911-8
chicago: Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake
Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture
across Millimeter to Nanometer Scales.” Nature Biotechnology. Springer
Nature, 2023. https://doi.org/10.1038/s41587-023-01911-8.
ieee: J. M. Michalska et al., “Imaging brain tissue architecture across millimeter
to nanometer scales,” Nature Biotechnology. Springer Nature, 2023.
ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer
CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino
G, Jonas PM, Danzl JG. 2023. Imaging brain tissue architecture across millimeter
to nanometer scales. Nature Biotechnology.
mla: Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter
to Nanometer Scales.” Nature Biotechnology, Springer Nature, 2023, doi:10.1038/s41587-023-01911-8.
short: J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri,
C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S.
Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology (2023).
date_created: 2023-09-03T22:01:15Z
date_published: 2023-08-31T00:00:00Z
date_updated: 2024-02-21T12:18:18Z
day: '31'
department:
- _id: SaSi
- _id: GaNo
- _id: PeJo
- _id: JoDa
- _id: Bio
- _id: RySh
doi: 10.1038/s41587-023-01911-8
ec_funded: 1
external_id:
isi:
- '001065254200001'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1038/s41587-023-01911-8
month: '08'
oa: 1
oa_version: Published Version
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
name: Optical control of synaptic function via adhesion molecules
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
- _id: 23889792-32DE-11EA-91FC-C7463DDC885E
name: High content imaging to decode human immune cell interactions in health and
allergic disease
- _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: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
publication: Nature Biotechnology
publication_identifier:
eissn:
- 1546-1696
issn:
- 1087-0156
publication_status: epub_ahead
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://github.com/danzllab/CATS
record:
- id: '13126'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Imaging brain tissue architecture across millimeter to nanometer scales
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2023'
...
---
_id: '12802'
abstract:
- lang: eng
text: Little is known about the critical metabolic changes that neural cells have
to undergo during development and how temporary shifts in this program can influence
brain circuitries and behavior. Inspired by the discovery that mutations in SLC7A5,
a transporter of metabolically essential large neutral amino acids (LNAAs), lead
to autism, we employed metabolomic profiling to study the metabolic states of
the cerebral cortex across different developmental stages. We found that the forebrain
undergoes significant metabolic remodeling throughout development, with certain
groups of metabolites showing stage-specific changes, but what are the consequences
of perturbing this metabolic program? By manipulating Slc7a5 expression in neural
cells, we found that the metabolism of LNAAs and lipids are interconnected in
the cortex. Deletion of Slc7a5 in neurons affects the postnatal metabolic state,
leading to a shift in lipid metabolism. Additionally, it causes stage- and cell-type-specific
alterations in neuronal activity patterns, resulting in a long-term circuit dysfunction.
acknowledged_ssus:
- _id: PreCl
- _id: EM-Fac
- _id: Bio
- _id: LifeSc
acknowledgement: We thank A. Freeman and V. Voronin for technical assistance, S. Deixler,
A. Stichelberger, M. Schunn, and the Preclinical Facility for managing our animal
colony. We thank L. Andersen and J. Sonntag, who were involved in generating the
MADM lines. We thank the ISTA LSF Mass Spectrometry Core Facility for assistance
with the proteomic analysis, as well as the ISTA electron microscopy and Imaging
and Optics facility for technical support. Metabolomics LC-MS/MS analysis was performed
by the Metabolomics Facility at Vienna BioCenter Core Facilities (VBCF). We acknowledge
the support of the EMBL Metabolomics Core Facility (MCF) for lipidomics and intracellular
metabolomics mass spectrometry data acquisition and analysis. RNA sequencing was
performed by the Next Generation Sequencing Facility at VBCF. Schematics were generated
using Biorender.com. This work was supported by the Austrian Science Fund (FWF,
DK W1232-B24) and by the European Union’s Horizon 2020 research and innovation program
(ERC) grant 725780 (LinPro) to S.H. and 715508 (REVERSEAUTISM) to G.N.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Lisa
full_name: Knaus, Lisa
id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87
last_name: Knaus
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Daniel
full_name: Malzl, Daniel
last_name: Malzl
- first_name: Maria
full_name: Gerykova Bujalkova, Maria
last_name: Gerykova Bujalkova
- first_name: Mateja
full_name: Smogavec, Mateja
last_name: Smogavec
- first_name: Lena A.
full_name: Schwarz, Lena A.
last_name: Schwarz
- first_name: Sarah
full_name: Gorkiewicz, Sarah
id: f141a35d-15a9-11ec-9fb2-fef6becc7b6f
last_name: Gorkiewicz
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Christian
full_name: Knittl-Frank, Christian
last_name: Knittl-Frank
- first_name: Marianna
full_name: Tassinari, Marianna
id: 7af593f1-d44a-11ed-bf94-a3646a6bb35e
last_name: Tassinari
- first_name: Nuno
full_name: Maulide, Nuno
last_name: Maulide
- first_name: Thomas
full_name: Rülicke, Thomas
last_name: Rülicke
- first_name: Jörg
full_name: Menche, Jörg
last_name: Menche
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Knaus L, Basilico B, Malzl D, et al. Large neutral amino acid levels tune perinatal
neuronal excitability and survival. Cell. 2023;186(9):1950-1967.e25. doi:10.1016/j.cell.2023.02.037
apa: Knaus, L., Basilico, B., Malzl, D., Gerykova Bujalkova, M., Smogavec, M., Schwarz,
L. A., … Novarino, G. (2023). Large neutral amino acid levels tune perinatal neuronal
excitability and survival. Cell. Elsevier. https://doi.org/10.1016/j.cell.2023.02.037
chicago: Knaus, Lisa, Bernadette Basilico, Daniel Malzl, Maria Gerykova Bujalkova,
Mateja Smogavec, Lena A. Schwarz, Sarah Gorkiewicz, et al. “Large Neutral Amino
Acid Levels Tune Perinatal Neuronal Excitability and Survival.” Cell. Elsevier,
2023. https://doi.org/10.1016/j.cell.2023.02.037.
ieee: L. Knaus et al., “Large neutral amino acid levels tune perinatal neuronal
excitability and survival,” Cell, vol. 186, no. 9. Elsevier, p. 1950–1967.e25,
2023.
ista: Knaus L, Basilico B, Malzl D, Gerykova Bujalkova M, Smogavec M, Schwarz LA,
Gorkiewicz S, Amberg N, Pauler F, Knittl-Frank C, Tassinari M, Maulide N, Rülicke
T, Menche J, Hippenmeyer S, Novarino G. 2023. Large neutral amino acid levels
tune perinatal neuronal excitability and survival. Cell. 186(9), 1950–1967.e25.
mla: Knaus, Lisa, et al. “Large Neutral Amino Acid Levels Tune Perinatal Neuronal
Excitability and Survival.” Cell, vol. 186, no. 9, Elsevier, 2023, p. 1950–1967.e25,
doi:10.1016/j.cell.2023.02.037.
short: L. Knaus, B. Basilico, D. Malzl, M. Gerykova Bujalkova, M. Smogavec, L.A.
