---
_id: '1137'
abstract:
- lang: eng
text: RASGRP1 is an important guanine nucleotide exchange factor and activator of
the RAS-MAPK pathway following T cell antigen receptor (TCR) signaling. The consequences
of RASGRP1 mutations in humans are unknown. In a patient with recurrent bacterial
and viral infections, born to healthy consanguineous parents, we used homozygosity
mapping and exome sequencing to identify a biallelic stop-gain variant in RASGRP1.
This variant segregated perfectly with the disease and has not been reported in
genetic databases. RASGRP1 deficiency was associated in T cells and B cells with
decreased phosphorylation of the extracellular-signal-regulated serine kinase
ERK, which was restored following expression of wild-type RASGRP1. RASGRP1 deficiency
also resulted in defective proliferation, activation and motility of T cells and
B cells. RASGRP1-deficient natural killer (NK) cells exhibited impaired cytotoxicity
with defective granule convergence and actin accumulation. Interaction proteomics
identified the dynein light chain DYNLL1 as interacting with RASGRP1, which links
RASGRP1 to cytoskeletal dynamics. RASGRP1-deficient cells showed decreased activation
of the GTPase RhoA. Treatment with lenalidomide increased RhoA activity and reversed
the migration and activation defects of RASGRP1-deficient lymphocytes.
article_processing_charge: No
article_type: original
author:
- first_name: Elisabeth
full_name: Salzer, Elisabeth
last_name: Salzer
- first_name: Deniz
full_name: Çaǧdaş, Deniz
last_name: Çaǧdaş
- first_name: Miroslav
full_name: Hons, Miroslav
id: 4167FE56-F248-11E8-B48F-1D18A9856A87
last_name: Hons
orcid: 0000-0002-6625-3348
- first_name: Emily
full_name: Mace, Emily
last_name: Mace
- first_name: Wojciech
full_name: Garncarz, Wojciech
last_name: Garncarz
- first_name: Oezlem
full_name: Petronczki, Oezlem
last_name: Petronczki
- first_name: René
full_name: Platzer, René
last_name: Platzer
- first_name: Laurène
full_name: Pfajfer, Laurène
last_name: Pfajfer
- first_name: Ivan
full_name: Bilic, Ivan
last_name: Bilic
- first_name: Sol
full_name: Ban, Sol
last_name: Ban
- first_name: Katharina
full_name: Willmann, Katharina
last_name: Willmann
- first_name: Malini
full_name: Mukherjee, Malini
last_name: Mukherjee
- first_name: Verena
full_name: Supper, Verena
last_name: Supper
- first_name: Hsiangting
full_name: Hsu, Hsiangting
last_name: Hsu
- first_name: Pinaki
full_name: Banerjee, Pinaki
last_name: Banerjee
- first_name: Papiya
full_name: Sinha, Papiya
last_name: Sinha
- first_name: Fabienne
full_name: Mcclanahan, Fabienne
last_name: Mcclanahan
- first_name: Gerhard
full_name: Zlabinger, Gerhard
last_name: Zlabinger
- first_name: Winfried
full_name: Pickl, Winfried
last_name: Pickl
- first_name: John
full_name: Gribben, John
last_name: Gribben
- first_name: Hannes
full_name: Stockinger, Hannes
last_name: Stockinger
- first_name: Keiryn
full_name: Bennett, Keiryn
last_name: Bennett
- first_name: Johannes
full_name: Huppa, Johannes
last_name: Huppa
- first_name: Loï̈C
full_name: Dupré, Loï̈C
last_name: Dupré
- first_name: Özden
full_name: Sanal, Özden
last_name: Sanal
- first_name: Ulrich
full_name: Jäger, Ulrich
last_name: Jäger
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
- first_name: Ilhan
full_name: Tezcan, Ilhan
last_name: Tezcan
- first_name: Jordan
full_name: Orange, Jordan
last_name: Orange
- first_name: Kaan
full_name: Boztug, Kaan
last_name: Boztug
citation:
ama: Salzer E, Çaǧdaş D, Hons M, et al. RASGRP1 deficiency causes immunodeficiency
with impaired cytoskeletal dynamics. Nature Immunology. 2016;17(12):1352-1360.
doi:10.1038/ni.3575
apa: Salzer, E., Çaǧdaş, D., Hons, M., Mace, E., Garncarz, W., Petronczki, O., …
Boztug, K. (2016). RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal
dynamics. Nature Immunology. Nature Publishing Group. https://doi.org/10.1038/ni.3575
chicago: Salzer, Elisabeth, Deniz Çaǧdaş, Miroslav Hons, Emily Mace, Wojciech Garncarz,
Oezlem Petronczki, René Platzer, et al. “RASGRP1 Deficiency Causes Immunodeficiency
with Impaired Cytoskeletal Dynamics.” Nature Immunology. Nature Publishing
Group, 2016. https://doi.org/10.1038/ni.3575.
ieee: E. Salzer et al., “RASGRP1 deficiency causes immunodeficiency with
impaired cytoskeletal dynamics,” Nature Immunology, vol. 17, no. 12. Nature
Publishing Group, pp. 1352–1360, 2016.
ista: Salzer E, Çaǧdaş D, Hons M, Mace E, Garncarz W, Petronczki O, Platzer R, Pfajfer
L, Bilic I, Ban S, Willmann K, Mukherjee M, Supper V, Hsu H, Banerjee P, Sinha
P, Mcclanahan F, Zlabinger G, Pickl W, Gribben J, Stockinger H, Bennett K, Huppa
J, Dupré L, Sanal Ö, Jäger U, Sixt MK, Tezcan I, Orange J, Boztug K. 2016. RASGRP1
deficiency causes immunodeficiency with impaired cytoskeletal dynamics. Nature
Immunology. 17(12), 1352–1360.
mla: Salzer, Elisabeth, et al. “RASGRP1 Deficiency Causes Immunodeficiency with
Impaired Cytoskeletal Dynamics.” Nature Immunology, vol. 17, no. 12, Nature
Publishing Group, 2016, pp. 1352–60, doi:10.1038/ni.3575.
short: E. Salzer, D. Çaǧdaş, M. Hons, E. Mace, W. Garncarz, O. Petronczki, R. Platzer,
L. Pfajfer, I. Bilic, S. Ban, K. Willmann, M. Mukherjee, V. Supper, H. Hsu, P.
Banerjee, P. Sinha, F. Mcclanahan, G. Zlabinger, W. Pickl, J. Gribben, H. Stockinger,
K. Bennett, J. Huppa, L. Dupré, Ö. Sanal, U. Jäger, M.K. Sixt, I. Tezcan, J. Orange,
K. Boztug, Nature Immunology 17 (2016) 1352–1360.
date_created: 2018-12-11T11:50:21Z
date_published: 2016-12-01T00:00:00Z
date_updated: 2025-09-22T14:13:22Z
day: '01'
department:
- _id: MiSi
doi: 10.1038/ni.3575
external_id:
isi:
- '000388056400005'
pmid:
- '27776107'
intvolume: ' 17'
isi: 1
issue: '12'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400263
month: '12'
oa: 1
oa_version: Submitted Version
page: 1352 - 1360
pmid: 1
publication: Nature Immunology
publication_status: published
publisher: Nature Publishing Group
publist_id: '6221'
quality_controlled: '1'
scopus_import: '1'
status: public
title: RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal dynamics
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 17
year: '2016'
...
---
_id: '1138'
abstract:
- lang: eng
text: Automata with monitor counters, where the transitions do not depend on counter
values, and nested weighted automata are two expressive automata-theoretic frameworks
for quantitative properties. For a well-studied and wide class of quantitative
functions, we establish that automata with monitor counters and nested weighted
automata are equivalent. We study for the first time such quantitative automata
under probabilistic semantics. We show that several problems that are undecidable
for the classical questions of emptiness and universality become decidable under
the probabilistic semantics. We present a complete picture of decidability for
such automata, and even an almost-complete picture of computational complexity,
for the probabilistic questions we consider. © 2016 ACM.
acknowledgement: This research was funded in part by the European Research Council
(ERC) under grant agreement 267989 (QUAREM), by the Austrian Science Fund (FWF)
projects S11402-N23 (RiSE) and Z211-N23 (Wittgenstein Award), FWF Grant No P23499-
N23, FWF NFN Grant No S114
article_processing_charge: No
arxiv: 1
author:
- first_name: Krishnendu
full_name: Chatterjee, Krishnendu
id: 2E5DCA20-F248-11E8-B48F-1D18A9856A87
last_name: Chatterjee
orcid: 0000-0002-4561-241X
- first_name: Thomas A
full_name: Henzinger, Thomas A
id: 40876CD8-F248-11E8-B48F-1D18A9856A87
last_name: Henzinger
orcid: 0000−0002−2985−7724
- first_name: Jan
full_name: Otop, Jan
id: 2FC5DA74-F248-11E8-B48F-1D18A9856A87
last_name: Otop
citation:
ama: 'Chatterjee K, Henzinger TA, Otop J. Quantitative automata under probabilistic
semantics. In: Proceedings of the 31st Annual ACM/IEEE Symposium. IEEE;
2016:76-85. doi:10.1145/2933575.2933588'
apa: 'Chatterjee, K., Henzinger, T. A., & Otop, J. (2016). Quantitative automata
under probabilistic semantics. In Proceedings of the 31st Annual ACM/IEEE Symposium
(pp. 76–85). New York, NY, USA: IEEE. https://doi.org/10.1145/2933575.2933588'
chicago: Chatterjee, Krishnendu, Thomas A Henzinger, and Jan Otop. “Quantitative
Automata under Probabilistic Semantics.” In Proceedings of the 31st Annual
ACM/IEEE Symposium, 76–85. IEEE, 2016. https://doi.org/10.1145/2933575.2933588.
ieee: K. Chatterjee, T. A. Henzinger, and J. Otop, “Quantitative automata under
probabilistic semantics,” in Proceedings of the 31st Annual ACM/IEEE Symposium,
New York, NY, USA, 2016, pp. 76–85.
ista: 'Chatterjee K, Henzinger TA, Otop J. 2016. Quantitative automata under probabilistic
semantics. Proceedings of the 31st Annual ACM/IEEE Symposium. LICS: Logic in Computer
Science, 76–85.'
mla: Chatterjee, Krishnendu, et al. “Quantitative Automata under Probabilistic Semantics.”
Proceedings of the 31st Annual ACM/IEEE Symposium, IEEE, 2016, pp. 76–85,
doi:10.1145/2933575.2933588.
short: K. Chatterjee, T.A. Henzinger, J. Otop, in:, Proceedings of the 31st Annual
ACM/IEEE Symposium, IEEE, 2016, pp. 76–85.
conference:
end_date: 2016-07-08
location: New York, NY, USA
name: 'LICS: Logic in Computer Science'
start_date: 2016-07-05
date_created: 2018-12-11T11:50:21Z
date_published: 2016-07-05T00:00:00Z
date_updated: 2025-09-22T14:12:47Z
day: '05'
department:
- _id: KrCh
- _id: ToHe
doi: 10.1145/2933575.2933588
ec_funded: 1
external_id:
arxiv:
- '1604.06764'
isi:
- '000387609200008'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://arxiv.org/abs/1604.06764
month: '07'
oa: 1
oa_version: Preprint
page: 76 - 85
project:
- _id: 25EE3708-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '267989'
name: Quantitative Reactive Modeling
- _id: 25832EC2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: S 11407_N23
name: Rigorous Systems Engineering
- _id: 25F42A32-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z211
name: Formal methods for the design and analysis of complex systems
- _id: 2584A770-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P 23499-N23
name: Modern Graph Algorithmic Techniques in Formal Verification
- _id: 2581B60A-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '279307'
name: 'Quantitative Graph Games: Theory and Applications'
- _id: 25892FC0-B435-11E9-9278-68D0E5697425
grant_number: ICT15-003
name: Efficient Algorithms for Computer Aided Verification
publication: Proceedings of the 31st Annual ACM/IEEE Symposium
publication_status: published
publisher: IEEE
publist_id: '6220'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Quantitative automata under probabilistic semantics
type: conference
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
year: '2016'
...
---
_id: '1140'
abstract:
- lang: eng
text: 'Given a model of a system and an objective, the model-checking question asks
whether the model satisfies the objective. We study polynomial-time problems in
two classical models, graphs and Markov Decision Processes (MDPs), with respect
to several fundamental -regular objectives, e.g., Rabin and Streett objectives.
For many of these problems the best-known upper bounds are quadratic or cubic,
yet no super-linear lower bounds are known. In this work our contributions are
two-fold: First, we present several improved algorithms, and second, we present
the first conditional super-linear lower bounds based on widely believed assumptions
about the complexity of CNF-SAT and combinatorial Boolean matrix multiplication.
