--- _id: '15033' abstract: - lang: eng text: The GNOM (GN) Guanine nucleotide Exchange Factor for ARF small GTPases (ARF-GEF) is among the best studied trafficking regulators in plants, playing crucial and unique developmental roles in patterning and polarity. The current models place GN at the Golgi apparatus (GA), where it mediates secretion/recycling, and at the plasma membrane (PM) presumably contributing to clathrin-mediated endocytosis (CME). The mechanistic basis of the developmental function of GN, distinct from the other ARF-GEFs including its closest homologue GNOM-LIKE1 (GNL1), remains elusive. Insights from this study largely extend the current notions of GN function. We show that GN, but not GNL1, localizes to the cell periphery at long-lived structures distinct from clathrin-coated pits, while CME and secretion proceed normally in gn knockouts. The functional GN mutant variant GNfewerroots, absent from the GA, suggests that the cell periphery is the major site of GN action responsible for its developmental function. Following inhibition by Brefeldin A, GN, but not GNL1, relocates to the PM likely on exocytic vesicles, suggesting selective molecular associations en route to the cell periphery. A study of GN-GNL1 chimeric ARF-GEFs indicates that all GN domains contribute to the specific GN function in a partially redundant manner. Together, this study offers significant steps toward the elucidation of the mechanism underlying unique cellular and development functions of GNOM. acknowledgement: "The authors would like to gratefully acknowledge Dr Xixi Zhang for cloning the GNL1/pDONR221 construct and for useful discussions.H2020 European Research\r\nCouncil Advanced Grant ETAP742985 to Jiří Friml, Austrian Science Fund I 3630-B25 to Jiří Friml" article_processing_charge: Yes article_type: original author: - first_name: Maciek full_name: Adamowski, Maciek id: 45F536D2-F248-11E8-B48F-1D18A9856A87 last_name: Adamowski orcid: 0000-0001-6463-5257 - first_name: Ivana full_name: Matijevic, Ivana id: 83c17ce3-15b2-11ec-abd3-f486545870bd last_name: Matijevic - first_name: Jiří full_name: Friml, Jiří id: 4159519E-F248-11E8-B48F-1D18A9856A87 last_name: Friml orcid: 0000-0002-8302-7596 citation: ama: Adamowski M, Matijevic I, Friml J. Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery. eLife. 2024;13. doi:10.7554/elife.68993 apa: Adamowski, M., Matijevic, I., & Friml, J. (2024). Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.68993 chicago: Adamowski, Maciek, Ivana Matijevic, and Jiří Friml. “Developmental Patterning Function of GNOM ARF-GEF Mediated from the Cell Periphery.” ELife. eLife Sciences Publications, 2024. https://doi.org/10.7554/elife.68993. ieee: M. Adamowski, I. Matijevic, and J. Friml, “Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery,” eLife, vol. 13. eLife Sciences Publications, 2024. ista: Adamowski M, Matijevic I, Friml J. 2024. Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery. eLife. 13. mla: Adamowski, Maciek, et al. “Developmental Patterning Function of GNOM ARF-GEF Mediated from the Cell Periphery.” ELife, vol. 13, eLife Sciences Publications, 2024, doi:10.7554/elife.68993. short: M. Adamowski, I. Matijevic, J. Friml, ELife 13 (2024). date_created: 2024-02-27T07:10:11Z date_published: 2024-02-21T00:00:00Z date_updated: 2024-02-28T12:29:43Z day: '21' ddc: - '580' department: - _id: JiFr doi: 10.7554/elife.68993 ec_funded: 1 has_accepted_license: '1' intvolume: ' 13' keyword: - General Immunology and Microbiology - General Biochemistry - Genetics and Molecular Biology - General Medicine - General Neuroscience language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ main_file_link: - open_access: '1' url: https://doi.org/10.7554/eLife.68993 month: '02' oa: 1 oa_version: Published Version project: - _id: 261099A6-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '742985' name: Tracing Evolution of Auxin Transport and Polarity in Plants - _id: 26538374-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I03630 name: Molecular mechanisms of endocytic cargo recognition in plants publication: eLife publication_identifier: issn: - 2050-084X publication_status: epub_ahead publisher: eLife Sciences Publications quality_controlled: '1' status: public title: Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 13 year: '2024' ... --- _id: '14683' abstract: - lang: eng text: "Mosaic analysis with double markers (MADM) technology enables the generation of genetic mosaic tissue in mice and high-resolution phenotyping at the individual cell level. Here, we present a protocol for isolating MADM-labeled cells with high yield for downstream molecular analyses using fluorescence-activated cell sorting (FACS). We describe steps for generating MADM-labeled mice, perfusion, single-cell suspension, and debris removal. We then detail procedures for cell sorting by FACS and downstream analysis. This protocol is suitable for embryonic to adult mice.\r\nFor complete details on the use and execution of this protocol, please refer to Contreras et al. (2021).1" acknowledged_ssus: - _id: Bio - _id: PreCl acknowledgement: This research was supported by the Scientific Service Units (SSU) at IST Austria through resources provided by the Imaging & Optics Facility (IOF) and Preclinical Facilities (PCF). N.A. received support from FWF Firnberg-Programme (T 1031). G.C. received support from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 754411 as an ISTplus postdoctoral fellow. This work was also supported by IST Austria institutional funds, FWF SFB F78 to S.H., and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 725780 LinPro) to S.H. article_number: '102771' article_processing_charge: No article_type: review author: - first_name: Nicole full_name: Amberg, Nicole id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87 last_name: Amberg orcid: 0000-0002-3183-8207 - first_name: Giselle T full_name: Cheung, Giselle T id: 471195F6-F248-11E8-B48F-1D18A9856A87 last_name: Cheung orcid: 0000-0001-8457-2572 - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 citation: ama: Amberg N, Cheung GT, Hippenmeyer S. Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. STAR Protocols. 2023;5(1). doi:10.1016/j.xpro.2023.102771 apa: Amberg, N., Cheung, G. T., & Hippenmeyer, S. (2023). Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. STAR Protocols. Elsevier. https://doi.org/10.1016/j.xpro.2023.102771 chicago: Amberg, Nicole, Giselle T Cheung, and Simon Hippenmeyer. “Protocol for Sorting Cells from Mouse Brains Labeled with Mosaic Analysis with Double Markers by Flow Cytometry.” STAR Protocols. Elsevier, 2023. https://doi.org/10.1016/j.xpro.2023.102771. ieee: N. Amberg, G. T. Cheung, and S. Hippenmeyer, “Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry,” STAR Protocols, vol. 5, no. 1. Elsevier, 2023. ista: Amberg N, Cheung GT, Hippenmeyer S. 2023. Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. STAR Protocols. 5(1), 102771. mla: Amberg, Nicole, et al. “Protocol for Sorting Cells from Mouse Brains Labeled with Mosaic Analysis with Double Markers by Flow Cytometry.” STAR Protocols, vol. 5, no. 1, 102771, Elsevier, 2023, doi:10.1016/j.xpro.2023.102771. short: N. Amberg, G.T. Cheung, S. Hippenmeyer, STAR Protocols 5 (2023). date_created: 2023-12-13T11:48:05Z date_published: 2023-12-08T00:00:00Z date_updated: 2023-12-18T08:06:14Z day: '08' ddc: - '570' department: - _id: SiHi doi: 10.1016/j.xpro.2023.102771 ec_funded: 1 external_id: pmid: - '38070137' intvolume: ' 5' issue: '1' keyword: - General Immunology and Microbiology - General Biochemistry - Genetics and Molecular Biology - General Neuroscience language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1016/j.xpro.2023.102771 month: '12' oa: 1 oa_version: Submitted Version pmid: 1 project: - _id: 268F8446-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: T0101031 name: Role of Eed in neural stem cell lineage progression - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships - _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E grant_number: F07805 name: Molecular Mechanisms of Neural Stem Cell Lineage Progression - _id: 260018B0-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '725780' name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development publication: STAR Protocols publication_identifier: issn: - 2666-1667 publication_status: epub_ahead publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 5 year: '2023' ... --- _id: '14274' abstract: - lang: eng text: Immune responses rely on the rapid and coordinated migration of leukocytes. Whereas it is well established that single-cell migration is often guided by gradients of chemokines and other chemoattractants, it remains poorly understood how these gradients are generated, maintained, and modulated. By combining experimental data with theory on leukocyte chemotaxis guided by the G protein–coupled receptor (GPCR) CCR7, we demonstrate that in addition to its role as the sensory receptor that steers migration, CCR7 also acts as a generator and a modulator of chemotactic gradients. Upon exposure to the CCR7 ligand CCL19, dendritic cells (DCs) effectively internalize the receptor and ligand as part of the canonical GPCR desensitization response. We show that CCR7 internalization also acts as an effective sink for the chemoattractant, dynamically shaping the spatiotemporal distribution of the chemokine. This mechanism drives complex collective migration patterns, enabling DCs to create or sharpen chemotactic gradients. We further show that these self-generated gradients can sustain the long-range guidance of DCs, adapt collective migration patterns to the size and geometry of the environment, and provide a guidance cue for other comigrating cells. Such a dual role of CCR7 as a GPCR that both senses and consumes its ligand can thus provide a novel mode of cellular self-organization. acknowledgement: "We thank I. de Vries and the Scientific Service Units (Life Sciences, Bioimaging, Nanofabrication, Preclinical and Miba Machine Shop) of the Institute of Science and Technology Austria for excellent support, as well as all the rotation students assisting in the laboratory work (B. Zens, H. Schön, and D. Babic).\r\nThis work was supported by grants from the European Research Council under the European Union’s Horizon 2020 research to M.S. (grant agreement no. 724373) and to E.H. (grant agreement no. 851288), and a grant by the Austrian Science Fund (DK Nanocell W1250-B20) to M.S. J.A. was supported by the Jenny and Antti Wihuri Foundation and Research Council of Finland's Flagship Programme InFLAMES (decision number: 357910). M.C.U. was supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 754411." article_number: adc9584 article_processing_charge: No article_type: original author: - 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: Mehmet C full_name: Ucar, Mehmet C id: 50B2A802-6007-11E9-A42B-EB23E6697425 last_name: Ucar orcid: 0000-0003-0506-4217 - first_name: Nikola full_name: Canigova, Nikola id: 3795523E-F248-11E8-B48F-1D18A9856A87 last_name: Canigova orcid: 0000-0002-8518-5926 - first_name: Julian A full_name: Stopp, Julian A id: 489E3F00-F248-11E8-B48F-1D18A9856A87 last_name: Stopp - first_name: Jan full_name: Schwarz, Jan id: 346C1EC6-F248-11E8-B48F-1D18A9856A87 last_name: Schwarz - first_name: Jack full_name: Merrin, Jack id: 4515C308-F248-11E8-B48F-1D18A9856A87 last_name: Merrin orcid: 0000-0001-5145-4609 - first_name: Edouard B full_name: Hannezo, Edouard B id: 3A9DB764-F248-11E8-B48F-1D18A9856A87 last_name: Hannezo orcid: 0000-0001-6005-1561 - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 citation: ama: Alanko JH, Ucar MC, Canigova N, et al. CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration. Science Immunology. 2023;8(87). doi:10.1126/sciimmunol.adc9584 apa: Alanko, J. H., Ucar, M. C., Canigova, N., Stopp, J. A., Schwarz, J., Merrin, J., … Sixt, M. K. (2023). CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration. Science Immunology. American Association for the Advancement of Science. https://doi.org/10.1126/sciimmunol.adc9584 chicago: Alanko, Jonna H, Mehmet C Ucar, Nikola Canigova, Julian A Stopp, Jan Schwarz, Jack Merrin, Edouard B Hannezo, and Michael K Sixt. “CCR7 Acts as Both a Sensor and a Sink for CCL19 to Coordinate Collective Leukocyte Migration.” Science Immunology. American Association for the Advancement of Science, 2023. https://doi.org/10.1126/sciimmunol.adc9584. ieee: J. H. Alanko et al., “CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration,” Science Immunology, vol. 8, no. 87. American Association for the Advancement of Science, 2023. ista: Alanko JH, Ucar MC, Canigova N, Stopp JA, Schwarz J, Merrin J, Hannezo EB, Sixt MK. 2023. CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration. Science Immunology. 8(87), adc9584. mla: Alanko, Jonna H., et al. “CCR7 Acts as Both a Sensor and a Sink for CCL19 to Coordinate Collective Leukocyte Migration.” Science Immunology, vol. 8, no. 87, adc9584, American Association for the Advancement of Science, 2023, doi:10.1126/sciimmunol.adc9584. short: J.H. Alanko, M.C. Ucar, N. Canigova, J.A. Stopp, J. Schwarz, J. Merrin, E.B. Hannezo, M.K. Sixt, Science Immunology 8 (2023). date_created: 2023-09-06T08:07:51Z date_published: 2023-09-01T00:00:00Z date_updated: 2023-12-21T14:30:01Z day: '01' department: - _id: MiSi - _id: EdHa - _id: NanoFab doi: 10.1126/sciimmunol.adc9584 ec_funded: 1 external_id: isi: - '001062110600003' pmid: - '37656776' intvolume: ' 8' isi: 1 issue: '87' keyword: - General Medicine - Immunology language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1126/sciimmunol.adc9584 month: '09' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 25FE9508-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '724373' name: Cellular navigation along spatial gradients - _id: 05943252-7A3F-11EA-A408-12923DDC885E call_identifier: H2020 grant_number: '851288' name: Design Principles of Branching Morphogenesis - _id: 265E2996-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W01250-B20 name: Nano-Analytics of Cellular Systems - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships publication: Science Immunology publication_identifier: issn: - 2470-9468 publication_status: published publisher: American Association for the Advancement of Science quality_controlled: '1' related_material: record: - id: '14279' relation: research_data status: public - id: '14697' relation: dissertation_contains status: public scopus_import: '1' status: public title: CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 8 year: '2023' ... --- _id: '10639' abstract: - lang: eng text: With more than 80 members worldwide, the Orthobunyavirus genus in the Peribunyaviridae family is a large genus of enveloped RNA viruses, many of which are emerging pathogens in humans and livestock. How orthobunyaviruses (OBVs) penetrate and infect mammalian host cells remains poorly characterized. Here, we investigated the entry mechanisms of the OBV Germiston (GERV). Viral particles were visualized by cryo-electron microscopy and appeared roughly spherical with an average diameter of 98 nm. Labeling of the virus with