Functional Characterization of a Novel Family of Acetylcholine-Gated Chloride Channels in Schistosoma mansoni

Acetylcholine is the canonical excitatory neurotransmitter of the mammalian neuromuscular system. However, in the trematode parasite Schistosoma mansoni, cholinergic stimulation leads to muscle relaxation and a flaccid paralysis, suggesting an inhibitory mode of action. Information about the pharmacological mechanism of this inhibition is lacking. Here, we used a combination of techniques to assess the role of cholinergic receptors in schistosome motor function. The neuromuscular effects of acetylcholine are typically mediated by gated cation channels of the nicotinic receptor (nAChR) family. Bioinformatics analyses identified numerous nAChR subunits in the S. mansoni genome but, interestingly, nearly half of these subunits carried a motif normally associated with chloride-selectivity. These putative schistosome acetylcholine-gated chloride channels (SmACCs) are evolutionarily divergent from those of nematodes and form a unique clade within the larger family of nAChRs. Pharmacological and RNA interference (RNAi) behavioral screens were used to assess the role of the SmACCs in larval motor function. Treatment with antagonists produced the same effect as RNAi suppression of SmACCs; both led to a hypermotile phenotype consistent with abrogation of an inhibitory neuromuscular mediator. Antibodies were then generated against two of the SmACCs for use in immunolocalization studies. SmACC-1 and SmACC-2 localize to regions of the peripheral nervous system that innervate the body wall muscles, yet neither appears to be expressed directly on the musculature. One gene, SmACC-1, was expressed in HEK-293 cells and characterized using an iodide flux assay. The results indicate that SmACC-1 formed a functional homomeric chloride channel and was activated selectively by a panel of cholinergic agonists. The results described in this study identify a novel clade of nicotinic chloride channels that act as inhibitory modulators of schistosome neuromuscular function. Additionally, the iodide flux assay used to characterize SmACC-1 represents a new high-throughput tool for drug screening against these unique parasite ion channels

Modelling spectral and timing properties of accreting black holes: the hybrid hot flow paradigm

The general picture that emerged by the end of 1990s from a large set of optical and X-ray, spectral and timing data was that the X-rays are produced in the innermost hot part of the accretion flow, while the optical/infrared (OIR) emission is mainly produced by the irradiated outer thin accretion disc. Recent multiwavelength observations of Galactic black hole transients show that the situation is not so simple. Fast variability in the OIR band, OIR excesses above the thermal emission and a complicated interplay between the X-ray and the OIR light curves imply that the OIR emitting region is much more compact. One of the popular hypotheses is that the jet contributes to the OIR emission and even is responsible for the bulk of the X-rays. However, this scenario is largely ad hoc and is in contradiction with many previously established facts. Alternatively, the hot accretion flow, known to be consistent with the X-ray spectral and timing data, is also a viable candidate to produce the OIR radiation. The hot-flow scenario naturally explains the power-law like OIR spectra, fast OIR variability and its complex relation to the X-rays if the hot flow contains non-thermal electrons (even in energetically negligible quantities), which are required by the presence of the MeV tail in Cyg X-1. The presence of non-thermal electrons also lowers the equilibrium electron temperature in the hot flow model to <100 keV, making it more consistent with observations. Here we argue that any viable model should simultaneously explain a large set of spectral and timing data and show that the hybrid (thermal/non-thermal) hot flow model satisfies most of the constraints.Comment: 26 pages, 13 figures. To be published in the Space Science Reviews and as hard cover in the Space Sciences Series of ISSI - The Physics of Accretion on to Black Holes (Springer Publisher

Evidence that the negative BOLD response is neuronal in origin: a simultaneous EEG–BOLD–CBF study in humans

Unambiguous interpretation of changes in the BOLD signal is challenging because of the complex neurovascular coupling that translates changes in neuronal activity into the subsequent haemodynamic response. In particular, the neurophysiological origin of the negative BOLD response (NBR) remains incompletely understood. Here, we simultaneously recorded BOLD, EEG and cerebral blood flow (CBF) responses to 10 s blocks of unilateral median nerve stimulation (MNS) in order to interrogate the NBR. Both negative BOLD and negative CBF responses to MNS were observed in the same region of the ipsilateral primary sensorimotor cortex (S1/M1) and calculations showed that MNS induced a decrease in the cerebral metabolic rate of oxygen consumption (CMRO2) in this NBR region. The ∆CMRO2/∆CBF coupling ratio (n) was found to be significantly larger in this ipsilateral S1/M1 region (n = 0.91 ± 0.04, M = 10.45%) than in the contralateral S1/M1 (n = 0.65 ± 0.03, M = 10.45%) region that exhibited a positive BOLD response (PBR) and positive CBF response, and a consequent increase in CMRO2 during MNS. The fMRI response amplitude in ipsilateral S1/M1 was negatively correlated with both the power of the 8–13 Hz EEG mu oscillation and somatosensory evoked potential amplitude. Blocks in which the largest magnitude of negative BOLD and CBF responses occurred therefore showed greatest mu power, an electrophysiological index of cortical inhibition, and largest somatosensory evoked potentials. Taken together, our results suggest that a neuronal mechanism underlies the NBR, but that the NBR may originate from a different neurovascular coupling mechanism to the PBR, suggesting that caution should be taken in assuming the NBR simply represents the neurophysiological inverse of the PBR

Global signal modulation of single-trial fMRI response variability: effect on positive vs negative BOLD response relationship

