---
_id: '9540'
abstract:
- lang: eng
text: The hexameric AAA-ATPase Drg1 is a key factor in eukaryotic ribosome biogenesis
and initiates cytoplasmic maturation of the large ribosomal subunit by releasing
the shuttling maturation factor Rlp24. Drg1 monomers contain two AAA-domains (D1
and D2) that act in a concerted manner. Rlp24 release is inhibited by the drug
diazaborine which blocks ATP hydrolysis in D2. The mode of inhibition was unknown.
Here we show the first cryo-EM structure of Drg1 revealing the inhibitory mechanism.
Diazaborine forms a covalent bond to the 2′-OH of the nucleotide in D2, explaining
its specificity for this site. As a consequence, the D2 domain is locked in a
rigid, inactive state, stalling the whole Drg1 hexamer. Resistance mechanisms
identified include abolished drug binding and altered positioning of the nucleotide.
Our results suggest nucleotide-modifying compounds as potential novel inhibitors
for AAA-ATPases.
acknowledged_ssus:
- _id: EM-Fac
acknowledgement: We are deeply grateful to the late Gregor Högenauer who built the
foundation for this study with his visionary work on the inhibitor diazaborine and
its bacterial target. We thank Rolf Breinbauer for insightful discussions on boron
chemistry. We thank Anton Meinhart and Tim Clausen for the valuable discussion of
the manuscript. We are indebted to Thomas Köcher for the MS measurement of the diazaborine-ATPγS
adduct. We thank the team of the VBCF for support during early phases of this work
and the IST Austria Electron Microscopy Facility for providing equipment. The lab
of D.H. is supported by Boehringer Ingelheim. The work was funded by FWF projects
P32536 and P32977 (to H.B.).
article_number: '3483'
article_processing_charge: No
article_type: original
author:
- first_name: Michael
full_name: Prattes, Michael
last_name: Prattes
- first_name: Irina
full_name: Grishkovskaya, Irina
last_name: Grishkovskaya
- first_name: Victor-Valentin
full_name: Hodirnau, Victor-Valentin
id: 3661B498-F248-11E8-B48F-1D18A9856A87
last_name: Hodirnau
- first_name: Ingrid
full_name: Rössler, Ingrid
last_name: Rössler
- first_name: Isabella
full_name: Klein, Isabella
last_name: Klein
- first_name: Christina
full_name: Hetzmannseder, Christina
last_name: Hetzmannseder
- first_name: Gertrude
full_name: Zisser, Gertrude
last_name: Zisser
- first_name: Christian C.
full_name: Gruber, Christian C.
last_name: Gruber
- first_name: Karl
full_name: Gruber, Karl
last_name: Gruber
- first_name: David
full_name: Haselbach, David
last_name: Haselbach
- first_name: Helmut
full_name: Bergler, Helmut
last_name: Bergler
citation:
ama: Prattes M, Grishkovskaya I, Hodirnau V-V, et al. Structural basis for inhibition
of the AAA-ATPase Drg1 by diazaborine. Nature Communications. 2021;12(1).
doi:10.1038/s41467-021-23854-x
apa: Prattes, M., Grishkovskaya, I., Hodirnau, V.-V., Rössler, I., Klein, I., Hetzmannseder,
C., … Bergler, H. (2021). Structural basis for inhibition of the AAA-ATPase Drg1
by diazaborine. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-021-23854-x
chicago: Prattes, Michael, Irina Grishkovskaya, Victor-Valentin Hodirnau, Ingrid
Rössler, Isabella Klein, Christina Hetzmannseder, Gertrude Zisser, et al. “Structural
Basis for Inhibition of the AAA-ATPase Drg1 by Diazaborine.” Nature Communications.
Springer Nature, 2021. https://doi.org/10.1038/s41467-021-23854-x.
ieee: M. Prattes et al., “Structural basis for inhibition of the AAA-ATPase
Drg1 by diazaborine,” Nature Communications, vol. 12, no. 1. Springer Nature,
2021.
ista: Prattes M, Grishkovskaya I, Hodirnau V-V, Rössler I, Klein I, Hetzmannseder
C, Zisser G, Gruber CC, Gruber K, Haselbach D, Bergler H. 2021. Structural basis
for inhibition of the AAA-ATPase Drg1 by diazaborine. Nature Communications. 12(1),
3483.
mla: Prattes, Michael, et al. “Structural Basis for Inhibition of the AAA-ATPase
Drg1 by Diazaborine.” Nature Communications, vol. 12, no. 1, 3483, Springer
Nature, 2021, doi:10.1038/s41467-021-23854-x.
short: M. Prattes, I. Grishkovskaya, V.-V. Hodirnau, I. Rössler, I. Klein, C. Hetzmannseder,
G. Zisser, C.C. Gruber, K. Gruber, D. Haselbach, H. Bergler, Nature Communications
12 (2021).
date_created: 2021-06-10T14:57:45Z
date_published: 2021-06-09T00:00:00Z
date_updated: 2023-08-08T14:05:26Z
day: '09'
ddc:
- '570'
department:
- _id: EM-Fac
doi: 10.1038/s41467-021-23854-x
external_id:
isi:
- '000664874700014'
pmid:
- '34108481'
file:
- access_level: open_access
checksum: 40fc24c1310930990b52a8ad1142ee97
content_type: application/pdf
creator: cziletti
date_created: 2021-06-15T18:55:59Z
date_updated: 2021-06-15T18:55:59Z
file_id: '9556'
file_name: 2021_NatureComm_Prattes.pdf
file_size: 3397292
relation: main_file
success: 1
file_date_updated: 2021-06-15T18:55:59Z
has_accepted_license: '1'
intvolume: ' 12'
isi: 1
issue: '1'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
- General Physics and Astronomy
- General Chemistry
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
status: public
title: Structural basis for inhibition of the AAA-ATPase Drg1 by diazaborine
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: '9607'
abstract:
- lang: eng
text: While high risk of failure is an inherent part of developing innovative therapies,
it can be reduced by adherence to evidence-based rigorous research practices.
