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NMDA receptor activation requires remodelling of intersubunit contacts within ligand-binding heterodimers
In non-NMDA glutamate receptors, intersubunit contacts within agonist binding domains affect functional desensitization. Now, NMDA receptor activation, but not desensitization, is shown to involve rearrangements at the heterodimer interface, suggesting that the intersubunit contacts of NMDA and non-NMDA receptors may have distinct functional roles.
- William F. Borschel
- , Swetha E. Murthy
- & Gabriela K. Popescu
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Electrosensory ampullary organs are derived from lateral line placodes in bony fishes
Ampullary organs are involved in electroreception, but whether these are derived from placodes, thickened ectoderm, is unclear. In this study, the ampullary organs of the primitive ray-finned fish,Polyodon spathula, are shown to develop from lateral line placodes, suggesting that this is the ancestral state in bony fishes.
- Melinda S. Modrell
- , William E. Bemis
- & Clare V.H. Baker
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Phosphatidylinositol(4,5)bisphosphate coordinates actin-mediated mobilization and translocation of secretory vesicles to the plasma membrane of chromaffin cells
The role of phosphatidylinositol(4,5)bisphosphate in exocytosis is unclear. This study shows that inhibition of the p110δ isoform of PI3-kinase promotes a transient increase in phosphatidylinositol(4,5)bisphosphate, leading to a potentiation of exocytosis in chromaffin cells.
- Peter J. Wen
- , Shona L. Osborne
- & Frédéric A. Meunier
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| Open AccessInformation processing using a single dynamical node as complex system
The paradigm of reservoir computing shows that, like the human brain, complex networks can perform efficient information processing. Here, a simple delay dynamical system is demonstrated that can efficiently perform computations capable of replacing a complex network in reservoir computing.
- L. Appeltant
- , M.C. Soriano
- & I. Fischer
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| Open AccessBacterial Pili exploit integrin machinery to promote immune activation and efficient blood-brain barrier penetration
Group BStreptococcuscauses meningitis in newborn infants but how the bacterium crosses the blood-brain barrier is unknown. Here, the bacterial pili adhesion molecule, PilA, is shown to bind to collagen and promote binding of the bacteria to integrins expressed on the blood-brain endothelium.
- Anirban Banerjee
- , Brandon J. Kim
- & Kelly S. Doran
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| Open AccessMolecular mechanism for 3:1 subunit stoichiometry of rod cyclic nucleotide-gated ion channels
The assembly mechanisms of heteromeric ion channels are poorly understood. Using a range of techniques, Shuartet al.determine the mechanism by which rod photoreceptor cyclic nucleotide-gated channels assume a 3:1 stoichiometry of CNGA1 and CNGB1 subunits.
- Noah G. Shuart
- , Yoni Haitin
- & William N. Zagotta
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Direct visualization of microtubules using a genetic tool to analyse radial progenitor-astrocyte continuum in brain
The development of radial progenitor cells and astroglia in the cerebral cortex depends on the microtubule cytoskeleton. Eomet al. have developed a new mouse model where the microtubules of astrocytes and radial glia cells are fluorescently tagged, facilitating the detailed study of microtubule dynamics and development in these cells.
- Tae-Yeon Eom
- , Amelia Stanco
- & E.S. Anton
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| Open AccessActive sampling and decision making in Drosophila chemotaxis
Drosophila melanogaster larvae demonstrate chemotaxis towards odours but their navigation mechanism is poorly understood. Using computer-vision tracking, Gomez-Marinet al.show that larvae ascend odour gradients using an active sampling strategy that is analogous to sniffing in vertebrates.
- Alex Gomez-Marin
- , Greg J. Stephens
- & Matthieu Louis
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| Open AccessParkinson's disease induced pluripotent stem cells with triplication of the α-synuclein locus
Pluripotent stem cells can be generated from the somatic cells of humans and are a useful model to study disease. Here, pluripotent stem cells are made from a patient with familial Parkinson's disease, and the resulting neurons exhibit elevated levels of α-synuclein, recapitulating the molecular features of the patient's disease.
