--- _id: '7340' abstract: - lang: eng text: Coupling of endoplasmic reticulum stress to dimerisation‑dependent activation of the UPR transducer IRE1 is incompletely understood. Whilst the luminal co-chaperone ERdj4 promotes a complex between the Hsp70 BiP and IRE1's stress-sensing luminal domain (IRE1LD) that favours the latter's monomeric inactive state and loss of ERdj4 de-represses IRE1, evidence linking these cellular and in vitro observations is presently lacking. We report that enforced loading of endogenous BiP onto endogenous IRE1α repressed UPR signalling in CHO cells and deletions in the IRE1α locus that de-repressed the UPR in cells, encode flexible regions of IRE1LD that mediated BiP‑induced monomerisation in vitro. Changes in the hydrogen exchange mass spectrometry profile of IRE1LD induced by ERdj4 and BiP confirmed monomerisation and were consistent with active destabilisation of the IRE1LD dimer. Together, these observations support a competition model whereby waning ER stress passively partitions ERdj4 and BiP to IRE1LD to initiate active repression of UPR signalling. acknowledgement: We thank the CIMR flow cytometry core facility team (Reiner Schulte, Chiara Cossetti and Gabriela Grondys-Kotarba) for assistance with FACS, the Huntington lab for access to the Octet machine, Steffen Preissler for advice on data interpretation, Roman Kityk and Nicole Luebbehusen for help and advice with HX-MS experiments. article_number: e50793 article_processing_charge: No article_type: original author: - first_name: Niko Paresh full_name: Amin-Wetzel, Niko Paresh id: E95D3014-9D8C-11E9-9C80-D2F8E5697425 last_name: Amin-Wetzel - first_name: Lisa full_name: Neidhardt, Lisa last_name: Neidhardt - first_name: Yahui full_name: Yan, Yahui last_name: Yan - first_name: Matthias P. full_name: Mayer, Matthias P. last_name: Mayer - first_name: David full_name: Ron, David last_name: Ron citation: ama: Amin-Wetzel NP, Neidhardt L, Yan Y, Mayer MP, Ron D. Unstructured regions in IRE1α specify BiP-mediated destabilisation of the luminal domain dimer and repression of the UPR. eLife. 2019;8. doi:10.7554/eLife.50793 apa: Amin-Wetzel, N. P., Neidhardt, L., Yan, Y., Mayer, M. P., & Ron, D. (2019). Unstructured regions in IRE1α specify BiP-mediated destabilisation of the luminal domain dimer and repression of the UPR. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.50793 chicago: Amin-Wetzel, Niko Paresh, Lisa Neidhardt, Yahui Yan, Matthias P. Mayer, and David Ron. “Unstructured Regions in IRE1α Specify BiP-Mediated Destabilisation of the Luminal Domain Dimer and Repression of the UPR.” ELife. eLife Sciences Publications, 2019. https://doi.org/10.7554/eLife.50793. ieee: N. P. Amin-Wetzel, L. Neidhardt, Y. Yan, M. P. Mayer, and D. Ron, “Unstructured regions in IRE1α specify BiP-mediated destabilisation of the luminal domain dimer and repression of the UPR,” eLife, vol. 8. eLife Sciences Publications, 2019. ista: Amin-Wetzel NP, Neidhardt L, Yan Y, Mayer MP, Ron D. 2019. Unstructured regions in IRE1α specify BiP-mediated destabilisation of the luminal domain dimer and repression of the UPR. eLife. 8, e50793. mla: Amin-Wetzel, Niko Paresh, et al. “Unstructured Regions in IRE1α Specify BiP-Mediated Destabilisation of the Luminal Domain Dimer and Repression of the UPR.” ELife, vol. 8, e50793, eLife Sciences Publications, 2019, doi:10.7554/eLife.50793. short: N.P. Amin-Wetzel, L. Neidhardt, Y. Yan, M.P. Mayer, D. Ron, ELife 8 (2019). date_created: 2020-01-19T23:00:39Z date_published: 2019-12-24T00:00:00Z date_updated: 2023-09-06T14:58:02Z day: '24' ddc: - '570' department: - _id: MaDe doi: 10.7554/eLife.50793 external_id: isi: - '000512303700001' pmid: - '31873072' file: - access_level: open_access checksum: 29fcbcd8c1fc7f11a596ed7f14ea1c82 content_type: application/pdf creator: dernst date_created: 2020-11-19T11:37:41Z date_updated: 2020-11-19T11:37:41Z file_id: '8777' file_name: 2019_eLife_AminWetzel.pdf file_size: 4817384 relation: main_file success: 1 file_date_updated: 2020-11-19T11:37:41Z has_accepted_license: '1' intvolume: ' 8' isi: 1 language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '12' oa: 1 oa_version: Published Version pmid: 1 publication: eLife publication_identifier: eissn: - 2050084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: Unstructured regions in IRE1α specify BiP-mediated destabilisation of the luminal domain dimer and repression of the UPR 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 8 year: '2019' ... --- _id: '7422' abstract: - lang: eng text: Biochemical reactions often occur at low copy numbers but at once in crowded and diverse environments. Space and stochasticity therefore play an essential role in biochemical networks. Spatial-stochastic simulations have become a prominent tool for understanding how stochasticity at the microscopic level influences the macroscopic behavior of such systems. While particle-based models guarantee the level of detail necessary to accurately describe the microscopic dynamics at very low copy numbers, the algorithms used to simulate them typically imply trade-offs between computational efficiency and biochemical accuracy. eGFRD (enhanced Green’s Function Reaction Dynamics) is an exact algorithm that evades such trade-offs by partitioning the N-particle system into M ≤ N analytically tractable one- and two-particle systems; the analytical solutions (Green’s functions) then are used to implement an event-driven particle-based scheme that allows particles to make large jumps in time and space while retaining access to their state variables at arbitrary simulation times. Here we present “eGFRD2,” a new eGFRD version that implements the principle of eGFRD in all dimensions, thus enabling efficient particle-based simulation of biochemical reaction-diffusion processes in the 3D cytoplasm, on 2D planes representing membranes, and on 1D elongated cylinders representative of, e.g., cytoskeletal tracks or DNA; in 1D, it also incorporates convective motion used to model active transport. We find that, for low particle densities, eGFRD2 is up to 6 orders of magnitude faster than conventional Brownian dynamics. We exemplify the capabilities of eGFRD2 by simulating an idealized model of Pom1 gradient formation, which involves 3D diffusion, active transport on microtubules, and autophosphorylation on the membrane, confirming recent experimental and theoretical results on this system to hold under genuinely stochastic conditions. article_number: '054108' article_processing_charge: No article_type: original author: - first_name: Thomas R full_name: Sokolowski, Thomas R id: 3E999752-F248-11E8-B48F-1D18A9856A87 last_name: Sokolowski orcid: 0000-0002-1287-3779 - first_name: Joris full_name: Paijmans, Joris last_name: Paijmans - first_name: Laurens full_name: Bossen, Laurens last_name: Bossen - first_name: Thomas full_name: Miedema, Thomas last_name: Miedema - first_name: Martijn full_name: Wehrens, Martijn last_name: Wehrens - first_name: Nils B. full_name: Becker, Nils B. last_name: Becker - first_name: Kazunari full_name: Kaizu, Kazunari last_name: Kaizu - first_name: Koichi full_name: Takahashi, Koichi last_name: Takahashi - first_name: Marileen full_name: Dogterom, Marileen last_name: Dogterom - first_name: Pieter Rein full_name: ten Wolde, Pieter Rein last_name: ten Wolde citation: ama: Sokolowski TR, Paijmans J, Bossen L, et al. eGFRD in all dimensions. The Journal of Chemical Physics. 2019;150(5). doi:10.1063/1.5064867 apa: Sokolowski, T. R., Paijmans, J., Bossen, L., Miedema, T., Wehrens, M., Becker, N. B., … ten Wolde, P. R. (2019). eGFRD in all dimensions. The Journal of Chemical Physics. AIP Publishing. https://doi.org/10.1063/1.5064867 chicago: Sokolowski, Thomas R, Joris Paijmans, Laurens Bossen, Thomas Miedema, Martijn Wehrens, Nils B. Becker, Kazunari Kaizu, Koichi Takahashi, Marileen Dogterom, and Pieter Rein ten Wolde. “EGFRD in All Dimensions.” The Journal of Chemical Physics. AIP Publishing, 2019. https://doi.org/10.1063/1.5064867. ieee: T. R. Sokolowski et al., “eGFRD in all dimensions,” The Journal of Chemical Physics, vol. 150, no. 5. AIP Publishing, 2019. ista: Sokolowski TR, Paijmans J, Bossen L, Miedema T, Wehrens M, Becker NB, Kaizu K, Takahashi K, Dogterom M, ten Wolde PR. 2019. eGFRD in all dimensions. The Journal of Chemical Physics. 