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1. The eVe reference polarisation lidar system for the calibration and validation of the Aeolus L2A product

Author

P. Paschou, N. Siomos, A. Tsekeri, A. Louridas, G. Georgoussis, V. Freudenthaler, I. Binietoglou, G. Tsaknakis, A. Tavernarakis, C. Evangelatos, J. von Bismarck, T. Kanitz, C. Meleti, E. Marinou, and V. Amiridis

Subjects
Environmental engineering, TA170-171, Earthwork. Foundations, TA715-787
Abstract

The eVe dual-laser/dual-telescope lidar system is introduced here, focusing on the optical and mechanical parts of the system's emission and receiver units. The compact design of the linear–circular emission unit along with the linear–circular analyser in the receiver unit allows eVe to simultaneously reproduce the operation of the ALADIN lidar on board Aeolus as well as to operate it as a traditional ground-based polarisation lidar system with linear emission. As such, the eVe lidar aims to provide (a) ground reference measurements for the validation of the Aeolus L2A aerosol products and (b) the conditions for which linear polarisation lidar systems can be considered for Aeolus L2A validation, by identifying any possible biases arising from the different polarisation state in the emission between ALADIN and these systems, and the detection of only the co-polar component of the returned signal from ALADIN for the L2A products' retrieval. In addition, a brief description is given concerning the polarisation calibration techniques that are applied in the system, as well as the developed software for the analysis of the collected signals and the retrieval of the optical products. More specifically, the system's dual configuration enables the retrieval of the optical properties of particle backscatter and extinction coefficients originating from the two different polarisation states of the emission and the linear and circular depolarisation ratios, as well as the direct calculation of the Aeolus-like backscatter coefficient, i.e. the backscatter coefficient that Aeolus would measure from the ground. Two cases, one with slightly depolarising particles and one with moderately depolarising particles, were selected from the first conducted measurements of eVe in Athens in September 2020, in order to demonstrate the system's capabilities. In the slightly depolarising scene, the Aeolus-like backscatter coefficient agrees well with the actual backscatter coefficient, which is also true when non-depolarising particles are present. The agreement however fades out for strongly depolarising scenes, where an underestimation of ∼18 % of the Aeolus like backscatter coefficient is observed when moderately depolarising particles are probed.

Published
2022
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2. Optomechanics with a hybrid carbon nanotube resonator

Author

A. Tavernarakis, A. Stavrinadis, A. Nowak, I. Tsioutsios, A. Bachtold, and P. Verlot

Subjects
Science
Abstract

Optomechanics has recently moved into the quantum regime. Here, Tavernarakis et al. demonstrate that a hybrid optomechanical device made up of a carbon nanotube with a metal nanoparticle at its tip can push force measurements towards the quantum regime at room temperature.

Published
2018
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3. Spermidine is essential for fasting-mediated autophagy and longevity

Author

Hofer, Sebastian J., Daskalaki, Ioanna, Bergmann, Martina, Friščić, Jasna, Zimmermann, Andreas, Mueller, Melanie I., Abdellatif, Mahmoud, Nicastro, Raffaele, Masser, Sarah, Durand, Sylvère, Nartey, Alexander, Waltenstorfer, Mara, Enzenhofer, Sarah, Faimann, Isabella, Gschiel, Verena, Bajaj, Thomas, Niemeyer, Christine, Gkikas, Ilias, Pein, Lukas, Cerrato, Giulia, Pan, Hui, Liang, YongTian, Tadic, Jelena, Jerkovic, Andrea, Aprahamian, Fanny, Robbins, Christine E., Nirmalathasan, Nitharsshini, Habisch, Hansjörg, Annerer, Elisabeth, Dethloff, Frederik, Stumpe, Michael, Grundler, Franziska, Wilhelmi de Toledo, Françoise, Heinz, Daniel E., Koppold, Daniela A., Rajput Khokhar, Anika, Michalsen, Andreas, Tripolt, Norbert J., Sourij, Harald, Pieber, Thomas R., de Cabo, Rafael, McCormick, Mark A., Magnes, Christoph, Kepp, Oliver, Dengjel, Joern, Sigrist, Stephan J., Gassen, Nils C., Sedej, Simon, Madl, Tobias, De Virgilio, Claudio, Stelzl, Ulrich, Hoffmann, Markus H., Eisenberg, Tobias, Tavernarakis, Nektarios, Kroemer, Guido, and Madeo, Frank

Published
2024
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7. Reproductive regulation of the mitochondrial stress response in Caenorhabditis elegans

Author

Nikolaos Charmpilas, Aggeliki Sotiriou, Konstantinos Axarlis, Nektarios Tavernarakis, and Thorsten Hoppe

Subjects
CP: Developmental biology, CP: Molecular biology, Biology (General), QH301-705.5
Abstract

Summary: Proteome integrity is fundamental for cellular and organismal homeostasis. The mitochondrial unfolded protein response (UPRmt), a key component of the proteostasis network, is activated in a non-cell-autonomous manner in response to mitochondrial stress in distal tissues. However, the importance of inter-tissue communication for UPRmt inducibility under physiological conditions remains elusive. Here, we show that an intact germline is essential for robust UPRmt induction in the Caenorhabditis elegans somatic tissues. A series of nematode mutants with germline defects are unable to respond to genetic or chemical UPRmt inducers. Our genetic analysis suggests that reproductive signals, rather than germline stem cells, are responsible for somatic UPRmt induction. Consistent with this observation, we show that UPRmt is sexually dimorphic, as male nematodes are inherently unresponsive to mitochondrial stress. Our findings highlight a paradigm of germline-somatic communication and suggest that reproductive cessation is a primary cause of age-related UPRmt decline.

Published
2024
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8. Mass sensing for the advanced fabrication of nanomechanical resonators

Author

Gruber, G., Urgell, C., Tavernarakis, A., Stavrinadis, A., Tepsic, S., Magen, C., Sangiao, S., de Teresa, J. M., Verlot, P., and Bachtold, A.

Subjects
Physics - Applied Physics, Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

We report on a nanomechanical engineering method to monitor matter growth in real time via e-beam electromechanical coupling. This method relies on the exceptional mass sensing capabilities of nanomechanical resonators. Focused electron beam induced deposition (FEBID) is employed to selectively grow platinum particles at the free end of singly clamped nanotube cantilevers. The electron beam has two functions: it allows both to grow material on the nanotube and to track in real time the deposited mass by probing the noise-driven mechanical resonance of the nanotube. On the one hand, this detection method is highly effective as it can resolve mass deposition with a resolution in the zeptogram range; on the other hand, this method is simple to use and readily available to a wide range of potential users, since it can be operated in existing commercial FEBID systems without making any modification. The presented method allows to engineer hybrid nanomechanical resonators with precisely tailored functionality. It also appears as a new tool for studying growth dynamics of ultra-thin nanostructures, opening new opportunities for investigating so far out-of-reach physics of FEBID and related methods., Comment: Published in Nano Letters

Published
2021
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9. Apoptotic cell death in disease—Current understanding of the NCCD 2023