Schwarz, S. Gorkiewicz, N. Amberg, F. Pauler, C. Knittl-Frank, M. Tassinari, N.
Maulide, T. Rülicke, J. Menche, S. Hippenmeyer, G. Novarino, Cell 186 (2023) 1950–1967.e25.
date_created: 2023-04-05T08:15:40Z
date_published: 2023-04-27T00:00:00Z
date_updated: 2024-02-07T08:03:32Z
day: '27'
ddc:
- '570'
department:
- _id: SiHi
- _id: GaNo
doi: 10.1016/j.cell.2023.02.037
ec_funded: 1
external_id:
isi:
- '000991468700001'
file:
- access_level: open_access
checksum: 47e94fbe19e86505b429cb7a5b503ce6
content_type: application/pdf
creator: dernst
date_created: 2023-05-02T09:26:21Z
date_updated: 2023-05-02T09:26:21Z
file_id: '12889'
file_name: 2023_Cell_Knaus.pdf
file_size: 15712841
relation: main_file
success: 1
file_date_updated: 2023-05-02T09:26:21Z
has_accepted_license: '1'
intvolume: ' 186'
isi: 1
issue: '9'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: 1950-1967.e25
project:
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _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
publication: Cell
publication_identifier:
issn:
- 0092-8674
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on ISTA Website
relation: press_release
url: https://ista.ac.at/en/news/feed-them-or-lose-them/
record:
- id: '13107'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Large neutral amino acid levels tune perinatal neuronal excitability and survival
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: 186
year: '2023'
...
---
_id: '10818'
abstract:
- lang: eng
text: Microglia cells are active players in regulating synaptic development and
plasticity in the brain. However, how they influence the normal functioning of
synapses is largely unknown. In this study, we characterized the effects of pharmacological
microglia depletion, achieved by administration of PLX5622, on hippocampal CA3-CA1
synapses of adult wild type mice. Following microglial depletion, we observed
a reduction of spontaneous and evoked glutamatergic activity associated with a
decrease of dendritic spine density. We also observed the appearance of immature
synaptic features and higher levels of plasticity. Microglia depleted mice showed
a deficit in the acquisition of the Novel Object Recognition task. These events
were accompanied by hippocampal astrogliosis, although in the absence ofneuroinflammatory
condition. PLX-induced synaptic changes were absent in Cx3cr1−/− mice, highlighting
the role of CX3CL1/CX3CR1 axis in microglia control of synaptic functioning. Remarkably,
microglia repopulation after PLX5622 withdrawal was associated with the recovery
of hippocampal synapses and learning functions. Altogether, these data demonstrate
that microglia contribute to normal synaptic functioning in the adult brain and
that their removal induces reversible changes in organization and activity of
glutamatergic synapses.
acknowledgement: The work was supported by a grant from MIUR (PRIN 2017HPTFFC_003)
to Davide Ragozzino and in part by funds to Silvia Di Angelantonio (CrestOptics-IIT
JointLab for Advanced Microscopy) and Daniele Caprioli (Istituto Pasteur-Fondazione
Cenci Bolognetti). Bernadette Basilico, and Laura Ferrucci were supported by the
PhD program in Clinical-Experimental Neuroscience and Psychiatry, Sapienza University,
Rome; Caterina Sanchini was supported by the PhD program in Life Science, Sapienza
University, Rome and by the Italian Institute of Technology, Rome. The authors thank
Alessandro Felici, Claudia Valeri, Arsenio Armagno, and Senthilkumar Deivasigamani
for help with animal husbandry and transgenic colonies management. They also wish
to thank Piotr Bregestovski and Michal Schwartz for helpful discussions and criticism.
PLX5622 was provided under Materials Transfer Agreement by Plexxikon Inc. (Berkeley,
CA). Open Access Funding provided by Universita degli Studi di Roma La Sapienza
within the CRUI-CARE Agreement.
article_processing_charge: No
article_type: original
author:
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Laura
full_name: Ferrucci, Laura
last_name: Ferrucci
- first_name: Patrizia
full_name: Ratano, Patrizia
last_name: Ratano
- first_name: Maria T.
full_name: Golia, Maria T.
last_name: Golia
- first_name: Alfonso
full_name: Grimaldi, Alfonso
last_name: Grimaldi
- first_name: Maria
full_name: Rosito, Maria
last_name: Rosito
- first_name: Valentina
full_name: Ferretti, Valentina
last_name: Ferretti
- first_name: Ingrid
full_name: Reverte, Ingrid
last_name: Reverte
- first_name: Caterina
full_name: Sanchini, Caterina
last_name: Sanchini
- first_name: Maria C.
full_name: Marrone, Maria C.
last_name: Marrone
- first_name: Maria
full_name: Giubettini, Maria
last_name: Giubettini
- first_name: Valeria
full_name: De Turris, Valeria
last_name: De Turris
- first_name: Debora
full_name: Salerno, Debora
last_name: Salerno
- first_name: Stefano
full_name: Garofalo, Stefano
last_name: Garofalo
- first_name: Marie‐Kim
full_name: St‐Pierre, Marie‐Kim
last_name: St‐Pierre
- first_name: Micael
full_name: Carrier, Micael
last_name: Carrier
- first_name: Massimiliano
full_name: Renzi, Massimiliano
last_name: Renzi
- first_name: Francesca
full_name: Pagani, Francesca
last_name: Pagani
- first_name: Brijesh
full_name: Modi, Brijesh
last_name: Modi
- first_name: Marcello
full_name: Raspa, Marcello
last_name: Raspa
- first_name: Ferdinando
full_name: Scavizzi, Ferdinando
last_name: Scavizzi
- first_name: Cornelius T.
full_name: Gross, Cornelius T.
