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2. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Author

Théry, Clotilde, Witwer, Kenneth W, Aikawa, Elena, Alcaraz, Maria Jose, Anderson, Johnathon D, Andriantsitohaina, Ramaroson, Antoniou, Anna, Arab, Tanina, Archer, Fabienne, Atkin‐Smith, Georgia K, Ayre, D Craig, Bach, Jean‐Marie, Bachurski, Daniel, Baharvand, Hossein, Balaj, Leonora, Baldacchino, Shawn, Bauer, Natalie N, Baxter, Amy A, Bebawy, Mary, Beckham, Carla, Zavec, Apolonija Bedina, Benmoussa, Abderrahim, Berardi, Anna C, Bergese, Paolo, Bielska, Ewa, Blenkiron, Cherie, Bobis‐Wozowicz, Sylwia, Boilard, Eric, Boireau, Wilfrid, Bongiovanni, Antonella, Borràs, Francesc E, Bosch, Steffi, Boulanger, Chantal M, Breakefield, Xandra, Breglio, Andrew M, Brennan, Meadhbh Á, Brigstock, David R, Brisson, Alain, Broekman, Marike LD, Bromberg, Jacqueline F, Bryl‐Górecka, Paulina, Buch, Shilpa, Buck, Amy H, Burger, Dylan, Busatto, Sara, Buschmann, Dominik, Bussolati, Benedetta, Buzás, Edit I, Byrd, James Bryan, Camussi, Giovanni, Carter, David RF, Caruso, Sarah, Chamley, Lawrence W, Chang, Yu‐Ting, Chen, Chihchen, Chen, Shuai, Cheng, Lesley, Chin, Andrew R, Clayton, Aled, Clerici, Stefano P, Cocks, Alex, Cocucci, Emanuele, Coffey, Robert J, Cordeiro‐da‐Silva, Anabela, Couch, Yvonne, Coumans, Frank AW, Coyle, Beth, Crescitelli, Rossella, Criado, Miria Ferreira, D'Souza‐Schorey, Crislyn, Das, Saumya, Chaudhuri, Amrita Datta, de Candia, Paola, De Santana, Eliezer F, De Wever, Olivier, del Portillo, Hernando A, Demaret, Tanguy, Deville, Sarah, Devitt, Andrew, Dhondt, Bert, Di Vizio, Dolores, Dieterich, Lothar C, Dolo, Vincenza, Rubio, Ana Paula Dominguez, Dominici, Massimo, Dourado, Mauricio R, Driedonks, Tom AP, Duarte, Filipe V, Duncan, Heather M, Eichenberger, Ramon M, Ekström, Karin, Andaloussi, Samir EL, Elie‐Caille, Celine, Erdbrügger, Uta, Falcón‐Pérez, Juan M, Fatima, Farah, Fish, Jason E, Flores‐Bellver, Miguel, Försönits, András, and Frelet‐Barrand, Annie

Subjects
Biochemistry and Cell Biology, Biological Sciences, extracellular vesicles, exosomes, ectosomes, microvesicles, minimal information requirements, guidelines, standardization, microparticles, rigor, reproducibility, Biochemistry and cell biology
Abstract

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

Published
2018

3. Rapamycin Treatment Reduces Brain Pericyte Constriction in Ischemic Stroke

Author

Beard, Daniel, primary, Brown, Lachlan S, additional, Morris, Gary P, additional, Couch, Yvonne, additional, Adriaanse, Bryan A, additional, Simoglou Karali, Christina, additional, Schneider, Anna M, additional, Howells, David W, additional, Redzic, Zoran B, additional, Sutherland, Brad A., additional, and Buchan, Alastair M, additional

Published
2024
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6. The effect of inflammation on the central 5-HT system in mood disorders

Author

Couch, Yvonne H., Anthony, Daniel C., Sibson, Nicola R., and Sharp, Trevor

Subjects
616.8527, Immunology, Pharmacology, Neuropsychology, Emotion research, inflammation, cytokines, depression
Abstract

Inflammation appears to play a major role in the pathogenesis of Major Depression, and understanding the relationship between the immune system and mood disorders is a growing area of research. Patients undergoing cytokine therapy frequently develop depressive-like signs which cease upon termination of treatment. In addition, depressed patients often present with high levels of circulating pro-inflammatory cytokines. There are also significant behavioural correlates between inflammation-associated sickness behaviours and Major Depression, suggesting there is a bidirectional relationship between the immune system and central systems regulating behaviour. Both sickness behaviours in animals and cytokine-induced depression in humans can be reversed with antidepressants targeting the serotonergic (5-HT) system. Against this background, this thesis sought to investigate the role of inflammation in the development of certain specific characteristics of depressive-like states in animal models. Specifically, a single systemic endotoxin challenge (LPS) was used to model acute sickness behaviour and to study the behaviour and molecular effects of this challenge on the 5-HT system. These studies indicated that a single systemic challenge changed the function of the 5-HT system, as well as increasing expression levels of a number of 5-HT-related genes, and markers of inflammation in the CNS. A rodent chronic stress paradigm was employed to investigate whether these changes also occur in animals displaying depressive-like signs. Chronically stressed mice were shown to display significant features of rodent depression; decreased sucrose preference and increased forced swim immobility. These changes were also accompanied by increased expression of 5-HT-related genes and inflammatory markers within the CNS. Importantly, many of the molecular changes observed in LPS-induced sickness behaviour were conserved in the model of stress-induced Major Depression. In particular, increased TNF expression within the CNS was highlighted as a feature in both models. Novel anti-inflammatory agents were used to study the role of TNF in the development of sickness behaviours. Anti-TNF therapy, specifically the fusion protein etanercept, ameliorated sickness behaviour induced by LPS. Together, these data demonstrate that inflammation is capable of significantly changing the 5-HT system, and that stress per se is capable of inducing an inflammatory state within the CNS, which support the thesis that sickness and Major Depression are closely related at a molecular level.

Published
2012

9. Placental capillary pericytes release excess extracellular vesicles under hypoxic conditions inducing a pro-angiogenic profile in term pregnancy

Author

Kandzija, Neva, primary, Rahbar, Maryam, additional, Jones, Gabriel Davis, additional, Motta-Mejia, Carolina, additional, Zhang, Wei, additional, Couch, Yvonne, additional, Neuhaus, Ain A., additional, Kishore, Uday, additional, Sutherland, Brad A., additional, Redman, Christopher, additional, and Vatish, Manu, additional

Published
2023
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11. Challenges associated with using extracellular vesicles as biomarkers in neurodegenerative disease.

Author

Couch, Yvonne

Abstract

The hunt for new biomarkers – for the diagnosis of subcategories of disease, or for the monitoring of the efficacy of novel therapeutics – is an increasingly relevant challenge in the current era of precision medicine. In neurodegenerative research, the aim is to look for simple tools which can predict cognitive or motor decline early, and to determine whether these can also be used to test the efficacy of new interventions. Extracellular vesicles (EVs) are thought to play an important role in intercellular communication and have been shown to play a vital role in a number of diseases. The aim of this review is to examine what we know about EVs in neurodegeneration and to discuss their potential to be diagnostic and prognostic biomarkers in the future. It will cover the techniques used to isolate and study EVs and what is currently known about their presence in neurodegenerative diseases. In particular, we will discuss what is required for standardization in biomarker research, and the challenges associated with using EVs within this framework. The technical challenges associated with isolating EVs consistently, combined with the complex techniques required for their efficient analysis, might preclude 'pure' EV populations from being used as effective biomarkers. Whilst biomarker discovery is important for more effective diagnosis, monitoring, prediction and prognosis in neurodegenerative disease, reproducibility and ease-of-use should be the priorities. [ABSTRACT FROM AUTHOR]

Published
2023
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15. Metabolic clearance rate modeling: A translational approach to quantifying cerebral metabolism using hyperpolarized [1-13C]pyruvate.