Numerous analyses conducted to date have clearly identified measures that need
to be taken to improve research rigor. Supported through the European Union's
Innovative Medicines Initiative, the EQIPD consortium has developed a novel preclinical
research quality system that can be applied in both public and private sectors
and is free for anyone to use. The EQIPD Quality System was designed to be suited
to boost innovation by ensuring the generation of robust and reliable preclinical
data while being lean, effective and not becoming a burden that could negatively
impact the freedom to explore scientific questions. EQIPD defines research quality
as the extent to which research data are fit for their intended use. Fitness,
in this context, is defined by the stakeholders, who are the scientists directly
involved in the research, but also their funders, sponsors, publishers, research
tool manufacturers and collaboration partners such as peers in a multi-site research
project. The essence of the EQIPD Quality System is the set of 18 core requirements
that can be addressed flexibly, according to user-specific needs and following
a user-defined trajectory. The EQIPD Quality System proposes guidance on expectations
for quality-related measures, defines criteria for adequate processes (i.e., performance
standards) and provides examples of how such measures can be developed and implemented.
However, it does not prescribe any pre-determined solutions. EQIPD has also developed
tools (for optional use) to support users in implementing the system and assessment
services for those research units that successfully implement the quality system
and seek formal accreditation. Building upon the feedback from users and continuous
improvement, a sustainable EQIPD Quality System will ultimately serve the entire
community of scientists conducting non-regulated preclinical research, by helping
them generate reliable data that are fit for their intended use.
acknowledgement: This project has received funding from the Innovative Medicines Initiative
2 Joint Undertaking under grant agreement No 777364. This Joint Undertaking receives
support from the European Union’s Horizon 2020 research and innovation programme
and EFPIA. The authors are very grateful to Martin Heinrich (Abbvie, Ludwigshafen,
Germany) for the exceptional IT support and programming the EQIPD Planning Tool
and the Creator Tool and to Dr Shai Silberberg (NINDS, USA), Dr. Renza Roncarati
(PAASP Italy) and Dr Judith Homberg (Radboud University, Nijmegen) for highly stimulating
contributions to the discussions and comments on earlier versions of this manuscript.
We also wish to express our thanks to Dr. Sara Stöber (concentris research management
GmbH, Fürstenfeldbruck, Germany) for excellent and continuous support of this project.
Creation of the EQIPD Stakeholder group was supported by Noldus Information Technology
bv (Wageningen, the Netherlands).
article_processing_charge: No
article_type: original
author:
- first_name: Anton
full_name: Bespalov, Anton
last_name: Bespalov
- first_name: René
full_name: Bernard, René
last_name: Bernard
- first_name: Anja
full_name: Gilis, Anja
last_name: Gilis
- first_name: Björn
full_name: Gerlach, Björn
last_name: Gerlach
- first_name: Javier
full_name: Guillén, Javier
last_name: Guillén
- first_name: Vincent
full_name: Castagné, Vincent
last_name: Castagné
- first_name: Isabel A.
full_name: Lefevre, Isabel A.
last_name: Lefevre
- first_name: Fiona
full_name: Ducrey, Fiona
last_name: Ducrey
- first_name: Lee
full_name: Monk, Lee
last_name: Monk
- first_name: Sandrine
full_name: Bongiovanni, Sandrine
last_name: Bongiovanni
- first_name: Bruce
full_name: Altevogt, Bruce
last_name: Altevogt
- first_name: María
full_name: Arroyo-Araujo, María
last_name: Arroyo-Araujo
- first_name: Lior
full_name: Bikovski, Lior
last_name: Bikovski
- first_name: Natasja
full_name: De Bruin, Natasja
last_name: De Bruin
- first_name: Esmeralda
full_name: Castaños-Vélez, Esmeralda
last_name: Castaños-Vélez
- first_name: Alexander
full_name: Dityatev, Alexander
last_name: Dityatev
- first_name: Christoph H.
full_name: Emmerich, Christoph H.
last_name: Emmerich
- first_name: Raafat
full_name: Fares, Raafat
last_name: Fares
- first_name: Chantelle
full_name: Ferland-Beckham, Chantelle
last_name: Ferland-Beckham
- first_name: Christelle
full_name: Froger-Colléaux, Christelle
last_name: Froger-Colléaux
- first_name: Valerie
full_name: Gailus-Durner, Valerie
last_name: Gailus-Durner
- first_name: Sabine M.
full_name: Hölter, Sabine M.
last_name: Hölter
- first_name: Martine Cj
full_name: Hofmann, Martine Cj
last_name: Hofmann
- first_name: Patricia
full_name: Kabitzke, Patricia
last_name: Kabitzke
- first_name: Martien Jh
full_name: Kas, Martien Jh
last_name: Kas
- first_name: Claudia
full_name: Kurreck, Claudia
last_name: Kurreck
- first_name: Paul
full_name: Moser, Paul
last_name: Moser
- first_name: Malgorzata
full_name: Pietraszek, Malgorzata
last_name: Pietraszek
- first_name: Piotr
full_name: Popik, Piotr
last_name: Popik
- first_name: Heidrun
full_name: Potschka, Heidrun
last_name: Potschka
- first_name: Ernesto
full_name: Prado Montes De Oca, Ernesto
last_name: Prado Montes De Oca
- first_name: Leonardo
full_name: Restivo, Leonardo
last_name: Restivo
- first_name: Gernot
full_name: Riedel, Gernot
last_name: Riedel
- first_name: Merel
full_name: Ritskes-Hoitinga, Merel
last_name: Ritskes-Hoitinga
- first_name: Janko
full_name: Samardzic, Janko
last_name: Samardzic
- first_name: Michael
full_name: Schunn, Michael
id: 4272DB4A-F248-11E8-B48F-1D18A9856A87
last_name: Schunn
orcid: 0000-0003-4326-5300
- first_name: Claudia
full_name: Stöger, Claudia
last_name: Stöger
- first_name: Vootele
full_name: Voikar, Vootele
last_name: Voikar
- first_name: Jan
full_name: Vollert, Jan
last_name: Vollert
- first_name: Kimberley E.