last_name: Gross
- first_name: Silvia
full_name: Marinelli, Silvia
last_name: Marinelli
- first_name: Marie‐Ève
full_name: Tremblay, Marie‐Ève
last_name: Tremblay
- first_name: Daniele
full_name: Caprioli, Daniele
last_name: Caprioli
- first_name: Laura
full_name: Maggi, Laura
last_name: Maggi
- first_name: Cristina
full_name: Limatola, Cristina
last_name: Limatola
- first_name: Silvia
full_name: Di Angelantonio, Silvia
last_name: Di Angelantonio
- first_name: Davide
full_name: Ragozzino, Davide
last_name: Ragozzino
citation:
ama: Basilico B, Ferrucci L, Ratano P, et al. Microglia control glutamatergic synapses
in the adult mouse hippocampus. Glia. 2022;70(1):173-195. doi:10.1002/glia.24101
apa: Basilico, B., Ferrucci, L., Ratano, P., Golia, M. T., Grimaldi, A., Rosito,
M., … Ragozzino, D. (2022). Microglia control glutamatergic synapses in the adult
mouse hippocampus. Glia. Wiley. https://doi.org/10.1002/glia.24101
chicago: Basilico, Bernadette, Laura Ferrucci, Patrizia Ratano, Maria T. Golia,
Alfonso Grimaldi, Maria Rosito, Valentina Ferretti, et al. “Microglia Control
Glutamatergic Synapses in the Adult Mouse Hippocampus.” Glia. Wiley, 2022.
https://doi.org/10.1002/glia.24101.
ieee: B. Basilico et al., “Microglia control glutamatergic synapses in the
adult mouse hippocampus,” Glia, vol. 70, no. 1. Wiley, pp. 173–195, 2022.
ista: Basilico B, Ferrucci L, Ratano P, Golia MT, Grimaldi A, Rosito M, Ferretti
V, Reverte I, Sanchini C, Marrone MC, Giubettini M, De Turris V, Salerno D, Garofalo
S, St‐Pierre M, Carrier M, Renzi M, Pagani F, Modi B, Raspa M, Scavizzi F, Gross
CT, Marinelli S, Tremblay M, Caprioli D, Maggi L, Limatola C, Di Angelantonio
S, Ragozzino D. 2022. Microglia control glutamatergic synapses in the adult mouse
hippocampus. Glia. 70(1), 173–195.
mla: Basilico, Bernadette, et al. “Microglia Control Glutamatergic Synapses in the
Adult Mouse Hippocampus.” Glia, vol. 70, no. 1, Wiley, 2022, pp. 173–95,
doi:10.1002/glia.24101.
short: B. Basilico, L. Ferrucci, P. Ratano, M.T. Golia, A. Grimaldi, M. Rosito,
V. Ferretti, I. Reverte, C. Sanchini, M.C. Marrone, M. Giubettini, V. De Turris,
D. Salerno, S. Garofalo, M. St‐Pierre, M. Carrier, M. Renzi, F. Pagani, B. Modi,
M. Raspa, F. Scavizzi, C.T. Gross, S. Marinelli, M. Tremblay, D. Caprioli, L.
Maggi, C. Limatola, S. Di Angelantonio, D. Ragozzino, Glia 70 (2022) 173–195.
date_created: 2022-03-04T08:53:37Z
date_published: 2022-01-01T00:00:00Z
date_updated: 2023-09-05T16:01:23Z
day: '01'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.1002/glia.24101
external_id:
isi:
- '000708025800001'
pmid:
- '34661306'
file:
- access_level: open_access
checksum: f10a897290e66c0a062e04ba91db6c17
content_type: application/pdf
creator: dernst
date_created: 2022-03-04T08:55:27Z
date_updated: 2022-03-04T08:55:27Z
file_id: '10819'
file_name: 2021_Glia_Basilico.pdf
file_size: 5340294
relation: main_file
success: 1
file_date_updated: 2022-03-04T08:55:27Z
has_accepted_license: '1'
intvolume: ' 70'
isi: 1
issue: '1'
keyword:
- Cellular and Molecular Neuroscience
- Neurology
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: 173-195
pmid: 1
publication: Glia
publication_identifier:
eissn:
- 1098-1136
issn:
- 0894-1491
publication_status: published
publisher: Wiley
quality_controlled: '1'
scopus_import: '1'
status: public
title: Microglia control glutamatergic synapses in the adult mouse hippocampus
tmp:
image: /images/cc_by_nc.png
legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
short: CC BY-NC (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 70
year: '2022'
...
---
_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: 2024-03-25T23:30:25Z
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: '11943'
abstract:
- lang: eng
text: Complex wiring between neurons underlies the information-processing network
enabling all brain functions, including cognition and memory. For understanding
how the network is structured, processes information, and changes over time, comprehensive
visualization of the architecture of living brain tissue with its cellular and
molecular components would open up major opportunities. However, electron microscopy
(EM) provides nanometre-scale resolution required for full in-silico
reconstruction1–5, yet is limited to fixed specimens and
static representations. Light microscopy allows live observation, with super-resolution
approaches6–12 facilitating nanoscale visualization, but
comprehensive 3D-reconstruction of living brain tissue has been hindered by tissue
photo-burden, photobleaching, insufficient 3D-resolution, and inadequate signal-to-noise
ratio (SNR). Here we demonstrate saturated reconstruction of living brain tissue.
We developed an integrated imaging and analysis technology, adapting stimulated
emission depletion (STED) microscopy6,13 in extracellularly
labelled tissue14 for high SNR and near-isotropic resolution.
Centrally, a two-stage deep-learning approach leveraged previously obtained information
on sample structure to drastically reduce photo-burden and enable automated volumetric
reconstruction down to single synapse level. Live reconstruction provides unbiased
analysis of tissue architecture across time in relation to functional activity
and targeted activation, and contextual understanding of molecular labelling.
This adoptable technology will facilitate novel insights into the dynamic functional
architecture of living brain tissue.
article_processing_charge: No
author:
- first_name: Philipp
full_name: Velicky, Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
- first_name: Eder
full_name: Miguel Villalba, Eder
id: 3FB91342-F248-11E8-B48F-1D18A9856A87
last_name: Miguel Villalba
orcid: 0000-0001-5665-0430
- first_name: Julia M
full_name: Michalska, Julia M
id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
last_name: Michalska
orcid: 0000-0003-3862-1235
- first_name: Donglai
full_name: Wei, Donglai
last_name: Wei
- first_name: Zudi
full_name: Lin, Zudi
last_name: Lin
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Jakob
full_name: Troidl, Jakob
last_name: Troidl
- first_name: Johanna
full_name: Beyer, Johanna
last_name: Beyer
- first_name: Yoav
full_name: Ben Simon, Yoav
id: 43DF3136-F248-11E8-B48F-1D18A9856A87
last_name: Ben Simon
- 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: Wiebke
full_name: Jahr, Wiebke
id: 425C1CE8-F248-11E8-B48F-1D18A9856A87
last_name: Jahr
- first_name: Alban
full_name: Cenameri, Alban
id: 9ac8f577-2357-11eb-997a-e566c5550886
last_name: Cenameri
- first_name: Johannes
full_name: Broichhagen, Johannes
last_name: Broichhagen
- first_name: Seth G. N.