Author

Grist, James T, primary, Boegh, Nikolaj, additional, Hansen, Esben, additional, Schneider, Anna, additional, Healicon, Richard, additional, Ball, Vicky, additional, Miller, Jack, additional, Smart, Sean, additional, Couch, Yvonne, additional, Buchan, Alastair, additional, Tyler, Damian, additional, and Laustsen, Christoffer, additional

Published
2022
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19. In sickness and in health : The functional role of extracellular vesicles in physiology and pathology in vivo Part II: Pathology

Author

Yates, Abi G., Pink, Ryan C., Erdbrugger, Uta, Siljander, Pia R-M., Dellar, Elizabeth R., Pantazi, Paschalia, Akbar, Naveed, Cooke, William R., Vatish, Manu, Dias-Neto, Emmanuel, Anthony, Daniel C., Couch, Yvonne, Extracellular Vesicles, Drug Research Program, Molecular and Integrative Biosciences Research Programme, and Biosciences

Subjects
CIRCULATING ENDOTHELIAL MICROPARTICLES, 1184 Genetics, developmental biology, physiology, GESTATIONAL DIABETES-MELLITUS, MATERNAL CIRCULATION, EPITHELIAL-CELLS, exosomes, POLYCYSTIC-OVARY-SYNDROME, INSULINOMA-RELEASED EXOSOMES, in vivo, PLATELET-DERIVED MICROPARTICLES, physiology, T-CELLS, pathology, OXIDATIVE STRESS, extracellular vesicles, microvesicles
Abstract

It is clear from Part I of this series that extracellular vesicles (EVs) play a critical role in maintaining the homeostasis of most, if not all, normal physiological systems. However, the majority of our knowledge about EV signalling has come from studying them in disease. Indeed, EVs have consistently been associated with propagating disease pathophysiology. The analysis of EVs in biofluids, obtained in the clinic, has been an essential of the work to improve our understanding of their role in disease. However, to interfere with EV signalling for therapeutic gain, a more fundamental understanding of the mechanisms by which they contribute to pathogenic processes is required. Only by discovering how the EV populations in different biofluids change-size, number, and physicochemical composition-in clinical samples, may we then begin to unravel their functional roles in translational models in vitro and in vivo, which can then feedback to the clinic. In Part II of this review series, the functional role of EVs in pathology and disease will be discussed, with a focus on in vivo evidence and their potential to be used as both biomarkers and points of therapeutic intervention.

Published
2022

20. In sickness and in health: The functional role of extracellular vesicles in physiology and pathology in vivo. Part1

Author

Yates, Abi G., Pink, Ryan C., Erdbrügger, Uta, Siljander, Pia R-M., Dellar, Elizabeth R., Pantazi, Paschalia, Akbar, Naveed, Cooke, William R., Vatish, Manu, Dias-Neto, Emmanuel, Anthony, Daniel C., and Couch, Yvonne

Abstract

Previously thought to be nothing more than cellular debris, extracellular vesicles (EVs) are now known to mediate physiological and pathological functions throughout the body.We now understand more about their capacity to transfer nucleic acids and proteins between distant organs, the interaction of their surface proteins with target cells, and the role of vesicle-bound lipids in health and disease. To date, most observations have been made in reductionist cell culture systems, or as snapshots from patient cohorts. The heterogenous population of vesicles produced in vivo likely act in concert to mediate both beneficial and detrimental effects. EVs play crucial roles in both the pathogenesis of diseases, from cancer to neurodegenerative disease, as well as in the maintenance of system and organ homeostasis. This two-part review draws on the expertise of researchers working in the field of EV biology and aims to cover the functional role of EVs in physiology and pathology. Part I will outline the role of EVs in normal physiology.

Published
2022

21. In sickness and in health: The functional role of extracellular vesicles in physiology and pathology in vivo

Author

Yates, Abi G., Pink, Ryan C., Erdbrügger, Uta, Siljander, Pia R‐M., Dellar, Elizabeth R., Pantazi, Paschalia, Akbar, Naveed, Cooke, William R., Vatish, Manu, Dias‐Neto, Emmanuel, Anthony, Daniel C., and Couch, Yvonne

Subjects
Blood Platelets, Central Nervous System, Inflammation, QH573-671, Musculoskeletal Physiological Phenomena, Immunity, Urogenital System, Review Article, exosomes, Gastrointestinal Microbiome, Cardiovascular Physiological Phenomena, in vivo, Cell-Derived Microparticles, physiology, Homeostasis, Humans, pathology, extracellular vesicles, Cytology, Review Articles, microvesicles, Signal Transduction
Abstract

It is clear from Part I of this series that extracellular vesicles (EVs) play a critical role in maintaining the homeostasis of most, if not all, normal physiological systems. However, the majority of our knowledge about EV signalling has come from studying them in disease. Indeed, EVs have consistently been associated with propagating disease pathophysiology. The analysis of EVs in biofluids, obtained in the clinic, has been an essential of the work to improve our understanding of their role in disease. However, to interfere with EV signalling for therapeutic gain, a more fundamental understanding of the mechanisms by which they contribute to pathogenic processes is required. Only by discovering how the EV populations in different biofluids change—size, number, and physicochemical composition—in clinical samples, may we then begin to unravel their functional roles in translational models in vitro and in vivo, which can then feedback to the clinic. In Part II of this review series, the functional role of EVs in pathology and disease will be discussed, with a focus on in vivo evidence and their potential to be used as both biomarkers and points of therapeutic intervention.

Published
2022

24. Developing a metabolic clearance rate framework as a translational analysis approach for hyperpolarized 13C magnetic resonance imaging.

Author

Grist, James T., Bøgh, Nikolaj, Hansen, Esben Søvsø, Schneider, Anna M., Healicon, Richard, Ball, Vicky, Miller, Jack J. J. J., Smart, Sean, Couch, Yvonne, Buchan, Alastair M., Tyler, Damian J., and Laustsen, Christoffer

Subjects
METABOLIC clearance rate, MAGNETIC resonance imaging, RATS, CEREBRAL circulation
Abstract

Hyperpolarized carbon-13 magnetic resonance imaging is a promising technique for in vivo metabolic interrogation of alterations between health and disease. This study introduces a formalism for quantifying the metabolic information in hyperpolarized imaging. This study investigated a novel perfusion formalism and metabolic clearance rate (MCR) model in pre-clinical stroke and in the healthy human brain. Simulations showed that the proposed model was robust to perturbations in T1, transmit B1, and kPL. A significant difference in ipsilateral vs contralateral pyruvate derived cerebral blood flow (CBF) was detected in rats (140 ± 2 vs 89 ± 6 mL/100 g/min, p < 0.01, respectively) and pigs (139 ± 12 vs 95 ± 5 mL/100 g/min, p = 0.04, respectively), along with an increase in fractional metabolism (26 ± 5 vs 4 ± 2%, p < 0.01, respectively) in the rodent brain. In addition, a significant increase in ipsilateral vs contralateral MCR (0.034 ± 0.007 vs 0.017 ± 0.02/s, p = 0.03, respectively) and a decrease in mean transit time (31 ± 8 vs 60 ± 2 s, p = 0.04, respectively) was observed in the porcine brain. In conclusion, MCR mapping is a simple and robust approach to the post-processing of hyperpolarized magnetic resonance imaging. [ABSTRACT FROM AUTHOR]

Published
2023
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33. Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Author