full_name: Wever, Kimberley E.
last_name: Wever
- first_name: Kathleen
full_name: Wuyts, Kathleen
last_name: Wuyts
- first_name: Malcolm R.
full_name: Macleod, Malcolm R.
last_name: Macleod
- first_name: Ulrich
full_name: Dirnagl, Ulrich
last_name: Dirnagl
- first_name: Thomas
full_name: Steckler, Thomas
last_name: Steckler
citation:
ama: Bespalov A, Bernard R, Gilis A, et al. Introduction to the EQIPD quality system.
eLife. 2021;10. doi:10.7554/eLife.63294
apa: Bespalov, A., Bernard, R., Gilis, A., Gerlach, B., Guillén, J., Castagné, V.,
… Steckler, T. (2021). Introduction to the EQIPD quality system. ELife.
eLife Sciences Publications. https://doi.org/10.7554/eLife.63294
chicago: Bespalov, Anton, René Bernard, Anja Gilis, Björn Gerlach, Javier Guillén,
Vincent Castagné, Isabel A. Lefevre, et al. “Introduction to the EQIPD Quality
System.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/eLife.63294.
ieee: A. Bespalov et al., “Introduction to the EQIPD quality system,” eLife,
vol. 10. eLife Sciences Publications, 2021.
ista: Bespalov A, Bernard R, Gilis A, Gerlach B, Guillén J, Castagné V, Lefevre
IA, Ducrey F, Monk L, Bongiovanni S, Altevogt B, Arroyo-Araujo M, Bikovski L,
De Bruin N, Castaños-Vélez E, Dityatev A, Emmerich CH, Fares R, Ferland-Beckham
C, Froger-Colléaux C, Gailus-Durner V, Hölter SM, Hofmann MC, Kabitzke P, Kas
MJ, Kurreck C, Moser P, Pietraszek M, Popik P, Potschka H, Prado Montes De Oca
E, Restivo L, Riedel G, Ritskes-Hoitinga M, Samardzic J, Schunn M, Stöger C, Voikar
V, Vollert J, Wever KE, Wuyts K, Macleod MR, Dirnagl U, Steckler T. 2021. Introduction
to the EQIPD quality system. eLife. 10.
mla: Bespalov, Anton, et al. “Introduction to the EQIPD Quality System.” ELife,
vol. 10, eLife Sciences Publications, 2021, doi:10.7554/eLife.63294.
short: A. Bespalov, R. Bernard, A. Gilis, B. Gerlach, J. Guillén, V. Castagné, I.A.
Lefevre, F. Ducrey, L. Monk, S. Bongiovanni, B. Altevogt, M. Arroyo-Araujo, L.
Bikovski, N. De Bruin, E. Castaños-Vélez, A. Dityatev, C.H. Emmerich, R. Fares,
C. Ferland-Beckham, C. Froger-Colléaux, V. Gailus-Durner, S.M. Hölter, M.C. Hofmann,
P. Kabitzke, M.J. Kas, C. Kurreck, P. Moser, M. Pietraszek, P. Popik, H. Potschka,
E. Prado Montes De Oca, L. Restivo, G. Riedel, M. Ritskes-Hoitinga, J. Samardzic,
M. Schunn, C. Stöger, V. Voikar, J. Vollert, K.E. Wever, K. Wuyts, M.R. Macleod,
U. Dirnagl, T. Steckler, ELife 10 (2021).
date_created: 2021-06-27T22:01:49Z
date_published: 2021-05-24T00:00:00Z
date_updated: 2023-08-10T13:36:50Z
day: '24'
ddc:
- '570'
department:
- _id: PreCl
doi: 10.7554/eLife.63294
external_id:
isi:
- '000661272000001'
pmid:
- '34028353'
file:
- access_level: open_access
checksum: 885b746051a7a6b6e24e3d2781a48fde
content_type: application/pdf
creator: asandaue
date_created: 2021-06-28T11:35:30Z
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month: '05'
oa: 1
oa_version: Published Version
pmid: 1
publication: eLife
publication_identifier:
eissn:
- 2050084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Introduction to the EQIPD quality system
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 10
year: '2021'
...
