Featured
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Article
| Open AccessStructural basis of CDNF interaction with the UPR regulator GRP78
CDNF is a clinical trial candidate in Parkinson’s disease but the mechanism of action is not fully understood. Here, the authors use SAXS and NMR techniques to resolve the structure of CDNF in complex with GRP78 and show that this interaction is required for the neuroprotective action of CDNF.
- Melissa A. Graewert
- , Maria Volkova
- & Henri J. Huttunen
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Article
| Open AccessA human Tau expressing zebrafish model of progressive supranuclear palsy identifies Brd4 as a regulator of microglial synaptic elimination
Progressive supranuclear palsy (PSP) is an incurable neurodegenerative disease characterised by accumulation of 4R-Tau protein in the brain. Transgenic zebrafish overexpressing human 4R-Tau showed rapid PSP-like phenotypes, allowing an unbiased small molecule screen coupled with reverse genetics to identify Brd4-dependent microglial synapse removal as a mechanism mediating neurological phenotypes.
- Qing Bai
- , Enhua Shao
- & Edward A. Burton
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Article
| Open AccessDistinct medial amygdala oxytocin receptor neurons projections respectively control consolation or aggression in male mandarin voles
Empathy and aggression are essential to well-being and survival, but its circuit mechanism remains unclear. Here, authors show two specific pathways from the medial amygdala as brain switches that control the consolation or attacking respectively.
- Yishan Qu
- , Lizi Zhang
- & Fadao Tai
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Article
| Open AccessDopamine neurons encode trial-by-trial subjective reward value in an auction-like task
The dopamine reward prediction error signal encodes subjective reward value estimated from trial averages. Here, the authors show that the dopamine signal follows trial-by-trial changes in value estimates assessed by an auction-like situation.
- Daniel F. Hill
- , Robert W. Hickman
- & Wolfram Schultz
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Article
| Open AccessAuditory areas are recruited for naturalistic visual meaning in early deaf people
In people who are deaf, the parts of the brain usually responsible for processing audition can take over visual tasks. Here, the authors show that the auditory cortex in early deaf individuals processes visual meaning conveyed in naturalistic stimuli.
- Maria Zimmermann
- , Rhodri Cusack
- & Marcin Szwed
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Article
| Open AccessFrontoparietal network topology as a neural marker of musical perceptual abilities
Here, the authors show through an analysis of brain scans from over 200 non-musicians that individuals with an efficiently organized network connecting frontal and parietal regions, critical for working memory, tend to have better musical perceptual abilities.
- M. Lumaca
- , P. E. Keller
- & K. Sandberg
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Article
| Open AccessEndolysosomal dysfunction in radial glia progenitor cells leads to defective cerebral angiogenesis and compromised blood-brain barrier integrity
Neuronal and vascular crosstalk is essential for proper brain development and function. Here, the authors show that mutations in scarb2 cause abnormal glial differentiation and excessive neurogenesis, leading to impaired blood-brain barrier formation.
- Ivan Bassi
- , Moshe Grunspan
- & Karina Yaniv
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Article
| Open AccessCortical sites critical to language function act as connectors between language subnetworks
It is unknown how cortical stimulation identifies brain regions critical to speech and language when they depend upon broader brain networks. Here the authors show that these critical areas function as connectors between modules in the language network.
- Jason K. Hsieh
- , Prashanth R. Prakash
- & Marc W. Slutzky
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Article
| Open AccessNeurotransmitter recognition by human vesicular monoamine transporter 2
VMAT2 regulates neurotransmitter uptake into synaptic vesicles. Here, the authors determined the cryo-EM structures of VMAT2, providing a structural basis for understanding VMAT2- mediated vesicular transport of neurotransmitters.
- Dohyun Im
- , Mika Jormakka
- & So Iwata
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Article
| Open AccessIn vivo imaging of vagal-induced myenteric plexus responses in gastrointestinal tract with an optical window
In vivo optical recording of the real-time effects of extrinsic afferents on the activity of the enteric nervous system has been challenging. Here, the authors show a method that allows long-term imaging of the mouse gastric antrum and stable recording of the gastric myenteric plexus in response to vagal activation.
- Longjie Jiang
- , Jie Yang
- & Ling Fu
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Article
| Open AccessConserved transcriptional regulation by BRN1 and BRN2 in neocortical progenitors drives mammalian neural specification and neocortical expansion
How the diversity and number of neuronal subtypes across species drives neocortical size and complexity remains incompletely understood. Here authors demonstrate BRN1/2 act in concert with NOTCH and primary microcephaly genes to regulate evolutionarily conserved neocortical progenitor behavior across species and determine brain size.
