---
_id: '8741'
abstract:
- lang: eng
text: "In ecology, climate and other fields, (sub)systems have been identified that
can transition into a qualitatively different state when a critical threshold
or tipping point in a driving process is crossed. An understanding of those tipping
elements is of great interest given the increasing influence of humans on the
biophysical Earth system. Complex interactions exist between tipping elements,
e.g. physical mechanisms connect subsystems of the climate system. Based on earlier
work on such coupled nonlinear systems, we systematically assessed the qualitative
long-term behaviour of interacting tipping elements. We developed an understanding
of the consequences of interactions\r\non the tipping behaviour allowing for tipping
cascades to emerge under certain conditions. The (narrative) application of\r\nthese
qualitative results to real-world examples of interacting tipping elements indicates
that tipping cascades with profound consequences may occur: the interacting Greenland
ice sheet and thermohaline ocean circulation might tip before the tipping points
of the isolated subsystems are crossed. The eutrophication of the first lake in
a lake chain might propagate through the following lakes without a crossing of
their individual critical nutrient input levels. The possibility of emerging cascading
tipping dynamics calls for the development of a unified theory of interacting
tipping elements and the quantitative analysis of interacting real-world tipping
elements."
acknowledgement: "V.K. thanks the German National Academic Foundation (Studienstiftung
des deutschen Volkes) for financial\r\nsupport. J.F.D. is grateful for financial
support by the Stordalen Foundation via the Planetary Boundary Research\r\nNetwork
(PB.net), the Earth League’s EarthDoc program and the European Research Council
Advanced Grant\r\nproject ERA (Earth Resilience in the Anthropocene). We are thankful
for support by the Leibniz Association\r\n(project DominoES).\r\nAcknowledgements.
This work has been performed in the context of the copan collaboration and the FutureLab
on Earth\r\nResilience in the Anthropocene at the Potsdam Institute for Climate
Impact Research. Furthermore, we acknowledge\r\ndiscussions with and helpful comments
by N. Wunderling, J. Heitzig and M. Wiedermann."
article_number: '200599'
article_processing_charge: No
article_type: original
author:
- first_name: Ann Kristin
full_name: Klose, Ann Kristin
last_name: Klose
- first_name: Volker
full_name: Karle, Volker
id: D7C012AE-D7ED-11E9-95E8-1EC5E5697425
last_name: Karle
orcid: 0000-0002-6963-0129
- first_name: Ricarda
full_name: Winkelmann, Ricarda
last_name: Winkelmann
- first_name: Jonathan F.
full_name: Donges, Jonathan F.
last_name: Donges
citation:
ama: 'Klose AK, Karle V, Winkelmann R, Donges JF. Emergence of cascading dynamics
in interacting tipping elements of ecology and climate: Cascading dynamics in
tipping elements. Royal Society Open Science. 2020;7(6). doi:10.1098/rsos.200599'
apa: 'Klose, A. K., Karle, V., Winkelmann, R., & Donges, J. F. (2020). Emergence
of cascading dynamics in interacting tipping elements of ecology and climate:
Cascading dynamics in tipping elements. Royal Society Open Science. The
Royal Society. https://doi.org/10.1098/rsos.200599'
chicago: 'Klose, Ann Kristin, Volker Karle, Ricarda Winkelmann, and Jonathan F.
Donges. “Emergence of Cascading Dynamics in Interacting Tipping Elements of Ecology
and Climate: Cascading Dynamics in Tipping Elements.” Royal Society Open Science.
The Royal Society, 2020. https://doi.org/10.1098/rsos.200599.'
ieee: 'A. K. Klose, V. Karle, R. Winkelmann, and J. F. Donges, “Emergence of cascading
dynamics in interacting tipping elements of ecology and climate: Cascading dynamics
in tipping elements,” Royal Society Open Science, vol. 7, no. 6. The Royal
Society, 2020.'
ista: 'Klose AK, Karle V, Winkelmann R, Donges JF. 2020. Emergence of cascading
dynamics in interacting tipping elements of ecology and climate: Cascading dynamics
in tipping elements. Royal Society Open Science. 7(6), 200599.'
mla: 'Klose, Ann Kristin, et al. “Emergence of Cascading Dynamics in Interacting
Tipping Elements of Ecology and Climate: Cascading Dynamics in Tipping Elements.”
Royal Society Open Science, vol. 7, no. 6, 200599, The Royal Society, 2020,
doi:10.1098/rsos.200599.'
short: A.K. Klose, V. Karle, R. Winkelmann, J.F. Donges, Royal Society Open Science
7 (2020).
date_created: 2020-11-08T23:01:25Z
date_published: 2020-06-01T00:00:00Z
date_updated: 2024-03-12T12:31:30Z
day: '01'
ddc:
- '530'
- '550'
department:
- _id: MiLe
doi: 10.1098/rsos.200599
external_id:
arxiv:
- '1910.12042'
isi:
- '000545625200001'
file:
- access_level: open_access
checksum: 5505c445de373bfd836eb4d3b48b1f37
content_type: application/pdf
creator: dernst
date_created: 2020-11-09T09:07:11Z
date_updated: 2020-11-09T09:07:11Z
file_id: '8748'
file_name: 2020_RoyalSocOpenScience_Klose.pdf
file_size: 1611485
relation: main_file
success: 1
file_date_updated: 2020-11-09T09:07:11Z
has_accepted_license: '1'
intvolume: ' 7'
isi: 1
issue: '6'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '06'
oa: 1
oa_version: Published Version
publication: Royal Society Open Science
publication_identifier:
eissn:
- '20545703'
publication_status: published
publisher: The Royal Society
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Emergence of cascading dynamics in interacting tipping elements of ecology
and climate: Cascading dynamics in tipping elements'
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 7
year: '2020'
...
---
_id: '7687'
abstract:
- lang: eng
text: A working group, which was established within the Network of Repository Managers (RepManNet), has dealt with common certifications for repositories. In
addition, current requirements of the research funding agencies FWF and EU were
also taken into account. The Core Trust Seal was examined in more detail. For
this purpose, a questionnaire was sent to those organizations that are already certified
with CTS in Austria. The answers were summarized and evaluated anonymously. It
is recommended to go for a repository certification. Moreover, the development
of a DINI certificate in Austria is strongly suggested.