In functional magnetic resonance imaging (fMRI), the relationship between positive BOLD responses (PBRs) and negative BOLD responses (NBRs) to stimulation is potentially informative about the balance of excitatory and inhibitory brain responses in sensory cortex. In this study, we performed three separate experiments delivering visual, motor or somatosensory stimulation unilaterally, to one side of the sensory field, to induce PBR and NBR in opposite brain hemispheres. We then assessed the relationship between the evoked amplitudes of contralateral PBR and ipsilateral NBR at the level of both single-trial and average responses. We measure single-trial PBR and NBR peak amplitudes from individual time-courses, and show that they were positively correlated in all experiments. In contrast, in the average response across trials the absolute magnitudes of both PBR and NBR increased with increasing stimulus intensity, resulting in a negative correlation between mean response amplitudes. Subsequent analysis showed that the amplitude of single-trial PBR was positively correlated with the BOLD response across all grey-matter voxels and was not specifically related to the ipsilateral sensory cortical response. We demonstrate that the global component of this single-trial response modulation could be fully explained by voxel-wise vascular reactivity, the BOLD signal standard deviation measured in a separate resting-state scan (resting state fluctuation amplitude, RSFA). However, bilateral positive correlation between PBR and NBR regions remained. We further report that modulations in the global brain fMRI signal cannot fully account for this positive PBR-NBR coupling and conclude that the local sensory network response reflects a combination of superimposed vascular and neuronal signals. More detailed quantification of physiological and noise contributions to the BOLD signal is required to fully understand the trial-by-trial PBR and NBR relationship compared with that of average responses

ϒ production in p–Pb collisions at √sNN=8.16 TeV

ϒ production in p–Pb interactions is studied at the centre-of-mass energy per nucleon–nucleon collision √sNN = 8.16 TeV with the ALICE detector at the CERN LHC. The measurement is performed reconstructing bottomonium resonances via their dimuon decay channel, in the centre-of-mass rapidity intervals 2.03 < ycms < 3.53 and −4.46 < ycms < −2.96, down to zero transverse momentum. In this work, results on the ϒ(1S) production cross section as a function of rapidity and transverse momentum are presented. The corresponding nuclear modification factor shows a suppression of the ϒ(1S) yields with respect to pp collisions, both at forward and backward rapidity. This suppression is stronger in the low transverse momentum region and shows no significant dependence on the centrality of the interactions. Furthermore, the ϒ(2S) nuclear modification factor is evaluated, suggesting a suppression similar to that of the ϒ(1S). A first measurement of the ϒ(3S) has also been performed. Finally, results are compared with previous ALICE measurements in p–Pb collisions at √sNN = 5.02 TeV and with theoretical calculations.publishedVersio

(Anti-)deuteron production in pp collisions at 1as=13TeV

The study of (anti-)deuteron production in pp collisions has proven to be a powerful tool to investigate the formation mechanism of loosely bound states in high-energy hadronic collisions. In this paper the production of (anti-)deuterons is studied as a function of the charged particle multiplicity in inelastic pp collisions at s=13 TeV using the ALICE experiment. Thanks to the large number of accumulated minimum bias events, it has been possible to measure (anti-)deuteron production in pp collisions up to the same charged particle multiplicity (d Nch/ d \u3b7 3c 26) as measured in p\u2013Pb collisions at similar centre-of-mass energies. Within the uncertainties, the deuteron yield in pp collisions resembles the one in p\u2013Pb interactions, suggesting a common formation mechanism behind the production of light nuclei in hadronic interactions. In this context the measurements are compared with the expectations of coalescence and statistical hadronisation models (SHM)

Multiplicity dependence of (anti-)deuteron production in pp collisions at root s=7 TeV