A separation result for two models with respect to an objective means a conditional
lower bound for one model that is strictly higher than the existing upper bound
for the other model, and similarly for two objectives with respect to a model.
Our results establish the following separation results: (1) A separation of models
(graphs and MDPs) for disjunctive queries of reachability and Büchi objectives.
(2) Two kinds of separations of objectives, both for graphs and MDPs, namely,
(2a) the separation of dual objectives such as Streett/Rabin objectives, and (2b)
the separation of conjunction and disjunction of multiple objectives of the same
type such as safety, Büchi, and coBüchi. In summary, our results establish the
first model and objective separation results for graphs and MDPs for various classical
-regular objectives. Quite strikingly, we establish conditional lower bounds for
the disjunction of objectives that are strictly higher than the existing upper
bounds for the conjunction of the same objectives. © 2016 ACM.'
acknowledgement: "K. C., M. H., and W. D. are partially supported by the
\ Vienna\r\nScience and Technology Fund (WWTF) through project ICT15-003.\r\nK.
C. is partially supported by the Austrian Science Fund (FWF)\r\nNFN Grant No S11407-N23
(RiSE/SHiNE) and an ERC Start grant\r\n(279307: Graph Games). For W. D., M. H.,
and V. L. the research\r\nleading to these results has received funding from the
European\r\nResearch Council under the European Union’s Seventh Framework\r\nProgramme
(FP/2007-2013) / ERC Grant Agreement no. 340506."
alternative_title:
- Proceedings Symposium on Logic in Computer Science
article_processing_charge: No
arxiv: 1
author:
- first_name: Krishnendu
full_name: Chatterjee, Krishnendu
id: 2E5DCA20-F248-11E8-B48F-1D18A9856A87
last_name: Chatterjee
orcid: 0000-0002-4561-241X
- first_name: Wolfgang
full_name: Dvoák, Wolfgang
last_name: Dvoák
- first_name: Monika H
full_name: Henzinger, Monika H
id: 540c9bbd-f2de-11ec-812d-d04a5be85630
last_name: Henzinger
orcid: 0000-0002-5008-6530
- first_name: Veronika
full_name: Loitzenbauer, Veronika
last_name: Loitzenbauer
citation:
ama: 'Chatterjee K, Dvoák W, Henzinger M, Loitzenbauer V. Model and objective separation
with conditional lower bounds: disjunction is harder than conjunction. In: Proceedings
of the 31st Annual ACM/IEEE Symposium on Logic in Computer Science. IEEE;
2016:197-206. doi:10.1145/2933575.2935304'
apa: 'Chatterjee, K., Dvoák, W., Henzinger, M., & Loitzenbauer, V. (2016). Model
and objective separation with conditional lower bounds: disjunction is harder
than conjunction. In Proceedings of the 31st Annual ACM/IEEE Symposium on Logic
in Computer Science (pp. 197–206). New York, NY, USA: IEEE. https://doi.org/10.1145/2933575.2935304'
chicago: 'Chatterjee, Krishnendu, Wolfgang Dvoák, Monika Henzinger, and Veronika
Loitzenbauer. “Model and Objective Separation with Conditional Lower Bounds: Disjunction
Is Harder than Conjunction.” In Proceedings of the 31st Annual ACM/IEEE Symposium
on Logic in Computer Science, 197–206. IEEE, 2016. https://doi.org/10.1145/2933575.2935304.'
ieee: 'K. Chatterjee, W. Dvoák, M. Henzinger, and V. Loitzenbauer, “Model and objective
separation with conditional lower bounds: disjunction is harder than conjunction,”
in Proceedings of the 31st Annual ACM/IEEE Symposium on Logic in Computer Science,
New York, NY, USA, 2016, pp. 197–206.'
ista: 'Chatterjee K, Dvoák W, Henzinger M, Loitzenbauer V. 2016. Model and objective
separation with conditional lower bounds: disjunction is harder than conjunction.
Proceedings of the 31st Annual ACM/IEEE Symposium on Logic in Computer Science.
LICS: Logic in Computer Science, Proceedings Symposium on Logic in Computer Science,
, 197–206.'
mla: 'Chatterjee, Krishnendu, et al. “Model and Objective Separation with Conditional
Lower Bounds: Disjunction Is Harder than Conjunction.” Proceedings of the 31st
Annual ACM/IEEE Symposium on Logic in Computer Science, IEEE, 2016, pp. 197–206,
doi:10.1145/2933575.2935304.'
short: K. Chatterjee, W. Dvoák, M. Henzinger, V. Loitzenbauer, in:, Proceedings
of the 31st Annual ACM/IEEE Symposium on Logic in Computer Science, IEEE, 2016,
pp. 197–206.
conference:
end_date: 2016-07-08
location: New York, NY, USA
name: 'LICS: Logic in Computer Science'
start_date: 2016-07-05
date_created: 2018-12-11T11:50:22Z
date_published: 2016-07-05T00:00:00Z
date_updated: 2025-09-22T14:12:05Z
day: '05'
department:
- _id: KrCh
doi: 10.1145/2933575.2935304
external_id:
arxiv:
- '1602.02670'
isi:
- '000387609200020'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://arxiv.org/abs/1602.02670
month: '07'
oa: 1
oa_version: Preprint
page: 197 - 206
project:
- _id: 25832EC2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: S 11407_N23
name: Rigorous Systems Engineering
- _id: 25892FC0-B435-11E9-9278-68D0E5697425
grant_number: ICT15-003
name: Efficient Algorithms for Computer Aided Verification
publication: Proceedings of the 31st Annual ACM/IEEE Symposium on Logic in Computer
Science
publication_status: published
publisher: IEEE
publist_id: '6219'
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Model and objective separation with conditional lower bounds: disjunction
is harder than conjunction'
type: conference
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
year: '2016'
...
---
_id: '1142'
abstract:
- lang: eng
text: Hemolysis drives susceptibility to bacterial infections and predicts poor
outcome from sepsis. These detrimental effects are commonly considered to be a
consequence of heme-iron serving as a nutrient for bacteria. We employed a Gram-negative
sepsis model and found that elevated heme levels impaired the control of bacterial
proliferation independently of heme-iron acquisition by pathogens. Heme strongly
inhibited phagocytosis and the migration of human and mouse phagocytes by disrupting
actin cytoskeletal dynamics via activation of the GTP-binding Rho family protein
Cdc42 by the guanine nucleotide exchange factor DOCK8. A chemical screening approach
revealed that quinine effectively prevented heme effects on the cytoskeleton,
restored phagocytosis and improved survival in sepsis. These mechanistic insights
provide potential therapeutic targets for patients with sepsis or hemolytic disorders.
acknowledgement: 'Y. Fukui (Medical Institute of Bioregulation, Kyushu University)
and J. Stein (Theodor Kocher Institute, University of Bern) are acknowledged for
providing the DOCK8 deficient bone marrow. and H. Häcker (St. Judes Children''s
Research Hospital) for providing the ERHBD-HoxB8-encoding retroviral construct.
pSpCas9(BB)-2a-Puro (PX459) was a gift from F. Zhang (Massachusetts Institute of
Technology) (Addgene plasmid # 48139) and pGRG36 was a gift from N. Craig (Johns
Hopkins University School of Medicine) (Addgene plasmid # 16666). LifeAct-GFP-encoding
retrovirus was kindly provided by A. Leithner (Institute of Science and Technology
Austria). pSIM8 and TKC E. coli were gifts from D.L. Court (Center for Cancer Research,
National Cancer Institute). We acknowledge M. Gröger and S. Rauscher for excellent
technical support (Core imaging facility, Medical University of Vienna). We thank
D.P. Barlow and L.R. Cheever for critical reading of the manuscript. This work was
supported by the Austrian Academy of Sciences, the Science Fund of the Austrian
National Bank (14107) and the Austrian Science Fund FWF (I1620-B22) in the Infect-ERA
framework (to S.Knapp).'
article_processing_charge: No
author:
- first_name: Rui
full_name: Martins, Rui
last_name: Martins
- first_name: Julia
full_name: Maier, Julia
last_name: Maier
- first_name: Anna
full_name: Gorki, Anna
last_name: Gorki
- first_name: Kilian
full_name: Huber, Kilian
last_name: Huber
- first_name: Omar
full_name: Sharif, Omar
last_name: Sharif
- first_name: Philipp
full_name: Starkl, Philipp
last_name: Starkl
- first_name: Simona
full_name: Saluzzo, Simona
last_name: Saluzzo
- first_name: Federica
full_name: Quattrone, Federica
last_name: Quattrone
- first_name: Riem
full_name: Gawish, Riem
last_name: Gawish
- first_name: Karin
full_name: Lakovits, Karin
last_name: Lakovits
- first_name: Michael
full_name: Aichinger, Michael
last_name: Aichinger
- first_name: Branka
full_name: Radic Sarikas, Branka
last_name: Radic Sarikas
- first_name: Charles
full_name: Lardeau, Charles
last_name: Lardeau
- first_name: Anastasiya
full_name: Hladik, Anastasiya
last_name: Hladik
- first_name: Ana
full_name: Korosec, Ana
last_name: Korosec
- first_name: Markus
full_name: Brown, Markus
id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87
last_name: Brown
- first_name: Kari
full_name: Vaahtomeri, Kari
id: 368EE576-F248-11E8-B48F-1D18A9856A87
last_name: Vaahtomeri
orcid: 0000-0001-7829-3518
- first_name: Michelle
full_name: Duggan, Michelle
id: 2EDEA62C-F248-11E8-B48F-1D18A9856A87
last_name: Duggan
- first_name: Dontscho
full_name: Kerjaschki, Dontscho
last_name: Kerjaschki
- first_name: Harald
full_name: Esterbauer, Harald
last_name: Esterbauer
- first_name: Jacques
full_name: Colinge, Jacques
last_name: Colinge
- first_name: Stephanie
full_name: Eisenbarth, Stephanie
last_name: Eisenbarth
- first_name: Thomas
full_name: Decker, Thomas
last_name: Decker
- first_name: Keiryn
full_name: Bennett, Keiryn
last_name: Bennett
- first_name: Stefan
full_name: Kubicek, Stefan
last_name: Kubicek
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
- first_name: Giulio
full_name: Superti Furga, Giulio
last_name: Superti Furga
- first_name: Sylvia
full_name: Knapp, Sylvia
last_name: Knapp
citation:
ama: Martins R, Maier J, Gorki A, et al. Heme drives hemolysis-induced susceptibility
to infection via disruption of phagocyte functions. Nature Immunology.
2016;17(12):1361-1372. doi:10.1038/ni.3590
apa: Martins, R., Maier, J., Gorki, A., Huber, K., Sharif, O., Starkl, P., … Knapp,
S. (2016). Heme drives hemolysis-induced susceptibility to infection via disruption
of phagocyte functions. Nature Immunology. Nature Publishing Group. https://doi.org/10.1038/ni.3590
chicago: Martins, Rui, Julia Maier, Anna Gorki, Kilian Huber, Omar Sharif, Philipp
Starkl, Simona Saluzzo, et al. “Heme Drives Hemolysis-Induced Susceptibility to
Infection via Disruption of Phagocyte Functions.” Nature Immunology. Nature
Publishing Group, 2016. https://doi.org/10.1038/ni.3590.
ieee: R. Martins et al., “Heme drives hemolysis-induced susceptibility to
infection via disruption of phagocyte functions,” Nature Immunology, vol.
17, no. 12. Nature Publishing Group, pp. 1361–1372, 2016.
ista: Martins R, Maier J, Gorki A, Huber K, Sharif O, Starkl P, Saluzzo S, Quattrone
F, Gawish R, Lakovits K, Aichinger M, Radic Sarikas B, Lardeau C, Hladik A, Korosec
A, Brown M, Vaahtomeri K, Duggan M, Kerjaschki D, Esterbauer H, Colinge J, Eisenbarth
S, Decker T, Bennett K, Kubicek S, Sixt MK, Superti Furga G, Knapp S. 2016. Heme
drives hemolysis-induced susceptibility to infection via disruption of phagocyte
functions. Nature Immunology. 17(12), 1361–1372.
mla: Martins, Rui, et al. “Heme Drives Hemolysis-Induced Susceptibility to Infection
via Disruption of Phagocyte Functions.” Nature Immunology, vol. 17, no.
