--- _id: '7783' abstract: - lang: eng text: The Drosophila Genetic Reference Panel (DGRP) serves as a valuable resource to better understand the genetic landscapes underlying quantitative traits. However, such DGRP studies have so far only focused on nuclear genetic variants. To address this, we sequenced the mitochondrial genomes of >170 DGRP lines, identifying 229 variants including 21 indels and 7 frameshifts. We used our mitochondrial variation data to identify 12 genetically distinct mitochondrial haplotypes, thus revealing important population structure at the mitochondrial level. We further examined whether this population structure was reflected on the nuclear genome by screening for the presence of potential mito-nuclear genetic incompatibilities in the form of significant genotype ratio distortions (GRDs) between mitochondrial and nuclear variants. In total, we detected a remarkable 1,845 mito-nuclear GRDs, with the highest enrichment observed in a 40 kb region around the gene Sex-lethal (Sxl). Intriguingly, downstream phenotypic analyses did not uncover major fitness effects associated with these GRDs, suggesting that a large number of mito-nuclear GRDs may reflect population structure at the mitochondrial level rather than actual genomic incompatibilities. This is further supported by the GRD landscape showing particular large genomic regions associated with a single mitochondrial haplotype. Next, we explored the functional relevance of the detected mitochondrial haplotypes through an association analysis on a set of 259 assembled, non-correlating DGRP phenotypes. We found multiple significant associations with stress- and metabolism-related phenotypes, including food intake in males. We validated the latter observation by reciprocal swapping of mitochondrial genomes from high food intake DGRP lines to low food intake ones. In conclusion, our study uncovered important mitochondrial population structure and haplotype-specific metabolic variation in the DGRP, thus demonstrating the significance of incorporating mitochondrial haplotypes in geno-phenotype relationship studies. article_processing_charge: No author: - first_name: Roel P.J. full_name: Bevers, Roel P.J. last_name: Bevers - first_name: Maria full_name: Litovchenko, Maria last_name: Litovchenko - first_name: Adamandia full_name: Kapopoulou, Adamandia last_name: Kapopoulou - first_name: Virginie S. full_name: Braman, Virginie S. last_name: Braman - first_name: Matthew Richard full_name: Robinson, Matthew Richard id: E5D42276-F5DA-11E9-8E24-6303E6697425 last_name: Robinson orcid: 0000-0001-8982-8813 - first_name: Johan full_name: Auwerx, Johan last_name: Auwerx - first_name: Brian full_name: Hollis, Brian last_name: Hollis - first_name: Bart full_name: Deplancke, Bart last_name: Deplancke citation: ama: Bevers RPJ, Litovchenko M, Kapopoulou A, et al. Extensive mitochondrial population structure and haplotype-specific phenotypic variation in the Drosophila Genetic Reference Panel. bioRxiv. 2018. apa: Bevers, R. P. J., Litovchenko, M., Kapopoulou, A., Braman, V. S., Robinson, M. R., Auwerx, J., … Deplancke, B. (2018). Extensive mitochondrial population structure and haplotype-specific phenotypic variation in the Drosophila Genetic Reference Panel. bioRxiv. Cold Spring Harbor Laboratory. chicago: Bevers, Roel P.J., Maria Litovchenko, Adamandia Kapopoulou, Virginie S. Braman, Matthew Richard Robinson, Johan Auwerx, Brian Hollis, and Bart Deplancke. “Extensive Mitochondrial Population Structure and Haplotype-Specific Phenotypic Variation in the Drosophila Genetic Reference Panel.” BioRxiv. Cold Spring Harbor Laboratory, 2018. ieee: R. P. J. Bevers et al., “Extensive mitochondrial population structure and haplotype-specific phenotypic variation in the Drosophila Genetic Reference Panel,” bioRxiv. Cold Spring Harbor Laboratory, 2018. ista: Bevers RPJ, Litovchenko M, Kapopoulou A, Braman VS, Robinson MR, Auwerx J, Hollis B, Deplancke B. 2018. Extensive mitochondrial population structure and haplotype-specific phenotypic variation in the Drosophila Genetic Reference Panel. bioRxiv, . mla: Bevers, Roel P. J., et al. “Extensive Mitochondrial Population Structure and Haplotype-Specific Phenotypic Variation in the Drosophila Genetic Reference Panel.” BioRxiv, Cold Spring Harbor Laboratory, 2018. short: R.P.J. Bevers, M. Litovchenko, A. Kapopoulou, V.S. Braman, M.R. Robinson, J. Auwerx, B. Hollis, B. Deplancke, BioRxiv (2018). date_created: 2020-04-30T13:09:37Z date_published: 2018-11-09T00:00:00Z date_updated: 2021-01-12T08:15:30Z day: '09' extern: '1' language: - iso: eng main_file_link: - open_access: '1' url: 'https://doi.org/10.1101/466771 ' month: '11' oa: 1 oa_version: Preprint page: '49' publication: bioRxiv publication_status: published publisher: Cold Spring Harbor Laboratory status: public title: Extensive mitochondrial population structure and haplotype-specific phenotypic variation in the Drosophila Genetic Reference Panel type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2018' ... --- _id: '6001' abstract: - lang: eng text: "The concurrent memory reclamation problem is that of devising a way for a deallocating thread to verify that no other concurrent threads hold references to a memory block being deallocated. To date, in the absence of automatic garbage collection, there is no satisfactory solution to this problem; existing tracking methods like hazard pointers, reference counters, or epoch-based techniques like RCU are either prohibitively expensive or require significant programming expertise to the extent that implementing them efficiently can be worthy of a publication. None of the existing techniques are automatic or even semi-automated.\r\nIn this article, we take a new approach to concurrent memory reclamation. Instead of manually tracking access to memory locations as done in techniques like hazard pointers, or restricting shared accesses to specific epoch boundaries as in RCU, our algorithm, called ThreadScan, leverages operating system signaling to automatically detect which memory locations are being accessed by concurrent threads.\r\nInitial empirical evidence shows that ThreadScan scales surprisingly well and requires negligible programming effort beyond the standard use of Malloc and Free." article_number: '18' author: - first_name: Dan-Adrian full_name: Alistarh, Dan-Adrian id: 4A899BFC-F248-11E8-B48F-1D18A9856A87 last_name: Alistarh orcid: 0000-0003-3650-940X - first_name: William full_name: Leiserson, William last_name: Leiserson - first_name: Alexander full_name: Matveev, Alexander last_name: Matveev - first_name: Nir full_name: Shavit, Nir last_name: Shavit citation: ama: 'Alistarh D-A, Leiserson W, Matveev A, Shavit N. ThreadScan: Automatic and scalable memory reclamation. ACM Transactions on Parallel Computing. 2018;4(4). doi:10.1145/3201897' apa: 'Alistarh, D.-A., Leiserson, W., Matveev, A., & Shavit, N. (2018). ThreadScan: Automatic and scalable memory reclamation. ACM Transactions on Parallel Computing. Association for Computing Machinery. https://doi.org/10.1145/3201897' chicago: 'Alistarh, Dan-Adrian, William Leiserson, Alexander Matveev, and Nir Shavit. “ThreadScan: Automatic and Scalable Memory Reclamation.” ACM Transactions on Parallel Computing. Association for Computing Machinery, 2018. https://doi.org/10.1145/3201897.' ieee: 'D.-A. Alistarh, W. Leiserson, A. Matveev, and N. Shavit, “ThreadScan: Automatic and scalable memory reclamation,” ACM Transactions on Parallel Computing, vol. 4, no. 4. Association for Computing Machinery, 2018.' ista: 'Alistarh D-A, Leiserson W, Matveev A, Shavit N. 2018. ThreadScan: Automatic and scalable memory reclamation. ACM Transactions on Parallel Computing. 4(4), 18.' mla: 'Alistarh, Dan-Adrian, et al. “ThreadScan: Automatic and Scalable Memory Reclamation.” ACM Transactions on Parallel Computing, vol. 4, no. 4, 18, Association for Computing Machinery, 2018, doi:10.1145/3201897.' short: D.-A. Alistarh, W. Leiserson, A. Matveev, N. Shavit, ACM Transactions on Parallel Computing 4 (2018). date_created: 2019-02-14T13:24:11Z date_published: 2018-09-01T00:00:00Z date_updated: 2023-02-23T13:17:54Z day: '01' department: - _id: DaAl doi: 10.1145/3201897 intvolume: ' 4' issue: '4' language: - iso: eng month: '09' oa_version: None publication: ACM Transactions on Parallel Computing publication_identifier: issn: - 2329-4949 publication_status: published publisher: Association for Computing Machinery quality_controlled: '1' related_material: record: - id: '779' relation: earlier_version status: public scopus_import: 1 status: public title: 'ThreadScan: Automatic and scalable memory reclamation' type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 4 year: '2018' ... --- _id: '7812' abstract: - lang: eng text: Deep neural networks (DNNs) continue to make significant advances, solving tasks from image classification to translation or reinforcement learning. One aspect of the field receiving considerable attention is efficiently executing deep models in resource-constrained environments, such as mobile or embedded devices. This paper focuses on this problem, and proposes two new compression methods, which jointly leverage weight quantization and distillation of larger teacher networks into smaller student networks. The first method we propose is called quantized distillation and leverages distillation during the training process, by incorporating distillation loss, expressed with respect to the teacher, into the training of a student network whose weights are quantized to a limited set of levels. The second method, differentiable quantization, optimizes the location of quantization points through stochastic gradient descent, to better fit the behavior of the teacher model. We validate both methods through experiments on convolutional and recurrent architectures. We show that quantized shallow students can reach similar accuracy levels to full-precision teacher models, while providing order of magnitude compression, and inference speedup that is linear in the depth reduction. In sum, our results enable DNNs for resource-constrained environments to leverage architecture and accuracy advances developed on more powerful devices. article_processing_charge: No author: - first_name: Antonio full_name: Polino, Antonio last_name: Polino - first_name: Razvan full_name: Pascanu, Razvan last_name: Pascanu - first_name: Dan-Adrian full_name: Alistarh, Dan-Adrian id: 4A899BFC-F248-11E8-B48F-1D18A9856A87 last_name: Alistarh orcid: 0000-0003-3650-940X citation: ama: 'Polino A, Pascanu R, Alistarh D-A. Model compression via distillation and quantization. In: 6th International Conference on Learning Representations. ; 2018.' apa: Polino, A., Pascanu, R., & Alistarh, D.