150(5), 054108. mla: Sokolowski, Thomas R., et al. “EGFRD in All Dimensions.” The Journal of Chemical Physics, vol. 150, no. 5, 054108, AIP Publishing, 2019, doi:10.1063/1.5064867. short: T.R. Sokolowski, J. Paijmans, L. Bossen, T. Miedema, M. Wehrens, N.B. Becker, K. Kaizu, K. Takahashi, M. Dogterom, P.R. ten Wolde, The Journal of Chemical Physics 150 (2019). date_created: 2020-01-30T10:34:36Z date_published: 2019-02-07T00:00:00Z date_updated: 2023-09-06T14:59:28Z day: '07' department: - _id: GaTk doi: 10.1063/1.5064867 external_id: arxiv: - '1708.09364' isi: - '000458109300009' intvolume: ' 150' isi: 1 issue: '5' language: - iso: eng main_file_link: - open_access: '1' url: https://arxiv.org/abs/1708.09364 month: '02' oa: 1 oa_version: Preprint publication: The Journal of Chemical Physics publication_identifier: eissn: - 1089-7690 issn: - 0021-9606 publication_status: published publisher: AIP Publishing quality_controlled: '1' status: public title: eGFRD in all dimensions type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 150 year: '2019' ... --- _id: '7230' abstract: - lang: eng text: Simple drawings of graphs are those in which each pair of edges share at most one point, either a common endpoint or a proper crossing. In this paper we study the problem of extending a simple drawing D(G) of a graph G by inserting a set of edges from the complement of G into D(G) such that the result is a simple drawing. In the context of rectilinear drawings, the problem is trivial. For pseudolinear drawings, the existence of such an extension follows from Levi’s enlargement lemma. In contrast, we prove that deciding if a given set of edges can be inserted into a simple drawing is NP-complete. Moreover, we show that the maximization version of the problem is APX-hard. We also present a polynomial-time algorithm for deciding whether one edge uv can be inserted into D(G) when {u,v} is a dominating set for the graph G. alternative_title: - LNCS article_processing_charge: No author: - first_name: Alan M full_name: Arroyo Guevara, Alan M id: 3207FDC6-F248-11E8-B48F-1D18A9856A87 last_name: Arroyo Guevara orcid: 0000-0003-2401-8670 - first_name: Martin full_name: Derka, Martin last_name: Derka - first_name: Irene full_name: Parada, Irene last_name: Parada citation: ama: 'Arroyo Guevara AM, Derka M, Parada I. Extending simple drawings. In: 27th International Symposium on Graph Drawing and Network Visualization. Vol 11904. Springer Nature; 2019:230-243. doi:10.1007/978-3-030-35802-0_18' apa: 'Arroyo Guevara, A. M., Derka, M., & Parada, I. (2019). Extending simple drawings. In 27th International Symposium on Graph Drawing and Network Visualization (Vol. 11904, pp. 230–243). Prague, Czech Republic: Springer Nature. https://doi.org/10.1007/978-3-030-35802-0_18' chicago: Arroyo Guevara, Alan M, Martin Derka, and Irene Parada. “Extending Simple Drawings.” In 27th International Symposium on Graph Drawing and Network Visualization, 11904:230–43. Springer Nature, 2019. https://doi.org/10.1007/978-3-030-35802-0_18. ieee: A. M. Arroyo Guevara, M. Derka, and I. Parada, “Extending simple drawings,” in 27th International Symposium on Graph Drawing and Network Visualization, Prague, Czech Republic, 2019, vol. 11904, pp. 230–243. ista: 'Arroyo Guevara AM, Derka M, Parada I. 2019. Extending simple drawings. 27th International Symposium on Graph Drawing and Network Visualization. GD: Graph Drawing and Network Visualization, LNCS, vol. 11904, 230–243.' mla: Arroyo Guevara, Alan M., et al. “Extending Simple Drawings.” 27th International Symposium on Graph Drawing and Network Visualization, vol. 11904, Springer Nature, 2019, pp. 230–43, doi:10.1007/978-3-030-35802-0_18. short: A.M. Arroyo Guevara, M. Derka, I. Parada, in:, 27th International Symposium on Graph Drawing and Network Visualization, Springer Nature, 2019, pp. 230–243. conference: end_date: 2019-09-20 location: Prague, Czech Republic name: 'GD: Graph Drawing and Network Visualization' start_date: 2019-09-17 date_created: 2020-01-05T23:00:47Z date_published: 2019-11-28T00:00:00Z date_updated: 2023-09-06T14:56:00Z day: '28' department: - _id: UlWa doi: 10.1007/978-3-030-35802-0_18 ec_funded: 1 external_id: arxiv: - '1908.08129' isi: - '000612918800018' intvolume: ' 11904' isi: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://arxiv.org/abs/1908.08129 