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2. Proposed Regulation Against Harmful Foreign Subsidies In The EU

Author

Lebrun, Bruno

Subjects
Industrial policy -- Evaluation -- Belgium, Foreign corporations -- Laws, regulations and rules, Subsidies -- Laws, regulations and rules, Competition (Economics) -- Laws, regulations and rules, Government regulation, Business, international
Abstract

On 5 May 2021, the European Commission (the 'Commission') proposed a legislation that regulates foreign subsidies causing some distortion of competition in the European Union (seeProposal for regulation). This major [...]

Published
2023

3. The Council Adopts The EU Regulation To Control Distortive Foreign Subsidies

Author

Lebrun, Bruno

Subjects
Subsidies -- Laws, regulations and rules -- International aspects, Government regulation, Business, international, European Union -- Powers and duties
Abstract

On 28 November 2022, the EU Council gave its final approval to the new Regulation on foreign subsidies distorting the EU internal market and is due to apply by mid-2023. [...]

Published
2023

6. International Anti-Trust

Author

Macias, Maria José Rodriguez, Rovira, Alfredo, Schoff, Paul, Reidlinger, Axel, Kühnert, Heinrich, Balthazar, Thibault, Lebrun, Bruno, Nogueria, Mário, de Souza, Ricardo Inglez, Drago, Bruno, Katz, Mark, Dinning, Jim, Lizana, Claudio, Rfos, Marcos, Pavic, Lorena, Wang, Peter, Zhang, Yizhe, Wolf, Gunmar, Clancy, Michael, Trabucchi, Maria, Fabre, Jéröme, Baldon, Clémentine, Genevois, Caroline, Weitbrecht, Andreas, Zuehlke, Susanne, Nagy-Koppany, Kornelia, Wldyawan, Prawoko, Ponco, Andrews, Philip, Fitzgerald, Gerald, Butler, Úna, Epstein, Eytan, Dolev-Green, Tamar, Morrison, Michelle, Pera, Alberto, Carpagnano, Michele, Ezaki, Shigeyoshi, Yun, Sai Ree, Jung, Youngjin, Jung, Sung Moo, Cardenas, Lucia Ojeda, Knibbeler, Winfred, Lorje, Nima, Pradhan, Devendra, Peterson, Andrew, Pilkington, Troy, Norum, Trygve, Sletten, Gaute, Arrus, Oscar, Vitorino, Antonio, Silva, Stéphanie Sa, Cvetkovic, Olga, Cabrera, Susana, Jörgens, Konstantin, Karlsson, Per, Dufva, Emma, Sommer, Patrick, Brunnschweiler, Stefan, Christen, Marquard, Lin, John, Lysenko, Denis, Nizhnik, Mariya, Kon, Stephen, Christian, Gordon, Rampling, Anna, Schaeffer, Fiona, Roberts, Christopher, Sickler, Jonathan, Webb, Claire, Cook, Robin, and Fruitman, David

Published
2009

7. International Antitrust

Author

Rovira, Alfredo, Macias, María José Rodríguez, Schoff, Paul, Mortensen, Jackie, Lebrun, Bruno, Balthazar, Thibault, Nogueria, Mário, de Souza, Ricardo Inglez, Drago, Bruno, Schmitt, Stefanie, Katz, Mark, Kearney, Elisa, Lizana, Claudio, Rios, Marcos, Henríquez, María José, Wang, Peter, Zhang, Yizhe, Colmenares, Mary Elena Lares, Wolf, Gunnar, Clancy, Michael, Rantala, Satu, Couadou, Cyrille, Fabre, Jérôme, Genevois, Caroline, Zuehlke, Susanne, Powell, Simon, Pong, Brian, Nagy-Koppany, Kornelia, Widyawan, Prawoko, Ponco, Andrews, Philip, FitzGerald, Gerald, Butler, Una, Epstein, Eytan, Dolev, Tamar, Pera, Alberto, Ezaki, Shigeyoshi, Yun, Sai Ree, Jung, Youngjin, Jung, Sung Moo, Cárdenas, Lucía Ojeda, Peterson, Andrew, Norum, Trygve, Bellido, Oscar Arrús, Najbauer, Lech, Cabrera, Susana, Sopeña, Vera, Lundström, Jakob, Göransson, Irina, Sommer, Patrick, Brunnschweiler, Stefan, Christen, Marquard, Niznik, Mariya, Lysenko, Denis, Kon, Stephen, Christian, Gordon, Dhir, Simran, Schaeffer, Fiona, Leto, Marisa, Yolkut, David, and Wagner, Justin