-A. (2018). Model compression via distillation and quantization. In 6th International Conference on Learning Representations. Vancouver, Canada. chicago: Polino, Antonio, Razvan Pascanu, and Dan-Adrian Alistarh. “Model Compression via Distillation and Quantization.” In 6th International Conference on Learning Representations, 2018. ieee: A. Polino, R. Pascanu, and D.-A. Alistarh, “Model compression via distillation and quantization,” in 6th International Conference on Learning Representations, Vancouver, Canada, 2018. ista: 'Polino A, Pascanu R, Alistarh D-A. 2018. Model compression via distillation and quantization. 6th International Conference on Learning Representations. ICLR: International Conference on Learning Representations.' mla: Polino, Antonio, et al. “Model Compression via Distillation and Quantization.” 6th International Conference on Learning Representations, 2018. short: A. Polino, R. Pascanu, D.-A. Alistarh, in:, 6th International Conference on Learning Representations, 2018. conference: end_date: 2018-05-03 location: Vancouver, Canada name: 'ICLR: International Conference on Learning Representations' start_date: 2018-04-30 date_created: 2020-05-10T22:00:51Z date_published: 2018-05-01T00:00:00Z date_updated: 2023-02-23T13:18:41Z day: '01' ddc: - '000' department: - _id: DaAl external_id: arxiv: - '1802.05668' file: - access_level: open_access checksum: a4336c167978e81891970e4e4517a8c3 content_type: application/pdf creator: dernst date_created: 2020-05-26T13:02:00Z date_updated: 2020-07-14T12:48:03Z file_id: '7894' file_name: 2018_ICLR_Polino.pdf file_size: 308339 relation: main_file file_date_updated: 2020-07-14T12:48:03Z has_accepted_license: '1' language: - iso: eng month: '05' oa: 1 oa_version: Published Version publication: 6th International Conference on Learning Representations publication_status: published quality_controlled: '1' scopus_import: 1 status: public title: Model compression via distillation and quantization type: conference user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2018' ... --- _id: '7983' abstract: - lang: ger text: 'Feste Alkalicarbonate sind universelle Bestandteile von Passivierungsschichten an Materialien für Interkalationsbatterien, übliche Nebenprodukte in Metall‐O2‐Batterien, und es wird angenommen, dass sie sich reversibel in Metall‐O2 /CO2‐Zellen bilden und zersetzen. In all diesen Kathoden zersetzt sich Li2CO3 zu CO2, sobald es Spannungen >3.8 V vs. Li/Li+ ausgesetzt wird. Beachtenswert ist, dass keine O2‐Entwicklung detektiert wird, wie gemäß der Zersetzungsreaktion 2 Li2CO3 → 4 Li+ + 4 e− + 2 CO2 + O2 zu erwarten wäre. Deswegen war der Verbleib eines der O‐Atome ungeklärt und wurde nicht identifizierten parasitären Reaktionen zugerechnet. Hier zeigen wir, dass hochreaktiver Singulett‐Sauerstoff (1O2) bei der Oxidation von Li2CO3 in einem aprotischen Elektrolyten gebildet und daher nicht als O2 freigesetzt wird. Diese Ergebnisse haben weitreichende Auswirkungen auf die langfristige Zyklisierbarkeit von Batterien: sie untermauern die Wichtigkeit, 1O2 in Metall‐O2‐Batterien zu verhindern, stellen die Möglichkeit einer reversiblen Metall‐O2 /CO2‐Batterie basierend auf einem Carbonat‐Entladeprodukt in Frage und helfen, Grenzflächenreaktivität von Übergangsmetallkathoden mit Li2CO3‐Resten zu erklären.' article_processing_charge: No article_type: original author: - first_name: Nika full_name: Mahne, Nika last_name: Mahne - first_name: Sara E. full_name: Renfrew, Sara E. last_name: Renfrew - first_name: Bryan D. full_name: McCloskey, Bryan D. last_name: McCloskey - first_name: Stefan Alexander full_name: Freunberger, Stefan Alexander id: A8CA28E6-CE23-11E9-AD2D-EC27E6697425 last_name: Freunberger orcid: 0000-0003-2902-5319 citation: ama: Mahne N, Renfrew SE, McCloskey BD, Freunberger SA. Elektrochemische Oxidation von Lithiumcarbonat generiert Singulett-Sauerstoff. Angewandte Chemie. 2018;130(19):5627-5631. doi:10.1002/ange.201802277 apa: Mahne, N., Renfrew, S. E., McCloskey, B. D., & Freunberger, S. A. (2018). Elektrochemische Oxidation von Lithiumcarbonat generiert Singulett-Sauerstoff. Angewandte Chemie. Wiley. https://doi.org/10.1002/ange.201802277 chicago: Mahne, Nika, Sara E. Renfrew, Bryan D. McCloskey, and Stefan Alexander Freunberger. “Elektrochemische Oxidation von Lithiumcarbonat Generiert Singulett-Sauerstoff.” Angewandte Chemie. Wiley, 2018. https://doi.org/10.1002/ange.201802277. ieee: N. Mahne, S. E. Renfrew, B. D. McCloskey, and S. A. Freunberger, “Elektrochemische Oxidation von Lithiumcarbonat generiert Singulett-Sauerstoff,” Angewandte Chemie, vol. 130, no. 19. Wiley, pp. 5627–5631, 2018. ista: Mahne N, Renfrew SE, McCloskey BD, Freunberger SA. 2018. Elektrochemische Oxidation von Lithiumcarbonat generiert Singulett-Sauerstoff. Angewandte Chemie. 130(19), 5627–5631. mla: Mahne, Nika, et al. “Elektrochemische Oxidation von Lithiumcarbonat Generiert Singulett-Sauerstoff.” Angewandte Chemie, vol. 130, no. 19, Wiley, 2018, pp. 5627–31, doi:10.1002/ange.201802277. short: N. Mahne, S.E. Renfrew, B.D. McCloskey, S.A. Freunberger, Angewandte Chemie 130 (2018) 5627–5631. date_created: 2020-06-19T08:33:24Z date_published: 2018-05-04T00:00:00Z date_updated: 2021-01-12T08:16:21Z day: '04' ddc: - '540' doi: 10.1002/ange.201802277 extern: '1' file: - access_level: open_access checksum: 81506e0f7079e1e3591f3cd9f626bf67 content_type: application/pdf creator: dernst date_created: 2020-06-19T11:58:06Z date_updated: 2020-07-14T12:48:06Z file_id: '7988' file_name: 2018_AngChemieDT_Mahne.pdf file_size: 674789 relation: main_file file_date_updated: 2020-07-14T12:48:06Z has_accepted_license: '1' intvolume: ' 130' issue: '19' language: - iso: eng month: '05' oa: 1 oa_version: Published Version page: 5627-5631 publication: Angewandte Chemie publication_identifier: issn: - 0044-8249 publication_status: published publisher: Wiley quality_controlled: '1' status: public title: Elektrochemische Oxidation von Lithiumcarbonat generiert Singulett-Sauerstoff 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 130 year: '2018' ... --- _id: '8015' abstract: - lang: eng text: 'The neural code of cortical processing remains uncracked; however, it must necessarily rely on faithful signal propagation between cortical areas. In this issue of Neuron, Joglekar et al. (2018) show that strong inter-areal excitation balanced by local inhibition can enable reliable signal propagation in data-constrained network models of macaque cortex. ' article_processing_charge: No article_type: original author: - first_name: Jake P. full_name: Stroud, Jake P. last_name: Stroud - first_name: Tim P full_name: Vogels, Tim P id: CB6FF8D2-008F-11EA-8E08-2637E6697425 last_name: Vogels orcid: 0000-0003-3295-6181 citation: ama: 'Stroud JP, Vogels TP. Cortical signal propagation: Balance, amplify, transmit. Neuron. 2018;98(1):8-9. doi:10.1016/j.neuron.2018.03.028' apa: 'Stroud, J. P., & Vogels, T. P. (2018). Cortical signal propagation: Balance, amplify, transmit. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2018.03.028' chicago: 'Stroud, Jake P., and Tim P Vogels. “Cortical Signal Propagation: Balance, Amplify, Transmit.” Neuron. Elsevier, 2018. https://doi.org/10.1016/j.neuron.2018.03.028.' ieee: 'J. P. Stroud and T. P. Vogels, “Cortical signal propagation: Balance, amplify, transmit,” Neuron, vol. 98, no. 1. Elsevier, pp. 8–9, 2018.' ista: 'Stroud JP, Vogels TP. 2018. Cortical signal propagation: Balance, amplify, transmit. Neuron. 98(1), 8–9.' mla: 'Stroud, Jake P., and Tim P. Vogels. “Cortical Signal Propagation: Balance, Amplify, Transmit.” Neuron, vol. 98, no. 1, Elsevier, 2018, pp. 8–9, doi:10.1016/j.neuron.2018.03.028.' short: J.P. Stroud, T.P. Vogels, Neuron 98 (2018) 8–9. date_created: 2020-06-25T12:53:39Z date_published: 2018-04-04T00:00:00Z date_updated: 2021-01-12T08:16:31Z day: '04' doi: 10.1016/j.neuron.2018.03.028 extern: '1' external_id: pmid: - '29621492' intvolume: ' 98' issue: '1' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1016/j.neuron.2018.03.028 month: '04' oa: 1 oa_version: Published Version page: 8-9 pmid: 1 publication: Neuron publication_identifier: issn: - 0896-6273 publication_status: published publisher: Elsevier quality_controlled: '1' status: public title: 'Cortical signal propagation: Balance, amplify, transmit' type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 98 year: '2018' ... --- _id: '8073' abstract: - lang: eng text: Motor cortex (M1) exhibits a rich repertoire of neuronal activities to support the generation of complex movements. Although recent neuronal-network models capture many qualitative aspects of M1 dynamics, they can generate only a few distinct movements. Additionally, it is unclear how M1 efficiently controls movements over a wide range of shapes and speeds. We demonstrate that modulation of neuronal input–output gains in recurrent neuronal-network models with a fixed architecture can dramatically reorganize neuronal activity and thus downstream muscle outputs. Consistent with the observation of diffuse neuromodulatory projections to M1, a relatively small number of modulatory control units provide sufficient flexibility to adjust high-dimensional network activity using a simple reward-based learning rule. Furthermore, it is possible to assemble novel movements from previously learned primitives, and one can separately change movement speed while preserving movement shape. Our results provide a new perspective on the role of modulatory systems in controlling recurrent cortical activity. article_processing_charge: No article_type: original author: - first_name: Jake P. full_name: Stroud, Jake P. last_name: Stroud - first_name: Mason A. full_name: Porter, Mason A. last_name: Porter - first_name: Guillaume full_name: Hennequin, Guillaume last_name: Hennequin - first_name: Tim P full_name: Vogels, Tim P id: CB6FF8D2-008F-11EA-8E08-2637E6697425 last_name: Vogels orcid: 0000-0003-3295-6181 citation: ama: Stroud JP, Porter MA, Hennequin G, Vogels TP. Motor primitives in space and time via targeted gain modulation in cortical networks. Nature Neuroscience. 2018;21(12):1774-1783. doi:10.1038/s41593-018-0276-0 apa: Stroud, J. P., Porter, M. A., Hennequin, G., & Vogels, T. P. (2018). Motor primitives in space and time via targeted gain modulation in cortical networks. Nature Neuroscience. Springer Nature. https://doi.org/10.1038/s41593-018-0276-0 chicago: Stroud, Jake P., Mason A. Porter, Guillaume Hennequin, and Tim P Vogels. “Motor Primitives in Space and Time via Targeted Gain Modulation in Cortical Networks.” Nature Neuroscience. Springer Nature, 2018. https://doi.org/10.1038/s41593-018-0276-0. ieee: J. P. Stroud, M. A. Porter, G. Hennequin, and T. P. Vogels, “Motor primitives in space and time via targeted gain modulation in cortical networks,” Nature Neuroscience, vol. 21, no. 12. Springer Nature, pp. 1774–1783, 2018. ista: Stroud JP, Porter MA, Hennequin G, Vogels TP. 2018. Motor primitives in space and time via targeted gain modulation in cortical networks. Nature Neuroscience. 