12, Nature Publishing Group, 2016, pp. 1361–72, doi:10.1038/ni.3590.
short: R. Martins, J. Maier, A. Gorki, K. Huber, O. Sharif, P. Starkl, S. Saluzzo,
F. Quattrone, R. Gawish, K. Lakovits, M. Aichinger, B. Radic Sarikas, C. Lardeau,
A. Hladik, A. Korosec, M. Brown, K. Vaahtomeri, M. Duggan, D. Kerjaschki, H. Esterbauer,
J. Colinge, S. Eisenbarth, T. Decker, K. Bennett, S. Kubicek, M.K. Sixt, G. Superti
Furga, S. Knapp, Nature Immunology 17 (2016) 1361–1372.
date_created: 2018-12-11T11:50:22Z
date_published: 2016-12-01T00:00:00Z
date_updated: 2025-09-22T14:10:50Z
day: '01'
department:
- _id: MiSi
- _id: PeJo
doi: 10.1038/ni.3590
external_id:
isi:
- '000388056400006'
intvolume: ' 17'
isi: 1
issue: '12'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://ora.ox.ac.uk/objects/uuid:f53a464e-1e5b-4f08-a7d8-b6749b852b9d
month: '12'
oa: 1
oa_version: Submitted Version
page: 1361 - 1372
publication: Nature Immunology
publication_status: published
publisher: Nature Publishing Group
publist_id: '6216'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Heme drives hemolysis-induced susceptibility to infection via disruption of
phagocyte functions
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 17
year: '2016'
...
---
_id: '1143'
abstract:
- lang: eng
text: We study the ground state of a dilute Bose gas in a scaling limit where the
Gross-Pitaevskii functional emerges. This is a repulsive nonlinear Schrödinger
functional whose quartic term is proportional to the scattering length of the
interparticle interaction potential. We propose a new derivation of this limit
problem, with a method that bypasses some of the technical difficulties that previous
derivations had to face. The new method is based on a combination of Dyson\'s
lemma, the quantum de Finetti theorem and a second moment estimate for ground
states of the effective Dyson Hamiltonian. It applies equally well to the case
where magnetic fields or rotation are present.
article_processing_charge: No
arxiv: 1
author:
- first_name: Phan
full_name: Nam, Phan
id: 404092F4-F248-11E8-B48F-1D18A9856A87
last_name: Nam
- first_name: Nicolas
full_name: Rougerie, Nicolas
last_name: Rougerie
- first_name: Robert
full_name: Seiringer, Robert
id: 4AFD0470-F248-11E8-B48F-1D18A9856A87
last_name: Seiringer
orcid: 0000-0002-6781-0521
citation:
ama: 'Nam P, Rougerie N, Seiringer R. Ground states of large bosonic systems: The
gross Pitaevskii limit revisited. Analysis and PDE. 2016;9(2):459-485.
doi:10.2140/apde.2016.9.459'
apa: 'Nam, P., Rougerie, N., & Seiringer, R. (2016). Ground states of large
bosonic systems: The gross Pitaevskii limit revisited. Analysis and PDE.
Mathematical Sciences Publishers. https://doi.org/10.2140/apde.2016.9.459'
chicago: 'Nam, Phan, Nicolas Rougerie, and Robert Seiringer. “Ground States of Large
Bosonic Systems: The Gross Pitaevskii Limit Revisited.” Analysis and PDE.
Mathematical Sciences Publishers, 2016. https://doi.org/10.2140/apde.2016.9.459.'
ieee: 'P. Nam, N. Rougerie, and R. Seiringer, “Ground states of large bosonic systems:
The gross Pitaevskii limit revisited,” Analysis and PDE, vol. 9, no. 2.
Mathematical Sciences Publishers, pp. 459–485, 2016.'
ista: 'Nam P, Rougerie N, Seiringer R. 2016. Ground states of large bosonic systems:
The gross Pitaevskii limit revisited. Analysis and PDE. 9(2), 459–485.'
mla: 'Nam, Phan, et al. “Ground States of Large Bosonic Systems: The Gross Pitaevskii
Limit Revisited.” Analysis and PDE, vol. 9, no. 2, Mathematical Sciences
Publishers, 2016, pp. 459–85, doi:10.2140/apde.2016.9.459.'
short: P. Nam, N. Rougerie, R. Seiringer, Analysis and PDE 9 (2016) 459–485.
date_created: 2018-12-11T11:50:23Z
date_published: 2016-03-24T00:00:00Z
date_updated: 2025-09-22T14:10:16Z
day: '24'
department:
- _id: RoSe
doi: 10.2140/apde.2016.9.459
ec_funded: 1
external_id:
arxiv:
- '1503.07061'
isi:
- '000378287000006'
intvolume: ' 9'
isi: 1
issue: '2'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://arxiv.org/abs/1503.07061
month: '03'
oa: 1
oa_version: Preprint
page: 459 - 485
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
publication: Analysis and PDE
publication_status: published
publisher: Mathematical Sciences Publishers
publist_id: '6215'
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Ground states of large bosonic systems: The gross Pitaevskii limit revisited'
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 9
year: '2016'
...
---
_id: '100'
abstract:
- lang: eng
text: We introduce a scheme for preparation, manipulation, and read out of Majorana
zero modes in semiconducting wires with mesoscopic superconducting islands. Our
approach synthesizes recent advances in materials growth with tools commonly used
in quantum-dot experiments, including gate control of tunnel barriers and Coulomb
effects, charge sensing, and charge pumping. We outline a sequence of milestones
interpolating between zero-mode detection and quantum computing that includes
(1) detection of fusion rules for non-Abelian anyons using either proximal charge
sensors or pumped current, (2) validation of a prototype topological qubit, and
(3) demonstration of non-Abelian statistics by braiding in a branched geometry.
The first two milestones require only a single wire with two islands, and additionally
enable sensitive measurements of the system\'s excitation gap, quasiparticle poisoning
rates, residual Majorana zero-mode splittings, and topological-qubit coherence
times. These pre-braiding experiments can be adapted to other manipulation and
read out schemes as well.
acknowledgement: We acknowledge support from Microsoft Research, the National Science
Foundation through Grant No. DMR-1341822 (J. A.); the Alfred P. Sloan Foundation
(J. A.); the Caltech Institute for Quantum Information and Matter, an NSF Physics
Frontiers Center with support of the Gordon and Betty Moore Foundation through Grant
No. GBMF1250; the Walter Burke Institute for Theoretical Physics at Caltech; the
NSERC PGSD program (D. A.); the Crafoord Foundation (M. L. and M. H.) and the Swedish
Research Council (M. L.); The Danish National Research Foundation, and the Villum
Foundation (C. M.); The Danish Council for Independent Research/Natural Sciences,
and Danmarks Nationalbank (J. F.). Part of this work was performed at the Aspen
Center for Physics, which is supported by National Science Foundation Grant No.
PHY-1066293 (R. V. M.).
article_number: '031016'
author:
- first_name: David
full_name: Aasen, David
last_name: Aasen
- first_name: Michael
full_name: Hell, Michael
last_name: Hell
- first_name: Ryan
full_name: Mishmash, Ryan
last_name: Mishmash
- first_name: Andrew P
full_name: Higginbotham, Andrew P
id: 4AD6785A-F248-11E8-B48F-1D18A9856A87
last_name: Higginbotham
orcid: 0000-0003-2607-2363
- first_name: Jeroen
full_name: Danon, Jeroen
last_name: Danon
- first_name: Martin
full_name: Leijnse, Martin
last_name: Leijnse
- first_name: Thomas
full_name: Jespersen, Thomas
last_name: Jespersen
- first_name: Joshua
full_name: Folk, Joshua
last_name: Folk
- first_name: Charles
full_name: Marcs, Charles
last_name: Marcs
- first_name: Karsten
full_name: Flensberg, Karsten
last_name: Flensberg
- first_name: Jason
full_name: Alicea, Jason
last_name: Alicea
citation:
ama: Aasen D, Hell M, Mishmash R, et al. Milestones toward Majorana-based quantum
computing. Physical Review X. 2016;6(3). doi:10.1103/PhysRevX.6.031016
apa: Aasen, D., Hell, M., Mishmash, R., Higginbotham, A. P., Danon, J., Leijnse,
M., … Alicea, J. (2016). Milestones toward Majorana-based quantum computing. Physical
Review X. American Physical Society. https://doi.org/10.1103/PhysRevX.6.031016
chicago: Aasen, David, Michael Hell, Ryan Mishmash, Andrew P Higginbotham, Jeroen
Danon, Martin Leijnse, Thomas Jespersen, et al. “Milestones toward Majorana-Based
Quantum Computing.” Physical Review X. American Physical Society, 2016.
https://doi.org/10.1103/PhysRevX.6.031016.
ieee: D. Aasen et al., “Milestones toward Majorana-based quantum computing,”
Physical Review X, vol. 6, no. 3. American Physical Society, 2016.
ista: Aasen D, Hell M, Mishmash R, Higginbotham AP, Danon J, Leijnse M, Jespersen
T, Folk J, Marcs C, Flensberg K, Alicea J. 2016. Milestones toward Majorana-based
quantum computing. Physical Review X. 6(3), 031016.
mla: Aasen, David, et al. “Milestones toward Majorana-Based Quantum Computing.”
Physical Review X, vol. 6, no. 3, 031016, American Physical Society, 2016,
doi:10.1103/PhysRevX.6.031016.
short: D. Aasen, M. Hell, R. Mishmash, A.P. Higginbotham, J. Danon, M. Leijnse,
T. Jespersen, J. Folk, C. Marcs, K. Flensberg, J. Alicea, Physical Review X 6
(2016).
date_created: 2018-12-11T11:44:37Z
date_published: 2016-08-03T00:00:00Z
date_updated: 2021-01-12T06:47:33Z
day: '03'
ddc:
- '530'
doi: 10.1103/PhysRevX.6.031016
extern: '1'
file:
- access_level: open_access
content_type: application/pdf
creator: kschuh
date_created: 2019-05-15T14:12:31Z
date_updated: 2019-05-15T14:12:31Z
file_id: '6458'
file_name: 2016_PhysRevX_Aasen.pdf
file_size: 2142676
relation: main_file
success: 1
file_date_updated: 2019-05-15T14:12:31Z
has_accepted_license: '1'
intvolume: ' 6'
issue: '3'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
publication: Physical Review X
publication_status: published
publisher: American Physical Society
publist_id: '7954'
quality_controlled: '1'
status: public
title: Milestones toward Majorana-based quantum computing
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 6
year: '2016'
...
---
_id: '101'
abstract:
- lang: eng
text: Majorana zero modes are quasiparticle excitations in condensed matter systems
that have been proposed as building blocks of fault-tolerant quantum computers.
They are expected to exhibit non-Abelian particle statistics, in contrast to the
usual statistics of fermions and bosons, enabling quantum operations to be performed
by braiding isolated modes around one another. Quantum braiding operations are
topologically protected insofar as these modes are pinned near zero energy, with
the departure from zero expected to be exponentially small as the modes become
spatially separated. Following theoretical proposals, several experiments have
identified signatures of Majorana modes in nanowires with proximity-induced superconductivity
and atomic chains, with small amounts of mode splitting potentially explained
by hybridization of Majorana modes. Here, we use Coulomb-blockade spectroscopy
in an InAs nanowire segment with epitaxial aluminium, which forms a proximity-induced
superconducting Coulomb island (a â ∼ Majorana islandâ (tm)) that is isolated
from normal-metal leads by tunnel barriers, to measure the splitting of near-zero-energy
Majorana modes. We observe exponential suppression of energy splitting with increasing
wire length. For short devices of a few hundred nanometres, sub-gap state energies
oscillate as the magnetic field is varied, as is expected for hybridized Majorana
modes. Splitting decreases by a factor of about ten for each half a micrometre
of increased wire length. For devices longer than about one micrometre, transport
in strong magnetic fields occurs through a zero-energy state that is energetically
isolated from a continuum, yielding uniformly spaced Coulomb-blockade conductance
peaks, consistent with teleportation via Majorana modes. Our results help to explain
the trivial-to-topological transition in finite systems and to quantify the scaling
of topological protection with end-mode separation.
acknowledgement: This research was supported by Microsoft Project Q, the Danish National
Research Foundation, the Lundbeck Foundation, the Carlsberg Foundation and the European
Commission. C.M.M. acknowledges support from the Villum Foundation.
arxiv: 1
author:
- first_name: S M
full_name: Albrecht, S M
last_name: Albrecht
- first_name: Andrew P
full_name: Higginbotham, Andrew P
id: 4AD6785A-F248-11E8-B48F-1D18A9856A87
last_name: Higginbotham
orcid: 0000-0003-2607-2363
- first_name: Thomas
full_name: Jespersen, Thomas
last_name: Jespersen
- first_name: Morten
full_name: Madsen, Morten
last_name: Madsen
- first_name: Ferdinand
full_name: Kuemmeth, Ferdinand
last_name: Kuemmeth
- first_name: Jesper
full_name: Nygård, Jesper
last_name: Nygård
- first_name: Peter
full_name: Krogstrup, Peter
last_name: Krogstrup
- first_name: Charles
full_name: Marcus, Charles
last_name: Marcus
citation:
ama: Albrecht SM, Higginbotham AP, Jespersen T, et al. Exponential protection of
zero modes in Majorana islands. Nature. 2016;531(7593):206-209. doi:10.1038/nature17162
apa: Albrecht, S. M., Higginbotham, A. P., Jespersen, T., Madsen, M., Kuemmeth,
F., Nygård, J., … Marcus, C. (2016). Exponential protection of zero modes in Majorana
islands. Nature. Nature Publishing Group. https://doi.org/10.1038/nature17162
chicago: Albrecht, S M, Andrew P Higginbotham, Thomas Jespersen, Morten Madsen,
Ferdinand Kuemmeth, Jesper Nygård, Peter Krogstrup, and Charles Marcus. “Exponential
Protection of Zero Modes in Majorana Islands.” Nature. Nature Publishing
Group, 2016. https://doi.org/10.1038/nature17162.
ieee: S. M. Albrecht et al., “Exponential protection of zero modes in Majorana
islands,” Nature, vol. 531, no. 7593. Nature Publishing Group, pp. 206–209,
2016.
ista: Albrecht SM, Higginbotham AP, Jespersen T, Madsen M, Kuemmeth F, Nygård J,
Krogstrup P, Marcus C. 2016. Exponential protection of zero modes in Majorana
islands. Nature. 531(7593), 206–209.
mla: Albrecht, S. M., et al. “Exponential Protection of Zero Modes in Majorana Islands.”