Published
2008

10. Blockade of Glial Connexin 43 Hemichannels Reduces Food Intake

Author

Guillebaud, Florent, Barbot, Manon, Barbouche, Rym, Brézun, Jean-Michel, Poirot, Kevin, Vasile, Flora, Lebrun, Bruno, Rouach, Nathalie, Dallaporta, Michel, Gaige, Stéphanie, Troadec, Jean-Denis, Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-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)-Aix Marseille Université (AMU), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Ependymoglial Cells, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, Article, brainstem, tanycytes, Eating, Mice, Solitary Nucleus, Animals, Homeostasis, hypothalamus, lcsh:QH301-705.5, ComputingMilieux_MISCELLANEOUS, Metabolic Syndrome, Neurons, [SCCO.NEUR]Cognitive science/Neuroscience, astrocytes, mimetic peptide, Peptide Fragments, Mice, Inbred C57BL, lcsh:Biology (General), Gene Expression Regulation, Connexin 43, sense organs, Energy Metabolism, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Neuroglia, Proto-Oncogene Proteins c-fos
Abstract

The metabolic syndrome, which comprises obesity and diabetes, is a major public health problem and the awareness of energy homeostasis control remains an important worldwide issue. The energy balance is finely regulated by the central nervous system (CNS), notably through neuronal networks, located in the hypothalamus and the dorsal vagal complex (DVC), which integrate nutritional, humoral and nervous information from the periphery. The glial cells&rsquo, contribution to these processes emerged few year ago. However, its underlying mechanism remains unclear. Glial connexin 43 hemichannels (Cx43 HCs) enable direct exchange with the extracellular space and can regulate neuronal network activity. In the present study, we sought to determine the possible involvement of glial Cx43 HCs in energy balance regulation. We here show that Cx43 is strongly expressed in the hypothalamus and DVC and is associated with glial cells. Remarkably, we observed a close apposition of Cx43 with synaptic elements in both the hypothalamus and DVC. Moreover, the expression of hypothalamic Cx43 mRNA and protein is modulated in response to fasting and diet-induced obesity. Functionally, we found that Cx43 HCs are largely open in the arcuate nucleus (ARC) from acute mice hypothalamic slices under basal condition, and significantly inhibited by TAT-GAP19, a mimetic peptide that specifically blocks Cx43 HCs activity. Moreover, intracerebroventricular (i.c.v.) TAT-GAP19 injection strongly decreased food intake, without further alteration of glycaemia, energy expenditures or locomotor activity. Using the immediate early gene c-Fos expression, we found that i.c.v. TAT-GAP19 injection induced neuronal activation in hypothalamic and brainstem nuclei dedicated to food intake regulation. Altogether, these results suggest a tonic delivery of orexigenic molecules associated with glial Cx43 HCs activity and a possible modulation of this tonus during fasting and obesity.

Published
2020
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14. Glial Endozepines Reverse High-Fat Diet-Induced Obesity by Enhancing Hypothalamic Response to Peripheral Leptin

Author

Guillebaud, Florent, primary, Duquenne, Manon, additional, Djelloul, Mehdi, additional, Pierre, Clément, additional, Poirot, Kevin, additional, Roussel, Guenièvre, additional, Riad, Seddik, additional, Lanfray, Damien, additional, Morin, Fabrice, additional, Jean, André, additional, Tonon, Marie-Christine, additional, Gaigé, Stéphanie, additional, Lebrun, Bruno, additional, Dallaporta, Michel, additional, Leprince, Jérôme, additional, Prevot, Vincent, additional, and Troadec, Jean-Denis, additional

Published
2020
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17. Purification, characterization, and synthesis of three novel toxins from the Chinese scorpion Buthus martensi, which act on K+ channels

Author

Romi-Lebrun, Regine, Lebrun, Bruno, Martin-Eauclaire, Marie-France, Ishiguro, Masaji, Escoubas, Pierre, Wu, Fang Qi, Hisada, Miki, Pongs, Olaf, and Nakajima, Terumi

Subjects
Scorpions -- Venom, Venom -- Research, Potassium channels -- Research, Ion channels -- Research, Neurotoxic agents -- Research, Biological sciences, Chemistry
Abstract

The venom of the Chinese scorpion Buthus martensi was purified and characterized for its content in toxins active on potassium ion channels. The physicochemical characterization of three toxins from Buthus martensi as well as their pharmacological properties toward the potassium ion channels were described. Results showed that the toxins are lethal neurotoxic agents in mice and potent inhibitors of the voltage-gated potassium ion channels.