21(12), 1774–1783. mla: Stroud, Jake P., et al. “Motor Primitives in Space and Time via Targeted Gain Modulation in Cortical Networks.” Nature Neuroscience, vol. 21, no. 12, Springer Nature, 2018, pp. 1774–83, doi:10.1038/s41593-018-0276-0. short: J.P. Stroud, M.A. Porter, G. Hennequin, T.P. Vogels, Nature Neuroscience 21 (2018) 1774–1783. date_created: 2020-06-30T13:18:02Z date_published: 2018-12-01T00:00:00Z date_updated: 2021-01-12T08:16:46Z day: '01' doi: 10.1038/s41593-018-0276-0 extern: '1' external_id: pmid: - '30482949' intvolume: ' 21' issue: '12' language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276991/ month: '12' oa: 1 oa_version: Submitted Version page: 1774-1783 pmid: 1 publication: Nature Neuroscience publication_identifier: issn: - 1097-6256 - 1546-1726 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - relation: erratum url: https://doi.org/10.1038/s41593-018-0307-x status: public title: Motor primitives in space and time via targeted gain modulation in cortical networks type: journal_article user_id: D865714E-FA4E-11E9-B85B-F5C5E5697425 volume: 21 year: '2018' ... --- _id: '8231' article_processing_charge: No article_type: letter_note author: - first_name: Judit full_name: Fazekas-Singer, Judit id: 36432834-F248-11E8-B48F-1D18A9856A87 last_name: Fazekas-Singer orcid: 0000-0002-8777-3502 - first_name: Josef full_name: Singer, Josef last_name: Singer - first_name: Kristina M. full_name: Ilieva, Kristina M. last_name: Ilieva - first_name: Miroslawa full_name: Matz, Miroslawa last_name: Matz - first_name: Ina full_name: Herrmann, Ina last_name: Herrmann - first_name: Edzard full_name: Spillner, Edzard last_name: Spillner - first_name: Sophia N. full_name: Karagiannis, Sophia N. last_name: Karagiannis - first_name: Erika full_name: Jensen-Jarolim, Erika last_name: Jensen-Jarolim citation: ama: 'Singer J, Singer J, Ilieva KM, et al. AllergoOncology: Generating a canine anticancer IgE against the epidermal growth factor receptor. Journal of Allergy and Clinical Immunology. 2018;142(3):973-976.e11. doi:10.1016/j.jaci.2018.04.021' apa: 'Singer, J., Singer, J., Ilieva, K. M., Matz, M., Herrmann, I., Spillner, E., … Jensen-Jarolim, E. (2018). AllergoOncology: Generating a canine anticancer IgE against the epidermal growth factor receptor. Journal of Allergy and Clinical Immunology. Elsevier. https://doi.org/10.1016/j.jaci.2018.04.021' chicago: 'Singer, Judit, Josef Singer, Kristina M. Ilieva, Miroslawa Matz, Ina Herrmann, Edzard Spillner, Sophia N. Karagiannis, and Erika Jensen-Jarolim. “AllergoOncology: Generating a Canine Anticancer IgE against the Epidermal Growth Factor Receptor.” Journal of Allergy and Clinical Immunology. Elsevier, 2018. https://doi.org/10.1016/j.jaci.2018.04.021.' ieee: 'J. Singer et al., “AllergoOncology: Generating a canine anticancer IgE against the epidermal growth factor receptor,” Journal of Allergy and Clinical Immunology, vol. 142, no. 3. Elsevier, p. 973–976.e11, 2018.' ista: 'Singer J, Singer J, Ilieva KM, Matz M, Herrmann I, Spillner E, Karagiannis SN, Jensen-Jarolim E. 2018. AllergoOncology: Generating a canine anticancer IgE against the epidermal growth factor receptor. Journal of Allergy and Clinical Immunology. 142(3), 973–976.e11.' mla: 'Singer, Judit, et al. “AllergoOncology: Generating a Canine Anticancer IgE against the Epidermal Growth Factor Receptor.” Journal of Allergy and Clinical Immunology, vol. 142, no. 3, Elsevier, 2018, p. 973–976.e11, doi:10.1016/j.jaci.2018.04.021.' short: J. Singer, J. Singer, K.M. Ilieva, M. Matz, I. Herrmann, E. Spillner, S.N. Karagiannis, E. Jensen-Jarolim, Journal of Allergy and Clinical Immunology 142 (2018) 973–976.e11. date_created: 2020-08-10T11:51:36Z date_published: 2018-09-01T00:00:00Z date_updated: 2021-01-12T08:17:37Z day: '01' doi: 10.1016/j.jaci.2018.04.021 extern: '1' intvolume: ' 142' issue: '3' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1016/j.jaci.2018.04.021 month: '09' oa: 1 oa_version: Published Version page: 973-976.e11 publication: Journal of Allergy and Clinical Immunology publication_identifier: issn: - 0091-6749 publication_status: published publisher: Elsevier quality_controlled: '1' status: public title: 'AllergoOncology: Generating a canine anticancer IgE against the epidermal growth factor receptor' type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 142 year: '2018' ... --- _id: '8234' abstract: - lang: eng text: Molecular imaging probes such as PET-tracers have the potential to improve the accuracy of tumor characterization by directly visualizing the biochemical situation. Thus, molecular changes can be detected early before morphological manifestation. The A3 adenosine receptor (A3AR) is described to be highly expressed in colon cancer cell lines and human colorectal cancer (CRC), suggesting this receptor as a tumor marker. The aim of this preclinical study was the evaluation of FE@SUPPY as a PET-tracer for CRC using in vitro imaging and in vivo PET imaging. First, affinity and selectivity of FE@SUPPY and its metabolites were determined, proving the favorable binding profile of FE@SUPPY. The human adenocarcinoma cell line HT-29 was characterized regarding its hA3AR expression and was subsequently chosen as tumor graft. Promising results regarding the potential of FE@SUPPY as a PET-tracer for CRC imaging were obtained by autoradiography as ≥2.3-fold higher accumulation of FE@SUPPY was found in CRC tissue compared to adjacent healthy colon tissue from the same patient. Nevertheless, first in vivo studies using HT-29 xenografts showed insufficient tumor uptake due to (1) poor conservation of target expression in xenografts and (2) unfavorable pharmacokinetics of FE@SUPPY in mice. We therefore conclude that HT-29 xenografts are not adequate to visualize hA3ARs using FE@SUPPY. article_number: '1269830' article_processing_charge: No article_type: original author: - first_name: T. full_name: Balber, T. last_name: Balber - first_name: Judit full_name: Singer, Judit id: 36432834-F248-11E8-B48F-1D18A9856A87 last_name: Singer orcid: 0000-0002-8777-3502 - first_name: N. full_name: Berroterán-Infante, N. last_name: Berroterán-Infante - first_name: M. full_name: Dumanic, M. last_name: Dumanic - first_name: L. full_name: Fetty, L. last_name: Fetty - first_name: J. full_name: Fazekas-Singer, J. last_name: Fazekas-Singer orcid: 0000-0002-8777-3502 - first_name: C. full_name: Vraka, C. last_name: Vraka - first_name: L. full_name: Nics, L. last_name: Nics - first_name: M. full_name: Bergmann, M. last_name: Bergmann - first_name: K. full_name: Pallitsch, K. last_name: Pallitsch - first_name: H. full_name: Spreitzer, H. last_name: Spreitzer - first_name: W. full_name: Wadsak, W. last_name: Wadsak orcid: 0000-0003-4479-8053 - first_name: M. full_name: Hacker, M. last_name: Hacker - first_name: E. full_name: Jensen-Jarolim, E. last_name: Jensen-Jarolim - first_name: H. full_name: Viernstein, H. last_name: Viernstein - first_name: M. full_name: Mitterhauser, M. last_name: Mitterhauser orcid: 0000-0003-3173-5272 citation: ama: 'Balber T, Singer J, Berroterán-Infante N, et al. Preclinical in vitro and in vivo evaluation of [18F]FE@SUPPY for cancer PET imaging: Limitations of a xenograft model for colorectal cancer. Contrast Media & Molecular Imaging. 2018;2018. doi:10.1155/2018/1269830' apa: 'Balber, T., Singer, J., Berroterán-Infante, N., Dumanic, M., Fetty, L., Fazekas-Singer, J., … Mitterhauser, M. (2018). Preclinical in vitro and in vivo evaluation of [18F]FE@SUPPY for cancer PET imaging: Limitations of a xenograft model for colorectal cancer. Contrast Media & Molecular Imaging. Hindawi. https://doi.org/10.1155/2018/1269830' chicago: 'Balber, T., Judit Singer, N. Berroterán-Infante, M. Dumanic, L. Fetty, J. Fazekas-Singer, C. Vraka, et al. “Preclinical in Vitro and in Vivo Evaluation of [18F]FE@SUPPY for Cancer PET Imaging: Limitations of a Xenograft Model for Colorectal Cancer.” Contrast Media & Molecular Imaging. Hindawi, 2018. https://doi.org/10.1155/2018/1269830.' ieee: 'T. Balber et al., “Preclinical in vitro and in vivo evaluation of [18F]FE@SUPPY for cancer PET imaging: Limitations of a xenograft model for colorectal cancer,” Contrast Media & Molecular Imaging, vol. 2018. Hindawi, 2018.' ista: 'Balber T, Singer J, Berroterán-Infante N, Dumanic M, Fetty L, Fazekas-Singer J, Vraka C, Nics L, Bergmann M, Pallitsch K, Spreitzer H, Wadsak W, Hacker M, Jensen-Jarolim E, Viernstein H, Mitterhauser M. 2018. Preclinical in vitro and in vivo evaluation of [18F]FE@SUPPY for cancer PET imaging: Limitations of a xenograft model for colorectal cancer. Contrast Media & Molecular Imaging. 2018, 1269830.' mla: 'Balber, T., et al. “Preclinical in Vitro and in Vivo Evaluation of [18F]FE@SUPPY for Cancer PET Imaging: Limitations of a Xenograft Model for Colorectal Cancer.” Contrast Media & Molecular Imaging, vol. 2018, 1269830, Hindawi, 2018, doi:10.1155/2018/1269830.' short: T. Balber, J. Singer, N. Berroterán-Infante, M. Dumanic, L. Fetty, J. Fazekas-Singer, C. Vraka, L. Nics, M. Bergmann, K. Pallitsch, H. Spreitzer, W. Wadsak, M. Hacker, E. Jensen-Jarolim, H. Viernstein, M. Mitterhauser, Contrast Media & Molecular Imaging 2018 (2018). date_created: 2020-08-10T11:53:07Z date_published: 2018-02-13T00:00:00Z date_updated: 2021-01-12T08:17:38Z day: '13' doi: 10.1155/2018/1269830 extern: '1' intvolume: ' 2018' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1155/2018/1269830 month: '02' oa: 1 oa_version: Published Version publication: Contrast Media & Molecular Imaging publication_identifier: issn: - 1555-4309 - 1555-4317 publication_status: published publisher: Hindawi quality_controlled: '1' status: public title: 'Preclinical in vitro and in vivo evaluation of [18F]FE@SUPPY for cancer PET imaging: Limitations of a xenograft model for colorectal cancer' type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 2018 year: '2018' ... --- _id: '8232' abstract: - lang: eng text: 'Anti-epidermal growth factor receptor (EGFR) antibody therapy is used in EGFR expressing cancers including lung, colon, head and neck, and bladder cancers, however results have been modest. Near infrared photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that employs an antibody-photo-absorber conjugate which is activated by NIR light. NIR-PIT is in clinical trials in patients with recurrent head and neck cancers using cetuximab-IR700 as the conjugate. However, its use has otherwise been restricted to mouse models. This is an effort to explore larger animal