fluorescent dyes did not adversely affect its infectivity and allowed the monitoring of single particles in fixed and live cells. Using this approach, we found that endocytic internalization of bound viruses was asynchronous and occurred within 30-40 min. The virus entered Rab5a+ early endosomes and, subsequently, late endosomal vacuoles containing Rab7a but not LAMP-1. Infectious entry did not require proteolytic cleavage, and endosomal acidification was sufficient and necessary for viral fusion. Acid-activated penetration began 15-25 min after initiation of virus internalization and relied on maturation of early endosomes to late endosomes. The optimal pH for viral membrane fusion was slightly below 6.0, and penetration was hampered when the potassium influx was abolished. Overall, our study provides real-time visualization of GERV entry into host cells and demonstrates the importance of late endosomal maturation in facilitating OBV penetration. acknowledged_ssus: - _id: EM-Fac acknowledgement: This work was supported by INRAE starter funds, Project IDEXLYON (University of Lyon) within the Programme Investissements d’Avenir (ANR-16-IDEX-0005), and FINOVIAO14 (Fondation pour l’Université de Lyon), all to P.Y.L. This work was also supported by CellNetworks Research Group funds and Deutsche Forschungsgemeinschaft (DFG) funding (grant numbers LO-2338/1-1 and LO-2338/3-1) awarded to P.Y.L., Austrian Science Fund (FWF) grant P31445 to F.K.M.S., a Chinese Scholarship Council (CSC;no. 201904910701) fellowship to Q.X., and a ministére de l’enseignement supérieur, de la recherche et de l’innovation (MESRI) doctoral thesis grant to M.D. article_number: e02146-21 article_processing_charge: No article_type: original author: - first_name: Stefan full_name: Windhaber, Stefan last_name: Windhaber - first_name: Qilin full_name: Xin, Qilin last_name: Xin - first_name: Zina M. full_name: Uckeley, Zina M. last_name: Uckeley - first_name: Jana full_name: Koch, Jana last_name: Koch - first_name: Martin full_name: Obr, Martin id: 4741CA5A-F248-11E8-B48F-1D18A9856A87 last_name: Obr - first_name: Céline full_name: Garnier, Céline last_name: Garnier - first_name: Catherine full_name: Luengo-Guyonnot, Catherine last_name: Luengo-Guyonnot - first_name: Maëva full_name: Duboeuf, Maëva last_name: Duboeuf - first_name: Florian KM full_name: Schur, Florian KM id: 48AD8942-F248-11E8-B48F-1D18A9856A87 last_name: Schur orcid: 0000-0003-4790-8078 - first_name: Pierre-Yves full_name: Lozach, Pierre-Yves last_name: Lozach citation: ama: Windhaber S, Xin Q, Uckeley ZM, et al. The Orthobunyavirus Germiston enters host cells from late endosomes. Journal of Virology. 2022;96(5). doi:10.1128/jvi.02146-21 apa: Windhaber, S., Xin, Q., Uckeley, Z. M., Koch, J., Obr, M., Garnier, C., … Lozach, P.-Y. (2022). The Orthobunyavirus Germiston enters host cells from late endosomes. Journal of Virology. American Society for Microbiology. https://doi.org/10.1128/jvi.02146-21 chicago: Windhaber, Stefan, Qilin Xin, Zina M. Uckeley, Jana Koch, Martin Obr, Céline Garnier, Catherine Luengo-Guyonnot, Maëva Duboeuf, Florian KM Schur, and Pierre-Yves Lozach. “The Orthobunyavirus Germiston Enters Host Cells from Late Endosomes.” Journal of Virology. American Society for Microbiology, 2022. https://doi.org/10.1128/jvi.02146-21. ieee: S. Windhaber et al., “The Orthobunyavirus Germiston enters host cells from late endosomes,” Journal of Virology, vol. 96, no. 5. American Society for Microbiology, 2022. ista: Windhaber S, Xin Q, Uckeley ZM, Koch J, Obr M, Garnier C, Luengo-Guyonnot C, Duboeuf M, Schur FK, Lozach P-Y. 2022. The Orthobunyavirus Germiston enters host cells from late endosomes. Journal of Virology. 96(5), e02146-21. mla: Windhaber, Stefan, et al. “The Orthobunyavirus Germiston Enters Host Cells from Late Endosomes.” Journal of Virology, vol. 96, no. 5, e02146-21, American Society for Microbiology, 2022, doi:10.1128/jvi.02146-21. short: S. Windhaber, Q. Xin, Z.M. Uckeley, J. Koch, M. Obr, C. Garnier, C. Luengo-Guyonnot, M. Duboeuf, F.K. Schur, P.-Y. Lozach, Journal of Virology 96 (2022). date_created: 2022-01-18T10:04:18Z date_published: 2022-03-01T00:00:00Z date_updated: 2023-08-02T13:52:33Z day: '01' department: - _id: FlSc doi: 10.1128/jvi.02146-21 external_id: isi: - '000779305000033' pmid: - '35019710' intvolume: ' 96' isi: 1 issue: '5' keyword: - virology - insect science - immunology - microbiology language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906410 month: '03' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 26736D6A-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P31445 name: Structural conservation and diversity in retroviral capsid publication: Journal of Virology publication_identifier: eissn: - 1098-5514 issn: - 0022-538X publication_status: published publisher: American Society for Microbiology quality_controlled: '1' scopus_import: '1' status: public title: The Orthobunyavirus Germiston enters host cells from late endosomes type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 96 year: '2022' ... --- _id: '10812' abstract: - lang: eng text: Several promising strategies based on combining or cycling different antibiotics have been proposed to increase efficacy and counteract resistance evolution, but we still lack a deep understanding of the physiological responses and genetic mechanisms that underlie antibiotic interactions and the clinical applicability of these strategies. In antibiotic-exposed bacteria, the combined effects of physiological stress responses and emerging resistance mutations (occurring at different time scales) generate complex and often unpredictable dynamics. In this Review, we present our current understanding of bacterial cell physiology and genetics of responses to antibiotics. We emphasize recently discovered mechanisms of synergistic and antagonistic drug interactions, hysteresis in temporal interactions between antibiotics that arise from microbial physiology and interactions between antibiotics and resistance mutations that can cause collateral sensitivity or cross-resistance. We discuss possible connections between the different phenomena and indicate relevant research directions. A better and more unified understanding of drug and genetic interactions is likely to advance antibiotic therapy. acknowledgement: The authors thank B. Kavčič and H. Schulenburg for constructive feedback on the manuscript. article_processing_charge: No article_type: review author: - first_name: Roderich full_name: Römhild, Roderich id: 68E56E44-62B0-11EA-B963-444F3DDC885E last_name: Römhild orcid: 0000-0001-9480-5261 - first_name: Mark Tobias full_name: Bollenbach, Mark Tobias id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87 last_name: Bollenbach orcid: 0000-0003-4398-476X - first_name: Dan I. full_name: Andersson, Dan I. last_name: Andersson citation: ama: Römhild R, Bollenbach MT, Andersson DI. The physiology and genetics of bacterial responses to antibiotic combinations. Nature Reviews Microbiology. 2022;20:478-490. doi:10.1038/s41579-022-00700-5 apa: Römhild, R., Bollenbach, M. T., & Andersson, D. I. (2022). The physiology and genetics of bacterial responses to antibiotic combinations. Nature Reviews Microbiology. Springer Nature. https://doi.org/10.1038/s41579-022-00700-5 chicago: Römhild, Roderich, Mark Tobias Bollenbach, and Dan I. Andersson. “The Physiology and Genetics of Bacterial Responses to Antibiotic Combinations.” Nature Reviews Microbiology. Springer Nature, 2022. https://doi.org/10.1038/s41579-022-00700-5. ieee: R. Römhild, M. T. Bollenbach, and D. I. Andersson, “The physiology and genetics of bacterial responses to antibiotic combinations,” Nature Reviews Microbiology, vol. 20. Springer Nature, pp. 478–490, 2022. ista: Römhild R, Bollenbach MT, Andersson DI. 2022. The physiology and genetics of bacterial responses to antibiotic combinations. Nature Reviews Microbiology. 20, 478–490. mla: Römhild, Roderich, et al. “The Physiology and Genetics of Bacterial Responses to Antibiotic Combinations.” Nature Reviews Microbiology, vol. 20, Springer Nature, 2022, pp. 478–90, doi:10.1038/s41579-022-00700-5. short: R. Römhild, M.T. Bollenbach, D.I. Andersson, Nature Reviews Microbiology 20 (2022) 478–490. date_created: 2022-03-04T04:33:49Z date_published: 2022-08-01T00:00:00Z date_updated: 2023-08-02T14:41:44Z day: '01' department: - _id: CaGu doi: 10.1038/s41579-022-00700-5 external_id: isi: - '000763891900001' pmid: - '35241807' intvolume: ' 20' isi: 1 keyword: - General Immunology and Microbiology - Microbiology - Infectious Diseases language: - iso: eng month: '08' oa_version: None page: 478-490 pmid: 1 publication: Nature Reviews Microbiology publication_identifier: eissn: - 1740-1534 issn: - 1740-1526 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: The physiology and genetics of bacterial responses to antibiotic combinations type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 20 year: '2022' ... --- _id: '11448' abstract: - lang: eng text: Studies of protein fitness landscapes reveal biophysical constraints guiding protein evolution and empower prediction of functional proteins. However, generalisation of these findings is limited due to scarceness of systematic data on fitness landscapes of proteins with a defined evolutionary relationship. We characterized the fitness peaks of four orthologous fluorescent proteins with a broad range of sequence divergence. While two of the four studied fitness peaks were sharp, the other two were considerably flatter, being almost entirely free of epistatic interactions. Mutationally robust proteins, characterized by a flat fitness peak, were not optimal templates for machine-learning-driven protein design – instead, predictions were more accurate for fragile proteins with epistatic landscapes. Our work paves insights for practical application of fitness landscape heterogeneity in protein engineering. acknowledged_ssus: - _id: LifeSc - _id: Bio acknowledgement: "We thank Ondřej Draganov, Rodrigo Redondo, Bor Kavčič, Mia Juračić and Andrea Pauli for discussion and technical advice. We thank Anita Testa Salmazo for advice on resin protein purification, Dmitry Bolotin and the Milaboratory (milaboratory.com) for access to computing and storage infrastructure, and Josef Houser and Eva Fujdiarova for technical assistance and data interpretation. Core facility Biomolecular Interactions and Crystallization of CEITEC Masaryk University is gratefully acknowledged for the obtaining of the scientific data presented in this paper. This research was supported by the Scientific Service Units (SSU) of IST-Austria\r\nthrough resources provided by the Bioimaging Facility (BIF), and the Life Science Facility (LSF). MiSeq and HiSeq NGS sequencing was performed by the Next Generation Sequencing Facility at Vienna BioCenter Core Facilities (VBCF), member of the Vienna BioCenter (VBC), Austria. FACS was performed at the BioOptics Facility of the Institute of Molecular Pathology (IMP), Austria. We also thank the Biomolecular Crystallography Facility in the Vanderbilt University Center for Structural Biology. We are grateful to Joel M Harp for help with X-ray data collection. This work was supported by the ERC Consolidator grant to FAK (771209—CharFL). KSS acknowledges support by President’s Grant МК–5405.2021.1.4, the Imperial College Research Fellowship and the MRC London Institute of Medical Sciences (UKRI MC-A658-5QEA0).\r\nAF is supported by the Marie Skłodowska-Curie Fellowship (H2020-MSCA-IF-2019, Grant Agreement No. 898203, Project acronym \"FLINDIP\"). Experiments were partially carried out using equipment provided by the Institute of Bioorganic Chemistry of the Russian Academy of Sciences Сore Facility (CKP IBCH). This work was supported by a Russian Science Foundation grant 19-74-10102.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 665,385." article_number: '75842' article_processing_charge: No article_type: original author: - first_name: Louisa full_name: Gonzalez Somermeyer, Louisa id: 4720D23C-F248-11E8-B48F-1D18A9856A87 last_name: Gonzalez Somermeyer orcid: 0000-0001-9139-5383 - first_name: Aubin full_name: Fleiss, Aubin last_name: Fleiss - first_name: Alexander S full_name: Mishin, Alexander S last_name: Mishin - first_name: Nina G full_name: Bozhanova, Nina G last_name: Bozhanova - first_name: Anna A full_name: Igolkina, Anna A last_name: Igolkina - first_name: Jens full_name: Meiler, Jens last_name: Meiler - first_name: Maria-Elisenda full_name: Alaball Pujol, Maria-Elisenda last_name: Alaball Pujol - first_name: Ekaterina V full_name: Putintseva, Ekaterina V last_name: Putintseva - first_name: Karen S full_name: Sarkisyan, Karen S last_name: Sarkisyan - first_name: Fyodor full_name: Kondrashov, Fyodor id: 44FDEF62-F248-11E8-B48F-1D18A9856A87 last_name: Kondrashov orcid: 0000-0001-8243-4694 citation: ama: Gonzalez Somermeyer L, Fleiss A, Mishin AS, et al. Heterogeneity of the GFP fitness landscape and data-driven protein design. eLife. 2022;11. doi:10.7554/elife.75842 apa: Gonzalez Somermeyer, L., Fleiss, A., Mishin, A. S., Bozhanova, N. G., Igolkina, A. A., Meiler, J., … Kondrashov, F. (2022). Heterogeneity of the GFP fitness landscape and data-driven protein design. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.75842 chicago: Gonzalez Somermeyer, Louisa, Aubin Fleiss, Alexander S Mishin, Nina G Bozhanova, Anna A Igolkina, Jens Meiler, Maria-Elisenda Alaball Pujol, Ekaterina V Putintseva, Karen S Sarkisyan, and Fyodor Kondrashov. “Heterogeneity of the GFP Fitness Landscape and Data-Driven Protein Design.” ELife. eLife Sciences Publications, 2022. https://doi.org/10.7554/elife.75842. ieee: L. Gonzalez Somermeyer et al., “Heterogeneity of the GFP fitness landscape and data-driven protein design,” eLife, vol. 11. eLife Sciences Publications, 2022. ista: Gonzalez Somermeyer L, Fleiss A, Mishin AS, Bozhanova NG, Igolkina AA, Meiler J, Alaball Pujol M-E, Putintseva EV, Sarkisyan KS, Kondrashov F. 2022. Heterogeneity of the GFP fitness landscape and data-driven protein design. eLife. 11, 75842. mla: Gonzalez Somermeyer, Louisa, et al. “Heterogeneity of the GFP Fitness Landscape and Data-Driven Protein Design.” ELife, vol. 11, 75842, eLife Sciences Publications, 2022, doi:10.7554/elife.75842. short: L. Gonzalez Somermeyer, A. Fleiss, A.S. Mishin, N.G. Bozhanova, A.A. Igolkina, J. Meiler, M.