Author

Vitale, Ilio, Pietrocola, Federico, Guilbaud, Emma, Aaronson, Stuart A., Abrams, John M., Adam, Dieter, Agostini, Massimiliano, Agostinis, Patrizia, Alnemri, Emad S., Altucci, Lucia, Amelio, Ivano, Andrews, David W., Aqeilan, Rami I., Arama, Eli, Baehrecke, Eric H., Balachandran, Siddharth, Bano, Daniele, Barlev, Nickolai A., Bartek, Jiri, Bazan, Nicolas G., Becker, Christoph, Bernassola, Francesca, Bertrand, Mathieu J. M., Bianchi, Marco E., Blagosklonny, Mikhail V., Blander, J. Magarian, Blandino, Giovanni, Blomgren, Klas, Borner, Christoph, Bortner, Carl D., Bove, Pierluigi, Boya, Patricia, Brenner, Catherine, Broz, Petr, Brunner, Thomas, Damgaard, Rune Busk, Calin, George A., Campanella, Michelangelo, Candi, Eleonora, Carbone, Michele, Carmona-Gutierrez, Didac, Cecconi, Francesco, Chan, Francis K. -M., Chen, Guo-Qiang, Chen, Quan, Chen, Youhai H., Cheng, Emily H., Chipuk, Jerry E., Cidlowski, John A., Ciechanover, Aaron, Ciliberto, Gennaro, Conrad, Marcus, Cubillos-Ruiz, Juan R., Czabotar, Peter E., D’Angiolella, Vincenzo, Daugaard, Mads, Dawson, Ted M., Dawson, Valina L., De Maria, Ruggero, De Strooper, Bart, Debatin, Klaus-Michael, Deberardinis, Ralph J., Degterev, Alexei, Del Sal, Giannino, Deshmukh, Mohanish, Di Virgilio, Francesco, Diederich, Marc, Dixon, Scott J., Dynlacht, Brian D., El-Deiry, Wafik S., Elrod, John W., Engeland, Kurt, Fimia, Gian Maria, Galassi, Claudia, Ganini, Carlo, Garcia-Saez, Ana J., Garg, Abhishek D., Garrido, Carmen, Gavathiotis, Evripidis, Gerlic, Motti, Ghosh, Sourav, Green, Douglas R., Greene, Lloyd A., Gronemeyer, Hinrich, Häcker, Georg, Hajnóczky, György, Hardwick, J. Marie, Haupt, Ygal, He, Sudan, Heery, David M., Hengartner, Michael O., Hetz, Claudio, Hildeman, David A., Ichijo, Hidenori, Inoue, Satoshi, Jäättelä, Marja, Janic, Ana, Joseph, Bertrand, Jost, Philipp J., Kanneganti, Thirumala-Devi, Karin, Michael, Kashkar, Hamid, Kaufmann, Thomas, Kelly, Gemma L., Kepp, Oliver, Kimchi, Adi, Kitsis, Richard N., Klionsky, Daniel J., Kluck, Ruth, Krysko, Dmitri V., Kulms, Dagmar, Kumar, Sharad, Lavandero, Sergio, Lavrik, Inna N., Lemasters, John J., Liccardi, Gianmaria, Linkermann, Andreas, Lipton, Stuart A., Lockshin, Richard A., López-Otín, Carlos, Luedde, Tom, MacFarlane, Marion, Madeo, Frank, Malorni, Walter, Manic, Gwenola, Mantovani, Roberto, Marchi, Saverio, Marine, Jean-Christophe, Martin, Seamus J., Martinou, Jean-Claude, Mastroberardino, Pier G., Medema, Jan Paul, Mehlen, Patrick, Meier, Pascal, Melino, Gerry, Melino, Sonia, Miao, Edward A., Moll, Ute M., Muñoz-Pinedo, Cristina, Murphy, Daniel J., Niklison-Chirou, Maria Victoria, Novelli, Flavia, Núñez, Gabriel, Oberst, Andrew, Ofengeim, Dimitry, Opferman, Joseph T., Oren, Moshe, Pagano, Michele, Panaretakis, Theocharis, Pasparakis, Manolis, Penninger, Josef M., Pentimalli, Francesca, Pereira, David M., Pervaiz, Shazib, Peter, Marcus E., Pinton, Paolo, Porta, Giovanni, Prehn, Jochen H. M., Puthalakath, Hamsa, Rabinovich, Gabriel A., Rajalingam, Krishnaraj, Ravichandran, Kodi S., Rehm, Markus, Ricci, Jean-Ehrland, Rizzuto, Rosario, Robinson, Nirmal, Rodrigues, Cecilia M. P., Rotblat, Barak, Rothlin, Carla V., Rubinsztein, David C., Rudel, Thomas, Rufini, Alessandro, Ryan, Kevin M., Sarosiek, Kristopher A., Sawa, Akira, Sayan, Emre, Schroder, Kate, Scorrano, Luca, Sesti, Federico, Shao, Feng, Shi, Yufang, Sica, Giuseppe S., Silke, John, Simon, Hans-Uwe, Sistigu, Antonella, Stephanou, Anastasis, Stockwell, Brent R., Strapazzon, Flavie, Strasser, Andreas, Sun, Liming, Sun, Erwei, Sun, Qiang, Szabadkai, Gyorgy, Tait, Stephen W. G., Tang, Daolin, Tavernarakis, Nektarios, Troy, Carol M., Turk, Boris, Urbano, Nicoletta, Vandenabeele, Peter, Vanden Berghe, Tom, Vander Heiden, Matthew G., Vanderluit, Jacqueline L., Verkhratsky, Alexei, Villunger, Andreas, von Karstedt, Silvia, Voss, Anne K., Vousden, Karen H., Vucic, Domagoj, Vuri, Daniela, Wagner, Erwin F., Walczak, Henning, Wallach, David, Wang, Ruoning, Wang, Ying, Weber, Achim, Wood, Will, Yamazaki, Takahiro, Yang, Huang-Tian, Zakeri, Zahra, Zawacka-Pankau, Joanna E., Zhang, Lin, Zhang, Haibing, Zhivotovsky, Boris, Zhou, Wenzhao, Piacentini, Mauro, Kroemer, Guido, and Galluzzi, Lorenzo

Published
2023
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10. Assessing locomotory rate in response to food for the identification of neuronal and muscular defects in C. elegans

Author

Dionysia Petratou, Persefoni Fragkiadaki, Eirini Lionaki, and Nektarios Tavernarakis

Subjects
Genetics, Microscopy, Model Organisms, Signal Transduction, Behavior, Science (General), Q1-390
Abstract

Summary: C. elegans is a bacteria-eating soil-dwelling nematode. Typical cultivation of laboratory-reared populations occurs on bacteria-covered solid media, where they move along with sinusoidal undulations. Nematodes decelerate when they encounter food. Dopaminergic and serotonergic neurotransmission regulate this behavior. Here, we describe the procedure for determining food-dependent locomotion rate of fed and fasting nematodes. We detail steps for assay plate preparation, C. elegans synchronization, and assessment of locomotion. The behaviors we describe provide information regarding the animal’s physiological neuronal and muscular function.For complete details on the use and execution of this protocol, please refer to Petratou et al. (2023)1 and Sawin et al. (2000).2 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Published
2024
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17. Inhibition of autophagy curtails visual loss in a model of autosomal dominant optic atrophy.

Author

Zaninello, Marta, Palikaras, Konstantinos, Naon, Deborah, Iwata, Keiko, Herkenne, Stephanie, Quintana-Cabrera, Ruben, Semenzato, Martina, Grespi, Francesca, Ross-Cisneros, Fred, Carelli, Valerio, Sadun, Alfredo, Tavernarakis, Nektarios, and Scorrano, Luca

Subjects
Adenylate Kinase, Animals, Autophagy, Axons, Caenorhabditis elegans, Disease Models, Animal, Enzyme Activation, GTP Phosphohydrolases, Mice, Inbred C57BL, Mice, Knockout, Mitochondria, Mitophagy, Mutation, Optic Atrophy, Autosomal Dominant, Phosphorylation, Retinal Ganglion Cells, Vision Disorders
Abstract

In autosomal dominant optic atrophy (ADOA), caused by mutations in the mitochondrial cristae biogenesis and fusion protein optic atrophy 1 (Opa1), retinal ganglion cell (RGC) dysfunction and visual loss occur by unknown mechanisms. Here, we show a role for autophagy in ADOA pathogenesis. In RGCs expressing mutated Opa1, active 5 AMP-activated protein kinase (AMPK) and its autophagy effector ULK1 accumulate at axonal hillocks. This AMPK activation triggers localized hillock autophagosome accumulation and mitophagy, ultimately resulting in reduced axonal mitochondrial content that is restored by genetic inhibition of AMPK and autophagy. In C. elegans, deletion of AMPK or of key autophagy and mitophagy genes normalizes the axonal mitochondrial content that is reduced upon mitochondrial dysfunction. In conditional, RGC specific Opa1-deficient mice, depletion of the essential autophagy gene Atg7 normalizes the excess autophagy and corrects the visual defects caused by Opa1 ablation. Thus, our data identify AMPK and autophagy as targetable components of ADOA pathogenesis.

Published
2020

18. UniProt-Related Documents (UniReD): assisting wet lab biologists in their quest on finding novel counterparts in a protein network.

Author

Theodosiou, Theodosios, Papanikolaou, Nikolaos, Savvaki, Maria, Bonetto, Giulia, Maxouri, Stella, Fakoureli, Eirini, Eliopoulos, Aristides, Tavernarakis, Nektarios, Amoutzias, Grigoris, Pavlopoulos, Georgios, Aivaliotis, Michalis, Nikoletopoulou, Vasiliki, Tzamarias, Dimitris, Karagogeos, Domna, and Iliopoulos, Ioannis

Abstract

The in-depth study of protein-protein interactions (PPIs) is of key importance for understanding how cells operate. Therefore, in the past few years, many experimental as well as computational approaches have been developed for the identification and discovery of such interactions. Here, we present UniReD, a user-friendly, computational prediction tool which analyses biomedical literature in order to extract known protein associations and suggest undocumented ones. As a proof of concept, we demonstrate its usefulness by experimentally validating six predicted interactions and by benchmarking it against public databases of experimentally validated PPIs succeeding a high coverage. We believe that UniReD can become an important and intuitive resource for experimental biologists in their quest for finding novel associations within a protein network and a useful tool to complement experimental approaches (e.g. mass spectrometry) by producing sorted lists of candidate proteins for further experimental validation. UniReD is available at http://bioinformatics.med.uoc.gr/unired/.