- Michael J. Devine
- , Mina Ryten
- & Tilo Kunath
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Critical roles for EphB and ephrin-B bidirectional signalling in retinocollicular mapping
How retinoganglion cell axons project correctly to the superior colliculus is poorly understood. Here, projections are shown to require EphB1, EphB2 and ephrin-B1 to terminate in the medial superior colliculus, while ephrin-B2 is essential for the mapping of both dorsal and ventral axons.
- Sonal Thakar
- , George Chenaux
- & Mark Henkemeyer
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Relative comparisons of call parameters enable auditory grouping in frogs
Male túngara frogs produce overlapping mating calls, which poses a challenge for the female frog to group and assign multiple auditory signals to the correct source. Farris and Ryan shows that, like humans, the female frogs compare and group signals using the smallest relative difference in call parameters.
- Hamilton E. Farris
- & Michael J. Ryan
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Outlines of the pore in open and closed conformations describe the gating mechanism of ASIC1
The pore gating mechanism of the proton-activated sodium channel ASIC1 is poorly understood. Canessaet al.study the shape of the ion pathway in the ASIC1 channel in its open and closed states, and reveal the opening, closing and desensitization mechanisms of the channel.
- Tianbo Li
- , Youshan Yang
- & Cecilia M. Canessa
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| Open AccessTonic excitation or inhibition is set by GABAA conductance in hippocampal interneurons
Ambient levels of the neurotransmitter GABA tonically activate GABAA. Song et al.show that GABA can have both excitatory and inhibitory effects on hippocampal interneurons and find that low levels of GABA-mediated conductance are excitatory, whereas higher levels result in shunting inhibition.
- Inseon Song
- , Leonid Savtchenko
- & Alexey Semyanov
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TRPV3 regulates nitric oxide synthase-independent nitric oxide synthesis in the skin
Nitric oxide can be produced by nitric oxide synthase or by nitrite reduction, but whether the latter occurs inside cells is unknown. Here, the TRPV3 ion channel is shown to induce nitrite-dependent nitric oxide production in keratinocytes, where it has a role in thermosensory behaviour and wound healing.
- Takashi Miyamoto
- , Matt J. Petrus
- & Ardem Patapoutian
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| Open AccessHuman cryptochrome exhibits light-dependent magnetosensitivity
In animals, cryptochrome proteins are thought to be the detectors of the Earth's magnetic field, but humans have not been shown to posess mangetosensing capabilities. Foleyet al. demonstrate that the human cryptochrome protein, CRY2, when expressed in Drosophila melanogastercan mediate magnetoreception in a light-dependent manner.
- Lauren E. Foley
- , Robert J. Gegear
- & Steven M. Reppert
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| Open AccessRequirement of calcium-activated chloride channels in the activation of mouse vomeronasal neurons
The vomeronasal organ detects pheromones, which are thought to activate TRPC2 channels on the surface of vomeronasal neurons. Using TRPC2 knockout mice, the authors show that urinary pheromones can also activate these neurons via calcium-activated chloride channels, suggesting a TRPC2-independent pathway for sensing pheromones.
- SangSeong Kim
- , Limei Ma
- & C. Ron Yu
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Ultrasonic frogs show extraordinary sex differences in auditory frequency sensitivity
Acoustic communication is important for the reproductive behaviour of frogs. Using acoustic playback experiments, Shenet al. show that calls from male concave-eared frogs (Odorrana tormota) evoke vocal responses and phonotaxis from females, but the females show no ultrasonic sensitivity.
- Jun-Xian Shen
- , Zhi-Min Xu
- & Shang-Chun Fan
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Vocalization frequency and duration are coded in separate hindbrain nuclei
Vocal communication is relatively common among fish: the midshipman being an example with a particularly wide dynamic range. In this paper, the authors demonstrate that different populations of hindbrain neurons are responsible for the frequency and duration of these calls.
- Boris P. Chagnaud
- , Robert Baker
- & Andrew H. Bass
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| Open AccessNeural coding in a single sensory neuron controlling opposite seeking behaviours in Caenorhabditis elegans
The neuronal mechanisms responsible for thermal seeking behaviour inCaenorhabditis. elegansare not fully understood. In this study, the sensory neuron AFD is shown to be involved in the responses to both cold and warm temperatures by transmitting inhibitory and excitatory signals to the interneuron AIY.