full_name: Grant, Seth G. N.
last_name: Grant
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Hanspeter
full_name: Pfister, Hanspeter
last_name: Pfister
- first_name: Bernd
full_name: Bickel, Bernd
id: 49876194-F248-11E8-B48F-1D18A9856A87
last_name: Bickel
orcid: 0000-0001-6511-9385
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
citation:
ama: Velicky P, Miguel Villalba E, Michalska JM, et al. Saturated reconstruction
of living brain tissue. bioRxiv. doi:10.1101/2022.03.16.484431
apa: Velicky, P., Miguel Villalba, E., Michalska, J. M., Wei, D., Lin, Z., Watson,
J., … Danzl, J. G. (n.d.). Saturated reconstruction of living brain tissue. bioRxiv.
Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.03.16.484431
chicago: Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Donglai Wei,
Zudi Lin, Jake Watson, Jakob Troidl, et al. “Saturated Reconstruction of Living
Brain Tissue.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2022.03.16.484431.
ieee: P. Velicky et al., “Saturated reconstruction of living brain tissue,”
bioRxiv. Cold Spring Harbor Laboratory.
ista: Velicky P, Miguel Villalba E, Michalska JM, Wei D, Lin Z, Watson J, Troidl
J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN,
Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. Saturated reconstruction
of living brain tissue. bioRxiv, 10.1101/2022.03.16.484431.
mla: Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.”
BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2022.03.16.484431.
short: P. Velicky, E. Miguel Villalba, J.M. Michalska, D. Wei, Z. Lin, J. Watson,
J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen,
S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, BioRxiv
(n.d.).
date_created: 2022-08-23T11:07:59Z
date_published: 2022-05-09T00:00:00Z
date_updated: 2024-03-25T23:30:11Z
day: '09'
department:
- _id: PeJo
- _id: GaNo
- _id: BeBi
- _id: JoDa
doi: 10.1101/2022.03.16.484431
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2022.03.16.484431
month: '05'
oa: 1
oa_version: Preprint
publication: bioRxiv
publication_status: submitted
publisher: Cold Spring Harbor Laboratory
related_material:
record:
- id: '12470'
relation: dissertation_contains
status: public
status: public
title: Saturated reconstruction of living brain tissue
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...
---
_id: '11950'
abstract:
- lang: eng
text: Mapping the complex and dense arrangement of cells and their connectivity
in brain tissue demands nanoscale spatial resolution imaging. Super-resolution
optical microscopy excels at visualizing specific molecules and individual cells
but fails to provide tissue context. Here we developed Comprehensive Analysis
of Tissues across Scales (CATS), a technology to densely map brain tissue architecture
from millimeter regional to nanoscopic synaptic scales in diverse chemically fixed
brain preparations, including rodent and human. CATS leverages fixation-compatible
extracellular labeling and advanced optical readout, in particular stimulated-emission
depletion and expansion microscopy, to comprehensively delineate cellular structures.
It enables 3D-reconstructing single synapses and mapping synaptic connectivity
by identification and tailored analysis of putative synaptic cleft regions. Applying
CATS to the hippocampal mossy fiber circuitry, we demonstrate its power to reveal
the system’s molecularly informed ultrastructure across spatial scales and assess
local connectivity by reconstructing and quantifying the synaptic input and output
structure of identified neurons.
article_processing_charge: No
author:
- first_name: Julia M
full_name: Michalska, Julia M
id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
last_name: Michalska
orcid: 0000-0003-3862-1235
- first_name: Julia
full_name: Lyudchik, Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Philipp
full_name: Velicky, Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
- first_name: Hana
full_name: Korinkova, Hana
id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed
last_name: Korinkova
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Alban
full_name: Cenameri, Alban
id: 9ac8f577-2357-11eb-997a-e566c5550886
last_name: Cenameri
- 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: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Karl
full_name: Roessler, Karl
last_name: Roessler
- first_name: Thomas
full_name: Czech, Thomas
last_name: Czech
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
citation:
ama: Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture
across scales with super-resolution light microscopy. bioRxiv. doi:10.1101/2022.08.17.504272
apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri,
A., … Danzl, J. G. (n.d.). Uncovering brain tissue architecture across scales
with super-resolution light microscopy. bioRxiv. Cold Spring Harbor Laboratory.
https://doi.org/10.1101/2022.08.17.504272
chicago: Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake
Watson, Alban Cenameri, Christoph M Sommer, et al. “Uncovering Brain Tissue Architecture
across Scales with Super-Resolution Light Microscopy.” BioRxiv. Cold Spring
Harbor Laboratory, n.d. https://doi.org/10.1101/2022.08.17.504272.
ieee: J. M. Michalska et al., “Uncovering brain tissue architecture across
scales with super-resolution light microscopy,” bioRxiv. Cold Spring Harbor
Laboratory.
ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer
CM, Venturino A, Roessler K, Czech T, Siegert S, Novarino G, Jonas PM, Danzl JG.
Uncovering brain tissue architecture across scales with super-resolution light
microscopy. bioRxiv, 10.1101/2022.08.17.504272.
mla: Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales
with Super-Resolution Light Microscopy.” BioRxiv, Cold Spring Harbor Laboratory,
doi:10.1101/2022.08.17.504272.
short: J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri,
C.M. Sommer, A. Venturino, K. Roessler, T. Czech, S. Siegert, G. Novarino, P.M.
Jonas, J.G. Danzl, BioRxiv (n.d.).
date_created: 2022-08-24T08:24:52Z
date_published: 2022-08-18T00:00:00Z
date_updated: 2024-03-25T23:30:11Z
day: '18'
department:
- _id: SaSi
- _id: GaNo
- _id: PeJo
- _id: JoDa
doi: 10.1101/2022.08.17.504272
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2022.08.17.504272
month: '08'
oa: 1
oa_version: Preprint
publication: bioRxiv
publication_status: submitted
publisher: Cold Spring Harbor Laboratory
related_material:
record:
- id: '12470'
relation: dissertation_contains
status: public
status: public
title: Uncovering brain tissue architecture across scales with super-resolution light
microscopy
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...