Published
2020

19. Coupling of autophagy and the mitochondrial intrinsic apoptosis pathway modulates proteostasis and ageing in Caenorhabditis elegans

Author

Christina Ploumi, Emmanouil Kyriakakis, and Nektarios Tavernarakis

Subjects
Cytology, QH573-671
Abstract

Abstract Mitochondria preserve metabolic homeostasis and integrate stress signals, to trigger cytoprotective, or cell death pathways. Mitochondrial homeostasis and function decline with age. The mechanisms underlying the deterioration of mitochondrial homeostasis during ageing, or in age-associated pathologies, remain unclear. Here, we show that CISD-1, a mitochondrial iron-sulfur cluster binding protein, implicated in the pathogenesis of Wolfram neurodegenerative syndrome type 2, modulates longevity in the nematode Caenorhabditis elegans by engaging autophagy and the mitochondrial intrinsic apoptosis pathway. The anti-apoptotic protein CED-9 is the downstream effector that mediates CISD-1-dependent effects on proteostasis, neuronal integrity and lifespan. Moreover, intracellular iron abundance is critical for CISD-1 function, since mild iron supplementation is sufficient to decelerate ageing and partly ameliorate the disturbed mitochondrial bioenergetics and proteostasis of CISD-1 deficient animals. Our findings reveal that CISD-1 serves as a mechanistic link between autophagy and the apoptotic pathway in mitochondria to differentially modulate organismal proteostasis and ageing, and suggest novel approaches which could facilitate the treatment of Wolfram Syndrome or related diseases.

Published
2023
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21. List of contributors

Author

Abrantes, Margarida, primary, Alves, Raquel, additional, Anugula, Sharath, additional, Aran, Veronica, additional, Badimon, Lina, additional, Barreto, Jorge N., additional, Bartosz, Grzegorz, additional, Borges, Fernanda, additional, Borrás, Consuelo, additional, Botelho, Maria Filomena, additional, Bousquet, Jean, additional, Brehm, António M.D., additional, Brito, Gerly A.C., additional, Bultje, Daan, additional, Cabral, Ana Cristina, additional, Caetano, André, additional, Canhão, Helena, additional, Carreira, Isabel Marques, additional, Carriazo, Ana Maria, additional, Carvalho, Cristina, additional, Carvalho, Eugenia, additional, Castel-Branco, Margarida, additional, Chen, Yaohua, additional, Coelho-Filho, João M., additional, Constâncio, Vera, additional, Correia e Silva, António, additional, Costa, Deiziane V.S., additional, Costa, Elísio, additional, Costa, Inês, additional, Cunha-Oliveira, Teresa, additional, de Carvalho, Paulo, additional, De Luca, Vicenzo, additional, de Natale, Edoardo R., additional, Dias, Jorge, additional, Dias, Ronaldo P., additional, Duarte, Ana I., additional, Farrel, John, additional, Fernandez-Llimos, Fernando, additional, Ferreira, Lino, additional, Ferrucci, Luigi, additional, Figueiredo, Isabel Vitoria, additional, Ford, Jamie K., additional, Franceschi, Claudio, additional, Freitas, Alex A., additional, Furlan de Brito, Maja, additional, Giacomin, Karla C., additional, Girao, Henrique, additional, Gkikas, Ilias, additional, Gomes, Bárbara, additional, Gomes, Rodrigo M., additional, Gonçalves, Ana Cristina, additional, Goulden, Peter, additional, Grant, Marcus, additional, Grilo, Luís F., additional, Guldemond, Nick, additional, Henriques, Jorge, additional, Heringer, Manoela, additional, Illario, Maddalena, additional, Jerónimo, Carmen, additional, Jones, John G., additional, Jorge, Joana, additional, Kabiri, Yaschar, additional, Karkucinska-Wieckowska, Agnieszka, additional, Kelly, George, additional, Kirkland, James L., additional, Kitaeva, Kristina, additional, Kiyasov, Andrey, additional, Korolchuk, Viktor I., additional, Laranjo, Mafalda, additional, LaRocca, Thomas J., additional, Lavrador, Marta, additional, Lebiedzinska-Arciszewska, Magdalena, additional, Li, Zhiquan, additional, Liu, Yuezhong, additional, Lourenço, Alexandre, additional, Ma, Lina, additional, Malva, João O., additional, Martens, Christopher R., additional, Mas-Bargues, Cristina, additional, Matafome, Paulo, additional, Melo, Joana Barbosa, additional, Mendonça, Maria L. Lima, additional, Metaxakis, Athanasios, additional, Middleton, Lefkos T., additional, Moreira, Paula I., additional, Nascimento, Judite M., additional, Neto, Vivaldo M., additional, Oliveira, Paulo J., additional, Ori, Alessandro, additional, Oriá, Reinaldo B., additional, Ozanne, Susan E., additional, Padeiro, Miguel, additional, Padro, Teresa, additional, Palmeira, Carlos M., additional, Pan, Yiming, additional, Paredes, Simão, additional, Passos, João F., additional, Pereira, Edith, additional, Pereira, Francisco B., additional, Pereira, Susana P., additional, Pinton, Paolo, additional, Pires, Joana F., additional, Pires, Salomé, additional, Polidori, M. Cristina, additional, Politis, Marios, additional, Raimundo, Nuno, additional, Ramalho-Santos, João, additional, Rasmussen, Lene Juel, additional, Regateiro, Fernando J., additional, Reis, Dario D., additional, Ribeiro, Caio, additional, Ribeiro, Ilda Patrícia, additional, Ribeiro-Rodrigues, Teresa M., additional, Rizvanov, Albert, additional, Rocha, Teresa, additional, Röhr, Susanne, additional, Rolo, Anabela P., additional, Román-Domínguez, Aurora, additional, Romero-Ortuno, Roman, additional, Rosa, Manuel Santos, additional, Rutland, Catrin, additional, Sadowska-Bartosz, Izabela, additional, Santana, Paula, additional, Santinha, Deolinda, additional, Santos, Marcos, additional, Sarmento Ribeiro, Ana Bela, additional, Semedo, Deisa S.R.C., additional, Sequeira, João, additional, Sierra, Felipe, additional, Silva, Maria Natalina L., additional, Solana, Rafael, additional, Solovyeva, Valeriya, additional, Spínola, Hélder, additional, Tavares, Renata S., additional, Tavernarakis, Nektarios, additional, Tchkonia, Tamar, additional, Theng, Yin-Leng, additional, Traver-Salcedo, Vicente, additional, Udeh-Momoh, Chi, additional, Verma, Rakhi, additional, Victorelli, Stella, additional, Vilaça, Andreia, additional, Vilahur, Gemma, additional, Viña, José, additional, von Zglinicki, Thomas, additional, Wahl, Devin, additional, Werle, Berenice Maria, additional, Wieckowski, Mariusz R., additional, Wilson, Heather, additional, Wissler Gerdes, Erin O., additional, Wozniak, Lucyna A., additional, Zavan, Barbara, additional, Zhu, Yi, additional, and Zischka, Hans, additional

Published
2023
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23. A proton-inhibited DEG/ENaC ion channel maintains neuronal ionstasis and promotes neuronal survival under stress

Author

Dionysia Petratou, Martha Gjikolaj, Eva Kaulich, William Schafer, and Nektarios Tavernarakis

Subjects
Neurology, Neurogenetics, Science
Abstract

Summary: The nervous system participates in the initiation and modulation of systemic stress. Ionstasis is of utmost importance for neuronal function. Imbalance in neuronal sodium homeostasis is associated with pathologies of the nervous system. However, the effects of stress on neuronal Na+ homeostasis, excitability, and survival remain unclear. We report that the DEG/ENaC family member DEL-4 assembles into a proton-inactivated sodium channel. DEL-4 operates at the neuronal membrane and synapse to modulate Caenorhabditis elegans locomotion. Heat stress and starvation alter DEL-4 expression, which in turn alters the expression and activity of key stress-response transcription factors and triggers appropriate motor adaptations. Similar to heat stress and starvation, DEL-4 deficiency causes hyperpolarization of dopaminergic neurons and affects neurotransmission. Using humanized models of neurodegenerative diseases in C. elegans, we showed that DEL-4 promotes neuronal survival. Our findings provide insights into the molecular mechanisms by which sodium channels promote neuronal function and adaptation under stress.

Published
2023
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24. Improving the read-out of the resonance frequency of nanotube mechanical resonators

Author

Schwender, Jil, Tsioutsios, Ioannis, Tavernarakis, Alexandros, Dong, Quan, Jin, Yong, Staufer, Urs, and Bachtold, Adrian

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

We report on an electrical detection method of ultrasensitive carbon nanotube mechanical resonators. The noise floor of the detection method is reduced using a RLC resonator and an amplifier based on a high electron mobility transistor cooled at 4.2 K. This allows us to resolve the resonance frequency of nanotube resonators with an unprecedented quality. We show that the noise of the resonance frequency measured at 4.2 K is limited by the resonator itself, and not by the imprecision of the measurement. The Allan deviation reaches ~10^-5 at 125 ms integration time. When comparing the integration time dependence of the Allan deviation to a power law, the exponent approaches ~1/4. The Allan deviation might be limited by the diffusion of particles over the surface of the nanotube. Our work holds promise for mass spectrometry and surface science experiments based on mechanical nano-resonators.