Théry, Clotilde, Witwer, Kenneth W, Aikawa, Elena, Alcaraz, Maria Jose, Anderson, Johnathon D, Andriantsitohaina, Ramaroson, Antoniou, Anna, Arab, Tanina, Archer, Fabienne, Atkin-Smith, Georgia K, Ayre, D Craig, Bach, Jean-Marie, Bachurski, Daniel, Baharvand, Hossein, Balaj, Leonora, Baldacchino, Shawn, Bauer, Natalie N, Baxter, Amy A, Bebawy, Mary, Beckham, Carla, Bedina Zavec, Apolonija, Benmoussa, Abderrahim, Berardi, Anna C, Bergese, Paolo, Bielska, Ewa, Blenkiron, Cherie, Bobis-Wozowicz, Sylwia, Boilard, Eric, Boireau, Wilfrid, Bongiovanni, Antonella, Borràs, Francesc E, Bosch, Steffi, Boulanger, Chantal M, Breakefield, Xandra, Breglio, Andrew M, Brennan, Meadhbh Á, Brigstock, David R, Brisson, Alain, Broekman, Marike Ld, Bromberg, Jacqueline F, Bryl-Górecka, Paulina, Buch, Shilpa, Buck, Amy H, Burger, Dylan, Busatto, Sara, Buschmann, Dominik, Bussolati, Benedetta, Buzás, Edit I, Byrd, James Bryan, Camussi, Giovanni, Carter, David Rf, Caruso, Sarah, Chamley, Lawrence W, Chang, Yu-Ting, Chen, Chihchen, Chen, Shuai, Cheng, Lesley, Chin, Andrew R, Clayton, Aled, Clerici, Stefano P, Cocks, Alex, Cocucci, Emanuele, Coffey, Robert J, Cordeiro-da-Silva, Anabela, Couch, Yvonne, Coumans, Frank Aw, Coyle, Beth, Crescitelli, Rossella, Criado, Miria Ferreira, D'Souza-Schorey, Crislyn, Das, Saumya, Datta Chaudhuri, Amrita, de Candia, Paola, De Santana, Eliezer F, De Wever, Olivier, Del Portillo, Hernando A, Demaret, Tanguy, Deville, Sarah, Devitt, Andrew, Dhondt, Bert, Di Vizio, Dolores, Dieterich, Lothar C, Dolo, Vincenza, Dominguez Rubio, Ana Paula, Dominici, Massimo, Dourado, Mauricio R, Driedonks, Tom Ap, Duarte, Filipe V, Duncan, Heather M, Eichenberger, Ramon M, Ekström, Karin, El Andaloussi, Samir, Elie-Caille, Celine, Erdbrügger, Uta, Falcón-Pérez, Juan M, Fatima, Farah, Fish, Jason E, Flores-Bellver, Miguel, Försönits, András, Frelet-Barrand, Annie, Fricke, Fabia, Fuhrmann, Gregor, Gabrielsson, Susanne, Gámez-Valero, Ana, Gardiner, Chris, Gärtner, Kathrin, Gaudin, Raphael, Gho, Yong Song, Giebel, Bernd, Gilbert, Caroline, Gimona, Mario, Giusti, Ilaria, Goberdhan, Deborah Ci, Görgens, André, Gorski, Sharon M, Greening, David W, Gross, Julia Christina, Gualerzi, Alice, Gupta, Gopal N, Gustafson, Dakota, Handberg, Aase, Haraszti, Reka A, Harrison, Paul, Hegyesi, Hargita, Hendrix, An, Hill, Andrew F, Hochberg, Fred H, Hoffmann, Karl F, Holder, Beth, Holthofer, Harry, Hosseinkhani, Baharak, Hu, Guoku, Huang, Yiyao, Huber, Veronica, Hunt, Stuart, Ibrahim, Ahmed Gamal-Eldin, Ikezu, Tsuneya, Inal, Jameel M, Isin, Mustafa, Ivanova, Alena, Jackson, Hannah K, Jacobsen, Soren, Jay, Steven M, Jayachandran, Muthuvel, Jenster, Guido, Jiang, Lanzhou, Johnson, Suzanne M, Jones, Jennifer C, Jong, Ambrose, Jovanovic-Talisman, Tijana, Jung, Stephanie, Kalluri, Raghu, Kano, Shin-Ichi, Kaur, Sukhbir, Kawamura, Yumi, Keller, Evan T, Khamari, Delaram, Khomyakova, Elena, Khvorova, Anastasia, Kierulf, Peter, Kim, Kwang Pyo, Kislinger, Thomas, Klingeborn, Mikael, Klinke, David J, Kornek, Miroslaw, Kosanović, Maja M, Kovács, Árpád Ferenc, Krämer-Albers, Eva-Maria, Krasemann, Susanne, Krause, Mirja, Kurochkin, Igor V, Kusuma, Gina D, Kuypers, Sören, Laitinen, Saara, Langevin, Scott M, Languino, Lucia R, Lannigan, Joanne, Lässer, Cecilia, Laurent, Louise C, Lavieu, Gregory, Lázaro-Ibáñez, Elisa, Le Lay, Soazig, Lee, Myung-Shin, Lee, Yi Xin Fiona, Lemos, Debora S, Lenassi, Metka, Leszczynska, Aleksandra, Li, Isaac Ts, Liao, Ke, Libregts, Sten F, Ligeti, Erzsebet, Lim, Rebecca, Lim, Sai Kiang, Linē, Aija, Linnemannstöns, Karen, Llorente, Alicia, Lombard, Catherine A, Lorenowicz, Magdalena J, Lörincz, Ákos M, Lötvall, Jan, Lovett, Jason, Lowry, Michelle C, Loyer, Xavier, Lu, Quan, Lukomska, Barbara, Lunavat, Taral R, Maas, Sybren Ln, Malhi, Harmeet, Marcilla, Antonio, Mariani, Jacopo, Mariscal, Javier, Martens-Uzunova, Elena S, Martin-Jaular, Lorena, Martinez, M Carmen, Martins, Vilma Regina, Mathieu, Mathilde, Mathivanan, Suresh, Maugeri, Marco, McGinnis, Lynda K, McVey, Mark J, Meckes, David G, Meehan, Katie L, Mertens, Inge, Minciacchi, Valentina R, Möller, Andreas, Møller Jørgensen, Malene, Morales-Kastresana, Aizea, Morhayim, Jess, Mullier, François, Muraca, Maurizio, Musante, Luca, Mussack, Veronika, Muth, Dillon C, Myburgh, Kathryn H, Najrana, Tanbir, Nawaz, Muhammad, Nazarenko, Irina, Nejsum, Peter, Neri, Christian, Neri, Tommaso, Nieuwland, Rienk, Nimrichter, Leonardo, Nolan, John P, Nolte-'t Hoen, Esther NM, Noren Hooten, Nicole, O'Driscoll, Lorraine, O'Grady, Tina, O'Loghlen, Ana, Ochiya, Takahiro, Olivier, Martin, Ortiz, Alberto, Ortiz, Luis A, Osteikoetxea, Xabier, Østergaard, Ole, Ostrowski, Matias, Park, Jaesung, Pegtel, D Michiel, Peinado, Hector, Perut, Francesca, Pfaffl, Michael W, Phinney, Donald G, Pieters, Bartijn Ch, Pink, Ryan C, Pisetsky, David S, Pogge von Strandmann, Elke, Polakovicova, Iva, Poon, Ivan Kh, Powell, Bonita H, Prada, Ilaria, Pulliam, Lynn, Quesenberry, Peter, Radeghieri, Annalisa, Raffai, Robert L, Raimondo, Stefania, Rak, Janusz, Ramirez, Marcel I, Raposo, Graça, Rayyan, Morsi S, Regev-Rudzki, Neta, Ricklefs, Franz L, Robbins, Paul D, Roberts, David D, Rodrigues, Silvia C, Rohde, Eva, Rome, Sophie, Rouschop, Kasper Ma, Rughetti, Aurelia, Russell, Ashley E, Saá, Paula, Sahoo, Susmita, Salas-Huenuleo, Edison, Sánchez, Catherine, Saugstad, Julie A, Saul, Meike J, Schiffelers, Raymond M, Schneider, Raphael, Schøyen, Tine Hiorth, Scott, Aaron, Shahaj, Eriomina, Sharma, Shivani, Shatnyeva, Olga, Shekari, Faezeh, Shelke, Ganesh Vilas, Shetty, Ashok K, Shiba, Kiyotaka, Siljander, Pia R-M, Silva, Andreia M, Skowronek, Agata, Snyder, Orman L, Soares, Rodrigo Pedro, Sódar, Barbara W, Soekmadji, Carolina, Sotillo, Javier, Stahl, Philip D, Stoorvogel, Willem, Stott, Shannon L, Strasser, Erwin F, Swift, Simon, Tahara, Hidetoshi, Tewari, Muneesh, Timms, Kate, Tiwari, Swasti, Tixeira, Rochelle, Tkach, Mercedes, Toh, Wei Seong, Tomasini, Richard, Torrecilhas, Ana Claudia, Tosar, Juan Pablo, Toxavidis, Vasilis, Urbanelli, Lorena, Vader, Pieter, van Balkom, Bas Wm, van der Grein, Susanne G, Van Deun, Jan, van Herwijnen, Martijn Jc, Van Keuren-Jensen, Kendall, van Niel, Guillaume, van Royen, Martin E, van Wijnen, Andre J, Vasconcelos, M Helena, Vechetti, Ivan J, Veit, Tiago D, Vella, Laura J, Velot, Émilie, Verweij, Frederik J, Vestad, Beate, Viñas, Jose L, Visnovitz, Tamás, Vukman, Krisztina V, Wahlgren, Jessica, Watson, Dionysios C, Wauben, Marca Hm, Weaver, Alissa, Webber, Jason P, Weber, Viktoria, Wehman, Ann M, Weiss, Daniel J, Welsh, Joshua A, Wendt, Sebastian, Wheelock, Asa M, Wiener, Zoltán, Witte, Leonie, Wolfram, Joy, Xagorari, Angeliki, Xander, Patricia, Xu, Jing, Yan, Xiaomei, Yáñez-Mó, María, Yin, Hang, Yuana, Yuana, Zappulli, Valentina, Zarubova, Jana, Žėkas, Vytautas, Zhang, Jian-Ye, Zhao, Zezhou, Zheng, Lei, Zheutlin, Alexander R, Zickler, Antje M, Zimmermann, Pascale, Zivkovic, Angela M, Zocco, Davide, Zuba-Surma, Ewa K, dB&C I&I, LS Celbiologie-Algemeen, Celbiologie, Afd Pharmaceutics, Sub General Pharmaceutics, Sub Biomol.Mass Spect. and Proteomics, Afd Pharmacology, Urology, Pathology, Medical Oncology, Immunité et cancer, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Johns Hopkins University School of Medicine [Baltimore], Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Infections Virales et Pathologie Comparée - UMR 754 (IVPC), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Immuno-Endocrinologie Cellulaire et Moléculaire [Nantes] (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Department for Molecular Biology and Nanobiotechnology, National Institute of chemitry, Slovenia, Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Imagerie Moléculaire et Nanobiotechnologies - Institut Européen de Chimie et Biologie (IECB), Université Sciences et Technologies - Bordeaux 1-Centre National de la Recherche Scientifique (CNRS), Molecular Biotechnology Center, Università degli studi di Torino = University of Turin (UNITO), Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Centre for Sustainable Tropical Fisheries and Aquaculture, James Cook University (JCU), Department of Oncology - Pathology, Cancer Center Karolinska [Karolinska Institutet] (CCK), Karolinska Institutet [Stockholm]-Karolinska Institutet [Stockholm], Departamento de Ciências Biológicas, Universidade do Porto = University of Porto, Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Cancer Research Institute Ghent (CRIG), Universiteit Gent = Ghent University [Belgium] (UGENT), Department of Medical and Surgical Sciences for Children and Adults [Modena, Italy] (Laboratory of Cellular Therapy), Università degli Studi di Modena e Reggio Emilia (UNIMORE), Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Center for Cooperative Research in Biosciences (CIC bioGUNE), Partner site Munich, German Centre for Infection Research (DZIF), Institute for Transfusion Medicine, University Hospital Essen, Universität Duisburg-Essen [Essen], Mécanismes Adaptatifs et Evolution (MECADEV), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Psychiatry, Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University, Department of Bacteriology and Immunology [Helsinki], Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Rigshospitalet [Copenhagen], Copenhagen University Hospital, Dalhousie University [Halifax], Department of Biology, Molecular Cell Biology, University of Mainz, Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Glycobiologie et signalisation cellulaire, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg (GU), Universidad de Alicante, École supérieure du professorat et de l'éducation - Académie de Créteil (UPEC ESPE Créteil), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), University of Antwerp (UA), Université Catholique de Louvain = Catholic University of Louvain (UCL), Research Institute, IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Department of Veterinary Disease Biology [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Biologie et Pathologie du Neurone (Brain-C), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Mathematics and Statistics, American University, University of Pretoria [South Africa], Ecole des Ingénieurs de la Ville de Paris (EIVP), Universitat Pompeu Fabra [Barcelona] (UPF), Instituto de Investigaciones Biomedicas, Universidad Nacional Autónoma de México (UNAM), Istituto Ortopedico Rizzoli, Department of Molecular Therapeutics, The Scripps Research Institute, Laboratoire d'Informatique de Grenoble (LIG ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Montreal Children's Hospital, McGill University Health Center [Montreal] (MUHC), Compartimentation et dynamique cellulaires (CDC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular Research Center, Massachusetts General Hospital [Boston], University Medical Center [Utrecht], University of Toronto, Fiocruz Minas - René Rachou Research Center / Instituto René Rachou [Belo Horizonte, Brésil], Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Federal University of Sao Paulo (Unifesp), Functional Genomics / Genómica Funcional [Montevideo], Institut Pasteur de Montevideo, Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Università degli Studi di Perugia (UNIPG), Hospital Santa Cristina Instituto de Investigación Sanitaria Princesa C, Unidad de Investigación, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Department of Physiology, University of California [San Francisco] (UCSF), University of California-University of California, University of Vermont [Burlington], Peking University [Beijing], Shandong Agricultural University (SDAU), State Key Laboratory of Quality Research in Chinese Medicine Taipa, Macau SAR, (Institute of Chinese Medical Sciences), Human Genetics, Universität Ulm - Ulm University [Ulm, Allemagne], INSERM, Institut Curie, INCa [INCA-11548], French National Research Agency [ANR-10-IDEX-0001-02 PSL*, ANR-11-LABX-0043], SIDACTION [17-1-AAE-1138], Fondation ARC [PGA1 RF20180206962, PJA 20171206453], NIDA [DA040385, DA047807], Ministry of Education, NIA [AG057430], NIMH [MH118164], Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Université Sciences et Technologies - Bordeaux 1 (UB)-Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University (UGENT), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Biotechnology and Biological Sciences Research Council (BBSRC)-Aberystwyth University, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), The Scripps Research Institute [La Jolla, San Diego], Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Università degli Studi di Perugia = University of Perugia (UNIPG), Instituto de Investigacion Sanitaria del Hospital de la Princesa, Hospital Universitario de La Princesa, University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), ANR-17-CE09-0025,MADNESS,Une approche microfluidique générique pour la qualification des nanoparticules biologiques(2017), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), Biomedical Engineering and Physics, ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation, Laboratory Specialized Diagnostics & Research, Radiotherapie, RS: GROW - R2 - Basic and Translational Cancer Biology, Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Université Nice Sophia Antipolis (... - 2019) (UNS), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Università degli studi di Torino (UNITO), Universidade do Porto, University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Johannes Gutenberg - Universität Mainz (JGU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Université de Toronto [Canada], Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192 (PRISM), Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidade do Porto [Porto], Ghent University [Belgium] (UGENT), FEMTO-ST Institute, Université de Technologie de Belfort-Montbeliard (UTBM)-Université de Franche-Comté (UFC)-CNRS : UMR6174, Mécanismes adaptatifs : des organismes aux communautés (MECADEV), Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN), Johannes Gutenberg - University of Mainz (JGU), Université Catholique de Louvain (UCL), Universitat Pompeu Fabra [Barcelona], Laboratoire d'Informatique de Grenoble (LIG), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Laboratoire Réactions et Génie des Procédés (LRGP), Fiocruz Minas - René Rachou Research Center / Instituto René Rachou, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Functional Genomics Unit, Institut Curie-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Vermont College of Medicine [Burlington, VT, USA], Extracellular Vesicles, Molecular and Integrative Biosciences Research Programme, Thery, C., Witwer, K. W., Aikawa, E., Alcaraz, M. J., Anderson, J. D., Andriantsitohaina, R., Antoniou, A., Arab, T., Archer, F., Atkin-Smith, G. K., Ayre, D. C., Bach, J. -M., Bachurski, D., Baharvand, H., Balaj, L., Baldacchino, S., Bauer, N. N., Baxter, A. A., Bebawy, M., Beckham, C., Bedina Zavec, A., Benmoussa, A., Berardi, A. C., Bergese, P., Bielska, E., Blenkiron, C., Bobis-Wozowicz, S., Boilard, E., Boireau, W., Bongiovanni, A., Borras, F. E., Bosch, S., Boulanger, C. M., Breakefield, X., Breglio, A. M., Brennan, M. A., Brigstock, D. R., Brisson, A., Broekman, M. L. D., Bromberg, J. F., Bryl-Gorecka, P., Buch, S., Buck, A. H., Burger, D., Busatto, S., Buschmann, D., Bussolati, B., Buzas, E. I., Byrd, J. B., Camussi, G., Carter, D. R. F., Caruso, S., Chamley, L. W., Chang, Y. -T., Chaudhuri, A. D., Chen, C., Chen, S., Cheng, L., Chin, A. R., Clayton, A., Clerici, S. P., Cocks, A., Cocucci, E., Coffey, R. J., Cordeiro-da-Silva, A., Couch, Y., Coumans, F. A. W., Coyle, B., Crescitelli, R., Criado, M. F., D'Souza-Schorey, C., Das, S., de Candia, P., De Santana, E. F., De Wever, O., del Portillo, H. A., Demaret, T., Deville, S., Devitt, A., Dhondt, B., Di Vizio, D., Dieterich, L. C., Dolo, V., Dominguez Rubio, A. P., Dominici, M., Dourado, M. R., Driedonks, T. A. P., Duarte, F. V., Duncan, H. M., Eichenberger, R. M., Ekstrom, K., EL Andaloussi, S., Elie-Caille, C., Erdbrugger, U., Falcon-Perez, J. M., Fatima, F., Fish, J. E., Flores-Bellver, M., Forsonits, A., Frelet-Barrand, A., Fricke, F., Fuhrmann, G., Gabrielsson, S., Gamez-Valero, A., Gardiner, C., Gartner, K., Gaudin, R., Gho, Y. S., Giebel, B., Gilbert, C., Gimona, M., Giusti, I., Goberdhan, D. C. I., Gorgens, A., Gorski, S. M., Greening, D. W., Gross, J. C., Gualerzi, A., Gupta, G. N., Gustafson, D., Handberg, A., Haraszti, R. A., Harrison, P., Hegyesi, H., Hendrix, A., Hill, A. F., Hochberg, F. H., Hoffmann, K. F., Holder, B., Holthofer, H., Hosseinkhani, B., Hu, G., Huang, Y., Huber, V., Hunt, S., Ibrahim, A. G. -E., Ikezu, T., Inal, J. M., Isin, M., Ivanova, A., Jackson, H. K., Jacobsen, S., Jay, S. M., Jayachandran, M., Jenster, G., Jiang, L., Johnson, S. M., Jones, J. C., Jong, A., Jovanovic-Talisman, T., Jung, S., Kalluri, R., Kano, S. -I., Kaur, S., Kawamura, Y., Keller, E. T., Khamari, D., Khomyakova, E., Khvorova, A., Kierulf, P., Kim, K. P., Kislinger, T., Klingeborn, M., Klinke, D. J., Kornek, M., Kosanovic, M. M., Kovacs, A. F., Kramer-Albers, E. -M., Krasemann, S., Krause, M., Kurochkin, I. V., Kusuma, G. D., Kuypers, S., Laitinen, S., Langevin, S. M., Languino, L. R., Lannigan, J., Lasser, C., Laurent, L. C., Lavieu, G., Lazaro-Ibanez, E., Le Lay, S., Lee, M. -S., Lee, Y. X. F., Lemos, D. S., Lenassi, M., Leszczynska, A., Li, I. T. S., Liao, K., Libregts, S. F., Ligeti, E., Lim, R., Lim, S. K., Line, A., Linnemannstons, K., Llorente, A., Lombard, C. A., Lorenowicz, M. J., Lorincz, A. M., Lotvall, J., Lovett, J., Lowry, M. C., Loyer, X., Lu, Q., Lukomska, B., Lunavat, T. R., Maas, S. L. N., Malhi, H., Marcilla, A., Mariani, J., Mariscal, J., Martens-Uzunova, E. S., Martin-Jaular, L., Martinez, M. C., Martins, V. R., Mathieu, M., Mathivanan, S., Maugeri, M., Mcginnis, L. K., Mcvey, M. J., Meckes, D. G., Meehan, K. L., Mertens, I., Minciacchi, V. R., Moller, A., Moller Jorgensen, M., Morales-Kastresana, A., Morhayim, J., Mullier, F., Muraca, M., Musante, L., Mussack, V., Muth, D. C., Myburgh, K. H., Najrana, T., Nawaz, M., Nazarenko, I., Nejsum, P., Neri, C., Neri, T., Nieuwland, R., Nimrichter, L., Nolan, J. P., Nolte-'t Hoen, E. N. M., Noren Hooten, N., O'Driscoll, L., O'Grady, T., O'Loghlen, A., Ochiya, T., Olivier, M., Ortiz, A., Ortiz, L. A., Osteikoetxea, X., Ostegaard, O., Ostrowski, M., Park, J., Pegtel, D. M., Peinado, H., Perut, F., Pfaffl, M. W., Phinney, D. G., Pieters, B. C. H., Pink, R. C., Pisetsky, D. S., Pogge von Strandmann, E., Polakovicova, I., Poon, I. K. H., Powell, B. H., Prada, I., Pulliam, L., Quesenberry, P., Radeghieri, A., Raffai, R. L., Raimondo, S., Rak, J., Ramirez, M. I., Raposo, G., Rayyan, M. S., Regev-Rudzki, N., Ricklefs, F. L., Robbins, P. D., Roberts, D. D., Rodrigues, S. C., Rohde, E., Rome, S., Rouschop, K. M. A., Rughetti, A., Russell, A. E., Saa, P., Sahoo, S., Salas-Huenuleo, E., Sanchez, C., Saugstad, J. A., Saul, M. J., Schiffelers, R. M., Schneider, R., Schoyen, T. H., Scott, A., Shahaj, E., Sharma, S., Shatnyeva, O., Shekari, F., Shelke, G. V., Shetty, A. K., Shiba, K., Siljander, P. R. -M., Silva, A. M., Skowronek, A., Snyder, O. L., Soares, R. P., Sodar, B. W., Soekmadji, C., Sotillo, J., Stahl, P. D., Stoorvogel, W., Stott, S. L., Strasser, E. F., Swift, S., Tahara, H., Tewari, M., Timms, K., Tiwari, S., Tixeira, R., Tkach, M., Toh, W. S., Tomasini, R., Torrecilhas, A. C., Tosar, J. P., Toxavidis, V., Urbanelli, L., Vader, P., van Balkom, B. W. M., van der Grein, S. G., Van Deun, J., van Herwijnen, M. J. C., Van Keuren-Jensen, K., van Niel, G., van Royen, M. E., van Wijnen, A. J., Vasconcelos, M. H., Vechetti, I. J., Veit, T. D., Vella, L. J., Velot, E., Verweij, F. J., Vestad, B., Vinas, J. L., Visnovitz, T., Vukman, K. V., Wahlgren, J., Watson, D. C., Wauben, M. H. M., Weaver, A., Webber, J. P., Weber, V., Wehman, A. M., Weiss, D. J., Welsh, J. A., Wendt, S., Wheelock, A. M., Wiener, Z., Witte, L., Wolfram, J., Xagorari, A., Xander, P., Xu, J., Yan, X., Yanez-Mo, M., Yin, H., Yuana, Y., Zappulli, V., Zarubova, J., Zekas, V., Zhang, J. -Y., Zhao, Z., Zheng, L., Zheutlin, A. R., Zickler, A. M., Zimmermann, P., Zivkovic, A. M., Zocco, D., Zuba-Surma, E. K., dB&C I&I, LS Celbiologie-Algemeen, Celbiologie, Afd Pharmaceutics, Sub General Pharmaceutics, Sub Biomol.Mass Spect. and Proteomics, Afd Pharmacology, CCA - Imaging and biomarkers, Amsterdam Neuroscience - Neuroinfection & -inflammation, and Amsterdam Neuroscience - Cellular & Molecular Mechanisms