---
_id: '12140'
abstract:
- lang: eng
text: Microglia are dynamic cells, constantly surveying their surroundings and interacting
with neurons and synapses. Indeed, a wealth of knowledge has revealed a critical
role of microglia in modulating synaptic transmission and plasticity in the developing
brain. In the past decade, novel pharmacological and genetic strategies have allowed
the acute removal of microglia, opening the possibility to explore and understand
the role of microglia also in the adult brain. In this review, we summarized and
discussed the contribution of microglia depletion strategies to the current understanding
of the role of microglia on synaptic function, learning and memory, and behavior
both in physiological and pathological conditions. We first described the available
microglia depletion methods highlighting their main strengths and weaknesses.
We then reviewed the impact of microglia depletion on structural and functional
synaptic plasticity. Next, we focused our analysis on the effects of microglia
depletion on behavior, including general locomotor activity, sensory perception,
motor function, sociability, learning and memory both in healthy animals and animal
models of disease. Finally, we integrated the findings from the reviewed studies
and discussed the emerging roles of microglia on the maintenance of synaptic function,
learning, memory strength and forgetfulness, and the implications of microglia
depletion in models of brain disease.
acknowledgement: "The write-up of the review was supported by Sapienza University
of Rome (Fondi di Ateneo, grant numbers #MA32117A7B698029 and #PH12017270934C3C
to SD), Regione Lazio (POR FSE 2014/20, grant number #19036AP000000019 to SD), Fulbright
2019 (grant number\r\n#FSP-P005556 to SD), Institute Pasteur Italia (Fondi Cenci
Bolognetti #363 to DR), and Network of European Funding for Neuroscience Research
(ERA-NET NEURON Transnational\r\nResearch Projects on Neurodevelopmental Disorders
2021, grant acronym #JTC2021-SHANKAstro to DR)."
article_number: '1022431'
article_processing_charge: No
article_type: original
author:
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Laura
full_name: Ferrucci, Laura
last_name: Ferrucci
- first_name: Azka
full_name: Khan, Azka
last_name: Khan
- first_name: Silvia
full_name: Di Angelantonio, Silvia
last_name: Di Angelantonio
- first_name: Davide
full_name: Ragozzino, Davide
last_name: Ragozzino
- first_name: Ingrid
full_name: Reverte, Ingrid
last_name: Reverte
citation:
ama: Basilico B, Ferrucci L, Khan A, Di Angelantonio S, Ragozzino D, Reverte I.
What microglia depletion approaches tell us about the role of microglia on synaptic
function and behavior. Frontiers in Cellular Neuroscience. 2022;16. doi:10.3389/fncel.2022.1022431
apa: Basilico, B., Ferrucci, L., Khan, A., Di Angelantonio, S., Ragozzino, D., &
Reverte, I. (2022). What microglia depletion approaches tell us about the role
of microglia on synaptic function and behavior. Frontiers in Cellular Neuroscience.
Frontiers Media. https://doi.org/10.3389/fncel.2022.1022431
chicago: Basilico, Bernadette, Laura Ferrucci, Azka Khan, Silvia Di Angelantonio,
Davide Ragozzino, and Ingrid Reverte. “What Microglia Depletion Approaches Tell
Us about the Role of Microglia on Synaptic Function and Behavior.” Frontiers
in Cellular Neuroscience. Frontiers Media, 2022. https://doi.org/10.3389/fncel.2022.1022431.
ieee: B. Basilico, L. Ferrucci, A. Khan, S. Di Angelantonio, D. Ragozzino, and I.
Reverte, “What microglia depletion approaches tell us about the role of microglia
on synaptic function and behavior,” Frontiers in Cellular Neuroscience,
vol. 16. Frontiers Media, 2022.
ista: Basilico B, Ferrucci L, Khan A, Di Angelantonio S, Ragozzino D, Reverte I.
2022. What microglia depletion approaches tell us about the role of microglia
on synaptic function and behavior. Frontiers in Cellular Neuroscience. 16, 1022431.
mla: Basilico, Bernadette, et al. “What Microglia Depletion Approaches Tell Us about
the Role of Microglia on Synaptic Function and Behavior.” Frontiers in Cellular
Neuroscience, vol. 16, 1022431, Frontiers Media, 2022, doi:10.3389/fncel.2022.1022431.
short: B. Basilico, L. Ferrucci, A. Khan, S. Di Angelantonio, D. Ragozzino, I. Reverte,
Frontiers in Cellular Neuroscience 16 (2022).
date_created: 2023-01-12T12:04:50Z
date_published: 2022-11-04T00:00:00Z
date_updated: 2023-08-04T08:56:10Z
day: '04'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.3389/fncel.2022.1022431
external_id:
isi:
- '000886526600001'
pmid:
- '36406752'
file:
- access_level: open_access
checksum: 84696213ecf99182c58a9f34b9ff2e23
content_type: application/pdf
creator: dernst
date_created: 2023-01-24T09:16:29Z
date_updated: 2023-01-24T09:16:29Z
file_id: '12352'
file_name: 2022_FrontiersNeuroscience_Basilico.pdf
file_size: 6399987
relation: main_file
success: 1
file_date_updated: 2023-01-24T09:16:29Z
has_accepted_license: '1'
intvolume: ' 16'
isi: 1
keyword:
- Cellular and Molecular Neuroscience
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
pmid: 1
publication: Frontiers in Cellular Neuroscience
publication_identifier:
issn:
- 1662-5102
publication_status: published
publisher: Frontiers Media
quality_controlled: '1'
scopus_import: '1'
status: public
title: What microglia depletion approaches tell us about the role of microglia on
synaptic function and behavior
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: 16
year: '2022'
...
---
_id: '12174'
abstract:
- lang: eng
text: "Vacuolar-type H+-ATPase (V-ATPase) is a multimeric complex present in a variety
of cellular membranes that acts as an ATP-dependent proton pump and plays a key
role in pH homeostasis and intracellular signalling pathways. In humans, 22 autosomal
genes encode for a redundant set of subunits allowing the composition of diverse
V-ATPase complexes with specific properties and expression. Sixteen subunits have
been linked to human disease.\r\nHere we describe 26 patients harbouring 20 distinct
pathogenic de novo missense ATP6V1A variants, mainly clustering within the ATP
synthase α/β family-nucleotide-binding domain. At a mean age of 7 years (extremes:
6 weeks, youngest deceased patient to 22 years, oldest patient) clinical pictures
included early lethal encephalopathies with rapidly progressive massive brain
atrophy, severe developmental epileptic encephalopathies and static intellectual
disability with epilepsy. The first clinical manifestation was early hypotonia,
in 70%; 81% developed epilepsy, manifested as developmental epileptic encephalopathies
in 58% of the cohort and with infantile spasms in 62%; 63% of developmental epileptic
encephalopathies failed to achieve any developmental, communicative or motor skills.