Published
2018
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26. Chemotaxis assay for evaluation of memory-like behavior in wild-type and Alzheimer’s-disease-like C. elegans models

Author

Shu-qin Cao, He-Ling Wang, Konstantinos Palikaras, Nektarios Tavernarakis, and Evandro Fei Fang

Subjects
Molecular Biology, Neuroscience, Science (General), Q1-390
Abstract

Summary: Here, we present an olfactory-dependent chemotaxis assay for evaluating changes in memory-like behavior in both wild-type and Alzheimer’s-disease-like C. elegans models. We describe steps for synchronizing and preparing C. elegans populations and for performing isoamyl alcohol conditioning during starvation and chemotaxis assaying. We then detail counting and quantification procedures. This protocol is applicable to mechanistic exploration and drug screening in neurodegenerative diseases and brain aging. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Published
2023
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28. Mitophagy

Author

Palikaras, Konstantinos, Tavernarakis, Nektarios, Offermanns, Stefan, editor, and Rosenthal, Walter, editor

Published
2021
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33. Real-time measurement of nanotube resonator fluctuations in an electron microscope

Author

Tsioutsios, I., Tavernarakis, A., Osmond, J., Verlot, P., and Bachtold, A.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

Mechanical resonators based on low-dimensional materials provide a unique platform for exploring a broad range of physical phenomena. The mechanical vibrational states are indeed extremely sensitive to charges, spins, photons, and adsorbed masses. However, the roadblock is often the readout of the resonator, since the detection of the vibrational states becomes increasingly difficult for smaller resonators. Here, we report an unprecedentedly sensitive method to detect nanotube resonators with effective masses in the 10^-20 kg range. We use the beam of an electron microscope to resolve the mechanical fluctuations of a nanotube in real-time for the first time. We obtain full access to the thermally-driven Brownian motion of the resonator, both in space and time domains. Our results establish the viability of carbon nanotube resonator technology at room temperature and pave the way towards the observation of novel thermodynamics regimes and quantum effects in nano-mechanics.

Published
2016
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34. Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Author