-E. Alaball Pujol, E.V. Putintseva, K.S. Sarkisyan, F. Kondrashov, ELife 11 (2022). date_created: 2022-06-18T09:06:59Z date_published: 2022-05-05T00:00:00Z date_updated: 2023-08-03T07:20:15Z day: '05' ddc: - '570' department: - _id: GradSch - _id: FyKo doi: 10.7554/elife.75842 ec_funded: 1 external_id: isi: - '000799197200001' file: - access_level: open_access checksum: 7573c28f44028ab0cc81faef30039e44 content_type: application/pdf creator: dernst date_created: 2022-06-20T07:44:19Z date_updated: 2022-06-20T07:44:19Z file_id: '11454' file_name: 2022_eLife_Somermeyer.pdf file_size: 5297213 relation: main_file success: 1 file_date_updated: 2022-06-20T07:44:19Z has_accepted_license: '1' intvolume: ' 11' isi: 1 keyword: - General Immunology and Microbiology - General Biochemistry - Genetics and Molecular Biology - General Medicine - General Neuroscience language: - iso: eng month: '05' oa: 1 oa_version: Published Version project: - _id: 26580278-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '771209' name: Characterizing the fitness landscape on population and global scales - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication: eLife publication_identifier: issn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: Heterogeneity of the GFP fitness landscape and data-driven protein design tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 11 year: '2022' ... --- _id: '11447' abstract: - lang: eng text: Empirical essays of fitness landscapes suggest that they may be rugged, that is having multiple fitness peaks. Such fitness landscapes, those that have multiple peaks, necessarily have special local structures, called reciprocal sign epistasis (Poelwijk et al. in J Theor Biol 272:141–144, 2011). Here, we investigate the quantitative relationship between the number of fitness peaks and the number of reciprocal sign epistatic interactions. Previously, it has been shown (Poelwijk et al. in J Theor Biol 272:141–144, 2011) that pairwise reciprocal sign epistasis is a necessary but not sufficient condition for the existence of multiple peaks. Applying discrete Morse theory, which to our knowledge has never been used in this context, we extend this result by giving the minimal number of reciprocal sign epistatic interactions required to create a given number of peaks. acknowledgement: We are grateful to Herbert Edelsbrunner and Jeferson Zapata for helpful discussions. Open access funding provided by Austrian Science Fund (FWF). Partially supported by the ERC Consolidator (771209–CharFL) and the FWF Austrian Science Fund (I5127-B) grants to FAK. article_number: '74' article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Raimundo J full_name: Saona Urmeneta, Raimundo J id: BD1DF4C4-D767-11E9-B658-BC13E6697425 last_name: Saona Urmeneta orcid: 0000-0001-5103-038X - first_name: Fyodor full_name: Kondrashov, Fyodor id: 44FDEF62-F248-11E8-B48F-1D18A9856A87 last_name: Kondrashov orcid: 0000-0001-8243-4694 - first_name: Kseniia full_name: Khudiakova, Kseniia id: 4E6DC800-AE37-11E9-AC72-31CAE5697425 last_name: Khudiakova orcid: 0000-0002-6246-1465 citation: ama: Saona Urmeneta RJ, Kondrashov F, Khudiakova K. Relation between the number of peaks and the number of reciprocal sign epistatic interactions. Bulletin of Mathematical Biology. 2022;84(8). doi:10.1007/s11538-022-01029-z apa: Saona Urmeneta, R. J., Kondrashov, F., & Khudiakova, K. (2022). Relation between the number of peaks and the number of reciprocal sign epistatic interactions. Bulletin of Mathematical Biology. Springer Nature. https://doi.org/10.1007/s11538-022-01029-z chicago: Saona Urmeneta, Raimundo J, Fyodor Kondrashov, and Kseniia Khudiakova. “Relation between the Number of Peaks and the Number of Reciprocal Sign Epistatic Interactions.” Bulletin of Mathematical Biology. Springer Nature, 2022. https://doi.org/10.1007/s11538-022-01029-z. ieee: R. J. Saona Urmeneta, F. Kondrashov, and K. Khudiakova, “Relation between the number of peaks and the number of reciprocal sign epistatic interactions,” Bulletin of Mathematical Biology, vol. 84, no. 8. Springer Nature, 2022. ista: Saona Urmeneta RJ, Kondrashov F, Khudiakova K. 2022. Relation between the number of peaks and the number of reciprocal sign epistatic interactions. Bulletin of Mathematical Biology. 84(8), 74. mla: Saona Urmeneta, Raimundo J., et al. “Relation between the Number of Peaks and the Number of Reciprocal Sign Epistatic Interactions.” Bulletin of Mathematical Biology, vol. 84, no. 8, 74, Springer Nature, 2022, doi:10.1007/s11538-022-01029-z. short: R.J. Saona Urmeneta, F. Kondrashov, K. Khudiakova, Bulletin of Mathematical Biology 84 (2022). date_created: 2022-06-17T16:16:15Z date_published: 2022-06-17T00:00:00Z date_updated: 2023-08-03T07:20:53Z day: '17' ddc: - '510' - '570' department: - _id: GradSch - _id: NiBa - _id: JaMa doi: 10.1007/s11538-022-01029-z ec_funded: 1 external_id: isi: - '000812509800001' file: - access_level: open_access checksum: 05a1fe7d10914a00c2bca9b447993a65 content_type: application/pdf creator: dernst date_created: 2022-06-20T07:51:32Z date_updated: 2022-06-20T07:51:32Z file_id: '11455' file_name: 2022_BulletinMathBiology_Saona.pdf file_size: 463025 relation: main_file success: 1 file_date_updated: 2022-06-20T07:51:32Z has_accepted_license: '1' intvolume: ' 84' isi: 1 issue: '8' keyword: - Computational Theory and Mathematics - General Agricultural and Biological Sciences - Pharmacology - General Environmental Science - General Biochemistry - Genetics and Molecular Biology - General Mathematics - Immunology - General Neuroscience language: - iso: eng month: '06' oa: 1 oa_version: Published Version project: - _id: 26580278-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '771209' name: Characterizing the fitness landscape on population and global scales - _id: c098eddd-5a5b-11eb-8a69-abe27170a68f grant_number: I05127 name: Evolutionary analysis of gene regulation publication: Bulletin of Mathematical Biology publication_identifier: eissn: - 1522-9602 issn: - 0092-8240 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - relation: erratum url: https://doi.org/10.1007/s11538-022-01118-z scopus_import: '1' status: public title: Relation between the number of peaks and the number of reciprocal sign epistatic interactions tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 84 year: '2022' ... --- _id: '12119' abstract: - lang: eng text: Intravascular neutrophils and platelets collaborate in maintaining host integrity, but their interaction can also trigger thrombotic complications. We report here that cooperation between neutrophil and platelet lineages extends to the earliest stages of platelet formation by megakaryocytes in the bone marrow. Using intravital microscopy, we show that neutrophils “plucked” intravascular megakaryocyte extensions, termed proplatelets, to control platelet production. Following CXCR4-CXCL12-dependent migration towards perisinusoidal megakaryocytes, plucking neutrophils actively pulled on proplatelets and triggered myosin light chain and extracellular-signal-regulated kinase activation through reactive oxygen species. By these mechanisms, neutrophils accelerate proplatelet growth and facilitate continuous release of platelets in steady state. Following myocardial infarction, plucking neutrophils drove excessive release of young, reticulated platelets and boosted the risk of recurrent ischemia. Ablation of neutrophil plucking normalized thrombopoiesis and reduced recurrent thrombosis after myocardial infarction and thrombus burden in venous thrombosis. We establish neutrophil plucking as a target to reduce thromboischemic events. acknowledgement: "We thank Coung Kieu and Dominik van den Heuvel for excellent technical assistance. This work was supported by the German Research Foundation (PE2704/2-1, PE2704/3-1 to T.P., SFB 1123-project B06 to S.M., SFB1525 project A07 to D.S, TRR 332 project A7 to C.S., PO 2247/2-1 to A.P., SFB1116-project B11 to A.P. and B12 to M.K.), LMU Munich’s Institutional\r\nStrategy LMUexcellent within the framework of the German Excellence Initiative (No. 806 32 006 to T.P.), and by the German Centre for Cardiovascular Research (DZHK) to T.P. (Postdoc Start-up grant No. 100378833). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No. 833440 to S.M.). F.G. received funding from the European Union’s\r\nHorizon 2020 research and innovation program under the Marie Sk1odowska-Curie grant agreement no. 747687. A.H. was funded by RTI2018-095497-B-I00 from Ministerio de Ciencia e Innovacio´ n (MICINN), HR17_00527 from Fundacion La Caixa, and Transatlantic Network of Excellence (TNE-18CVD04) from the Leducq Foundation. The CNIC is supported by the MICINN and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (CEX2020-001041-S). A.P. was supported by the Forschungskommission of the Medical Faculty of the Heinrich-Heine-Universität Düsseldorf (No. 18-2019 to A.P.). C.G. was supported by the Helmholtz Alliance ‘Aging and Metabolic Programming, AMPro,’ by the German Federal\r\nMinistry of Education and Research to the German Center for Diabetes Research (DZD), and by the Bavarian State Ministry of Health and Care through the research project DigiMed Bayern." article_processing_charge: No article_type: original author: - first_name: Tobias full_name: Petzold, Tobias last_name: Petzold - first_name: Zhe full_name: Zhang, Zhe last_name: Zhang - first_name: Iván full_name: Ballesteros, Iván last_name: Ballesteros - first_name: Inas full_name: Saleh, Inas last_name: Saleh - first_name: Amin full_name: Polzin, Amin last_name: Polzin - first_name: Manuela full_name: Thienel, Manuela last_name: Thienel - first_name: Lulu full_name: Liu, Lulu last_name: Liu - first_name: Qurrat full_name: Ul Ain, Qurrat last_name: Ul Ain - first_name: Vincent full_name: Ehreiser, Vincent last_name: Ehreiser - first_name: Christian full_name: Weber, Christian last_name: Weber - first_name: Badr full_name: Kilani, Badr last_name: Kilani - first_name: Pontus full_name: Mertsch, Pontus last_name: Mertsch - first_name: Jeremias full_name: Götschke, Jeremias last_name: Götschke - first_name: Sophie full_name: Cremer, Sophie last_name: Cremer - first_name: Wenwen full_name: Fu, Wenwen last_name: Fu - first_name: Michael full_name: Lorenz, Michael last_name: Lorenz - first_name: Hellen full_name: Ishikawa-Ankerhold, Hellen last_name: Ishikawa-Ankerhold - first_name: Elisabeth full_name: Raatz, Elisabeth last_name: Raatz - first_name: Shaza full_name: El-Nemr, Shaza last_name: El-Nemr - first_name: Agnes full_name: Görlach, Agnes last_name: Görlach - first_name: Esther full_name: Marhuenda, Esther last_name: Marhuenda - first_name: Konstantin full_name: Stark, Konstantin last_name: Stark - first_name: Joachim full_name: Pircher, Joachim last_name: Pircher - first_name: David full_name: Stegner, David last_name: Stegner - first_name: Christian full_name: Gieger, Christian last_name: Gieger - first_name: Marc full_name: Schmidt-Supprian, Marc last_name: Schmidt-Supprian - first_name: Florian R full_name: Gärtner, Florian R id: 397A88EE-F248-11E8-B48F-1D18A9856A87 last_name: Gärtner orcid: 0000-0001-6120-3723 - first_name: Isaac full_name: Almendros, Isaac last_name: Almendros - first_name: Malte full_name: Kelm, Malte last_name: Kelm - first_name: Christian full_name: Schulz, Christian last_name: Schulz - first_name: Andrés full_name: Hidalgo, Andrés last_name: Hidalgo - first_name: Steffen full_name: Massberg, Steffen last_name: Massberg citation: ama: Petzold T, Zhang Z, Ballesteros I, et al. Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease. Immunity. 2022;55(12):2285-2299.e7. doi:10.1016/j.immuni.2022.10.001 apa: Petzold, T., Zhang, Z., Ballesteros, I., Saleh, I., Polzin, A., Thienel, M., … Massberg, S. (2022). Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease. Immunity. Elsevier. https://doi.org/10.1016/j.immuni.2022.10.001 chicago: Petzold, Tobias, Zhe Zhang, Iván Ballesteros, Inas Saleh, Amin Polzin, Manuela Thienel, Lulu Liu, et al. “Neutrophil ‘Plucking’ on Megakaryocytes Drives Platelet Production and Boosts Cardiovascular Disease.” Immunity. Elsevier, 2022. https://doi.org/10.1016/j.immuni.2022.10.001. ieee: T. Petzold et al., “Neutrophil ‘plucking’ on megakaryocytes drives platelet production and boosts cardiovascular disease,” Immunity, vol. 55, no. 12. Elsevier, p. 2285–2299.e7, 2022. ista: Petzold T, Zhang Z, Ballesteros I, Saleh I, Polzin A, Thienel M, Liu L, Ul Ain Q, Ehreiser V, Weber C, Kilani B, Mertsch P, Götschke J, Cremer S, Fu W, Lorenz M, Ishikawa-Ankerhold H, Raatz E, El-Nemr S, Görlach A, Marhuenda E, Stark K, Pircher J, Stegner D, Gieger C, Schmidt-Supprian M, Gärtner FR, Almendros I, Kelm M, Schulz C, Hidalgo A, Massberg S. 2022. Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease. Immunity. 55(12), 2285–2299.e7. mla: Petzold, Tobias, et al. “Neutrophil ‘Plucking’ on Megakaryocytes Drives Platelet Production and Boosts Cardiovascular Disease.” Immunity, vol. 55, no. 12, Elsevier, 2022, p. 2285–2299.e7, doi:10.1016/j.immuni.2022.10.001. short: T. Petzold, Z. Zhang, I. Ballesteros, I. Saleh, A. Polzin, M. Thienel, L. Liu, Q. Ul Ain, V. Ehreiser, C. Weber, B. Kilani, P. Mertsch, J. Götschke, S. Cremer, W. Fu, M. Lorenz, H. Ishikawa-Ankerhold, E. Raatz, S. El-Nemr, A. Görlach, E. Marhuenda, K. Stark, J. Pircher, D. Stegner, C. Gieger, M. Schmidt-Supprian, F.R. Gärtner, I. Almendros, M. Kelm, C. Schulz, A. Hidalgo, S. Massberg, Immunity 55 (2022) 2285–2299.e7. date_created: 2023-01-12T11:56:54Z date_published: 2022-12-13T00:00:00Z date_updated: 2023-08-03T14:21:51Z day: '13' ddc: - '570' department: - _id: MiSi doi: 10.1016/j.immuni.2022.10.001 ec_funded: 1 external_id: isi: - '000922019600003' pmid: - '36272416' file: - access_level: open_access checksum: 073267a9c0ad9f85a650053bc7b23777 content_type: application/pdf creator: dernst date_created: 2023-01-23T10:18:48Z date_updated: 2023-01-23T10:18:48Z file_id: '12341' file_name: 2022_Immunity_Petzold.pdf file_size: 5299475 relation: main_file success: 1 file_date_updated: 2023-01-23T10:18:48Z has_accepted_license: '1' intvolume: ' 55' isi: 1 issue: '12' keyword: - Infectious Diseases - Immunology - Immunology and Allergy language: - iso: eng license: https://creativecommons.org/licenses/by-nc-nd/4.0/ month: '12' oa: 1 oa_version: Published Version page: 2285-2299.e7 pmid: 1 project: - _id: 260AA4E2-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '747687' name: Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells publication: Immunity publication_identifier: issn: - 1074-7613 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 55 year: '2022' ... --- _id: '12131' abstract: - lang: eng text: Replication-incompetent adenoviral vectors have been extensively used as a platform for vaccine design, with at least four anti-COVID-19 vaccines authorized to date. These vaccines elicit neutralizing antibody responses directed against SARS-CoV-2 Spike protein and confer significant level of protection against SARS-CoV-2 infection. Immunization with adenovirus-vectored vaccines is known to be accompanied by the production of anti-vector antibodies, which may translate into reduced efficacy of booster or repeated rounds of revaccination. Here, we used blood samples from patients who received an adenovirus-based Gam-COVID-Vac vaccine to address the question of whether anti-vector antibodies may influence the magnitude of SARS-CoV-2-specific humoral response after booster vaccination. We observed that rAd26-based prime vaccination with Gam-COVID-Vac induced the development of Ad26-neutralizing antibodies, which persisted in circulation for at least 9 months. Our analysis further indicates that high pre-boost Ad26 neutralizing antibody titers do not appear to affect the humoral immunogenicity of the Gam-COVID-Vac boost. The titers of anti-SARS-CoV-2 RBD IgGs and antibodies, which neutralized both the wild type and the circulating variants of concern of SARS-CoV-2 such as Delta and Omicron, were independent of the pre-boost levels of Ad26-neutralizing antibodies. Thus, our results support the development of repeated immunization schedule with adenovirus-based COVID-19 vaccines. acknowledgement: We thank Sergey Kulemzin, Grigory Efimov, Yuri Lebedin, Alexander Taranin and Rudolf Valenta for providing reagents. Figures were created with the help of BioRender.com. This work was supported by the Russian Science Foundation (Project 21-15-00286). Byazrova M.G. was supported by the RUDN University Strategic Academic Leadership Program. article_number: '145' article_processing_charge: No article_type: original author: - first_name: Maria G. full_name: Byazrova, Maria G. last_name: Byazrova - first_name: Ekaterina A. full_name: Astakhova, Ekaterina A. last_name: Astakhova - first_name: Aygul full_name: Minnegalieva, Aygul id: 87DF77F0-1D9A-11EA-B6AE-CE443DDC885E last_name: Minnegalieva - first_name: Maria M. full_name: Sukhova, Maria M. last_name: Sukhova - first_name: Artem A. full_name: Mikhailov, Artem A. last_name: Mikhailov - first_name: Alexey G. full_name: Prilipov, Alexey G. last_name: Prilipov - first_name: Andrey A. full_name: Gorchakov, Andrey A. last_name: Gorchakov - first_name: Alexander V. full_name: Filatov, Alexander V. last_name: Filatov citation: ama: Byazrova MG, Astakhova EA, Minnegalieva A, et al. Anti-Ad26 humoral immunity does not compromise SARS-COV-2 neutralizing antibody responses following Gam-COVID-Vac booster vaccination. npj Vaccines. 