none1019siIn this letter, the production of deuterons and anti-deuterons in pp collisions at root s = 7 TeV is studied as a function of the charged-particle multiplicity density at mid-rapidity with the ALICE detector at the LHC. Production yields are measured at mid-rapidity in five multiplicity classes and as a function of the deuteron transverse momentum (p(T)). The measurements are discussed in the context of hadron-coalescence models. The coalescence parameter B-2, extracted from the measured spectra of (anti-)deuteronsand primary (anti-)protons, exhibits no significant p(T)-dependence for p(T) < 3 GeV/c, in agreement with the expectations of a simple coalescence picture. At fixed transverse momentum per nucleon, the B-2 parameter is found to decrease smoothly from low multiplicity pp to Pb-Pb collisions, in qualitative agreement with more elaborate coalescence models. The measured mean transverse momentum of (anti-)deuterons in pp is not reproduced by the Blast-Wave model calculations that simultaneously describe pion, kaon and proton spectra, in contrast to central Pb-Pb collisions. The ratio between the p(T)-integrated yield of deuterons to protons, d/p, is found to increase with the charged-particle multiplicity, as observed in inelastic pp collisions at different centre-of-mass energies. The d/p ratios are reported in a wide range, from the lowest to the highest multiplicity values measured in pp collisions at the LHC. (C) 2019 The Author(s). Published by Elsevier B.VnoneAcharya, S.; Acosta, F. T.; Adamova, D.; Adhya, S. P.; Adler, A.; Adolfsson, J.; Aggarwal, M. M.; Rinella, G. Aglieri; Agnello, M.; Ahammed, Z.; Ahmad, S.; Ahn, S. U.; Aiola, S.; Akindinov, A.; Al-Turany, M.; Alam, S. N.; Albuquerque, D. S. D.; Aleksandrov, D.; Alessandro, B.; Alfanda, H. M.; Alfaro Molina, R.; Ali, B.; Ali, Y.; Alici, A.; Alkin, A.; Alme, J.; Alt, T.; Altenkamper, L.; Altsybeev, I; Anaam, M. N.; Andrei, C.; Andreou, D.; Andrews, H. A.; Andronic, A.; Angeletti, M.; Anguelov, V; Anson, C.; Anticic, T.; Antinori, F.; Antonioli, P.; Anwar, R.; Apadula, N.; Aphecetche, L.; Appelshaeuser, H.; Arcelli, S.; Arnaldi, R.; Arratia, M.; Arsene, I. C.; Arslandok, M.; Augustinus, A.; Averbeck, R.; Azmi, M. D.; Badala, A.; Baek, Y. W.; Bagnasco, S.; Bailhache, R.; Bala, R.; Baldisseri, A.; Ball, M.; Baral, R. C.; Barbera, R.; Barioglio, L.; Barnafoldi, G. G.; Barnby, L. S.; Barret, V; Bartalini, P.; Barth, K.; Bartsch, E.; Bastid, N.; Basu, S.; Batigne, G.; Batyunya, B.; Batzing, P. C.; Bauri, D.; Bazo Alba, J. L.; Bearden, I. G.; Bedda, C.; Behera, N. K.; Belikov, I; Bellini, F.; Bello Martinez, H.; Bellwied, R.; Beltran, L. G. E.; Belyaev, V; Bencedi, G.; Beole, S.; Bercuci, A.; Berdnikov, Y.; Berenyi, D.; Bertens, R. A.; Berzano, D.; Betev, L.; Bhasin, A.; Bhat, I. R.; Bhatt, H.; Bhattacharjee, B.; Bianchi, A.; Bianchi, L.; Bianchi, N.; Bielcik, J.; Bielcikova, J.; Bilandzic, A.; Biro, G.; Biswas, R.; Biswas, S.; Blair, J. T.; Blau, D.; Blume, C.; Boca, G.; Bock, F.; Bogdanov, A.; Boldizsar, L.; Bolozdynya, A.; Bombara, M.; Bonomi, G.; Bonora, M.; Borel, H.; Borissov, A.; Borri, M.; Botta, E.; Bourjau, C.; Bratrud, L.; Braun-Munzinger, P.; Bregant, M.; Broker, T. A.; Broz, M.; Brucken, E. J.; Bruna, E.; Bruno, G. E.; Buckland, M. D.; Budnikov, D.; Buesching, H.; Bufalino, S.; Buhler, P.; Buncic, P.; Busch, O.; Buthelezi, Z.; Butt, J. B.; Buxton, J. T.; Caffarri, D.; Caines, H.; Caliva, A.; Calvo Villar, E.; Camacho, R. S.; Camerini, P.; Capon, A. A.; Carnesecchi, F.; Castellanos, J. Castillo; Castro, A. J.; Casula, E. A. R.; Sanchez, C. Ceballos; Chakraborty, P.; Chandra, S.; Chang, B.; Chang, W.; Chapeland, S.; Chartier, M.; Chattopadhyay, S.; Chauvin, A.; Cheshkov, C.; Cheynis, B.; Barroso, V. Chibante; Chinellato, D. D.; Cho, S.; Chochula, P.; Chowdhury, T.; Christakoglou, P.; Christensen, C. H.; Christiansen, P.; Chujo, T.; Cicalo, C.; Cifarelli, L.; Cindolo, F.; Cleymans, J.; Colamaria, F.; Colella, D.; Collu, A.; Colocci, M.; Concas, M.; Balbastre, G. Conesa; del