Published
1997

22. Coal and steel treaty is no more: does it matter?

Author

Lebrun, Bruno and Croce, Ricardo

Subjects
Coal industry -- Laws, regulations and rules, Steel industry -- Laws, regulations and rules, Antitrust law -- Interpretation and construction, Acquisitions and mergers -- Laws, regulations and rules, Antitrust issue, Government regulation, Treaty Establishing the European Coal and Steel Community, 1951
Published
2002

23. Glial Endozepines Inhibit Feeding-Related Autonomic Functions by Acting at the Brainstem Level

Author

Guillebaud, Florent, primary, Girardet, Clémence, additional, Abysique, Anne, additional, Gaigé, Stéphanie, additional, Barbouche, Rym, additional, Verneuil, Jérémy, additional, Jean, André, additional, Leprince, Jérôme, additional, Tonon, Marie-Christine, additional, Dallaporta, Michel, additional, Lebrun, Bruno, additional, and Troadec, Jean-Denis, additional

Published
2017
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24. Acute oral metformin enhances satiation and activates brainstem nesfatinergic neurons

Author

Troadec, Jean Denis, Rouquet, Thaïs, Clément, Pierre, Gaigé, Stéphanie, Tardivel, Catherine, Roux, Julien, Dallaporta, Michel, Bariohay, Bruno, Troadec, Jean-Denis, Lebrun, Bruno, Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biomeostasis, Nutritional Behavior and Metabolic Disorders, Physiologie et physiopathologie du système nerveux somato-moteur et neurovégétatif (PPSN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU), Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bureau eau, sols et économie circulaire - MAA/DGPE/SDPE, Ministère de l'Agriculture, de l'Alimentation et de la Pêche, Laboratoire de Géologie, Muséum National d'Histoire Naturelle, Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Troadec, Jean denis

Subjects
[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, [SDV.TOX.TCA] Life Sciences [q-bio]/Toxicology/Toxicology and food chain, [SCCO.NEUR]Cognitive science/Neuroscience, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SCCO.NEUR] Cognitive science/Neuroscience, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2014

25. Acute oral metformin enhances satiation and activates brainstem nesfatinergic neurons

Author

Rouquet, Thaïs, Clément, Pierre, Gaigé, Stéphanie, Tardivel, Catherine, Roux, Julien, Dallaporta, Michel, Bariohay, Bruno, Troadec, Jean-Denis, Lebrun, Bruno, Physiologie et physiopathologie du système nerveux somato-moteur et neurovégétatif (PPSN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU), Biomeostasis, Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Neurons, c-Fos, db, NUCB2, Appetite Regulation, db mice, digestive, oral, and skin physiology, nesfatin-1, POMC, Mice, Transgenic, Nerve Tissue Proteins, Satiation, Metformin, Mice, Inbred C57BL, Eating, Mice, Taste, energy expenditure, Animals, Hypoglycemic Agents, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Proto-Oncogene Proteins c-fos
Abstract

International audience; Objective: The study was designed to determine metformin effects on meal pattern, gastric emptying, energy expenditure, and to identify metformin-sensitive neurons and their phenotype. Methods: This study was performed on C57BL/6J and obese/diabetic (db/db) mice. Metformin (300 mg/kg) was administered by oral gavage. Food intake, meal pattern, oxygen consumption (VO2), and carbon dioxide production (VCO2) were obtained using an Oxylet Physiocage System. Gastric emptying assay and real-time RT-PCR from dorsal vagal complex extracts were also performed. C-Fos expression was used as a marker of neuronal activation. Phenotypic characterization of activated neurons was performed using either proopiomelanocortin (POMC)-Tau-Topaz GFP transgenic mice or NUCB2/nesfatin-1 and tyrosine hydroxylase (TH) labeling. Results: Acute per os metformin treatment slowed down gastric emptying, reduced meal size, but not meal number in a leptin-independent manner, and transiently decreased energy expenditure in a leptin-dependent manner. Metformin specifically activated central circuitry within the brainstem, independently of vagal afferents. Finally, while POMC neurons seemed sparsely activated, we report that a high proportion of the c-Fos positive cells were nesfatinergic neurons, some of which coexpressing TH. Conclusions: Altogether, these results show that metformin modifies satiation by activating brainstem circuitry and suggest that NUCB2/nesfatin-1 could be involved in this metformin effect