Subjects
ectosome, ectosomes, exosomes, extracellular vesicles, guidelines, microparticles, microvesicles, minimal information requirements, reproducibility, rigor, standardization, Histology, Cell Biology, [SDV]Life Sciences [q-bio], size-exclusion, Medicine and Health Sciences, CELL-DERIVED MICROPARTICLES, FIELD-FLOW FRACTIONATION, requirements, circulating, ComputingMilieux_MISCELLANEOUS, Manchester Cancer Research Centre, lcsh:Cytology, PROSTATE-CANCER, microparticle, Cell interaction, microvesicle, chromatography, Position Paper, guideline, Life Sciences & Biomedicine, ectosomes, exosomes, extracellular vesicles, guidelines, microparticles, microvesicles, minimal information requirements, reproducibility, rigor, standardization, MEMBRANE-VESICLES, FETAL BOVINE, Ectosomes, Exosomes, Extracellular Vesicles, Guidelines, Microparticles, Microvesicles, Minimal Information Requirements, Reproducibility, Rigor, Standardization, CIRCULATING MICROPARTICLES, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, ddc:570, exosome, SURFACE-PLASMON RESONANCE, ddc:610, lcsh:QH573-671, Biology, Interacció cel·lular, Science & Technology, ResearchInstitutes_Networks_Beacons/mcrc, Cell membranes, HUMAN URINARY EXOSOMES, PREANALYTICAL PARAMETERS, minimal information requirement, SIZE-EXCLUSION CHROMATOGRAPHY, 1182 Biochemistry, cell and molecular biology, extracellular vesicle, Human medicine, Membranes cel·lulars
Abstract