Nature, vol. 531, no. 7593, Nature Publishing Group, 2016, pp. 206–09,
doi:10.1038/nature17162.
short: S.M. Albrecht, A.P. Higginbotham, T. Jespersen, M. Madsen, F. Kuemmeth, J.
Nygård, P. Krogstrup, C. Marcus, Nature 531 (2016) 206–209.
date_created: 2018-12-11T11:44:38Z
date_published: 2016-03-10T00:00:00Z
date_updated: 2021-01-12T06:47:37Z
day: '10'
doi: 10.1038/nature17162
extern: '1'
external_id:
arxiv:
- '1603.03217'
intvolume: ' 531'
issue: '7593'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://arxiv.org/abs/1603.03217
month: '03'
oa: 1
oa_version: Submitted Version
page: 206 - 209
publication: Nature
publication_status: published
publisher: Nature Publishing Group
publist_id: '7953'
quality_controlled: '1'
status: public
title: Exponential protection of zero modes in Majorana islands
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 531
year: '2016'
...
---
_id: '102'
abstract:
- lang: eng
text: 'Recent experiments have produced mounting evidence of Majorana zero modes
in nanowire-superconductor hybrids. Signatures of an expected topological phase
transition accompanying the onset of these modes nevertheless remain elusive.
We investigate a fundamental question concerning this issue: Do well-formed Majorana
modes necessarily entail a sharp phase transition in these setups? Assuming reasonable
parameters, we argue that finite-size effects can dramatically smooth this putative
transition into a crossover, even in systems large enough to support well-localized
Majorana modes. We propose overcoming such finite-size effects by examining the
behavior of low-lying excited states through tunneling spectroscopy. In particular,
the excited-state energies exhibit characteristic field and density dependence,
and scaling with system size, that expose an approaching topological phase transition.
We suggest several experiments for extracting the predicted behavior. As a useful
byproduct, the protocols also allow one to measure the wire''s spin-orbit coupling
directly in its superconducting environment.'
article_number: '245404'
arxiv: 1
author:
- first_name: Ryan
full_name: Mishmash, Ryan
last_name: Mishmash
- first_name: David
full_name: Aasen, David
last_name: Aasen
- first_name: Andrew P
full_name: Higginbotham, Andrew P
id: 4AD6785A-F248-11E8-B48F-1D18A9856A87
last_name: Higginbotham
orcid: 0000-0003-2607-2363
- first_name: Jason
full_name: Alicea, Jason
last_name: Alicea
citation:
ama: Mishmash R, Aasen D, Higginbotham AP, Alicea J. Approaching a topological phase
transition in Majorana nanowires. Physical Review B. 2016;93(24). doi:10.1103/PhysRevB.93.245404
apa: Mishmash, R., Aasen, D., Higginbotham, A. P., & Alicea, J. (2016). Approaching
a topological phase transition in Majorana nanowires. Physical Review B.
American Physical Society. https://doi.org/10.1103/PhysRevB.93.245404
chicago: Mishmash, Ryan, David Aasen, Andrew P Higginbotham, and Jason Alicea. “Approaching
a Topological Phase Transition in Majorana Nanowires.” Physical Review B.
American Physical Society, 2016. https://doi.org/10.1103/PhysRevB.93.245404.
ieee: R. Mishmash, D. Aasen, A. P. Higginbotham, and J. Alicea, “Approaching a topological
phase transition in Majorana nanowires,” Physical Review B, vol. 93, no.
24. American Physical Society, 2016.
ista: Mishmash R, Aasen D, Higginbotham AP, Alicea J. 2016. Approaching a topological
phase transition in Majorana nanowires. Physical Review B. 93(24), 245404.
mla: Mishmash, Ryan, et al. “Approaching a Topological Phase Transition in Majorana
Nanowires.” Physical Review B, vol. 93, no. 24, 245404, American Physical
Society, 2016, doi:10.1103/PhysRevB.93.245404.
short: R. Mishmash, D. Aasen, A.P. Higginbotham, J. Alicea, Physical Review B 93
(2016).
date_created: 2018-12-11T11:44:38Z
date_published: 2016-06-08T00:00:00Z
date_updated: 2021-01-12T06:47:42Z
day: '08'
doi: 10.1103/PhysRevB.93.245404
extern: '1'
external_id:
arxiv:
- '1601.07908'
intvolume: ' 93'
issue: '24'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://arxiv.org/abs/1601.07908
month: '06'
oa: 1
oa_version: Preprint
publication: Physical Review B
publication_status: published
publisher: American Physical Society
publist_id: '7952'
quality_controlled: '1'
status: public
title: Approaching a topological phase transition in Majorana nanowires
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 93
year: '2016'
...
---
_id: '10376'
abstract:
- lang: eng
text: Nucleation processes are at the heart of a large number of phenomena, from
cloud formation to protein crystallization. A recently emerging area where nucleation
is highly relevant is the initiation of filamentous protein self-assembly, a process
that has broad implications in many research areas ranging from medicine to nanotechnology.
As such, spontaneous nucleation of protein fibrils has received much attention
in recent years with many theoretical and experimental studies focusing on the
underlying physical principles. In this paper we make a step forward in this direction
and explore the early time behaviour of filamentous protein growth in the context
of nucleation theory. We first provide an overview of the thermodynamics and kinetics
of spontaneous nucleation of protein filaments in the presence of one relevant
degree of freedom, namely the cluster size. In this case, we review how key kinetic
observables, such as the reaction order of spontaneous nucleation, are directly
related to the physical size of the critical nucleus. We then focus on the increasingly
prominent case of filament nucleation that includes a conformational conversion
of the nucleating building-block as an additional slow step in the nucleation
process. Using computer simulations, we study the concentration dependence of
the nucleation rate. We find that, under these circumstances, the reaction order
of spontaneous nucleation with respect to the free monomer does no longer relate
to the overall physical size of the nucleating aggregate but rather to the portion
of the aggregate that actively participates in the conformational conversion.
Our results thus provide a novel interpretation of the common kinetic descriptors
of protein filament formation, including the reaction order of the nucleation
step or the scaling exponent of lag times, and put into perspective current theoretical
descriptions of protein aggregation.
acknowledgement: We acknowledge support from the Human Frontier Science Program and
Emmanuel College (A.Š.), St John’s and Peterhouse Colleges (T.C.T.M.), the Swiss
National Science Foundation (T.C.T.M.), the Biotechnology and Biological Sciences
Research Council (T.P.J.K.), the Frances and Augustus Newman Foundation (T.P.J.K.),
the European Research Council (T.C.T.M., T.P.J.K., and D.F.), and the Engineering
and Physical Sciences Research Council (D.F.).
article_number: '211926'
article_processing_charge: No
article_type: original
arxiv: 1
author:
- first_name: Anđela
full_name: Šarić, Anđela
id: bf63d406-f056-11eb-b41d-f263a6566d8b
last_name: Šarić
orcid: 0000-0002-7854-2139
- first_name: Thomas C. T.
full_name: Michaels, Thomas C. T.
last_name: Michaels
- first_name: Alessio
full_name: Zaccone, Alessio
last_name: Zaccone
- first_name: Tuomas P. J.
full_name: Knowles, Tuomas P. J.
last_name: Knowles
- first_name: Daan
full_name: Frenkel, Daan
last_name: Frenkel
citation:
ama: 'Šarić A, Michaels TCT, Zaccone A, Knowles TPJ, Frenkel D. Kinetics of spontaneous
filament nucleation via oligomers: Insights from theory and simulation. The
Journal of Chemical Physics. 2016;145(21). doi:10.1063/1.4965040'
apa: 'Šarić, A., Michaels, T. C. T., Zaccone, A., Knowles, T. P. J., & Frenkel,
D. (2016). Kinetics of spontaneous filament nucleation via oligomers: Insights
from theory and simulation. The Journal of Chemical Physics. American Institute
of Physics. https://doi.org/10.1063/1.4965040'
chicago: 'Šarić, Anđela, Thomas C. T. Michaels, Alessio Zaccone, Tuomas P. J. Knowles,
and Daan Frenkel. “Kinetics of Spontaneous Filament Nucleation via Oligomers:
Insights from Theory and Simulation.” The Journal of Chemical Physics.
American Institute of Physics, 2016. https://doi.org/10.1063/1.4965040.'
ieee: 'A. Šarić, T. C. T. Michaels, A. Zaccone, T. P. J. Knowles, and D. Frenkel,
“Kinetics of spontaneous filament nucleation via oligomers: Insights from theory
and simulation,” The Journal of Chemical Physics, vol. 145, no. 21. American
Institute of Physics, 2016.'
ista: 'Šarić A, Michaels TCT, Zaccone A, Knowles TPJ, Frenkel D. 2016. Kinetics
of spontaneous filament nucleation via oligomers: Insights from theory and simulation.
The Journal of Chemical Physics. 145(21), 211926.'
mla: 'Šarić, Anđela, et al. “Kinetics of Spontaneous Filament Nucleation via Oligomers:
Insights from Theory and Simulation.” The Journal of Chemical Physics,
vol. 145, no. 21, 211926, American Institute of Physics, 2016, doi:10.1063/1.4965040.'
short: A. Šarić, T.C.T. Michaels, A. Zaccone, T.P.J. Knowles, D. Frenkel, The Journal
of Chemical Physics 145 (2016).
date_created: 2021-11-29T10:01:57Z
date_published: 2016-12-01T00:00:00Z
date_updated: 2021-11-29T10:33:11Z
day: '01'
doi: 10.1063/1.4965040
extern: '1'
external_id:
arxiv:
- '1610.02320'
pmid:
- '28799382'
intvolume: ' 145'
issue: '21'
keyword:
- physical and theoretical chemistry
- general physics and astronomy
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://arxiv.org/abs/1610.02320
month: '12'
oa: 1
oa_version: Preprint
pmid: 1
publication: The Journal of Chemical Physics
publication_identifier:
eissn:
- 1089-7690
issn:
- 0021-9606
publication_status: published
publisher: American Institute of Physics
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Kinetics of spontaneous filament nucleation via oligomers: Insights from theory
and simulation'
type: journal_article
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
volume: 145
year: '2016'
...