Halliday, Alison, Bulbulia, Richard, Bonati, Leo H, Peto, Richard, Pan, Hongchao, Potter, John, Henning Eckstein, Hans, Farrell, Barbara, Flather, Marcus, Mansfield, Averil, Mihaylova, Boby, Rahimi, Kazim, Simpson, David, Thomas, Dafydd, Sandercock, Peter, Gray, Richard, Molyneux, Andrew, Shearman, Cliff P, Rothwell, Peter, Belli, Anna, Herrington, Will, Judge, Parminder, Leopold, Peter, Mafham, Marion, Gough, Michael, Cao, Piergiorgio, MacDonald, Sumaira, Bari, Vasha, Berry, Clive, Bradshaw, S, Brudlo, Wojciech, Clarke, Alison, Chester, Johanna, Cox, Robin, Cradduck-Bamford, Andrea, Fathers, Susan, Gaba, Kamran, Gray, Mo, Hayter, Elizabeth, Holliday, Constance, Kurien, Rijo, Lay, Michael, le Conte, Steffi, McManus, Jessica, Madgwick, Zahra, Morris, Dylan, Munday, Andrew, Pickworth, Sandra, Ostasz, Wiktor, Poorthuis, Michiel, Richards, Sue, Teixeira, Louisa, Tochlin, Sergey, Tully, Lynda, Wallis, Carol, Willet, Monique, Young, Alan, Casana, Renato, Malloggi, Chiara, Odero Jr, Andrea, Silani, Vincenzo, Parati, Gianfranco, Malchiodi, Giuseppe, Malferrari, Giovanni, Strozzi, Francesco, Tusini, Nicola, Vecchiati, Enrico, Coppi, Gioacchino, Lauricella, Antonio, Moratto, Roberto, Silingardi, Roberto, Veronesi, Jessica, Zini, Andrea, Ferrero, Emanuele, Ferri, Michelangelo, Gaggiano, Andrea, Labate, Carmelo, Nessi, Franco, Psacharopulo, Daniele, Viazzo, Andrea, Malacrida, Giovanni, Mazzaccaro, Daniela, Meola, Giovanni, Modafferi, Alfredo, Nano, Giovanni, Occhiuto, Maria Teresa, Righini, Paolo, Stegher, Silvia, Chiarandini, Stefano, Griselli, Filippo, Lepidi, Sandro, Pozzi Mucelli, Fabio, Naccarato, Marcello, D'Oria, Mario, Ziani, Barbara, Stella, Andrea, Dieng, Mortalla, Faggioli, Gianluca, Gargiulo, Mauro, Palermo, Sergio, Pini, Rodolfo, Puddu, Giovanni Maria, Vacirca, Andrea, Angiletta, Domenico, Desantis, Claudio, Marinazzo, Davide, Mastrangelo, Giovanni, Regina, Guido, Pulli, Raffaele, Bianchi, Paolo, Cireni, Lea, Coppi, Elisabetta, Pizzirusso, Rocco, Scalise, Filippo, Sorropago, Giovanni, Tolva, Valerio, Caso, Valeria, Cieri, Enrico, DeRango, Paola, Farchioni, Luca, Isernia, Giacomo, Lenti, Massimo, Parlani, Gian Battista, Pupo, Guglielmo, Pula, Grazia, Simonte, Gioele, Verzini, Fabio, Carimati, Federico, Delodovici, Maria Luisa, Fontana, Federico, Piffaretti, Gabriele, Tozzi, Matteo, Civilini, Efrem, Poletto, Giorgio, Reimers, Bernhard, Praquin, Barbara, Ronchey, Sonia, Capoccia, Laura, Mansour, Wassim, Sbarigia, Enrico, Speziale, Francesco, Sirignano, Pasqualino, Toni, Danilo, Galeotti, Roberto, Gasbarro, Vincenzo, Mascoli, Francesco, Rocca, Tiberio, Tsolaki, Elpiniki, Bernardini, Giulia, DeMarco, Ester, Giaquinta, Alessia, Patti, Francesco, Veroux, Massimiliano, Veroux, Pierfrancesco, Virgilio, Carla, Mangialardi, Nicola, Orrico, Matteo, Di Lazzaro, Vincenzo, Montelione, Nunzio, Spinelli, Francesco, Stilo, Francesco, Cernetti, Carlo, Irsara, Sandro, Maccarrone, Giuseppe, Tonello, Diego, Visonà, Adriana, Zalunardo, Beniamino, Chisci, Emiliano, Michelagnoli, Stefano, Troisi, Nicola, Masato, Maela, Dei Negri, Massimo, Pacchioni, Andrea, Saccà, Salvatore, Amatucci, Giovanni, Cannizzaro, Alfredo, Accrocca, Federico, Ambrogi, Cesare, Barbazza, Renzo, Marcucci, Giustino, Siani, Andrea, Bajardi, Guido, Savettieri, Giovanni, Argentieri, Angelo, Corbetta, Riccardo, Odero, Attilio, Quaretti, Pietro, Thyrion, Federico Z, Cappelli, Alessandro, Benevento, Domenico, De Donato, Gianmarco, Mele, Maria Agnese, Palasciano, Giancarlo, Pieragalli, Daniela, Rossi, Alessandro, Setacci, Carlo, Setacci, Francesco, Palombo, Domenico, Perfumo, Maria Cecilia, Martelli, Edoardo, Paolucci, Aldo, Trimarchi, Santi, Grassi, Viviana, Grimaldi, Luigi, La Rosa, Giuliana, Mirabella, Domenico, Scialabba, Matteo, Sichel, Leonildo, D'Angelo, Costantino L, Fadda, Gian Franco, Kasemi, Holta, Marino, Mario, Burzotta, Francesco, Codispoti, Francesco Alberto, Ferrante, Angela, Tinelli, Giovanni, Tshomba, Yamume, Vincenzoni, Claudio, Amis, Deborah, Anderson, Dawn, Catterson, Martin, Clarke, Mike, Davis, Michelle, Dixit, Anand, Dyker, Alexander, Ford, Gary, Jackson, Ralph, Kappadath, Sreevalsan, Lambert, David, Lees, Tim, Louw, Stephen, McCaslin, James, Parr, Noala, Robson, Rebecca, Stansby, Gerard, Wales, Lucy, Wealleans, Vera, Wilson, Lesley, Wyatt, Michael, Baht, Hardeep, Balogun, Ibrahim, Burger, Ilse, Cosier, Tracy, Cowie, Linda, Gunathilagan, Gunaratnam, Hargroves, David, Insall, Robert, Jones, Sally, Rudenko, Hannah, Schumacher, Natasha, Senaratne, Jawaharlal, Thomas, George, Thomson, Audrey, Webb, Tom, Brown, Ellen, Esisi, Bernard, Mehrzad, Ali, MacSweeney, Shane, McConachie, Norman, Southam, Alison, Sunman, Wayne, Abdul-Hamiq, Ahmed, Bryce, Jenny, Chetter, Ian, Ettles, Duncan, Lakshminarayan, Raghuram, Mitchelson, Kim, Rhymes, Christopher, Robinson, Graham, Scott, Paul, Vickers, Alison, Ashleigh, Ray, Butterfield, Stephen, Gamble, Ed, Ghosh, Jonathan, McCollum, Charles N, Welch, Mark, Welsh, Sarah, Wolowczyk, Leszek, Donnelly, Mary, D'Souza, Stephen, Egun, Anselm A, Gregary, Bindu, Joseph, Thomas, Kelly, Christine, Punekar, Shuja, Rahi, M Asad, Raj, Sonia, Seriki, Dare, Thomson, George, Brown, James, Durairajan, Ragunath, Grunwald, Iris, Guyler, Paul, Harman, Paula, Jakeways, Matthew, Khuoge, Christopher, Kundu, Ashish, Loganathan, Thayalini, Menon, Nisha, Prabakaran, Raji O, Sinha, Devesh, Thompson, Vicky, Tysoe, Sharon, Briley, Dennis, Darby, Chris, Hands, Linda, Howard, Dominic, Kuker, Wilhelm, Schulz, Ursula, Teal, Rachel, Barer, David, Brown, Andrew, Crawford, Susan, Dunlop, Paul, Krishnamurthy, Ramesh, Majmudar, Nikhil, Mitchell, Duncan, Myint, Min P, O'Brien, Richard, O'Connell, Janice, Sattar, Naweed, Vetrivel, Shanmugam, Beard, Jonathan, Cleveland, Trevor, Gaines, Peter, Humphreys, John, Jenkins, Alison, King, Craig, Kusuma, Daniel, Lindert, Ralph, Lonsdale, Robbie, Nair, Raj, Nawaz, Shah, Okhuoya, Faith, Turner, Douglas, Venables, Graham, Dorman, Paul, Hughes, Andrea, Jones, Deborah, Mendelow, David, Rodgers, Helen, Raudoniitis, Aidas, Enevoldson, Peter, Nahser, Hans, O'Brien, Imelda, Torella, Francesco, Watling, Dave, White, Richard, Brown, Pauline, Dutta, Dipankar, Emerson, Lorraine, Hilltout, Paula, Kulkarni, Sachin, Morrison, Jackie, Poskitt, Keith, Slim, Fiona, Smith, Sarah, Tyler, Amanda, Waldron, Joanne, Whyman, Mark, Bajoriene, Milda, Baker, Lucy, Colston, Amanda, Eliot-Jones, Bekky, Gramizadeh, Gita, Lewis-Clarke, Catherine, McCafferty, Laura, Oliver, Deborah, Palmer, Debbie, Patil, Abhijeet, Pegler, Suzannah, Ramadurai, Gopi, Roberts, Aisling, Sargent, Tracey, Siddegowda, Shivaprasad, Singh-Ranger, Ravi, Williams, Akintunde, Williams, Lucy, Windebank, Steve, Zuromskis, Tadas, Alwis, Lanka, Angus, Jane, Asokanathan, Asaipillai, Fornolles, Caroline, Hardy, Diana, Hunte, Sophy, Justin, Frances, Phiri, Duke, Mitabouana-Kibou, Marie, Sekaran, Lakshmanan, Sethuraman, Sakthivel, Tate, Margaret L, Akyea-Mensah, Joyce, Ball, Stephen, Chrisopoulou, Angela, Keene, Elizabeth, Phair, Alison, Rogers, Steven, Smyth, John V, Bicknell, Colin, Chataway, Jeremy, Cheshire, Nicholas, Clifton, Andrew, Eley, Caroline, Gibbs, Richard, Hamady, Mohammad, Hazel, Beth, James, Alex, Jenkins, Michael, Khanom, Nyma, Lacey, Austin, Mireskandari, Maz, O'Reilly, Joanna, Pereira, Antony, Sachs, Tina, Wolfe, John, Davey, Philip, Rogers, Gill, Smith, Gemma, Tervit, Gareth, Nichol, Ian, Parry, Andrew, Young, Gavin, Ashley, Simon, Barwell, James, Dix, Francis, Nor, Azlisham M, Parry, Chris, Birt, Angela, Davies, Paul, George, Jim, Graham, Anne, Jonker, Leon, Kelsall, Nicci, Potts, Caroline, Wilson, Toni, Crinnion, Jamie, Cuenoud, Larissa, Aleksic, Nikola, Babic, Srdan, Ilijevski, Nenad, Radak, Đorde, Sagic, Dragan, Tanaskovic, Slobodan, Colic, Momcilo, Cvetic, Vladimir, Davidovic, Lazar, Jovanovic, Dejana R, Koncar, Igor, Mutavdžic, Perica, Sladojevic, Miloš, Tomic, Ivan, Debus, Eike S, Grzyska, Ulrich, Otto, Dagmar, Thomalla, Götz, Barlinn, Jessica, Gerber, Johannes, Haase, Kathrin, Hartmann, Christian, Ludwig, Stefan, Pütz, Volker, Reeps, Christian, Schmidt, Christine, Weiss, Norbert, Werth, Sebastian, Winzer, Simon, Gemper, Janine, Günther, Albrecht, Heiling, Bianka, Jochmann, Elisabeth, Karvouniari, Panagiota, Klingner, Carsten, Mayer, Thomas, Schubert, Julia, Schulze-Hartung, Friederike, Zanow, Jürgen, Bausback, Yvonne, Borger, Franka, Botsios, Spiridon, Branzan, Daniela, Bräunlich, Sven, Hölzer, Henryk, Lenzer, Janin, Piorkowski, Christopher, Richter, Nadine, Schuster, Johannes, Scheinert, Dierk, Schmidt, Andrej, Staab, Holger, Ulrich, Matthias, Werner, Martin, Berger, Hermann, Biró, Gábor, Eckstein, Hans-Henning, Kallmayer, Michael, Kreiser, Kornelia, Zimmermann, Alexander, Berekoven, Bärbel, Frerker, Klaus, Gordon, Vera, Torsello, Giovanni, Arnold, Sebastian, Dienel, Cora, Storck, Martin, Biermaier, Bernhard, Gissler, Hans Martin, Klötzsch, Christof, Pfeiffer, Tomas, Schneider, Ralph, Söhl, Leander, Wennrich, Michael, Alonso, Angelika, Keese, Michael, Groden, Christoph, Cöster, Andreas, Engelhardt, Andreas, Ratusinski, Christoph-Maria, Berg, Bengt, Delle, Martin, Formgren, Johan, Gillgren, Peter, Jarl, Lotta, Kall, Torbjörn B, Konrad, Peter, Nyman, Niklas, Skiöldebrand, Claes, Steuer, Johnny, Takolander, Rabbe, Malmstedt, Jonas, Acosta, Stefan, Björses, Katarina, Brandt, Kerstin, Dias, Nuno, Gottsäter, Anders, Holst, Jan, Kristmundsson, Thorarinn, Kühme, Tobias, Kölbel, Tilo, Lindblad, Bengt, Lindh, Mats, Malina, Martin, Ohrlander, Tomas, Resch, Tim, Rönnle, Viola, Sonesson, Björn, Warvsten, Margareta, Zdanowski, Zbigniew, Campbell, Erik, Kjellin, Per, Lindgren, Hans, Nyberg, Johan, Petersen, Björn, Plate, Gunnar, Pärsson, Håkan, Qvarfordt, Peter, Ignatenko, Pavel, Karpenko, Andrey, Starodubtsev, Vladimir, Chernyavsky, Mikhail A, Golovkova, Maria S, Komakha, Boris B, Zherdev, Nikolay N, Belyasnik, Andrey, Chechulov, Pavel, Kandyba, Dmitry, Stepanishchev, Igor, Csobay-Novák, Csaba, Dósa, Edit, Entz, László, Nemes, Balázs, Szeberin, Zoltán, Barzó, Pál, Bodosi, Mihaly, Fákó, Eniko, Fülöp, Béla, Németh, Tamás, Pazdernyik, Szilárd, Skoba, Krisztina, Vörös, Erika, Chatzinikou, Eleni, Giannoukas, Athanasios, Karathanos, Christos, Koutsias, Stylianos, Kouvelos, Georgios, Matsagkas, Miltiadis, Ralli, Styliani, Rountas, Christos, Rousas, Nikolaos, Spanos, Konstantinos, Brountzos, Elias, Kakisis, John D, Lazaris, Andreas, Moulakakis, Konstantinos G, Stefanis, Leonidas, Tsivgoulis, Georgios, Vasdekis, Spyros, Antonopoulos, Constantine N, Bellenis, Ion, Maras, Dimitrios, Polydorou, Antonios, Polydorou, Victoria, Tavernarakis, Antonios, Ioannou, Nikolaos, Terzoudi, Maria, Lazarides, Miltos, Mantatzis, Michalis, Vadikolias, Kostas, Dzieciuchowicz, Lukasz, Gabriel, Marcin, Krasinski, Zbigniew, Oszkinis, Grzegorz, Pukacki, Fryderyk, Slowinski, Maciej, Stanišic, Michal-Goran, Staniszewski, Ryszard, Tomczak, Jolanta, Zielinski, Maciej, Myrcha, Piotr, Rózanski, Dorota, Drelichowski, Stanislaw, Iwanowski, Wojciech, Koncewicz, Katarzyna, Bialek, Pawel, Biejat, Zbigniew, Czepel, Wojciech, Czlonkowska, Anna, Dowzenko, Anatol, Jedrzejewska, Julia, Kobayashi, Adam, Leszczynski, Jerzy, Malek, Andrzej, Polanski, Jerzy, Proczka, Robert, Skorski, Maciej, Szostek, Mieczyslaw, Andziak, Piotr, Dratwicki, Maciej, Gil, Robert, Nowicki, Miroslaw, Pniewski, Jaroslaw, Rzezak, Jaroslaw, Seweryniak, Piotr, Dabek, Pawel, Juszynski, Michal, Madycki, Grzegorz, Pacewski, Bartosz, Raciborski, Witold, Slowinski, Piotr, Staszkiewicz, Walerian, Bombic, Martin, Chlouba, Vladimír, Fiedler, Jirí, Hes, Karel, Koštál, Petr, Sova, Jindrich, Kríž, Zdenek, Prívara, Mojmír, Reif, Michal, Staffa, Robert, Vlachovský, Robert, Vojtíšek, Bohuslav, Hrbác, Tomáš, Kuliha, Martin, Procházka, Václav, Roubec, Martin, Školoudík, David, Netuka, David, Šteklácová, Anna, Beneš III, Vladimír, Buchvald, Pavel, Endrych, Ladislav, Šercl, Miroslav, Campos Jr, Walter, Casella, Ivan B, de Luccia, Nelson, Estenssoro, André E V, Presti, Calógero, Puech-Leão, Pedro, Neves, Celso R B, da Silva, Erasmo S, Sitrângulo Jr, Cid J, Monteiro, José A T, Tinone, Gisela, Bellini Dalio, Marcelo, Joviliano, Edwaldo E, Pontes Neto, Octávio M, Serra Ribeiro, Mauricio, Cras, Patrick, Hendriks, Jeroen M H, Hoppenbrouwers, Mieke, Lauwers, Patrick, Loos, Caroline, Yperzeele, Laetitia, Geenens, Mia, Hemelsoet, Dimitri, van Herzeele, Isabelle, Vermassen, Frank, Astarci, Parla, Hammer, Frank, Lacroix, Valérie, Peeters, André, Verhelst, Robert, Cirelli, Silvana, Dormal, Pol, Grimonprez, Annelies, Lambrecht, Bart, Lerut, Philipe, Thues, Eddy, De Koster, Guy, Desiron, Quentin, Maertens de Noordhout, Alain, Malmendier, Danielle, Massoz, Mireille, Saad, Georges, Bosiers, Marc, Callaert, Joren, Deloose, Koen, Blanco Cañibano, Estrella, García Fresnillo, Beatriz, Guerra Requena, Mercedes, Morata Barrado, Pilar C, Muela Méndez, Miguel, Yusta Izquierdo, Antonio, Aparici Robles, Fernando, Blanes Orti, Paula, García Dominguez, Luis, Martínez López, Rafael, Miralles Hernández, Manuel, Tembl Ferrairo, José I, Chamorro, Ángel, Macho, Juan, Obach, Víctor, Riambau, Vincent, San Román, Luis, Ahlhelm, Frank J, Blackham, Kristine, Engelter, Stefan, Eugster, Thomas, Gensicke, Henrik, Gürke, Lorenz, Lyrer, Philippe, Mariani, Luigi, Maurer, Marina, Mujagic, Edin, Müller, Mandy, Psychogios, Marios, Stierli, Peter, Stippich, Christoph, Traenka, Christopher, Wolff, Thomas, Wagner, Benjamin, Wiegert, Martina M, Clarke, Sandra, Diepers, Michael, Gröchenig, Ernst, Gruber, Philipp, Isaak, Andrej, Kahles, Timo, Marti, Regula, Nedeltchev, Krassen, Remonda, Luca, Tissira, Nadir, Valença Falcão, Martina, de Borst, Gert J, Lo, Rob H, Moll, Frans L, Toorop, Raechel, van der Worp, Bart H, Vonken, Evert J, Kappelle, Jaap L, Jahrome, Ommid, Vos, Floris, Schuiling, Wouter, van Overhagen, Hendrik, Keunen, Rudolf W M, Knippenberg, Bob, Wever, Jan J, Lardenoije, Jan W, Reijnen, Michel, Smeets, Luuk, van Sterkenburg, Steven, Fraedrich, Gustav, Gizewski, Elke, Gruber, Ingrid, Knoflach, Michael, Kiechl, Stefan, Rantner, Barbara, Abdulamit, Timur, Bergeron, Patrice, Padovani, Raymond, Trastour, Jean-Christophe, Cardon, Jean-Marie, Le Gallou-Wittenberg, Anne, Allaire, Eric, Becquemin, Jean-Pierre, Cochennec-Paliwoda, Frédéric, Desgranges, Pascal, Hosseini, Hassan, Kobeiter, Hicham, Marzelle, Jean, Almekhlafi, Mohammed A, Bal, Simerpreet, Barber, Phillip A, Coutts, Shelagh B, Demchuk, Andrew M, Eesa, Muneer, Gillies, Michelle, Goyal, Mayank, Hill, Michael D, Hudon, Mark E, Jambula, Anitha, Kenney, Carol, Klein, Gary, McClelland, Marie, Mitha, Alim, Menon, Bijoy K, Morrish, William F, Peters, Steven, Ryckborst, Karla J, Samis, Greg, Save, Supriya, Smith, Eric E, Stys, Peter, Subramaniam, Suresh, Sutherland, Garnette R, Watson, Tim, Wong, John H, Zimmel, L, Flis, Vojko, Matela, Jože, Miksic, Kazimir, Milotic, Franko, Mrdja, Božidar, Stirn, Barbara, Tetickovic, Erih, Gasparini, Mladen, Grad, Anton, Kompara, Ingrid, Miloševic, Zoren, Palmiste, Veronika, Toomsoo, Toomas, Aidashova, Balzhan, Kospanov, Nursultan, Lyssenko, Roman, Mussagaliev, Daulet, Beyar, Rafi, Hoffman, Aaron, Karram, Tony, Kerner, Arthur, Nikolsky, Eugenia, Nitecki, Samy, Andonova, Silva, Bachvarov, Chavdar, Petrov, Vesko, Cvjetko, Ivan, Vidjak, Vinko, Halužan, Damir, Petrunic, Mladen, Liu, Bao, Liu, Chang-Wei, Bartko, Daniel, Beno, Peter, Rusnák, František, Zelenák, Kamil, Ezura, Masayuki, Inoue, Takashi, Kimura, Naoto, Kondo, Ryushi, Matsumoto, Yasushi, Shimizu, Hiroaki, Endo, Hidenori, Furui, Eisuke, Bakke, Søren, Krohg-Sørensen, Kristen, Nome, Terje, Skjelland, Mona, Tennøe, Bjørn, Albuquerque e Castro, João, Alves, Gonçalo, Bastos Gonçalves, Frederico, de Aragão Morais, José, Garcia, Ana C, Valentim, Hugo, Vasconcelos, Leonor, Belcastro, Fernando, Cura, Fernando, Zaefferer, Patricio, Abd-Allah, Foad, Eldessoki, Mohamed H, Heshmat Kassem, Hussein, Soliman Gharieb, Haytham, Colgan, Mary P, Haider, Syed N, Harbison, Joe, Madhavan, Prakash, Moore, Dermot, Shanik, Gregor, Kazan, Viviane, Nazzal, Munier, and Ramsey-Williams, Vicki