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

Published
2018

34. Technical challenges of working with extracellular vesicles

Author

Ramirez, Marcel I., Amorim, Maria G., Gadelha, Catarina, Milic, Ivana, Welsh, Joshua A., Freitas, Vanessa M., Nawaz, Muhammad, Akbar, Naveed, Couch, Yvonne, Makin, Laura, Cooke, Fiona, Vettore, Andre L., Batista, Patricia X., Freezor, Roberta, Pezuk, Julia A., Carreira, Ana Claudia O., Devitt, Andrew, Jacobs, Laura, Silva, Israel T., Coakley, Gillian, Nunes, Diana N., Carter, Dave, Palmisano, Giuseppe, and Dias-Neto, Emmanuel

Abstract

© 2018 The Royal Society of Chemistry. Extracellular Vesicles (EVs) are gaining interest as central players in liquid biopsies, with potential applications in diagnosis, prognosis and therapeutic guidance in most pathological conditions. These nanosized particles transmit signals determined by their protein, lipid, nucleic acid and sugar content, and the unique molecular pattern of EVs dictates the type of signal to be transmitted to recipient cells. However, their small sizes and the limited quantities that can usually be obtained from patient-derived samples pose a number of challenges to their isolation, study and characterization. These challenges and some possible options to overcome them are discussed in this review.

Published
2018

36. The acute inflammatory response to intranigral α-synuclein differs significantly from intranigral lipopolysaccharide and is exacerbated by peripheral inflammation

Author

Couch Yvonne, Alvarez-Erviti Lydia, Sibson Nicola R, Wood Matthew JA, and Anthony Daniel C

Subjects
brain, inflammation, α-synuclein, SNCA, cytokine, Parkinson's, chemokine, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Activated microglia are a feature of the host response to neurodegeneration in Parkinson's disease (PD) and are thought to contribute to disease progression. Recent evidence suggests that extracellular α-synuclein (eSNCA) may play an important role in the pathogenesis of PD and that this may be mediated by a microglial response. Methods We wished to discover whether the host response to eSNCA would be sufficient to induce significant cytokine production. In vitro cultured BV-2 microglia were used to determine the basic inflammatory response to eSNCA. In vivo, 8-week old Biozzi mice were subjected to a single intranigral injection of either 3 μg SNCA, lipopolysaccharide (LPS) or serum protein (BSA) and allowed to recover for 24 hours. A second cohort of animals were peripherally challenged with LPS (0.5 mg/kg) 6 hours prior to tissue collection. Inflammation was studied by quantitative real-time PCR for a number of pro-inflammatory genes and immunohistochemistry for microglial activation, endothelial activation and cell death. Results In vitro data showed a robust microglial response to SNCA, including a positive NFĸB response and the production of pro-inflammatory cytokines. Direct injection of SNCA into the substantia nigra resulted in the upregulation of mRNA expression of proinflammatory cytokines, the expression of endothelial markers of inflammation and microglial activation. However, these results were significantly different to those obtained after direct injection of LPS. By contrast, when the animals were injected intracerebrally with SNCA and subsequently challenged with systemic LPS, the level of production of IL-1β in the substantia nigra became comparable to that induced by the direct injection of LPS into the brain. The injection of albumin into the nigra with a peripheral LPS challenge did not provoke the production of a significant inflammatory response. Direct injection of LPS into the substantia nigra also induces cell death in a more robust manner than direct injection of either SNCA or BSA. Conclusion These results suggest that the presence of eSNCA protein 'primes' microglia, making them susceptible to environmental proinflammatory challenge. For this reason, we hypothesise that where 'inflammation' contributes to the disease progression in PD, it does so in a punctuate manner (on-off) as a result of systemic events.

Published
2011
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37. Update in the methodology of the chronic stress paradigm: internal control matters

Author

Boyks Marco, Kholod Natalia, Couch Yvonne, Strekalova Tatyana, Malin Dmitry, Leprince Pierre, and Steinbusch Harry MW

Subjects
animal model of depression, chronic stress, sucrose test, anhedonia, antidepressant treatment, gene expression profiling, neuroinflammation, mouse, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract To date, the reliability of induction of a depressive-like state using chronic stress models is confronted by many methodological limitations. We believe that the modifications to the stress paradigm in mice proposed herein allow some of these limitations to be overcome. Here, we discuss a variant of the standard stress paradigm, which results in anhedonia. This anhedonic state was defined by a decrease in sucrose preference that was not exhibited by all animals. As such, we propose the use of non-anhedonic, stressed mice as an internal control in experimental mouse models of depression. The application of an internal control for the effects of stress, along with optimized behavioural testing, can enable the analysis of biological correlates of stress-induced anhedonia versus the consequences of stress alone in a chronic-stress depression model. This is illustrated, for instance, by distinct physiological and molecular profiles in anhedonic and non-anhedonic groups subjected to stress. These results argue for the use of a subgroup of individuals who are negative for the induction of a depressive phenotype during experimental paradigms of depression as an internal control, for more refined modeling of this disorder in animals.

Published
2011
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38. Rapamycin in ischemic stroke: Old drug, new tricks?

Author

Hadley, Gina, primary, Beard, Daniel J, additional, Couch, Yvonne, additional, Neuhaus, Ain A, additional, Adriaanse, Bryan A, additional, DeLuca, Gabriele C, additional, Sutherland, Brad A, additional, and Buchan, Alastair M, additional

Published
2018
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39. Circulating endothelial cell-derived extracellular vesicles mediate the acute phase response and sickness behaviour associated with CNS inflammation

Author

Couch, Yvonne, Akbar, Naveed, Roodselaar, Jay, Evans, Matthew C, Gardiner, Chris, Sargent, Ian, Romero, Ignacio A., Bristow, Adrian, Buchan, Alastair M, Haughey, Norman, and Anthony, Daniel C

Subjects
Male, Behavior, Animal, Kupffer Cells, lcsh:R, Endothelial Cells, lcsh:Medicine, Article, Hepatitis, Rats, Disease Models, Animal, Extracellular Vesicles, Animals, Cytokines, Encephalitis, lcsh:Q, Inflammation Mediators, Acute-Phase Reaction, lcsh:Science, Illness Behavior
Abstract

Brain injury elicits a systemic acute-phase response (APR), which is responsible for co-ordinating the peripheral immunological response to injury. To date, the mechanisms responsible for signalling the presence of injury or disease to selectively activate responses in distant organs were unclear. Circulating endogenous extracellular vesicles (EVs) are increased after brain injury and have the potential to carry targeted injury signals around the body. Here, we examined the potential of EVs, isolated from rats after focal inflammatory brain lesions using IL-1β, to activate a systemic APR in recipient naïve rats, as well as the behavioural consequences of EV transfer. Focal brain lesions increased EV release, and, following isolation and transfer, the EVs were sequestered by the liver where they initiated an APR. Transfer of blood-borne EVs from brain-injured animals was also enough to suppress exploratory behaviours in recipient naïve animals. EVs derived from brain endothelial cell cultures treated with IL-1β also activated an APR and altered behaviour in recipient animals. These experiments reveal that inflammation-induced circulating EVs derived from endothelial cells are able to initiate the APR to brain injury and are sufficient to generate the associated sickness behaviours, and are the first demonstration that EVs are capable of modifying behavioural responses.

