---
_id: '10766'
abstract:
- lang: eng
text: Tension of the actomyosin cell cortex plays a key role in determining cell–cell
contact growth and size. The level of cortical tension outside of the cell–cell
contact, when pulling at the contact edge, scales with the total size to which
a cell–cell contact can grow [J.-L. Maître et al., Science 338, 253–256 (2012)].
Here, we show in zebrafish primary germ-layer progenitor cells that this monotonic
relationship only applies to a narrow range of cortical tension increase and that
above a critical threshold, contact size inversely scales with cortical tension.
This switch from cortical tension increasing to decreasing progenitor cell–cell
contact size is caused by cortical tension promoting E-cadherin anchoring to the
actomyosin cytoskeleton, thereby increasing clustering and stability of E-cadherin
at the contact. After tension-mediated E-cadherin stabilization at the contact
exceeds a critical threshold level, the rate by which the contact expands in response
to pulling forces from the cortex sharply drops, leading to smaller contacts at
physiologically relevant timescales of contact formation. Thus, the activity of
cortical tension in expanding cell–cell contact size is limited by tension-stabilizing
E-cadherin–actin complexes at the contact.
acknowledged_ssus:
- _id: Bio
- _id: EM-Fac
- _id: PreCl
acknowledgement: 'We thank Guillaume Salbreaux, Silvia Grigolon, Edouard Hannezo,
and Vanessa Barone for discussions and comments on the manuscript and Shayan Shamipour
and Daniel Capek for help with data analysis. We also thank the Imaging & Optics,
Electron Microscopy, and Zebrafish Facility Scientific Service Units at the Institute
of Science and Technology Austria (ISTA)Nasser Darwish-Miranda for continuous support.
We acknowledge Hitoshi Morita for the gift of VinculinB-GFP plasmid. This research
was supported by an ISTA Fellow Marie-Curie Co-funding of regional, national, and
international programmes Grant P_IST_EU01 (to J.S.), European Molecular Biology
Organization Long-Term Fellowship Grant, ALTF reference number: 187-2013 (to M.S.),
Schroedinger Fellowship J4332-B28 (to M.S.), and European Research Council Advanced
Grant (MECSPEC; to C.-P.H.).'
article_number: e2122030119
article_processing_charge: No
article_type: original
author:
- first_name: Jana
full_name: Slovakova, Jana
id: 30F3F2F0-F248-11E8-B48F-1D18A9856A87
last_name: Slovakova
- first_name: Mateusz K
full_name: Sikora, Mateusz K
id: 2F74BCDE-F248-11E8-B48F-1D18A9856A87
last_name: Sikora
- first_name: Feyza N
full_name: Arslan, Feyza N
id: 49DA7910-F248-11E8-B48F-1D18A9856A87
last_name: Arslan
orcid: 0000-0001-5809-9566
- first_name: Silvia
full_name: Caballero Mancebo, Silvia
id: 2F1E1758-F248-11E8-B48F-1D18A9856A87
last_name: Caballero Mancebo
orcid: 0000-0002-5223-3346
- first_name: Gabriel
full_name: Krens, Gabriel
id: 2B819732-F248-11E8-B48F-1D18A9856A87
last_name: Krens
orcid: 0000-0003-4761-5996
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Jack
full_name: Merrin, Jack
id: 4515C308-F248-11E8-B48F-1D18A9856A87
last_name: Merrin
orcid: 0000-0001-5145-4609
- first_name: Carl-Philipp J
full_name: Heisenberg, Carl-Philipp J
id: 39427864-F248-11E8-B48F-1D18A9856A87
last_name: Heisenberg
orcid: 0000-0002-0912-4566
citation:
ama: Slovakova J, Sikora MK, Arslan FN, et al. Tension-dependent stabilization of
E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor
cells. Proceedings of the National Academy of Sciences of the United States
of America. 2022;119(8). doi:10.1073/pnas.2122030119
apa: Slovakova, J., Sikora, M. K., Arslan, F. N., Caballero Mancebo, S., Krens,
G., Kaufmann, W., … Heisenberg, C.-P. J. (2022). Tension-dependent stabilization
of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor
cells. Proceedings of the National Academy of Sciences of the United States
of America. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2122030119
chicago: Slovakova, Jana, Mateusz K Sikora, Feyza N Arslan, Silvia Caballero Mancebo,
Gabriel Krens, Walter Kaufmann, Jack Merrin, and Carl-Philipp J Heisenberg. “Tension-Dependent
Stabilization of E-Cadherin Limits Cell-Cell Contact Expansion in Zebrafish Germ-Layer
Progenitor Cells.” Proceedings of the National Academy of Sciences of the United
States of America. Proceedings of the National Academy of Sciences, 2022.
https://doi.org/10.1073/pnas.2122030119.
ieee: J. Slovakova et al., “Tension-dependent stabilization of E-cadherin
limits cell-cell contact expansion in zebrafish germ-layer progenitor cells,”
Proceedings of the National Academy of Sciences of the United States of America,
vol. 119, no. 8. Proceedings of the National Academy of Sciences, 2022.
ista: Slovakova J, Sikora MK, Arslan FN, Caballero Mancebo S, Krens G, Kaufmann
W, Merrin J, Heisenberg C-PJ. 2022. Tension-dependent stabilization of E-cadherin
limits cell-cell contact expansion in zebrafish germ-layer progenitor cells. Proceedings
of the National Academy of Sciences of the United States of America. 119(8), e2122030119.
mla: Slovakova, Jana, et al. “Tension-Dependent Stabilization of E-Cadherin Limits
Cell-Cell Contact Expansion in Zebrafish Germ-Layer Progenitor Cells.” Proceedings
of the National Academy of Sciences of the United States of America, vol.
119, no. 8, e2122030119, Proceedings of the National Academy of Sciences, 2022,
doi:10.1073/pnas.2122030119.
short: J. Slovakova, M.K. Sikora, F.N. Arslan, S. Caballero Mancebo, G. Krens, W.