- lang: ger
text: ' Eine Arbeitsgruppe, die im Rahmen des Netzwerks für RepositorienmanagerInnen
(RepManNet) entstanden ist, hat sich mit gängigen Zertifizierungen für Repositorien
beschäftigt. Weiters wurden aktuelle Vorgaben der Forschungsförderer FWF und EU
herangezogen. Das Core Trust Seal wurde genauer betrachtet. Hierfür wurden jenen Organisationen, die in Österreich bereits mit CTS zertifiziert
sind, ein Fragebogen übermittelt. Die Antworten wurden anonymisiert zusammengefasst
und ausgewertet. Plädiert wird für eine Zertifizierung von Repositorien und die
Entwicklung einer DINI-Zertifizierung in Österreich.'
article_processing_charge: No
article_type: original
author:
- first_name: Doris
full_name: Ernst, Doris
id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
last_name: Ernst
orcid: 0000-0002-2354-0195
- first_name: Gertraud
full_name: Novotny, Gertraud
last_name: Novotny
- first_name: Eva Maria
full_name: Schönher, Eva Maria
last_name: Schönher
citation:
ama: Ernst D, Novotny G, Schönher EM. (Core Trust) Seal your repository! Mitteilungen
der Vereinigung Österreichischer Bibliothekarinnen und Bibliothekare. 2020;73(1):46-59.
doi:10.31263/voebm.v73i1.3491
apa: Ernst, D., Novotny, G., & Schönher, E. M. (2020). (Core Trust) Seal your
repository! Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen
und Bibliothekare. Vereinigung Osterreichischer Bibliothekarinnen und Bibliothekare.
https://doi.org/10.31263/voebm.v73i1.3491
chicago: Ernst, Doris, Gertraud Novotny, and Eva Maria Schönher. “(Core Trust) Seal
your repository!” Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen
und Bibliothekare. Vereinigung Osterreichischer Bibliothekarinnen und Bibliothekare,
2020. https://doi.org/10.31263/voebm.v73i1.3491.
ieee: D. Ernst, G. Novotny, and E. M. Schönher, “(Core Trust) Seal your repository!,”
Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen und Bibliothekare,
vol. 73, no. 1. Vereinigung Osterreichischer Bibliothekarinnen und Bibliothekare,
pp. 46–59, 2020.
ista: Ernst D, Novotny G, Schönher EM. 2020. (Core Trust) Seal your repository!
Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen und Bibliothekare.
73(1), 46–59.
mla: Ernst, Doris, et al. “(Core Trust) Seal your repository!” Mitteilungen der
Vereinigung Österreichischer Bibliothekarinnen und Bibliothekare, vol. 73,
no. 1, Vereinigung Osterreichischer Bibliothekarinnen und Bibliothekare, 2020,
pp. 46–59, doi:10.31263/voebm.v73i1.3491.
short: D. Ernst, G. Novotny, E.M. Schönher, Mitteilungen der Vereinigung Österreichischer
Bibliothekarinnen und Bibliothekare 73 (2020) 46–59.
date_created: 2020-04-28T08:37:38Z
date_published: 2020-04-28T00:00:00Z
date_updated: 2024-03-12T10:12:33Z
day: '28'
ddc:
- '020'
department:
- _id: E-Lib
doi: 10.31263/voebm.v73i1.3491
file:
- access_level: open_access
checksum: fee784f15a489deb7def6ccf8c5bf8c3
content_type: application/pdf
creator: dernst
date_created: 2020-06-17T10:50:13Z
date_updated: 2024-03-12T10:12:33Z
file_id: '7970'
file_name: 2020_VOEB_Ernst.pdf
file_size: 579291
relation: main_file
file_date_updated: 2024-03-12T10:12:33Z
has_accepted_license: '1'
intvolume: ' 73'
issue: '1'
language:
- iso: ger
month: '04'
oa: 1
oa_version: Published Version
page: 46-59
popular_science: '1'
publication: Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen und Bibliothekare
publication_identifier:
issn:
- 1022-2588
publication_status: published
publisher: Vereinigung Osterreichischer Bibliothekarinnen und Bibliothekare
scopus_import: '1'
status: public
title: (Core Trust) Seal your repository!
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 73
year: '2020'
...
---
_id: '15071'
abstract:
- lang: eng
text: "A mesophilic methanogenic culture, designated JL01, was isolated from Holocene
permafrost in the Russian Arctic [1]. After long-term extensive cultivation at
15°C it turned out to be a tied binary culture of archaeal (JL01) and bacterial
(Sphaerochaeta associata GLS2) strains.\r\nStrain JL01 was a strict anaerobe and
grew on methanol, acetate and methylamines as energy and carbon sources. Cells
were irregular coccoid, non-motile, non-spore-forming, and Gram-stainpositive.
Optimum conditions for growth were 24-28 oC, pH 6.8–7.3 and 0.075-0.1 M NaCl.\r\nPhylogenetic
tree reconstructions based on 16S rRNA and concatenated alignment of broadly\r\nconserved
protein-coding genes revealed its close relation to Methanosarcina mazei S-6\r\nT
(similarity 99.5%). The comparison of whole genomic sequences (ANI) of the isolate
and the type strain of M.mazei was 98.5%, which is higher than the values recommended
for new species. Thus strain JL01 (=VKM B-2370=JCM 31898) represents the first
M. mazei isolated from permanently subzero Arcticsediments. The long-term co-cultivation
of JL01 with S. associata GLS2T showed the methane production without any additional
carbon and energy sources. Genome analysis of S. associata GLS2T revealed putative
genes involved in methanochondroithin catabolism."
acknowledgement: "The work was supported by of Russian Foundation of Basic Research:
grant № 19-04-00831 for Viktoria Shcherbakova and Olga Troshina, grant № 18-34-00334
for Viktoriia Oshurkova and Vladimir Trubitsyn. \r\nWe thank Dr Natalia Suzina (IBPM
RAS, Federal Research Center Pushchino Center for\r\nBiological Research RAS) for
the help with the microscopic studies, respectively; Dr. Margarita Meyer (Division
of Genetics, Department of Medicine, BWH and HMS, USA) and Dr Fedor Kondrashov (IST,
Austria) for their help in obtaining the genomic sequence of strain JL01. "
article_processing_charge: Yes
author:
- first_name: Viktoriia
full_name: Oshurkova, Viktoriia
last_name: Oshurkova
- first_name: Olga
full_name: Troshina, Olga
last_name: Troshina
- first_name: Vladimir
full_name: Trubitsyn, Vladimir
last_name: Trubitsyn
- first_name: Yana
full_name: Ryzhmanova, Yana
last_name: Ryzhmanova
- first_name: Olga
full_name: Bochkareva, Olga
id: C4558D3C-6102-11E9-A62E-F418E6697425
last_name: Bochkareva
orcid: 0000-0003-1006-6639
- first_name: Viktoria
full_name: Shcherbakova, Viktoria
last_name: Shcherbakova
citation:
ama: 'Oshurkova V, Troshina O, Trubitsyn V, Ryzhmanova Y, Bochkareva O, Shcherbakova
V. Characterization of methanosarcina mazei JL01 isolated from holocene arctic
permafrost and study of the archaeon cooperation with bacterium Sphaerochaeta
associata GLS2T. In: Proceedings of 1st International Electronic Conference
on Microbiology. MDPI; 2020. doi:10.3390/ecm2020-07116'
apa: 'Oshurkova, V., Troshina, O., Trubitsyn, V., Ryzhmanova, Y., Bochkareva, O.,
& Shcherbakova, V. (2020). Characterization of methanosarcina mazei JL01 isolated
from holocene arctic permafrost and study of the archaeon cooperation with bacterium
Sphaerochaeta associata GLS2T. In Proceedings of 1st International Electronic
Conference on Microbiology. Virtual: MDPI. https://doi.org/10.3390/ecm2020-07116'
chicago: Oshurkova, Viktoriia, Olga Troshina, Vladimir Trubitsyn, Yana Ryzhmanova,
Olga Bochkareva, and Viktoria Shcherbakova. “Characterization of Methanosarcina
Mazei JL01 Isolated from Holocene Arctic Permafrost and Study of the Archaeon
Cooperation with Bacterium Sphaerochaeta Associata GLS2T.” In Proceedings of
1st International Electronic Conference on Microbiology. MDPI, 2020. https://doi.org/10.3390/ecm2020-07116.