---
_id: '9603'
abstract:
- lang: eng
text: Mosaic analysis with double markers (MADM) offers one approach to visualize
and concomitantly manipulate genetically defined cells in mice with single-cell
resolution. MADM applications include the analysis of lineage, single-cell morphology
and physiology, genomic imprinting phenotypes, and dissection of cell-autonomous
gene functions in vivo in health and disease. Yet, MADM can only be applied to
<25% of all mouse genes on select chromosomes to date. To overcome this limitation,
we generate transgenic mice with knocked-in MADM cassettes near the centromeres
of all 19 autosomes and validate their use across organs. With this resource,
>96% of the entire mouse genome can now be subjected to single-cell genetic mosaic
analysis. Beyond a proof of principle, we apply our MADM library to systematically
trace sister chromatid segregation in distinct mitotic cell lineages. We find
striking chromosome-specific biases in segregation patterns, reflecting a putative
mechanism for the asymmetric segregation of genetic determinants in somatic stem
cell division.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: We thank the Bioimaging, Life Science, and Pre-Clinical Facilities
at IST Austria; M.P. Postiglione, C. Simbriger, K. Valoskova, C. Schwayer, T. Hussain,
M. Pieber, and V. Wimmer for initial experiments, technical support, and/or assistance;
R. Shigemoto for sharing iv (Dnah11 mutant) mice; and M. Sixt and all members of
the Hippenmeyer lab for discussion. This work was supported by National Institutes
of Health grants ( R01-NS050580 to L.L. and F32MH096361 to L.A.S.). L.L. is an investigator
of HHMI. N.A. received support from FWF Firnberg-Programm ( T 1031 ). A.H.H. is
a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences . This
work also received support from IST Austria institutional funds , FWF SFB F78 to
S.H., the People Programme (Marie Curie Actions) of the European Union’s Seventh
Framework Programme ( FP7/2007-2013 ) under REA grant agreement no 618444 to S.H.,
and the European Research Council (ERC) under the European Union’s Horizon 2020
Research and Innovation Programme (grant agreement no. 725780 LinPro ) to S.H.
article_number: '109274'
article_processing_charge: No
article_type: original
author:
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Amarbayasgalan
full_name: Davaatseren, Amarbayasgalan
id: 70ADC922-B424-11E9-99E3-BA18E6697425
last_name: Davaatseren
- first_name: Andi H
full_name: Hansen, Andi H
id: 38853E16-F248-11E8-B48F-1D18A9856A87
last_name: Hansen
- first_name: Johanna
full_name: Sonntag, Johanna
id: 32FE7D7C-F248-11E8-B48F-1D18A9856A87
last_name: Sonntag
- first_name: Lill
full_name: Andersen, Lill
last_name: Andersen
- first_name: Tina
full_name: Bernthaler, Tina
last_name: Bernthaler
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Anna-Magdalena
full_name: Heger, Anna-Magdalena
id: 4B76FFD2-F248-11E8-B48F-1D18A9856A87
last_name: Heger
- first_name: Randy L.
full_name: Johnson, Randy L.
last_name: Johnson
- first_name: Lindsay A.
full_name: Schwarz, Lindsay A.
last_name: Schwarz
- first_name: Liqun
full_name: Luo, Liqun
last_name: Luo
- first_name: Thomas
full_name: Rülicke, Thomas
last_name: Rülicke
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Contreras X, Amberg N, Davaatseren A, et al. A genome-wide library of MADM
mice for single-cell genetic mosaic analysis. Cell Reports. 2021;35(12).
doi:10.1016/j.celrep.2021.109274
apa: Contreras, X., Amberg, N., Davaatseren, A., Hansen, A. H., Sonntag, J., Andersen,
L., … Hippenmeyer, S. (2021). A genome-wide library of MADM mice for single-cell
genetic mosaic analysis. Cell Reports. Cell Press. https://doi.org/10.1016/j.celrep.2021.109274
chicago: Contreras, Ximena, Nicole Amberg, Amarbayasgalan Davaatseren, Andi H Hansen,
Johanna Sonntag, Lill Andersen, Tina Bernthaler, et al. “A Genome-Wide Library
of MADM Mice for Single-Cell Genetic Mosaic Analysis.” Cell Reports. Cell
Press, 2021. https://doi.org/10.1016/j.celrep.2021.109274.
ieee: X. Contreras et al., “A genome-wide library of MADM mice for single-cell
genetic mosaic analysis,” Cell Reports, vol. 35, no. 12. Cell Press, 2021.
ista: Contreras X, Amberg N, Davaatseren A, Hansen AH, Sonntag J, Andersen L, Bernthaler
T, Streicher C, Heger A-M, Johnson RL, Schwarz LA, Luo L, Rülicke T, Hippenmeyer
S. 2021. A genome-wide library of MADM mice for single-cell genetic mosaic analysis.
Cell Reports. 35(12), 109274.
mla: Contreras, Ximena, et al. “A Genome-Wide Library of MADM Mice for Single-Cell
Genetic Mosaic Analysis.” Cell Reports, vol. 35, no. 12, 109274, Cell Press,
2021, doi:10.1016/j.celrep.2021.109274.
short: X. Contreras, N. Amberg, A. Davaatseren, A.H. Hansen, J. Sonntag, L. Andersen,
T. Bernthaler, C. Streicher, A.-M. Heger, R.L. Johnson, L.A. Schwarz, L. Luo,
T. Rülicke, S. Hippenmeyer, Cell Reports 35 (2021).
date_created: 2021-06-27T22:01:48Z
date_published: 2021-06-22T00:00:00Z
date_updated: 2023-08-10T13:55:00Z
day: '22'
ddc:
- '570'
department:
- _id: SiHi
- _id: LoSw
- _id: PreCl
doi: 10.1016/j.celrep.2021.109274
ec_funded: 1
external_id:
isi:
- '000664463600016'
file:
- access_level: open_access
checksum: d49520fdcbbb5c2f883bddb67cee5d77
content_type: application/pdf
creator: asandaue
date_created: 2021-06-28T14:06:24Z
date_updated: 2021-06-28T14:06:24Z
file_id: '9613'
file_name: 2021_CellReports_Contreras.pdf
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relation: main_file
success: 1
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has_accepted_license: '1'
intvolume: ' 35'
isi: 1
issue: '12'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
project:
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
grant_number: '24812'
name: Molecular Mechanisms of Radial Neuronal Migration
- _id: 25D61E48-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '618444'
name: Molecular Mechanisms of Cerebral Cortex Development
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Cell Reports
publication_identifier:
eissn:
- '22111247'
publication_status: published
publisher: Cell Press
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/boost-for-mouse-genetic-analysis/
scopus_import: '1'
status: public
title: A genome-wide library of MADM mice for single-cell genetic mosaic analysis
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 35
year: '2021'
...