- Atsushi Kuhara
- , Noriyuki Ohnishi
- & Ikue Mori
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Atomistic mechanism for the activation and desensitization of an AMPA-subtype glutamate receptor
Upon agonist binding, ionotropic glutamate receptors are activated and then become desensitized, but the detailed molecular events of this process are unclear. Here, molecular dynamics simulations are used to probe how conformational changes of the ligand-binding domain are transmitted to the transmembrane domain.
- Hao Dong
- & Huan-Xiang Zhou
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Developmental correspondence between action prediction and motor ability in early infancy
It is believed that infants map observed actions onto their own representation of the action, a hypothesis known as direct matching. By observing the gaze of infants and their grasping response, experimental evidence is provided to support the direct matching theory.
- Yasuhiro Kanakogi
- & Shoji Itakura
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| Open AccessInteraction between prion protein and toxic amyloid β assemblies can be therapeutically targeted at multiple sites
The ability of synthetic amyloid β-protein to bind to prion proteins and alter synaptic plasticity has been previously reported. Here the relevance of this binding is investigated in brains of Alzheimer's disease patients and the interaction is shown to be blocked by antibodies to two distinct regions of prion proteins.
- Darragh B. Freir
- , Andrew J. Nicoll
- & John Collinge
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| Open AccessCircadian regulation of intracellular G-protein signalling mediates intercellular synchrony and rhythmicity in the suprachiasmatic nucleus
Circadian rhythm is controlled by the suprachiasmatic nucleus and the mechanisms that control the rhythm are largely undiscovered. In this study, a G protein regulator, RGS16, is shown to be involved in the production of cyclic AMP that is required for the suprachiasmatic nucleus to maintain rhythm
- Masao Doi
- , Atsushi Ishida
- & Hitoshi Okamura
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The neural circuits and sensory channels mediating harsh touch sensation in Caenorhabditis elegans
The mechanisms by which animals distinguish between harsh and gentle touch are unclear. UsingCaenorhabditis elegansas a model system, the authors identify neural circuits and touch-sensitive ion channels that are required for harsh touch sensation.
- Wei Li
- , Lijun Kang
- & X.Z. Shawn Xu
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Recovery from chronic monocular deprivation following reactivation of thalamocortical plasticity by dark exposure
Amblyopia induced by chronic monocular deprivation can be reversed by dark exposure, followed by reverse deprivation in adulthood. The authors show that dark exposure in adulthood reactivates plasticity in the visual cortex, including thalamocortical synapses, promoting recovery from deprivation amblyopia.
- Karen L. Montey
- & Elizabeth M. Quinlan
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Food restriction enhances visual cortex plasticity in adulthood
Calorie restriction has been associated with increased life span and delayed decline of memory in animals, suggesting a role in neuronal plasticity. In this study, food restriction is demonstrated to enhance plasticity in the central nervous system and trigger the recovery from ocular deprivation in adulthood.
- Maria Spolidoro
- , Laura Baroncelli
- & Lamberto Maffei
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Engineering biosynthetic excitable tissues from unexcitable cells for electrophysiological and cell therapy studies
Patch-clamp recordings are used to study the function of ion channels, but the method does not allow the assessment of tissue-level function. Kirkton and Bursac introduce a biosynthetic system for the study of channel activity and electrical conduction, facilitating studies of ion channel function.
- Robert D. Kirkton
- & Nenad Bursac
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Optogenetic analysis of synaptic transmission in the central nervous system of the nematode Caenorhabditis elegans
Pair-wise electrophysiology is difficult inCaenorhabditis elegansbecause the recordings are relatively short-lived. In this study, the authors investigate the synaptic currents associated with escape responses by immobilizing worms on a micropatterned agar substrate and stimulating neurons using channelrhodopsin-2.
- Theodore H. Lindsay
- , Tod R. Thiele
- & Shawn R. Lockery
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Ligand-specific deactivation time course of GluN1/GluN2D NMDA receptors
N-methyl-D-aspartate receptors mediate excitatory synaptic transmission, and those containing GluN2D subunits have an unusually long deactivation time. Vance et al. show that the conformational variability of the ligand-binding domain and the structure of the activating ligand influence deactivation time.