Kaufmann, J. Merrin, C.-P.J. Heisenberg, Proceedings of the National Academy of
Sciences of the United States of America 119 (2022).
date_created: 2022-02-20T23:01:31Z
date_published: 2022-02-14T00:00:00Z
date_updated: 2023-08-02T14:26:51Z
day: '14'
ddc:
- '570'
department:
- _id: CaHe
- _id: EM-Fac
- _id: Bio
doi: 10.1073/pnas.2122030119
ec_funded: 1
external_id:
isi:
- '000766926900009'
file:
- access_level: open_access
checksum: d49f83c3580613966f71768ddb9a55a5
content_type: application/pdf
creator: dernst
date_created: 2022-02-21T08:45:11Z
date_updated: 2022-02-21T08:45:11Z
file_id: '10780'
file_name: 2022_PNAS_Slovakova.pdf
file_size: 1609678
relation: main_file
success: 1
file_date_updated: 2022-02-21T08:45:11Z
has_accepted_license: '1'
intvolume: ' 119'
isi: 1
issue: '8'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '02'
oa: 1
oa_version: Published Version
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
- _id: 260F1432-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '742573'
name: Interaction and feedback between cell mechanics and fate specification in
vertebrate gastrulation
- _id: 2521E28E-B435-11E9-9278-68D0E5697425
grant_number: 187-2013
name: Modulation of adhesion function in cell-cell contact formation by cortical
tension
publication: Proceedings of the National Academy of Sciences of the United States
of America
publication_identifier:
eissn:
- '10916490'
publication_status: published
publisher: Proceedings of the National Academy of Sciences
quality_controlled: '1'
related_material:
record:
- id: '9750'
relation: earlier_version
status: public
scopus_import: '1'
status: public
title: Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion
in zebrafish germ-layer progenitor cells
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: 119
year: '2022'
...
---
_id: '8988'
abstract:
- lang: eng
text: The differentiation of cells depends on a precise control of their internal
organization, which is the result of a complex dynamic interplay between the cytoskeleton,
molecular motors, signaling molecules, and membranes. For example, in the developing
neuron, the protein ADAP1 (ADP-ribosylation factor GTPase-activating protein [ArfGAP]
with dual pleckstrin homology [PH] domains 1) has been suggested to control dendrite
branching by regulating the small GTPase ARF6. Together with the motor protein
KIF13B, ADAP1 is also thought to mediate delivery of the second messenger phosphatidylinositol
(3,4,5)-trisphosphate (PIP3) to the axon tip, thus contributing to PIP3 polarity.
However, what defines the function of ADAP1 and how its different roles are coordinated
are still not clear. Here, we studied ADAP1’s functions using in vitro reconstitutions.
We found that KIF13B transports ADAP1 along microtubules, but that PIP3 as well
as PI(3,4)P2 act as stop signals for this transport instead of being transported.
We also demonstrate that these phosphoinositides activate ADAP1’s enzymatic activity
to catalyze GTP hydrolysis by ARF6. Together, our results support a model for
the cellular function of ADAP1, where KIF13B transports ADAP1 until it encounters
high PIP3/PI(3,4)P2 concentrations in the plasma membrane. Here, ADAP1 disassociates
from the motor to inactivate ARF6, promoting dendrite branching.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: EM-Fac
acknowledgement: "We thank Urban Bezeljak, Natalia Baranova, Mar Lopez-Pelegrin, Catarina
Alcarva, and Victoria Faas for sharing reagents and helpful discussions. We thank
Veronika Szentirmai for help with protein purifications. We thank Carrie Bernecky,
Sascha Martens, and the M.L. lab for comments on the manuscript. We thank the bioimaging
facility, the life science facility, and Armel Nicolas from the mass spec facility
at the Institute of Science and Technology (IST) Austria for technical support.
C.D. acknowledges funding from the IST fellowship program; this work was supported
by Human Frontier Science Program Young Investigator Grant\r\nRGY0083/2016. "
article_number: e2010054118
article_processing_charge: No
article_type: original
author:
- first_name: Christian F
full_name: Düllberg, Christian F
id: 459064DC-F248-11E8-B48F-1D18A9856A87
last_name: Düllberg
orcid: 0000-0001-6335-9748
- first_name: Albert
full_name: Auer, Albert
id: 3018E8C2-F248-11E8-B48F-1D18A9856A87
last_name: Auer
orcid: 0000-0002-3580-2906
- first_name: Nikola
full_name: Canigova, Nikola
id: 3795523E-F248-11E8-B48F-1D18A9856A87
last_name: Canigova
orcid: 0000-0002-8518-5926
- first_name: Katrin
full_name: Loibl, Katrin
id: 3760F32C-F248-11E8-B48F-1D18A9856A87
last_name: Loibl
orcid: 0000-0002-2429-7668
- first_name: Martin
full_name: Loose, Martin
id: 462D4284-F248-11E8-B48F-1D18A9856A87
last_name: Loose
orcid: 0000-0001-7309-9724
citation:
ama: Düllberg CF, Auer A, Canigova N, Loibl K, Loose M. In vitro reconstitution
reveals phosphoinositides as cargo-release factors and activators of the ARF6
GAP ADAP1. PNAS. 2021;118(1). doi:10.1073/pnas.2010054118
apa: Düllberg, C. F., Auer, A., Canigova, N., Loibl, K., & Loose, M. (2021).
In vitro reconstitution reveals phosphoinositides as cargo-release factors and
activators of the ARF6 GAP ADAP1. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.2010054118
chicago: Düllberg, Christian F, Albert Auer, Nikola Canigova, Katrin Loibl, and
Martin Loose. “In Vitro Reconstitution Reveals Phosphoinositides as Cargo-Release
Factors and Activators of the ARF6 GAP ADAP1.” PNAS. National Academy of
Sciences, 2021. https://doi.org/10.1073/pnas.2010054118.
ieee: C. F. Düllberg, A. Auer, N. Canigova, K. Loibl, and M. Loose, “In vitro reconstitution
reveals phosphoinositides as cargo-release factors and activators of the ARF6
GAP ADAP1,” PNAS, vol. 118, no. 1. National Academy of Sciences, 2021.
ista: Düllberg CF, Auer A, Canigova N, Loibl K, Loose M. 2021. In vitro reconstitution
reveals phosphoinositides as cargo-release factors and activators of the ARF6
GAP ADAP1. PNAS. 118(1), e2010054118.
mla: Düllberg, Christian F., et al. “In Vitro Reconstitution Reveals Phosphoinositides
as Cargo-Release Factors and Activators of the ARF6 GAP ADAP1.” PNAS, vol.
118, no. 1, e2010054118, National Academy of Sciences, 2021, doi:10.1073/pnas.2010054118.
short: C.F. Düllberg, A. Auer, N. Canigova, K. Loibl, M. Loose, PNAS 118 (2021).
date_created: 2021-01-03T23:01:23Z
date_published: 2021-01-05T00:00:00Z
date_updated: 2023-08-04T11:20:46Z
day: '05'
department:
- _id: MaLo
- _id: MiSi
doi: 10.1073/pnas.2010054118
external_id:
isi:
- '000607270100018'
pmid:
- '33443153'
intvolume: ' 118'
isi: 1
issue: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1073/pnas.2010054118
month: '01'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2599F062-B435-11E9-9278-68D0E5697425
grant_number: RGY0083/2016
name: Reconstitution of cell polarity and axis determination in a cell-free system
publication: PNAS
publication_identifier:
eissn:
- '10916490'
issn:
- '00278424'
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
scopus_import: '1'
status: public
title: In vitro reconstitution reveals phosphoinositides as cargo-release factors
and activators of the ARF6 GAP ADAP1
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 118
year: '2021'
...