models with NIR-PIT. We describe the use of a recombinant canine anti-EGFR monoclonal antibody (mAb), can225IgG, conjugated to the photo-absorber, IR700DX, in three EGFR expressing canine transitional cell carcinoma (TCC) cell lines as a prelude to possible canine clinical studies. Can225-IR700 conjugate showed specific binding and cell-specific killing after NIR-PIT on EGFR expressing cells in vitro. In the in vivo study, can225-IR700 conjugate demonstrated accumulation of the fluorescent conjugate with high tumor-to-background ratio. Tumor-bearing mice were separated into 4 groups: (1) no treatment; (2) 100 μg of can225-IR700 i.v. only; (3) NIR light exposure only; (4) 100 μg of can225-IR700 i.v., NIR light exposure. Tumor growth was significantly inhibited by NIR-PIT treatment compared with the other groups (p < 0.001), and significantly prolonged survival was achieved (p < 0.001 vs. other groups) in the treatment groups. In conclusion, NIR-PIT with can225-IR700 is a promising treatment for canine EGFR-expressing cancers, including invasive transitional cell carcinoma in pet dogs, that could provide a pathway to translation to humans.' article_processing_charge: No article_type: original author: - first_name: Tadanobu full_name: Nagaya, Tadanobu last_name: Nagaya - first_name: Shuhei full_name: Okuyama, Shuhei last_name: Okuyama - first_name: Fusa full_name: Ogata, Fusa last_name: Ogata - first_name: Yasuhiro full_name: Maruoka, Yasuhiro last_name: Maruoka - first_name: Deborah W. full_name: Knapp, Deborah W. last_name: Knapp - first_name: Sophia N. full_name: Karagiannis, Sophia N. last_name: Karagiannis - first_name: Judit full_name: Fazekas-Singer, Judit id: 36432834-F248-11E8-B48F-1D18A9856A87 last_name: Fazekas-Singer orcid: 0000-0002-8777-3502 - first_name: Peter L. full_name: Choyke, Peter L. last_name: Choyke - first_name: Amy K. full_name: LeBlanc, Amy K. last_name: LeBlanc - first_name: Erika full_name: Jensen-Jarolim, Erika last_name: Jensen-Jarolim - first_name: Hisataka full_name: Kobayashi, Hisataka last_name: Kobayashi citation: ama: Nagaya T, Okuyama S, Ogata F, et al. Near infrared photoimmunotherapy targeting bladder cancer with a canine anti-epidermal growth factor receptor (EGFR) antibody. Oncotarget. 2018;9:19026-19038. doi:10.18632/oncotarget.24876 apa: Nagaya, T., Okuyama, S., Ogata, F., Maruoka, Y., Knapp, D. W., Karagiannis, S. N., … Kobayashi, H. (2018). Near infrared photoimmunotherapy targeting bladder cancer with a canine anti-epidermal growth factor receptor (EGFR) antibody. Oncotarget. Impact Journals. https://doi.org/10.18632/oncotarget.24876 chicago: Nagaya, Tadanobu, Shuhei Okuyama, Fusa Ogata, Yasuhiro Maruoka, Deborah W. Knapp, Sophia N. Karagiannis, Judit Singer, et al. “Near Infrared Photoimmunotherapy Targeting Bladder Cancer with a Canine Anti-Epidermal Growth Factor Receptor (EGFR) Antibody.” Oncotarget. Impact Journals, 2018. https://doi.org/10.18632/oncotarget.24876. ieee: T. Nagaya et al., “Near infrared photoimmunotherapy targeting bladder cancer with a canine anti-epidermal growth factor receptor (EGFR) antibody,” Oncotarget, vol. 9. Impact Journals, pp. 19026–19038, 2018. ista: Nagaya T, Okuyama S, Ogata F, Maruoka Y, Knapp DW, Karagiannis SN, Singer J, Choyke PL, LeBlanc AK, Jensen-Jarolim E, Kobayashi H. 2018. Near infrared photoimmunotherapy targeting bladder cancer with a canine anti-epidermal growth factor receptor (EGFR) antibody. Oncotarget. 9, 19026–19038. mla: Nagaya, Tadanobu, et al. “Near Infrared Photoimmunotherapy Targeting Bladder Cancer with a Canine Anti-Epidermal Growth Factor Receptor (EGFR) Antibody.” Oncotarget, vol. 9, Impact Journals, 2018, pp. 19026–38, doi:10.18632/oncotarget.24876. short: T. Nagaya, S. Okuyama, F. Ogata, Y. Maruoka, D.W. Knapp, S.N. Karagiannis, J. Singer, P.L. Choyke, A.K. LeBlanc, E. Jensen-Jarolim, H. Kobayashi, Oncotarget 9 (2018) 19026–19038. date_created: 2020-08-10T11:52:54Z date_published: 2018-04-10T00:00:00Z date_updated: 2021-01-12T08:17:37Z day: '10' doi: 10.18632/oncotarget.24876 extern: '1' intvolume: ' 9' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.18632/oncotarget.24876 month: '04' oa: 1 oa_version: Published Version page: 19026-19038 publication: Oncotarget publication_identifier: eissn: - 1949-2553 publication_status: published publisher: Impact Journals quality_controlled: '1' status: public title: Near infrared photoimmunotherapy targeting bladder cancer with a canine anti-epidermal growth factor receptor (EGFR) antibody type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 9 year: '2018' ... --- _id: '8233' abstract: - lang: eng text: The M2a subtype of macrophages plays an important role in human immunoglobulin E (IgE-mediated allergies) and other Th2 type immune reactions. In contrast, very little is known about these cells in the dog. Here we describe an in vitro method to activate canine histiocytic DH82 cells and primary canine monocyte-derived macrophages (MDMs) toward the M2a macrophages using human cytokines. For a side-by-side comparison, we compared the canine cells to human MDMs, and the human monocytic cell line U937 activated towards M1 and M2a cells on the cellular and molecular level. In analogy to activated human M2a cells, canine M2a, differentiated from both DH82 and MDMs, showed an increase in CD206 surface receptor expression compared to M1. Interestingly, canine M2a, but not M1 derived from MDM, upregulated the high-affinity IgE receptor (FcεRI). Transcription levels of M2a-associated genes (IL10, CCL22, TGFβ, CD163) showed a diverse pattern between the human and dog species, whereas M1 genes (IDO1, CXCL11, IL6, TNF-α) were similarly upregulated in canine and human M1 cells (cell lines and MDMs). We suggest that our novel in vitro method will be suitable in comparative allergology studies focussing on macrophages. article_processing_charge: No article_type: original author: - first_name: Ina full_name: Herrmann, Ina last_name: Herrmann - first_name: Jelena full_name: Gotovina, Jelena last_name: Gotovina - first_name: Judit full_name: Fazekas-Singer, Judit id: 36432834-F248-11E8-B48F-1D18A9856A87 last_name: Fazekas-Singer orcid: 0000-0002-8777-3502 - first_name: Michael B. full_name: Fischer, Michael B. last_name: Fischer - first_name: Karin full_name: Hufnagl, Karin last_name: Hufnagl - first_name: Rodolfo full_name: Bianchini, Rodolfo last_name: Bianchini - first_name: Erika full_name: Jensen-Jarolim, Erika last_name: Jensen-Jarolim citation: ama: Herrmann I, Gotovina J, Singer J, et al. Canine macrophages can like human macrophages be in vitro activated toward the M2a subtype relevant in allergy. Developmental & Comparative Immunology. 2018;82(5):118-127. doi:10.1016/j.dci.2018.01.005 apa: Herrmann, I., Gotovina, J., Singer, J., Fischer, M. B., Hufnagl, K., Bianchini, R., & Jensen-Jarolim, E. (2018). Canine macrophages can like human macrophages be in vitro activated toward the M2a subtype relevant in allergy. Developmental & Comparative Immunology. Elsevier. https://doi.org/10.1016/j.dci.2018.01.005 chicago: Herrmann, Ina, Jelena Gotovina, Judit Singer, Michael B. Fischer, Karin Hufnagl, Rodolfo Bianchini, and Erika Jensen-Jarolim. “Canine Macrophages Can like Human Macrophages Be in Vitro Activated toward the M2a Subtype Relevant in Allergy.” Developmental & Comparative Immunology. Elsevier, 2018. https://doi.org/10.1016/j.dci.2018.01.005. ieee: I. Herrmann et al., “Canine macrophages can like human macrophages be in vitro activated toward the M2a subtype relevant in allergy,” Developmental & Comparative Immunology, vol. 82, no. 5. Elsevier, pp. 118–127, 2018. ista: Herrmann I, Gotovina J, Singer J, Fischer MB, Hufnagl K, Bianchini R, Jensen-Jarolim E. 2018. Canine macrophages can like human macrophages be in vitro activated toward the M2a subtype relevant in allergy. Developmental & Comparative Immunology. 82(5), 118–127. mla: Herrmann, Ina, et al. “Canine Macrophages Can like Human Macrophages Be in Vitro Activated toward the M2a Subtype Relevant in Allergy.” Developmental & Comparative Immunology, vol. 82, no. 5, Elsevier, 2018, pp. 118–27, doi:10.1016/j.dci.2018.01.005. short: I. Herrmann, J. Gotovina, J. Singer, M.B. Fischer, K. Hufnagl, R. Bianchini, E. Jensen-Jarolim, Developmental & Comparative Immunology 82 (2018) 118–127. date_created: 2020-08-10T11:53:01Z date_published: 2018-05-01T00:00:00Z date_updated: 2021-01-12T08:17:38Z day: '01' doi: 10.1016/j.dci.2018.01.005 extern: '1' intvolume: ' 82' issue: '5' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1016/j.dci.2018.01.005 month: '05' oa: 1 oa_version: Published Version page: 118-127 publication: Developmental & Comparative Immunology publication_identifier: issn: - 0145-305X publication_status: published publisher: Elsevier quality_controlled: '1' status: public title: Canine macrophages can like human macrophages be in vitro activated toward the M2a subtype relevant in allergy type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 82 year: '2018' ... --- _id: '8262' abstract: - lang: eng text: "Background: The genus Burkholderia consists of species that occupy remarkably diverse ecological niches. Its best known members are important pathogens, B. mallei and B. pseudomallei, which cause glanders and melioidosis, respectively. Burkholderia genomes are unusual due to their multichromosomal organization, generally comprised of 2-3 chromosomes.\r\n\r\nResults: We performed integrated genomic analysis of 127 Burkholderia strains. The pan-genome is open with the saturation to be reached between 86,000 and 88,000 genes. The reconstructed rearrangements indicate a strong avoidance of intra-replichore inversions that is likely caused by selection against the transfer of large groups of genes between the leading and the lagging strands. Translocated genes also tend to retain their position in the leading or the lagging strand, and this selection is stronger for large syntenies. Integrated reconstruction of chromosome rearrangements in the context of strains phylogeny reveals parallel rearrangements that may indicate inversion-based phase variation and integration of new genomic islands. In particular, we detected parallel inversions in the second chromosomes of B. pseudomallei with breakpoints formed by genes encoding membrane components of multidrug resistance complex, that may be linked to a phase variation mechanism. Two genomic islands, spreading horizontally between chromosomes, were detected in the B. cepacia group.