---
_id: '10377'
abstract:
- lang: eng
text: The interplay of membrane proteins is vital for many biological processes,
such as cellular transport, cell division, and signal transduction between nerve
cells. Theoretical considerations have led to the idea that the membrane itself
mediates protein self-organization in these processes through minimization of
membrane curvature energy. Here, we present a combined experimental and numerical
study in which we quantify these interactions directly for the first time. In
our experimental model system we control the deformation of a lipid membrane by
adhering colloidal particles. Using confocal microscopy, we establish that these
membrane deformations cause an attractive interaction force leading to reversible
binding. The attraction extends over 2.5 times the particle diameter and has a
strength of three times the thermal energy (−3.3 kBT). Coarse-grained Monte-Carlo
simulations of the system are in excellent agreement with the experimental results
and prove that the measured interaction is independent of length scale. Our combined
experimental and numerical results reveal membrane curvature as a common physical
origin for interactions between any membrane-deforming objects, from nanometre-sized
proteins to micrometre-sized particles.
acknowledgement: This work was supported by the Netherlands Organisation for Scientific
Research (NWO/OCW), as part of the Frontiers of Nanoscience program and VENI grant
680-47-431. We thank Jeroen Appel and Wim Pomp for advice on the protocol design
and Marcel Winter and Ruben Verweij for experimental support.
article_number: '32825'
article_processing_charge: No
article_type: original
arxiv: 1
author:
- first_name: Casper
full_name: van der Wel, Casper
last_name: van der Wel
- first_name: Afshin
full_name: Vahid, Afshin
last_name: Vahid
- first_name: Anđela
full_name: Šarić, Anđela
id: bf63d406-f056-11eb-b41d-f263a6566d8b
last_name: Šarić
orcid: 0000-0002-7854-2139
- first_name: Timon
full_name: Idema, Timon
last_name: Idema
- first_name: Doris
full_name: Heinrich, Doris
last_name: Heinrich
- first_name: Daniela J.
full_name: Kraft, Daniela J.
last_name: Kraft
citation:
ama: van der Wel C, Vahid A, Šarić A, Idema T, Heinrich D, Kraft DJ. Lipid membrane-mediated
attraction between curvature inducing objects. Scientific Reports. 2016;6(1).
doi:10.1038/srep32825
apa: van der Wel, C., Vahid, A., Šarić, A., Idema, T., Heinrich, D., & Kraft,
D. J. (2016). Lipid membrane-mediated attraction between curvature inducing objects.
Scientific Reports. Springer Nature. https://doi.org/10.1038/srep32825
chicago: Wel, Casper van der, Afshin Vahid, Anđela Šarić, Timon Idema, Doris Heinrich,
and Daniela J. Kraft. “Lipid Membrane-Mediated Attraction between Curvature Inducing
Objects.” Scientific Reports. Springer Nature, 2016. https://doi.org/10.1038/srep32825.
ieee: C. van der Wel, A. Vahid, A. Šarić, T. Idema, D. Heinrich, and D. J. Kraft,
“Lipid membrane-mediated attraction between curvature inducing objects,” Scientific
Reports, vol. 6, no. 1. Springer Nature, 2016.
ista: van der Wel C, Vahid A, Šarić A, Idema T, Heinrich D, Kraft DJ. 2016. Lipid
membrane-mediated attraction between curvature inducing objects. Scientific Reports.
6(1), 32825.
mla: van der Wel, Casper, et al. “Lipid Membrane-Mediated Attraction between Curvature
Inducing Objects.” Scientific Reports, vol. 6, no. 1, 32825, Springer Nature,
2016, doi:10.1038/srep32825.
short: C. van der Wel, A. Vahid, A. Šarić, T. Idema, D. Heinrich, D.J. Kraft, Scientific
Reports 6 (2016).
date_created: 2021-11-29T10:34:08Z
date_published: 2016-09-13T00:00:00Z
date_updated: 2021-11-29T11:08:15Z
day: '13'
ddc:
- '540'
doi: 10.1038/srep32825
extern: '1'
external_id:
arxiv:
- '1603.04644'
pmid:
- '27618764'
file:
- access_level: open_access
checksum: d6cf16dd511e15726b001e7cc287cf1d
content_type: application/pdf
creator: cchlebak
date_created: 2021-11-29T10:50:00Z
date_updated: 2021-11-29T10:50:00Z
file_id: '10379'
file_name: 2016_SciRep_vanderWel.pdf
file_size: 1598289
relation: main_file
success: 1
file_date_updated: 2021-11-29T10:50:00Z
has_accepted_license: '1'
intvolume: ' 6'
issue: '1'
keyword:
- multidisciplinary
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.nature.com/articles/srep32825
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
publication: Scientific Reports
publication_identifier:
issn:
- 2045-2322
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: erratum
url: https://doi.org/10.1038/srep37382
scopus_import: '1'
status: public
title: Lipid membrane-mediated attraction between curvature inducing objects
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: 8b945eb4-e2f2-11eb-945a-df72226e66a9
volume: 6
year: '2016'
...
---
_id: '10378'
abstract:
- lang: eng
text: The ability of biological molecules to replicate themselves is the foundation
of life, requiring a complex cellular machinery. However, a range of aberrant
processes involve the self-replication of pathological protein structures without
any additional assistance. One example is the autocatalytic generation of pathological
protein aggregates, including amyloid fibrils, involved in neurodegenerative disorders.
Here, we use computer simulations to identify the necessary requirements for the
self-replication of fibrillar assemblies of proteins. We establish that a key
physical determinant for this process is the affinity of proteins for the surfaces
of fibrils. We find that self-replication can take place only in a very narrow
regime of inter-protein interactions, implying a high level of sensitivity to
system parameters and experimental conditions. We then compare our theoretical
predictions with kinetic and biosensor measurements of fibrils formed from the
Aβ peptide associated with Alzheimer’s disease. Our results show a quantitative
connection between the kinetics of self-replication and the surface coverage of
fibrils by monomeric proteins. These findings reveal the fundamental physical
requirements for the formation of supra-molecular structures able to replicate
themselves, and shed light on mechanisms in play in the proliferation of protein
aggregates in nature.
acknowledgement: We acknowledge support from the Human Frontier Science Program and
Emmanuel College (A.Š.), the Leverhulme Trust and Magdalene College (A.K.B.), St
John’s College (T.C.T.M.), the Biotechnology and Biological Sciences Research Council
(T.P.J.K. and C.M.D.), the Frances and Augustus Newman Foundation (T.P.J.K.), the
European Research Council (T.P.J.K., T.C.T.M., S.L. and D.F.), and the Engineering
and Physical Sciences Research Council (D.F.).
article_processing_charge: No
article_type: original
author:
- first_name: Anđela
full_name: Šarić, Anđela
id: bf63d406-f056-11eb-b41d-f263a6566d8b
last_name: Šarić
orcid: 0000-0002-7854-2139
- first_name: Alexander K.
full_name: Buell, Alexander K.
last_name: Buell
- first_name: Georg
full_name: Meisl, Georg
last_name: Meisl
- first_name: Thomas C. T.
full_name: Michaels, Thomas C. T.
last_name: Michaels
- first_name: Christopher M.
full_name: Dobson, Christopher M.
last_name: Dobson
- first_name: Sara
full_name: Linse, Sara
last_name: Linse
- first_name: Tuomas P. J.
full_name: Knowles, Tuomas P. J.
last_name: Knowles
- first_name: Daan
full_name: Frenkel, Daan
last_name: Frenkel
citation:
ama: Šarić A, Buell AK, Meisl G, et al. Physical determinants of the self-replication
of protein fibrils. Nature Physics. 2016;12(9):874-880. doi:10.1038/nphys3828
apa: Šarić, A., Buell, A. K., Meisl, G., Michaels, T. C. T., Dobson, C. M., Linse,
S., … Frenkel, D. (2016). Physical determinants of the self-replication of protein
fibrils. Nature Physics. Springer Nature. https://doi.org/10.1038/nphys3828
chicago: Šarić, Anđela, Alexander K. Buell, Georg Meisl, Thomas C. T. Michaels,
Christopher M. Dobson, Sara Linse, Tuomas P. J. Knowles, and Daan Frenkel. “Physical
Determinants of the Self-Replication of Protein Fibrils.” Nature Physics.
Springer Nature, 2016. https://doi.org/10.1038/nphys3828.
ieee: A. Šarić et al., “Physical determinants of the self-replication of
protein fibrils,” Nature Physics, vol. 12, no. 9. Springer Nature, pp.
874–880, 2016.
ista: Šarić A, Buell AK, Meisl G, Michaels TCT, Dobson CM, Linse S, Knowles TPJ,
Frenkel D. 2016. Physical determinants of the self-replication of protein fibrils.
Nature Physics. 12(9), 874–880.
mla: Šarić, Anđela, et al. “Physical Determinants of the Self-Replication of Protein
Fibrils.” Nature Physics, vol. 12, no. 9, Springer Nature, 2016, pp. 874–80,
doi:10.1038/nphys3828.
short: A. Šarić, A.K. Buell, G. Meisl, T.C.T. Michaels, C.M. Dobson, S. Linse, T.P.J.
Knowles, D. Frenkel, Nature Physics 12 (2016) 874–880.
date_created: 2021-11-29T10:36:11Z
date_published: 2016-07-18T00:00:00Z
date_updated: 2021-11-29T11:07:25Z
day: '18'
doi: 10.1038/nphys3828
extern: '1'
external_id:
pmid:
- '31031819'
intvolume: ' 12'
issue: '9'
keyword:
- general physics and astronomy
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://discovery.ucl.ac.uk/id/eprint/1517406/
month: '07'
oa: 1
oa_version: Preprint
page: 874-880
pmid: 1
publication: Nature Physics
publication_identifier:
eissn:
- 1745-2481
issn:
- 1745-2473
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Physical determinants of the self-replication of protein fibrils
type: journal_article
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
volume: 12
year: '2016'
...
---
_id: '10380'
abstract:
- lang: eng
text: Using non-equilibrium molecular dynamics simulations, it has been recently
demonstrated that water molecules align in response to an imposed temperature
gradient, resulting in an effective electric field. Here, we investigate how thermally
induced fields depend on the underlying treatment of long-ranged interactions.
For the short-ranged Wolf method and Ewald summation, we find the peak strength
of the field to range between 2 × 107 and 5 × 107 V/m for a temperature gradient
of 5.2 K/Å. Our value for the Wolf method is therefore an order of magnitude lower
than the literature value [J. A. Armstrong and F. Bresme, J. Chem. Phys. 139,
014504 (2013); J. Armstrong et al., J. Chem. Phys. 143, 036101 (2015)]. We show
that this discrepancy can be traced back to the use of an incorrect kernel in
the calculation of the electrostatic field. More seriously, we find that the Wolf
method fails to predict correct molecular orientations, resulting in dipole densities
with opposite sign to those computed using Ewald summation. By considering two
different multipole expansions, we show that, for inhomogeneous polarisations,
the quadrupole contribution can be significant and even outweigh the dipole contribution
to the field. Finally, we propose a more accurate way of calculating the electrostatic
potential and the field. In particular, we show that averaging the microscopic
field analytically to obtain the macroscopic Maxwell field reduces the error bars
by up to an order of magnitude. As a consequence, the simulation times required
to reach a given statistical accuracy decrease by up to two orders of magnitude.
acknowledgement: The authors should like to dedicate this paper to the memory of Simon
de Leeuw, who was a pioneer in the calculation of Coulomb effects in simulations.
P.W. would like to thank the Austrian Academy of Sciences for financial support
through a DOC Fellowship, and for covering the travel expenses for the CECAM workshop
in Zaragoza in May 2015, where these results were first presented. P.W. would also
like to thank Chao Zhang for pointing out the equivalence of the two expressions
for the electric field discussed in Sec. VI D, Michiel Sprik for emphasising the
importance of the quadrupole contribution in experimental studies of interfacial
systems, as well as Aleks Reinhardt and other members of the Frenkel and Dellago
groups for their advice. We further acknowledge support from the Federation of Austrian
Industry (IV) Carinthia (P.W.), the University of Zagreb and Erasmus SMP (D. Fijan),
the Human Frontier Science Program and Emmanuel College (A.Š.), the Austrian Science
Fund FWF within the SFB Vicom project F41 (C.D.), and the Engineering and Physical
Sciences Research Council Programme Grant No. EP/I001352/1 (D.F.). Additional data
related to this publication are available at the University of Cambridge data repository
(http://dx.doi.org/10.17863/CAM.118).
article_number: '224102'
article_processing_charge: No
article_type: original
arxiv: 1
author:
- first_name: P.
full_name: Wirnsberger, P.
last_name: Wirnsberger
- first_name: D.
full_name: Fijan, D.
last_name: Fijan
- first_name: Anđela
full_name: Šarić, Anđela
id: bf63d406-f056-11eb-b41d-f263a6566d8b
last_name: Šarić
orcid: 0000-0002-7854-2139
- first_name: M.
full_name: Neumann, M.
last_name: Neumann
- first_name: C.
full_name: Dellago, C.
last_name: Dellago
- first_name: D.
full_name: Frenkel, D.
last_name: Frenkel
citation:
ama: Wirnsberger P, Fijan D, Šarić A, Neumann M, Dellago C, Frenkel D. Non-equilibrium
simulations of thermally induced electric fields in water. The Journal of Chemical
Physics. 2016;144(22). doi:10.1063/1.4953036
apa: Wirnsberger, P., Fijan, D., Šarić, A., Neumann, M., Dellago, C., & Frenkel,
D. (2016). Non-equilibrium simulations of thermally induced electric fields in
water. The Journal of Chemical Physics. American Institute of Physics.
https://doi.org/10.1063/1.4953036
chicago: Wirnsberger, P., D. Fijan, Anđela Šarić, M. Neumann, C. Dellago, and D.