---
_id: '8993'
abstract:
- lang: eng
text: N-1-naphthylphthalamic acid (NPA) is a key inhibitor of directional (polar)
transport of the hormone auxin in plants. For decades, it has been a pivotal tool
in elucidating the unique polar auxin transport-based processes underlying plant
growth and development. Its exact mode of action has long been sought after and
is still being debated, with prevailing mechanistic schemes describing only indirect
connections between NPA and the main transporters responsible for directional
transport, namely PIN auxin exporters. Here we present data supporting a model
in which NPA associates with PINs in a more direct manner than hitherto postulated.
We show that NPA inhibits PIN activity in a heterologous oocyte system and that
expression of NPA-sensitive PINs in plant, yeast, and oocyte membranes leads to
specific saturable NPA binding. We thus propose that PINs are a bona fide NPA
target. This offers a straightforward molecular basis for NPA inhibition of PIN-dependent
auxin transport and a logical parsimonious explanation for the known physiological
effects of NPA on plant growth, as well as an alternative hypothesis to interpret
past and future results. We also introduce PIN dimerization and describe an effect
of NPA on this, suggesting that NPA binding could be exploited to gain insights
into structural aspects of PINs related to their transport mechanism.
acknowledgement: "This work was supported by Austrian Science Fund Grant FWF P21533-B20
(to L.A.); German Research Foundation Grant DFG HA3468/6-1 (to U.Z.H.); and European
Research Council Grant 742985 (to J.F.). We thank Herta Steinkellner and Alexandra
Castilho for N. benthamiana plants, Fabian Nagelreiter for statistical advice, Lanassa
Bassukas for help with [ɣ32P]-\r\nATP assays, and Josef Penninger for providing
access to mass spectrometry instruments at the Vienna BioCenter Core Facilities.
We thank PNAS reviewers for the many comments and suggestions that helped to improve
this manuscript."
article_number: e2020857118
article_processing_charge: No
article_type: original
author:
- first_name: Lindy
full_name: Abas, Lindy
last_name: Abas
- first_name: Martina
full_name: Kolb, Martina
last_name: Kolb
- first_name: Johannes
full_name: Stadlmann, Johannes
last_name: Stadlmann
- first_name: Dorina P.
full_name: Janacek, Dorina P.
last_name: Janacek
- first_name: Kristina
full_name: Lukic, Kristina
id: 2B04DB84-F248-11E8-B48F-1D18A9856A87
last_name: Lukic
orcid: 0000-0003-1581-881X
- first_name: Claus
full_name: Schwechheimer, Claus
last_name: Schwechheimer
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
- first_name: Lukas
full_name: Mach, Lukas
last_name: Mach
- first_name: Jiří
full_name: Friml, Jiří
id: 4159519E-F248-11E8-B48F-1D18A9856A87
last_name: Friml
orcid: 0000-0002-8302-7596
- first_name: Ulrich Z.
full_name: Hammes, Ulrich Z.
last_name: Hammes
citation:
ama: Abas L, Kolb M, Stadlmann J, et al. Naphthylphthalamic acid associates with
and inhibits PIN auxin transporters. PNAS. 2021;118(1). doi:10.1073/pnas.2020857118
apa: Abas, L., Kolb, M., Stadlmann, J., Janacek, D. P., Lukic, K., Schwechheimer,
C., … Hammes, U. Z. (2021). Naphthylphthalamic acid associates with and inhibits
PIN auxin transporters. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.2020857118
chicago: Abas, Lindy, Martina Kolb, Johannes Stadlmann, Dorina P. Janacek, Kristina
Lukic, Claus Schwechheimer, Leonid A Sazanov, Lukas Mach, Jiří Friml, and Ulrich
Z. Hammes. “Naphthylphthalamic Acid Associates with and Inhibits PIN Auxin Transporters.”
PNAS. National Academy of Sciences, 2021. https://doi.org/10.1073/pnas.2020857118.
ieee: L. Abas et al., “Naphthylphthalamic acid associates with and inhibits
PIN auxin transporters,” PNAS, vol. 118, no. 1. National Academy of Sciences,
2021.
ista: Abas L, Kolb M, Stadlmann J, Janacek DP, Lukic K, Schwechheimer C, Sazanov
LA, Mach L, Friml J, Hammes UZ. 2021. Naphthylphthalamic acid associates with
and inhibits PIN auxin transporters. PNAS. 118(1), e2020857118.
mla: Abas, Lindy, et al. “Naphthylphthalamic Acid Associates with and Inhibits PIN
Auxin Transporters.” PNAS, vol. 118, no. 1, e2020857118, National Academy
of Sciences, 2021, doi:10.1073/pnas.2020857118.
short: L. Abas, M. Kolb, J. Stadlmann, D.P. Janacek, K. Lukic, C. Schwechheimer,
L.A. Sazanov, L. Mach, J. Friml, U.Z. Hammes, PNAS 118 (2021).
date_created: 2021-01-03T23:01:23Z
date_published: 2021-01-05T00:00:00Z
date_updated: 2023-08-07T13:29:23Z
day: '05'
department:
- _id: JiFr
- _id: LeSa
doi: 10.1073/pnas.2020857118
ec_funded: 1
external_id:
isi:
- '000607270100073'
pmid:
- '33443187'
intvolume: ' 118'
isi: 1
issue: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1073/pnas.2020857118
month: '01'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 261099A6-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '742985'
name: Tracing Evolution of Auxin Transport and Polarity in Plants
publication: PNAS
publication_identifier:
eissn:
- '10916490'
issn:
- '00278424'
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
link:
- relation: erratum
url: https://doi.org/10.1073/pnas.2102232118
scopus_import: '1'
status: public
title: Naphthylphthalamic acid associates with and inhibits PIN auxin transporters
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 118
year: '2021'
...
---
_id: '7932'
abstract:
- lang: eng
text: Pulsating flows through tubular geometries are laminar provided that velocities
are moderate. This in particular is also believed to apply to cardiovascular flows
where inertial forces are typically too low to sustain turbulence. On the other
hand, flow instabilities and fluctuating shear stresses are held responsible for
a variety of cardiovascular diseases. Here we report a nonlinear instability mechanism
for pulsating pipe flow that gives rise to bursts of turbulence at low flow rates.