Valle, Z. Conesa; Contin, G.; Contreras, J. G.; Cormier, T. M.; Morales, Y. Corrales; Cortese, P.; Cosentino, M. R.; Costa, F.; Costanza, S.; Crkovska, J.; Crochet, P.; Cuautle, E.; Cunqueiro, L.; Dabrowski, D.; Dahms, T.; Dainese, A.; Damas, F. P. A.; Dani, S.; Danisch, M. C.; Danu, A.; Das, D.; Das, I; Das, S.; Dash, A.; Dash, S.; Dashi, A.; De, S.; De Caro, A.; de Cataldo, G.; de Conti, C.; de Cuveland, J.; De Falco, A.; De Gruttola, D.; De Marco, N.; De Pasquale, S.; De Souza, R. D.; Degenhardt, H. F.; Deisting, A.; Deloff, A.; Delsanto, S.; Dhankher, P.; Di Bari, D.; Di Mauro, A.; Diaz, R. A.; Dietel, T.; Dillenseger, P.; Ding, Y.; Divia, R.; Djuvsland, O.; Dobrin, A.; Domenicis Gimenez, D.; Doenigus, B.; Dordic, O.; Dubey, A. K.; Dubla, A.; Dudi, S.; Duggal, A. K.; Dukhishyam, M.; Dupieux, P.; Ehlers, R. J.; Elia, D.; Engel, H.; Epple, E.; Erazmus, B.; Erhardt, F.; Erokhin, A.; Ersdal, M. R.; Espagnon, B.; Eulisse, G.; Eum, J.; Evans, D.; Evdokimov, S.; Fabbietti, L.; Faggin, M.; Faivre, J.; Fantoni, A.; Fasel, M.; Feldkamp, L.; Feliciello, A.; Feofilov, G.; Fernandez Tellez, A.; Ferrero, A.; Ferretti, A.; Festanti, A.; Feuillard, V. J. G.; Figiel, J.; Filchagin, S.; Finogeev, D.; Fionda, F. M.; Fiorenza, G.; Flor, F.; Floris, M.; Foertsch, S.; Foka, P.; Fokin, S.; Fragiacomo, E.; Francisco, A.; Frankenfeld, U.; Fronze, G. G.; Fuchs, U.; Furget, C.; Furs, A.; Girard, M. Fusco; Gaardhoje, J. J.; Gagliardi, M.; Gago, A. M.; Gajdosova, K.; Galvan, C. D.; Ganoti, P.; Garabatos, C.; Garcia-Solis, E.; Garg, K.; Gargiulo, C.; Garner, K.; Gasik, P.; Gauger, E. F.; Gay Ducati, M. B.; Germain, M.; Ghosh, J.; Ghosh, P.; Ghosh, S. K.; Gianotti, P.; Giubellino, P.; Giubilato, P.; Glaessel, P.; Gomez Coral, D. M.; Ramirez, A. Gomez; Gonzalez, V; Gonzalez-Zamora, P.; Gorbunov, S.; Gorlich, L.; Gotovac, S.; Grabski, V; Graczykowski, L. K.; Graham, K. L.; Greiner, L.; Grelli, A.; Grigoras, C.; Grigoriev, V; Grigoryan, A.; Grigoryan, S.; Gronefeld, J. M.; Grosa, F.; Grosse-Oetringhaus, J. F.; Grosso, R.; Guernane, R.; Guerzoni, B.; Guittiere, M.; Gulbrandsen, K.; Gunji, T.; Gupta, A.; Gupta, R.; Guzman, I. B.; Haake, R.; Habib, M. K.; Hadjidakis, C.; Hamagaki, H.; Hamar, G.; Hamid, M.; Hamon, J. C.; Hannigan, R.; Haque, M. R.; Harlenderova, A.; Harris, J. W.; Harton, A.; Hassan, H.; Hatzifotiadou, D.; Hauer, P.; Hayashi, S.; Heckel, S. T.; Hellbaer, E.; Helstrup, H.; Herghelegiu, A.; Hernandez, E. G.; Herrera Corral, G.; Herrmann, F.; Hetland, K. F.; Hilden, T. E.; Hillemanns, H.; Hills, C.; Hippolyte, B.; Hohlweger, B.; Horak, D.; Hornung, S.; Hosokawa, R.; Hota, J.; Hristov, P.; Huang, C.; Hughes, C.; Huhn, P.; Humanic, T. J.; Hushnud, H.; Husova, L. A.; Hussain, N.; Hussain, T.; Hutter, D.; Hwang, D. S.; Iddon, J. P.; Ilkaev, R.; Inaba, M.; Ippolitov, M.; Islam, M. S.; Ivanov, M.; Ivanov, V; Izucheev, V; Jacak, B.; Jacazio, N.; Jacobs, P. M.; Jadhav, M. B.; Jadlovska, S.; Jadlovsky, J.; Jaelani, S.; Jahnke, C.; Jakubowska, M. J.; Janik, M. A.; Jercic, M.; Jevons, O.; Bustamante, R. T. Jimenez; Jin, M.; Jones, P. G.; Jusko, A.; Kalinak, P.; Kalweit, A.; Kang, J. H.; Kaplin, V; Kar, S.; Uysal, A. Karasu; Karavichev, O.; Karavicheva, T.; Karczmarczyk, P.; Karpechev, E.; Kebschull, U.; Keidel, R.; Keil, M.; Ketzer, B.; Khabanova, Z.; Khan, A. M.; Khan, S.; Khan, S. A.; Khanzadeev, A.; Kharlov, Y.; Khatun, A.; Khuntia, A.; Kielbowicz, M. M.; Kileng, B.; Kim, B.; Kim, D.; Kim, D. J.; Kim, E. J.; Kim, H.; Kim, J. S.; Kim, J.; Kim, M.; Kim, S.; Kim, T.; Kindra, K.; Kirsch, S.; Kisel, I; Kiselev, S.; Kisiel, A.; Klay, J. L.; Klein, C.; Klein, J.; Klein, S.; Klein-Boesing, C.; Klewin, S.; Kluge, A.; Knichel, M. L.; Knospe, A. G.; Kobdaj, C.; Kofarago, M.; Koehler, M. K.; Kollegger, T.; Kondratyeva, N.; Kondratyuk, E.; Konopka, P. J.; Konyushikhin, M.; Koska, L.; Kovalenko, O.; Kovalenko, V; Kowalski, M.; Kralik, I; Kravcakova, A.; Kreis, L.; Krivda, M.; Krizek, F.; Krueger, M.; Kryshen, E.; Krzewicki, M.; Kubera, A. M.; Kucera, V; Kuhn, C.; Kuijer, P. G.; Kumar, L.; Kumar, S.; Kundu, S.; Kurashvili, P.; Kurepin, A.; Kurepin, A. B.; Kushpil, S.; Kvapil, J.; Kweon, M. J.; Kwon, Y.; La Pointe, S. L.; La Rocca, P.; Lai, Y. S.; Langoy, R.; Lapidus, K.; Lardeux, A.; Larionov, P.; Laudi, E.; Lavicka, R.; Lazareva, T.; Lea, R.; Leardini, L.; Lee, S.; Lehas, F.; Lehner, S.; Lehrbach, J.; Lemmon, R. C.; Leon Monzon, I; Levai, P.; Li, X.; Li, X. L.; Lien, J.; Lietava, R.; Lim, B.; Lindal, S.; Lindenstruth, V; Lindsay, S. W.; Lippmann, C.; Lisa, M. A.; Litichevskyi, V; Liu, A.; Ljunggren, H. M.; Llope, W. J.; Lodato, D. F.; Loginov, V; Loizides, C.; Loncar, P.; Lopez, X.; Lopez Torres, E.; Luettig, P.; Luhder, J. R.; Lunardon, M.; Luparello, G.; Lupi, M.; Maevskaya, A.; Mager, M.; Mahmood, S. M.; Mahmoud, T.; Maire, A.; Majka, R. D.; Malaev, M.; Malik, Q. W.; Malinina, L.; Mal'Kevich, D.; Malzacher, P.; Mamonov, A.; Manko, V; Manso, F.; Manzari, V; Mao, Y.; Marchisone, M.; Mares, J.; Margagliotti, G., V; Margotti, A.; Margutti, J.; Marin, A.; Markert, C.; Marquard, M.; Martin, N. A.; Martinengo, P.; Martinez, J. L.; Martinez, M., I; Garcia, G. Martinez; Pedreira, M. Martinez; Masciocchi, S.; Masera, M.; Masoni, A.; Massacrier, L.; Masson, E.; Mastroserio, A.; Mathis, A. M.; Matuoka, P. F. T.; Matyja, A.; Mayer, C.; Mazzilli, M.; Mazzoni, M. A.; Meddi, F.; Melikyan, Y.; Menchaca-Rocha, A.; Meninno, E.; Meres, M.; Mhlanga, S.; Miake, Y.; Micheletti, L.; Mieskolainen, M. M.; Mihaylov, D. L.; Mikhaylov, K.; Mischke, A.; Mishra, A. N.; Miskowiec, D.; Mitra, J.; Mitu, C. M.; Mohammadi, N.; Mohanty, A. P.; Mohanty, B.; Khan, M. Mohisin; Mondal, M. M.; Mordasini, C.; De Godoy, D. A. Moreira; Moreno, L. A. P.; Moretto, S.; Morreale, A.; Morsch, A.; Mrnjavac, T.; Muccifora, V; Mudnic, E.; Muehlheim, D.; Muhuri, S.; Mukherjee, M.; Mulligan, J. D.; Munhoz, M. G.; Muenning, K.; Munzer, R. H.; Murakami, H.; Murray, S.; Musa, L.; Musinsky, J.; Myers, C. J.; Myrcha, J. W.; Naik, B.; Nair, R.; Nandi, B. K.; Nania, R.; Nappi, E.; Naru, M. U.; Nassirpour, A. F.; Natal da Luz, H.; Nattrass, C.; Navarro, S. R.; Nayak, K.; Nayak, R.; Nayak, T. K.; Nazarenko, S.; De Oliveira, R. A. Negrao; Nellen, L.; Nesbo, S., V; Neskovic, G.; Ng, F.; Nielsen, B. S.; Nikolaev, S.; Nikulin, S.; Nikulin, V; Noferini, F.; Nomokonov, P.; Nooren, G.; Noris, J. C. C.; Norman, J.; Nyanin, A.; Nystrand, J.; Ogino, M.; Ohlson, A.; Oleniacz, J.; Oliveira Da Silva, A. C.; Oliver, M. H.; Onderwaater, J.; Oppedisano, C.; Orava, R.; Ortiz Velasquez, A.; Oskarsson, A.; Otwinowski, J.; Oyama, K.; Pachmayer, Y.; Pacik, V; Pagano, D.; Paic, G.; Palni, P.; Pan, J.; Pandey, A. K.; Panebianco, S.; Papikyan, V; Pareek, P.; Park, J.; Parkkila, J. E.; Parmar, S.; Passfeld, A.; Pathak, S. P.; Patra, R. N.; Paul, B.; Pei, H.; Peitzmann, T.; Peng, X.; Pereira, L. G.; Da