2022;7. doi:10.1038/s41541-022-00566-x apa: Byazrova, M. G., Astakhova, E. A., Minnegalieva, A., Sukhova, M. M., Mikhailov, A. A., Prilipov, A. G., … Filatov, A. V. (2022). Anti-Ad26 humoral immunity does not compromise SARS-COV-2 neutralizing antibody responses following Gam-COVID-Vac booster vaccination. Npj Vaccines. Springer Nature. https://doi.org/10.1038/s41541-022-00566-x chicago: Byazrova, Maria G., Ekaterina A. Astakhova, Aygul Minnegalieva, Maria M. Sukhova, Artem A. Mikhailov, Alexey G. Prilipov, Andrey A. Gorchakov, and Alexander V. Filatov. “Anti-Ad26 Humoral Immunity Does Not Compromise SARS-COV-2 Neutralizing Antibody Responses Following Gam-COVID-Vac Booster Vaccination.” Npj Vaccines. Springer Nature, 2022. https://doi.org/10.1038/s41541-022-00566-x. ieee: M. G. Byazrova et al., “Anti-Ad26 humoral immunity does not compromise SARS-COV-2 neutralizing antibody responses following Gam-COVID-Vac booster vaccination,” npj Vaccines, vol. 7. Springer Nature, 2022. ista: Byazrova MG, Astakhova EA, Minnegalieva A, Sukhova MM, Mikhailov AA, Prilipov AG, Gorchakov AA, Filatov AV. 2022. Anti-Ad26 humoral immunity does not compromise SARS-COV-2 neutralizing antibody responses following Gam-COVID-Vac booster vaccination. npj Vaccines. 7, 145. mla: Byazrova, Maria G., et al. “Anti-Ad26 Humoral Immunity Does Not Compromise SARS-COV-2 Neutralizing Antibody Responses Following Gam-COVID-Vac Booster Vaccination.” Npj Vaccines, vol. 7, 145, Springer Nature, 2022, doi:10.1038/s41541-022-00566-x. short: M.G. Byazrova, E.A. Astakhova, A. Minnegalieva, M.M. Sukhova, A.A. Mikhailov, A.G. Prilipov, A.A. Gorchakov, A.V. Filatov, Npj Vaccines 7 (2022). date_created: 2023-01-12T12:02:54Z date_published: 2022-11-15T00:00:00Z date_updated: 2023-08-04T08:52:40Z day: '15' ddc: - '570' department: - _id: FyKo doi: 10.1038/s41541-022-00566-x external_id: isi: - '000884278600004' pmid: - '36379998' file: - access_level: open_access checksum: ddaac096381565b2b4b7dcc34cdbc4ee content_type: application/pdf creator: dernst date_created: 2023-01-23T11:22:09Z date_updated: 2023-01-23T11:22:09Z file_id: '12347' file_name: 2022_njpVaccines_Byazrova.pdf file_size: 1856046 relation: main_file success: 1 file_date_updated: 2023-01-23T11:22:09Z has_accepted_license: '1' intvolume: ' 7' isi: 1 keyword: - Pharmacology (medical) - Infectious Diseases - Pharmacology - Immunology - SARS-COV-2 - COVID language: - iso: eng month: '11' oa: 1 oa_version: Published Version pmid: 1 publication: npj Vaccines publication_identifier: issn: - 2059-0105 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Anti-Ad26 humoral immunity does not compromise SARS-COV-2 neutralizing antibody responses following Gam-COVID-Vac booster vaccination tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 7 year: '2022' ... --- _id: '12157' abstract: - lang: eng text: 'Polygenic adaptation is thought to be ubiquitous, yet remains poorly understood. Here, we model this process analytically, in the plausible setting of a highly polygenic, quantitative trait that experiences a sudden shift in the fitness optimum. We show how the mean phenotype changes over time, depending on the effect sizes of loci that contribute to variance in the trait, and characterize the allele dynamics at these loci. Notably, we describe the two phases of the allele dynamics: The first is a rapid phase, in which directional selection introduces small frequency differences between alleles whose effects are aligned with or opposed to the shift, ultimately leading to small differences in their probability of fixation during a second, longer phase, governed by stabilizing selection. As we discuss, key results should hold in more general settings and have important implications for efforts to identify the genetic basis of adaptation in humans and other species.' acknowledgement: "We thank Guy Amster, Jeremy Berg, Nick Barton, Yuval Simons and Molly Przeworski for many helpful discussions, and Jeremy Berg, Graham Coop, Joachim Hermisson, Guillaume Martin, Will Milligan, Peter Ralph, Yuval Simons, Leo Speidel and Molly Przeworski for comments on the manuscript.\r\nNational Institutes of Health GM115889 Laura Katharine Hayward Guy Sella \r\nNational Institutes of Health GM121372 Laura Katharine Hayward" article_number: '66697' article_processing_charge: No article_type: original author: - first_name: Laura full_name: Hayward, Laura id: fc885ee5-24bf-11eb-ad7b-bcc5104c0c1b last_name: Hayward - first_name: Guy full_name: Sella, Guy last_name: Sella citation: ama: Hayward L, Sella G. Polygenic adaptation after a sudden change in environment. eLife. 2022;11. doi:10.7554/elife.66697 apa: Hayward, L., & Sella, G. (2022). Polygenic adaptation after a sudden change in environment. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.66697 chicago: Hayward, Laura, and Guy Sella. “Polygenic Adaptation after a Sudden Change in Environment.” ELife. eLife Sciences Publications, 2022. https://doi.org/10.7554/elife.66697. ieee: L. Hayward and G. Sella, “Polygenic adaptation after a sudden change in environment,” eLife, vol. 11. eLife Sciences Publications, 2022. ista: Hayward L, Sella G. 2022. Polygenic adaptation after a sudden change in environment. eLife. 11, 66697. mla: Hayward, Laura, and Guy Sella. “Polygenic Adaptation after a Sudden Change in Environment.” ELife, vol. 11, 66697, eLife Sciences Publications, 2022, doi:10.7554/elife.66697. short: L. Hayward, G. Sella, ELife 11 (2022). date_created: 2023-01-12T12:09:00Z date_published: 2022-09-26T00:00:00Z date_updated: 2023-08-04T09:04:58Z day: '26' ddc: - '570' department: - _id: NiBa doi: 10.7554/elife.66697 external_id: isi: - '000890735600001' file: - access_level: open_access checksum: 28de155b231ac1c8d4501c98b2fb359a content_type: application/pdf creator: dernst date_created: 2023-01-24T12:21:32Z date_updated: 2023-01-24T12:21:32Z file_id: '12363' file_name: 2022_eLife_Hayward.pdf file_size: 18935612 relation: main_file success: 1 file_date_updated: 2023-01-24T12:21:32Z has_accepted_license: '1' intvolume: ' 11' isi: 1 keyword: - General Immunology and Microbiology - General Biochemistry - Genetics and Molecular Biology - General Medicine - General Neuroscience language: - iso: eng month: '09' oa: 1 oa_version: Published Version publication: eLife publication_identifier: eissn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: Polygenic adaptation after a sudden change in environment tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 11 year: '2022' ... --- _id: '12261' abstract: - lang: eng text: 'Dose–response relationships are a general concept for quantitatively describing biological systems across multiple scales, from the molecular to the whole-cell level. A clinically relevant example is the bacterial growth response to antibiotics, which is routinely characterized by dose–response curves. The shape of the dose–response curve varies drastically between antibiotics and plays a key role in treatment, drug interactions, and resistance evolution. However, the mechanisms shaping the dose–response curve remain largely unclear. Here, we show in Escherichia coli that the distinctively shallow dose–response curve of the antibiotic trimethoprim is caused by a negative growth-mediated feedback loop: Trimethoprim slows growth, which in turn weakens the effect of this antibiotic. At the molecular level, this feedback is caused by the upregulation of the drug target dihydrofolate reductase (FolA/DHFR). We show that this upregulation is not a specific response to trimethoprim but follows a universal trend line that depends primarily on the growth rate, irrespective of its cause. Rewiring the feedback loop alters the dose–response curve in a predictable manner, which we corroborate using a mathematical model of cellular resource allocation and growth. Our results indicate that growth-mediated feedback loops may shape drug responses more generally and could be exploited to design evolutionary traps that enable selection against drug resistance.' acknowledged_ssus: - _id: M-Shop acknowledgement: This work was in part supported by Human Frontier Science Program GrantRGP0042/2013, Marie Curie Career Integration Grant303507, AustrianScience Fund (FWF) Grant P27201-B22, and German Research Foundation(DFG) Collaborative Research Center (SFB)1310to TB. SAA was supportedby the European Union’s Horizon2020Research and Innovation Programunder the Marie Skłodowska-Curie Grant agreement No707352. We wouldlike to thank the Bollenbach group for regular fruitful discussions. We areparticularly thankful for the technical assistance of Booshini Fernando andfor discussions of the theoretical aspects with Gerrit Ansmann. We areindebted to Bor Kavˇciˇc for invaluable advice, help with setting up theluciferase-based growth monitoring system, and for sharing plasmids. Weacknowledge the IST Austria Miba Machine Shop for their support inbuilding a housing for the stacker of the plate reader, which enabled thehigh-throughput luciferase-based experiments. We are grateful to RosalindAllen, Bor Kavˇciˇc and Dor Russ for feedback on the manuscript. Open Accessfunding enabled and organized by Projekt DEAL. article_number: e10490 article_processing_charge: No article_type: original author: - first_name: Andreas full_name: Angermayr, Andreas id: 4677C796-F248-11E8-B48F-1D18A9856A87 last_name: Angermayr orcid: 0000-0001-8619-2223 - first_name: Tin Yau full_name: Pang, Tin Yau last_name: Pang - first_name: Guillaume full_name: Chevereau, Guillaume last_name: Chevereau - first_name: Karin full_name: Mitosch, Karin id: 39B66846-F248-11E8-B48F-1D18A9856A87 last_name: Mitosch - first_name: Martin J full_name: Lercher, Martin J last_name: Lercher - first_name: Mark Tobias full_name: Bollenbach, Mark Tobias id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87 last_name: Bollenbach orcid: 0000-0003-4398-476X citation: ama: Angermayr A, Pang TY, Chevereau G, Mitosch K, Lercher MJ, Bollenbach MT. Growth‐mediated negative feedback shapes quantitative antibiotic response. Molecular Systems Biology. 2022;18(9). doi:10.15252/msb.202110490 apa: Angermayr, A., Pang, T. Y., Chevereau, G., Mitosch, K., Lercher, M. J., & Bollenbach, M. T. (2022). Growth‐mediated negative feedback shapes quantitative antibiotic response. Molecular Systems Biology. Embo Press. https://doi.org/10.15252/msb.202110490 chicago: Angermayr, Andreas, Tin Yau Pang, Guillaume Chevereau, Karin Mitosch, Martin J Lercher, and Mark Tobias Bollenbach. “Growth‐mediated Negative Feedback Shapes Quantitative Antibiotic Response.” Molecular Systems Biology. Embo Press, 2022. https://doi.org/10.15252/msb.202110490. ieee: A. Angermayr, T. Y. Pang, G. Chevereau, K. Mitosch, M. J. Lercher, and M. T. Bollenbach, “Growth‐mediated negative feedback shapes quantitative antibiotic response,” Molecular Systems Biology, vol. 18, no. 9. Embo Press, 2022. ista: Angermayr A, Pang TY, Chevereau G, Mitosch K, Lercher MJ, Bollenbach MT. 2022. Growth‐mediated negative feedback shapes quantitative antibiotic response. Molecular Systems Biology. 18(9), e10490. mla: Angermayr, Andreas, et al. “Growth‐mediated Negative Feedback Shapes Quantitative Antibiotic Response.” Molecular Systems Biology, vol. 18, no. 9, e10490, Embo Press, 2022, doi:10.15252/msb.202110490. short: A. Angermayr, T.Y. Pang, G. Chevereau, K. Mitosch, M.J. Lercher, M.T. Bollenbach, Molecular Systems Biology 18 (2022). date_created: 2023-01-16T09:58:34Z date_published: 2022-09-01T00:00:00Z date_updated: 2023-08-04T09:51:49Z day: '01' ddc: - '570' department: - _id: ToBo doi: 10.15252/msb.202110490 external_id: isi: - '000856482800001' file: - access_level: open_access checksum: 8b1d8f5ea20c8408acf466435fb6ae01 content_type: application/pdf creator: dernst date_created: 2023-01-30T09:49:55Z date_updated: 2023-01-30T09:49:55Z file_id: '12446' file_name: 2022_MolecularSystemsBio_Angermayr.pdf file_size: 1098812 relation: main_file success: 1 file_date_updated: 2023-01-30T09:49:55Z has_accepted_license: '1' intvolume: ' 18' isi: 1 issue: '9' keyword: - Applied Mathematics - Computational Theory and Mathematics - General Agricultural and Biological Sciences - General Immunology and Microbiology - General Biochemistry - Genetics and Molecular Biology - Information Systems language: - iso: eng month: '09' oa: 1 oa_version: Published Version publication: Molecular Systems Biology publication_identifier: eissn: - 1744-4292 publication_status: published publisher: Embo Press quality_controlled: '1' scopus_import: '1' status: public title: Growth‐mediated negative feedback shapes quantitative antibiotic response tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 18 year: '2022' ... --- _id: '12252' abstract: - lang: eng text: The COVID−19 pandemic not only resulted in a global crisis, but also accelerated vaccine development and antibody discovery. Herein we report a synthetic humanized VHH library development pipeline for nanomolar-range affinity VHH binders to SARS-CoV-2 variants of concern (VoC) receptor binding domains (RBD) isolation. Trinucleotide-based randomization of CDRs by Kunkel mutagenesis with the subsequent rolling-cycle amplification resulted in more than 1011 diverse phage display library in a manageable for a single person number of electroporation reactions. We identified a number of nanomolar-range affinity VHH binders to SARS-CoV-2 variants of concern (VoC) receptor binding domains (RBD) by screening a novel synthetic humanized antibody library. In order to explore the most robust and fast method for affinity improvement, we performed affinity maturation by CDR1 and CDR2 shuffling and avidity engineering by multivalent trimeric VHH fusion protein construction. As a result, H7-Fc and G12x3-Fc binders were developed with the affinities in nM and pM range respectively. Importantly, these affinities are weakly influenced by most of SARS-CoV-2 VoC mutations and they retain moderate binding to BA.4\5. The plaque reduction neutralization test (PRNT) resulted in IC50 = 100 ng\ml and 9.6 ng\ml for H7-Fc and G12x3-Fc antibodies, respectively, for the emerging Omicron BA.1 variant. Therefore, these VHH could expand the present landscape of SARS-CoV-2 neutralization binders with the therapeutic potential for present and future SARS-CoV-2 variants. acknowledgement: The authors declare that this study received funding from Immunofusion. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. article_number: '965446' article_processing_charge: No article_type: original author: - first_name: Dmitri full_name: Dormeshkin, Dmitri last_name: Dormeshkin - first_name: Michail full_name: Shapira, Michail last_name: Shapira - first_name: Simon full_name: Dubovik, Simon last_name: Dubovik - first_name: Anton full_name: Kavaleuski, Anton id: 4968f7ad-eb97-11eb-a6c2-8ed382e8912c last_name: Kavaleuski orcid: 0000-0003-2091-526X - first_name: Mikalai full_name: Katsin, Mikalai last_name: Katsin - first_name: Alexandr full_name: Migas, Alexandr last_name: Migas - first_name: Alexander full_name: Meleshko, Alexander last_name: Meleshko - first_name: Sergei full_name: Semyonov, Sergei last_name: Semyonov citation: ama: Dormeshkin D, Shapira M, Dubovik S, et al. Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library. Frontiers in Immunology. 2022;13. doi:10.3389/fimmu.2022.965446 apa: Dormeshkin, D., Shapira, M., Dubovik, S., Kavaleuski, A., Katsin, M., Migas, A., … Semyonov, S. (2022). Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library. Frontiers in Immunology. Frontiers Media. https://doi.org/10.3389/fimmu.2022.965446 chicago: Dormeshkin, Dmitri, Michail Shapira, Simon Dubovik, Anton Kavaleuski, Mikalai Katsin, Alexandr Migas, Alexander Meleshko, and Sergei Semyonov. “Isolation of an Escape-Resistant SARS-CoV-2 Neutralizing Nanobody from a Novel Synthetic Nanobody Library.” Frontiers in Immunology. Frontiers Media, 2022. https://doi.org/10.3389/fimmu.2022.965446. ieee: D. Dormeshkin et al., “Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library,” Frontiers in Immunology, vol. 13. Frontiers Media, 2022. ista: Dormeshkin D, Shapira M, Dubovik S, Kavaleuski A, Katsin M, Migas A, Meleshko A, Semyonov S. 2022. Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library. Frontiers in Immunology. 13, 965446. mla: Dormeshkin, Dmitri, et al. “Isolation of an Escape-Resistant SARS-CoV-2 Neutralizing Nanobody from a Novel Synthetic Nanobody Library.” Frontiers in Immunology, vol. 13, 965446, Frontiers Media, 2022, doi:10.3389/fimmu.2022.965446. short: D. Dormeshkin, M. Shapira, S. Dubovik, A. Kavaleuski, M. Katsin, A. Migas, A. Meleshko, S. Semyonov, Frontiers in Immunology 13 (2022). date_created: 2023-01-16T09:56:57Z date_published: 2022-09-16T00:00:00Z date_updated: 2023-08-04T09:49:24Z day: '16' ddc: - '570' department: - _id: LeSa doi: 10.3389/fimmu.2022.965446 external_id: isi: - '000862479100001' file: - access_level: open_access checksum: f8f5d8110710033d0532e7e08bf9dad4 content_type: application/pdf creator: dernst date_created: 2023-01-30T09:22:26Z date_updated: 2023-01-30T09:22:26Z file_id: '12443' file_name: 2022_FrontiersImmunology_Dormeshkin.pdf file_size: 5695892 relation: main_file success: 1 file_date_updated: 2023-01-30T09:22:26Z has_accepted_license: '1' intvolume: ' 13' isi: 1 keyword: - Immunology - Immunology and Allergy - COVID-19 - SARS-CoV-2 - synthetic library - RBD - neutralization nanobody - VHH language: - iso: eng month: '09' oa: 1 oa_version: Published Version publication: Frontiers in Immunology publication_identifier: issn: - 1664-3224 publication_status: published publisher: Frontiers Media quality_controlled: '1' scopus_import: '1' status: public title: Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 13 year: '2022' ... --- _id: '12288' abstract: - lang: eng text: To understand the function of neuronal circuits, it is crucial to disentangle the connectivity patterns within the network. However, most tools currently used to explore connectivity have low throughput, low selectivity, or limited accessibility. Here, we report the development of an improved packaging system for the production of the highly neurotropic RVdGenvA-CVS-N2c rabies viral vectors, yielding titers orders of magnitude higher with no background contamination, at a fraction of the production time, while preserving the efficiency of transsynaptic labeling. Along with the production pipeline, we developed suites of ‘starter’ AAV and bicistronic RVdG-CVS-N2c vectors, enabling retrograde labeling from a wide range of neuronal populations, tailored for diverse experimental requirements. We demonstrate the power and flexibility of the new system by uncovering hidden local and distal inhibitory connections in the mouse hippocampal formation and by imaging the functional properties of a cortical microcircuit across weeks. Our novel production pipeline provides a convenient approach to generate new rabies vectors, while our toolkit flexibly and efficiently expands the current capacity to label, manipulate and image the neuronal activity of interconnected neuronal circuits in vitro and in vivo. acknowledged_ssus: - _id: Bio - _id: PreCl acknowledgement: We thank F Marr for technical assistance, A Murray for RVdG-CVS-N2c viruses and Neuro2A packaging cell-lines and J Watson for reading the manuscript. This research was supported by the Scientific Service Units (SSU) of IST-Austria through resources provided by the Imaging and Optics Facility (IOF) and the Preclinical Facility (PCF). This project was funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC advanced grant No 692692, PJ, ERC starting grant No 756502, MJ), the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award, PJ), the Human Frontier Science Program (LT000256/2018-L, AS) and EMBO (ALTF 1098-2017, AS). article_number: '79848' article_processing_charge: No article_type: original author: - first_name: Anton L full_name: Sumser, Anton L id: 3320A096-F248-11E8-B48F-1D18A9856A87 last_name: Sumser orcid: 0000-0002-4792-1881 - first_name: Maximilian A full_name: Jösch, Maximilian A id: 2BD278E6-F248-11E8-B48F-1D18A9856A87 last_name: Jösch orcid: 0000-0002-3937-1330 - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 - first_name: Yoav full_name: Ben Simon, Yoav id: 43DF3136-F248-11E8-B48F-1D18A9856A87 last_name: Ben Simon citation: ama: Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. eLife. 2022;11. doi:10.7554/elife.79848 apa: Sumser, A. L., Jösch, M. A., Jonas, P. M., & Ben Simon, Y. (2022). Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.79848 chicago: Sumser, Anton L, Maximilian A Jösch, Peter M Jonas, and Yoav Ben Simon. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” ELife. eLife Sciences Publications, 2022. https://doi.org/10.7554/elife.79848. ieee: A. L. Sumser, M. A. Jösch, P. M. Jonas, and Y. Ben Simon, “Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling,” eLife, vol. 11. eLife Sciences Publications, 2022. ista: Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. 2022. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. eLife. 11, 79848. mla: Sumser, Anton L., et al. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” ELife, vol. 11, 79848, eLife Sciences Publications, 2022, doi:10.7554/elife.79848. short: A.L. Sumser, M.A. Jösch, P.M. Jonas, Y. Ben Simon, ELife 11 (2022). date_created: 2023-01-16T10:04:15Z date_published: 2022-09-15T00:00:00Z date_updated: 2023-08-04T10:29:48Z day: '15' ddc: - '570' department: - _id: MaJö - _id: PeJo doi: 10.7554/elife.79848 ec_funded: 1 external_id: isi: - '000892204300001' pmid: - '36040301' file: - access_level: open_access checksum: 5a2a65e3e7225090c3d8199f3bbd7b7b content_type: application/pdf creator: dernst date_created: 2023-01-30T11:50:53Z date_updated: 2023-01-30T11:50:53Z file_id: '12463' file_name: 2022_eLife_Sumser.pdf file_size: 8506811 relation: main_file success: 1 file_date_updated: 2023-01-30T11:50:53Z has_accepted_license: '1' intvolume: ' 11' isi: 1 keyword: - General Immunology and Microbiology - General Biochemistry - Genetics and Molecular Biology - General Medicine - General Neuroscience language: - iso: eng month: '09' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 2634E9D2-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '756502' name: Circuits of Visual Attention - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize - _id: 266D407A-B435-11E9-9278-68D0E5697425 grant_number: LT000256 name: Neuronal networks of salience and spatial detection in the murine superior colliculus - _id: 264FEA02-B435-11E9-9278-68D0E5697425 grant_number: ALTF 1098-2017 name: Connecting sensory with motor processing in the superior colliculus publication: eLife publication_identifier: eissn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 11 year: '2022' ... --- _id: '12117' abstract: - lang: eng text: "To understand how potential gene manipulations affect in vitro microglia, we provide a set of short protocols to evaluate microglia identity and function. We detail steps for immunostaining to determine microglia identity. We describe three functional assays for microglia: phagocytosis, calcium response following ATP stimulation, and cytokine expression upon inflammatory stimuli. We apply these protocols to human induced-pluripotent-stem-cell (hiPSC)-derived microglia, but they can be also applied to other in vitro microglial models including primary mouse microglia.\r\nFor complete details on the use and execution of this protocol, please refer to Bartalska et al. (2022).1" acknowledged_ssus: - _id: Bio acknowledgement: This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant No. 715571 to S.S.) and from the Gesellschaft für Forschungsförderung Niederösterreich (grant No. Sc19-017 to V.H.). We thank Rouven Schulz and Alessandro Venturino for their insights into functional assays and data analysis, Verena Seiboth for insights into necessary institutional permission, and ISTA imaging & optics facility (IOF) especially Bernhard Hochreiter for their support. article_number: '101866' article_processing_charge: No article_type: letter_note author: - first_name: Verena full_name: Hübschmann, Verena id: 32B7C918-F248-11E8-B48F-1D18A9856A87 last_name: Hübschmann - first_name: Medina full_name: Korkut, Medina id: 4B51CE74-F248-11E8-B48F-1D18A9856A87 last_name: Korkut orcid: 0000-0003-4309-2251 - first_name: Sandra full_name: Siegert, Sandra id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 citation: ama: Hübschmann V, Korkut M, Siegert S. Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay. STAR Protocols. 2022;3(4). doi:10.1016/j.xpro.2022.101866 apa: Hübschmann, V., Korkut, M., & Siegert, S. (2022). Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay. STAR Protocols. Elsevier. https://doi.org/10.1016/j.xpro.2022.101866 chicago: Hübschmann, Verena, Medina Korkut, and Sandra Siegert. “Assessing Human IPSC-Derived Microglia Identity and Function by Immunostaining, Phagocytosis, Calcium Activity, and Inflammation Assay.” STAR Protocols. Elsevier, 2022. https://doi.org/10.1016/j.xpro.2022.101866. ieee: V. Hübschmann, M. Korkut, and S. Siegert, “Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay,” STAR Protocols, vol. 3, no. 4. Elsevier, 2022. ista: Hübschmann V, Korkut M, Siegert S. 2022. Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay. STAR Protocols. 3(4), 101866. mla: Hübschmann, Verena, et al. “Assessing Human IPSC-Derived Microglia Identity and Function by Immunostaining, Phagocytosis, Calcium Activity, and Inflammation Assay.” STAR Protocols, vol. 3, no. 4, 101866, Elsevier, 2022, doi:10.1016/j.xpro.2022.101866. short: V. Hübschmann, M. Korkut, S. Siegert, STAR Protocols 3 (2022). date_created: 2023-01-12T11:56:38Z date_published: 2022-12-16T00:00:00Z date_updated: 2023-11-02T12:21:32Z day: '16' ddc: - '570' department: - _id: SaSi - _id: GradSch doi: 10.1016/j.xpro.2022.101866 ec_funded: 1 file: - access_level: open_access checksum: 3c71b8a60633d42c2f77c49025d5559b content_type: application/pdf creator: dernst date_created: 2023-01-23T09:50:51Z date_updated: 2023-01-23T09:50:51Z file_id: '12340' file_name: 2022_STARProtocols_Huebschmann.pdf file_size: 6251945 relation: main_file success: 1 file_date_updated: 2023-01-23T09:50:51Z has_accepted_license: '1' intvolume: ' 3' issue: '4' keyword: - General Immunology and Microbiology - General Biochemistry - Genetics and Molecular Biology - General Neuroscience language: - iso: eng month: '12' oa: 1 oa_version: Published Version project: - _id: 25D4A630-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715571' name: Microglia action towards neuronal circuit formation and function in health and disease - _id: 9B99D380-BA93-11EA-9121-9846C619BF3A grant_number: SC19-017 name: How human microglia shape developing neurons during health and inflammation publication: STAR Protocols publication_identifier: issn: - 2666-1667 publication_status: published publisher: Elsevier quality_controlled: '1' related_material: record: - id: '11478' relation: other status: public scopus_import: '1' status: public title: Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay 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: 3 year: '2022' ... --- _id: '9387' abstract: - lang: eng text: We report the complete analysis of a deterministic model of deleterious mutations and negative selection against them at two haploid loci without recombination. As long as mutation is a weaker force than selection, mutant alleles remain rare at the only stable equilibrium, and otherwise, a variety of dynamics are possible. If the mutation-free genotype is absent, generally the only stable equilibrium is the one that corresponds to fixation of the mutant allele at the locus where it is less deleterious. This result suggests that fixation of a deleterious allele that follows a click of the Muller’s ratchet is governed by natural selection, instead of random drift. acknowledgement: This work was supported by the Russian Science Foundation grant N 16-14-10173. article_number: '110729' article_processing_charge: No article_type: original author: - first_name: Kseniia full_name: Khudiakova, Kseniia id: 4E6DC800-AE37-11E9-AC72-31CAE5697425 last_name: Khudiakova orcid: 0000-0002-6246-1465 - first_name: Tatiana Yu. full_name: Neretina, Tatiana Yu. last_name: Neretina - first_name: Alexey S. full_name: Kondrashov, Alexey S. last_name: Kondrashov citation: ama: Khudiakova K, Neretina TY, Kondrashov AS. Two linked loci under mutation-selection balance and Muller’s ratchet. Journal of Theoretical Biology. 