Geometrical distortions of small, yet finite, amplitude are found to excite a
state consisting of helical vortices during flow deceleration. The resulting flow
pattern grows rapidly in magnitude, breaks down into turbulence, and eventually
returns to laminar when the flow accelerates. This scenario causes shear stress
fluctuations and flow reversal during each pulsation cycle. Such unsteady conditions
can adversely affect blood vessels and have been shown to promote inflammation
and dysfunction of the shear stress-sensitive endothelial cell layer.
article_processing_charge: No
article_type: original
arxiv: 1
author:
- first_name: Duo
full_name: Xu, Duo
id: 3454D55E-F248-11E8-B48F-1D18A9856A87
last_name: Xu
- first_name: Atul
full_name: Varshney, Atul
id: 2A2006B2-F248-11E8-B48F-1D18A9856A87
last_name: Varshney
orcid: 0000-0002-3072-5999
- first_name: Xingyu
full_name: Ma, Xingyu
id: 34BADBA6-F248-11E8-B48F-1D18A9856A87
last_name: Ma
orcid: 0000-0002-0179-9737
- first_name: Baofang
full_name: Song, Baofang
last_name: Song
- first_name: Michael
full_name: Riedl, Michael
id: 3BE60946-F248-11E8-B48F-1D18A9856A87
last_name: Riedl
orcid: 0000-0003-4844-6311
- first_name: Marc
full_name: Avila, Marc
last_name: Avila
- first_name: Björn
full_name: Hof, Björn
id: 3A374330-F248-11E8-B48F-1D18A9856A87
last_name: Hof
orcid: 0000-0003-2057-2754
citation:
ama: Xu D, Varshney A, Ma X, et al. Nonlinear hydrodynamic instability and turbulence
in pulsatile flow. Proceedings of the National Academy of Sciences of the United
States of America. 2020;117(21):11233-11239. doi:10.1073/pnas.1913716117
apa: Xu, D., Varshney, A., Ma, X., Song, B., Riedl, M., Avila, M., & Hof, B.
(2020). Nonlinear hydrodynamic instability and turbulence in pulsatile flow. Proceedings
of the National Academy of Sciences of the United States of America. National
Academy of Sciences. https://doi.org/10.1073/pnas.1913716117
chicago: Xu, Duo, Atul Varshney, Xingyu Ma, Baofang Song, Michael Riedl, Marc Avila,
and Björn Hof. “Nonlinear Hydrodynamic Instability and Turbulence in Pulsatile
Flow.” Proceedings of the National Academy of Sciences of the United States
of America. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.1913716117.
ieee: D. Xu et al., “Nonlinear hydrodynamic instability and turbulence in
pulsatile flow,” Proceedings of the National Academy of Sciences of the United
States of America, vol. 117, no. 21. National Academy of Sciences, pp. 11233–11239,
2020.
ista: Xu D, Varshney A, Ma X, Song B, Riedl M, Avila M, Hof B. 2020. Nonlinear hydrodynamic
instability and turbulence in pulsatile flow. Proceedings of the National Academy
of Sciences of the United States of America. 117(21), 11233–11239.
mla: Xu, Duo, et al. “Nonlinear Hydrodynamic Instability and Turbulence in Pulsatile
Flow.” Proceedings of the National Academy of Sciences of the United States
of America, vol. 117, no. 21, National Academy of Sciences, 2020, pp. 11233–39,
doi:10.1073/pnas.1913716117.
short: D. Xu, A. Varshney, X. Ma, B. Song, M. Riedl, M. Avila, B. Hof, Proceedings
of the National Academy of Sciences of the United States of America 117 (2020)
11233–11239.
date_created: 2020-06-07T22:00:51Z
date_published: 2020-05-26T00:00:00Z
date_updated: 2023-11-30T10:55:13Z
day: '26'
department:
- _id: BjHo
doi: 10.1073/pnas.1913716117
ec_funded: 1
external_id:
arxiv:
- '2005.11190'
isi:
- '000536797100014'
intvolume: ' 117'
isi: 1
issue: '21'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://arxiv.org/abs/2005.11190
month: '05'
oa: 1
oa_version: Preprint
page: 11233-11239
project:
- _id: 238B8092-32DE-11EA-91FC-C7463DDC885E
call_identifier: FWF
grant_number: I04188
name: Instabilities in pulsating pipe flow of Newtonian and complex fluids
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
publication: Proceedings of the National Academy of Sciences of the United States
of America
publication_identifier:
eissn:
- '10916490'
issn:
- '00278424'
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/blood-flows-more-turbulent-than-previously-expected/
record:
- id: '12726'
relation: dissertation_contains
status: public
- id: '14530'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Nonlinear hydrodynamic instability and turbulence in pulsatile flow
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 117
year: '2020'
...
---
_id: '8220'
abstract:
- lang: eng
text: Understanding to what extent stem cell potential is a cell-intrinsic property
or an emergent behavior coming from global tissue dynamics and geometry is a key
outstanding question of systems and stem cell biology. Here, we propose a theory
of stem cell dynamics as a stochastic competition for access to a spatially localized
niche, giving rise to a stochastic conveyor-belt model. Cell divisions produce
a steady cellular stream which advects cells away from the niche, while random
rearrangements enable cells away from the niche to be favorably repositioned.
Importantly, even when assuming that all cells in a tissue are molecularly equivalent,
we predict a common (“universal”) functional dependence of the long-term clonal
survival probability on distance from the niche, as well as the emergence of a
well-defined number of functional stem cells, dependent only on the rate of random
movements vs. mitosis-driven advection. We test the predictions of this theory
on datasets of pubertal mammary gland tips and embryonic kidney tips, as well
as homeostatic intestinal crypts. Importantly, we find good agreement for the
predicted functional dependency of the competition as a function of position,
and thus functional stem cell number in each organ. This argues for a key role
of positional fluctuations in dictating stem cell number and dynamics, and we
discuss the applicability of this theory to other settings.
acknowledgement: "We thank all members of the E.H., B.D.S., and J.v.R. groups for
stimulating discussions. This project was supported by\r\nthe European Research
Council (648804 to J.v.R. and 851288 to E.H.). It has also received support from
the CancerGenomics.nl (Netherlands Organization for Scientific Research) program
(J.v.R.) and the Doctor Josef Steiner Foundation (J.v.R). B.D.S. was supported by
Royal Society E. P. Abraham Research Professorship RP/R1/180165 and Wellcome Trust
Grant 098357/Z/12/Z."
article_processing_charge: No
article_type: original
author:
- first_name: Bernat
full_name: Corominas-Murtra, Bernat
id: 43BE2298-F248-11E8-B48F-1D18A9856A87
last_name: Corominas-Murtra
orcid: 0000-0001-9806-5643
- first_name: Colinda L.G.J.