Frenkel. “Non-Equilibrium Simulations of Thermally Induced Electric Fields in
Water.” The Journal of Chemical Physics. American Institute of Physics,
2016. https://doi.org/10.1063/1.4953036.
ieee: P. Wirnsberger, D. Fijan, A. Šarić, M. Neumann, C. Dellago, and D. Frenkel,
“Non-equilibrium simulations of thermally induced electric fields in water,” The
Journal of Chemical Physics, vol. 144, no. 22. American Institute of Physics,
2016.
ista: Wirnsberger P, Fijan D, Šarić A, Neumann M, Dellago C, Frenkel D. 2016. Non-equilibrium
simulations of thermally induced electric fields in water. The Journal of Chemical
Physics. 144(22), 224102.
mla: Wirnsberger, P., et al. “Non-Equilibrium Simulations of Thermally Induced Electric
Fields in Water.” The Journal of Chemical Physics, vol. 144, no. 22, 224102,
American Institute of Physics, 2016, doi:10.1063/1.4953036.
short: P. Wirnsberger, D. Fijan, A. Šarić, M. Neumann, C. Dellago, D. Frenkel, The
Journal of Chemical Physics 144 (2016).
date_created: 2021-11-29T11:08:52Z
date_published: 2016-06-10T00:00:00Z
date_updated: 2021-11-29T13:09:08Z
day: '10'
doi: 10.1063/1.4953036
extern: '1'
external_id:
arxiv:
- '1602.02734'
pmid:
- '27305991'
intvolume: ' 144'
issue: '22'
keyword:
- physical and theoretical chemistry
- general physics and astronomy
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://arxiv.org/abs/1602.02734
month: '06'
oa: 1
oa_version: Preprint
pmid: 1
publication: The Journal of Chemical Physics
publication_identifier:
eissn:
- 1089-7690
issn:
- 0021-9606
publication_status: published
publisher: American Institute of Physics
quality_controlled: '1'
scopus_import: '1'
status: public
title: Non-equilibrium simulations of thermally induced electric fields in water
type: journal_article
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
volume: 144
year: '2016'
...
---
_id: '10381'
abstract:
- lang: eng
text: We study phase behaviour of lipid-bilayer vesicles functionalised by ligand–receptor
complexes made of synthetic DNA by introducing a modelling framework and a dedicated
experimental platform. In particular, we perform Monte Carlo simulations that
combine a coarse grained description of the lipid bilayer with state of art analytical
models for multivalent ligand–receptor interactions. Using density of state calculations,
we derive the partition function in pairs of vesicles and compute the number of
ligand–receptor bonds as a function of temperature. Numerical results are compared
to microscopy and fluorimetry experiments on large unilamellar vesicles decorated
by DNA linkers carrying complementary overhangs. We find that vesicle aggregation
is suppressed when the total number of linkers falls below a threshold value.
Within the model proposed here, this is due to the higher configurational costs
required to form inter-vesicle bridges as compared to intra-vesicle loops, which
are in turn related to membrane deformability. Our findings and our numerical/experimental
methodologies are applicable to the rational design of liposomes used as functional
materials and drug delivery applications, as well as to study inter-membrane interactions
in living systems, such as cell adhesion.
article_processing_charge: No
article_type: original
arxiv: 1
author:
- first_name: Stephan Jan
full_name: Bachmann, Stephan Jan
last_name: Bachmann
- first_name: Jurij
full_name: Kotar, Jurij
last_name: Kotar
- first_name: Lucia
full_name: Parolini, Lucia
last_name: Parolini
- first_name: Anđela
full_name: Šarić, Anđela
id: bf63d406-f056-11eb-b41d-f263a6566d8b
last_name: Šarić
orcid: 0000-0002-7854-2139
- first_name: Pietro
full_name: Cicuta, Pietro
last_name: Cicuta
- first_name: Lorenzo
full_name: Di Michele, Lorenzo
last_name: Di Michele
- first_name: Bortolo Matteo
full_name: Mognetti, Bortolo Matteo
last_name: Mognetti
citation:
ama: Bachmann SJ, Kotar J, Parolini L, et al. Melting transition in lipid vesicles
functionalised by mobile DNA linkers. Soft Matter. 2016;12(37):7804-7817.
doi:10.1039/c6sm01515h
apa: Bachmann, S. J., Kotar, J., Parolini, L., Šarić, A., Cicuta, P., Di Michele,
L., & Mognetti, B. M. (2016). Melting transition in lipid vesicles functionalised
by mobile DNA linkers. Soft Matter. Royal Society of Chemistry. https://doi.org/10.1039/c6sm01515h
chicago: Bachmann, Stephan Jan, Jurij Kotar, Lucia Parolini, Anđela Šarić, Pietro
Cicuta, Lorenzo Di Michele, and Bortolo Matteo Mognetti. “Melting Transition in
Lipid Vesicles Functionalised by Mobile DNA Linkers.” Soft Matter. Royal
Society of Chemistry, 2016. https://doi.org/10.1039/c6sm01515h.
ieee: S. J. Bachmann et al., “Melting transition in lipid vesicles functionalised
by mobile DNA linkers,” Soft Matter, vol. 12, no. 37. Royal Society of
Chemistry, pp. 7804–7817, 2016.
ista: Bachmann SJ, Kotar J, Parolini L, Šarić A, Cicuta P, Di Michele L, Mognetti
BM. 2016. Melting transition in lipid vesicles functionalised by mobile DNA linkers.
Soft Matter. 12(37), 7804–7817.
mla: Bachmann, Stephan Jan, et al. “Melting Transition in Lipid Vesicles Functionalised
by Mobile DNA Linkers.” Soft Matter, vol. 12, no. 37, Royal Society of
Chemistry, 2016, pp. 7804–17, doi:10.1039/c6sm01515h.
short: S.J. Bachmann, J. Kotar, L. Parolini, A. Šarić, P. Cicuta, L. Di Michele,
B.M. Mognetti, Soft Matter 12 (2016) 7804–7817.
date_created: 2021-11-29T11:09:55Z
date_published: 2016-08-19T00:00:00Z
date_updated: 2021-11-29T13:09:00Z
day: '19'
doi: 10.1039/c6sm01515h
extern: '1'
external_id:
arxiv:
- '1608.05788'
pmid:
- '27722701'
intvolume: ' 12'
issue: '37'
keyword:
- condensed matter physics
- general chemistry
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://arxiv.org/abs/1608.05788
month: '08'
oa: 1
oa_version: Preprint
page: 7804-7817
pmid: 1
publication: Soft Matter
publication_identifier:
eissn:
- 1744-6848
issn:
- 1744-683X
publication_status: published
publisher: Royal Society of Chemistry
quality_controlled: '1'
scopus_import: '1'
status: public
title: Melting transition in lipid vesicles functionalised by mobile DNA linkers
type: journal_article
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
volume: 12
year: '2016'
...
---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '21101'
abstract:
- lang: eng
text: It has previously been shown that the use of racemic mixtures of naturally
chiral macromolecules such as protein and DNA can significantly aid the crystallogenesis
process, thereby addressing one of the major bottlenecks to structure determination
by X-ray crystallographic methods—that of crystal growth. Although previous studies
have provided convincing evidence of the applicability of the racemic crystallization
technique to DNA through the study of well-characterized DNA structures, we sought
to apply this method to a historically challenging DNA sequence. For this purpose
we chose a non-self-complementary DNA duplex containing the biologically-relevant
Pribnow box consensus sequence ‘TATAAT’. Four racemic crystal structures of this
previously un-crystallizable DNA target are reported (with resolutions in the
range of 1.65–2.3 Å), with further crystallographic studies and structural analysis
providing insight into the racemic crystallization process as well as structural
details of this highly pertinent DNA sequence.
article_processing_charge: No
article_type: original
author:
- first_name: Pradeep K
full_name: Mandal, Pradeep K
id: 6a3def15-d4b4-11ef-9fa9-a24c1f545ec3
last_name: Mandal
orcid: 0000-0001-5996-956X
- first_name: Gavin W.
full_name: Collie, Gavin W.
last_name: Collie
- first_name: Suresh C.
full_name: Srivastava, Suresh C.
last_name: Srivastava
- first_name: Brice
full_name: Kauffmann, Brice
last_name: Kauffmann
- first_name: Ivan
full_name: Huc, Ivan
last_name: Huc
citation:
ama: Mandal PK, Collie GW, Srivastava SC, Kauffmann B, Huc I. Structure elucidation
of the Pribnow box consensus promoter sequence by racemic DNA crystallography.
Nucleic Acids Research. 2016;44(12):5936-5943. doi:10.1093/nar/gkw367
apa: Mandal, P. K., Collie, G. W., Srivastava, S. C., Kauffmann, B., & Huc,
I. (2016). Structure elucidation of the Pribnow box consensus promoter sequence
by racemic DNA crystallography. Nucleic Acids Research. Oxford University
Press. https://doi.org/10.1093/nar/gkw367
chicago: Mandal, Pradeep K, Gavin W. Collie, Suresh C. Srivastava, Brice Kauffmann,
and Ivan Huc. “Structure Elucidation of the Pribnow Box Consensus Promoter Sequence
by Racemic DNA Crystallography.” Nucleic Acids Research. Oxford University
Press, 2016. https://doi.org/10.1093/nar/gkw367.
ieee: P. K. Mandal, G. W. Collie, S. C. Srivastava, B. Kauffmann, and I. Huc, “Structure
elucidation of the Pribnow box consensus promoter sequence by racemic DNA crystallography,”
Nucleic Acids Research, vol. 44, no. 12. Oxford University Press, pp. 5936–5943,
2016.
ista: Mandal PK, Collie GW, Srivastava SC, Kauffmann B, Huc I. 2016. Structure elucidation
of the Pribnow box consensus promoter sequence by racemic DNA crystallography.
Nucleic Acids Research. 44(12), 5936–5943.
mla: Mandal, Pradeep K., et al. “Structure Elucidation of the Pribnow Box Consensus
Promoter Sequence by Racemic DNA Crystallography.” Nucleic Acids Research,
vol. 44, no. 12, Oxford University Press, 2016, pp. 5936–43, doi:10.1093/nar/gkw367.
short: P.K. Mandal, G.W. Collie, S.C. Srivastava, B. Kauffmann, I. Huc, Nucleic
Acids Research 44 (2016) 5936–5943.
date_created: 2026-01-29T21:46:40Z
date_published: 2016-07-08T00:00:00Z
date_updated: 2026-02-23T09:16:14Z
day: '08'
ddc:
- '570'
doi: 10.1093/nar/gkw367
extern: '1'
has_accepted_license: '1'
intvolume: ' 44'
issue: '12'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc/4.0/
main_file_link:
- open_access: '1'
url: https://doi.org/10.1093/nar/gkw367
month: '07'
oa: 1
oa_version: Published Version
page: 5936-5943
publication: Nucleic Acids Research
publication_identifier:
eissn:
- 1362-4962
issn:
- 0305-1048
publication_status: published
publisher: Oxford University Press
quality_controlled: '1'
status: public
title: Structure elucidation of the Pribnow box consensus promoter sequence by racemic
DNA crystallography
tmp:
image: /images/cc_by_nc.png
legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
short: CC BY-NC (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 44
year: '2016'
...
---
_id: '1552'
abstract:
- lang: eng
text: Antibiotic resistance carries a fitness cost that must be overcome in order
for resistance to persist over the long term. Compensatory mutations that recover
the functional defects associated with resistance mutations have been argued to
play a key role in overcoming the cost of resistance, but compensatory mutations
are expected to be rare relative to generally beneficial mutations that increase
fitness, irrespective of antibiotic resistance. Given this asymmetry, population
genetics theory predicts that populations should adapt by compensatory mutations
when the cost of resistance is large, whereas generally beneficial mutations should
drive adaptation when the cost of resistance is small. We tested this prediction
by determining the genomic mechanisms underpinning adaptation to antibiotic-free
conditions in populations of the pathogenic bacterium Pseudomonas aeruginosa that
carry costly antibiotic resistance mutations. Whole-genome sequencing revealed
that populations founded by high-cost rifampicin-resistant mutants adapted via
compensatory mutations in three genes of the RNA polymerase core enzyme, whereas
populations founded by low-cost mutants adapted by generally beneficial mutations,
predominantly in the quorum-sensing transcriptional regulator gene lasR. Even
though the importance of compensatory evolution in maintaining resistance has
been widely recognized, our study shows that the roles of general adaptation in
maintaining resistance should not be underestimated and highlights the need to
understand how selection at other sites in the genome influences the dynamics
of resistance alleles in clinical settings.
acknowledgement: "We thank the High-Throughput Genomics Group at the Wellcome Trust
Centre for Human Genetics funded by Wellcome\r\nTrust grant reference 090532/Z/09/Z
and Medical Research Council Hub grant no. G0900747 91070 for generation of the
high-throughput sequencing data. We thank Wook Kim and two anonymous reviewers for
their constructive feedback on previous versions of our manuscript."
article_number: '20152452'
article_processing_charge: No
author:
- first_name: Qin
full_name: Qi, Qin
id: 3B22D412-F248-11E8-B48F-1D18A9856A87
last_name: Qi
orcid: 0000-0002-6148-2416
- first_name: Macarena
full_name: Toll Riera, Macarena
last_name: Toll Riera
- first_name: Karl
full_name: Heilbron, Karl
last_name: Heilbron
- first_name: Gail
full_name: Preston, Gail
last_name: Preston
- first_name: R Craig
full_name: Maclean, R Craig
last_name: Maclean
citation:
ama: Qi Q, Toll Riera M, Heilbron K, Preston G, Maclean RC. The genomic basis of
adaptation to the fitness cost of rifampicin resistance in Pseudomonas aeruginosa.