Costa, H. Pereira; Peresunko, D.; Perez, G. M.; Lezama, E. Perez; Peskov, V; Pestov, Y.; Petracek, V; Petrovici, M.; Pezzi, R. P.; Piano, S.; Pikna, M.; Pillot, P.; Pimentel, L. O. D. L.; Pinazza, O.; Pinsky, L.; Pisano, S.; Piyarathna, D. B.; Ploskon, M.; Planinic, M.; Pliquett, F.; Pluta, J.; Pochybova, S.; Podesta-Lerma, P. L. M.; Poghosyan, M. G.; Polichtchouk, B.; Poljak, N.; Poonsawat, W.; Pop, A.; Poppenborg, H.; Porteboeuf-Houssais, S.; Pozdniakov, V; Prasad, S. K.; Preghenella, R.; Prino, F.; Pruneau, C. A.; Pshenichnov, I; Puccio, M.; Punin, V; Puranapanda, K.; Putschke, J.; Quishpe, R. E.; Ragoni, S.; Raha, S.; Rajput, S.; Rak, J.; Rakotozafindrabe, A.; Ramello, L.; Rami, F.; Raniwala, R.; Raniwala, S.; Rasanen, S. S.; Rascanu, B. T.; Rath, R.; Ratza, V; Ravasenga, I; Read, K. F.; Redlich, K.; Rehman, A.; Reichelt, P.; Reidt, F.; Ren, X.; Renfordt, R.; Reshetin, A.; Revol, J-P; Reygers, K.; Riabov, V; Richert, T.; Richter, M.; Riedler, P.; Riegler, W.; Riggi, F.; Ristea, C.; Rode, S. P.; Rodriguez Cahuantzi, M.; Roed, K.; Rogalev, R.; Rogochaya, E.; Rohr, D.; Rohrich, D.; Rokita, P. S.; Ronchetti, F.; Rosas, E. D.; Roslon, K.; Rosnet, P.; Rossi, A.; Rotondi, A.; Roukoutakis, F.; Roy, A.; Roy, P.; Rueda, O., V; Rui, R.; Rumyantsev, B.; Rustamov, A.; Ryabinkin, E.; Ryabov, Y.; Rybicki, A.; Saarinen, S.; Sadhu, S.; Sadovsky, S.; Safarik, K.; Saha, S. K.; Sahoo, B.; Sahoo, P.; Sahoo, R.; Sahoo, S.; Sahu, P. K.; Saini, J.; Sakai, S.; Sambyal, S.; Samsonov, V; Sandoval, A.; Sarkar, A.; Sarkar, D.; Sarkar, N.; Sarma, P.; Sarti, V. M.; Sas, M. H. P.; Scapparone, E.; Schaefer, B.; Schambach, J.; Scheid, H. S.; Schiaua, C.; Schicker, R.; Schmah, A.; Schmidt, C.; Schmidt, H. R.; Schmidt, M. O.; Schmidt, M.; Schmidt, N., V; Schmier, A. R.; Schukraft, J.; Schutz, Y.; Schwarz, K.; Schweda, K.; Scioli, G.; Scomparin, E.; Sefcik, M.; Seger, J. E.; Sekiguchi, Y.; Sekihata, D.; Selyuzhenkov, I; Senyukov, S.; Serradilla, E.; Sett, P.; Sevcenco, A.; Shabanov, A.; Shabetai, A.; Shahoyan, R.; Shaikh, W.; Shangaraev, A.; Sharma, A.; Sharma, M.; Sharma, N.; Sheikh, A., I; Shigaki, K.; Shimomura, M.; Shirinkin, S.; Shou, Q.; Sibiriak, Y.; Siddhanta, S.; Siemiarczuk, T.; Silvermyr, D.; Simatovic, G.; Simonetti, G.; Singh, R.; Singhal, V; Sinha, T.; Sitar, B.; Sitta, M.; Skaali, T. B.; Slupecki, M.; Smirnov, N.; Snellings, R. J. M.; Snellman, T. W.; Sochan, J.; Soncco, C.; Song, J.; Songmoolnak, A.; Soramel, F.; Sorensen, S.; Sozzi, F.; Sputowska, I; Stachel, J.; Stan, I; Stankus, P.; Stenlund, E.; Stocco, D.; Storetvedt, M. M.; Strmen, P.; Suaide, A. A. P.; Sugitate, T.; Suire, C.; Suleymanov, M.; Suljic, M.; Sultanov, R.; Sumbera, M.; Sumowidagdo, S.; Suzuki, K.; Swain, S.; Szabo, A.; Szarka, I; Tabassam, U.; Takahashi, J.; Tambave, G. J.; Tanaka, N.; Tarhini, M.; Tarzila, M. G.; Tauro, A.; Tejeda Munoz, G.; Telesca, A.; Terrevoli, C.; Thakur, D.; Thakur, S.; Thomas, D.; Thoresen, F.; Tieulent, R.; Tikhonov, A.; Timmins, A. R.; Toia, A.; Topilskaya, N.; Toppi, M.; Torres, S. R.; Tripathy, S.; Tripathy, T.; Trogolo, S.; Trombetta, G.; Tropp, L.; Trubnikov, V; Trzaska, W. H.; Trzcinski, T. P.; Trzeciak, B. A.; Tsuji, T.; Tumkin, A.; Turrisi, R.; Tveter, T. S.; Ullaland, K.; Umaka, E. N.; Uras, A.; Usai, G. L.; Utrobicic, A.; Vala, M.; Valencia Palomo, L.; Valle, N.; van der Kolk, N.; van Doremalen, L. V. R.; Van Hoorne, J. W.; van Leeuwen, M.; Vande Vyvre, P.; Varga, D.; Vargas, A.; Vargyas, M.; Varma, R.; Vasileiou, M.; Vasiliev, A.; Doce, O. Vazquez; Vechernin, V.; Veen, A. M.; Vercellin, E.; Vergara Limon, S.; Vermunt, L.; Vernet, R.; Vertesi, R.; Vickovic, L.; Viinikainen, J.; Vilakazi, Z.; Baillie, O. Villalobos; Villatoro Tello, A.; Vino, G.; Vinogradov, A.; Virgili, T.; Vislavicius, V.; Vodopyanov, A.; Volkel, B.; Voelkl, M. A.; Voloshin, K.; Voloshin, S. A.; Volpe, G.; von