full_name: Scheele, Colinda L.G.J.
last_name: Scheele
- first_name: Kasumi
full_name: Kishi, Kasumi
id: 3065DFC4-F248-11E8-B48F-1D18A9856A87
last_name: Kishi
- first_name: Saskia I.J.
full_name: Ellenbroek, Saskia I.J.
last_name: Ellenbroek
- first_name: Benjamin D.
full_name: Simons, Benjamin D.
last_name: Simons
- first_name: Jacco
full_name: Van Rheenen, Jacco
last_name: Van Rheenen
- first_name: Edouard B
full_name: Hannezo, Edouard B
id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
last_name: Hannezo
orcid: 0000-0001-6005-1561
citation:
ama: Corominas-Murtra B, Scheele CLGJ, Kishi K, et al. Stem cell lineage survival
as a noisy competition for niche access. Proceedings of the National Academy
of Sciences of the United States of America. 2020;117(29):16969-16975. doi:10.1073/pnas.1921205117
apa: Corominas-Murtra, B., Scheele, C. L. G. J., Kishi, K., Ellenbroek, S. I. J.,
Simons, B. D., Van Rheenen, J., & Hannezo, E. B. (2020). Stem cell lineage
survival as a noisy competition for niche access. Proceedings of the National
Academy of Sciences of the United States of America. National Academy of Sciences.
https://doi.org/10.1073/pnas.1921205117
chicago: Corominas-Murtra, Bernat, Colinda L.G.J. Scheele, Kasumi Kishi, Saskia
I.J. Ellenbroek, Benjamin D. Simons, Jacco Van Rheenen, and Edouard B Hannezo.
“Stem Cell Lineage Survival as a Noisy Competition for Niche Access.” Proceedings
of the National Academy of Sciences of the United States of America. National
Academy of Sciences, 2020. https://doi.org/10.1073/pnas.1921205117.
ieee: B. Corominas-Murtra et al., “Stem cell lineage survival as a noisy
competition for niche access,” Proceedings of the National Academy of Sciences
of the United States of America, vol. 117, no. 29. National Academy of Sciences,
pp. 16969–16975, 2020.
ista: Corominas-Murtra B, Scheele CLGJ, Kishi K, Ellenbroek SIJ, Simons BD, Van
Rheenen J, Hannezo EB. 2020. Stem cell lineage survival as a noisy competition
for niche access. Proceedings of the National Academy of Sciences of the United
States of America. 117(29), 16969–16975.
mla: Corominas-Murtra, Bernat, et al. “Stem Cell Lineage Survival as a Noisy Competition
for Niche Access.” Proceedings of the National Academy of Sciences of the United
States of America, vol. 117, no. 29, National Academy of Sciences, 2020, pp.
16969–75, doi:10.1073/pnas.1921205117.
short: B. Corominas-Murtra, C.L.G.J. Scheele, K. Kishi, S.I.J. Ellenbroek, B.D.
Simons, J. Van Rheenen, E.B. Hannezo, Proceedings of the National Academy of Sciences
of the United States of America 117 (2020) 16969–16975.
date_created: 2020-08-09T22:00:52Z
date_published: 2020-07-21T00:00:00Z
date_updated: 2023-08-22T08:29:30Z
day: '21'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.1073/pnas.1921205117
ec_funded: 1
external_id:
isi:
- '000553292900014'
pmid:
- '32611816'
file:
- access_level: open_access
content_type: application/pdf
creator: dernst
date_created: 2020-08-10T06:50:28Z
date_updated: 2020-08-10T06:50:28Z
file_id: '8223'
file_name: 2020_PNAS_Corominas.pdf
file_size: 1111604
relation: main_file
success: 1
file_date_updated: 2020-08-10T06:50:28Z
has_accepted_license: '1'
intvolume: ' 117'
isi: 1
issue: '29'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 16969-16975
pmid: 1
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
call_identifier: H2020
grant_number: '851288'
name: Design Principles of Branching Morphogenesis
publication: Proceedings of the National Academy of Sciences of the United States
of America
publication_identifier:
eissn:
- '10916490'
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
link:
- relation: press_release
url: https://ist.ac.at/en/news/order-from-noise/
scopus_import: '1'
status: public
title: Stem cell lineage survival as a noisy competition for niche access
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: 117
year: '2020'
...
---
_id: '8698'
abstract:
- lang: eng
text: The brain represents and reasons probabilistically about complex stimuli and
motor actions using a noisy, spike-based neural code. A key building block for
such neural computations, as well as the basis for supervised and unsupervised
learning, is the ability to estimate the surprise or likelihood of incoming high-dimensional
neural activity patterns. Despite progress in statistical modeling of neural responses
and deep learning, current approaches either do not scale to large neural populations
or cannot be implemented using biologically realistic mechanisms. Inspired by
the sparse and random connectivity of real neuronal circuits, we present a model
for neural codes that accurately estimates the likelihood of individual spiking
patterns and has a straightforward, scalable, efficient, learnable, and realistic
neural implementation. This model’s performance on simultaneously recorded spiking
activity of >100 neurons in the monkey visual and prefrontal cortices is comparable
with or better than that of state-of-the-art models. Importantly, the model can
be learned using a small number of samples and using a local learning rule that
utilizes noise intrinsic to neural circuits. Slower, structural changes in random
connectivity, consistent with rewiring and pruning processes, further improve
the efficiency and sparseness of the resulting neural representations. Our results
merge insights from neuroanatomy, machine learning, and theoretical neuroscience
to suggest random sparse connectivity as a key design principle for neuronal computation.
acknowledgement: We thank Udi Karpas, Roy Harpaz, Tal Tamir, Adam Haber, and Amir
Bar for discussions and suggestions; and especially Oren Forkosh and Walter Senn
for invaluable discussions of the learning rule. This work was supported by European
Research Council Grant 311238 (to E.S.) and Israel Science Foundation Grant 1629/12
(to E.S.); as well as research support from Martin Kushner Schnur and Mr. and Mrs.
Lawrence Feis (E.S.); National Institute of Mental Health Grant R01MH109180 (to
R.K.); a Pew Scholarship in Biomedical Sciences (to R.K.); Simons Collaboration
on the Global Brain Grant 542997 (to R.K. and E.S.); and a CRCNS (Collaborative
Research in Computational Neuroscience) grant (to R.K. and E.S.).
article_processing_charge: No
article_type: original
author:
- first_name: Ori
full_name: Maoz, Ori
last_name: Maoz
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
- first_name: Mohamad Saleh
full_name: Esteki, Mohamad Saleh
last_name: Esteki
- first_name: Roozbeh
full_name: Kiani, Roozbeh
last_name: Kiani
- first_name: Elad
full_name: Schneidman, Elad
last_name: Schneidman
citation:
ama: Maoz O, Tkačik G, Esteki MS, Kiani R, Schneidman E. Learning probabilistic
neural representations with randomly connected circuits. Proceedings of the
National Academy of Sciences of the United States of America. 2020;117(40):25066-25073.
doi:10.1073/pnas.1912804117
apa: Maoz, O., Tkačik, G., Esteki, M. S., Kiani, R., & Schneidman, E. (2020).