Published
2021
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35. Neuronal atg1 Coordinates Autophagy Induction and Physiological Adaptations to Balance mTORC1 Signalling

Author

Athanasios Metaxakis, Michail Pavlidis, and Nektarios Tavernarakis

Subjects
5HTR7 receptor, ageing, ATG1, autophagy, behaviour, cAMP/PKA, Cytology, QH573-671
Abstract

The mTORC1 nutrient-sensing pathway integrates metabolic and endocrine signals into the brain to evoke physiological responses to food deprivation, such as autophagy. Nevertheless, the impact of neuronal mTORC1 activity on neuronal circuits and organismal metabolism remains obscure. Here, we show that mTORC1 inhibition acutely perturbs serotonergic neurotransmission via proteostatic alterations evoked by the autophagy inducer atg1. Neuronal ATG1 alters the intracellular localization of the serotonin transporter, which increases the extracellular serotonin and stimulates the 5HTR7 postsynaptic receptor. 5HTR7 enhances food-searching behaviour and ecdysone-induced catabolism in Drosophila. Along similar lines, the pharmacological inhibition of mTORC1 in zebrafish also stimulates food-searching behaviour via serotonergic activity. These effects occur in parallel with neuronal autophagy induction, irrespective of the autophagic activity and the protein synthesis reduction. In addition, ectopic neuronal atg1 expression enhances catabolism via insulin pathway downregulation, impedes peptidergic secretion, and activates non-cell autonomous cAMP/PKA. The above exert diverse systemic effects on organismal metabolism, development, melanisation, and longevity. We conclude that neuronal atg1 aligns neuronal autophagy induction with distinct physiological modulations, to orchestrate a coordinated physiological response against reduced mTORC1 activity.