\r\n\r\nConclusions: This study demonstrates the power of integrated analysis of pan-genomes, chromosome rearrangements, and selection regimes. Non-random inversion patterns indicate selective pressure, inversions are particularly frequent in a recent pathogen B. mallei, and, together with periods of positive selection at other branches, may indicate adaptation to new niches. One such adaptation could be a possible phase variation mechanism in B. pseudomallei." article_number: '965' article_processing_charge: No article_type: original author: - first_name: Olga full_name: Bochkareva, Olga id: C4558D3C-6102-11E9-A62E-F418E6697425 last_name: Bochkareva orcid: 0000-0003-1006-6639 - first_name: Elena V. full_name: Moroz, Elena V. last_name: Moroz - first_name: Iakov I. full_name: Davydov, Iakov I. last_name: Davydov - first_name: Mikhail S. full_name: Gelfand, Mikhail S. last_name: Gelfand citation: ama: Bochkareva O, Moroz EV, Davydov II, Gelfand MS. Genome rearrangements and selection in multi-chromosome bacteria Burkholderia spp. BMC Genomics. 2018;19. doi:10.1186/s12864-018-5245-1 apa: Bochkareva, O., Moroz, E. V., Davydov, I. I., & Gelfand, M. S. (2018). Genome rearrangements and selection in multi-chromosome bacteria Burkholderia spp. BMC Genomics. Springer Nature. https://doi.org/10.1186/s12864-018-5245-1 chicago: Bochkareva, Olga, Elena V. Moroz, Iakov I. Davydov, and Mikhail S. Gelfand. “Genome Rearrangements and Selection in Multi-Chromosome Bacteria Burkholderia Spp.” BMC Genomics. Springer Nature, 2018. https://doi.org/10.1186/s12864-018-5245-1. ieee: O. Bochkareva, E. V. Moroz, I. I. Davydov, and M. S. Gelfand, “Genome rearrangements and selection in multi-chromosome bacteria Burkholderia spp.,” BMC Genomics, vol. 19. Springer Nature, 2018. ista: Bochkareva O, Moroz EV, Davydov II, Gelfand MS. 2018. Genome rearrangements and selection in multi-chromosome bacteria Burkholderia spp. BMC Genomics. 19, 965. mla: Bochkareva, Olga, et al. “Genome Rearrangements and Selection in Multi-Chromosome Bacteria Burkholderia Spp.” BMC Genomics, vol. 19, 965, Springer Nature, 2018, doi:10.1186/s12864-018-5245-1. short: O. Bochkareva, E.V. Moroz, I.I. Davydov, M.S. Gelfand, BMC Genomics 19 (2018). date_created: 2020-08-15T11:02:08Z date_published: 2018-12-27T00:00:00Z date_updated: 2023-02-23T13:28:52Z day: '27' doi: 10.1186/s12864-018-5245-1 extern: '1' intvolume: ' 19' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1186/s12864-018-5245-1 month: '12' oa: 1 oa_version: Published Version publication: BMC Genomics publication_identifier: issn: - 1471-2164 publication_status: published publisher: Springer Nature quality_controlled: '1' status: public title: Genome rearrangements and selection in multi-chromosome bacteria Burkholderia spp. type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 19 year: '2018' ... --- _id: '8265' abstract: - lang: eng text: Genome rearrangements have played an important role in the evolution of Yersinia pestis from its progenitor Yersinia pseudotuberculosis. Traditional phylogenetic trees for Y. pestis based on sequence comparison have short internal branches and low bootstrap supports as only a small number of nucleotide substitutions have occurred. On the other hand, even a small number of genome rearrangements may resolve topological ambiguities in a phylogenetic tree. We reconstructed phylogenetic trees based on genome rearrangements using several popular approaches such as Maximum likelihood for Gene Order and the Bayesian model of genome rearrangements by inversions. We also reconciled phylogenetic trees for each of the three CRISPR loci to obtain an integrated scenario of the CRISPR cassette evolution. Analysis of contradictions between the obtained evolutionary trees yielded numerous parallel inversions and gain/loss events. Our data indicate that an integrated analysis of sequence-based and inversion-based trees enhances the resolution of phylogenetic reconstruction. In contrast, reconstructions of strain relationships based on solely CRISPR loci may not be reliable, as the history is obscured by large deletions, obliterating the order of spacer gains. Similarly, numerous parallel gene losses preclude reconstruction of phylogeny based on gene content. article_number: e4545 article_processing_charge: No article_type: original author: - first_name: Olga full_name: Bochkareva, Olga id: C4558D3C-6102-11E9-A62E-F418E6697425 last_name: Bochkareva orcid: 0000-0003-1006-6639 - first_name: Natalia O. full_name: Dranenko, Natalia O. last_name: Dranenko - first_name: Elena S. full_name: Ocheredko, Elena S. last_name: Ocheredko - first_name: German M. full_name: Kanevsky, German M. last_name: Kanevsky - first_name: Yaroslav N. full_name: Lozinsky, Yaroslav N. last_name: Lozinsky - first_name: Vera A. full_name: Khalaycheva, Vera A. last_name: Khalaycheva - first_name: Irena I. full_name: Artamonova, Irena I. last_name: Artamonova - first_name: Mikhail S. full_name: Gelfand, Mikhail S. last_name: Gelfand citation: ama: Bochkareva O, Dranenko NO, Ocheredko ES, et al. Genome rearrangements and phylogeny reconstruction in Yersinia pestis. PeerJ. 2018;6. doi:10.7717/peerj.4545 apa: Bochkareva, O., Dranenko, N. O., Ocheredko, E. S., Kanevsky, G. M., Lozinsky, Y. N., Khalaycheva, V. A., … Gelfand, M. S. (2018). Genome rearrangements and phylogeny reconstruction in Yersinia pestis. PeerJ. PeerJ. https://doi.org/10.7717/peerj.4545 chicago: Bochkareva, Olga, Natalia O. Dranenko, Elena S. Ocheredko, German M. Kanevsky, Yaroslav N. Lozinsky, Vera A. Khalaycheva, Irena I. Artamonova, and Mikhail S. Gelfand. “Genome Rearrangements and Phylogeny Reconstruction in Yersinia Pestis.” PeerJ. PeerJ, 2018. https://doi.org/10.7717/peerj.4545. ieee: O. Bochkareva et al., “Genome rearrangements and phylogeny reconstruction in Yersinia pestis,” PeerJ, vol. 6. PeerJ, 2018. ista: Bochkareva O, Dranenko NO, Ocheredko ES, Kanevsky GM, Lozinsky YN, Khalaycheva VA, Artamonova II, Gelfand MS. 2018. Genome rearrangements and phylogeny reconstruction in Yersinia pestis. PeerJ. 6, e4545. mla: Bochkareva, Olga, et al. “Genome Rearrangements and Phylogeny Reconstruction in Yersinia Pestis.” PeerJ, vol. 6, e4545, PeerJ, 2018, doi:10.7717/peerj.4545. short: O. Bochkareva, N.O. Dranenko, E.S. Ocheredko, G.M. Kanevsky, Y.N. Lozinsky, V.A. Khalaycheva, I.I. Artamonova, M.S. Gelfand, PeerJ 6 (2018). date_created: 2020-08-15T11:08:23Z date_published: 2018-03-27T00:00:00Z date_updated: 2023-02-23T13:28:57Z day: '27' doi: 10.7717/peerj.4545 extern: '1' external_id: pmid: - '29607260' intvolume: ' 6' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.7717/peerj.4545 month: '03' oa: 1 oa_version: Published Version pmid: 1 publication: PeerJ publication_identifier: issn: - 2167-8359 publication_status: published publisher: PeerJ quality_controlled: '1' status: public title: Genome rearrangements and phylogeny reconstruction in Yersinia pestis type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 6 year: '2018' ... --- _id: '8274' abstract: - lang: eng text: 'Background/Aim: Our aim was to investigate the crosstalk between tumor and immune cells (M2 macrophages) and its effects on cyclo-oxygenase-2 (COX2) regulation in canine mammary tumors (CMT). Materials and Methods: Sh1b CMT cells and human BT474 mammary or HT29 colon cancer cells were co-cultured with canine peripheral blood mononuclear cells (PBMCs) or with macrophage-like differentiated THP1 monocytes (dTHP1). Intracellular COX2 expression by PBMCs, dTHP1 and cancer cells was evaluated by flow cytometry. Results: Co-culturing of Sh1b and canine PBMCs induced COX2 overexpression in CMT cells. In turn, COX2 expression by PBMCs, mostly CD68+ macrophages, was attenuated by co-culture with Sh1b (p=0.0001). In accordance, co-culture with dTHP1 prompted intracellular production of COX2 in both Sh1b CMT cells and HT29 human colon cancer cells and reduced production of COX2 in BT474 human mammary cancer cells. The intracellular COX2 expression from dTHP1 decreased when treated with conditioned medium from cultured Sh1b and HT29 cancer cells. Conclusion: Bidirectional COX2 regulation between cancer and monocytes/macrophages might shape a tolerogenic tumor microenvironment in CMT.' article_processing_charge: No article_type: original author: - first_name: Maria Isabel full_name: Carvalho, Maria Isabel last_name: Carvalho - first_name: Rodolfo full_name: Bianchini, Rodolfo last_name: Bianchini - first_name: Judit full_name: Fazekas-Singer, Judit id: 36432834-F248-11E8-B48F-1D18A9856A87 last_name: Fazekas-Singer orcid: 0000-0002-8777-3502 - first_name: Ina full_name: Herrmann, Ina last_name: Herrmann - first_name: Irene full_name: Flickinger, Irene last_name: Flickinger - first_name: Johann G. full_name: Thalhammer, Johann G. last_name: Thalhammer - first_name: Isabel full_name: Pires, Isabel last_name: Pires - first_name: Erika full_name: Jensen-Jarolim, Erika last_name: Jensen-Jarolim - first_name: Felisbina L. full_name: Queiroga, Felisbina L. last_name: Queiroga citation: ama: Carvalho MI, Bianchini R, Singer J, et al. Bidirectional regulation of COX-2 expression between cancer cells and macrophages. Anticancer Research. 2018;38(5):2811-2817. doi:10.21873/anticanres.12525 apa: Carvalho, M. I., Bianchini, R., Singer, J., Herrmann, I., Flickinger, I., Thalhammer, J. G., … Queiroga, F. L. (2018). Bidirectional regulation of COX-2 expression between cancer cells and macrophages. Anticancer Research. International Institute of Anticancer Research. https://doi.org/10.21873/anticanres.12525 chicago: Carvalho, Maria Isabel, Rodolfo Bianchini, Judit Singer, Ina Herrmann, Irene Flickinger, Johann G. Thalhammer, Isabel Pires, Erika Jensen-Jarolim, and Felisbina L. Queiroga. “Bidirectional Regulation of COX-2 Expression between Cancer Cells and Macrophages.” Anticancer Research. International Institute of Anticancer Research, 2018. https://doi.org/10.21873/anticanres.12525. ieee: M. I. Carvalho et al., “Bidirectional regulation of COX-2 expression between cancer cells and macrophages,” Anticancer Research, vol. 38, no. 5. International Institute of Anticancer Research, pp. 2811–2817, 2018. ista: Carvalho MI, Bianchini R, Singer J, Herrmann I, Flickinger I, Thalhammer JG, Pires I, Jensen-Jarolim E, Queiroga FL. 2018. Bidirectional regulation of COX-2 expression between cancer cells and macrophages. Anticancer Research. 