---
_id: '9822'
abstract:
- lang: eng
text: Attachment of adhesive molecules on cell culture surfaces to restrict cell
adhesion to defined areas and shapes has been vital for the progress of in vitro
research. In currently existing patterning methods, a combination of pattern properties
such as stability, precision, specificity, high-throughput outcome, and spatiotemporal
control is highly desirable but challenging to achieve. Here, we introduce a versatile
and high-throughput covalent photoimmobilization technique, comprising a light-dose-dependent
patterning step and a subsequent functionalization of the pattern via click chemistry.
This two-step process is feasible on arbitrary surfaces and allows for generation
of sustainable patterns and gradients. The method is validated in different biological
systems by patterning adhesive ligands on cell-repellent surfaces, thereby constraining
the growth and migration of cells to the designated areas. We then implement a
sequential photopatterning approach by adding a second switchable patterning step,
allowing for spatiotemporal control over two distinct surface patterns. As a proof
of concept, we reconstruct the dynamics of the tip/stalk cell switch during angiogenesis.
Our results show that the spatiotemporal control provided by our “sequential photopatterning”
system is essential for mimicking dynamic biological processes and that our innovative
approach has great potential for further applications in cell science.
acknowledgement: We would like to thank Charlott Leu for the production of our chromium
wafers, Louise Ritter for her contribution of the IF stainings in Figure 4, Shokoufeh
Teymouri for her help with the Bioinert coated slides, and finally Prof. Dr. Joachim
Rädler for his valuable scientific guidance.
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Themistoklis
full_name: Zisis, Themistoklis
last_name: Zisis
- first_name: Jan
full_name: Schwarz, Jan
id: 346C1EC6-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
- first_name: Miriam
full_name: Balles, Miriam
last_name: Balles
- first_name: Maibritt
full_name: Kretschmer, Maibritt
last_name: Kretschmer
- first_name: Maria
full_name: Nemethova, Maria
id: 34E27F1C-F248-11E8-B48F-1D18A9856A87
last_name: Nemethova
- first_name: Remy P
full_name: Chait, Remy P
id: 3464AE84-F248-11E8-B48F-1D18A9856A87
last_name: Chait
orcid: 0000-0003-0876-3187
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Janina
full_name: Lange, Janina
last_name: Lange
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-4561-241X
- first_name: Stefan
full_name: Zahler, Stefan
last_name: Zahler
citation:
ama: Zisis T, Schwarz J, Balles M, et al. Sequential and switchable patterning for
studying cellular processes under spatiotemporal control. ACS Applied Materials
and Interfaces. 2021;13(30):35545–35560. doi:10.1021/acsami.1c09850
apa: Zisis, T., Schwarz, J., Balles, M., Kretschmer, M., Nemethova, M., Chait, R.
P., … Zahler, S. (2021). Sequential and switchable patterning for studying cellular
processes under spatiotemporal control. ACS Applied Materials and Interfaces.
American Chemical Society. https://doi.org/10.1021/acsami.1c09850
chicago: Zisis, Themistoklis, Jan Schwarz, Miriam Balles, Maibritt Kretschmer, Maria
Nemethova, Remy P Chait, Robert Hauschild, et al. “Sequential and Switchable Patterning
for Studying Cellular Processes under Spatiotemporal Control.” ACS Applied
Materials and Interfaces. American Chemical Society, 2021. https://doi.org/10.1021/acsami.1c09850.
ieee: T. Zisis et al., “Sequential and switchable patterning for studying
cellular processes under spatiotemporal control,” ACS Applied Materials and
Interfaces, vol. 13, no. 30. American Chemical Society, pp. 35545–35560, 2021.
ista: Zisis T, Schwarz J, Balles M, Kretschmer M, Nemethova M, Chait RP, Hauschild
R, Lange J, Guet CC, Sixt MK, Zahler S. 2021. Sequential and switchable patterning
for studying cellular processes under spatiotemporal control. ACS Applied Materials
and Interfaces. 13(30), 35545–35560.
mla: Zisis, Themistoklis, et al. “Sequential and Switchable Patterning for Studying
Cellular Processes under Spatiotemporal Control.” ACS Applied Materials and
Interfaces, vol. 13, no. 30, American Chemical Society, 2021, pp. 35545–35560,
doi:10.1021/acsami.1c09850.
short: T. Zisis, J. Schwarz, M. Balles, M. Kretschmer, M. Nemethova, R.P. Chait,
R. Hauschild, J. Lange, C.C. Guet, M.K. Sixt, S. Zahler, ACS Applied Materials
and Interfaces 13 (2021) 35545–35560.
date_created: 2021-08-08T22:01:28Z
date_published: 2021-08-04T00:00:00Z
date_updated: 2023-08-10T14:22:48Z
day: '04'
ddc:
- '620'
- '570'
department:
- _id: MiSi
- _id: GaTk
- _id: Bio
- _id: CaGu
doi: 10.1021/acsami.1c09850
ec_funded: 1
external_id:
isi:
- '000683741400026'
pmid:
- '34283577'
file:
- access_level: open_access
checksum: b043a91d9f9200e467b970b692687ed3
content_type: application/pdf
creator: asandaue
date_created: 2021-08-09T09:44:03Z
date_updated: 2021-08-09T09:44:03Z
file_id: '9833'
file_name: 2021_ACSAppliedMaterialsAndInterfaces_Zisis.pdf
file_size: 7123293
relation: main_file
success: 1
file_date_updated: 2021-08-09T09:44:03Z
has_accepted_license: '1'
intvolume: ' 13'
isi: 1
issue: '30'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: 35545–35560
pmid: 1
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular navigation along spatial gradients
publication: ACS Applied Materials and Interfaces
publication_identifier:
eissn:
- '19448252'
issn:
- '19448244'
publication_status: published
publisher: American Chemical Society
quality_controlled: '1'
scopus_import: '1'
status: public
title: Sequential and switchable patterning for studying cellular processes under
spatiotemporal control
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 13
year: '2021'
...