Learning probabilistic neural representations with randomly connected circuits.
Proceedings of the National Academy of Sciences of the United States of America.
National Academy of Sciences. https://doi.org/10.1073/pnas.1912804117
chicago: Maoz, Ori, Gašper Tkačik, Mohamad Saleh Esteki, Roozbeh Kiani, and Elad
Schneidman. “Learning Probabilistic Neural Representations with Randomly Connected
Circuits.” Proceedings of the National Academy of Sciences of the United States
of America. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.1912804117.
ieee: O. Maoz, G. Tkačik, M. S. Esteki, R. Kiani, and E. Schneidman, “Learning probabilistic
neural representations with randomly connected circuits,” Proceedings of the
National Academy of Sciences of the United States of America, vol. 117, no.
40. National Academy of Sciences, pp. 25066–25073, 2020.
ista: Maoz O, Tkačik G, Esteki MS, Kiani R, Schneidman E. 2020. Learning probabilistic
neural representations with randomly connected circuits. Proceedings of the National
Academy of Sciences of the United States of America. 117(40), 25066–25073.
mla: Maoz, Ori, et al. “Learning Probabilistic Neural Representations with Randomly
Connected Circuits.” Proceedings of the National Academy of Sciences of the
United States of America, vol. 117, no. 40, National Academy of Sciences,
2020, pp. 25066–73, doi:10.1073/pnas.1912804117.
short: O. Maoz, G. Tkačik, M.S. Esteki, R. Kiani, E. Schneidman, Proceedings of
the National Academy of Sciences of the United States of America 117 (2020) 25066–25073.
date_created: 2020-10-25T23:01:16Z
date_published: 2020-10-06T00:00:00Z
date_updated: 2023-08-22T12:11:23Z
day: '06'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1073/pnas.1912804117
external_id:
isi:
- '000579045200012'
pmid:
- '32948691'
file:
- access_level: open_access
checksum: c6a24fdecf3f28faf447078e7a274a88
content_type: application/pdf
creator: cziletti
date_created: 2020-10-27T14:57:50Z
date_updated: 2020-10-27T14:57:50Z
file_id: '8713'
file_name: 2020_PNAS_Maoz.pdf
file_size: 1755359
relation: main_file
success: 1
file_date_updated: 2020-10-27T14:57:50Z
has_accepted_license: '1'
intvolume: ' 117'
isi: 1
issue: '40'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: 25066-25073
pmid: 1
publication: Proceedings of the National Academy of Sciences of the United States
of America
publication_identifier:
eissn:
- '10916490'
issn:
- '00278424'
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
scopus_import: '1'
status: public
title: Learning probabilistic neural representations with randomly connected circuits
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: 117
year: '2020'
...
---
_id: '8699'
abstract:
- lang: eng
text: In the high spin–orbit-coupled Sr2IrO4, the high sensitivity of the ground
state to the details of the local lattice structure shows a large potential for
the manipulation of the functional properties by inducing local lattice distortions.
We use epitaxial strain to modify the Ir–O bond geometry in Sr2IrO4 and perform
momentum-dependent resonant inelastic X-ray scattering (RIXS) at the metal and
at the ligand sites to unveil the response of the low-energy elementary excitations.
We observe that the pseudospin-wave dispersion for tensile-strained Sr2IrO4 films
displays large softening along the [h,0] direction, while along the [h,h] direction
it shows hardening. This evolution reveals a renormalization of the magnetic interactions
caused by a strain-driven cross-over from anisotropic to isotropic interactions
between the magnetic moments. Moreover, we detect dispersive electron–hole pair
excitations which shift to lower (higher) energies upon compressive (tensile)
strain, manifesting a reduction (increase) in the size of the charge gap. This
behavior shows an intimate coupling between charge excitations and lattice distortions
in Sr2IrO4, originating from the modified hopping elements between the t2g orbitals.
Our work highlights the central role played by the lattice degrees of freedom
in determining both the pseudospin and charge excitations of Sr2IrO4 and provides
valuable information toward the control of the ground state of complex oxides
in the presence of high spin–orbit coupling.
acknowledgement: 'We gratefully acknowledge C. Sahle for experimental support at the
ID20 beamline of the ESRF. The soft X-ray experiments were carried out at the ADRESS
beamline of the Swiss Light Source, Paul Scherrer Institut (PSI). E. Paris and T.S.
thank X. Lu and C. Monney for valuable discussions. The work at PSI is supported
by the Swiss National Science Foundation (SNSF) through Project 200021_178867, the
NCCR (National Centre of Competence in Research) MARVEL (Materials’ Revolution:
Computational Design and Discovery of Novel Materials) and the Sinergia network
Mott Physics Beyond the Heisenberg Model (MPBH) (SNSF Research Grants CRSII2_160765/1
and CRSII2_141962). K.W. acknowledges support by the Narodowe Centrum Nauki Projects
2016/22/E/ST3/00560 and 2016/23/B/ST3/00839. E.M.P. and M.N. acknowledge funding
from the European Union’s Horizon 2020 research and innovation programme under the
Marie Sklodowska-Curie Grant Agreements 754411 and 701647, respectively. M.R. was
supported by the Swiss National Science Foundation under Project 200021 – 182695.