ieee: V. Oshurkova, O. Troshina, V. Trubitsyn, Y. Ryzhmanova, O. Bochkareva, and
V. Shcherbakova, “Characterization of methanosarcina mazei JL01 isolated from
holocene arctic permafrost and study of the archaeon cooperation with bacterium
Sphaerochaeta associata GLS2T,” in Proceedings of 1st International Electronic
Conference on Microbiology, Virtual, 2020.
ista: 'Oshurkova V, Troshina O, Trubitsyn V, Ryzhmanova Y, Bochkareva O, Shcherbakova
V. 2020. Characterization of methanosarcina mazei JL01 isolated from holocene
arctic permafrost and study of the archaeon cooperation with bacterium Sphaerochaeta
associata GLS2T. Proceedings of 1st International Electronic Conference on Microbiology.
ECM: Electronic Conference on Microbiology.'
mla: Oshurkova, Viktoriia, et al. “Characterization of Methanosarcina Mazei JL01
Isolated from Holocene Arctic Permafrost and Study of the Archaeon Cooperation
with Bacterium Sphaerochaeta Associata GLS2T.” Proceedings of 1st International
Electronic Conference on Microbiology, MDPI, 2020, doi:10.3390/ecm2020-07116.
short: V. Oshurkova, O. Troshina, V. Trubitsyn, Y. Ryzhmanova, O. Bochkareva, V.
Shcherbakova, in:, Proceedings of 1st International Electronic Conference on Microbiology,
MDPI, 2020.
conference:
end_date: 2020-11-30
location: Virtual
name: 'ECM: Electronic Conference on Microbiology'
start_date: 2020-11-02
date_created: 2024-03-04T11:41:31Z
date_published: 2020-11-02T00:00:00Z
date_updated: 2024-03-20T08:06:22Z
day: '02'
ddc:
- '570'
department:
- _id: FyKo
doi: 10.3390/ecm2020-07116
file:
- access_level: open_access
checksum: d1914af7811a21a4b2744eb51b5834e3
content_type: application/pdf
creator: dernst
date_created: 2024-03-20T08:05:46Z
date_updated: 2024-03-20T08:05:46Z
file_id: '15127'
file_name: 2020_ECM_Oshurkova.pdf
file_size: 595543
relation: main_file
success: 1
file_date_updated: 2024-03-20T08:05:46Z
has_accepted_license: '1'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
publication: Proceedings of 1st International Electronic Conference on Microbiology
publication_status: published
publisher: MDPI
quality_controlled: '1'
status: public
title: Characterization of methanosarcina mazei JL01 isolated from holocene arctic
permafrost and study of the archaeon cooperation with bacterium Sphaerochaeta associata
GLS2T
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: conference
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '15153'
abstract:
- lang: eng
text: Mammalian circadian rhythms are generated by a transcription-based feedback
loop in which CLOCK:BMAL1 drives transcription of its repressors (PER1/2, CRY1/2),
which ultimately interact with CLOCK:BMAL1 to close the feedback loop with ~24
hr periodicity. Here we pinpoint a key difference between CRY1 and CRY2 that underlies
their differential strengths as transcriptional repressors. Both cryptochromes
bind the BMAL1 transactivation domain similarly to sequester it from coactivators
and repress CLOCK:BMAL1 activity. However, we find that CRY1 is recruited with
much higher affinity to the PAS domain core of CLOCK:BMAL1, allowing it to serve
as a stronger repressor that lengthens circadian period. We discovered a dynamic
serine-rich loop adjacent to the secondary pocket in the photolyase homology region
(PHR) domain that regulates differential binding of cryptochromes to the PAS domain
core of CLOCK:BMAL1. Notably, binding of the co-repressor PER2 remodels the serine
loop of CRY2, making it more CRY1-like and enhancing its affinity for CLOCK:BMAL1.
article_number: '55275'
article_processing_charge: No
article_type: original
author:
- first_name: Jennifer L
full_name: Fribourgh, Jennifer L
last_name: Fribourgh
- first_name: Ashutosh
full_name: Srivastava, Ashutosh
last_name: Srivastava
- first_name: Colby R
full_name: Sandate, Colby R
last_name: Sandate
- first_name: Alicia Kathleen
full_name: Michael, Alicia Kathleen
id: 6437c950-2a03-11ee-914d-d6476dd7b75c
last_name: Michael
- first_name: Peter L
full_name: Hsu, Peter L
last_name: Hsu
- first_name: Christin
full_name: Rakers, Christin
last_name: Rakers
- first_name: Leslee T
full_name: Nguyen, Leslee T
last_name: Nguyen
- first_name: Megan R
full_name: Torgrimson, Megan R
last_name: Torgrimson
- first_name: Gian Carlo G
full_name: Parico, Gian Carlo G
last_name: Parico
- first_name: Sarvind
full_name: Tripathi, Sarvind
last_name: Tripathi
- first_name: Ning
full_name: Zheng, Ning
last_name: Zheng
- first_name: Gabriel C
full_name: Lander, Gabriel C
last_name: Lander
- first_name: Tsuyoshi
full_name: Hirota, Tsuyoshi
last_name: Hirota
- first_name: Florence
full_name: Tama, Florence
last_name: Tama
- first_name: Carrie L
full_name: Partch, Carrie L
last_name: Partch
citation:
ama: Fribourgh JL, Srivastava A, Sandate CR, et al. Dynamics at the serine loop
underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian
timing. eLife. 2020;9. doi:10.7554/elife.55275
apa: Fribourgh, J. L., Srivastava, A., Sandate, C. R., Michael, A. K., Hsu, P. L.,
Rakers, C., … Partch, C. L. (2020). Dynamics at the serine loop underlie differential
affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing. ELife.
eLife Sciences Publications. https://doi.org/10.7554/elife.55275
chicago: Fribourgh, Jennifer L, Ashutosh Srivastava, Colby R Sandate, Alicia K.