month: '11' oa: 1 oa_version: Preprint page: 230-243 project: - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships publication: 27th International Symposium on Graph Drawing and Network Visualization publication_identifier: eissn: - 1611-3349 isbn: - 978-3-0303-5801-3 issn: - 0302-9743 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Extending simple drawings type: conference user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 11904 year: '2019' ... --- _id: '7232' abstract: - lang: eng text: 'We present Mixed-time Signal Temporal Logic (STL−MX), a specification formalism which extends STL by capturing the discrete/ continuous time duality found in many cyber-physical systems (CPS), as well as mixed-signal electronic designs. In STL−MX, properties of components with continuous dynamics are expressed in STL, while specifications of components with discrete dynamics are written in LTL. To combine the two layers, we evaluate formulas on two traces, discrete- and continuous-time, and introduce two interface operators that map signals, properties and their satisfaction signals across the two time domains. We show that STL-mx has the expressive power of STL supplemented with an implicit T-periodic clock signal. We develop and implement an algorithm for monitoring STL-mx formulas and illustrate the approach using a mixed-signal example. ' alternative_title: - LNCS article_processing_charge: No author: - first_name: Thomas full_name: Ferrere, Thomas id: 40960E6E-F248-11E8-B48F-1D18A9856A87 last_name: Ferrere orcid: 0000-0001-5199-3143 - first_name: Oded full_name: Maler, Oded last_name: Maler - first_name: Dejan full_name: Nickovic, Dejan id: 41BCEE5C-F248-11E8-B48F-1D18A9856A87 last_name: Nickovic citation: ama: 'Ferrere T, Maler O, Nickovic D. Mixed-time signal temporal logic. In: 17th International Conference on Formal Modeling and Analysis of Timed Systems. Vol 11750. Springer Nature; 2019:59-75. doi:10.1007/978-3-030-29662-9_4' apa: 'Ferrere, T., Maler, O., & Nickovic, D. (2019). Mixed-time signal temporal logic. In 17th International Conference on Formal Modeling and Analysis of Timed Systems (Vol. 11750, pp. 59–75). Amsterdam, The Netherlands: Springer Nature. https://doi.org/10.1007/978-3-030-29662-9_4' chicago: Ferrere, Thomas, Oded Maler, and Dejan Nickovic. “Mixed-Time Signal Temporal Logic.” In 17th International Conference on Formal Modeling and Analysis of Timed Systems, 11750:59–75. Springer Nature, 2019. https://doi.org/10.1007/978-3-030-29662-9_4. ieee: T. Ferrere, O. Maler, and D. Nickovic, “Mixed-time signal temporal logic,” in 17th International Conference on Formal Modeling and Analysis of Timed Systems, Amsterdam, The Netherlands, 2019, vol. 11750, pp. 59–75. ista: 'Ferrere T, Maler O, Nickovic D. 2019. Mixed-time signal temporal logic. 17th International Conference on Formal Modeling and Analysis of Timed Systems. FORMATS: Formal Modeling and Anaysis of Timed Systems, LNCS, vol. 11750, 59–75.' mla: Ferrere, Thomas, et al. “Mixed-Time Signal Temporal Logic.” 17th International Conference on Formal Modeling and Analysis of Timed Systems, vol. 11750, Springer Nature, 2019, pp. 59–75, doi:10.1007/978-3-030-29662-9_4. short: T. Ferrere, O. Maler, D. Nickovic, in:, 17th International Conference on Formal Modeling and Analysis of Timed Systems, Springer Nature, 2019, pp. 59–75. conference: end_date: 2019-08-29 location: Amsterdam, The Netherlands name: 'FORMATS: Formal Modeling and Anaysis of Timed Systems' start_date: 2019-08-27 date_created: 2020-01-05T23:00:48Z date_published: 2019-08-13T00:00:00Z date_updated: 2023-09-06T14:57:17Z day: '13' department: - _id: ToHe doi: 10.1007/978-3-030-29662-9_4 external_id: isi: - '000611677700004' intvolume: ' 11750' isi: 1 language: - iso: eng month: '08' oa_version: None page: 59-75 project: - _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: The Wittgenstein Prize publication: 17th International Conference on Formal Modeling and Analysis of Timed Systems publication_identifier: eissn: - 1611-3349 isbn: - 978-3-0302-9661-2 issn: - 0302-9743 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Mixed-time signal temporal logic type: conference user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 