Haller, B.; Vorobyev, I; Voscek, D.; Vrlakova, J.; Wagner, B.; Wang, M.; Watanabe, Y.; Weber, M.; Weber, S. G.; Wegrzynek, A.; Weiser, D. F.; Wenzel, S. C.; Wessels, J. P.; Westerhoff, U.; Whitehead, A. M.; Widmann, E.; Wiechula, J.; Wikne, J.; Wilk, G.; Wilkinson, J.; Willems, G. A.; Willsher, E.; Windelband, B.; Witt, W. E.; Wu, Y.; Xu, R.; Yalcin, S.; Yamakawa, K.; Yano, S.; Yin, Z.; Yokoyama, H.; Yoo, I-K; Yoon, J. H.; Yuan, S.; Yurchenko, V; Zaccolo, V; Zaman, A.; Zampolli, C.; Zanoli, H. J. C.; Zardoshti, N.; Zarochentsev, A.; Zavada, P.; Zaviyalov, N.; Zbroszczyk, H.; Zhalov, M.; Zhang, X.; Zhang, Y.; Zhang, Z.; Zhao, C.; Zherebchevskii, V; Zhigareva, N.; Zhou, D.; Zhou, Y.; Zhou, Z.; Zhu, H.; Zhu, J.; Zhu, Y.; Zichichi, A.; Zimmermann, M. B.; Zinovjev, G.; Zurlo, N.Acharya, S.; Acosta, F. T.; Adamova, D.; Adhya, S. P.; Adler, A.; Adolfsson, J.; Aggarwal, M. M.; Rinella, G. Aglieri; Agnello, M.; Ahammed, Z.; Ahmad, S.; Ahn, S. U.; Aiola, S.; Akindinov, A.; Al-Turany, M.; Alam, S. N.; Albuquerque, D. S. D.; Aleksandrov, D.; Alessandro, B.; Alfanda, H. M.; Alfaro Molina, R.; Ali, B.; Ali, Y.; Alici, A.; Alkin, A.; Alme, J.; Alt, T.; Altenkamper, L.; Altsybeev, I; Anaam, M. N.; Andrei, C.; Andreou, D.; Andrews, H. A.; Andronic, A.; Angeletti, M.; Anguelov, V; Anson, C.; Anticic, T.; Antinori, F.; Antonioli, P.; Anwar, R.; Apadula, N.; Aphecetche, L.; Appelshaeuser, H.; Arcelli, S.; Arnaldi, R.; Arratia, M.; Arsene, I. C.; Arslandok, M.; Augustinus, A.; Averbeck, R.; Azmi, M. D.; Badala, A.; Baek, Y. W.; Bagnasco, S.; Bailhache, R.; Bala, R.; Baldisseri, A.; Ball, M.; Baral, R. C.; Barbera, R.; Barioglio, L.; Barnafoldi, G. G.; Barnby, L. S.; Barret, V; Bartalini, P.; Barth, K.; Bartsch, E.; Bastid, N.; Basu, S.; Batigne, G.; Batyunya, B.; Batzing, P. C.; Bauri, D.; Bazo Alba, J. L.; Bearden, I. G.; Bedda, C.; Behera, N. K.; Belikov, I; Bellini, F.; Bello Martinez, H.; Bellwied, R.; Beltran, L. G. E.; Belyaev, V; Bencedi, G.; Beole, S.; Bercuci, A.; Berdnikov, Y.; Berenyi, D.; Bertens, R. A.; Berzano, D.; Betev, L.; Bhasin, A.; Bhat, I. R.; Bhatt, H.; Bhattacharjee, B.; Bianchi, A.; Bianchi, L.; Bianchi, N.; Bielcik, J.; Bielcikova, J.; Bilandzic, A.; Biro, G.; Biswas, R.; Biswas, S.; Blair, J. T.; Blau, D.; Blume, C.; Boca, G.; Bock, F.; Bogdanov, A.; Boldizsar, L.; Bolozdynya, A.; Bombara, M.; Bonomi, G.; Bonora, M.; Borel, H.; Borissov, A.; Borri, M.; Botta, E.; Bourjau, C.; Bratrud, L.; Braun-Munzinger, P.; Bregant, M.; Broker, T. A.; Broz, M.; Brucken, E. J.; Bruna, E.; Bruno, G. E.; Buckland, M. D.; Budnikov, D.; Buesching, H.; Bufalino, S.; Buhler, P.; Buncic, P.; Busch, O.; Buthelezi, Z.; Butt, J. B.; Buxton, J. T.; Caffarri, D.; Caines, H.; Caliva, A.; Calvo Villar, E.; Camacho, R. S.; Camerini, P.; Capon, A. A.; Carnesecchi, F.; Castellanos, J. Castillo; Castro, A. J.; Casula, E. A. R.; Sanchez, C. Ceballos; Chakraborty, P.; Chandra, S.; Chang, B.; Chang, W.; Chapeland, S.; Chartier, M.; Chattopadhyay, S.; Chauvin, A.; Cheshkov, C.; Cheynis, B.; Barroso, V. Chibante; Chinellato, D. D.; Cho, S.; Chochula, P.; Chowdhury, T.; Christakoglou, P.; Christensen, C. H.; Christiansen, P.; Chujo, T.; Cicalo, C.; Cifarelli, L.; Cindolo, F.; Cleymans, J.; Colamaria, F.; Colella, D.; Collu, A.; Colocci, M.; Concas, M.; Balbastre, G. Conesa; del Valle, Z. Conesa; Contin, G.; Contreras, J. G.; Cormier, T. M.; Morales, Y. Corrales; Cortese, P.; Cosentino, M. R.; Costa, F.; Costanza, S.; Crkovska, J.; Crochet, P.; Cuautle, E.; Cunqueiro, L.; Dabrowski, D.; Dahms, T.; Dainese, A.; Damas, F. P. A.; Dani, S.; Danisch, M. C.; Danu, A.; Das, D.; Das, I; Das, S.; Dash, A.; Dash, S.; Dashi, A.; De, S.; De Caro, A.; de Cataldo, G.; de Conti, C.; de Cuveland, J.; De Falco, A.; De Gruttola, D.; De Marco, N.; De Pasquale, S.; De Souza, R. D.; Degenhardt, H. F.; Deisting, A.; Deloff, A.; Delsanto, S.; Dhankher, P.; Di Bari, D.; Di Mauro, A.; Diaz, R. A.; Dietel, T.; Dillenseger, P.; Ding, Y.; Divia, R.; Djuvsland, O.; Dobrin, A.; Domenicis