Michael, Peter L Hsu, Christin Rakers, Leslee T Nguyen, et al. “Dynamics at the
Serine Loop Underlie Differential Affinity of Cryptochromes for CLOCK:BMAL1 to
Control Circadian Timing.” ELife. eLife Sciences Publications, 2020. https://doi.org/10.7554/elife.55275.
ieee: J. L. Fribourgh et al., “Dynamics at the serine loop underlie differential
affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing,” eLife,
vol. 9. eLife Sciences Publications, 2020.
ista: Fribourgh JL, Srivastava A, Sandate CR, Michael AK, Hsu PL, Rakers C, Nguyen
LT, Torgrimson MR, Parico GCG, Tripathi S, Zheng N, Lander GC, Hirota T, Tama
F, Partch CL. 2020. Dynamics at the serine loop underlie differential affinity
of cryptochromes for CLOCK:BMAL1 to control circadian timing. eLife. 9, 55275.
mla: Fribourgh, Jennifer L., et al. “Dynamics at the Serine Loop Underlie Differential
Affinity of Cryptochromes for CLOCK:BMAL1 to Control Circadian Timing.” ELife,
vol. 9, 55275, eLife Sciences Publications, 2020, doi:10.7554/elife.55275.
short: J.L. Fribourgh, A. Srivastava, C.R. Sandate, A.K. Michael, P.L. Hsu, C. Rakers,
L.T. Nguyen, M.R. Torgrimson, G.C.G. Parico, S. Tripathi, N. Zheng, G.C. Lander,
T. Hirota, F. Tama, C.L. Partch, ELife 9 (2020).
date_created: 2024-03-21T07:55:12Z
date_published: 2020-02-26T00:00:00Z
date_updated: 2024-03-25T12:25:02Z
day: '26'
doi: 10.7554/elife.55275
extern: '1'
intvolume: ' 9'
keyword:
- General Immunology and Microbiology
- General Biochemistry
- Genetics and Molecular Biology
- General Medicine
- General Neuroscience
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.7554/eLife.55275
month: '02'
oa: 1
oa_version: Published Version
publication: eLife
publication_identifier:
issn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Dynamics at the serine loop underlie differential affinity of cryptochromes
for CLOCK:BMAL1 to control circadian timing
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 9
year: '2020'
...
---
_id: '7525'
abstract:
- lang: eng
text: "The medial habenula (MHb) is an evolutionary conserved epithalamic structure
important for the modulation of emotional memory. It is involved in regulation
of anxiety, compulsive behavior, addiction (nicotinic and opioid), sexual and
feeding behavior. MHb receives inputs from septal regions and projects exclusively
to the interpeduncular nucleus (IPN). Distinct sub-regions of the septum project
to different subnuclei of MHb: the bed nucleus of anterior commissure projects
to dorsal MHb and the triangular septum projects to ventral MHb. Furthermore,
the dorsal and ventral MHb project to the lateral and rostral/central IPN, respectively.
Importantly, these projections have unique features of prominent co-release of
different neurotransmitters and requirement of a peculiar type of calcium channel
for release. In general, synaptic neurotransmission requires an activity-dependent
influx of Ca2+ into the presynaptic terminal through voltage-gated calcium channels.
The calcium channel family most commonly involved in neurotransmitter release
comprises three members, P/Q-, N- and R-type with Cav2.1, Cav2.2 and Cav2.3 subunits,
respectively. In contrast to most CNS synapses that mainly express Cav2.1 and/or
Cav2.2, MHb terminals in the IPN exclusively express Cav2.3. In other parts of
the brain, such as the hippocampus, Cav2.3 is mostly located to postsynaptic elements.
This unusual presynaptic location of Cav2.3 in the MHb-IPN pathway implies unique
mechanisms of glutamate release in this pathway. One potential example of such
uniqueness is the facilitation of release by GABAB receptor (GBR) activation.
Presynaptic GBRs usually inhibit the release of neurotransmitters by inhibiting
presynaptic calcium channels. MHb shows the highest expression levels of GBR in
the brain. GBRs comprise two subunits, GABAB1 (GB1) and GABAB2 (GB2), and are
associated with auxiliary subunits, called potassium channel tetramerization domain
containing proteins (KCTD) 8, 12, 12b and 16. Among these four subunits, KCTD12b
is exclusively expressed in ventral MHb, and KCTD8 shows the strongest expression
in the whole MHb among other brain regions, indicating that KCTD8 and KCTD12b
may be involved in the unique mechanisms of neurotransmitter release mediated
by Cav2.3 and regulated by GBRs in this pathway. \r\nIn the present study, we
first verified that neurotransmission in both dorsal and ventral MHb-IPN pathways
is mainly mediated by Cav2.3 using a selective blocker of R-type channels, SNX-482.
We next found that baclofen, a GBR agonist, has facilitatory effects on release
from ventral MHb terminal in rostral IPN, whereas it has inhibitory effects on
release from dorsal MHb terminals in lateral IPN, indicating that KCTD12b expressed
exclusively in ventral MHb may have a role in the facilitatory effects of GBR
activation. In a heterologous expression system using HEK cells, we found that
KCTD8 and KCTD12b but not KCTD12 directly bind with Cav2.3. Pre-embedding immunogold
electron microscopy data show that Cav2.3 and KCTD12b are distributed most densely
in presynaptic active zone in IPN with KCTD12b being present only in rostral/central
but not lateral IPN, whereas GABAB, KCTD8 and KCTD12 are distributed most densely
in perisynaptic sites with KCTD12 present more frequently in postsynaptic elements
and only in rostral/central IPN. In freeze-fracture replica labelling, Cav2.3,
KCTD8 and KCTD12b are co-localized with each other in the same active zone indicating
that they may form complexes regulating vesicle release in rostral IPN. \r\nOn
electrophysiological studies of wild type (WT) mice, we found that paired-pulse
ratio in rostral IPN of KCTD12b knock-out (KO) mice is lower than those of WT
and KCTD8 KO mice. Consistent with this finding, in mean variance analysis, release
probability in rostral IPN of KCTD12b KO mice is higher than that of WT and KCTD8
KO mice. Although paired-pulse ratios are not different between WT and KCTD8 KO
mice, the mean variance analysis revealed significantly lower release probability
in rostral IPN of KCTD8 KO than WT mice. These results demonstrate bidirectional
regulation of Cav2.3-mediated release by KCTD8 and KCTD12b without GBR activation
in rostral IPN. Finally, we examined the baclofen effects in rostral IPN of KCTD8
and KCTD12b KO mice, and found the facilitation of release remained in both KO
mice, indicating that the peculiar effects of the GBR activation in this pathway
do not depend on the selective expression of these KCTD subunits in ventral MHb.
However, we found that presynaptic potentiation of evoked EPSC amplitude by baclofen
falls to baseline after washout faster in KCTD12b KO mice than WT, KCTD8 KO and
KCTD8/12b double KO mice. This result indicates that KCTD12b is involved in sustained
potentiation of vesicle release by GBR activation, whereas KCTD8 is involved in
its termination in the absence of KCTD12b. Consistent with these functional findings,
replica labelling revealed an increase in density of KCTD8, but not Cav2.3 or
GBR at active zone in rostral IPN of KCTD12b KO mice compared with that of WT
mice, suggesting that increased association of KCTD8 with Cav2.3 facilitates the
release probability and termination of the GBR effect in the absence of KCTD12b.\r\nIn
summary, our study provided new insights into the physiological roles of presynaptic
Cav2.3, GBRs and their auxiliary subunits KCTDs at an evolutionary conserved neuronal
circuit. Future studies will be required to identify the exact molecular mechanism
underlying the GBR-mediated presynaptic potentiation on ventral MHb terminals.