38(5), 2811–2817. mla: Carvalho, Maria Isabel, et al. “Bidirectional Regulation of COX-2 Expression between Cancer Cells and Macrophages.” Anticancer Research, vol. 38, no. 5, International Institute of Anticancer Research, 2018, pp. 2811–17, doi:10.21873/anticanres.12525. short: M.I. Carvalho, R. Bianchini, J. Singer, I. Herrmann, I. Flickinger, J.G. Thalhammer, I. Pires, E. Jensen-Jarolim, F.L. Queiroga, Anticancer Research 38 (2018) 2811–2817. date_created: 2020-08-17T07:13:55Z date_published: 2018-05-01T00:00:00Z date_updated: 2021-01-12T08:17:52Z day: '01' doi: 10.21873/anticanres.12525 extern: '1' intvolume: ' 38' issue: '5' language: - iso: eng month: '05' oa_version: None page: 2811-2817 publication: Anticancer Research publication_identifier: eissn: - 1791-7530 issn: - 0250-7005 publication_status: published publisher: International Institute of Anticancer Research quality_controlled: '1' status: public title: Bidirectional regulation of COX-2 expression between cancer cells and macrophages type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 38 year: '2018' ... --- _id: '8298' abstract: - lang: eng text: Sharding, or partitioning the system’s state so that different subsets of participants handle it, is a proven approach to building distributed systems whose total capacity scales horizontally with the number of participants. Many distributed ledgers have adopted this approach to increase their performance, however, they focus on the permissionless setting that assumes the existence of a strong adversary. In this paper, we deploy channels for permissioned blockchains. Our first contribution is to adapt sharding on asset-management applications for the permissioned setting, while preserving liveness and safety even on transactions spanning across-channels. Our second contribution is to leverage channels as a confidentiality boundary, enabling different organizations and consortia to preserve their privacy within their channels and still be part of a bigger collaborative ecosystem. To make our system concrete we map it on top of Hyperledger Fabric. alternative_title: - LNCS article_processing_charge: No author: - first_name: Elli full_name: Androulaki, Elli last_name: Androulaki - first_name: Christian full_name: Cachin, Christian last_name: Cachin - first_name: Angelo full_name: De Caro, Angelo last_name: De Caro - first_name: Eleftherios full_name: Kokoris Kogias, Eleftherios id: f5983044-d7ef-11ea-ac6d-fd1430a26d30 last_name: Kokoris Kogias citation: ama: 'Androulaki E, Cachin C, De Caro A, Kokoris Kogias E. Channels: Horizontal scaling and confidentiality on permissioned blockchains. In: Computer Security. Vol 11098. Springer Nature; 2018:111-131. doi:10.1007/978-3-319-99073-6_6' apa: 'Androulaki, E., Cachin, C., De Caro, A., & Kokoris Kogias, E. (2018). Channels: Horizontal scaling and confidentiality on permissioned blockchains. In Computer Security (Vol. 11098, pp. 111–131). Barcelona, Spain: Springer Nature. https://doi.org/10.1007/978-3-319-99073-6_6' chicago: 'Androulaki, Elli, Christian Cachin, Angelo De Caro, and Eleftherios Kokoris Kogias. “Channels: Horizontal Scaling and Confidentiality on Permissioned Blockchains.” In Computer Security, 11098:111–31. Springer Nature, 2018. https://doi.org/10.1007/978-3-319-99073-6_6.' ieee: 'E. Androulaki, C. Cachin, A. De Caro, and E. Kokoris Kogias, “Channels: Horizontal scaling and confidentiality on permissioned blockchains,” in Computer Security, Barcelona, Spain, 2018, vol. 11098, pp. 111–131.' ista: 'Androulaki E, Cachin C, De Caro A, Kokoris Kogias E. 2018. Channels: Horizontal scaling and confidentiality on permissioned blockchains. Computer Security. ESORICS: European Symposium on Research in Computer Security, LNCS, vol. 11098, 111–131.' mla: 'Androulaki, Elli, et al. “Channels: Horizontal Scaling and Confidentiality on Permissioned Blockchains.” Computer Security, vol. 11098, Springer Nature, 2018, pp. 111–31, doi:10.1007/978-3-319-99073-6_6.' short: E. Androulaki, C. Cachin, A. De Caro, E. Kokoris Kogias, in:, Computer Security, Springer Nature, 2018, pp. 111–131. conference: end_date: 2018-09-07 location: Barcelona, Spain name: 'ESORICS: European Symposium on Research in Computer Security' start_date: 2018-09-03 date_created: 2020-08-26T11:47:34Z date_published: 2018-08-08T00:00:00Z date_updated: 2021-01-12T08:17:57Z day: '08' doi: 10.1007/978-3-319-99073-6_6 extern: '1' intvolume: ' 11098' language: - iso: eng month: '08' oa_version: None page: 111-131 publication: Computer Security publication_identifier: eisbn: - '9783319990736' isbn: - '9783319990729' issn: - 0302-9743 - 1611-3349 publication_status: published publisher: Springer Nature quality_controlled: '1' status: public title: 'Channels: Horizontal scaling and confidentiality on permissioned blockchains' type: conference user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 11098 year: '2018' ... --- _id: '8297' abstract: - lang: eng text: "Designing a secure permissionless distributed ledger (blockchain) that performs on par with centralized payment\r\nprocessors, such as Visa, is a challenging task. Most existing distributed ledgers are unable to scale-out, i.e., to grow their totalprocessing capacity with the number of validators; and those that do, compromise security or decentralization. We present OmniLedger, a novel scale-out distributed ledger that preserves longterm security under permissionless operation. It ensures security and correctness by using a bias-resistant public-randomness protocol for choosing large, statistically representative shards that process transactions, and by introducing an efficient crossshard commit protocol that atomically handles transactions affecting multiple shards. OmniLedger also optimizes performance via parallel intra-shard transaction processing, ledger pruning via collectively-signed state blocks, and low-latency “trust-butverify” \r\nvalidation for low-value transactions. An evaluation ofour experimental prototype shows that OmniLedger’s throughput\r\nscales linearly in the number of active validators, supporting Visa-level workloads and beyond, while confirming typical transactions in under two seconds." article_processing_charge: No author: - first_name: Eleftherios full_name: Kokoris Kogias, Eleftherios id: f5983044-d7ef-11ea-ac6d-fd1430a26d30 last_name: Kokoris Kogias - first_name: Philipp full_name: Jovanovic, Philipp last_name: Jovanovic - first_name: Linus full_name: Gasser, Linus last_name: Gasser - first_name: Nicolas full_name: Gailly, Nicolas last_name: Gailly - first_name: Ewa full_name: Syta, Ewa last_name: Syta - first_name: Bryan full_name: Ford, Bryan last_name: Ford citation: ama: 'Kokoris Kogias E, Jovanovic P, Gasser L, Gailly N, Syta E, Ford B. OmniLedger: A secure, scale-out, decentralized ledger via sharding. In: 2018 IEEE Symposium on Security and Privacy. IEEE; 2018:583-598. doi:10.1109/sp.2018.000-5' apa: 'Kokoris Kogias, E., Jovanovic, P., Gasser, L., Gailly, N., Syta, E., & Ford, B. (2018). OmniLedger: A secure, scale-out, decentralized ledger via sharding. In 2018 IEEE Symposium on Security and Privacy (pp. 583–598). San Francisco, CA, United States: IEEE. https://doi.org/10.1109/sp.2018.000-5' chicago: 'Kokoris Kogias, Eleftherios, Philipp Jovanovic, Linus Gasser, Nicolas Gailly, Ewa Syta, and Bryan Ford. “OmniLedger: A Secure, Scale-out, Decentralized Ledger via Sharding.” In 2018 IEEE Symposium on Security and Privacy, 583–98. IEEE, 2018. https://doi.org/10.1109/sp.2018.000-5.' ieee: 'E. Kokoris Kogias, P. Jovanovic, L. Gasser, N. Gailly, E. Syta, and B. Ford, “OmniLedger: A secure, scale-out, decentralized ledger via sharding,” in 2018 IEEE Symposium on Security and Privacy, San Francisco, CA, United States, 2018, pp. 583–598.' ista: 'Kokoris Kogias E, Jovanovic P, Gasser L, Gailly N, Syta E, Ford B. 2018. OmniLedger: A secure, scale-out, decentralized ledger via sharding. 2018 IEEE Symposium on Security and Privacy. SP: Symposium on Security and Privacy, 583–598.' mla: 'Kokoris Kogias, Eleftherios, et al. “OmniLedger: A Secure, Scale-out, Decentralized Ledger via Sharding.” 2018 IEEE Symposium on Security and Privacy, IEEE, 2018, pp. 583–98, doi:10.1109/sp.2018.000-5.' short: E. Kokoris Kogias, P. Jovanovic, L. Gasser, N. Gailly, E. Syta, B. Ford, in:, 2018 IEEE Symposium on Security and Privacy, IEEE, 2018, pp. 583–598. conference: end_date: 2018-05-24 location: San Francisco, CA, United States name: 'SP: Symposium on Security and Privacy' start_date: 2018-05-20 date_created: 2020-08-26T11:46:35Z date_published: 2018-07-26T00:00:00Z date_updated: 2021-01-12T08:17:56Z day: '26' doi: 10.1109/sp.2018.000-5 extern: '1' language: - iso: eng main_file_link: - open_access: '1' url: https://eprint.iacr.org/2017/406 month: '07' oa: 1 oa_version: Preprint page: 583-598 publication: 2018 IEEE Symposium on Security and Privacy publication_identifier: isbn: - '9781538643532' issn: - 2375-1207 publication_status: published publisher: IEEE quality_controlled: '1' status: public title: 'OmniLedger: A secure, scale-out, decentralized ledger via sharding' type: conference user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2018' ... --- _id: '8443' abstract: - lang: eng text: Characterizing the structure of membrane proteins (MPs) generally requires extraction from their native environment, most commonly with detergents. Yet, the physicochemical properties of detergent micelles and lipid bilayers differ markedly and could alter the structural organization of MPs, albeit without general rules. Dodecylphosphocholine (DPC) is the most widely used detergent for MP structure determination by NMR, but the physiological relevance of several prominent structures has been questioned, though indirectly, by other biophysical techniques, e.g., functional/thermostability assay (TSA) and molecular dynamics (MD) simulations. Here, we resolve unambiguously this controversy by probing the functional relevance of three different mitochondrial carriers (MCs) in DPC at the atomic level, using an exhaustive set of solution-NMR experiments, complemented by functional/TSA and MD data. Our results provide atomic-level insight into the structure, substrate interaction and dynamics of the detergent–membrane protein complexes and demonstrates cogently that, while high-resolution NMR signals can be obtained for MCs in DPC, they systematically correspond to nonfunctional states. article_processing_charge: No article_type: original author: - first_name: Vilius full_name: Kurauskas, Vilius last_name: Kurauskas - first_name: Audrey full_name: Hessel, Audrey last_name: Hessel - first_name: Peixiang full_name: Ma, Peixiang last_name: Ma - first_name: Paola full_name: Lunetti, Paola last_name: Lunetti - first_name: Katharina full_name: Weinhäupl, Katharina last_name: Weinhäupl - first_name: Lionel full_name: Imbert, Lionel last_name: Imbert - first_name: Bernhard full_name: Brutscher, Bernhard last_name: Brutscher - first_name: Martin S. full_name: King, Martin S. last_name: King - first_name: Rémy full_name: Sounier, Rémy last_name: Sounier - first_name: Vincenza full_name: Dolce, Vincenza last_name: Dolce - first_name: Edmund R. S. full_name: Kunji, Edmund R. S. last_name: Kunji - first_name: Loredana full_name: Capobianco, Loredana last_name: Capobianco - first_name: Christophe full_name: Chipot, Christophe last_name: Chipot - first_name: François full_name: Dehez, François last_name: Dehez - first_name: Beate full_name: Bersch, Beate last_name: Bersch - first_name: Paul full_name: Schanda, Paul id: 7B541462-FAF6-11E9-A490-E8DFE5697425 last_name: Schanda orcid: 0000-0002-9350-7606 citation: ama: 'Kurauskas V, Hessel A, Ma P, et al. How detergent impacts membrane proteins: Atomic-level views of mitochondrial carriers in dodecylphosphocholine. The Journal of Physical Chemistry Letters. 