Proceedings of the Royal Society of London Series B Biological Sciences.
2016;283(1822). doi:10.1098/rspb.2015.2452
apa: Qi, Q., Toll Riera, M., Heilbron, K., Preston, G., & Maclean, R. C. (2016).
The genomic basis of adaptation to the fitness cost of rifampicin resistance in
Pseudomonas aeruginosa. Proceedings of the Royal Society of London Series B
Biological Sciences. Royal Society, The. https://doi.org/10.1098/rspb.2015.2452
chicago: Qi, Qin, Macarena Toll Riera, Karl Heilbron, Gail Preston, and R Craig
Maclean. “The Genomic Basis of Adaptation to the Fitness Cost of Rifampicin Resistance
in Pseudomonas Aeruginosa.” Proceedings of the Royal Society of London Series
B Biological Sciences. Royal Society, The, 2016. https://doi.org/10.1098/rspb.2015.2452.
ieee: Q. Qi, M. Toll Riera, K. Heilbron, G. Preston, and R. C. Maclean, “The genomic
basis of adaptation to the fitness cost of rifampicin resistance in Pseudomonas
aeruginosa,” Proceedings of the Royal Society of London Series B Biological
Sciences, vol. 283, no. 1822. Royal Society, The, 2016.
ista: Qi Q, Toll Riera M, Heilbron K, Preston G, Maclean RC. 2016. The genomic basis
of adaptation to the fitness cost of rifampicin resistance in Pseudomonas aeruginosa.
Proceedings of the Royal Society of London Series B Biological Sciences. 283(1822),
20152452.
mla: Qi, Qin, et al. “The Genomic Basis of Adaptation to the Fitness Cost of Rifampicin
Resistance in Pseudomonas Aeruginosa.” Proceedings of the Royal Society of
London Series B Biological Sciences, vol. 283, no. 1822, 20152452, Royal Society,
The, 2016, doi:10.1098/rspb.2015.2452.
short: Q. Qi, M. Toll Riera, K. Heilbron, G. Preston, R.C. Maclean, Proceedings
of the Royal Society of London Series B Biological Sciences 283 (2016).
date_created: 2018-12-11T11:52:40Z
date_published: 2016-01-13T00:00:00Z
date_updated: 2025-09-18T11:03:28Z
day: '13'
ddc:
- '570'
department:
- _id: ToBo
doi: 10.1098/rspb.2015.2452
external_id:
isi:
- '000368441200022'
file:
- access_level: open_access
checksum: 78ffe70c1c88af3856d31ca6b7195a27
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:11:43Z
date_updated: 2020-07-14T12:45:02Z
file_id: '4899'
file_name: IST-2016-488-v1+1_20152452.full.pdf
file_size: 626804
relation: main_file
file_date_updated: 2020-07-14T12:45:02Z
has_accepted_license: '1'
intvolume: ' 283'
isi: 1
issue: '1822'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
publication: Proceedings of the Royal Society of London Series B Biological Sciences
publication_status: published
publisher: Royal Society, The
publist_id: '5619'
pubrep_id: '488'
quality_controlled: '1'
scopus_import: '1'
status: public
title: The genomic basis of adaptation to the fitness cost of rifampicin resistance
in Pseudomonas aeruginosa
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 283
year: '2016'
...
---
_id: '1599'
abstract:
- lang: eng
text: "The addition of polysialic acid to N- and/or O-linked glycans, referred to
as polysialylation, is a rare posttranslational modification that is mainly known
to control the developmental plasticity of the nervous system. Here we show that
CCR7, the central chemokine receptor controlling immune cell trafficking to secondary
lymphatic organs, carries polysialic acid. This modification is essential for
the recognition of the CCR7 ligand CCL21. As a consequence, dendritic cell trafficking
is abrogated in polysialyltransferase-deficient mice, manifesting as disturbed
lymph node homeostasis and unresponsiveness to inflammatory stimuli. Structure-function
analysis of chemokine-receptor interactions reveals that CCL21 adopts an autoinhibited
conformation, which is released upon interaction with polysialic acid. Thus, we
describe a glycosylation-mediated immune cell trafficking disorder and its mechanistic
basis.\r\n"
acknowledged_ssus:
- _id: SSU
acknowledgement: 'We thank S. Schüchner and E. Ogris for kindly providing the antibody
to GFP, M. Helmbrecht and A. Huber for providing Nrp2−/− mice, the IST Scientific
Support Facilities for excellent services, and J. Renkawitz and K. Vaahtomeri for
critically reading the manuscript. '
article_processing_charge: No
article_type: original
author:
- first_name: Eva
full_name: Kiermaier, Eva
id: 3EB04B78-F248-11E8-B48F-1D18A9856A87
last_name: Kiermaier
orcid: 0000-0001-6165-5738
- first_name: Christine
full_name: Moussion, Christine
id: 3356F664-F248-11E8-B48F-1D18A9856A87
last_name: Moussion
- first_name: Christopher
full_name: Veldkamp, Christopher
last_name: Veldkamp
- first_name: Rita
full_name: Gerardy Schahn, Rita
last_name: Gerardy Schahn
- first_name: Ingrid
full_name: De Vries, Ingrid
id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
last_name: De Vries
- first_name: Larry
full_name: Williams, Larry
last_name: Williams
- first_name: Gary
full_name: Chaffee, Gary
last_name: Chaffee
- first_name: Andrew
full_name: Phillips, Andrew
last_name: Phillips
- first_name: Friedrich
full_name: Freiberger, Friedrich
last_name: Freiberger
- first_name: Richard
full_name: Imre, Richard
last_name: Imre
- first_name: Deni
full_name: Taleski, Deni
last_name: Taleski
- first_name: Richard
full_name: Payne, Richard
last_name: Payne
- first_name: Asolina
full_name: Braun, Asolina
last_name: Braun
- first_name: Reinhold
full_name: Förster, Reinhold
last_name: Förster
- first_name: Karl
full_name: Mechtler, Karl
last_name: Mechtler
- first_name: Martina
full_name: Mühlenhoff, Martina
last_name: Mühlenhoff
- first_name: Brian
full_name: Volkman, Brian
last_name: Volkman
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Kiermaier E, Moussion C, Veldkamp C, et al. Polysialylation controls dendritic
cell trafficking by regulating chemokine recognition. Science. 2016;351(6269):186-190.
doi:10.1126/science.aad0512
apa: Kiermaier, E., Moussion, C., Veldkamp, C., Gerardy Schahn, R., de Vries, I.,
Williams, L., … Sixt, M. K. (2016). Polysialylation controls dendritic cell trafficking
by regulating chemokine recognition. Science. American Association for
the Advancement of Science. https://doi.org/10.1126/science.aad0512
chicago: Kiermaier, Eva, Christine Moussion, Christopher Veldkamp, Rita Gerardy
Schahn, Ingrid de Vries, Larry Williams, Gary Chaffee, et al. “Polysialylation
Controls Dendritic Cell Trafficking by Regulating Chemokine Recognition.” Science.
American Association for the Advancement of Science, 2016. https://doi.org/10.1126/science.aad0512.
ieee: E. Kiermaier et al., “Polysialylation controls dendritic cell trafficking
by regulating chemokine recognition,” Science, vol. 351, no. 6269. American
Association for the Advancement of Science, pp. 186–190, 2016.
ista: Kiermaier E, Moussion C, Veldkamp C, Gerardy Schahn R, de Vries I, Williams
L, Chaffee G, Phillips A, Freiberger F, Imre R, Taleski D, Payne R, Braun A, Förster
R, Mechtler K, Mühlenhoff M, Volkman B, Sixt MK. 2016. Polysialylation controls
dendritic cell trafficking by regulating chemokine recognition. Science. 351(6269),
186–190.
mla: Kiermaier, Eva, et al. “Polysialylation Controls Dendritic Cell Trafficking
by Regulating Chemokine Recognition.” Science, vol. 351, no. 6269, American
Association for the Advancement of Science, 2016, pp. 186–90, doi:10.1126/science.aad0512.
short: E. Kiermaier, C. Moussion, C. Veldkamp, R. Gerardy Schahn, I. de Vries,
L. Williams, G. Chaffee, A. Phillips, F. Freiberger, R. Imre, D. Taleski, R. Payne,
A. Braun, R. Förster, K. Mechtler, M. Mühlenhoff, B. Volkman, M.K. Sixt, Science
351 (2016) 186–190.
corr_author: '1'
date_created: 2018-12-11T11:52:57Z
date_published: 2016-01-08T00:00:00Z
date_updated: 2025-09-18T11:01:30Z
day: '08'
department:
- _id: MiSi
doi: 10.1126/science.aad0512
ec_funded: 1
external_id:
isi:
- '000367806500045'
pmid:
- '26657283'
intvolume: ' 351'
isi: 1
issue: '6269'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583642/
month: '01'
oa: 1
oa_version: Submitted Version
page: 186 - 190
pmid: 1
project:
- _id: 25A603A2-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '281556'
name: Cytoskeletal force generation and force transduction of migrating leukocytes
- _id: 25A76F58-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '289720'
name: Stromal Cell-immune Cell Interactions in Health and Disease
- _id: 25A8E5EA-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Y 564-B12
name: Cytoskeletal force generation and force transduction of migrating leukocytes
publication: Science
publication_status: published
publisher: American Association for the Advancement of Science
publist_id: '5570'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Polysialylation controls dendritic cell trafficking by regulating chemokine
recognition
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 351
year: '2016'
...
---
_id: '1608'
abstract:
- lang: eng
text: 'We show that the Anderson model has a transition from localization to delocalization
at exactly 2 dimensional growth rate on antitrees with normalized edge weights
which are certain discrete graphs. The kinetic part has a one-dimensional structure
allowing a description through transfer matrices which involve some Schur complement.
For such operators we introduce the notion of having one propagating channel and
extend theorems from the theory of one-dimensional Jacobi operators that relate
the behavior of transfer matrices with the spectrum. These theorems are then applied
to the considered model. In essence, in a certain energy region the kinetic part
averages the random potentials along shells and the transfer matrices behave similar
as for a one-dimensional operator with random potential of decaying variance.
At d dimensional growth for d>2 this effective decay is strong enough to obtain
absolutely continuous spectrum, whereas for some uniform d dimensional growth
with d<2 one has pure point spectrum in this energy region. At exactly uniform
2 dimensional growth also some singular continuous spectrum appears, at least
at small disorder. As a corollary we also obtain a change from singular spectrum
(d≤2) to absolutely continuous spectrum (d≥3) for random operators of the type
rΔdr+λ on ℤd, where r is an orthogonal radial projection, Δd the discrete
adjacency operator (Laplacian) on ℤd and λ a random potential. '
article_processing_charge: No
arxiv: 1
author:
- first_name: Christian
full_name: Sadel, Christian
id: 4760E9F8-F248-11E8-B48F-1D18A9856A87
last_name: Sadel
orcid: 0000-0001-8255-3968
citation:
ama: Sadel C. Anderson transition at 2 dimensional growth rate on antitrees and
spectral theory for operators with one propagating channel. Annales Henri Poincare.
2016;17(7):1631-1675. doi:10.1007/s00023-015-0456-3
apa: Sadel, C. (2016). Anderson transition at 2 dimensional growth rate on antitrees
and spectral theory for operators with one propagating channel. Annales Henri
Poincare. Birkhäuser. https://doi.org/10.1007/s00023-015-0456-3
chicago: Sadel, Christian. “Anderson Transition at 2 Dimensional Growth Rate on
Antitrees and Spectral Theory for Operators with One Propagating Channel.” Annales
Henri Poincare. Birkhäuser, 2016. https://doi.org/10.1007/s00023-015-0456-3.
ieee: C. Sadel, “Anderson transition at 2 dimensional growth rate on antitrees and
spectral theory for operators with one propagating channel,” Annales Henri
Poincare, vol. 17, no. 7. Birkhäuser, pp. 1631–1675, 2016.
ista: Sadel C. 2016. Anderson transition at 2 dimensional growth rate on antitrees
and spectral theory for operators with one propagating channel. Annales Henri
Poincare. 17(7), 1631–1675.
mla: Sadel, Christian. “Anderson Transition at 2 Dimensional Growth Rate on Antitrees
and Spectral Theory for Operators with One Propagating Channel.” Annales Henri
Poincare, vol. 17, no. 7, Birkhäuser, 2016, pp. 1631–75, doi:10.1007/s00023-015-0456-3.
short: C. Sadel, Annales Henri Poincare 17 (2016) 1631–1675.
corr_author: '1'
date_created: 2018-12-11T11:53:00Z
date_published: 2016-07-01T00:00:00Z
date_updated: 2025-09-18T11:00:43Z
day: '01'
department:
- _id: LaEr
doi: 10.1007/s00023-015-0456-3
ec_funded: 1
external_id:
arxiv:
- '1501.04287'
isi:
- '000377994000003'
intvolume: ' 17'
isi: 1
issue: '7'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: http://arxiv.org/abs/1501.04287
month: '07'
oa: 1
oa_version: Preprint
page: 1631 - 1675
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
publication: Annales Henri Poincare
publication_status: published
publisher: Birkhäuser
publist_id: '5558'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Anderson transition at 2 dimensional growth rate on antitrees and spectral
theory for operators with one propagating channel
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 17
year: '2016'
...