It remains to be determined whether the prominent presence of presynaptic KCTDs
at active zone could exert similar neuromodulatory functions in different pathways
of the brain.\r\n"
acknowledged_ssus:
- _id: EM-Fac
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Pradeep
full_name: Bhandari, Pradeep
id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87
last_name: Bhandari
orcid: 0000-0003-0863-4481
citation:
ama: Bhandari P. Localization and functional role of Cav2.3 in the medial habenula
to interpeduncular nucleus pathway. 2020. doi:10.15479/AT:ISTA:7525
apa: Bhandari, P. (2020). Localization and functional role of Cav2.3 in the medial
habenula to interpeduncular nucleus pathway. Institute of Science and Technology
Austria. https://doi.org/10.15479/AT:ISTA:7525
chicago: Bhandari, Pradeep. “Localization and Functional Role of Cav2.3 in the Medial
Habenula to Interpeduncular Nucleus Pathway.” Institute of Science and Technology
Austria, 2020. https://doi.org/10.15479/AT:ISTA:7525.
ieee: P. Bhandari, “Localization and functional role of Cav2.3 in the medial habenula
to interpeduncular nucleus pathway,” Institute of Science and Technology Austria,
2020.
ista: Bhandari P. 2020. Localization and functional role of Cav2.3 in the medial
habenula to interpeduncular nucleus pathway. Institute of Science and Technology
Austria.
mla: Bhandari, Pradeep. Localization and Functional Role of Cav2.3 in the Medial
Habenula to Interpeduncular Nucleus Pathway. Institute of Science and Technology
Austria, 2020, doi:10.15479/AT:ISTA:7525.
short: P. Bhandari, Localization and Functional Role of Cav2.3 in the Medial Habenula
to Interpeduncular Nucleus Pathway, Institute of Science and Technology Austria,
2020.
date_created: 2020-02-26T10:56:37Z
date_published: 2020-02-28T00:00:00Z
date_updated: 2023-09-07T13:20:03Z
day: '28'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: RySh
doi: 10.15479/AT:ISTA:7525
file:
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checksum: 4589234fdb12b4ad72273b311723a7b4
content_type: application/pdf
creator: pbhandari
date_created: 2020-02-28T08:37:53Z
date_updated: 2021-03-01T23:30:04Z
embargo: 2021-02-28
file_id: '7538'
file_name: Pradeep Bhandari Thesis.pdf
file_size: 9646346
relation: main_file
title: Localization and functional role of Cav2.3 in the medial habenula to interpeduncular
nucleus pathway
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content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
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date_created: 2020-02-28T08:47:14Z
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file_name: Pradeep Bhandari Thesis.docx
file_size: 35252164
relation: source_file
title: Localization and functional role of Cav2.3 in the medial habenula to interpeduncular
nucleus pathway
file_date_updated: 2021-03-01T23:30:04Z
has_accepted_license: '1'
keyword:
- Cav2.3
- medial habenula (MHb)
- interpeduncular nucleus (IPN)
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
page: '79'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
title: Localization and functional role of Cav2.3 in the medial habenula to interpeduncular
nucleus pathway
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2020'
...
---
_id: '8586'
abstract:
- lang: eng
text: Cryo-electron microscopy (cryo-EM) of cellular specimens provides insights
into biological processes and structures within a native context. However, a major
challenge still lies in the efficient and reproducible preparation of adherent
cells for subsequent cryo-EM analysis. This is due to the sensitivity of many
cellular specimens to the varying seeding and culturing conditions required for
EM experiments, the often limited amount of cellular material and also the fragility
of EM grids and their substrate. Here, we present low-cost and reusable 3D printed
grid holders, designed to improve specimen preparation when culturing challenging
cellular samples directly on grids. The described grid holders increase cell culture
reproducibility and throughput, and reduce the resources required for cell culturing.
We show that grid holders can be integrated into various cryo-EM workflows, including
micro-patterning approaches to control cell seeding on grids, and for generating
samples for cryo-focused ion beam milling and cryo-electron tomography experiments.
Their adaptable design allows for the generation of specialized grid holders customized
to a large variety of applications.
acknowledged_ssus:
- _id: ScienComp
- _id: LifeSc
- _id: Bio
- _id: EM-Fac
acknowledgement: This work was supported by the Austrian Science Fund (FWF, P33367)
to FKMS. BZ acknowledges support by the Niederösterreich Fond. This research was
also supported by the Scientific Service Units (SSU) of IST Austria through resources
provided by Scientific Computing (SciComp), the Life Science Facility (LSF), the
BioImaging Facility (BIF) and the Electron Microscopy Facility (EMF). We thank Georgi
Dimchev (IST Austria) and Sonja Jacob (Vienna Biocenter Core Facilities) for testing
our grid holders in different experimental setups and Daniel Gütl and the Kondrashov
group (IST Austria) for granting us repeated access to their 3D printers. We also
thank Jonna Alanko and the Sixt lab (IST Austria) for providing us HeLa cells, primary
BL6 mouse tail fibroblasts, NIH 3T3 fibroblasts and human telomerase immortalised
foreskin fibroblasts for our experiments. We are thankful to Ori Avinoam and William
Wan for helpful comments on the manuscript and also thank Dorotea Fracchiolla (Art&Science)
for illustrating the graphical abstract.
article_number: '107633'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Florian
full_name: Fäßler, Florian
id: 404F5528-F248-11E8-B48F-1D18A9856A87
last_name: Fäßler
orcid: 0000-0001-7149-769X
- first_name: Bettina
full_name: Zens, Bettina
id: 45FD126C-F248-11E8-B48F-1D18A9856A87
last_name: Zens
orcid: 0000-0002-9561-1239
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Florian KM
full_name: Schur, Florian KM
id: 48AD8942-F248-11E8-B48F-1D18A9856A87
last_name: Schur
orcid: 0000-0003-4790-8078
citation:
ama: Fäßler F, Zens B, Hauschild R, Schur FK. 3D printed cell culture grid holders
for improved cellular specimen preparation in cryo-electron microscopy. Journal
of Structural Biology. 2020;212(3). doi:10.1016/j.jsb.2020.107633
apa: Fäßler, F., Zens, B., Hauschild, R., & Schur, F. K. (2020). 3D printed
cell culture grid holders for improved cellular specimen preparation in cryo-electron
microscopy. Journal of Structural Biology. Elsevier. https://doi.org/10.1016/j.jsb.2020.107633
chicago: Fäßler, Florian, Bettina Zens, Robert Hauschild, and Florian KM Schur.
“3D Printed Cell Culture Grid Holders for Improved Cellular Specimen Preparation
in Cryo-Electron Microscopy.” Journal of Structural Biology. Elsevier,
2020. https://doi.org/10.1016/j.jsb.2020.107633.
ieee: F. Fäßler, B. Zens, R. Hauschild, and F. K. Schur, “3D printed cell culture
grid holders for improved cellular specimen preparation in cryo-electron microscopy,”
Journal of Structural Biology, vol. 212, no. 3. Elsevier, 2020.
ista: Fäßler F, Zens B, Hauschild R, Schur FK. 2020. 3D printed cell culture grid
holders for improved cellular specimen preparation in cryo-electron microscopy.