Published
2017

42. Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers

Author

Małecki, Andrzej, primary, Skipor-Lahuta, Janina, additional, Toborek, Michal, additional, Abbott, N. Joan, additional, Antonetti, David A., additional, Su, Enming Joe, additional, Lawrence, Daniel A., additional, Atış, Müge, additional, Akcan, Uğur, additional, Yılmaz, Canan Uğur, additional, Orhan, Nurcan, additional, Düzgün, Poyraz, additional, Ceylan, Umut Deniz, additional, Arıcan, Nadir, additional, Karahüseyinoğlu, Serçin, additional, Şahin, Gizem Nur, additional, Ahıshalı, Bülent, additional, Kaya, Mehmet, additional, Aydin, Sidar, additional, Klopstein, Armelle, additional, Engelhardt, Britta, additional, Baumann, Julia, additional, Tsao, Chih-Chieh, additional, Huang, Sheng-Fu, additional, Ogunshola, Omolara, additional, Boytsova, Elizaveta B., additional, Morgun, Andrey V., additional, Khilazheva, Elena D., additional, Pozhilenkova, Elena A., additional, Gorina, Yana V., additional, Martynova, Galina P., additional, Salmina, Alla B., additional, Bueno, David, additional, Garcia-Fernàndez, Jordi, additional, Castro, Victor, additional, Skowronska, Marta, additional, Chupel, Matheus Uba, additional, Minuzzi, Luciele Guerra, additional, Filaire, Edith, additional, Teixeira, Ana Maria, additional, Corsi, Mariangela, additional, Versele, Romain, additional, Fuso, Andrea, additional, Sevin, Emmanuel, additional, Di Lorenzo, Cherubino, additional, Businaro, Rita, additional, Fenart, Laurence, additional, Gosselet, Fabien, additional, Candela, Pietra, additional, Deli, Mária A., additional, Delaney, Conor, additional, O’Keefe, Eoin, additional, Farrell, Michael, additional, Doyle, Sarah, additional, Campbell, Matthew, additional, Drewes, Lester R., additional, Appelt-Menzel, A., additional, Cubukova, A., additional, Metzger, M., additional, Fischer, R., additional, Francisco, David M. F., additional, Bruggmann, Rémy, additional, Fries, Alexa, additional, Blecharz, Kinga G., additional, Wagner, Josephin, additional, Winkler, Lars, additional, Schneider, Ulf, additional, Vajkoczy, Peter, additional, Furuse, Mikio, additional, Gabbert, Lydia, additional, Dilling, Christina, additional, Sisario, Dmitri, additional, Soukhoroukov, Vladimir, additional, Burek, Malgorzata, additional, Guérit, S., additional, Fidan, E., additional, Devraj, K., additional, Czupalla, C. J., additional, Macas, J., additional, Thom, S., additional, Plate, K. H., additional, Gerhardt, H., additional, Liebner, S., additional, Harazin, András, additional, Bocsik, Alexandra, additional, Váradi, Judit, additional, Fenyvesi, Ferenc, additional, Tubak, Vilmos, additional, Vecsernyés, Miklós, additional, Helms, Hans Christian, additional, Waagepetersen, Helle Sønderby, additional, Nielsen, Carsten Uhd, additional, Brodin, Birger, additional, Hoyk, Zsófia, additional, Tóth, Melinda E., additional, Lénárt, Nikolett, additional, Dukay, Brigitta, additional, Kittel, Ágnes, additional, Vígh, Judit, additional, Veszelka, Szilvia, additional, Walter, Fruzsina, additional, Zvara, Ágnes, additional, Puskás, László, additional, Sántha, Miklós, additional, Engelhardt, Sabrina, additional, Ogunshola, Omolara O., additional, Huber, Anna, additional, Reitner, Alexander, additional, Osmen, Samar, additional, Hahn, Kathrin, additional, Bounzina, Neli, additional, Gerhartl, Anna, additional, Schönegger, Anna, additional, Steinkellner, Hannes, additional, Laccone, Franco, additional, Neuhaus, Winfried, additional, Hudson, Natalie, additional, Celkova, Lucia, additional, Iltzsche, Anne, additional, Drndarski, Svetlana, additional, Begley, David J, additional, Janiurek, Mette Mathiesen, additional, Kucharz, Krzysztof, additional, Christoffersen, Christina, additional, Nielsen, Lars Bo, additional, Lauritzen, Martin, additional, Johnson, Rebecca H, additional, Kho, Dan T, additional, O’Carroll, Simon J, additional, Angel, Catherine E, additional, Graham, E. Scott, additional, Pereira, Jennifer, additional, Karali, Christina Simoglou, additional, Cheng, Vinton, additional, Zarghami, Niloufar, additional, Soto, Manuel Sarmiento, additional, Couch, Yvonne, additional, Anthony, Daniel C., additional, Sibson, Nicola R., additional, Kealy, John, additional, Keep, Richard F., additional, Routhe, Lisa J., additional, Xiang, Jianming, additional, Ye, Hong, additional, Hua, Ya, additional, Moos, Torben, additional, Xi, Guohua, additional, Kristensen, M., additional, Bach, A., additional, Strømgaard, K., additional, Kutuzov, Nikolay, additional, Lopes-Pinheiro, Melissa A., additional, Lim, Jamie, additional, Kamermans, Alwin, additional, van Horssen, Jack, additional, Unger, Wendy W.J., additional, Fontijn, Ruud, additional, de Vries, Helga E., additional, Majerova, Petra, additional, Garruto, Ralph M., additional, Marchetti, Luca, additional, Francisco, David, additional, Gruber, Isabelle, additional, Lyck, Ruth, additional, Mészáros, Mária, additional, Porkoláb, Gergő, additional, Kiss, Lóránd, additional, Pilbat, Ana-Maria, additional, Török, Zsolt, additional, Bozsó, Zsolt, additional, Fülöp, Lívia, additional, Michalicova, Alena, additional, Galba, Jaroslav, additional, Mihaljevic, Sandra, additional, Novak, Michal, additional, Kovac, Andrej, additional, Morofuji, Yoichi, additional, Fujimoto, Takashi, additional, Watanabe, Daisuke, additional, Nakagawa, Shinsuke, additional, Ujifuku, Kenta, additional, Horie, Nobutaka, additional, Izumo, Tsuyoshi, additional, Anda, Takeo, additional, Matsuo, Takayuki, additional, Niu, Fang, additional, Buch, Shilpa, additional, Nyúl-Tóth, Ádám, additional, Kozma, Mihály, additional, Nagyőszi, Péter, additional, Nagy, Krisztina, additional, Fazakas, Csilla, additional, Haskó, János, additional, Molnár, Kinga, additional, Farkas, Attila E., additional, Galajda, Péter, additional, Wilhelm, Imola, additional, Krizbai, István A., additional, Kelly, Eoin, additional, Wallace, Eugene, additional, Greene, Chris, additional, Hughes, Stephanie, additional, Doyle, Niamh, additional, Humphries, Marian M., additional, Grant, Gerald A., additional, Friedman, Alon, additional, Veksler, Ronel, additional, Molloy, Michael G., additional, Meaney, James F., additional, Pender, Niall, additional, Doherty, Colin P., additional, Park, Minseon, additional, Liskiewicz, Arkadiusz, additional, Przybyla, Marta, additional, Kasprowska-Liśkiewicz, Daniela, additional, Nowacka-Chmielewska, Marta, additional, Malecki, Andrzej, additional, Pombero, Ana, additional, Garcia-Lopez, Raquel, additional, Martinez-Morga, Marta, additional, Martinez, Salvador, additional, Prager, Ofer, additional, Solomon-Kamintsky, Lyna, additional, Schoknecht, Karl, additional, Bar-Klein, Guy, additional, Milikovsky, Dan, additional, Vazana, Udi, additional, Rosenbach, Dror, additional, Kovács, Richard, additional, Radak, Zsolt, additional, Rodríguez-Lorenzo, Sabela, additional, Bruggmann, Remy, additional, Kooij, Gijs, additional, de Vries, Helga E, additional, Oxana, Semyachkina-Glushkovskaya, additional, Denis, Bragin, additional, Elena, Vodovozova, additional, Anna, Alekseeva, additional, Alla, Salmina, additional, Vladimir, Salmin, additional, Andrey, Morgun, additional, Nataliya, Malinovskaya, additional, Elena, Khilazheva, additional, Elizaveta, Boytsova, additional, Alexander, Shirokov, additional, Nikita, Navolokin, additional, Alla, Bucharskaya, additional, Yirong, Yang, additional, Arkady, Abdurashitov, additional, Artem, Gekalyuk, additional, Mariya, Ulanova, additional, Anastasia, Shushunova, additional, Madina, Bodrova, additional, Artem, Sagatova, additional, Alexander, Khorovodov, additional, Esmat, Shareef Ali, additional, Valery, Pavlov, additional, Artem, Tuchin, additional, Jürgen, Kurths, additional, de Abreu, Marcelle Silva, additional, Calpena, Ana C., additional, Espina, Marta, additional, García, Maria Luisa, additional, Romero, Ignacio A., additional, Male, David, additional, Storck, Steffen, additional, Hartz, Anika, additional, Pahnke, Jens, additional, Surma, Claus U., additional, Surma, M., additional, Giżejewski, Z., additional, Zieliński, H., additional, Szczepkowska, Aleksandra, additional, Kowalewska, Marta, additional, Krawczynska, Agata, additional, Herman, Andrzej P., additional, Skipor, Janina, additional, Kachappilly, Nicole, additional, Veenstra, Mike, additional, Rivera, Rosiris Leon, additional, Williams, Dionna W., additional, Morgello, Susan, additional, Berman, Joan W., additional, Wyneken, Ursula, additional, Batiz, Luis Federico, additional, Temizyürek, Arzu, additional, Khodadust, Rouhollah, additional, Küçük, Mutlu, additional, Gürses, Candan, additional, Emik, Serkan, additional, Zielińska, Magdalena, additional, Obara-Michlewska, Marta, additional, Milewski, Krzysztof, additional, Skonieczna, Edyta, additional, Fręśko, Inez, additional, Neuwelt, Edward A., additional, Maria, Ana Raquel Santa, additional, Bras, Ana Rita, additional, Lipka, Dóra, additional, Valkai, Sándor, additional, Kincses, András, additional, Dér, András, additional, and Deli, Maria A., additional