Gimenez, D.; Doenigus, B.; Dordic, O.; Dubey, A. K.; Dubla, A.; Dudi, S.; Duggal, A. K.; Dukhishyam, M.; Dupieux, P.; Ehlers, R. J.; Elia, D.; Engel, H.; Epple, E.; Erazmus, B.; Erhardt, F.; Erokhin, A.; Ersdal, M. R.; Espagnon, B.; Eulisse, G.; Eum, J.; Evans, D.; Evdokimov, S.; Fabbietti, L.; Faggin, M.; Faivre, J.; Fantoni, A.; Fasel, M.; Feldkamp, L.; Feliciello, A.; Feofilov, G.; Fernandez Tellez, A.; Ferrero, A.; Ferretti, A.; Festanti, A.; Feuillard, V. J. G.; Figiel, J.; Filchagin, S.; Finogeev, D.; Fionda, F. M.; Fiorenza, G.; Flor, F.; Floris, M.; Foertsch, S.; Foka, P.; Fokin, S.; Fragiacomo, E.; Francisco, A.; Frankenfeld, U.; Fronze, G. G.; Fuchs, U.; Furget, C.; Furs, A.; Girard, M. Fusco; Gaardhoje, J. J.; Gagliardi, M.; Gago, A. M.; Gajdosova, K.; Galvan, C. D.; Ganoti, P.; Garabatos, C.; Garcia-Solis, E.; Garg, K.; Gargiulo, C.; Garner, K.; Gasik, P.; Gauger, E. F.; Gay Ducati, M. B.; Germain, M.; Ghosh, J.; Ghosh, P.; Ghosh, S. K.; Gianotti, P.; Giubellino, P.; Giubilato, P.; Glaessel, P.; Gomez Coral, D. M.; Ramirez, A. Gomez; Gonzalez, V; Gonzalez-Zamora, P.; Gorbunov, S.; Gorlich, L.; Gotovac, S.; Grabski, V; Graczykowski, L. K.; Graham, K. L.; Greiner, L.; Grelli, A.; Grigoras, C.; Grigoriev, V; Grigoryan, A.; Grigoryan, S.; Gronefeld, J. M.; Grosa, F.; Grosse-Oetringhaus, J. F.; Grosso, R.; Guernane, R.; Guerzoni, B.; Guittiere, M.; Gulbrandsen, K.; Gunji, T.; Gupta, A.; Gupta, R.; Guzman, I. B.; Haake, R.; Habib, M. K.; Hadjidakis, C.; Hamagaki, H.; Hamar, G.; Hamid, M.; Hamon, J. C.; Hannigan, R.; Haque, M. R.; Harlenderova, A.; Harris, J. W.; Harton, A.; Hassan, H.; Hatzifotiadou, D.; Hauer, P.; Hayashi, S.; Heckel, S. T.; Hellbaer, E.; Helstrup, H.; Herghelegiu, A.; Hernandez, E. G.; Herrera Corral, G.; Herrmann, F.; Hetland, K. F.; Hilden, T. E.; Hillemanns, H.; Hills, C.; Hippolyte, B.; Hohlweger, B.; Horak, D.; Hornung, S.; Hosokawa, R.; Hota, J.; Hristov, P.; Huang, C.; Hughes, C.; Huhn, P.; Humanic, T. J.; Hushnud, H.; Husova, L. A.; Hussain, N.; Hussain, T.; Hutter, D.; Hwang, D. S.; Iddon, J. P.; Ilkaev, R.; Inaba, M.; Ippolitov, M.; Islam, M. S.; Ivanov, M.; Ivanov, V; Izucheev, V; Jacak, B.; Jacazio, N.; Jacobs, P. M.; Jadhav, M. B.; Jadlovska, S.; Jadlovsky, J.; Jaelani, S.; Jahnke, C.; Jakubowska, M. J.; Janik, M. A.; Jercic, M.; Jevons, O.; Bustamante, R. T. Jimenez; Jin, M.; Jones, P. G.; Jusko, A.; Kalinak, P.; Kalweit, A.; Kang, J. H.; Kaplin, V; Kar, S.; Uysal, A. Karasu; Karavichev, O.; Karavicheva, T.; Karczmarczyk, P.; Karpechev, E.; Kebschull, U.; Keidel, R.; Keil, M.; Ketzer, B.; Khabanova, Z.; Khan, A. M.; Khan, S.; Khan, S. A.; Khanzadeev, A.; Kharlov, Y.; Khatun, A.; Khuntia, A.; Kielbowicz, M. M.; Kileng, B.; Kim, B.; Kim, D.; Kim, D. J.; Kim, E. J.; Kim, H.; Kim, J. S.; Kim, J.; Kim, M.; Kim, S.; Kim, T.; Kindra, K.; Kirsch, S.; Kisel, I; Kiselev, S.; Kisiel, A.; Klay, J. L.; Klein, C.; Klein, J.; Klein, S.; Klein-Boesing, C.; Klewin, S.; Kluge, A.; Knichel, M. L.; Knospe, A. G.; Kobdaj, C.; Kofarago, M.; Koehler, M. K.; Kollegger, T.; Kondratyeva, N.; Kondratyuk, E.; Konopka, P. J.; Konyushikhin, M.; Koska, L.; Kovalenko, O.; Kovalenko, V; Kowalski, M.; Kralik, I; Krav

Emodepside and SL0-1 potassium channels: a review

International audienceNematode parasites infect humans and domestic animals; treatment and prophylaxis require anthelmintic drugs because vaccination and sanitation is limited. Emodepside is a more recently introduced cyclooctadepsipeptide drug that has actions against GI nematodes, lungworm, and microfilaria. It has a novel mode of action which breaks resistance to the classical anthelmintics (benzimidazoles, macrocyclic lactones and cholinergic agonists). Here we review studies on its mode of action which suggest that it acts to inhibit neuronal and muscle activity of nematodes by increasing the opening of calcium-activated potassium (SLO-1) channels