2021;524. doi:10.1016/j.jtbi.2021.110729 apa: Khudiakova, K., Neretina, T. Y., & Kondrashov, A. S. (2021). Two linked loci under mutation-selection balance and Muller’s ratchet. Journal of Theoretical Biology. Elsevier . https://doi.org/10.1016/j.jtbi.2021.110729 chicago: Khudiakova, Kseniia, Tatiana Yu. Neretina, and Alexey S. Kondrashov. “Two Linked Loci under Mutation-Selection Balance and Muller’s Ratchet.” Journal of Theoretical Biology. Elsevier , 2021. https://doi.org/10.1016/j.jtbi.2021.110729. ieee: K. Khudiakova, T. Y. Neretina, and A. S. Kondrashov, “Two linked loci under mutation-selection balance and Muller’s ratchet,” Journal of Theoretical Biology, vol. 524. Elsevier , 2021. ista: Khudiakova K, Neretina TY, Kondrashov AS. 2021. Two linked loci under mutation-selection balance and Muller’s ratchet. Journal of Theoretical Biology. 524, 110729. mla: Khudiakova, Kseniia, et al. “Two Linked Loci under Mutation-Selection Balance and Muller’s Ratchet.” Journal of Theoretical Biology, vol. 524, 110729, Elsevier , 2021, doi:10.1016/j.jtbi.2021.110729. short: K. Khudiakova, T.Y. Neretina, A.S. Kondrashov, Journal of Theoretical Biology 524 (2021). date_created: 2021-05-12T05:58:42Z date_published: 2021-04-24T00:00:00Z date_updated: 2023-08-08T13:32:40Z day: '24' department: - _id: GradSch doi: 10.1016/j.jtbi.2021.110729 external_id: isi: - '000659161500002' intvolume: ' 524' isi: 1 keyword: - General Biochemistry - Genetics and Molecular Biology - Modelling and Simulation - Statistics and Probability - General Immunology and Microbiology - Applied Mathematics - General Agricultural and Biological Sciences - General Medicine language: - iso: eng main_file_link: - open_access: '1' url: https://www.biorxiv.org/content/10.1101/477489v1 month: '04' oa: 1 oa_version: Preprint publication: Journal of Theoretical Biology publication_identifier: issn: - 0022-5193 publication_status: published publisher: 'Elsevier ' quality_controlled: '1' status: public title: Two linked loci under mutation-selection balance and Muller’s ratchet type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 524 year: '2021' ... --- _id: '10301' abstract: - lang: eng text: De novo protein synthesis is required for synapse modifications underlying stable memory encoding. Yet neurons are highly compartmentalized cells and how protein synthesis can be regulated at the synapse level is unknown. Here, we characterize neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR activation and restricts the mTOR-dependent translation of specific activity-regulated mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent protein synthesis, and facilitates the consolidation of associative and spatial memories in mice. The memory enhancement becomes evident with light or spaced training, can be achieved by selectively deleting GluN3A from excitatory neurons during adulthood, and does not compromise other aspects of cognition such as memory flexibility or extinction. Our findings provide mechanistic insight into synaptic translational control and reveal a potentially selective target for cognitive enhancement. acknowledgement: We thank Stuart Lipton and Nobuki Nakanishi for providing the Grin3a knockout mice, Beverly Davidson for the AAV-caRheb, Jose Esteban for help with behavioral and biochemical experiments, and Noelia Campillo, Rebeca Martínez-Turrillas, and Ana Navarro for expert technical help. Work was funded by the UTE project CIMA; fellowships from the Fundación Tatiana Pérez de Guzmán el Bueno, FEBS, and IBRO (to M.J.C.D.), Generalitat Valenciana (to O.E.-Z.), Juan de la Cierva (to L.G.R.), FPI-MINECO (to E.R.V., to S.N.) and Intertalentum postdoctoral program (to V.B.); ANR (GluBrain3A) and ERC Advanced Grants (#693021) (to P.P.); Ramón y Cajal program RYC2014-15784, RETOS-MINECO SAF2016-76565-R, ERANET-Neuron JTC 2019 ISCIII AC19/00077 FEDER funds (to R.A.); RETOS-MINECO SAF2017-87928-R (to A.B.); an NIH grant (NS76637) and UTHSC College of Medicine funds (to S.J.T.); and NARSAD Independent Investigator Award and grants from the MINECO (CSD2008-00005, SAF2013-48983R, SAF2016-80895-R), Generalitat Valenciana (PROMETEO 2019/020)(to I.P.O.) and Severo-Ochoa Excellence Awards (SEV-2013-0317, SEV-2017-0723). article_number: e71575 article_processing_charge: No article_type: original author: - first_name: María J full_name: Conde-Dusman, María J last_name: Conde-Dusman - first_name: Partha N full_name: Dey, Partha N last_name: Dey - first_name: Óscar full_name: Elía-Zudaire, Óscar last_name: Elía-Zudaire - first_name: Luis E full_name: Garcia Rabaneda, Luis E id: 33D1B084-F248-11E8-B48F-1D18A9856A87 last_name: Garcia Rabaneda - first_name: Carmen full_name: García-Lira, Carmen last_name: García-Lira - first_name: Teddy full_name: Grand, Teddy last_name: Grand - first_name: Victor full_name: Briz, Victor last_name: Briz - first_name: Eric R full_name: Velasco, Eric R last_name: Velasco - first_name: Raül full_name: Andero Galí, Raül last_name: Andero Galí - first_name: Sergio full_name: Niñerola, Sergio last_name: Niñerola - first_name: Angel full_name: Barco, Angel last_name: Barco - first_name: Pierre full_name: Paoletti, Pierre last_name: Paoletti - first_name: John F full_name: Wesseling, John F last_name: Wesseling - first_name: Fabrizio full_name: Gardoni, Fabrizio last_name: Gardoni - first_name: Steven J full_name: Tavalin, Steven J last_name: Tavalin - first_name: Isabel full_name: Perez-Otaño, Isabel last_name: Perez-Otaño citation: ama: Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, et al. Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. eLife. 2021;10. doi:10.7554/elife.71575 apa: Conde-Dusman, M. J., Dey, P. N., Elía-Zudaire, Ó., Garcia Rabaneda, L. E., García-Lira, C., Grand, T., … Perez-Otaño, I. (2021). Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.71575 chicago: Conde-Dusman, María J, Partha N Dey, Óscar Elía-Zudaire, Luis E Garcia Rabaneda, Carmen García-Lira, Teddy Grand, Victor Briz, et al. “Control of Protein Synthesis and Memory by GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1 Assembly.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/elife.71575. ieee: M. J. Conde-Dusman et al., “Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly,” eLife, vol. 10. eLife Sciences Publications, 2021. ista: Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, Garcia Rabaneda LE, García-Lira C, Grand T, Briz V, Velasco ER, Andero Galí R, Niñerola S, Barco A, Paoletti P, Wesseling JF, Gardoni F, Tavalin SJ, Perez-Otaño I. 2021. Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. eLife. 10, e71575. mla: Conde-Dusman, María J., et al. “Control of Protein Synthesis and Memory by GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1 Assembly.” ELife, vol. 10, e71575, eLife Sciences Publications, 2021, doi:10.7554/elife.71575. short: M.J. Conde-Dusman, P.N. Dey, Ó. Elía-Zudaire, L.E. Garcia Rabaneda, C. García-Lira, T. Grand, V. Briz, E.R. Velasco, R. Andero Galí, S. Niñerola, A. Barco, P. Paoletti, J.F. Wesseling, F. Gardoni, S.J. Tavalin, I. Perez-Otaño, ELife 10 (2021). date_created: 2021-11-18T06:59:45Z date_published: 2021-11-17T00:00:00Z date_updated: 2023-08-14T11:50:50Z day: '17' ddc: - '570' department: - _id: GaNo doi: 10.7554/elife.71575 external_id: isi: - '000720945900001' file: - access_level: open_access checksum: 59318e9e41507cec83c2f4070e6ad540 content_type: application/pdf creator: lgarciar date_created: 2021-11-18T07:02:02Z date_updated: 2021-11-18T07:02:02Z file_id: '10302' file_name: elife-71575-v1.pdf file_size: 2477302 relation: main_file success: 1 file_date_updated: 2021-11-18T07:02:02Z has_accepted_license: '1' intvolume: ' 10' isi: 1 keyword: - general immunology and microbiology - general biochemistry - genetics and molecular biology - general medicine - general neuroscience language: - iso: eng month: '11' oa: 1 oa_version: Published Version publication: eLife publication_identifier: issn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' status: public title: Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 10 year: '2021' ... --- _id: '10836' acknowledgement: This work was supported by the Austrian Science Fund (FWF) grants MCCA W1248-B30 and SFB F4606-B28 to EJJ. CP received a short-term research fellowship of the European Federation of Immunological Societies (EFIS-IL) for a research visit at Biocruces Bizkaia Health Research Institute, Barakaldo, Spain. VKK received an EFIS-IL short-term research fellowship for a research visit at King’s College London. The research was funded by the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) based at Guy's and St Thomas' NHS Foundation Trust and King's College London (IS-BRC-1215-20006) (SNK). The authors acknowledge support by the Medical Research Council (MR/L023091/1) (SNK); Breast Cancer Now (147; KCL-BCN-Q3)(SNK); Cancer Research UK (C30122/A11527; C30122/A15774) (SNK); Cancer Research UK King's Health Partners Centre at King's College London (C604/A25135) (SNK); CRUK/NIHR in England/DoH for Scotland, Wales and Northern Ireland Experimental Cancer Medicine Centre (C10355/A15587) (SNK). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Additionally, this work was funded by Instituto de Salud Carlos III through the project "PI16/01223" (Co-funded by European Regional Development Fund; “A way to make Europe”) to FB and by the Department of Health, Basque Government through the project “2019111031” to OZ. OZ is recipient of a Sara Borrell 2017 post-doctoral contract “CD17/00128” funded by Instituto de Salud Carlos III (Co-funded by European Social Fund; “Investing in your future”). article_processing_charge: No article_type: letter_note author: - first_name: Christina L. full_name: Pranger, Christina L. last_name: Pranger - 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: Verena K. full_name: Köhler, Verena K. last_name: Köhler - first_name: Isabella full_name: Pali‐Schöll, Isabella last_name: Pali‐Schöll - first_name: Alessandro full_name: Fiocchi, Alessandro last_name: Fiocchi - first_name: Sophia N. full_name: Karagiannis, Sophia N. last_name: Karagiannis - first_name: Olatz full_name: Zenarruzabeitia, Olatz last_name: Zenarruzabeitia - first_name: Francisco full_name: Borrego, Francisco last_name: Borrego - first_name: Erika full_name: Jensen‐Jarolim, Erika last_name: Jensen‐Jarolim citation: ama: 'Pranger CL, Singer J, Köhler VK, et al. PIPE‐cloned human IgE and IgG4 antibodies: New tools for investigating cow’s milk allergy and tolerance. Allergy. 2021;76(5):1553-1556. doi:10.1111/all.14604' apa: 'Pranger, C. L., Singer, J., Köhler, V. K., Pali‐Schöll, I., Fiocchi, A., Karagiannis, S. N., … Jensen‐Jarolim, E. (2021). PIPE‐cloned human IgE and IgG4 antibodies: New tools for investigating cow’s milk allergy and tolerance. Allergy. Wiley. https://doi.org/10.1111/all.14604' chicago: 'Pranger, Christina L., Judit Singer, Verena K. Köhler, Isabella Pali‐Schöll, Alessandro Fiocchi, Sophia N. Karagiannis, Olatz Zenarruzabeitia, Francisco Borrego, and Erika Jensen‐Jarolim. “PIPE‐cloned Human IgE and IgG4 Antibodies: New Tools for Investigating Cow’s Milk Allergy and Tolerance.” Allergy. Wiley, 2021. https://doi.org/10.1111/all.14604.' ieee: 'C. L. Pranger et al., “PIPE‐cloned human IgE and IgG4 antibodies: New tools for investigating cow’s milk allergy and tolerance,” Allergy, vol. 76, no. 5. Wiley, pp. 1553–1556, 2021.' ista: 'Pranger CL, Singer J, Köhler VK, Pali‐Schöll I, Fiocchi A, Karagiannis SN, Zenarruzabeitia O, Borrego F, Jensen‐Jarolim E. 2021. PIPE‐cloned human IgE and IgG4 antibodies: New tools for investigating cow’s milk allergy and tolerance. Allergy. 76(5), 1553–1556.' mla: 'Pranger, Christina L., et al. “PIPE‐cloned Human IgE and IgG4 Antibodies: New Tools for Investigating Cow’s Milk Allergy and Tolerance.” Allergy, vol. 76, no. 5, Wiley, 2021, pp. 1553–56, doi:10.1111/all.14604.' short: C.L. Pranger, J. Singer, V.K. Köhler, I. Pali‐Schöll, A. Fiocchi, S.N. Karagiannis, O. Zenarruzabeitia, F. Borrego, E. Jensen‐Jarolim, Allergy 76 (2021) 1553–1556. date_created: 2022-03-08T11:19:05Z date_published: 2021-05-01T00:00:00Z date_updated: 2023-09-05T15:58:53Z day: '01' ddc: - '570' department: - _id: Bio doi: 10.1111/all.14604 external_id: isi: - '000577708800001' pmid: - '32990982' file: - access_level: open_access checksum: 9526f9554112fc027c9f7fa540c488cd content_type: application/pdf creator: dernst date_created: 2022-03-08T11:23:16Z date_updated: 2022-03-08T11:23:16Z file_id: '10837' file_name: 2021_Allergy_Pranger.pdf file_size: 626081 relation: main_file success: 1 file_date_updated: 2022-03-08T11:23:16Z has_accepted_license: '1' intvolume: ' 76' isi: 1 issue: '5' keyword: - Immunology - Immunology and Allergy language: - iso: eng month: '05' oa: 1 oa_version: Published Version page: 1553-1556 pmid: 1 publication: Allergy publication_identifier: eissn: - 1398-9995 issn: - 0105-4538 publication_status: published publisher: Wiley quality_controlled: '1' scopus_import: '1' status: public title: 'PIPE‐cloned human IgE and IgG4 antibodies: New tools for investigating cow''s milk allergy and tolerance' 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: 76 year: '2021' ... --- _id: '11055' abstract: - lang: eng text: Vascular dysfunctions are a common feature of multiple age-related diseases. However, modeling healthy and pathological aging of the human vasculature represents an unresolved experimental challenge. Here, we generated induced vascular endothelial cells (iVECs) and smooth muscle cells (iSMCs) by direct reprogramming of healthy human fibroblasts from donors of different ages and Hutchinson-Gilford Progeria Syndrome (HGPS) patients. iVECs induced from old donors revealed upregulation of GSTM1 and PALD1, genes linked to oxidative stress, inflammation and endothelial junction stability, as vascular aging markers. A functional assay performed on PALD1 KD VECs demonstrated a recovery in vascular permeability. We found that iSMCs from HGPS donors overexpressed bone morphogenetic protein (BMP)−4, which plays a key role in both vascular calcification and endothelial barrier damage observed in HGPS. Strikingly, BMP4 concentrations are higher in serum from HGPS vs. age-matched mice. Furthermore, targeting BMP4 with blocking antibody recovered the functionality of the vascular barrier in vitro, hence representing a potential future therapeutic strategy to limit cardiovascular dysfunction in HGPS. These results show that iVECs and iSMCs retain disease-related signatures, allowing modeling of vascular aging and HGPS in vitro. article_number: e54383 article_processing_charge: No article_type: original author: - first_name: Simone full_name: Bersini, Simone last_name: Bersini - first_name: Roberta full_name: Schulte, Roberta last_name: Schulte - first_name: Ling full_name: Huang, Ling last_name: Huang - first_name: Hannah full_name: Tsai, Hannah last_name: Tsai - first_name: Martin W full_name: HETZER, Martin W id: 86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed last_name: HETZER orcid: 0000-0002-2111-992X citation: ama: Bersini S, Schulte R, Huang L, Tsai H, Hetzer M. Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome. eLife. 2020;9. doi:10.7554/elife.54383 apa: Bersini, S., Schulte, R., Huang, L., Tsai, H., & Hetzer, M. (2020). Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.54383 chicago: Bersini, Simone, Roberta Schulte, Ling Huang, Hannah Tsai, and Martin Hetzer. “Direct Reprogramming of Human Smooth Muscle and Vascular Endothelial Cells Reveals Defects Associated with Aging and Hutchinson-Gilford Progeria Syndrome.” ELife. eLife Sciences Publications, 2020. https://doi.org/10.7554/elife.54383. ieee: S. Bersini, R. Schulte, L. Huang, H. Tsai, and M. Hetzer, “Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome,” eLife, vol. 9. eLife Sciences Publications, 2020. ista: Bersini S, Schulte R, Huang L, Tsai H, Hetzer M. 2020. Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome. eLife. 9, e54383. mla: Bersini, Simone, et al. “Direct Reprogramming of Human Smooth Muscle and Vascular Endothelial Cells Reveals Defects Associated with Aging and Hutchinson-Gilford Progeria Syndrome.” ELife, vol. 9, e54383, eLife Sciences Publications, 2020, doi:10.7554/elife.54383. short: S. Bersini, R. Schulte, L. Huang, H. Tsai, M. Hetzer, ELife 9 (2020). date_created: 2022-04-07T07:43:48Z date_published: 2020-09-08T00:00:00Z date_updated: 2022-07-18T08:30:37Z day: '08' ddc: - '570' doi: 10.7554/elife.54383 extern: '1' external_id: pmid: - '32896271' file: - access_level: open_access checksum: f8b3821349a194050be02570d8fe7d4b content_type: application/pdf creator: dernst date_created: 2022-04-08T06:53:10Z date_updated: 2022-04-08T06:53:10Z file_id: '11132' file_name: 2020_eLife_Bersini.pdf file_size: 4399825 relation: main_file success: 1 file_date_updated: 2022-04-08T06:53:10Z has_accepted_license: '1' intvolume: ' 9' keyword: - General Immunology and Microbiology - General Biochemistry - Genetics and Molecular Biology - General Medicine - General Neuroscience language: - iso: eng month: '09' oa: 1 oa_version: Published Version pmid: 1 publication: eLife publication_identifier: issn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome 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: 72615eeb-f1f3-11ec-aa25-d4573ddc34fd volume: 9 year: '2020' ... --- _id: '15153' abstract: - lang: eng text: Mammalian circadian rhythms are generated by a transcription-based feedback loop in which CLOCK:BMAL1 drives transcription of its repressors (PER1/2, CRY1/2), which ultimately interact with CLOCK:BMAL1 to close the feedback loop with ~24 hr periodicity. Here we pinpoint a key difference between CRY1 and CRY2 that underlies their differential strengths as transcriptional repressors. Both cryptochromes bind the BMAL1 transactivation domain similarly to sequester it from coactivators and repress CLOCK:BMAL1 activity. However, we find that CRY1 is recruited with much higher affinity to the PAS domain core of CLOCK:BMAL1, allowing it to serve as a stronger repressor that lengthens circadian period. We discovered a dynamic serine-rich loop adjacent to the secondary pocket in the photolyase homology region (PHR) domain that regulates differential binding of cryptochromes to the PAS domain core of CLOCK:BMAL1. Notably, binding of the co-repressor PER2 remodels the serine loop of CRY2, making it more CRY1-like and enhancing its affinity for CLOCK:BMAL1. article_number: '55275' article_processing_charge: No article_type: original author: - first_name: Jennifer L full_name: Fribourgh, Jennifer L last_name: Fribourgh - first_name: Ashutosh full_name: Srivastava, Ashutosh last_name: Srivastava - first_name: Colby R full_name: Sandate, Colby R last_name: Sandate - first_name: Alicia Kathleen full_name: Michael, Alicia Kathleen id: 6437c950-2a03-11ee-914d-d6476dd7b75c last_name: Michael - first_name: Peter L full_name: Hsu, Peter L last_name: Hsu - first_name: Christin full_name: Rakers, Christin last_name: Rakers - first_name: Leslee T full_name: Nguyen, Leslee T last_name: Nguyen - first_name: Megan R full_name: Torgrimson, Megan R last_name: Torgrimson - first_name: Gian Carlo G full_name: Parico, Gian Carlo G last_name: Parico - first_name: Sarvind full_name: Tripathi, Sarvind last_name: Tripathi - first_name: Ning full_name: Zheng, Ning last_name: Zheng - first_name: Gabriel C full_name: Lander, Gabriel C last_name: Lander - first_name: Tsuyoshi full_name: Hirota, Tsuyoshi last_name: Hirota - first_name: Florence full_name: Tama, Florence last_name: Tama - first_name: Carrie L full_name: Partch, Carrie L last_name: Partch citation: ama: Fribourgh JL, Srivastava A, Sandate CR, et al. Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing. eLife. 2020;9. doi:10.7554/elife.55275 apa: Fribourgh, J. L., Srivastava, A., Sandate, C. R., Michael, A. K., Hsu, P. L., Rakers, C., … Partch, C. L. (2020). Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.55275 chicago: Fribourgh, Jennifer L, Ashutosh Srivastava, Colby R Sandate, Alicia K. Michael, Peter L Hsu, Christin Rakers, Leslee T Nguyen, et al. “Dynamics at the Serine Loop Underlie Differential Affinity of Cryptochromes for CLOCK:BMAL1 to Control Circadian Timing.” ELife. eLife Sciences Publications, 2020. https://doi.org/10.7554/elife.55275. ieee: J. L. Fribourgh et al., “Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing,” eLife, vol. 9. eLife Sciences Publications, 2020. ista: Fribourgh JL, Srivastava A, Sandate CR, Michael AK, Hsu PL, Rakers C, Nguyen LT, Torgrimson MR, Parico GCG, Tripathi S, Zheng N, Lander GC, Hirota T, Tama F, Partch CL. 2020. Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing. eLife. 9, 55275. mla: Fribourgh, Jennifer L., et al. “Dynamics at the Serine Loop Underlie Differential Affinity of Cryptochromes for CLOCK:BMAL1 to Control Circadian Timing.” ELife, vol. 9, 55275, eLife Sciences Publications, 2020, doi:10.7554/elife.55275. short: J.L. Fribourgh, A. Srivastava, C.R. Sandate, A.K. Michael, P.L. Hsu, C. Rakers, L.T. Nguyen, M.R. Torgrimson, G.C.G. Parico, S. Tripathi, N. Zheng, G.C. Lander, T. Hirota, F. Tama, C.L. Partch, ELife 9 (2020). date_created: 2024-03-21T07:55:12Z date_published: 2020-02-26T00:00:00Z date_updated: 2024-03-25T12:25:02Z day: '26' doi: 10.7554/elife.55275 extern: '1' intvolume: ' 9' keyword: - General Immunology and Microbiology - General Biochemistry - Genetics and Molecular Biology - General Medicine - General Neuroscience language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.7554/eLife.55275 month: '02' oa: 1 oa_version: Published Version publication: eLife publication_identifier: issn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 9 year: '2020' ... --- _id: '12192' abstract: - lang: eng text: Transposable elements (TEs), the movement of which can damage the genome, are epigenetically silenced in eukaryotes. Intriguingly, TEs are activated in the sperm companion cell – vegetative cell (VC) – of the flowering plant Arabidopsis thaliana. However, the extent and mechanism of this activation are unknown. Here we show that about 100 heterochromatic TEs are activated in VCs, mostly by DEMETER-catalyzed DNA demethylation. We further demonstrate that DEMETER access to some of these TEs is permitted by the natural depletion of linker histone H1 in VCs. Ectopically expressed H1 suppresses TEs in VCs by reducing DNA demethylation and via a methylation-independent mechanism. We demonstrate that H1 is required for heterochromatin condensation in plant cells and show that H1 overexpression creates heterochromatic foci in the VC progenitor cell. Taken together, our results demonstrate that the natural depletion of H1 during male gametogenesis facilitates DEMETER-directed DNA demethylation, heterochromatin relaxation, and TE activation. acknowledgement: We thank David Twell for the pDONR-P4-P1R-pLAT52 and pDONR-P2R-P3-mRFP vectors, the John Innes Centre Bioimaging Facility (Elaine Barclay and Grant Calder) for their assistance with microscopy, and the Norwich BioScience Institute Partnership Computing infrastructure for Science Group for High Performance Computing resources. This work was funded by a Biotechnology and Biological Sciences Research Council (BBSRC) David Phillips Fellowship (BB/L025043/1; SH, JZ and XF), a European Research Council Starting Grant ('SexMeth' 804981; XF) and a Grant to Exceptional Researchers by the Gatsby Charitable Foundation (SH and XF). article_number: '42530' article_processing_charge: No article_type: original author: - first_name: Shengbo full_name: He, Shengbo last_name: He - first_name: Martin full_name: Vickers, Martin last_name: Vickers - first_name: Jingyi full_name: Zhang, Jingyi last_name: Zhang - first_name: Xiaoqi full_name: Feng, Xiaoqi id: e0164712-22ee-11ed-b12a-d80fcdf35958 last_name: Feng orcid: 0000-0002-4008-1234 citation: ama: He S, Vickers M, Zhang J, Feng X. Natural depletion of histone H1 in sex cells causes DNA demethylation, heterochromatin decondensation and transposon activation. eLife. 2019;8. doi:10.7554/elife.42530 apa: He, S., Vickers, M., Zhang, J., & Feng, X. (2019). Natural depletion of histone H1 in sex cells causes DNA demethylation, heterochromatin decondensation and transposon activation. ELife. eLife Sciences Publications, Ltd. https://doi.org/10.7554/elife.42530 chicago: He, Shengbo, Martin Vickers, Jingyi Zhang, and Xiaoqi Feng. “Natural Depletion of Histone H1 in Sex Cells Causes DNA Demethylation, Heterochromatin Decondensation and Transposon Activation.” ELife. eLife Sciences Publications, Ltd, 2019. https://doi.org/10.7554/elife.42530. ieee: S. He, M. Vickers, J. Zhang, and X. Feng, “Natural depletion of histone H1 in sex cells causes DNA demethylation, heterochromatin decondensation and transposon activation,” eLife, vol. 8. eLife Sciences Publications, Ltd, 2019. ista: He S, Vickers M, Zhang J, Feng X. 2019. Natural depletion of histone H1 in sex cells causes DNA demethylation, heterochromatin decondensation and transposon activation. eLife. 8, 42530. mla: He, Shengbo, et al. “Natural Depletion of Histone H1 in Sex Cells Causes DNA Demethylation, Heterochromatin Decondensation and Transposon Activation.” ELife, vol. 8, 42530, eLife Sciences Publications, Ltd, 2019, doi:10.7554/elife.42530. short: S. He, M. Vickers, J. Zhang, X. Feng, ELife 8 (2019). date_created: 2023-01-16T09:17:21Z date_published: 2019-05-28T00:00:00Z date_updated: 2023-05-08T10:54:12Z day: '28' ddc: - '580' department: - _id: XiFe doi: 10.7554/elife.42530 extern: '1' external_id: unknown: - '31135340' file: - access_level: open_access checksum: ea6b89c20d59e5eb3646916fe5d568ad content_type: application/pdf creator: alisjak date_created: 2023-02-07T09:42:46Z date_updated: 2023-02-07T09:42:46Z file_id: '12525' file_name: 2019_elife_He.pdf file_size: 2493837 relation: main_file success: 1 file_date_updated: 2023-02-07T09:42:46Z has_accepted_license: '1' intvolume: ' 8' keyword: - General Immunology and Microbiology - General Biochemistry - Genetics and Molecular Biology - General Medicine - General Neuroscience language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594752/ month: '05' oa: 1 oa_version: Published Version publication: eLife publication_identifier: issn: - 2050-084X publication_status: published publisher: eLife Sciences Publications, Ltd quality_controlled: '1' scopus_import: '1' status: public title: Natural depletion of histone H1 in sex cells causes DNA demethylation, heterochromatin decondensation and transposon activation tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 8 year: '2019' ... --- _id: '11060' abstract: - lang: eng text: The inner nuclear membrane (INM) is a subdomain of the endoplasmic reticulum (ER) that is gated by the nuclear pore complex. It is unknown whether proteins of the INM and ER are degraded through shared or distinct pathways in mammalian cells. We applied dynamic proteomics to profile protein half-lives and report that INM and ER residents turn over at similar rates, indicating that the INM’s unique topology is not a barrier to turnover. Using a microscopy approach, we observed that the proteasome can degrade INM proteins in situ. However, we also uncovered evidence for selective, vesicular transport-mediated turnover of a single INM protein, emerin, that is potentiated by ER stress. Emerin is rapidly cleared from the INM by a mechanism that requires emerin’s LEM domain to mediate vesicular trafficking to lysosomes. This work demonstrates that the INM can be dynamically remodeled in response to environmental inputs. article_number: e49796 article_processing_charge: No article_type: original author: - first_name: Abigail full_name: Buchwalter, Abigail last_name: Buchwalter - first_name: Roberta full_name: Schulte, Roberta last_name: Schulte - first_name: Hsiao full_name: Tsai, Hsiao last_name: Tsai - first_name: Juliana full_name: Capitanio, Juliana last_name: Capitanio - first_name: Martin W full_name: HETZER, Martin W id: 86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed last_name: HETZER orcid: 0000-0002-2111-992X citation: ama: Buchwalter A, Schulte R, Tsai H, Capitanio J, Hetzer M. Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress. eLife. 2019;8. doi:10.7554/elife.49796 apa: Buchwalter, A., Schulte, R., Tsai, H., Capitanio, J., & Hetzer, M. (2019). Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.49796 chicago: Buchwalter, Abigail, Roberta Schulte, Hsiao Tsai, Juliana Capitanio, and Martin Hetzer. “Selective Clearance of the Inner Nuclear Membrane Protein Emerin by Vesicular Transport during ER Stress.” ELife. eLife Sciences Publications, 2019. https://doi.org/10.7554/elife.49796. ieee: A. Buchwalter, R. Schulte, H. Tsai, J. Capitanio, and M. Hetzer, “Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress,” eLife, vol. 8. eLife Sciences Publications, 2019. ista: Buchwalter A, Schulte R, Tsai H, Capitanio J, Hetzer M. 2019. Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress. eLife. 