11750 year: '2019' ... --- _id: '7420' abstract: - lang: eng text: β1-integrins mediate cell–matrix interactions and their trafficking is important in the dynamic regulation of cell adhesion, migration and malignant processes, including cancer cell invasion. Here, we employ an RNAi screen to characterize regulators of integrin traffic and identify the association of Golgi-localized gamma ear-containing Arf-binding protein 2 (GGA2) with β1-integrin, and its role in recycling of active but not inactive β1-integrin receptors. Silencing of GGA2 limits active β1-integrin levels in focal adhesions and decreases cancer cell migration and invasion, which is in agreement with its ability to regulate the dynamics of active integrins. By using the proximity-dependent biotin identification (BioID) method, we identified two RAB family small GTPases, i.e. RAB13 and RAB10, as novel interactors of GGA2. Functionally, RAB13 silencing triggers the intracellular accumulation of active β1-integrin, and reduces integrin activity in focal adhesions and cell migration similarly to GGA2 depletion, indicating that both facilitate active β1-integrin recycling to the plasma membrane. Thus, GGA2 and RAB13 are important specificity determinants for integrin activity-dependent traffic. article_number: jcs233387 article_processing_charge: No article_type: original author: - first_name: Pranshu full_name: Sahgal, Pranshu last_name: Sahgal - first_name: Jonna H full_name: Alanko, Jonna H id: 2CC12E8C-F248-11E8-B48F-1D18A9856A87 last_name: Alanko orcid: 0000-0002-7698-3061 - first_name: Jaroslav full_name: Icha, Jaroslav last_name: Icha - first_name: Ilkka full_name: Paatero, Ilkka last_name: Paatero - first_name: Hellyeh full_name: Hamidi, Hellyeh last_name: Hamidi - first_name: Antti full_name: Arjonen, Antti last_name: Arjonen - first_name: Mika full_name: Pietilä, Mika last_name: Pietilä - first_name: Anne full_name: Rokka, Anne last_name: Rokka - first_name: Johanna full_name: Ivaska, Johanna last_name: Ivaska citation: ama: Sahgal P, Alanko JH, Icha J, et al. GGA2 and RAB13 promote activity-dependent β1-integrin recycling. Journal of Cell Science. 2019;132(11). doi:10.1242/jcs.233387 apa: Sahgal, P., Alanko, J. H., Icha, J., Paatero, I., Hamidi, H., Arjonen, A., … Ivaska, J. (2019). GGA2 and RAB13 promote activity-dependent β1-integrin recycling. Journal of Cell Science. The Company of Biologists. https://doi.org/10.1242/jcs.233387 chicago: Sahgal, Pranshu, Jonna H Alanko, Jaroslav Icha, Ilkka Paatero, Hellyeh Hamidi, Antti Arjonen, Mika Pietilä, Anne Rokka, and Johanna Ivaska. “GGA2 and RAB13 Promote Activity-Dependent Β1-Integrin Recycling.” Journal of Cell Science. The Company of Biologists, 2019. https://doi.org/10.1242/jcs.233387. ieee: P. Sahgal et al., “GGA2 and RAB13 promote activity-dependent β1-integrin recycling,” Journal of Cell Science, vol. 132, no. 11. The Company of Biologists, 2019. ista: Sahgal P, Alanko JH, Icha J, Paatero I, Hamidi H, Arjonen A, Pietilä M, Rokka A, Ivaska J. 2019. GGA2 and RAB13 promote activity-dependent β1-integrin recycling. Journal of Cell Science. 132(11), jcs233387. mla: Sahgal, Pranshu, et al. “GGA2 and RAB13 Promote Activity-Dependent Β1-Integrin Recycling.” Journal of Cell Science, vol. 132, no. 11, jcs233387, The Company of Biologists, 2019, doi:10.1242/jcs.233387. short: P. Sahgal, J.H. Alanko, J. Icha, I. Paatero, H. Hamidi, A. Arjonen, M. Pietilä, A. Rokka, J. Ivaska, Journal of Cell Science 132 (2019). date_created: 2020-01-30T10:31:42Z date_published: 2019-06-07T00:00:00Z date_updated: 2023-09-06T15:01:00Z day: '07' department: - _id: MiSi doi: 10.1242/jcs.233387 external_id: isi: - '000473327900017' pmid: - '31076515' intvolume: ' 132' isi: 1 issue: '11' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1242/jcs.233387 month: '06' oa: 1 oa_version: Published Version pmid: 1 publication: Journal of Cell Science publication_identifier: eissn: - 1477-9137 issn: - 0021-9533 publication_status: published publisher: The Company of Biologists quality_controlled: '1' status: public title: GGA2 and RAB13 promote activity-dependent β1-integrin recycling type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 132 year: '2019' ...