---
_id: '9911'
abstract:
- lang: eng
text: A modern day light microscope has evolved from a tool devoted to making primarily
empirical observations to what is now a sophisticated , quantitative device that
is an integral part of both physical and life science research. Nowadays, microscopes
are found in nearly every experimental laboratory. However, despite their prevalent
use in capturing and quantifying scientific phenomena, neither a thorough understanding
of the principles underlying quantitative imaging techniques nor appropriate knowledge
of how to calibrate, operate and maintain microscopes can be taken for granted.
This is clearly demonstrated by the well-documented and widespread difficulties
that are routinely encountered in evaluating acquired data and reproducing scientific
experiments. Indeed, studies have shown that more than 70% of researchers have
tried and failed to repeat another scientist's experiments, while more than half
have even failed to reproduce their own experiments. One factor behind the reproducibility
crisis of experiments published in scientific journals is the frequent underreporting
of imaging methods caused by a lack of awareness and/or a lack of knowledge of
the applied technique. Whereas quality control procedures for some methods used
in biomedical research, such as genomics (e.g. DNA sequencing, RNA-seq) or cytometry,
have been introduced (e.g. ENCODE), this issue has not been tackled for optical
microscopy instrumentation and images. Although many calibration standards and
protocols have been published, there is a lack of awareness and agreement on common
standards and guidelines for quality assessment and reproducibility. In April
2020, the QUality Assessment and REProducibility for instruments and images in
Light Microscopy (QUAREP-LiMi) initiative was formed. This initiative comprises
imaging scientists from academia and industry who share a common interest in achieving
a better understanding of the performance and limitations of microscopes and improved
quality control (QC) in light microscopy. The ultimate goal of the QUAREP-LiMi
initiative is to establish a set of common QC standards, guidelines, metadata
models and tools, including detailed protocols, with the ultimate aim of improving
reproducible advances in scientific research. This White Paper (1) summarizes
the major obstacles identified in the field that motivated the launch of the QUAREP-LiMi
initiative; (2) identifies the urgent need to address these obstacles in a grassroots
manner, through a community of stakeholders including, researchers, imaging scientists,
bioimage analysts, bioimage informatics developers, corporate partners, funding
agencies, standards organizations, scientific publishers and observers of such;
(3) outlines the current actions of the QUAREP-LiMi initiative and (4) proposes
future steps that can be taken to improve the dissemination and acceptance of
the proposed guidelines to manage QC. To summarize, the principal goal of the
QUAREP-LiMi initiative is to improve the overall quality and reproducibility of
light microscope image data by introducing broadly accepted standard practices
and accurately captured image data metrics.
acknowledgement: We thank https://www.somersault1824.com/somersault18:24 BV (Leuven,
Belgium) for help with Figure 1. E. C.-S. was supported by the project PPBI-POCI-01-0145-FEDER-022122,
in the scope of Fundação para a Ciência e Tecnologia, Portugal (FCT) National Roadmap
of Research Infrastructures. R.N. was funded by the Deutsche Forschungsgemeinschaft
(DFG, German Research Foundation) Grant number Ni 451/9-1 - MIAP-Freiburg.
article_processing_charge: Yes
article_type: original
author:
- first_name: Glyn
full_name: Nelson, Glyn
last_name: Nelson
- first_name: Ulrike
full_name: Boehm, Ulrike
last_name: Boehm
- first_name: Steve
full_name: Bagley, Steve
last_name: Bagley
- first_name: Peter
full_name: Bajcsy, Peter
last_name: Bajcsy
- first_name: Johanna
full_name: Bischof, Johanna
last_name: Bischof
- first_name: Claire M.
full_name: Brown, Claire M.
last_name: Brown
- first_name: Aurélien
full_name: Dauphin, Aurélien
last_name: Dauphin
- first_name: Ian M.
full_name: Dobbie, Ian M.
last_name: Dobbie
- first_name: John E.
full_name: Eriksson, John E.
last_name: Eriksson
- first_name: Orestis
full_name: Faklaris, Orestis
last_name: Faklaris
- first_name: Julia
full_name: Fernandez-Rodriguez, Julia
last_name: Fernandez-Rodriguez
- first_name: Alexia
full_name: Ferrand, Alexia
last_name: Ferrand
- first_name: Laurent
full_name: Gelman, Laurent
last_name: Gelman
- first_name: Ali
full_name: Gheisari, Ali
last_name: Gheisari
- first_name: Hella
full_name: Hartmann, Hella
last_name: Hartmann
- first_name: Christian
full_name: Kukat, Christian
last_name: Kukat
- first_name: Alex
full_name: Laude, Alex
last_name: Laude
- first_name: Miso
full_name: Mitkovski, Miso
last_name: Mitkovski
- first_name: Sebastian
full_name: Munck, Sebastian
last_name: Munck
- first_name: Alison J.
full_name: North, Alison J.
last_name: North
- first_name: Tobias M.
full_name: Rasse, Tobias M.
last_name: Rasse
- first_name: Ute
full_name: Resch-Genger, Ute
last_name: Resch-Genger
- first_name: Lucas C.
full_name: Schuetz, Lucas C.
last_name: Schuetz
- first_name: Arne
full_name: Seitz, Arne
last_name: Seitz
- first_name: Caterina
full_name: Strambio-De-Castillia, Caterina
last_name: Strambio-De-Castillia
- first_name: Jason R.
full_name: Swedlow, Jason R.