Journal of Structural Biology. 212(3), 107633.
mla: Fäßler, Florian, et al. “3D Printed Cell Culture Grid Holders for Improved
Cellular Specimen Preparation in Cryo-Electron Microscopy.” Journal of Structural
Biology, vol. 212, no. 3, 107633, Elsevier, 2020, doi:10.1016/j.jsb.2020.107633.
short: F. Fäßler, B. Zens, R. Hauschild, F.K. Schur, Journal of Structural Biology
212 (2020).
date_created: 2020-09-29T13:24:06Z
date_published: 2020-12-01T00:00:00Z
date_updated: 2024-03-28T23:30:05Z
day: '01'
ddc:
- '570'
department:
- _id: FlSc
doi: 10.1016/j.jsb.2020.107633
external_id:
isi:
- '000600997800008'
file:
- access_level: open_access
checksum: c48cbf594e84fc2f91966ffaafc0918c
content_type: application/pdf
creator: dernst
date_created: 2020-12-10T14:01:10Z
date_updated: 2020-12-10T14:01:10Z
file_id: '8937'
file_name: 2020_JourStrucBiology_Faessler.pdf
file_size: 7076870
relation: main_file
success: 1
file_date_updated: 2020-12-10T14:01:10Z
has_accepted_license: '1'
intvolume: ' 212'
isi: 1
issue: '3'
keyword:
- electron microscopy
- cryo-EM
- EM sample preparation
- 3D printing
- cell culture
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
project:
- _id: 9B954C5C-BA93-11EA-9121-9846C619BF3A
grant_number: P33367
name: Structure and isoform diversity of the Arp2/3 complex
- _id: 059B463C-7A3F-11EA-A408-12923DDC885E
name: NÖ-Fonds Preis für die Jungforscherin des Jahres am IST Austria
publication: Journal of Structural Biology
publication_identifier:
issn:
- 1047-8477
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
record:
- id: '14592'
relation: used_in_publication
status: public
- id: '12491'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: 3D printed cell culture grid holders for improved cellular specimen preparation
in cryo-electron microscopy
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: 212
year: '2020'
...
---
_id: '8657'
abstract:
- lang: eng
text: "Synthesis of proteins – translation – is a fundamental process of life. Quantitative
studies anchor translation into the context of bacterial physiology and reveal
several mathematical relationships, called “growth laws,” which capture physiological
feedbacks between protein synthesis and cell growth. Growth laws describe the
dependency of the ribosome abundance as a function of growth rate, which can change
depending on the growth conditions. Perturbations of translation reveal that bacteria
employ a compensatory strategy in which the reduced translation capability results
in increased expression of the translation machinery.\r\nPerturbations of translation
are achieved in various ways; clinically interesting is the application of translation-targeting
antibiotics – translation inhibitors. The antibiotic effects on bacterial physiology
are often poorly understood. Bacterial responses to two or more simultaneously
applied antibiotics are even more puzzling. The combined antibiotic effect determines
the type of drug interaction, which ranges from synergy (the effect is stronger
than expected) to antagonism (the effect is weaker) and suppression (one of the
drugs loses its potency).\r\nIn the first part of this work, we systematically
measure the pairwise interaction network for translation inhibitors that interfere
with different steps in translation. We find that the interactions are surprisingly
diverse and tend to be more antagonistic. To explore the underlying mechanisms,
we begin with a minimal biophysical model of combined antibiotic action. We base
this model on the kinetics of antibiotic uptake and binding together with the
physiological response described by the growth laws. The biophysical model explains
some drug interactions, but not all; it specifically fails to predict suppression.\r\nIn
the second part of this work, we hypothesize that elusive suppressive drug interactions
result from the interplay between ribosomes halted in different stages of translation.
To elucidate this putative mechanism of drug interactions between translation
inhibitors, we generate translation bottlenecks genetically using in- ducible
control of translation factors that regulate well-defined translation cycle steps.
These perturbations accurately mimic antibiotic action and drug interactions,
supporting that the interplay of different translation bottlenecks partially causes
these interactions.\r\nWe extend this approach by varying two translation bottlenecks
simultaneously. This approach reveals the suppression of translocation inhibition
by inhibited translation. We rationalize this effect by modeling dense traffic
of ribosomes that move on transcripts in a translation factor-mediated manner.
This model predicts a dissolution of traffic jams caused by inhibited translocation
when the density of ribosome traffic is reduced by lowered initiation. We base
this model on the growth laws and quantitative relationships between different
translation and growth parameters.\r\nIn the final part of this work, we describe
a set of tools aimed at quantification of physiological and translation parameters.
We further develop a simple model that directly connects the abundance of a translation
factor with the growth rate, which allows us to extract physiological parameters
describing initiation. We demonstrate the development of tools for measuring translation
rate.\r\nThis thesis showcases how a combination of high-throughput growth rate
mea- surements, genetics, and modeling can reveal mechanisms of drug interactions.
Furthermore, by a gradual transition from combinations of antibiotics to precise
genetic interventions, we demonstrated the equivalency between genetic and chemi-
cal perturbations of translation. These findings tile the path for quantitative
studies of antibiotic combinations and illustrate future approaches towards the
quantitative description of translation."
acknowledged_ssus:
- _id: LifeSc
- _id: M-Shop
acknowledgement: I thank Life Science Facilities for their continuous support with
providing top-notch laboratory materials, keeping the devices humming, and coordinating
the repairs and building of custom-designed laboratory equipment with the MIBA Machine
shop.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Bor
full_name: Kavcic, Bor
id: 350F91D2-F248-11E8-B48F-1D18A9856A87
last_name: Kavcic
orcid: 0000-0001-6041-254X
citation:
ama: 'Kavcic B. Perturbations of protein synthesis: from antibiotics to genetics
and physiology. 2020. doi:10.15479/AT:ISTA:8657'
apa: 'Kavcic, B. (2020). Perturbations of protein synthesis: from antibiotics
to genetics and physiology. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8657'
chicago: 'Kavcic, Bor. “Perturbations of Protein Synthesis: From Antibiotics to
Genetics and Physiology.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8657.'
ieee: 'B. Kavcic, “Perturbations of protein synthesis: from antibiotics to genetics
and physiology,” Institute of Science and Technology Austria, 2020.'
ista: 'Kavcic B. 2020. Perturbations of protein synthesis: from antibiotics to genetics
and physiology. Institute of Science and Technology Austria.'
mla: 'Kavcic, Bor. Perturbations of Protein Synthesis: From Antibiotics to Genetics
and Physiology. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8657.'
short: 'B. Kavcic, Perturbations of Protein Synthesis: From Antibiotics to Genetics
and Physiology, Institute of Science and Technology Austria, 2020.'
date_created: 2020-10-13T16:46:14Z
date_published: 2020-10-14T00:00:00Z
date_updated: 2023-09-07T13:20:48Z
day: '14'
ddc:
- '571'
- '530'
- '570'
degree_awarded: PhD
department:
- _id: GaTk
doi: 10.15479/AT:ISTA:8657
file:
- access_level: open_access
checksum: d708ecd62b6fcc3bc1feb483b8dbe9eb
content_type: application/pdf
creator: bkavcic
date_created: 2020-10-15T06:41:20Z
date_updated: 2021-10-07T22:30:03Z
embargo: 2021-10-06
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file_name: kavcicB_thesis202009.pdf
file_size: 52636162
relation: main_file
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checksum: bb35f2352a04db19164da609f00501f3
content_type: application/zip
creator: bkavcic
date_created: 2020-10-15T06:41:53Z
date_updated: 2021-10-07T22:30:03Z
embargo_to: open_access
file_id: '8664'
file_name: 2020b.zip
file_size: 321681247
relation: source_file
file_date_updated: 2021-10-07T22:30:03Z
has_accepted_license: '1'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: '271'
publication_identifier:
isbn:
- 978-3-99078-011-4
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '7673'
relation: part_of_dissertation
status: public
- id: '8250'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
- first_name: Mark Tobias
full_name: Bollenbach, Mark Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
title: 'Perturbations of protein synthesis: from antibiotics to genetics and physiology'
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2020'
...