Published
2017
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43. The CRTC1-SIK1 Pathway Regulates Entrainment of the Circadian Clock

Author

Jagannath, Aarti, Butler, Rachel, Godinho, Sofia I.H., Couch, Yvonne, Brown, Laurence A., Vasudevan, Sridhar R., Flanagan, Kevin C., Anthony, Daniel, Churchill, Grant C., Wood, Matthew J.A., Steiner, Guido, Ebeling, Martin, Hossbach, Markus, Wettstein, Joseph G., Duffield, Giles E., Gatti, Silvia, Hankins, Mark W., Foster, Russell G., and Peirson, Stuart N.

Subjects
genetic structures, Transcription, Genetic, Biochemistry, Genetics and Molecular Biology(all), Active Transport, Cell Nucleus, Rod Opsins, Protein Serine-Threonine Kinases, Article, Circadian Rhythm, Mice, Inbred C57BL, Mice, Circadian Clocks, Gene Knockdown Techniques, Animals, Suprachiasmatic Nucleus, sense organs, RNA, Small Interfering, Cyclic AMP Response Element-Binding Protein, Signal Transduction, Transcription Factors
Abstract

Summary Retinal photoreceptors entrain the circadian system to the solar day. This photic resetting involves cAMP response element binding protein (CREB)-mediated upregulation of Per genes within individual cells of the suprachiasmatic nuclei (SCN). Our detailed understanding of this pathway is poor, and it remains unclear why entrainment to a new time zone takes several days. By analyzing the light-regulated transcriptome of the SCN, we have identified a key role for salt inducible kinase 1 (SIK1) and CREB-regulated transcription coactivator 1 (CRTC1) in clock re-setting. An entrainment stimulus causes CRTC1 to coactivate CREB, inducing the expression of Per1 and Sik1. SIK1 then inhibits further shifts of the clock by phosphorylation and deactivation of CRTC1. Knockdown of Sik1 within the SCN results in increased behavioral phase shifts and rapid re-entrainment following experimental jet lag. Thus SIK1 provides negative feedback, acting to suppress the effects of light on the clock. This pathway provides a potential target for the regulation of circadian rhythms., Graphical Abstract, Highlights • Nocturnal light induces widespread transcriptional changes in the SCN • The CRTC1-SIK1 cascade regulates entrainment of the circadian clock • Negative feedback by SIK1 limits the effects of light on the clock • Homeostatic regulation of entrainment ensures gradual adaptation to a new time zone, A negative-feedback loop involving the kinase SIK1 and the transcriptional coactivator CRTC1 delays re-entrainment of the circadian clock to new time zones, causing jet lag. Remarkably, inhibition of SIK1 allows rapid re-entrainment after an experimental jet lag protocol in mice.

Published
2013

44. Additional file 1: Table S1. of Low-dose lipopolysaccharide (LPS) inhibits aggressive and augments depressive behaviours in a chronic mild stress model in mice

Author

Couch, Yvonne, Trofimov, Alexander, Natalyia Markova, Nikolenko, Vladimir, Steinbusch, Harry, Chekhonin, Vladimir, Careen Schroeter, Klaus-Peter Lesch, Anthony, Daniel, and Strekalova, Tatyana

Abstract

Primer sequences for qPCR. Primers were custom designed and validated by PrimerDesign Ltd. (Southampton, UK). Figure S1. The effect of a low dose of LPS on locomotor activity at 24 and 48 h post-challenge in naïve mice. Naïve animals were subjected to a single dose of LPS (0.1 or 0.5 mg/kg) or vehicle injection and were tested at 24 or 48 h post-injection. (A) Neither the resting time was unaltered by the treatment in the TruScan open field nor (B) rearing in the novel cage test for the total number of rear. (C–E) Aggressive behaviour was also unaltered. Data are mean ± SEM, two-way ANOVA throughout. Figure S2. (A, B) Body weight in the chronic stress experiment. Experimental groups were balanced upon baseline mean values of body weight measured 7 days prior the start of the chronic stress experiment and LPS challenge. Mice exposed to chronic stress had a significant reduction in body weight as compared with baseline measurements (*p 0.05, one-way ANOVA and post hoc Tukey test; see the text). (F) Naïve and stressed animals (10 days) were challenged with a single dose of LPS (0.1 mg/kg) or vehicle (saline) and tested 24 h thereafter in a novel cage test for total number of rears (see the text). Data are mean ± SEM. No differences between the groups were observed. Figure S3. (A–C) Baseline behaviour in a resident-intruder test. Experimental groups were balanced upon baseline mean scores of behaviours in a resident-intruder test that were studied 7 days prior the experimental chronic stress procedure and LPS challenge. Mice had similar mean measures of (A) latency to attack, (B) number of attack and (C )duration of crawl over behaviour. (p > 0.05, one-way ANOVA and post hoc Tukey test; see the text). (D) The latency to attack after the chronic stress was not significantly altered.

Published
2016
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45. The transient intraluminal filament middle cerebral artery occlusion model as a model of endovascular thrombectomy in stroke

Author

Sutherland, Brad A, Neuhaus, Ain A, Couch, Yvonne, Balami, Joyce S, DeLuca, Gabriele C, Hadley, Gina, Harris, Scarlett L, Grey, Adam N, and Buchan, Alastair M

Subjects
Disease Models, Animal, Ischemic stroke, middle cerebral artery occlusion, Cerebrovascular Circulation, cerebral blood flow, Endovascular Procedures, Animals, Humans, Infarction, Middle Cerebral Artery, endovascular thrombectomy, Brief Opinion, animal models, Thrombectomy
Abstract

The clinical relevance of the transient intraluminal filament model of middle cerebral artery occlusion (tMCAO) has been questioned due to distinct cerebral blood flow profiles upon reperfusion between tMCAO (abrupt reperfusion) and alteplase treatment (gradual reperfusion), resulting in differing pathophysiologies. Positive results from recent endovascular thrombectomy trials, where the occluding clot is mechanically removed, could revolutionize stroke treatment. The rapid cerebral blood flow restoration in both tMCAO and endovascular thrombectomy provides clinical relevance for this pre-clinical model. Any future clinical trials of neuroprotective agents as adjuncts to endovascular thrombectomy should consider tMCAO as the model of choice to determine pre-clinical efficacy.

Published
2015

50. Multi-modal assessment of neurovascular coupling during cerebral ischaemia and reperfusion using remote middle cerebral artery occlusion

Author

Sutherland, Brad A, primary, Fordsmann, Jonas C, additional, Martin, Chris, additional, Neuhaus, Ain A, additional, Witgen, Brent M, additional, Piilgaard, Henning, additional, Lønstrup, Micael, additional, Couch, Yvonne, additional, Sibson, Nicola R, additional, Lauritzen, Martin, additional, and Buchan, Alastair M, additional

Published
2016
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