8, e49796. mla: Buchwalter, Abigail, et al. “Selective Clearance of the Inner Nuclear Membrane Protein Emerin by Vesicular Transport during ER Stress.” ELife, vol. 8, e49796, eLife Sciences Publications, 2019, doi:10.7554/elife.49796. short: A. Buchwalter, R. Schulte, H. Tsai, J. Capitanio, M. Hetzer, ELife 8 (2019). date_created: 2022-04-07T07:45:02Z date_published: 2019-10-10T00:00:00Z date_updated: 2023-05-31T06:36:22Z day: '10' ddc: - '570' doi: 10.7554/elife.49796 extern: '1' external_id: pmid: - '31599721' file: - access_level: open_access checksum: 1e8672a1e9c3dc0a2d3d0dad89673616 content_type: application/pdf creator: dernst date_created: 2022-04-08T08:18:01Z date_updated: 2022-04-08T08:18:01Z file_id: '11138' file_name: 2019_eLife_Buchwalter.pdf file_size: 6984654 relation: main_file success: 1 file_date_updated: 2022-04-08T08:18:01Z has_accepted_license: '1' intvolume: ' 8' keyword: - General Immunology and Microbiology - General Biochemistry - Genetics and Molecular Biology - General Medicine - General Neuroscience language: - iso: eng month: '10' oa: 1 oa_version: Published Version pmid: 1 publication: eLife publication_identifier: issn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' related_material: record: - id: '13079' relation: research_data status: public scopus_import: '1' status: public title: Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress 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: 72615eeb-f1f3-11ec-aa25-d4573ddc34fd volume: 8 year: '2019' ... --- _id: '6891' abstract: - lang: eng text: "While cells of mesenchymal or epithelial origin perform their effector functions in a purely anchorage dependent manner, cells derived from the hematopoietic lineage are not committed to operate only within a specific niche. Instead, these cells are able to function autonomously of the molecular composition in a broad range of tissue compartments. By this means, cells of the hematopoietic lineage retain the capacity to disseminate into connective tissue and recirculate between organs, building the foundation for essential processes such as tissue regeneration or immune surveillance. \r\nCells of the immune system, specifically leukocytes, are extraordinarily good at performing this task. These cells are able to flexibly shift their mode of migration between an adhesion-mediated and an adhesion-independent manner, instantaneously accommodating for any changes in molecular composition of the external scaffold. The key component driving directed leukocyte migration is the chemokine receptor 7, which guides the cell along gradients of chemokine ligand. Therefore, the physical destination of migrating leukocytes is purely deterministic, i.e. given by global directional cues such as chemokine gradients. \r\nNevertheless, these cells typically reside in three-dimensional scaffolds of inhomogeneous complexity, raising the question whether cells are able to locally discriminate between multiple optional migration routes. Current literature provides evidence that leukocytes, specifically dendritic cells, do indeed probe their surrounding by virtue of multiple explorative protrusions. However, it remains enigmatic how these cells decide which one is the more favorable route to follow and what are the key players involved in performing this task. Due to the heterogeneous environment of most tissues, and the vast adaptability of migrating leukocytes, at this time it is not clear to what extent leukocytes are able to optimize their migratory strategy by adapting their level of adhesiveness. And, given the fact that leukocyte migration is characterized by branched cell shapes in combination with high migration velocities, it is reasonable to assume that these cells require fine tuned shape maintenance mechanisms that tightly coordinate protrusion and adhesion dynamics in a spatiotemporal manner. \r\nTherefore, this study aimed to elucidate how rapidly migrating leukocytes opt for an ideal migratory path while maintaining a continuous cell shape and balancing adhesive forces to efficiently navigate through complex microenvironments. \r\nThe results of this study unraveled a role for the microtubule cytoskeleton in promoting the decision making process during path finding and for the first time point towards a microtubule-mediated function in cell shape maintenance of highly ramified cells such as dendritic cells. Furthermore, we found that migrating low-adhesive leukocytes are able to instantaneously adapt to increased tensile load by engaging adhesion receptors. This response was only occurring tangential to the substrate while adhesive properties in the vertical direction were not increased. As leukocytes are primed for rapid migration velocities, these results demonstrate that leukocyte integrins are able to confer a high level of traction forces parallel to the cell membrane along the direction of migration without wasting energy in gluing the cell to the substrate. \r\nThus, the data in the here presented thesis provide new insights into the pivotal role of cytoskeletal dynamics and the mechanisms of force transduction during leukocyte migration. \r\nThereby the here presented results help to further define fundamental principles underlying leukocyte migration and open up potential therapeutic avenues of clinical relevance.\r\n" alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Aglaja full_name: Kopf, Aglaja id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87 last_name: Kopf orcid: 0000-0002-2187-6656 citation: ama: Kopf A. The implication of cytoskeletal dynamics on leukocyte migration. 2019. doi:10.15479/AT:ISTA:6891 apa: Kopf, A. (2019). The implication of cytoskeletal dynamics on leukocyte migration. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6891 chicago: Kopf, Aglaja. “The Implication of Cytoskeletal Dynamics on Leukocyte Migration.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6891. ieee: A. Kopf, “The implication of cytoskeletal dynamics on leukocyte migration,” Institute of Science and Technology Austria, 2019. ista: Kopf A. 2019. The implication of cytoskeletal dynamics on leukocyte migration. Institute of Science and Technology Austria. mla: Kopf, Aglaja. The Implication of Cytoskeletal Dynamics on Leukocyte Migration. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6891. short: A. Kopf, The Implication of Cytoskeletal Dynamics on Leukocyte Migration, Institute of Science and Technology Austria, 2019. date_created: 2019-09-19T08:19:44Z date_published: 2019-07-24T00:00:00Z date_updated: 2023-10-18T08:49:17Z day: '24' ddc: - '570' degree_awarded: PhD department: - _id: MiSi doi: 10.15479/AT:ISTA:6891 file: - access_level: closed checksum: 00d100d6468e31e583051e0a006b640c content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: akopf date_created: 2019-10-15T05:28:42Z date_updated: 2020-10-17T22:30:03Z embargo_to: open_access file_id: '6950' file_name: Kopf_PhD_Thesis.docx file_size: 74735267 relation: source_file - access_level: open_access checksum: 5d1baa899993ae6ca81aebebe1797000 content_type: application/pdf creator: akopf date_created: 2019-10-15T05:28:47Z date_updated: 2020-10-17T22:30:03Z embargo: 2020-10-16 file_id: '6951' file_name: Kopf_PhD_Thesis1.pdf file_size: 52787224 relation: main_file file_date_updated: 2020-10-17T22:30:03Z has_accepted_license: '1' keyword: - cell biology - immunology - leukocyte - migration - microfluidics language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: '171' project: - _id: 265E2996-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W01250-B20 name: Nano-Analytics of Cellular Systems publication_identifier: eissn: - 2663-337X isbn: - 978-3-99078-002-2 publication_status: published publisher: Institute of Science and Technology Austria related_material: link: - relation: press_release url: https://ist.ac.at/en/news/feeling-like-a-cell/ record: - id: '6328' relation: part_of_dissertation status: public - id: '15' relation: part_of_dissertation status: public - id: '6877' relation: part_of_dissertation status: public status: public supervisor: - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 title: The implication of cytoskeletal dynamics on leukocyte migration type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '10370' abstract: - lang: eng text: Eukaryotic cells are densely packed with macromolecular complexes and intertwining organelles, continually transported and reshaped. Intriguingly, organelles avoid clashing and entangling with each other in such limited space. Mitochondria form extensive networks constantly remodeled by fission and fusion. Here, we show that mitochondrial fission is triggered by mechanical forces. Mechano-stimulation of mitochondria – via encounter with motile intracellular pathogens, via external pressure applied by an atomic force microscope, or via cell migration across uneven microsurfaces – results in the recruitment of the mitochondrial fission machinery, and subsequent division. We propose that MFF, owing to affinity for narrow mitochondria, acts as a membrane-bound force sensor to recruit the fission machinery to mechanically strained sites. Thus, mitochondria adapt to the environment by sensing and responding to biomechanical cues. Our findings that mechanical triggers can be coupled to biochemical responses in membrane dynamics may explain how organelles orderly cohabit in the crowded cytoplasm. article_number: e30292 article_processing_charge: No article_type: original author: - first_name: Sebastian Carsten Johannes full_name: Helle, Sebastian Carsten Johannes last_name: Helle - first_name: Qian full_name: Feng, Qian last_name: Feng - first_name: Mathias J full_name: Aebersold, Mathias J last_name: Aebersold - first_name: Luca full_name: Hirt, Luca last_name: Hirt - first_name: Raphael R full_name: Grüter, Raphael R last_name: Grüter - first_name: Afshin full_name: Vahid, Afshin last_name: Vahid - first_name: Andrea full_name: Sirianni, Andrea last_name: Sirianni - first_name: Serge full_name: Mostowy, Serge last_name: Mostowy - first_name: Jess G full_name: Snedeker, Jess G last_name: Snedeker - first_name: Anđela full_name: Šarić, Anđela id: bf63d406-f056-11eb-b41d-f263a6566d8b last_name: Šarić orcid: 0000-0002-7854-2139 - first_name: Timon full_name: Idema, Timon last_name: Idema - first_name: Tomaso full_name: Zambelli, Tomaso last_name: Zambelli - first_name: Benoît full_name: Kornmann, Benoît last_name: Kornmann citation: ama: Helle SCJ, Feng Q, Aebersold MJ, et al. Mechanical force induces mitochondrial fission. eLife. 2017;6. doi:10.7554/elife.30292 apa: Helle, S. C. J., Feng, Q., Aebersold, M. J., Hirt, L., Grüter, R. R., Vahid, A., … Kornmann, B. (2017). Mechanical force induces mitochondrial fission. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.30292 chicago: Helle, Sebastian Carsten Johannes, Qian Feng, Mathias J Aebersold, Luca Hirt, Raphael R Grüter, Afshin Vahid, Andrea Sirianni, et al. “Mechanical Force Induces Mitochondrial Fission.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/elife.30292. ieee: S. C. J. Helle et al., “Mechanical force induces mitochondrial fission,” eLife, vol. 6. eLife Sciences Publications, 2017. ista: Helle SCJ, Feng Q, Aebersold MJ, Hirt L, Grüter RR, Vahid A, Sirianni A, Mostowy S, Snedeker JG, Šarić A, Idema T, Zambelli T, Kornmann B. 2017. Mechanical force induces mitochondrial fission. eLife. 6, e30292. mla: Helle, Sebastian Carsten Johannes, et al. “Mechanical Force Induces Mitochondrial Fission.” ELife, vol. 6, e30292, eLife Sciences Publications, 2017, doi:10.7554/elife.30292. short: S.C.J. Helle, Q. Feng, M.J. Aebersold, L. Hirt, R.R. Grüter, A. Vahid, A. Sirianni, S. Mostowy, J.G. Snedeker, A. Šarić, T. Idema, T. Zambelli, B. Kornmann, ELife 6 (2017). date_created: 2021-11-29T08:51:38Z date_published: 2017-11-09T00:00:00Z date_updated: 2021-11-29T09:28:14Z day: '09' ddc: - '572' doi: 10.7554/elife.30292 extern: '1' external_id: pmid: - '29119945' file: - access_level: open_access checksum: c35f42dcfb007f6d6c761a27e24c26d3 content_type: application/pdf creator: cchlebak date_created: 2021-11-29T09:07:41Z date_updated: 2021-11-29T09:07:41Z file_id: '10372' file_name: 2017_eLife_Helle.pdf file_size: 6120157 relation: main_file success: 1 file_date_updated: 2021-11-29T09:07:41Z has_accepted_license: '1' intvolume: ' 6' keyword: - general immunology and microbiology - general biochemistry - genetics and molecular biology - general medicine - general neuroscience language: - iso: eng main_file_link: - open_access: '1' url: https://elifesciences.org/articles/30292 month: '11' oa: 1 oa_version: Published Version pmid: 1 publication: eLife publication_identifier: issn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: Mechanical force induces mitochondrial fission tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 volume: 6 year: '2017' ... --- _id: '15154' abstract: - lang: eng text: Biofilm formation is critical for the infection cycle of Vibrio cholerae. Vibrio exopolysaccharides (VPS) and the matrix proteins RbmA, Bap1 and RbmC are required for the development of biofilm architecture. We demonstrate that RbmA binds VPS directly and uses a binary structural switch within its first fibronectin type III (FnIII-1) domain to control RbmA structural dynamics and the formation of VPS-dependent higher-order structures. The structural switch in FnIII-1 regulates interactions in trans with the FnIII-2 domain, leading to open (monomeric) or closed (dimeric) interfaces. The ability of RbmA to switch between open and closed states is important for V. cholerae biofilm formation, as RbmA variants with switches that are locked in either of the two states lead to biofilms with altered architecture and structural integrity. article_number: '26163' article_processing_charge: Yes article_type: original author: - first_name: Jiunn CN full_name: Fong, Jiunn CN last_name: Fong - first_name: Andrew full_name: Rogers, Andrew last_name: Rogers - first_name: Alicia Kathleen full_name: Michael, Alicia Kathleen id: 6437c950-2a03-11ee-914d-d6476dd7b75c last_name: Michael - first_name: Nicole C full_name: Parsley, Nicole C last_name: Parsley - first_name: William-Cole full_name: Cornell, William-Cole last_name: Cornell - first_name: Yu-Cheng full_name: Lin, Yu-Cheng last_name: Lin - first_name: Praveen K full_name: Singh, Praveen K last_name: Singh - first_name: Raimo full_name: Hartmann, Raimo last_name: Hartmann - first_name: Knut full_name: Drescher, Knut last_name: Drescher - first_name: Evgeny full_name: Vinogradov, Evgeny last_name: Vinogradov - first_name: Lars EP full_name: Dietrich, Lars EP last_name: Dietrich - first_name: Carrie L full_name: Partch, Carrie L last_name: Partch - first_name: Fitnat H full_name: Yildiz, Fitnat H last_name: Yildiz citation: ama: Fong JC, Rogers A, Michael AK, et al. Structural dynamics of RbmA governs plasticity of Vibrio cholerae biofilms. eLife. 2017;6. doi:10.7554/elife.26163 apa: Fong, J. C., Rogers, A., Michael, A. K., Parsley, N. C., Cornell, W.-C., Lin, Y.-C., … Yildiz, F. H. (2017). Structural dynamics of RbmA governs plasticity of Vibrio cholerae biofilms. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.26163 chicago: Fong, Jiunn CN, Andrew Rogers, Alicia K. Michael, Nicole C Parsley, William-Cole Cornell, Yu-Cheng Lin, Praveen K Singh, et al. “Structural Dynamics of RbmA Governs Plasticity of Vibrio Cholerae Biofilms.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/elife.26163. ieee: J. C. Fong et al., “Structural dynamics of RbmA governs plasticity of Vibrio cholerae biofilms,” eLife, vol. 6. eLife Sciences Publications, 2017. ista: Fong JC, Rogers A, Michael AK, Parsley NC, Cornell W-C, Lin Y-C, Singh PK, Hartmann R, Drescher K, Vinogradov E, Dietrich LE, Partch CL, Yildiz FH. 2017. Structural dynamics of RbmA governs plasticity of Vibrio cholerae biofilms. eLife. 6, 26163. mla: Fong, Jiunn CN, et al. “Structural Dynamics of RbmA Governs Plasticity of Vibrio Cholerae Biofilms.” ELife, vol. 6, 26163, eLife Sciences Publications, 2017, doi:10.7554/elife.26163. short: J.C. Fong, A. Rogers, A.K. Michael, N.C. Parsley, W.-C. Cornell, Y.-C. Lin, P.K. Singh, R. Hartmann, K. Drescher, E. Vinogradov, L.E. Dietrich, C.L. Partch, F.H. Yildiz, ELife 6 (2017). date_created: 2024-03-21T07:55:36Z date_published: 2017-08-01T00:00:00Z date_updated: 2024-03-25T12:22:54Z day: '01' doi: 10.7554/elife.26163 extern: '1' external_id: pmid: - '28762945' intvolume: ' 6' keyword: - General Immunology and Microbiology - General Biochemistry - Genetics and Molecular Biology - General Medicine - General Neuroscience language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.7554/eLife.26163 month: '08' oa: 1 oa_version: Published Version pmid: 1 publication: eLife publication_identifier: issn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: Structural dynamics of RbmA governs plasticity of Vibrio cholerae biofilms type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 6 year: '2017' ...