last_name: Swedlow
- first_name: Ioannis
full_name: Alexopoulos, Ioannis
last_name: Alexopoulos
- first_name: Karin
full_name: Aumayr, Karin
last_name: Aumayr
- first_name: Sergiy
full_name: Avilov, Sergiy
last_name: Avilov
- first_name: Gert Jan
full_name: Bakker, Gert Jan
last_name: Bakker
- first_name: Rodrigo R.
full_name: Bammann, Rodrigo R.
last_name: Bammann
- first_name: Andrea
full_name: Bassi, Andrea
last_name: Bassi
- first_name: Hannes
full_name: Beckert, Hannes
last_name: Beckert
- first_name: Sebastian
full_name: Beer, Sebastian
last_name: Beer
- first_name: Yury
full_name: Belyaev, Yury
last_name: Belyaev
- first_name: Jakob
full_name: Bierwagen, Jakob
last_name: Bierwagen
- first_name: Konstantin A.
full_name: Birngruber, Konstantin A.
last_name: Birngruber
- first_name: Manel
full_name: Bosch, Manel
last_name: Bosch
- first_name: Juergen
full_name: Breitlow, Juergen
last_name: Breitlow
- first_name: Lisa A.
full_name: Cameron, Lisa A.
last_name: Cameron
- first_name: Joe
full_name: Chalfoun, Joe
last_name: Chalfoun
- first_name: James J.
full_name: Chambers, James J.
last_name: Chambers
- first_name: Chieh Li
full_name: Chen, Chieh Li
last_name: Chen
- first_name: Eduardo
full_name: Conde-Sousa, Eduardo
last_name: Conde-Sousa
- first_name: Alexander D.
full_name: Corbett, Alexander D.
last_name: Corbett
- first_name: Fabrice P.
full_name: Cordelieres, Fabrice P.
last_name: Cordelieres
- first_name: Elaine Del
full_name: Nery, Elaine Del
last_name: Nery
- first_name: Ralf
full_name: Dietzel, Ralf
last_name: Dietzel
- first_name: Frank
full_name: Eismann, Frank
last_name: Eismann
- first_name: Elnaz
full_name: Fazeli, Elnaz
last_name: Fazeli
- first_name: Andreas
full_name: Felscher, Andreas
last_name: Felscher
- first_name: Hans
full_name: Fried, Hans
last_name: Fried
- first_name: Nathalie
full_name: Gaudreault, Nathalie
last_name: Gaudreault
- first_name: Wah Ing
full_name: Goh, Wah Ing
last_name: Goh
- first_name: Thomas
full_name: Guilbert, Thomas
last_name: Guilbert
- first_name: Roland
full_name: Hadleigh, Roland
last_name: Hadleigh
- first_name: Peter
full_name: Hemmerich, Peter
last_name: Hemmerich
- first_name: Gerhard A.
full_name: Holst, Gerhard A.
last_name: Holst
- first_name: Michelle S.
full_name: Itano, Michelle S.
last_name: Itano
- first_name: Claudia B.
full_name: Jaffe, Claudia B.
last_name: Jaffe
- first_name: Helena K.
full_name: Jambor, Helena K.
last_name: Jambor
- first_name: Stuart C.
full_name: Jarvis, Stuart C.
last_name: Jarvis
- first_name: Antje
full_name: Keppler, Antje
last_name: Keppler
- first_name: David
full_name: Kirchenbuechler, David
last_name: Kirchenbuechler
- first_name: Marcel
full_name: Kirchner, Marcel
last_name: Kirchner
- first_name: Norio
full_name: Kobayashi, Norio
last_name: Kobayashi
- first_name: Gabriel
full_name: Krens, Gabriel
id: 2B819732-F248-11E8-B48F-1D18A9856A87
last_name: Krens
orcid: 0000-0003-4761-5996
- first_name: Susanne
full_name: Kunis, Susanne
last_name: Kunis
- first_name: Judith
full_name: Lacoste, Judith
last_name: Lacoste
- first_name: Marco
full_name: Marcello, Marco
last_name: Marcello
- first_name: Gabriel G.
full_name: Martins, Gabriel G.
last_name: Martins
- first_name: Daniel J.
full_name: Metcalf, Daniel J.
last_name: Metcalf
- first_name: Claire A.
full_name: Mitchell, Claire A.
last_name: Mitchell
- first_name: Joshua
full_name: Moore, Joshua
last_name: Moore
- first_name: Tobias
full_name: Mueller, Tobias
last_name: Mueller
- first_name: Michael S.
full_name: Nelson, Michael S.
last_name: Nelson
- first_name: Stephen
full_name: Ogg, Stephen
last_name: Ogg
- first_name: Shuichi
full_name: Onami, Shuichi
last_name: Onami
- first_name: Alexandra L.
full_name: Palmer, Alexandra L.
last_name: Palmer
- first_name: Perrine
full_name: Paul-Gilloteaux, Perrine
last_name: Paul-Gilloteaux
- first_name: Jaime A.
full_name: Pimentel, Jaime A.
last_name: Pimentel
- first_name: Laure
full_name: Plantard, Laure
last_name: Plantard
- first_name: Santosh
full_name: Podder, Santosh
last_name: Podder
- first_name: Elton
full_name: Rexhepaj, Elton
last_name: Rexhepaj
- first_name: Arnaud
full_name: Royon, Arnaud
last_name: Royon
- first_name: Markku A.
full_name: Saari, Markku A.
last_name: Saari
- first_name: Damien
full_name: Schapman, Damien
last_name: Schapman
- first_name: Vincent
full_name: Schoonderwoert, Vincent
last_name: Schoonderwoert
- first_name: Britta
full_name: Schroth-Diez, Britta
last_name: Schroth-Diez
- first_name: Stanley
full_name: Schwartz, Stanley
last_name: Schwartz
- first_name: Michael
full_name: Shaw, Michael
last_name: Shaw
- first_name: Martin
full_name: Spitaler, Martin
last_name: Spitaler
- first_name: Martin T.