This research used resources of the APS, a U.S. Department of Energy (DOE) Office
of Science User Facility operated for the DOE Office of Science by Argonne National
Laboratory under Contract DE-AC02-06CH11357.'
article_processing_charge: No
article_type: original
arxiv: 1
author:
- first_name: Eugenio
full_name: Paris, Eugenio
last_name: Paris
- first_name: Yi
full_name: Tseng, Yi
last_name: Tseng
- first_name: Ekaterina
full_name: Paerschke, Ekaterina
id: 8275014E-6063-11E9-9B7F-6338E6697425
last_name: Paerschke
orcid: 0000-0003-0853-8182
- first_name: Wenliang
full_name: Zhang, Wenliang
last_name: Zhang
- first_name: Mary H
full_name: Upton, Mary H
last_name: Upton
- first_name: Anna
full_name: Efimenko, Anna
last_name: Efimenko
- first_name: Katharina
full_name: Rolfs, Katharina
last_name: Rolfs
- first_name: Daniel E
full_name: McNally, Daniel E
last_name: McNally
- first_name: Laura
full_name: Maurel, Laura
last_name: Maurel
- first_name: Muntaser
full_name: Naamneh, Muntaser
last_name: Naamneh
- first_name: Marco
full_name: Caputo, Marco
last_name: Caputo
- first_name: Vladimir N
full_name: Strocov, Vladimir N
last_name: Strocov
- first_name: Zhiming
full_name: Wang, Zhiming
last_name: Wang
- first_name: Diego
full_name: Casa, Diego
last_name: Casa
- first_name: Christof W
full_name: Schneider, Christof W
last_name: Schneider
- first_name: Ekaterina
full_name: Pomjakushina, Ekaterina
last_name: Pomjakushina
- first_name: Krzysztof
full_name: Wohlfeld, Krzysztof
last_name: Wohlfeld
- first_name: Milan
full_name: Radovic, Milan
last_name: Radovic
- first_name: Thorsten
full_name: Schmitt, Thorsten
last_name: Schmitt
citation:
ama: Paris E, Tseng Y, Paerschke E, et al. Strain engineering of the charge and
spin-orbital interactions in Sr2IrO4. Proceedings of the National Academy of
Sciences of the United States of America. 2020;117(40):24764-24770. doi:10.1073/pnas.2012043117
apa: Paris, E., Tseng, Y., Paerschke, E., Zhang, W., Upton, M. H., Efimenko, A.,
… Schmitt, T. (2020). Strain engineering of the charge and spin-orbital interactions
in Sr2IrO4. Proceedings of the National Academy of Sciences of the United States
of America. National Academy of Sciences. https://doi.org/10.1073/pnas.2012043117
chicago: Paris, Eugenio, Yi Tseng, Ekaterina Paerschke, Wenliang Zhang, Mary H Upton,
Anna Efimenko, Katharina Rolfs, et al. “Strain Engineering of the Charge and Spin-Orbital
Interactions in Sr2IrO4.” Proceedings of the National Academy of Sciences of
the United States of America. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.2012043117.
ieee: E. Paris et al., “Strain engineering of the charge and spin-orbital
interactions in Sr2IrO4,” Proceedings of the National Academy of Sciences of
the United States of America, vol. 117, no. 40. National Academy of Sciences,
pp. 24764–24770, 2020.
ista: Paris E, Tseng Y, Paerschke E, Zhang W, Upton MH, Efimenko A, Rolfs K, McNally
DE, Maurel L, Naamneh M, Caputo M, Strocov VN, Wang Z, Casa D, Schneider CW, Pomjakushina
E, Wohlfeld K, Radovic M, Schmitt T. 2020. Strain engineering of the charge and
spin-orbital interactions in Sr2IrO4. Proceedings of the National Academy of Sciences
of the United States of America. 117(40), 24764–24770.
mla: Paris, Eugenio, et al. “Strain Engineering of the Charge and Spin-Orbital Interactions
in Sr2IrO4.” Proceedings of the National Academy of Sciences of the United
States of America, vol. 117, no. 40, National Academy of Sciences, 2020, pp.
24764–70, doi:10.1073/pnas.2012043117.
short: E. Paris, Y. Tseng, E. Paerschke, W. Zhang, M.H. Upton, A. Efimenko, K. Rolfs,
D.E. McNally, L. Maurel, M. Naamneh, M. Caputo, V.N. Strocov, Z. Wang, D. Casa,
C.W. Schneider, E. Pomjakushina, K. Wohlfeld, M. Radovic, T. Schmitt, Proceedings
of the National Academy of Sciences of the United States of America 117 (2020)
24764–24770.
date_created: 2020-10-25T23:01:17Z
date_published: 2020-10-06T00:00:00Z
date_updated: 2023-08-22T12:11:52Z
day: '06'
ddc:
- '530'
department:
- _id: MiLe
doi: 10.1073/pnas.2012043117
ec_funded: 1
external_id:
arxiv:
- '2009.12262'
isi:
- '000579059100029'
pmid:
- '32958669'
file:
- access_level: open_access
checksum: 1638fa36b442e2868576c6dd7d6dc505
content_type: application/pdf
creator: cziletti
date_created: 2020-10-28T11:53:12Z
date_updated: 2020-10-28T11:53:12Z
file_id: '8715'
file_name: 2020_PNAS_Paris.pdf
file_size: 1176522
relation: main_file
success: 1
file_date_updated: 2020-10-28T11:53:12Z
has_accepted_license: '1'
intvolume: ' 117'
isi: 1
issue: '40'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: 24764-24770
pmid: 1
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
publication: Proceedings of the National Academy of Sciences of the United States
of America
publication_identifier:
eissn:
- '10916490'
issn:
- '00278424'
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
scopus_import: '1'
status: public
title: Strain engineering of the charge and spin-orbital interactions in Sr2IrO4
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: 117
year: '2020'
...
---
_id: '9000'
abstract:
- lang: eng
text: 'In prokaryotes, thermodynamic models of gene regulation provide a highly
quantitative mapping from promoter sequences to gene-expression levels that is
compatible with in vivo and in vitro biophysical measurements. Such concordance
has not been achieved for models of enhancer function in eukaryotes. In equilibrium
models, it is difficult to reconcile the reported short transcription factor (TF)
residence times on the DNA with the high specificity of regulation. In nonequilibrium
models, progress is difficult due to an explosion in the number of parameters.
Here, we navigate this complexity by looking for minimal nonequilibrium enhancer
models that yield desired regulatory phenotypes: low TF residence time, high specificity,
and tunable cooperativity. We find that a single extra parameter, interpretable
as the “linking rate,” by which bound TFs interact with Mediator components, enables
our models to escape equilibrium bounds and access optimal regulatory phenotypes,
while remaining consistent with the reported phenomenology and simple enough to
be inferred from upcoming experiments. We further find that high specificity in
nonequilibrium models is in a trade-off with gene-expression noise, predicting
bursty dynamics—an experimentally observed hallmark of eukaryotic transcription.
By drastically reducing the vast parameter space of nonequilibrium enhancer models
to a much smaller subspace that optimally realizes biological function, we deliver
a rich class of models that could be tractably inferred from data in the near
future.'
acknowledgement: G.T. was supported by Human Frontiers Science Program Grant RGP0034/2018.
R.G. was supported by the Austrian Academy of Sciences DOC Fellowship. R.G. thanks
S. Avvakumov for helpful discussions.
article_processing_charge: No
article_type: original
author:
- first_name: Rok
full_name: Grah, Rok
id: 483E70DE-F248-11E8-B48F-1D18A9856A87
last_name: Grah
orcid: 0000-0003-2539-3560
- first_name: Benjamin
full_name: Zoller, Benjamin
last_name: Zoller
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
citation:
ama: Grah R, Zoller B, Tkačik G. Nonequilibrium models of optimal enhancer function.