Less severe outcomes were observed in 23% of patients who, at a mean age of 10
years and 6 months, exhibited moderate intellectual disability, with independent
walking and variable epilepsy. None of the patients developed communicative language.
Microcephaly (38%) and amelogenesis imperfecta/enamel dysplasia (42%) were additional
clinical features. Brain MRI demonstrated hypomyelination and generalized atrophy
in 68%. Atrophy was progressive in all eight individuals undergoing repeated MRIs.\r\n
\ Fibroblasts of two patients with developmental epileptic
encephalopathies showed decreased LAMP1 expression, Lysotracker staining and increased
organelle pH, consistent with lysosomal impairment and loss of V-ATPase function.
Fibroblasts of two patients with milder disease, exhibited a different phenotype
with increased Lysotracker staining, decreased organelle pH and no significant
modification in LAMP1 expression. Quantification of substrates for lysosomal enzymes
in cellular extracts from four patients revealed discrete accumulation. Transmission
electron microscopy of fibroblasts of four patients with variable severity and
of induced pluripotent stem cell-derived neurons from two patients with developmental
epileptic encephalopathies showed electron-dense inclusions, lipid droplets, osmiophilic
material and lamellated membrane structures resembling phospholipids. Quantitative
assessment in induced pluripotent stem cell-derived neurons identified significantly
smaller lysosomes.\r\nATP6V1A-related encephalopathy represents a new paradigm
among lysosomal disorders. It results from a dysfunctional endo-lysosomal membrane
protein causing altered pH homeostasis. Its pathophysiology implies intracellular
accumulation of substrates whose composition remains unclear, and a combination
of developmental brain abnormalities and neurodegenerative changes established
during prenatal and early postanal development, whose severity is variably determined
by specific pathogenic variants."
acknowledged_ssus:
- _id: EM-Fac
- _id: LifeSc
acknowledgement: "We thank all patients and family members for their participation
in this study. We thank Melanie Pieraks and Eva Reinthaler (Neurolentech, Austria)
for generating the human iPSC lines and\r\nfor performing quality checks. We thank
Vanessa Zheden and Daniel Gütl for their excellent technical support in the specimen
preparation for transmission electron microscopy and Flavia Leite for preparing
the lentiviruses. The support from Electron Microscopy Facility and Molecular Biology
Services at IST Austria is greatly acknowledged. We would like to thank Doctors
Jane Hurst and Richard Scott for their help in retrieving the detailed clinical
information of Patient 17. The research team acknowledges the support of the National
Institute for Health Research, through the Comprehensive Clinical Research Network.
See Supplementary Material for Undiagnosed Disease Network consortium details. Genetic
information on Patient 23 was made available through access to the data and findings
generated by the 100 000 Genomes\r\nProject; www.genomicsengland.co.uk (to K.L.).
\r\nThis work was supported by the EU 7th Framework Programme (FP7) under the project
DESIRE grant N602531 (to R.G.); the Regione Toscana under the Call for Health 2018
(grant\r\nDECODE-EE) (to R.G.); the ‘Brain Project’ by Fondazione Cassa di Risparmio
di Firenze (to R.G.); IRCCS Ospedale Policlinico San Martino 5×1000 and Ricerca
Corrente (to A.F. and F.B.). The European Reference Network (ERN) for rare and complex
epilepsies (EpiCARE) provided financial support for meetings organization. The DDD
study presents independent research commissioned by the Health Innovation Challenge
Fund (grant number HICF-1009-003), a parallel funding partnership between Wellcome
and the Department of Health, and the Wellcome Sanger Institute (grant number WT098051).
The views expressed in this publication\r\nare those of the author(s) and not necessarily
those of Wellcome or the Department of Health. The study has UK Research Ethics
Committee approval (10/H0305/83, granted by the Cambridge South REC, and GEN/284/12
granted by the Republic of Ireland REC). This study makes use of DECIPHER (https://www.deciphergenomics.org),
which is funded by Wellcome. K.K.-S. was supported by the ISTplus fellowship. "
article_processing_charge: No
article_type: original
author:
- first_name: Renzo
full_name: Guerrini, Renzo
last_name: Guerrini
- first_name: Davide
full_name: Mei, Davide
last_name: Mei
- first_name: Margit Katalin
full_name: Szigeti, Margit Katalin
id: 44F4BDC0-F248-11E8-B48F-1D18A9856A87
last_name: Szigeti
orcid: 0000-0001-9500-8758
- first_name: Sara
full_name: Pepe, Sara
last_name: Pepe
- first_name: Mary Kay
full_name: Koenig, Mary Kay
last_name: Koenig
- first_name: Gretchen
full_name: Von Allmen, Gretchen
last_name: Von Allmen
- first_name: Megan T
full_name: Cho, Megan T
last_name: Cho
- first_name: Kimberly
full_name: McDonald, Kimberly
last_name: McDonald
- first_name: Janice
full_name: Baker, Janice
last_name: Baker
- first_name: Vikas
full_name: Bhambhani, Vikas
last_name: Bhambhani
- first_name: Zöe
full_name: Powis, Zöe
last_name: Powis
- first_name: Lance
full_name: Rodan, Lance
last_name: Rodan
- first_name: Rima
full_name: Nabbout, Rima
last_name: Nabbout
- first_name: Giulia
full_name: Barcia, Giulia
last_name: Barcia
- first_name: Jill A
full_name: Rosenfeld, Jill A
last_name: Rosenfeld
- first_name: Carlos A
full_name: Bacino, Carlos A
last_name: Bacino
- first_name: Cyril
full_name: Mignot, Cyril
last_name: Mignot