---
_id: '1612'
abstract:
- lang: eng
text: We prove that whenever A is a 3-conservative relational structure with only
binary and unary relations,then the algebra of polymorphisms of A either has no
Taylor operation (i.e.,CSP(A)is NP-complete),or it generates an SD(∧) variety
(i.e.,CSP(A)has bounded width).
article_processing_charge: No
arxiv: 1
author:
- first_name: Alexandr
full_name: Kazda, Alexandr
id: 3B32BAA8-F248-11E8-B48F-1D18A9856A87
last_name: Kazda
citation:
ama: Kazda A. CSP for binary conservative relational structures. Algebra Universalis.
2016;75(1):75-84. doi:10.1007/s00012-015-0358-8
apa: Kazda, A. (2016). CSP for binary conservative relational structures. Algebra
Universalis. Springer. https://doi.org/10.1007/s00012-015-0358-8
chicago: Kazda, Alexandr. “CSP for Binary Conservative Relational Structures.” Algebra
Universalis. Springer, 2016. https://doi.org/10.1007/s00012-015-0358-8.
ieee: A. Kazda, “CSP for binary conservative relational structures,” Algebra
Universalis, vol. 75, no. 1. Springer, pp. 75–84, 2016.
ista: Kazda A. 2016. CSP for binary conservative relational structures. Algebra
Universalis. 75(1), 75–84.
mla: Kazda, Alexandr. “CSP for Binary Conservative Relational Structures.” Algebra
Universalis, vol. 75, no. 1, Springer, 2016, pp. 75–84, doi:10.1007/s00012-015-0358-8.
short: A. Kazda, Algebra Universalis 75 (2016) 75–84.
corr_author: '1'
date_created: 2018-12-11T11:53:01Z
date_published: 2016-02-01T00:00:00Z
date_updated: 2025-09-18T11:00:04Z
day: '01'
department:
- _id: VlKo
doi: 10.1007/s00012-015-0358-8
external_id:
arxiv:
- '1112.1099'
isi:
- '000375422500006'
intvolume: ' 75'
isi: 1
issue: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: http://arxiv.org/abs/1112.1099
month: '02'
oa: 1
oa_version: Preprint
page: 75 - 84
publication: Algebra Universalis
publication_status: published
publisher: Springer
publist_id: '5554'
quality_controlled: '1'
scopus_import: '1'
status: public
title: CSP for binary conservative relational structures
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 75
year: '2016'
...
---
_id: '1613'
abstract:
- lang: eng
text: "In the last decade, induced pluripotent stem (iPS) cells have revolutionized
the utility of human in vitro models of neurological disease. The iPS-derived
and differentiated cells allow researchers to study the impact of a distinct cell
type in health and disease as well as performing therapeutic drug screens on a
human genetic background. In particular, clinical trials for Alzheimer's disease
(AD) have been often failing. Two of the potential reasons are first, the species
gap involved in proceeding from initial discoveries in rodent models to human
studies, and second, an unsatisfying patient stratification, meaning subgrouping
patients based on the disease severity due to the lack of phenotypic and genetic
markers. iPS cells overcome this obstacles and will improve our understanding
of disease subtypes in AD. They allow researchers conducting in depth characterization
of neural cells from both familial and sporadic AD patients as well as preclinical
screens on human cells.\r\n\r\nIn this review, we briefly outline the status quo
of iPS cell research in neurological diseases along with the general advantages
and pitfalls of these models. We summarize how genome-editing techniques such
as CRISPR/Cas will allow researchers to reduce the problem of genomic variability
inherent to human studies, followed by recent iPS cell studies relevant to AD.
We then focus on current techniques for the differentiation of iPS cells into
neural cell types that are relevant to AD research. Finally, we discuss how the
generation of three-dimensional cell culture systems will be important for understanding
AD phenotypes in a complex cellular milieu, and how both two- and three-dimensional
iPS cell models can provide platforms for drug discovery and translational studies
into the treatment of AD."
acknowledgement: This work was supported by NIH grant R01-AG047661 to LHT. The art
in Fig. 1 was created by Julian Wong.
article_processing_charge: No
author:
- first_name: Alison
full_name: Mungenast, Alison
last_name: Mungenast
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
- first_name: Li
full_name: Tsai, Li
last_name: Tsai
citation:
ama: Mungenast A, Siegert S, Tsai L. Modeling Alzheimer’s disease with human induced
pluripotent stem (iPS) cells. Molecular and Cellular Neuroscience. 2016;73:13-31.
doi:doi:10.1016/j.mcn.2015.11.010
apa: Mungenast, A., Siegert, S., & Tsai, L. (2016). Modeling Alzheimer’s disease
with human induced pluripotent stem (iPS) cells. Molecular and Cellular Neuroscience.
Academic Press. https://doi.org/doi:10.1016/j.mcn.2015.11.010
chicago: Mungenast, Alison, Sandra Siegert, and Li Tsai. “Modeling Alzheimer’s Disease
with Human Induced Pluripotent Stem (IPS) Cells.” Molecular and Cellular Neuroscience.
Academic Press, 2016. https://doi.org/doi:10.1016/j.mcn.2015.11.010.
ieee: A. Mungenast, S. Siegert, and L. Tsai, “Modeling Alzheimer’s disease with
human induced pluripotent stem (iPS) cells,” Molecular and Cellular Neuroscience,
vol. 73. Academic Press, pp. 13–31, 2016.
ista: Mungenast A, Siegert S, Tsai L. 2016. Modeling Alzheimer’s disease with human
induced pluripotent stem (iPS) cells. Molecular and Cellular Neuroscience. 73,
13–31.
mla: Mungenast, Alison, et al. “Modeling Alzheimer’s Disease with Human Induced
Pluripotent Stem (IPS) Cells.” Molecular and Cellular Neuroscience, vol.
73, Academic Press, 2016, pp. 13–31, doi:doi:10.1016/j.mcn.2015.11.010.
short: A. Mungenast, S. Siegert, L. Tsai, Molecular and Cellular Neuroscience 73
(2016) 13–31.
corr_author: '1'
date_created: 2018-12-11T11:53:02Z
date_published: 2016-06-01T00:00:00Z
date_updated: 2025-09-18T10:59:24Z
day: '01'
ddc:
- '616'
doi: doi:10.1016/j.mcn.2015.11.010
extern: '1'
external_id:
isi:
- '000376225300003'
file:
- access_level: open_access
checksum: 620254114e04d5d6e7f37d15e4b8ace4
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:12:50Z
date_updated: 2020-07-14T12:45:07Z
file_id: '4970'
file_name: IST-2018-979-v1+1_Mungenast_2015_acceptedManuscript.pdf
file_size: 632915
relation: main_file
file_date_updated: 2020-07-14T12:45:07Z
has_accepted_license: '1'
intvolume: ' 73'
isi: 1
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '06'
oa: 1
oa_version: Submitted Version
page: 13 - 31
publication: Molecular and Cellular Neuroscience
publication_status: published
publisher: Academic Press
publist_id: '5553'
pubrep_id: '979'
quality_controlled: '1'
status: public
title: Modeling Alzheimer's disease with human induced pluripotent stem (iPS) 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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 73
year: '2016'
...
---
_id: '1616'
abstract:
- lang: eng
text: The hippocampus plays a key role in learning and memory. Previous studies
suggested that the main types of principal neurons, dentate gyrus granule cells
(GCs), CA3 pyramidal neurons, and CA1 pyramidal neurons, differ in their activity
pattern, with sparse firing in GCs and more frequent firing in CA3 and CA1 pyramidal
neurons. It has been assumed but never shown that such different activity may
be caused by differential synaptic excitation. To test this hypothesis, we performed
high-resolution whole-cell patch-clamp recordings in anesthetized rats in vivo.
In contrast to previous in vitro data, both CA3 and CA1 pyramidal neurons fired
action potentials spontaneously, with a frequency of ∼3–6 Hz, whereas GCs were
silent. Furthermore, both CA3 and CA1 cells primarily fired in bursts. To determine
the underlying mechanisms, we quantitatively assessed the frequency of spontaneous
excitatory synaptic input, the passive membrane properties, and the active membrane
characteristics. Surprisingly, GCs showed comparable synaptic excitation to CA3
and CA1 cells and the highest ratio of excitation versus hyperpolarizing inhibition.
Thus, differential synaptic excitation is not responsible for differences in firing.
Moreover, the three types of hippocampal neurons markedly differed in their passive
properties. While GCs showed the most negative membrane potential, CA3 pyramidal
neurons had the highest input resistance and the slowest membrane time constant.
The three types of neurons also differed in the active membrane characteristics.
GCs showed the highest action potential threshold, but displayed the largest gain
of the input-output curves. In conclusion, our results reveal that differential
firing of the three main types of hippocampal principal neurons in vivo is not
primarily caused by differences in the characteristics of the synaptic input,
but by the distinct properties of synaptic integration and input-output transformation.
acknowledgement: "The authors thank Jose Guzman for critically reading prior versions
of the manuscript. They also thank T. Asenov for\r\nengineering mechanical devices,
A. Schlögl for efficient pro-gramming, F. Marr for technical assistance, and E. Kramberger
for manuscript editing."
article_processing_charge: No
author:
- first_name: Janina
full_name: Kowalski, Janina
id: 3F3CA136-F248-11E8-B48F-1D18A9856A87
last_name: Kowalski
- first_name: Jian
full_name: Gan, Jian
id: 3614E438-F248-11E8-B48F-1D18A9856A87
last_name: Gan
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Alejandro
full_name: Pernia-Andrade, Alejandro
id: 36963E98-F248-11E8-B48F-1D18A9856A87
last_name: Pernia-Andrade
citation:
ama: Kowalski J, Gan J, Jonas PM, Pernia-Andrade A. Intrinsic membrane properties
determine hippocampal differential firing pattern in vivo in anesthetized rats.
Hippocampus. 2016;26(5):668-682. doi:10.1002/hipo.22550
apa: Kowalski, J., Gan, J., Jonas, P. M., & Pernia-Andrade, A. (2016). Intrinsic
membrane properties determine hippocampal differential firing pattern in vivo
in anesthetized rats. Hippocampus. Wiley. https://doi.org/10.1002/hipo.22550
chicago: Kowalski, Janina, Jian Gan, Peter M Jonas, and Alejandro Pernia-Andrade.
“Intrinsic Membrane Properties Determine Hippocampal Differential Firing Pattern
in Vivo in Anesthetized Rats.” Hippocampus. Wiley, 2016. https://doi.org/10.1002/hipo.22550.
ieee: J. Kowalski, J. Gan, P. M. Jonas, and A. Pernia-Andrade, “Intrinsic membrane
properties determine hippocampal differential firing pattern in vivo in anesthetized
rats,” Hippocampus, vol. 26, no. 5. Wiley, pp. 668–682, 2016.
ista: Kowalski J, Gan J, Jonas PM, Pernia-Andrade A. 2016. Intrinsic membrane properties
determine hippocampal differential firing pattern in vivo in anesthetized rats.
Hippocampus. 26(5), 668–682.
mla: Kowalski, Janina, et al. “Intrinsic Membrane Properties Determine Hippocampal
Differential Firing Pattern in Vivo in Anesthetized Rats.” Hippocampus,
vol. 26, no. 5, Wiley, 2016, pp. 668–82, doi:10.1002/hipo.22550.
short: J. Kowalski, J. Gan, P.M. Jonas, A. Pernia-Andrade, Hippocampus 26 (2016)
668–682.
corr_author: '1'
date_created: 2018-12-11T11:53:03Z
date_published: 2016-05-01T00:00:00Z
date_updated: 2025-09-18T10:58:31Z
day: '01'
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department:
- _id: PeJo
doi: 10.1002/hipo.22550
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publication: Hippocampus
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title: Intrinsic membrane properties determine hippocampal differential firing pattern
in vivo in anesthetized rats
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