2018;9(5):933-938. doi:10.1021/acs.jpclett.8b00269' apa: 'Kurauskas, V., Hessel, A., Ma, P., Lunetti, P., Weinhäupl, K., Imbert, L., … Schanda, P. (2018). How detergent impacts membrane proteins: Atomic-level views of mitochondrial carriers in dodecylphosphocholine. The Journal of Physical Chemistry Letters. American Chemical Society. https://doi.org/10.1021/acs.jpclett.8b00269' chicago: 'Kurauskas, Vilius, Audrey Hessel, Peixiang Ma, Paola Lunetti, Katharina Weinhäupl, Lionel Imbert, Bernhard Brutscher, et al. “How Detergent Impacts Membrane Proteins: Atomic-Level Views of Mitochondrial Carriers in Dodecylphosphocholine.” The Journal of Physical Chemistry Letters. American Chemical Society, 2018. https://doi.org/10.1021/acs.jpclett.8b00269.' ieee: 'V. Kurauskas et al., “How detergent impacts membrane proteins: Atomic-level views of mitochondrial carriers in dodecylphosphocholine,” The Journal of Physical Chemistry Letters, vol. 9, no. 5. American Chemical Society, pp. 933–938, 2018.' ista: 'Kurauskas V, Hessel A, Ma P, Lunetti P, Weinhäupl K, Imbert L, Brutscher B, King MS, Sounier R, Dolce V, Kunji ERS, Capobianco L, Chipot C, Dehez F, Bersch B, Schanda P. 2018. How detergent impacts membrane proteins: Atomic-level views of mitochondrial carriers in dodecylphosphocholine. The Journal of Physical Chemistry Letters. 9(5), 933–938.' mla: 'Kurauskas, Vilius, et al. “How Detergent Impacts Membrane Proteins: Atomic-Level Views of Mitochondrial Carriers in Dodecylphosphocholine.” The Journal of Physical Chemistry Letters, vol. 9, no. 5, American Chemical Society, 2018, pp. 933–38, doi:10.1021/acs.jpclett.8b00269.' short: V. Kurauskas, A. Hessel, P. Ma, P. Lunetti, K. Weinhäupl, L. Imbert, B. Brutscher, M.S. King, R. Sounier, V. Dolce, E.R.S. Kunji, L. Capobianco, C. Chipot, F. Dehez, B. Bersch, P. Schanda, The Journal of Physical Chemistry Letters 9 (2018) 933–938. date_created: 2020-09-18T10:05:45Z date_published: 2018-02-03T00:00:00Z date_updated: 2021-01-12T08:19:18Z day: '03' doi: 10.1021/acs.jpclett.8b00269 extern: '1' intvolume: ' 9' issue: '5' keyword: - General Materials Science language: - iso: eng month: '02' oa_version: None page: 933-938 publication: The Journal of Physical Chemistry Letters publication_identifier: issn: - 1948-7185 publication_status: published publisher: American Chemical Society quality_controlled: '1' status: public title: 'How detergent impacts membrane proteins: Atomic-level views of mitochondrial carriers in dodecylphosphocholine' type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 9 year: '2018' ... --- _id: '8440' abstract: - lang: eng text: Mycobacterium tuberculosis can remain dormant in the host, an ability that explains the failure of many current tuberculosis treatments. Recently, the natural products cyclomarin, ecumicin, and lassomycin have been shown to efficiently kill Mycobacterium tuberculosis persisters. Their target is the N-terminal domain of the hexameric AAA+ ATPase ClpC1, which recognizes, unfolds, and translocates protein substrates, such as proteins containing phosphorylated arginine residues, to the ClpP1P2 protease for degradation. Surprisingly, these antibiotics do not inhibit ClpC1 ATPase activity, and how they cause cell death is still unclear. Here, using NMR and small-angle X-ray scattering, we demonstrate that arginine-phosphate binding to the ClpC1 N-terminal domain induces millisecond dynamics. We show that these dynamics are caused by conformational changes and do not result from unfolding or oligomerization of this domain. Cyclomarin binding to this domain specifically blocked these N-terminal dynamics. On the basis of these results, we propose a mechanism of action involving cyclomarin-induced restriction of ClpC1 dynamics, which modulates the chaperone enzymatic activity leading eventually to cell death. article_processing_charge: No article_type: original author: - first_name: Katharina full_name: Weinhäupl, Katharina last_name: Weinhäupl - first_name: Martha full_name: Brennich, Martha last_name: Brennich - first_name: Uli full_name: Kazmaier, Uli last_name: Kazmaier - first_name: Joel full_name: Lelievre, Joel last_name: Lelievre - first_name: Lluis full_name: Ballell, Lluis last_name: Ballell - first_name: Alfred full_name: Goldberg, Alfred last_name: Goldberg - first_name: Paul full_name: Schanda, Paul id: 7B541462-FAF6-11E9-A490-E8DFE5697425 last_name: Schanda orcid: 0000-0002-9350-7606 - first_name: Hugo full_name: Fraga, Hugo last_name: Fraga citation: ama: Weinhäupl K, Brennich M, Kazmaier U, et al. The antibiotic cyclomarin blocks arginine-phosphate–induced millisecond dynamics in the N-terminal domain of ClpC1 from Mycobacterium tuberculosis. Journal of Biological Chemistry. 2018;293(22):8379-8393. doi:10.1074/jbc.ra118.002251 apa: Weinhäupl, K., Brennich, M., Kazmaier, U., Lelievre, J., Ballell, L., Goldberg, A., … Fraga, H. (2018). The antibiotic cyclomarin blocks arginine-phosphate–induced millisecond dynamics in the N-terminal domain of ClpC1 from Mycobacterium tuberculosis. Journal of Biological Chemistry. American Society for Biochemistry & Molecular Biology. https://doi.org/10.1074/jbc.ra118.002251 chicago: Weinhäupl, Katharina, Martha Brennich, Uli Kazmaier, Joel Lelievre, Lluis Ballell, Alfred Goldberg, Paul Schanda, and Hugo Fraga. “The Antibiotic Cyclomarin Blocks Arginine-Phosphate–Induced Millisecond Dynamics in the N-Terminal Domain of ClpC1 from Mycobacterium Tuberculosis.” Journal of Biological Chemistry. American Society for Biochemistry & Molecular Biology, 2018. https://doi.org/10.1074/jbc.ra118.002251. ieee: K. Weinhäupl et al., “The antibiotic cyclomarin blocks arginine-phosphate–induced millisecond dynamics in the N-terminal domain of ClpC1 from Mycobacterium tuberculosis,” Journal of Biological Chemistry, vol. 293, no. 22. American Society for Biochemistry & Molecular Biology, pp. 8379–8393, 2018. ista: Weinhäupl K, Brennich M, Kazmaier U, Lelievre J, Ballell L, Goldberg A, Schanda P, Fraga H. 2018. The antibiotic cyclomarin blocks arginine-phosphate–induced millisecond dynamics in the N-terminal domain of ClpC1 from Mycobacterium tuberculosis. Journal of Biological Chemistry. 293(22), 8379–8393. mla: Weinhäupl, Katharina, et al. “The Antibiotic Cyclomarin Blocks Arginine-Phosphate–Induced Millisecond Dynamics in the N-Terminal Domain of ClpC1 from Mycobacterium Tuberculosis.” Journal of Biological Chemistry, vol. 293, no. 22, American Society for Biochemistry & Molecular Biology, 2018, pp. 8379–93, doi:10.1074/jbc.ra118.002251. short: K. Weinhäupl, M. Brennich, U. Kazmaier, J. Lelievre, L. Ballell, A. Goldberg, P. Schanda, H. Fraga, Journal of Biological Chemistry 293 (2018) 8379–8393. date_created: 2020-09-18T10:05:18Z date_published: 2018-06-01T00:00:00Z date_updated: 2021-01-12T08:19:17Z day: '01' doi: 10.1074/jbc.ra118.002251 extern: '1' intvolume: ' 293' issue: '22' keyword: - Cell Biology - Biochemistry - Molecular Biology language: - iso: eng month: '06' oa_version: None page: 8379-8393 publication: Journal of Biological Chemistry publication_identifier: issn: - 0021-9258 - 1083-351X publication_status: published publisher: American Society for Biochemistry & Molecular Biology quality_controlled: '1' status: public title: The antibiotic cyclomarin blocks arginine-phosphate–induced millisecond dynamics in the N-terminal domain of ClpC1 from Mycobacterium tuberculosis type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 293 year: '2018' ... --- _id: '8442' abstract: - lang: eng text: Membrane proteins perform a host of vital cellular functions. Deciphering the molecular mechanisms whereby they fulfill these functions requires detailed biophysical and structural investigations. Detergents have proven pivotal to extract the protein from its native surroundings. Yet, they provide a milieu that departs significantly from that of the biological membrane, to the extent that the structure, the dynamics, and the interactions of membrane proteins in detergents may considerably vary, as compared to the native environment. Understanding the impact of detergents on membrane proteins is, therefore, crucial to assess the biological relevance of results obtained in detergents. Here, we review the strengths and weaknesses of alkyl phosphocholines (or foscholines), the most widely used detergent in solution-NMR studies of membrane proteins. While this class of detergents is often successful for membrane protein solubilization, a growing list of examples points to destabilizing and denaturing properties, in particular for α-helical membrane proteins. Our comprehensive analysis stresses the importance of stringent controls when working with this class of detergents and when analyzing the structure and dynamics of membrane proteins in alkyl phosphocholine detergents. article_processing_charge: No article_type: original author: - first_name: Christophe full_name: Chipot, Christophe last_name: Chipot - first_name: François full_name: Dehez, François last_name: Dehez - first_name: Jason R. full_name: Schnell, Jason R. last_name: Schnell - first_name: Nicole full_name: Zitzmann, Nicole last_name: Zitzmann - first_name: Eva full_name: Pebay-Peyroula, Eva last_name: Pebay-Peyroula - first_name: Laurent J. full_name: Catoire, Laurent J. last_name: Catoire - first_name: Bruno full_name: Miroux, Bruno last_name: Miroux - first_name: Edmund R. S. full_name: Kunji, Edmund R. S. last_name: Kunji - first_name: Gianluigi full_name: Veglia, Gianluigi last_name: Veglia - first_name: Timothy A. full_name: Cross, Timothy A. last_name: Cross - first_name: Paul full_name: Schanda, Paul id: 7B541462-FAF6-11E9-A490-E8DFE5697425 last_name: Schanda orcid: 0000-0002-9350-7606 citation: ama: 'Chipot C, Dehez F, Schnell JR, et al. Perturbations of native membrane protein structure in alkyl phosphocholine detergents: A critical assessment of NMR and biophysical studies. Chemical Reviews. 