- Katie M. Vance
- , Noriko Simorowski
- & Hiro Furukawa
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Frequency-dependent recruitment of V2a interneurons during fictive locomotion in the mouse spinal cord
The spinal V2a interneurons control left–right limb alternation during mouse locomotion, but only at high frequencies. In this study, the authors show that only half of these neurons are active during locomotion, and that they receive increasing synaptic drive to increase their activity as locomotion accelerates.
- Guisheng Zhong
- , Kamal Sharma
- & Ronald M. Harris-Warrick
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| Open AccessNeural crest cells organize the eye via TGF-β and canonical Wnt signalling
In the developing eye, the lens and retina are derived from different embryonic tissues, and how these two structures develop next to each other is of interest. In this study, the authors show that transforming growth factor-β secreted by neural crest cells is critical for the positioning of the lens next to the retina.
- Timothy Grocott
- , Samuel Johnson
- & Andrea Streit
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Subcellular in vivo time-lapse imaging and optical manipulation of Caenorhabditis elegans in standard multiwell plates
The nematodeCaenorhabditis elegans is a widely used model organism for visualizing development, ageing and other phenomena, but high-throughput imaging requires immobilization of the animal. Rohde and Yanik report a rapid immobilization and imaging method for the high-throughput screening of C. elegans.
- Christopher B. Rohde
- & Mehmet Fatih Yanik
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| Open AccessRepresentational format determines numerical competence in monkeys
Many animals can do simple quantity discrimination, but they often perform poorly when food is used. Here, the authors show that monkeys are good at food quantity discrimination when they are not allowed to eat it, suggesting that the mental representation of the stimuli is more important than the physical quality.
- Vanessa Schmitt
- & Julia Fischer
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| Open AccessErrors in the measurement of voltage-activated ion channels in cell-attached patch-clamp recordings
Voltage-activated ion channels can be measured in neurons using the cell-attached patch-clamp technique. Williams and Wozny show that this technique is prone to errors that are caused by the flow of current through the ion channels; a method to correct for these discrepancies is described.
- Stephen R. Williams
- & Christian Wozny
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A modern ionotropic glutamate receptor with a K+ selectivity signature sequence
Glutamate is the major excitatory neurotransmitter in the mammalian nervous system. Here, a glutamate receptor is reported that has properties intermediate to those of bacterial and eukaryotic glutamate-gated ion channels, suggesting a link in the evolution of ionotropic glutamate receptors.
- H. Janovjak
- , G. Sandoz
- & E. Y. Isacoff
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Measurement of cochlear power gain in the sensitive gerbil ear
The cochlear amplifier in the inner ear is thought to mediate sensitivity to soft sounds, but this power gain has not been measured directly. Renet aluse an interferometer to measure the volume displacement and velocity of the cochlear partition and demonstrate experimentally that the cochlea amplifies soft sounds.
- Tianying Ren
- , Wenxuan He
- & Peter G. Gillespie
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| Open AccessRetinoid-independent motor neurogenesis from human embryonic stem cells reveals a medial columnar ground state
There is much interest in generating motor neurons from embryonic stem cells because they may be useful for the study of neurodegenerative disease. Pataniet al. show that in the absence of retinoic acid, neurons with features of medial motor columnar neurons can be generated from human embryonic stem cells.
- R. Patani
- , A. J. Hollins
- & S. Chandran
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| Open AccessIh-mediated depolarization enhances the temporal precision of neuronal integration
In neurons, GABAA receptors mediate feed-forward inhibition by shunting excitatory currents and hyperpolarizing neurons. Here, the authors show that the hyperpolarization-activated mixed cation current is critical for determining the resting membrane potential and reversal potential for GABAA-mediated currents.
- Ivan Pavlov
- , Annalisa Scimemi
- & Matthew C. Walker
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| Open AccessGipc3 mutations associated with audiogenic seizures and sensorineural hearing loss in mouse and human
Progressive sensorineural hearing loss affects many people, but the underlying genetics remain largely undefined. Here, the authors identify mutations inGIPC3in mice and two consanguineous families that lead to hearing loss and in mice cause defects in the structure of stereocilia bundles and audiogenic seizures.