full_name: Stoeckl, Martin T.
last_name: Stoeckl
- first_name: Damir
full_name: Sudar, Damir
last_name: Sudar
- first_name: Jeremie
full_name: Teillon, Jeremie
last_name: Teillon
- first_name: Stefan
full_name: Terjung, Stefan
last_name: Terjung
- first_name: Roland
full_name: Thuenauer, Roland
last_name: Thuenauer
- first_name: Christian D.
full_name: Wilms, Christian D.
last_name: Wilms
- first_name: Graham D.
full_name: Wright, Graham D.
last_name: Wright
- first_name: Roland
full_name: Nitschke, Roland
last_name: Nitschke
citation:
ama: 'Nelson G, Boehm U, Bagley S, et al. QUAREP-LiMi: A community-driven initiative
to establish guidelines for quality assessment and reproducibility for instruments
and images in light microscopy. Journal of Microscopy. 2021;284(1):56-73.
doi:10.1111/jmi.13041'
apa: 'Nelson, G., Boehm, U., Bagley, S., Bajcsy, P., Bischof, J., Brown, C. M.,
… Nitschke, R. (2021). QUAREP-LiMi: A community-driven initiative to establish
guidelines for quality assessment and reproducibility for instruments and images
in light microscopy. Journal of Microscopy. Wiley. https://doi.org/10.1111/jmi.13041'
chicago: 'Nelson, Glyn, Ulrike Boehm, Steve Bagley, Peter Bajcsy, Johanna Bischof,
Claire M. Brown, Aurélien Dauphin, et al. “QUAREP-LiMi: A Community-Driven Initiative
to Establish Guidelines for Quality Assessment and Reproducibility for Instruments
and Images in Light Microscopy.” Journal of Microscopy. Wiley, 2021. https://doi.org/10.1111/jmi.13041.'
ieee: 'G. Nelson et al., “QUAREP-LiMi: A community-driven initiative to establish
guidelines for quality assessment and reproducibility for instruments and images
in light microscopy,” Journal of Microscopy, vol. 284, no. 1. Wiley, pp.
56–73, 2021.'
ista: 'Nelson G et al. 2021. QUAREP-LiMi: A community-driven initiative to establish
guidelines for quality assessment and reproducibility for instruments and images
in light microscopy. Journal of Microscopy. 284(1), 56–73.'
mla: 'Nelson, Glyn, et al. “QUAREP-LiMi: A Community-Driven Initiative to Establish
Guidelines for Quality Assessment and Reproducibility for Instruments and Images
in Light Microscopy.” Journal of Microscopy, vol. 284, no. 1, Wiley, 2021,
pp. 56–73, doi:10.1111/jmi.13041.'
short: G. Nelson, U. Boehm, S. Bagley, P. Bajcsy, J. Bischof, C.M. Brown, A. Dauphin,
I.M. Dobbie, J.E. Eriksson, O. Faklaris, J. Fernandez-Rodriguez, A. Ferrand, L.
Gelman, A. Gheisari, H. Hartmann, C. Kukat, A. Laude, M. Mitkovski, S. Munck,
A.J. North, T.M. Rasse, U. Resch-Genger, L.C. Schuetz, A. Seitz, C. Strambio-De-Castillia,
J.R. Swedlow, I. Alexopoulos, K. Aumayr, S. Avilov, G.J. Bakker, R.R. Bammann,
A. Bassi, H. Beckert, S. Beer, Y. Belyaev, J. Bierwagen, K.A. Birngruber, M. Bosch,
J. Breitlow, L.A. Cameron, J. Chalfoun, J.J. Chambers, C.L. Chen, E. Conde-Sousa,
A.D. Corbett, F.P. Cordelieres, E.D. Nery, R. Dietzel, F. Eismann, E. Fazeli,
A. Felscher, H. Fried, N. Gaudreault, W.I. Goh, T. Guilbert, R. Hadleigh, P. Hemmerich,
G.A. Holst, M.S. Itano, C.B. Jaffe, H.K. Jambor, S.C. Jarvis, A. Keppler, D. Kirchenbuechler,
M. Kirchner, N. Kobayashi, G. Krens, S. Kunis, J. Lacoste, M. Marcello, G.G. Martins,
D.J. Metcalf, C.A. Mitchell, J. Moore, T. Mueller, M.S. Nelson, S. Ogg, S. Onami,
A.L. Palmer, P. Paul-Gilloteaux, J.A. Pimentel, L. Plantard, S. Podder, E. Rexhepaj,
A. Royon, M.A. Saari, D. Schapman, V. Schoonderwoert, B. Schroth-Diez, S. Schwartz,
M. Shaw, M. Spitaler, M.T. Stoeckl, D. Sudar, J. Teillon, S. Terjung, R. Thuenauer,
C.D. Wilms, G.D. Wright, R. Nitschke, Journal of Microscopy 284 (2021) 56–73.
date_created: 2021-08-15T22:01:29Z
date_published: 2021-08-11T00:00:00Z
date_updated: 2023-08-11T10:30:40Z
day: '11'
department:
- _id: Bio
doi: 10.1111/jmi.13041
external_id:
isi:
- '000683702700001'
intvolume: ' 284'
isi: 1
issue: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1111/jmi.13041
month: '08'
oa: 1
oa_version: Published Version
page: 56-73
publication: Journal of Microscopy
publication_identifier:
eissn:
- 1365-2818
issn:
- 0022-2720
publication_status: published
publisher: Wiley
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'QUAREP-LiMi: A community-driven initiative to establish guidelines for quality
assessment and reproducibility for instruments and images in light microscopy'
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 284
year: '2021'
...