2018;118(7):3559-3607. doi:10.1021/acs.chemrev.7b00570' apa: 'Chipot, C., Dehez, F., Schnell, J. R., Zitzmann, N., Pebay-Peyroula, E., Catoire, L. J., … Schanda, P. (2018). Perturbations of native membrane protein structure in alkyl phosphocholine detergents: A critical assessment of NMR and biophysical studies. Chemical Reviews. American Chemical Society. https://doi.org/10.1021/acs.chemrev.7b00570' chicago: 'Chipot, Christophe, François Dehez, Jason R. Schnell, Nicole Zitzmann, Eva Pebay-Peyroula, Laurent J. Catoire, Bruno Miroux, et al. “Perturbations of Native Membrane Protein Structure in Alkyl Phosphocholine Detergents: A Critical Assessment of NMR and Biophysical Studies.” Chemical Reviews. American Chemical Society, 2018. https://doi.org/10.1021/acs.chemrev.7b00570.' ieee: 'C. Chipot et al., “Perturbations of native membrane protein structure in alkyl phosphocholine detergents: A critical assessment of NMR and biophysical studies,” Chemical Reviews, vol. 118, no. 7. American Chemical Society, pp. 3559–3607, 2018.' ista: 'Chipot C, Dehez F, Schnell JR, Zitzmann N, Pebay-Peyroula E, Catoire LJ, Miroux B, Kunji ERS, Veglia G, Cross TA, Schanda P. 2018. Perturbations of native membrane protein structure in alkyl phosphocholine detergents: A critical assessment of NMR and biophysical studies. Chemical Reviews. 118(7), 3559–3607.' mla: 'Chipot, Christophe, et al. “Perturbations of Native Membrane Protein Structure in Alkyl Phosphocholine Detergents: A Critical Assessment of NMR and Biophysical Studies.” Chemical Reviews, vol. 118, no. 7, American Chemical Society, 2018, pp. 3559–607, doi:10.1021/acs.chemrev.7b00570.' short: C. Chipot, F. Dehez, J.R. Schnell, N. Zitzmann, E. Pebay-Peyroula, L.J. Catoire, B. Miroux, E.R.S. Kunji, G. Veglia, T.A. Cross, P. Schanda, Chemical Reviews 118 (2018) 3559–3607. date_created: 2020-09-18T10:05:35Z date_published: 2018-02-28T00:00:00Z date_updated: 2021-01-12T08:19:18Z day: '28' doi: 10.1021/acs.chemrev.7b00570 extern: '1' intvolume: ' 118' issue: '7' keyword: - General Chemistry language: - iso: eng month: '02' oa_version: None page: 3559-3607 publication: Chemical Reviews publication_identifier: issn: - 0009-2665 - 1520-6890 publication_status: published publisher: American Chemical Society quality_controlled: '1' status: public title: 'Perturbations of native membrane protein structure in alkyl phosphocholine detergents: A critical assessment of NMR and biophysical studies' type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 118 year: '2018' ... --- _id: '8441' abstract: - lang: eng text: Solid-state near-rotary-resonance measurements of the spin–lattice relaxation rate in the rotating frame (R1ρ) is a powerful NMR technique for studying molecular dynamics in the microsecond time scale. The small difference between the spin-lock (SL) and magic-angle-spinning (MAS) frequencies allows sampling very slow motions, at the same time it brings up some methodological challenges. In this work, several issues affecting correct measurements and analysis of 15N R1ρ data are considered in detail. Among them are signal amplitude as a function of the difference between SL and MAS frequencies, “dead time” in the initial part of the relaxation decay caused by transient spin-dynamic oscillations, measurements under HORROR condition and proper treatment of the multi-exponential relaxation decays. The multiple 15N R1ρ measurements at different SL fields and temperatures have been conducted in 1D mode (i.e. without site-specific resolution) for a set of four different microcrystalline protein samples (GB1, SH3, MPD-ubiquitin and cubic-PEG-ubiquitin) to study the overall protein rocking in a crystal. While the amplitude of this motion varies very significantly, its correlation time for all four sample is practically the same, 30–50 μs. The amplitude of the rocking motion correlates with the packing density of a protein crystal. It has been suggested that the rocking motion is not diffusive but likely a jump-like dynamic process. article_processing_charge: No article_type: original author: - first_name: Alexey full_name: Krushelnitsky, Alexey last_name: Krushelnitsky - first_name: Diego full_name: Gauto, Diego last_name: Gauto - first_name: Diana C. full_name: Rodriguez Camargo, Diana C. last_name: Rodriguez Camargo - first_name: Paul full_name: Schanda, Paul id: 7B541462-FAF6-11E9-A490-E8DFE5697425 last_name: Schanda orcid: 0000-0002-9350-7606 - first_name: Kay full_name: Saalwächter, Kay last_name: Saalwächter citation: ama: 'Krushelnitsky A, Gauto D, Rodriguez Camargo DC, Schanda P, Saalwächter K. Microsecond motions probed by near-rotary-resonance R1ρ 15N MAS NMR experiments: The model case of protein overall-rocking in crystals. Journal of Biomolecular NMR. 2018;71(1):53-67. doi:10.1007/s10858-018-0191-4' apa: 'Krushelnitsky, A., Gauto, D., Rodriguez Camargo, D. C., Schanda, P., & Saalwächter, K. (2018). Microsecond motions probed by near-rotary-resonance R1ρ 15N MAS NMR experiments: The model case of protein overall-rocking in crystals. Journal of Biomolecular NMR. Springer Nature. https://doi.org/10.1007/s10858-018-0191-4' chicago: 'Krushelnitsky, Alexey, Diego Gauto, Diana C. Rodriguez Camargo, Paul Schanda, and Kay Saalwächter. “Microsecond Motions Probed by Near-Rotary-Resonance R1ρ 15N MAS NMR Experiments: The Model Case of Protein Overall-Rocking in Crystals.” Journal of Biomolecular NMR. Springer Nature, 2018. https://doi.org/10.1007/s10858-018-0191-4.' ieee: 'A. Krushelnitsky, D. Gauto, D. C. Rodriguez Camargo, P. Schanda, and K. Saalwächter, “Microsecond motions probed by near-rotary-resonance R1ρ 15N MAS NMR experiments: The model case of protein overall-rocking in crystals,” Journal of Biomolecular NMR, vol. 71, no. 1. Springer Nature, pp. 53–67, 2018.' ista: 'Krushelnitsky A, Gauto D, Rodriguez Camargo DC, Schanda P, Saalwächter K. 2018. Microsecond motions probed by near-rotary-resonance R1ρ 15N MAS NMR experiments: The model case of protein overall-rocking in crystals. Journal of Biomolecular NMR. 71(1), 53–67.' mla: 'Krushelnitsky, Alexey, et al. “Microsecond Motions Probed by Near-Rotary-Resonance R1ρ 15N MAS NMR Experiments: The Model Case of Protein Overall-Rocking in Crystals.” Journal of Biomolecular NMR, vol. 71, no. 1, Springer Nature, 2018, pp. 53–67, doi:10.1007/s10858-018-0191-4.' short: A. Krushelnitsky, D. Gauto, D.C. Rodriguez Camargo, P. Schanda, K. Saalwächter, Journal of Biomolecular NMR 71 (2018) 53–67. date_created: 2020-09-18T10:05:28Z date_published: 2018-05-30T00:00:00Z date_updated: 2021-01-12T08:19:17Z day: '30' doi: 10.1007/s10858-018-0191-4 extern: '1' intvolume: ' 71' issue: '1' language: - iso: eng month: '05' oa_version: Published Version page: 53-67 publication: Journal of Biomolecular NMR publication_identifier: issn: - 0925-2738 - 1573-5001 publication_status: published publisher: Springer Nature quality_controlled: '1' status: public title: 'Microsecond motions probed by near-rotary-resonance R1ρ 15N MAS NMR experiments: The model case of protein overall-rocking in crystals' type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 71 year: '2018' ... --- _id: '8439' abstract: - lang: eng text: Lipopolysaccharides (LPS) are complex glycolipids forming the outside layer of Gram-negative bacteria. Their hydrophobic and heterogeneous nature greatly hampers their structural study in an environment similar to the bacterial surface. We have studied LPS purified from E. coli and pathogenic P. aeruginosa with long O-antigen polysaccharides assembled in solution as vesicles or elongated micelles. Solid-state NMR with magic-angle spinning permitted the identification of NMR signals arising from regions with different flexibilities in the LPS, from the lipid components to the O-antigen polysaccharides. Atomic scale data on the LPS enabled the study of the interaction of gentamicin antibiotic bound to P. aeruginosa LPS, for which we could confirm that a specific oligosaccharide is involved in the antibiotic binding. The possibility to study LPS alone and bound to a ligand when it is assembled in membrane-like structures opens great prospects for the investigation of proteins and antibiotics that specifically target such an important molecule at the surface of Gram-negative bacteria. article_processing_charge: No article_type: original author: - first_name: Cedric full_name: Laguri, Cedric last_name: Laguri - first_name: Alba full_name: Silipo, Alba last_name: Silipo - first_name: Alessandra M. full_name: Martorana, Alessandra M. last_name: Martorana - first_name: Paul full_name: Schanda, Paul id: 7B541462-FAF6-11E9-A490-E8DFE5697425 last_name: Schanda orcid: 0000-0002-9350-7606 - first_name: Roberta full_name: Marchetti, Roberta last_name: Marchetti - first_name: Alessandra full_name: Polissi, Alessandra last_name: Polissi - first_name: Antonio full_name: Molinaro, Antonio last_name: Molinaro - first_name: Jean-Pierre full_name: Simorre, Jean-Pierre last_name: Simorre citation: ama: Laguri C, Silipo A, Martorana AM, et al. Solid state NMR studies of intact lipopolysaccharide endotoxin. ACS Chemical Biology. 2018;13(8):2106-2113. doi:10.1021/acschembio.8b00271 apa: Laguri, C., Silipo, A., Martorana, A. M., Schanda, P., Marchetti, R., Polissi, A., … Simorre, J.-P. (2018). Solid state NMR studies of intact lipopolysaccharide endotoxin. ACS Chemical Biology. American Chemical Society. https://doi.org/10.1021/acschembio.8b00271 chicago: Laguri, Cedric, Alba Silipo, Alessandra M. Martorana, Paul Schanda, Roberta Marchetti, Alessandra Polissi, Antonio Molinaro, and Jean-Pierre Simorre. “Solid State NMR Studies of Intact Lipopolysaccharide Endotoxin.” ACS Chemical Biology. American Chemical Society, 2018. https://doi.org/10.1021/acschembio.8b00271. ieee: C. Laguri et al., “Solid state NMR studies of intact lipopolysaccharide endotoxin,” ACS Chemical Biology, vol. 13, no. 8. American Chemical Society, pp. 2106–2113, 2018. ista: Laguri C, Silipo A, Martorana AM, Schanda P, Marchetti R, Polissi A, Molinaro A, Simorre J-P. 2018. Solid state NMR studies of intact lipopolysaccharide endotoxin. ACS Chemical Biology. 13(8), 2106–2113. mla: Laguri, Cedric, et al. “Solid State NMR Studies of Intact Lipopolysaccharide Endotoxin.” ACS Chemical Biology, vol. 13, no. 8, American Chemical Society, 2018, pp. 2106–13, doi:10.1021/acschembio.8b00271. short: C. Laguri, A. Silipo, A.M. Martorana, P. Schanda, R. Marchetti, A. Polissi, A. Molinaro, J.-P. Simorre, ACS Chemical Biology 13 (2018) 2106–2113. date_created: 2020-09-18T10:05:09Z date_published: 2018-07-02T00:00:00Z date_updated: 2021-01-12T08:19:16Z day: '02' doi: 10.1021/acschembio.8b00271 extern: '1' intvolume: ' 13' issue: '8' keyword: - Molecular Medicine - Biochemistry - General Medicine language: - iso: eng month: '07' oa_version: None page: 2106-2113 publication: ACS Chemical Biology publication_identifier: issn: - 1554-8929 - 1554-8937 publication_status: published publisher: American Chemical Society quality_controlled: '1' status: public title: Solid state NMR studies of intact lipopolysaccharide endotoxin type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 13 year: '2018' ...