- Nikoletta Charizopoulou
- , Andrea Lelli
- & Konrad Noben-Trauth
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| Open AccessGlia- and neuron-specific functions of TrkB signalling during retinal degeneration and regeneration
The central nervous system contains glial cells, which have been shown to have an important role in neuronal survival. Haradaet al. use transgenic mouse models to show that TrkB, a receptor for the growth factor brain-derived neurotrophic factor, is required for retinal Müller glial cells to provide neuroprotection and regeneration.
- Chikako Harada
- , Xiaoli Guo
- & Takayuki Harada
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A hybrid bioorganic interface for neuronal photoactivation
Interfacing neurons with artificial functional materials could aid the development of neurological prosthetic devices. Here, primary neurons are incorporated into a polymer layer without adversely affecting their properties; the advance may contribute to the development of artificial retinas.
- Diego Ghezzi
- , Maria Rosa Antognazza
- & Guglielmo Lanzani
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Article
| Open AccessNeural stem and progenitor cells shorten S-phase on commitment to neuron production
During neurogenesis, neural stem and progenitor cells can either proliferate or produce neurons. Here, the authors show that proliferating neural stem and progenitor cells have a longer S-phase portion of the cell cycle than cells committed to neuron production, suggesting that this may enable faithful DNA replication.
- Yoko Arai
- , Jeremy N. Pulvers
- & Wieland B. Huttner
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Article
| Open AccessSubstrate docking to γ-secretase allows access of γ-secretase modulators to an allosteric site
γ-Secretase modulators have promise in the treatment of Alzheimer's disease, but their molecular target is uncertain. Here, fluorescence resonance energy transfer is used to determine that the γ-secretase allosteric site is within the γ-secretase complex and that substrate docking is required for modulators to access the site.
- Kengo Uemura
- , Katherine C. Farner
- & Oksana Berezovska
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Article
| Open AccessInnate recognition of water bodies in echolocating bats
Little is known about the way bats recognize large objects, such as trees, buildings or a lake. Greif and Siemers show that bodies of water are recognized solely by echolocation, and that this ability is innate, thus smooth surfaces are recognized as water by naive juvenile bats.
- Stefan Greif
- & Björn M. Siemers
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Article
| Open AccessA β-synuclein mutation linked to dementia produces neurodegeneration when expressed in mouse brain
Little is known about β-synuclein mutations in neurological disease. In this article, the authors demonstrate that mice with a mutation in β-synuclein show progressive neurodegenerative disease and suggest that this mutation can enhance the brain defects caused by α-synuclein mutations in mice.
- Masayo Fujita
- , Shuei Sugama
- & Makoto Hashimoto
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Article
| Open AccessTectorial membrane travelling waves underlie abnormal hearing in Tectb mutant mice
Mutation of theTectbgene reduces auditory sensitivity but increases frequency selectivity. Here the authors show that Tectb mutation reduces both the spatial and temporal propagation of travelling waves along the tectorial membrane, explaining the unexpected auditory abnormalities in this mutant.
- Roozbeh Ghaffari
- , Alexander J. Aranyosi
- & Dennis M. Freeman
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Development of a novel selective inhibitor of the Down syndrome-related kinase Dyrk1A
The kinase Dyrk1A is essential for brain function and development, and its excessive activity has been implicated in Down syndrome. In this study, a selective inhibitor of Dyrk1A is developed, which may help to elucidate the molecular mechanisms of normal and diseased brain.
- Yasushi Ogawa
- , Yosuke Nonaka
- & Masatoshi Hagiwara
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A subunit-selective potentiator of NR2C- and NR2D-containing NMDA receptors
NMDA receptors are complexes of NR1 and NR2 subunits that mediate excitatory synaptic transmission and have roles in neurological disorders. Here, a subunit-selective potentiator of NMDA receptors is identified, which may allow the evaluation of the functional roles of individual NMDA receptor subunits.
- Praseeda Mullasseril
- , Kasper B. Hansen
- & Stephen F. Traynelis
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Automated home-cage behavioural phenotyping of mice
Studying the behaviour of captive mice requires considerable time and effort. Here, video-based software is designed and implemented to automatically quantitate mouse behaviour; the system performs well in comparison with manual human observations.
- Hueihan Jhuang
- , Estibaliz Garrote
- & Thomas Serre
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