Published
2014
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26. Modification of energy balance induced by the food contaminant T-2 toxin: A multimodal gut-to-brain connection

Author

Guillebaud, Florent, Barbouche, Rym, Troadec, Jean-Denis, Gaigé, Stéphanie, Djelloul, Mehdi, Tardivel, Catherine, Airault, Coraline, Félix, Bernadette, Jean, André, Lebrun, Bruno, Jean, Jean-Denis, Dallaporta, Michel, Physiologie et physiopathologie du système nerveux somato-moteur et neurovégétatif (PPSN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU), Département AlimH, INRA U1189, Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Département Alimentation Humaine INRA (ALIM-H), Institut National de la Recherche Agronomique (INRA)-PRES Université Nantes Angers Le Mans (UNAM), and Airault, Coraline

Subjects
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2014

27. Modification of energy balance induced by the food contaminant T-2 toxin: A multimodal gut-to-brain connection

Author

Troadec, Jean Denis, Gaigé, Stéphanie, Djelloul, Mehdi, Tardivel, Catherine, Airault, Coraline, Félix, Bernadette, Jean, André, Lebrun, Bruno, Jean, Jean-Denis, Dallaporta, Michel, Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiologie et physiopathologie du système nerveux somato-moteur et neurovégétatif (PPSN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU), Cell Stem Cell Laboratory for CNS Disease Modeling, Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix-Marseille Université - Faculté des Sciences (AMU SCI), Aix Marseille Université (AMU), Département AlimH, INRA U1189, and Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)

Subjects
[SCCO.NEUR]Cognitive science/Neuroscience, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2014

28. Brain-derived neurotrophic factor/TrkB signaling regulates daily ă astroglial plasticity in the suprachiasmatic nucleus: ă Electron-microscopic evidence in mouse

Author

Girardet, Clémence, Lebrun, Bruno, Cabirol-Pol, Marie-Jeanne, ă Tardivel, Catherine, François-Bellan, Anne-Marie, Becquet, Denis ă, Bosler, Olivier, Physiologie et physiopathologie du système nerveux somato-moteur et neurovégétatif (PPSN), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)

Subjects
nervous system, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], sense organs
Abstract

International audience; Synchronization of circadian rhythms to the 24-h light/dark (L/D) cycle ă is associated with daily rearrangements of the neuronal-glial network of ă the suprachiasmatic nucleus of the hypothalamus (SCN), the central ă master clock orchestrating biological functions in mammals. These ă anatomical plastic events involve neurons synthesizing vasoactive ă intestinal peptide (VIP), known as major integrators of photic signals ă in the retinorecipient region of the SCN. Using an analog-sensitive ă kinase allele murine model (TrkBF616A), we presently show that the ă pharmacological blockade of the tropomyosin-related kinase receptor type ă B (TrkB), the high-affinity receptor of brain-derived neurotrophic ă factor (BDNF), abolished day/night changes in the dendrite enwrapping of ă VIP neurons by astrocytic processes (glial coverage), used as an index ă of SCN plasticity on electron-microscopic sections. Therefore, the ă BDNF/TrkB signaling pathway exerts a permissive role on the ă ultrastructural rearrangements that occur in SCN under L/D alternance, ă an action that could be a critical determinant of the well-established ă role played by BDNF in the photic regulation of the SCN. In contrast, ă the extent of glial coverage of non-VIP neighboring dendrites was not ă different at daytime and nighttime in TrkBF616A mice submitted to TrkB ă inactivation or not receiving any pharmacological treatment. These data ă not only show that BDNF regulates SCN structural plasticity across the ă 24-h cycle but also reinforce the view that the daily changes in SCN ă architecture subserve the light synchronization process.

Published
2013
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29. The Food-Contaminant Deoxynivalenol Modifies Eating by Targeting Anorexigenic Neurocircuitry

Author

Girardet, Clémence, primary, Bonnet, Marion S., additional, Jdir, Rajae, additional, Sadoud, Medhi, additional, Thirion, Sylvie, additional, Tardivel, Catherine, additional, Roux, Julien, additional, Lebrun, Bruno, additional, Wanaverbecq, Nicolas, additional, Mounien, Lourdes, additional, Trouslard, Jérôme, additional, Jean, André, additional, Dallaporta, Michel, additional, and Troadec, Jean-Denis, additional

Published
2011
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34. A new class of scorpion toxin binding sites related to an A‐type K+ channel: pharmacological characterization and localization in rat brain

Author

Vacher, Hélène, primary, Romi-Lebrun, Régine, additional, Mourre, Christiane, additional, Lebrun, Bruno, additional, Kourrich, Said, additional, Masméjean, Frédérique, additional, Nakajima, Terumi, additional, Legros, Christian, additional, Crest, Marcel, additional, Bougis, Pierre E., additional, and Martin-Eauclaire, Marie-France, additional

Published
2001
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45. Structural and functional consequences of the presence of a fourth disulfide bridge in the scorpion short toxins: Solution structure of the potassium channel inhibitor HsTX1.