Published
2023
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39. Molecular definitions of autophagy and related processes

Author

Galluzzi, Lorenzo, Baehrecke, Eric H, Ballabio, Andrea, Boya, Patricia, Pedro, José Manuel Bravo‐San, Cecconi, Francesco, Choi, Augustine M, Chu, Charleen T, Codogno, Patrice, Colombo, Maria Isabel, Cuervo, Ana Maria, Debnath, Jayanta, Deretic, Vojo, Dikic, Ivan, Eskelinen, Eeva‐Liisa, Fimia, Gian Maria, Fulda, Simone, Gewirtz, David A, Green, Douglas R, Hansen, Malene, Harper, J Wade, Jäättelä, Marja, Johansen, Terje, Juhasz, Gabor, Kimmelman, Alec C, Kraft, Claudine, Ktistakis, Nicholas T, Kumar, Sharad, Levine, Beth, Lopez‐Otin, Carlos, Madeo, Frank, Martens, Sascha, Martinez, Jennifer, Melendez, Alicia, Mizushima, Noboru, Münz, Christian, Murphy, Leon O, Penninger, Josef M, Piacentini, Mauro, Reggiori, Fulvio, Rubinsztein, David C, Ryan, Kevin M, Santambrogio, Laura, Scorrano, Luca, Simon, Anna Katharina, Simon, Hans‐Uwe, Simonsen, Anne, Tavernarakis, Nektarios, Tooze, Sharon A, Yoshimori, Tamotsu, Yuan, Junying, Yue, Zhenyu, Zhong, Qing, and Kroemer, Guido

Subjects
Animals, Autophagy, Caenorhabditis elegans, Drosophila melanogaster, Gene Regulatory Networks, Mice, Saccharomyces cerevisiae, Terminology as Topic, chaperone-mediated autophagy, LC3-associated phagocytosis, microautophagy, mitophagy, xenophagy, LC3‐associated phagocytosis, chaperone‐mediated autophagy, Biological Sciences, Information and Computing Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Over the past two decades, the molecular machinery that underlies autophagic responses has been characterized with ever increasing precision in multiple model organisms. Moreover, it has become clear that autophagy and autophagy-related processes have profound implications for human pathophysiology. However, considerable confusion persists about the use of appropriate terms to indicate specific types of autophagy and some components of the autophagy machinery, which may have detrimental effects on the expansion of the field. Driven by the overt recognition of such a potential obstacle, a panel of leading experts in the field attempts here to define several autophagy-related terms based on specific biochemical features. The ultimate objective of this collaborative exchange is to formulate recommendations that facilitate the dissemination of knowledge within and outside the field of autophagy research.

Published
2017

40. Autophagy in healthy aging and disease

Author

Aman, Yahyah, Schmauck-Medina, Tomas, Hansen, Malene, Morimoto, Richard I., Simon, Anna Katharina, Bjedov, Ivana, Palikaras, Konstantinos, Simonsen, Anne, Johansen, Terje, Tavernarakis, Nektarios, Rubinsztein, David C., Partridge, Linda, Kroemer, Guido, Labbadia, John, and Fang, Evandro F.

Published
2021
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41. Meeting summary of The NYO3 5th NO-Age/AD meeting and the 1st Norway-UK joint meeting on ageing and dementia: recent progress on the mechanisms and interventional strategies

Author

Wang, He-Ling, Siow, Richard, Schmauck-Medina, Tomas, Zhang, Jianying, Sandset, Per Morten, Filshie, Clare, Lund, Øystein, Partridge, Linda, Bergersen, Linda Hildegard, Juel Rasmussen, Lene, Palikaras, Konstantinos, Sotiropoulos, Ioannis, Storm-Mathisen, Jon, Rubinsztein, David C, Spillantini, Maria Grazia, De Zeeuw, Chris I, Watne, Leiv Otto, Vyhnalek, Martin, Veverova, Katerina, Liang, Kristina Xiao, Tavernarakis, Nektarios, Bohr, Vilhelm A, Yokote, Koutaro, Saarela, Janna, Nilsen, Hilde, Gonos, Efstathios S, Scheibye-Knudsen, Morten, Chen, Guobing, Kato, Hisaya, Selbæk, Geir, Fladby, Tormod, Nilsson, Per, Simonsen, Anne, Aarsland, Dag, Lautrup, Sofie, Ottersen, Ole Petter, Cox, Lynne S, Fang, Evandro F, Wang, He-Ling, Siow, Richard, Schmauck-Medina, Tomas, Zhang, Jianying, Sandset, Per Morten, Filshie, Clare, Lund, Øystein, Partridge, Linda, Bergersen, Linda Hildegard, Juel Rasmussen, Lene, Palikaras, Konstantinos, Sotiropoulos, Ioannis, Storm-Mathisen, Jon, Rubinsztein, David C, Spillantini, Maria Grazia, De Zeeuw, Chris I, Watne, Leiv Otto, Vyhnalek, Martin, Veverova, Katerina, Liang, Kristina Xiao, Tavernarakis, Nektarios, Bohr, Vilhelm A, Yokote, Koutaro, Saarela, Janna, Nilsen, Hilde, Gonos, Efstathios S, Scheibye-Knudsen, Morten, Chen, Guobing, Kato, Hisaya, Selbæk, Geir, Fladby, Tormod, Nilsson, Per, Simonsen, Anne, Aarsland, Dag, Lautrup, Sofie, Ottersen, Ole Petter, Cox, Lynne S, and Fang, Evandro F

Abstract

Unhealthy ageing poses a global challenge with profound healthcare and socioeconomic implications. Slowing down the ageing process offers a promising approach to reduce the burden of a number of age-related diseases, such as dementia, promoting healthy longevity in the old population. In response to the challenge of the ageing population and with a view to the future, Norway and the UK are fostering collaborations, supported by a "Money Follows Cooperation agreement" between the two nations. The inaugural Norway-UK joint meeting on ageing and dementia gathered leading experts on ageing and dementia from the two nations to share their latest discoveries in related fields. Since ageing is an international challenge, and to foster collaborations, we also invited leading scholars from 11 additional countries to join this event. This report provides a summary of the conference, highlighting recent progress on molecular ageing mechanisms, genetic risk factors, DNA damage and repair, mitophagy, autophagy, as well as progress on a series of clinical trials (e.g., using NAD+ precursors). The meeting facilitated dialogue among policy makers, administrative leaders, researchers, and clinical experts, aiming to promote international research collaborations and to translate findings into clinical applications and interventions to advance healthy ageing.

Published
2024

42. Meeting Summary of The NYO3 5th NO-Age/AD Meeting and the 1st Norway-UK Joint Meeting on Aging and Dementia:Recent Progress on the Mechanisms and Interventional Strategies

Author

Wang, He Ling, Siow, Richard, Schmauck-Medina, Tomas, Zhang, Jianying, Sandset, Per Morten, Filshie, Clare, Lund, Øystein, Partridge, Linda, Bergersen, Linda Hildegard, Juel Rasmussen, Lene, Palikaras, Konstantinos, Sotiropoulos, Ioannis, Storm-Mathisen, Jon, Rubinsztein, David C., Spillantini, Maria Grazia, De Zeeuw, Chris I., Watne, Leiv Otto, Vyhnalek, Martin, Veverova, Katerina, Liang, Kristina Xiao, Tavernarakis, Nektarios, Bohr, Vilhelm A., Yokote, Koutaro, Saarela, Janna, Nilsen, Hilde, Gonos, Efstathios S., Scheibye-Knudsen, Morten, Chen, Guobing, Kato, Hisaya, Selbæk, Geir, Fladby, Tormod, Nilsson, Per, Simonsen, Anne, Aarsland, Dag, Lautrup, Sofie, Ottersen, Ole Petter, Cox, Lynne S., Fang, Evandro F., Wang, He Ling, Siow, Richard, Schmauck-Medina, Tomas, Zhang, Jianying, Sandset, Per Morten, Filshie, Clare, Lund, Øystein, Partridge, Linda, Bergersen, Linda Hildegard, Juel Rasmussen, Lene, Palikaras, Konstantinos, Sotiropoulos, Ioannis, Storm-Mathisen, Jon, Rubinsztein, David C., Spillantini, Maria Grazia, De Zeeuw, Chris I., Watne, Leiv Otto, Vyhnalek, Martin, Veverova, Katerina, Liang, Kristina Xiao, Tavernarakis, Nektarios, Bohr, Vilhelm A., Yokote, Koutaro, Saarela, Janna, Nilsen, Hilde, Gonos, Efstathios S., Scheibye-Knudsen, Morten, Chen, Guobing, Kato, Hisaya, Selbæk, Geir, Fladby, Tormod, Nilsson, Per, Simonsen, Anne, Aarsland, Dag, Lautrup, Sofie, Ottersen, Ole Petter, Cox, Lynne S., and Fang, Evandro F.