---
_id: '7473'
abstract:
- lang: eng
text: How structural and functional properties of synapses relate to each other
is a fundamental question in neuroscience. Electrophysiology has elucidated mechanisms
of synaptic transmission, and electron microscopy (EM) has provided insight into
morphological properties of synapses. Here we describe an enhanced method for
functional EM (“flash and freeze”), combining optogenetic stimulation with high-pressure
freezing. We demonstrate that the improved method can be applied to intact networks
in acute brain slices and organotypic slice cultures from mice. As a proof of
concept, we probed vesicle pool changes during synaptic transmission at the hippocampal
mossy fiber-CA3 pyramidal neuron synapse. Our findings show overlap of the docked
vesicle pool and the functionally defined readily releasable pool and provide
evidence of fast endocytosis at this synapse. Functional EM with acute slices
and slice cultures has the potential to reveal the structural and functional mechanisms
of transmission in intact, genetically perturbed, and disease-affected synapses.
acknowledgement: This project has received funding from the European Research Council
(ERC) and European Commission (EC), under the European Union’s Horizon 2020 research
and innovation programme (ERC grant agreement No. 692692 and Marie Sklodowska-Curie
708497) and from Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27
Wittgenstein award and DK W1205-B09). We thank Johann Danzl and Ryuichi Shigemoto
for critically reading the manuscript; Walter Kaufmann, Daniel Gutl, and Vanessa
Zheden for extensive EM training, advice, and experimental assistance; Benjamin
Suter for substantial help with light stimulation, ImageJ plugins for analysis,
and manuscript editing; Florian Marr and Christina Altmutter for technical support;
Eleftheria Kralli-Beller for manuscript editing; Julia König and Paul Wurzinger
(Leica Microsystems) for helpful technical discussions; and Taija Makinen for providing
the Prox1-CreERT2 mouse line.
article_processing_charge: No
article_type: original
author:
- first_name: Carolina
full_name: Borges Merjane, Carolina
id: 4305C450-F248-11E8-B48F-1D18A9856A87
last_name: Borges Merjane
orcid: 0000-0003-0005-401X
- first_name: Olena
full_name: Kim, Olena
id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87
last_name: Kim
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Borges Merjane C, Kim O, Jonas PM. Functional electron microscopy (“Flash and
Freeze”) of identified cortical synapses in acute brain slices. Neuron.
2020;105:992-1006. doi:10.1016/j.neuron.2019.12.022
apa: Borges Merjane, C., Kim, O., & Jonas, P. M. (2020). Functional electron
microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain
slices. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2019.12.022
chicago: Borges Merjane, Carolina, Olena Kim, and Peter M Jonas. “Functional Electron
Microscopy (‘Flash and Freeze’) of Identified Cortical Synapses in Acute Brain
Slices.” Neuron. Elsevier, 2020. https://doi.org/10.1016/j.neuron.2019.12.022.
ieee: C. Borges Merjane, O. Kim, and P. M. Jonas, “Functional electron microscopy
(‘Flash and Freeze’) of identified cortical synapses in acute brain slices,” Neuron,
vol. 105. Elsevier, pp. 992–1006, 2020.
ista: Borges Merjane C, Kim O, Jonas PM. 2020. Functional electron microscopy (“Flash
and Freeze”) of identified cortical synapses in acute brain slices. Neuron. 105,
992–1006.
mla: Borges Merjane, Carolina, et al. “Functional Electron Microscopy (‘Flash and
Freeze’) of Identified Cortical Synapses in Acute Brain Slices.” Neuron,
vol. 105, Elsevier, 2020, pp. 992–1006, doi:10.1016/j.neuron.2019.12.022.
short: C. Borges Merjane, O. Kim, P.M. Jonas, Neuron 105 (2020) 992–1006.
date_created: 2020-02-10T15:59:45Z
date_published: 2020-03-18T00:00:00Z
date_updated: 2024-03-28T23:30:07Z
day: '18'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1016/j.neuron.2019.12.022
ec_funded: 1
external_id:
isi:
- '000520854700008'
pmid:
- '31928842'
file:
- access_level: open_access
checksum: 3582664addf26859e86ac5bec3e01416
content_type: application/pdf
creator: dernst
date_created: 2020-11-20T08:58:53Z
date_updated: 2020-11-20T08:58:53Z
file_id: '8778'
file_name: 2020_Neuron_BorgesMerjane.pdf
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month: '03'
oa: 1
oa_version: Published Version
page: 992-1006
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 25BAF7B2-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '708497'
name: Presynaptic calcium channels distribution and impact on coupling at the hippocampal
mossy fiber synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
- _id: 25C3DBB6-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W01205
name: Zellkommunikation in Gesundheit und Krankheit
publication: Neuron
publication_identifier:
issn:
- 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/flash-and-freeze-reveals-dynamics-of-nerve-connections/
record:
- id: '11196'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Functional electron microscopy (“Flash and Freeze”) of identified cortical
synapses in acute brain slices
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: 105
year: '2020'
...
---
_id: '8250'
abstract:
- lang: eng
text: 'Antibiotics that interfere with translation, when combined, interact in diverse
and difficult-to-predict ways. Here, we explain these interactions by “translation
bottlenecks”: points in the translation cycle where antibiotics block ribosomal
progression. To elucidate the underlying mechanisms of drug interactions between
translation inhibitors, we generate translation bottlenecks genetically using
inducible control of translation factors that regulate well-defined translation
cycle steps. These perturbations accurately mimic antibiotic action and drug interactions,
supporting that the interplay of different translation bottlenecks causes these
interactions. We further show that growth laws, combined with drug uptake and
binding kinetics, enable the direct prediction of a large fraction of observed
interactions, yet fail to predict suppression. However, varying two translation
bottlenecks simultaneously supports that dense traffic of ribosomes and competition
for translation factors account for the previously unexplained suppression. These
results highlight the importance of “continuous epistasis” in bacterial physiology.'
acknowledgement: "We thank M. Hennessey-Wesen, I. Tomanek, K. Jain, A. Staron, K.
Tomasek, M. Scott,\r\nK.C. Huang, and Z. Gitai for reading the manuscript and constructive
comments. B.K. is\r\nindebted to C. Guet for additional guidance and generous support,
which rendered this\r\nwork possible. B.K. thanks all members of Guet group for
many helpful discussions and\r\nsharing of resources. B.K. additionally acknowledges
the tremendous support from A.\r\nAngermayr and K. Mitosch with experimental work.
We further thank E. Brown for\r\nhelpful comments regarding lamotrigine, and A.