- first_name: Lillian H
full_name: Power, Lillian H
last_name: Power
- first_name: Catharine J
full_name: Harris, Catharine J
last_name: Harris
- first_name: Dragan
full_name: Marjanovic, Dragan
last_name: Marjanovic
- first_name: Rikke S
full_name: Møller, Rikke S
last_name: Møller
- first_name: Trine B
full_name: Hammer, Trine B
last_name: Hammer
- first_name: Riikka
full_name: Keski Filppula, Riikka
last_name: Keski Filppula
- first_name: Päivi
full_name: Vieira, Päivi
last_name: Vieira
- first_name: Clara
full_name: Hildebrandt, Clara
last_name: Hildebrandt
- first_name: Stephanie
full_name: Sacharow, Stephanie
last_name: Sacharow
- first_name: Luca
full_name: Maragliano, Luca
last_name: Maragliano
- first_name: Fabio
full_name: Benfenati, Fabio
last_name: Benfenati
- first_name: Katherine
full_name: Lachlan, Katherine
last_name: Lachlan
- first_name: Andreas
full_name: Benneche, Andreas
last_name: Benneche
- first_name: Florence
full_name: Petit, Florence
last_name: Petit
- first_name: Jean Madeleine
full_name: de Sainte Agathe, Jean Madeleine
last_name: de Sainte Agathe
- first_name: Barbara
full_name: Hallinan, Barbara
last_name: Hallinan
- first_name: Yue
full_name: Si, Yue
last_name: Si
- first_name: Ingrid M
full_name: Wentzensen, Ingrid M
last_name: Wentzensen
- first_name: Fanggeng
full_name: Zou, Fanggeng
last_name: Zou
- first_name: Vinodh
full_name: Narayanan, Vinodh
last_name: Narayanan
- first_name: Naomichi
full_name: Matsumoto, Naomichi
last_name: Matsumoto
- first_name: Alessandra
full_name: Boncristiano, Alessandra
last_name: Boncristiano
- first_name: Giancarlo
full_name: la Marca, Giancarlo
last_name: la Marca
- first_name: Mitsuhiro
full_name: Kato, Mitsuhiro
last_name: Kato
- first_name: Kristin
full_name: Anderson, Kristin
last_name: Anderson
- first_name: Carmen
full_name: Barba, Carmen
last_name: Barba
- first_name: Luisa
full_name: Sturiale, Luisa
last_name: Sturiale
- first_name: Domenico
full_name: Garozzo, Domenico
last_name: Garozzo
- first_name: Roberto
full_name: Bei, Roberto
last_name: Bei
- first_name: Laura
full_name: Masuelli, Laura
last_name: Masuelli
- first_name: Valerio
full_name: Conti, Valerio
last_name: Conti
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Anna
full_name: Fassio, Anna
last_name: Fassio
citation:
ama: 'Guerrini R, Mei D, Szigeti MK, et al. Phenotypic and genetic spectrum of ATP6V1A
encephalopathy: A disorder of lysosomal homeostasis. Brain. 2022;145(8):2687-2703.
doi:10.1093/brain/awac145'
apa: 'Guerrini, R., Mei, D., Szigeti, M. K., Pepe, S., Koenig, M. K., Von Allmen,
G., … Fassio, A. (2022). Phenotypic and genetic spectrum of ATP6V1A encephalopathy:
A disorder of lysosomal homeostasis. Brain. Oxford University Press. https://doi.org/10.1093/brain/awac145'
chicago: 'Guerrini, Renzo, Davide Mei, Margit Katalin Szigeti, Sara Pepe, Mary Kay
Koenig, Gretchen Von Allmen, Megan T Cho, et al. “Phenotypic and Genetic Spectrum
of ATP6V1A Encephalopathy: A Disorder of Lysosomal Homeostasis.” Brain.
Oxford University Press, 2022. https://doi.org/10.1093/brain/awac145.'
ieee: 'R. Guerrini et al., “Phenotypic and genetic spectrum of ATP6V1A encephalopathy:
A disorder of lysosomal homeostasis,” Brain, vol. 145, no. 8. Oxford University
Press, pp. 2687–2703, 2022.'
ista: 'Guerrini R, Mei D, Szigeti MK, Pepe S, Koenig MK, Von Allmen G, Cho MT, McDonald
K, Baker J, Bhambhani V, Powis Z, Rodan L, Nabbout R, Barcia G, Rosenfeld JA,
Bacino CA, Mignot C, Power LH, Harris CJ, Marjanovic D, Møller RS, Hammer TB,
Keski Filppula R, Vieira P, Hildebrandt C, Sacharow S, Maragliano L, Benfenati
F, Lachlan K, Benneche A, Petit F, de Sainte Agathe JM, Hallinan B, Si Y, Wentzensen
IM, Zou F, Narayanan V, Matsumoto N, Boncristiano A, la Marca G, Kato M, Anderson
K, Barba C, Sturiale L, Garozzo D, Bei R, Masuelli L, Conti V, Novarino G, Fassio
A. 2022. Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder
of lysosomal homeostasis. Brain. 145(8), 2687–2703.'
mla: 'Guerrini, Renzo, et al. “Phenotypic and Genetic Spectrum of ATP6V1A Encephalopathy:
A Disorder of Lysosomal Homeostasis.” Brain, vol. 145, no. 8, Oxford University
Press, 2022, pp. 2687–703, doi:10.1093/brain/awac145.'
short: R. Guerrini, D. Mei, M.K. Szigeti, S. Pepe, M.K. Koenig, G. Von Allmen, M.T.
Cho, K. McDonald, J. Baker, V. Bhambhani, Z. Powis, L. Rodan, R. Nabbout, G. Barcia,
J.A. Rosenfeld, C.A. Bacino, C. Mignot, L.H. Power, C.J. Harris, D. Marjanovic,
R.S. Møller, T.B. Hammer, R. Keski Filppula, P. Vieira, C. Hildebrandt, S. Sacharow,
L. Maragliano, F. Benfenati, K. Lachlan, A. Benneche, F. Petit, J.M. de Sainte
Agathe, B. Hallinan, Y. Si, I.M. Wentzensen, F. Zou, V. Narayanan, N. Matsumoto,
A. Boncristiano, G. la Marca, M. Kato, K. Anderson, C. Barba, L. Sturiale, D.
Garozzo, R. Bei, L. Masuelli, V. Conti, G. Novarino, A. Fassio, Brain 145 (2022)
2687–2703.
date_created: 2023-01-12T12:11:45Z
date_published: 2022-08-01T00:00:00Z
date_updated: 2023-08-04T09:13:08Z
day: '01'
department:
- _id: GaNo
doi: 10.1093/brain/awac145
ec_funded: 1
external_id:
isi:
- '000807770000001'
intvolume: ' 145'
isi: 1
issue: '8'
keyword:
- Neurology (clinical)
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1093/brain/awac145
month: '08'
oa: 1
oa_version: Published Version
page: 2687-2703
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
publication: Brain
publication_identifier:
eissn:
- 1460-2156
issn:
- 0006-8950
publication_status: published
publisher: Oxford University Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal
homeostasis'
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 145
year: '2022'
...