Author

Savarin, Philippe, Romi-Lebrun, Régine, Zinn-Justin, Sophie, Gilquin, Bernard, Ménez, André, Lebrun, Bruno, and Nakajima, Terumi

Abstract

We have determined the three-dimensional structure of the potassium channel inhibitor HsTX1, using nuclear magnetic resonance and molecular modeling. This protein belongs to the scorpion short toxin family, which essentially contains potassium channel blockers of 29 to 39 amino acids and three disulfide bridges. It is highly active on voltage-gated Kv1.3 potassium channels. Furthermore, it has the particularity to possess a fourth disulfide bridge. We show that HsTX1 has a fold similar to that of the three-disulfide-bridged toxins and conserves the hydrophobic core found in the scorpion short toxins. Thus, the fourth bridge has no influence on the global conformation of HsTX1. Most residues spatially analogous to those interacting with voltage-gated potassium channels in the three-disulfide-bridged toxins are conserved in HsTX1. Thus, we propose that Tyr21, Lys23, Met25, and Asn26 are involved in the biological activity of HsTX1. As an additional positively charged residue is always spatially close to the aromatic residue in toxins blocking the voltage-gated potassium channels, and as previous mutagenesis experiments have shown the critical role played by the C-terminus in HsTX1, we suggest that Arg33 is also important for the activity of the four disulfide-bridged toxin. Docking calculations confirm that, if Lys23 and Met25 interact with the GYGDMH motif of Kv1.3, Arg33 can contact Asp386 and, thus, play the role of the additional positively charged residue of the toxin functional site. This original configuration of the binding site of HsTX1 for Kv1.3, if confirmed experimentally, offers new structural possibilities for the construction of a molecule blocking the voltage-gated potassium channels. [ABSTRACT FROM AUTHOR]

Published
1999
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46. Slow inhibition of Na+ current in crayfish axons by 2-(1non-8enyl)-5-(1non-8enyl)pyrrolidine...

Author

Lebrun, Bruno and Cattaert, Daniel

Subjects
*EXPERIMENTAL biology, *PYRROLIDINE, *PROCAMBARUS clarkii
Abstract

Investigates the mechanism of action of 2-(1non-8enyl)-5-(1non-8enyl)pyrrolidine (Pyr9), a synthetic derivative of 2,5-dialkylpyrrolidines, in vitro on preparations of the ventral nerve cord of the crayfish Procambarus clarkii. Study methodology; Results of study; Indication that Pyr9 blocks spike conduction without affecting the resting potential; Discussion of the results.

Published
1997
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47. Characterization of four toxins from <em>Buthus martensi</em> scorpion venom, which act on apamin-sensitive Ca2+-activated K+ channels.

Author

Romi-Lebrun, Regine, Martin-Eauclaire, Marie-France, Escoubas, Pierre, Fang Qi Wu, Lebrun, Bruno, Hisada, Miki, and Nakajima, Terumi

Subjects
BUTHUS, SCORPIONS, SCORPION venom, NEUROTOXIC agents, MASS spectrometry, POTASSIUM channels, CAPILLARY electrophoresis
Abstract