Buskirk for valuable suggestions\r\nregarding the ribosome footprint size. This
work was supported in part by Austrian\r\nScience Fund (FWF) standalone grants P
27201-B22 (to T.B.) and P 28844 (to G.T.),\r\nHFSP program Grant RGP0042/2013 (to
T.B.), German Research Foundation (DFG)\r\nstandalone grant BO 3502/2-1 (to T.B.),
and German Research Foundation (DFG)\r\nCollaborative Research Centre (SFB) 1310
(to T.B.). Open access funding provided by\r\nProjekt DEAL."
article_number: '4013'
article_processing_charge: No
article_type: original
author:
- first_name: Bor
full_name: Kavcic, Bor
id: 350F91D2-F248-11E8-B48F-1D18A9856A87
last_name: Kavcic
orcid: 0000-0001-6041-254X
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
- first_name: Tobias
full_name: Bollenbach, Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
citation:
ama: Kavcic B, Tkačik G, Bollenbach MT. Mechanisms of drug interactions between
translation-inhibiting antibiotics. Nature Communications. 2020;11. doi:10.1038/s41467-020-17734-z
apa: Kavcic, B., Tkačik, G., & Bollenbach, M. T. (2020). Mechanisms of drug
interactions between translation-inhibiting antibiotics. Nature Communications.
Springer Nature. https://doi.org/10.1038/s41467-020-17734-z
chicago: Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “Mechanisms of
Drug Interactions between Translation-Inhibiting Antibiotics.” Nature Communications.
Springer Nature, 2020. https://doi.org/10.1038/s41467-020-17734-z.
ieee: B. Kavcic, G. Tkačik, and M. T. Bollenbach, “Mechanisms of drug interactions
between translation-inhibiting antibiotics,” Nature Communications, vol.
11. Springer Nature, 2020.
ista: Kavcic B, Tkačik G, Bollenbach MT. 2020. Mechanisms of drug interactions between
translation-inhibiting antibiotics. Nature Communications. 11, 4013.
mla: Kavcic, Bor, et al. “Mechanisms of Drug Interactions between Translation-Inhibiting
Antibiotics.” Nature Communications, vol. 11, 4013, Springer Nature, 2020,
doi:10.1038/s41467-020-17734-z.
short: B. Kavcic, G. Tkačik, M.T. Bollenbach, Nature Communications 11 (2020).
date_created: 2020-08-12T09:13:50Z
date_published: 2020-08-11T00:00:00Z
date_updated: 2024-03-28T23:30:08Z
day: '11'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1038/s41467-020-17734-z
external_id:
isi:
- '000562769300008'
file:
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checksum: 986bebb308850a55850028d3d2b5b664
content_type: application/pdf
creator: dernst
date_created: 2020-08-17T07:36:57Z
date_updated: 2020-08-17T07:36:57Z
file_id: '8275'
file_name: 2020_NatureComm_Kavcic.pdf
file_size: 1965672
relation: main_file
success: 1
file_date_updated: 2020-08-17T07:36:57Z
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
project:
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P27201-B22
name: Revealing the mechanisms underlying drug interactions
- _id: 254E9036-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P28844-B27
name: Biophysics of information processing in gene regulation
publication: Nature Communications
publication_identifier:
issn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
record:
- id: '8657'
relation: dissertation_contains
status: public
status: public
title: Mechanisms of drug interactions between translation-inhibiting antibiotics
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: 11
year: '2020'
...
---
_id: '7673'
abstract:
- lang: eng
text: Combining drugs can improve the efficacy of treatments. However, predicting
the effect of drug combinations is still challenging. The combined potency of
drugs determines the drug interaction, which is classified as synergistic, additive,
antagonistic, or suppressive. While probabilistic, non-mechanistic models exist,
there is currently no biophysical model that can predict antibiotic interactions.
Here, we present a physiologically relevant model of the combined action of antibiotics
that inhibit protein synthesis by targeting the ribosome. This model captures
the kinetics of antibiotic binding and transport, and uses bacterial growth laws
to predict growth in the presence of antibiotic combinations. We find that this
biophysical model can produce all drug interaction types except suppression. We
show analytically that antibiotics which cannot bind to the ribosome simultaneously
generally act as substitutes for one another, leading to additive drug interactions.
Previously proposed null expectations for higher-order drug interactions follow
as a limiting case of our model. We further extend the model to include the effects
of direct physical or allosteric interactions between individual drugs on the
ribosome. Notably, such direct interactions profoundly change the combined drug
effect, depending on the kinetic parameters of the drugs used. The model makes
additional predictions for the effects of resistance genes on drug interactions
and for interactions between ribosome-targeting antibiotics and antibiotics with
other targets. These findings enhance our understanding of the interplay between
drug action and cell physiology and are a key step toward a general framework
for predicting drug interactions.
article_processing_charge: No
author:
- first_name: Bor
full_name: Kavcic, Bor
id: 350F91D2-F248-11E8-B48F-1D18A9856A87
last_name: Kavcic
orcid: 0000-0001-6041-254X
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
- first_name: Tobias
full_name: Bollenbach, Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
citation:
ama: Kavcic B, Tkačik G, Bollenbach MT. A minimal biophysical model of combined
antibiotic action. bioRxiv. 2020. doi:10.1101/2020.04.18.047886
apa: Kavcic, B., Tkačik, G., & Bollenbach, M. T. (2020). A minimal biophysical
model of combined antibiotic action. bioRxiv. Cold Spring Harbor Laboratory.
https://doi.org/10.1101/2020.04.18.047886
chicago: Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “A Minimal Biophysical
Model of Combined Antibiotic Action.” BioRxiv. Cold Spring Harbor Laboratory,
2020. https://doi.org/10.1101/2020.04.18.047886.
ieee: B. Kavcic, G. Tkačik, and M. T. Bollenbach, “A minimal biophysical model of
combined antibiotic action,” bioRxiv. Cold Spring Harbor Laboratory, 2020.
ista: Kavcic B, Tkačik G, Bollenbach MT. 2020. A minimal biophysical model of combined
antibiotic action. bioRxiv, 10.1101/2020.04.18.047886.
mla: Kavcic, Bor, et al. “A Minimal Biophysical Model of Combined Antibiotic Action.”
BioRxiv, Cold Spring Harbor Laboratory, 2020, doi:10.1101/2020.04.18.047886.
short: B. Kavcic, G. Tkačik, M.T. Bollenbach, BioRxiv (2020).
date_created: 2020-04-22T08:27:56Z
date_published: 2020-04-18T00:00:00Z
date_updated: 2024-03-28T23:30:08Z
day: '18'
department:
- _id: GaTk
doi: 10.1101/2020.04.18.047886
language:
- iso: eng
main_file_link:
- open_access: '1'
url: 'https://doi.org/10.1101/2020.04.18.047886 '
month: '04'
oa: 1
oa_version: Preprint
project:
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P27201-B22
name: Revealing the mechanisms underlying drug interactions
- _id: 254E9036-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P28844-B27
name: Biophysics of information processing in gene regulation
publication: bioRxiv
publication_status: published
publisher: Cold Spring Harbor Laboratory
related_material:
record:
- id: '8997'
relation: later_version
status: public
- id: '8657'
relation: dissertation_contains
status: public
status: public
title: A minimal biophysical model of combined antibiotic action
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...