Abstract

Unhealthy aging poses a global challenge with profound healthcare and socioeconomic implications. Slowing down the aging process offers a promising approach to reduce the burden of a number of age-related diseases, such as dementia, and promoting healthy longevity in the old population. In response to the challenge of the aging population and with a view to the future, Norway and the United Kingdom are fostering collaborations, supported by a “Money Follows Cooperation agreement” between the 2 nations. The inaugural Norway–UK joint meeting on aging and dementia gathered leading experts on aging and dementia from the 2 nations to share their latest discoveries in related fields. Since aging is an international challenge, and to foster collaborations, we also invited leading scholars from 11 additional countries to join this event. This report provides a summary of the conference, highlighting recent progress on molecular aging mechanisms, genetic risk factors, DNA damage and repair, mitophagy, autophagy, as well as progress on a series of clinical trials (eg, using NAD+ precursors). The meeting facilitated dialogue among policymakers, administrative leaders, researchers, and clinical experts, aiming to promote international research collaborations and to translate findings into clinical applications and interventions to advance healthy aging., Unhealthy aging poses a global challenge with profound healthcare and socioeconomic implications. Slowing down the aging process offers a promising approach to reduce the burden of a number of age-related diseases, such as dementia, and promoting healthy longevity in the old population. In response to the challenge of the aging population and with a view to the future, Norway and the United Kingdom are fostering collaborations, supported by a "Money Follows Cooperation agreement" between the 2 nations. The inaugural Norway-UK joint meeting on aging and dementia gathered leading experts on aging and dementia from the 2 nations to share their latest discoveries in related fields. Since aging is an international challenge, and to foster collaborations, we also invited leading scholars from 11 additional countries to join this event. This report provides a summary of the conference, highlighting recent progress on molecular aging mechanisms, genetic risk factors, DNA damage and repair, mitophagy, autophagy, as well as progress on a series of clinical trials (eg, using NAD+ precursors). The meeting facilitated dialogue among policymakers, administrative leaders, researchers, and clinical experts, aiming to promote international research collaborations and to translate findings into clinical applications and interventions to advance healthy aging.

Published
2024

44. The Cytoskeleton as a Modulator of Aging and Neurodegeneration

Author

Kounakis, Konstantinos, Tavernarakis, Nektarios, COHEN, IRUN R., Editorial Board Member, LAJTHA, ABEL, Editorial Board Member, LAMBRIS, JOHN D., Editorial Board Member, PAOLETTI, RODOLFO, Editorial Board Member, REZAEI, NIMA, Editorial Board Member, and Guest, Paul C., editor

Published
2019
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46. Assessment of dopaminergic neuron degeneration in a C. elegans model of Parkinson’s disease

Author

Konstantinos Palikaras, Tanima SenGupta, Hilde Nilsen, and Nektarios Tavernarakis

Subjects
Cell Biology, Model Organisms, Molecular Biology, Neuroscience, Science (General), Q1-390
Abstract

Summary: Transgenic Caenorhabditis elegans that expresses the full-length wild-type human α-synuclein in dopaminergic neurons provides a well-established Parkinson’s disease (PD) nematode model. Here, we present a detailed protocol to monitor and dissect the molecular underpinnings of age-associated neurodegeneration using this PD nematode model. This protocol includes preparation of nematode growth media and bacterial food sources, as well as procedures for nematode growth, synchronization, and treatment. We then describe procedures to assess dopaminergic neuronal death in vivo using fluorescence imaging.For complete details on the use and execution of this protocol, please refer to SenGupta et al. (2021).

Published
2022
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48. Meeting summary of The NYO3 5th NO-Age/AD meeting and the 1st Norway-UK joint meeting on ageing and dementia: recent progress on the mechanisms and interventional strategies

Author

Wang, He-Ling, primary, Siow, Richard, additional, Schmauck-Medina, Tomas, additional, Zhang, Jianying, additional, Sandset, Per Morten, additional, Filshie, Clare, additional, Lund, Øystein, additional, Partridge, Linda, additional, Bergersen, Linda Hildegard, additional, Juel Rasmussen, Lene, additional, Palikaras, Konstantinos, additional, Sotiropoulos, Ioannis, additional, Storm-Mathisen, Jon, additional, Rubinsztein, David C, additional, Spillantini, Maria Grazia, additional, De Zeeuw, Chris I, additional, Watne, Leiv Otto, additional, Vyhnalek, Martin, additional, Veverova, Katerina, additional, Liang, Kristina Xiao, additional, Tavernarakis, Nektarios, additional, Bohr, Vilhelm A, additional, Yokote, Koutaro, additional, Saarela, Janna, additional, Nilsen, Hilde, additional, Gonos, Efstathios S, additional, Scheibye-Knudsen, Morten, additional, Chen, Guobing, additional, Kato, Hisaya, additional, Selbæk, Geir, additional, Fladby, Tormod, additional, Nilsson, Per, additional, Simonsen, Anne, additional, Aarsland, Dag, additional, Lautrup, Sofie, additional, Ottersen, Ole Petter, additional, Cox, Lynne S, additional, and Fang, Evandro F, additional

Published
2024
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49. Atomic monolayer deposition on the surface of nanotube mechanical resonators

Author

Tavernarakis, Alexandros, Chaste, Julien, Eichler, Alexander, Ceballos, Gustavo, Gordillo, Maria Carmen, Boronat, Jordi, and Bachtold, Adrian

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

We studied monolayers of noble gas atoms (Xe, Kr, Ar, and Ne) deposited on individual ultra- clean suspended nanotubes. For this, we recorded the resonance frequency of the mechanical motion of the nanotube, since it provides a direct measure of the coverage. The latter is the number of adsorbed atoms divided by the number of the carbon atoms of the suspended nanotube. Monolayers formed when the temperature was lowered in a constant pressure of noble gas atoms. The coverage of Xe monolayers remained constant at 1/6 over a large temperature range. This finding reveals that Xe monolayers are solid phases with a triangular atomic arrangement, and are commensurate with the underlying carbon nanotube. By comparing our measurements to theoretical calculations, we identify the phases of Ar and Ne monolayers as fluids, and we tentatively describe Kr monolayers as solid phases. These results underscore that mechanical resonators made from single nanotubes are excellent probes for surface science.

Published
2014
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50. A surge in endogenous spermidine is essential for rapamycin-induced autophagy and longevity.

Author

Hofer, Sebastian J., Daskalaki, Ioanna, Abdellatif, Mahmoud, Stelzl, Ulrich, Sedej, Simon, Tavernarakis, Nektarios, Kroemer, Guido, and Madeo, Frank

Subjects
TRANSCRIPTION factors, LOW-calorie diet, SPERMIDINE, GENETIC translation, BIOSYNTHESIS
Abstract

Acute nutrient deprivation (fasting) causes an immediate increase in spermidine biosynthesis in yeast, flies, mice and humans, as corroborated in four independent clinical studies. This fasting-induced surge in spermidine constitutes the critical first step of a phylogenetically conserved biochemical cascade that leads to spermidine-dependent hypusination of EIF5A (eukaryotic translation initiation factor 5A), which favors the translation of the pro-macroautophagic/autophagic TFEB (transcription factor EB), and hence an increase in autophagic flux. We observed that genetic or pharmacological inhibition of the spermidine increase by inhibition of ODC1 (ornithine decarboxylase 1) prevents the pro-autophagic and antiaging effects of fasting in yeast, nematodes, flies and mice. Moreover, knockout or knockdown of the enzymes required for EIF5A hypusination abolish fasting-mediated autophagy enhancement and longevity extension in these organisms. Of note, autophagy and longevity induced by rapamycin obey the same rule, meaning that they are tied to an increase in spermidine synthesis. These findings indicate that spermidine is not only a "caloric restriction mimetic" in the sense that its supplementation mimics the beneficial effects of nutrient deprivation on organismal health but that it is also an obligatory downstream effector of the antiaging effects of fasting and rapamycin. Abbreviation: EIF5A: eukaryotic translation initiation factor 5A; IGF1: insulin like growth factor 1; MTOR: mechanistic target of rapamycin kinase; ODC1: ornithine decarboxylase 1; TFEB: transcription factor EB. [ABSTRACT FROM AUTHOR]

Published
2024
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