Four peptidyl inhibitors of the small-conductance Ca2+-activated K+ channels (SKca) have been isolated from the venom of the Chinese scorpion Buthus martensi. These peptides were identified by screening C18 HPLC fractions of the crude venom by means of mass analysis by matrix-assisted-laser-desorption/ionization time-of-flight mass spectrometry, and toxicological tests in mice. Edman degradation analysis of the purified peptides showed sequences of 28–31 amino acids including 6 cysteine residues. Three of the sequences were similar to the P01 peptides from Androctonus scorpions, showing 76% sequence similarity for the most closely related, named BmP01. and 46% for the other two, named BmP02 and BmP03. Like the P01 peptides, these molecules showed a low toxic activity in mice after intracerebro-ventricular injection, and competed (K0.5 > 1 μM) with iodinated apamin for binding to its receptor site from rat brain, which has been proved to be the SKca channels. The fourth toxin was structurally related to the P05/leiurotixin I toxin family, with 90% similarity, and was named BmP05. This toxin exhibited a high toxic activity with lethal effects in mice. Due to its small representation in the venom [less than 0.01% (by mass)], its biological properties have been assessed on the synthetic analogue of BmP05. which was assembled on a solid phase by means of Fmoc methodology. The synthetic peptide was physicochemically identical to the natural peptide, as shown by comparison of their molecular masses and amino acid compositions, and by their coelution after coinjection on capillary electrophoresis. These results confirmed the primary structure of BmP05 including an amidated C-terminus. Similarly to natural BmP05, synthetic BmP05 produced toxic and lethal effects after intracerebroventricular injection in mice (LD50 = 37 rig). and was able to compete with iodinated apamin for binding to its receptor in rat brain (K0.5 = 20 pM). [ABSTRACT FROM AUTHOR]

Published
1997
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48. A new class of scorpion toxin binding sites related to an A‐type K+channel: pharmacological characterization and localization in rat brain

Author

Vacher, Hélène, Romi-Lebrun, Régine, Mourre, Christiane, Lebrun, Bruno, Kourrich, Said, Masméjean, Frédérique, Nakajima, Terumi, Legros, Christian, Crest, Marcel, Bougis, Pierre E., and Martin-Eauclaire, Marie-France

Abstract

A new scorpion toxin (3751.8 Da) was isolated from the Buthus martensivenom, sequenced and chemically synthesized (sBmTX3). The A‐type current of striatum neurons in culture completely disappeared when 1 μM sBmTX3 was applied (Kd=54 nM), whereas the sustained K+current was unaffected. 125I‐sBmTX3 specifically bound to rat brain synaptosomes (maximum binding=14 fmol mg−1of protein, Kd=0.21 nM). A panel of toxins yet described as specific ligands for K+channels were unable to compete with 125I‐sBmTX3. A high density of 125I‐sBmTX3 binding sites was found in the striatum, hippocampus, superior colliculus, and cerebellum in the adult rat brain.

Published
2001
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49. A new class of scorpion toxin binding sites related to an A-type K +channel: pharmacological characterization and localization in rat brain

Author

Vacher, Hélène, Romi-Lebrun, Régine, Mourre, Christiane, Lebrun, Bruno, Kourrich, Said, Masméjean, Frédérique, Nakajima, Terumi, Legros, Christian, Crest, Marcel, Bougis, Pierre E., and Martin-Eauclaire, Marie-France

Abstract

A new scorpion toxin (3751.8 Da) was isolated from the Buthus martensivenom, sequenced and chemically synthesized (sBmTX3). The A-type current of striatum neurons in culture completely disappeared when 1 μM sBmTX3 was applied ( Kd=54 nM), whereas the sustained K +current was unaffected. 125I-sBmTX3 specifically bound to rat brain synaptosomes (maximum binding=14 fmol mg −1of protein, Kd=0.21 nM). A panel of toxins yet described as specific ligands for K +channels were unable to compete with 125I-sBmTX3. A high density of 125I-sBmTX3 binding sites was found in the striatum, hippocampus, superior colliculus, and cerebellum in the adult rat brain.

Published
2001
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50. Commission v EnBW Energie: Non-Disclosure of Leniency Documents.

Author

Lebrun, Bruno and Bersou, Laure

Subjects
CARTELS, LEGAL documents, ACTIONS & defenses (Law)
Abstract

The European Commission may reject the request by a plaintiff in a national follow-on proceeding to access the documents discovered in the context of an EU cartel proceeding.The Court of Justice decided that the European Commission may reject the request by a plaintiff in a national follow-on proceeding to access the documents discovered in the context of an EU cartel proceeding. For the Court of the Justice, there is a general presumption that such an access may jeopardize the interests protected by the regulations implementing the EU antitrust rules. This judgment limits the access to DG COMP's documents defined under CDC v Commission (T-437/08, CDC v Commission, 15 December 2011) and may introduce another standard compared with the test defined under Pfleiderer to access documents detained by national competition authorities (C-360/09, Pfleiderer, 14 June 2011). In these cases, the Court of Justice decided that a plaintiff in a follow-on action could, under the supervision of the national court in charge of the case, access the documents of a national competition authority, including those submitted under the leniency proceeding, if they are necessary to demonstrate the fault and the scope of the damage suffered. [ABSTRACT FROM PUBLISHER]

Published
2014
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