---
_id: '12268'
abstract:
- lang: eng
text: The complexity of the microenvironment effects on cell response, show accumulating
evidence that glioblastoma (GBM) migration and invasiveness are influenced by
the mechanical rigidity of their surroundings. The epithelial–mesenchymal transition
(EMT) is a well-recognized driving force of the invasive behavior of cancer. However,
the primary mechanisms of EMT initiation and progression remain unclear. We have
previously showed that certain substrate stiffness can selectively stimulate human
GBM U251-MG and GL15 glioblastoma cell lines motility. The present study unifies
several known EMT mediators to uncover the reason of the regulation and response
to these stiffnesses. Our results revealed that changing the rigidity of the mechanical
environment tuned the response of both cell lines through change in morphological
features, epithelial-mesenchymal markers (E-, N-Cadherin), EGFR and ROS expressions
in an interrelated manner. Specifically, a stiffer microenvironment induced a
mesenchymal cell shape, a more fragmented morphology, higher intracellular cytosolic
ROS expression and lower mitochondrial ROS. Finally, we observed that cells more
motile showed a more depolarized mitochondrial membrane potential. Unravelling
the process that regulates GBM cells’ infiltrative behavior could provide new
opportunities for identification of new targets and less invasive approaches for
treatment.
acknowledgement: "The research leading to these results has received funding from
AIRC under IG 2021 - ID. 26328 project – P.I. Cortese Barbara and AIRC under MFAG
2015 - ID. 16803 project – “P.I. Cortese Barbara”. The authors are also grateful
to the ”Tecnopolo per la medicina di precisione” (TecnoMed Puglia) - Regione Puglia:
DGR n.2117 del 21/11/2018, CUP: B84I18000540002 and “Tecnopolo di Nanotecnologia
e Fotonica per la medicina di precisione” (TECNOMED) - FISR/MIUR-CNR: delibera CIPE
n.3449 del 7-08-2017, CUP: B83B17000010001.\r\nWe thank Dr. Francesca Pagani for
useful technical support. We thank also Irene Iacuitto, Giovanna Loffredo and Manuela
Marchetti for practical administrative support."
article_number: '983507'
article_processing_charge: No
article_type: original
author:
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Ilaria Elena
full_name: Palamà, Ilaria Elena
last_name: Palamà
- first_name: Stefania
full_name: D’Amone, Stefania
last_name: D’Amone
- first_name: Clotilde
full_name: Lauro, Clotilde
last_name: Lauro
- first_name: Maria
full_name: Rosito, Maria
last_name: Rosito
- first_name: Maddalena
full_name: Grieco, Maddalena
last_name: Grieco
- first_name: Patrizia
full_name: Ratano, Patrizia
last_name: Ratano
- first_name: Federica
full_name: Cordella, Federica
last_name: Cordella
- first_name: Caterina
full_name: Sanchini, Caterina
last_name: Sanchini
- first_name: Silvia
full_name: Di Angelantonio, Silvia
last_name: Di Angelantonio
- first_name: Davide
full_name: Ragozzino, Davide
last_name: Ragozzino
- first_name: Mariafrancesca
full_name: Cascione, Mariafrancesca
last_name: Cascione
- first_name: Giuseppe
full_name: Gigli, Giuseppe
last_name: Gigli
- first_name: Barbara
full_name: Cortese, Barbara
last_name: Cortese
citation:
ama: Basilico B, Palamà IE, D’Amone S, et al. Substrate stiffness effect on molecular
crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma
cells. Frontiers in Oncology. 2022;12. doi:10.3389/fonc.2022.983507
apa: Basilico, B., Palamà, I. E., D’Amone, S., Lauro, C., Rosito, M., Grieco, M.,
… Cortese, B. (2022). Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal
transition mediators of human glioblastoma cells. Frontiers in Oncology.
Frontiers Media. https://doi.org/10.3389/fonc.2022.983507
chicago: Basilico, Bernadette, Ilaria Elena Palamà, Stefania D’Amone, Clotilde Lauro,
Maria Rosito, Maddalena Grieco, Patrizia Ratano, et al. “Substrate Stiffness Effect
on Molecular Crosstalk of Epithelial-Mesenchymal Transition Mediators of Human
Glioblastoma Cells.” Frontiers in Oncology. Frontiers Media, 2022. https://doi.org/10.3389/fonc.2022.983507.
ieee: B. Basilico et al., “Substrate stiffness effect on molecular crosstalk
of epithelial-mesenchymal transition mediators of human glioblastoma cells,” Frontiers
in Oncology, vol. 12. Frontiers Media, 2022.
ista: Basilico B, Palamà IE, D’Amone S, Lauro C, Rosito M, Grieco M, Ratano P, Cordella
F, Sanchini C, Di Angelantonio S, Ragozzino D, Cascione M, Gigli G, Cortese B.
2022. Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal
transition mediators of human glioblastoma cells. Frontiers in Oncology. 12, 983507.
mla: Basilico, Bernadette, et al. “Substrate Stiffness Effect on Molecular Crosstalk
of Epithelial-Mesenchymal Transition Mediators of Human Glioblastoma Cells.” Frontiers
in Oncology, vol. 12, 983507, Frontiers Media, 2022, doi:10.3389/fonc.2022.983507.
short: B. Basilico, I.E. Palamà, S. D’Amone, C. Lauro, M. Rosito, M. Grieco, P.
Ratano, F. Cordella, C. Sanchini, S. Di Angelantonio, D. Ragozzino, M. Cascione,
G. Gigli, B. Cortese, Frontiers in Oncology 12 (2022).
date_created: 2023-01-16T10:00:28Z
date_published: 2022-08-25T00:00:00Z
date_updated: 2023-08-04T09:54:16Z
day: '25'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.3389/fonc.2022.983507
external_id:
isi:
- '000856524900001'
pmid:
- '36091138'
file:
- access_level: open_access
checksum: efc7edf9f626af31853790c5b598a68c
content_type: application/pdf
creator: dernst
date_created: 2023-01-30T10:25:21Z
date_updated: 2023-01-30T10:25:21Z
file_id: '12450'
file_name: 2022_FrontiersOntology_Basilico.pdf
file_size: 13588502
relation: main_file
success: 1
file_date_updated: 2023-01-30T10:25:21Z
has_accepted_license: '1'
intvolume: ' 12'
isi: 1
keyword:
- Cancer Research
- Oncology
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
publication: Frontiers in Oncology
publication_identifier:
issn:
- 2234-943X
publication_status: published
publisher: Frontiers Media
quality_controlled: '1'
scopus_import: '1'
status: public
title: Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal
transition mediators of human glioblastoma cells
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: '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: '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: 2024-09-10T12:04:26Z
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: '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'
...