PNAS. 2020;117(50):31614-31622. doi:10.1073/pnas.2006731117
apa: Grah, R., Zoller, B., & Tkačik, G. (2020). Nonequilibrium models of optimal
enhancer function. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.2006731117
chicago: Grah, Rok, Benjamin Zoller, and Gašper Tkačik. “Nonequilibrium Models of
Optimal Enhancer Function.” PNAS. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.2006731117.
ieee: R. Grah, B. Zoller, and G. Tkačik, “Nonequilibrium models of optimal enhancer
function,” PNAS, vol. 117, no. 50. National Academy of Sciences, pp. 31614–31622,
2020.
ista: Grah R, Zoller B, Tkačik G. 2020. Nonequilibrium models of optimal enhancer
function. PNAS. 117(50), 31614–31622.
mla: Grah, Rok, et al. “Nonequilibrium Models of Optimal Enhancer Function.” PNAS,
vol. 117, no. 50, National Academy of Sciences, 2020, pp. 31614–22, doi:10.1073/pnas.2006731117.
short: R. Grah, B. Zoller, G. Tkačik, PNAS 117 (2020) 31614–31622.
date_created: 2021-01-10T23:01:17Z
date_published: 2020-12-15T00:00:00Z
date_updated: 2023-08-24T11:10:22Z
day: '15'
ddc:
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doi: 10.1073/pnas.2006731117
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month: '12'
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project:
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grant_number: RGP0034/2018
name: Can evolution minimize spurious signaling crosstalk to reach optimal performance?
- _id: 267C84F4-B435-11E9-9278-68D0E5697425
name: Biophysically realistic genotype-phenotype maps for regulatory networks
publication: PNAS
publication_identifier:
eissn:
- '10916490'
issn:
- '00278424'
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/new-compact-model-for-gene-regulation-in-higher-organisms/
scopus_import: '1'
status: public
title: Nonequilibrium models of optimal enhancer function
tmp:
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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
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volume: 117
year: '2020'
...
---
_id: '6191'
abstract:
- lang: eng
text: The formation of self-organized patterns is key to the morphogenesis of multicellular
organisms, although a comprehensive theory of biological pattern formation is
still lacking. Here, we propose a minimal model combining tissue mechanics with
morphogen turnover and transport to explore routes to patterning. Our active description
couples morphogen reaction and diffusion, which impact cell differentiation and
tissue mechanics, to a two-phase poroelastic rheology, where one tissue phase
consists of a poroelastic cell network and the other one of a permeating extracellular
fluid, which provides a feedback by actively transporting morphogens. While this
model encompasses previous theories approximating tissues to inert monophasic
media, such as Turing’s reaction–diffusion model, it overcomes some of their key
limitations permitting pattern formation via any two-species biochemical kinetics
due to mechanically induced cross-diffusion flows. Moreover, we describe a qualitatively
different advection-driven Keller–Segel instability which allows for the formation
of patterns with a single morphogen and whose fundamental mode pattern robustly
scales with tissue size. We discuss the potential relevance of these findings
for tissue morphogenesis.
article_processing_charge: No
author:
- first_name: Pierre
full_name: Recho, Pierre
last_name: Recho
- first_name: Adrien
full_name: Hallou, Adrien
last_name: Hallou
- first_name: Edouard B
full_name: Hannezo, Edouard B
id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
last_name: Hannezo
orcid: 0000-0001-6005-1561
citation:
ama: Recho P, Hallou A, Hannezo EB. Theory of mechanochemical patterning in biphasic
biological tissues. Proceedings of the National Academy of Sciences of the
United States of America. 2019;116(12):5344-5349. doi:10.1073/pnas.1813255116
apa: Recho, P., Hallou, A., & Hannezo, E. B. (2019). Theory of mechanochemical
patterning in biphasic biological tissues. Proceedings of the National Academy
of Sciences of the United States of America. National Academy of Sciences.
https://doi.org/10.1073/pnas.1813255116
chicago: Recho, Pierre, Adrien Hallou, and Edouard B Hannezo. “Theory of Mechanochemical
Patterning in Biphasic Biological Tissues.” Proceedings of the National Academy
of Sciences of the United States of America. National Academy of Sciences,
2019. https://doi.org/10.1073/pnas.1813255116.
ieee: P. Recho, A. Hallou, and E. B. Hannezo, “Theory of mechanochemical patterning
in biphasic biological tissues,” Proceedings of the National Academy of Sciences
of the United States of America, vol. 116, no. 12. National Academy of Sciences,
pp. 5344–5349, 2019.
ista: Recho P, Hallou A, Hannezo EB. 2019. Theory of mechanochemical patterning
in biphasic biological tissues. Proceedings of the National Academy of Sciences
of the United States of America. 116(12), 5344–5349.
mla: Recho, Pierre, et al. “Theory of Mechanochemical Patterning in Biphasic Biological
Tissues.” Proceedings of the National Academy of Sciences of the United States
of America, vol. 116, no. 12, National Academy of Sciences, 2019, pp. 5344–49,
doi:10.1073/pnas.1813255116.
short: P. Recho, A. Hallou, E.B. Hannezo, Proceedings of the National Academy of
Sciences of the United States of America 116 (2019) 5344–5349.
date_created: 2019-03-31T21:59:13Z
date_published: 2019-03-19T00:00:00Z
date_updated: 2023-08-25T08:57:30Z
day: '19'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.1073/pnas.1813255116
external_id:
isi:
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pmid:
- '30819884'
file:
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content_type: application/pdf
creator: dernst
date_created: 2019-04-03T14:10:30Z
date_updated: 2020-07-14T12:47:23Z
file_id: '6193'
file_name: 2019_PNAS_Recho.pdf
file_size: 3456045
relation: main_file
file_date_updated: 2020-07-14T12:47:23Z
has_accepted_license: '1'
intvolume: ' 116'
isi: 1
issue: '12'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: 5344-5349
pmid: 1
project:
- _id: 268294B6-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P31639
name: Active mechano-chemical description of the cell cytoskeleton
publication: Proceedings of the National Academy of Sciences of the United States
of America
publication_identifier:
eissn:
- '10916490'
issn:
- '00278424'
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
link:
- relation: supplementary_material
url: www.pnas.org/lookup/suppl/doi:10.1073/pnas.1813255116/-/DCSupplemental
scopus_import: '1'
status: public
title: Theory of mechanochemical patterning in biphasic biological tissues
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: 116
year: '2019'
...