- Soraia Barão
- , Yijun Xu
- & Ulrich Müller
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Article
| Open AccessGain control of sensory input across polysynaptic circuitries in mouse visual cortex by a single G protein-coupled receptor type (5-HT2A)
G protein-coupled receptors (GPCRs) are expressed in different cell types of the brain. Their joint network function remains unclear due to lack of molecular tools allowing functional dissection targeting a single type of GPCR. Here the authors use optogenetics and show how serotonergic 5-HT2A receptors act across excitatory and inhibitory neurons in mouse visual cortex.
- Ruxandra Barzan
- , Beyza Bozkurt
- & Dirk Jancke
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Article
| Open AccessDistinct codes for environment structure and symmetry in postrhinal and retrosplenial cortices
Whether and how the postrhinal (POR) and retrosplenial (RSC) cortices interact with each other and impact downstream allocentric representations are not fully understood. Here authors present single neuron recordings from freely moving rats exploring different environments to reveal distinct egocentric (self-centered) and allocentric (world-centered) coding frameworks for landmarks and boundaries in interconnected cortical regions.
- Patrick A. LaChance
- & Michael E. Hasselmo
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Article
| Open AccessSex differences in neural representations of social and nonsocial reward in the medial prefrontal cortex
The medial prefrontal cortex (mPFC) has been implicated in both social and nonsocial reward-related behaviors, yet it is unclear if the same mPFC neurons represent both types of rewards. Combining a social-sucrose operant assay with calcium imaging and optogenetics, the authors show that largely non-overlapping neurons represent social and sucrose rewards in the mPFC.
- Jennifer Isaac
- , Sonia Corbett Karkare
- & Malavika Murugan
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Article
| Open AccessTherapeutic efficacy of intracerebral hematopoietic stem cell gene therapy in an Alzheimer’s disease mouse model
This study aims at enhancing hematopoietic stem cell (HSC) gene therapy potential to treat neurodegenerative diseases via innovative approaches. Findings demonstrate the therapeutic benefits of intracerebral transplantation of TREM2-engineered HSCs in an Alzheimer’s disease mouse model.
- Rita Milazzo
- , Annita Montepeloso
- & Alessandra Biffi
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Article
| Open AccessA sex-stratified analysis of the genetic architecture of human brain anatomy
Here, the authors screen for sex differences in the common genetic architecture of over 1000 neuroanatomical phenotypes, showing overall concordance between female and male individuals.
- Rebecca Shafee
- , Dustin Moraczewski
- & Armin Raznahan
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Article
| Open AccessUltrasound frequency-controlled microbubble dynamics in brain vessels regulate the enrichment of inflammatory pathways in the blood-brain barrier
The impact of ultrasound-controlled microbubble dynamics on the blood-brain barrier remains largely unexplored. Through theoretical and experimental research, the authors show that microbubble resonant effects in brain vessels can control the enrichment of inflammatory pathways and modulate cytotoxic T-cell infiltration in tumours.
- Yutong Guo
- , Hohyun Lee
- & Costas Arvanitis
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Article
| Open AccessSurprising sounds influence risky decision making
“People can quickly respond to surprising sensory events in the environment. Here, the authors show that surprising sounds, even when they are irrelevant, systematically increase risk taking, and this effect can be eliminated by changing the sensory statistics of the environment.”
- Gloria W. Feng
- & Robb B. Rutledge
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Article
| Open AccessRegional patterns of human cortex development correlate with underlying neurobiology
The neurobiology of human brain development and aging is hard to study in vivo. The authors report on distinct spatial associations between brain morphology and cellular as well as molecular brain properties throughout neurodevelopment and aging.
- Leon D. Lotter
- , Amin Saberi
- & Juergen Dukart
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Article
| Open AccessClearance and transport of amyloid β by peripheral monocytes correlate with Alzheimer’s disease progression
Impaired Aβ clearance in late-onset Alzheimer’s disease (AD) affects progression. Here, the authors show that CD14 + CD16+ monocytes carry Aβ in peripheral circulation and CSF in AD, suggesting a role in Aβ clearance.
- Xin Huang
- , Chris Fowler
- & Ben J. Gu
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Article
| Open AccessPrenatal environment is associated with the pace of cortical network development over the first three years of life
Early environmental factors, like disadvantage, are associated with neurocognitive development. Here, the authors find that neonates and toddlers from economically disadvantaged backgrounds show accelerated brain development, with implications for language abilities in toddlerhood.
- Ursula A. Tooley
- , Aidan Latham
- & Christopher D. Smyser
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Article
| Open AccessSub-threshold neuronal activity and the dynamical regime of cerebral cortex
Whether the cortex operates in a fluctuation-driven regime remains unclear. Here, the authors found that standard models explain spiking but not sub-threshold statistics; however, this was resolved by adding dendritic morphology, suggesting a functional role for dendrites in decision-making.
- Oren Amsalem
- , Hidehiko Inagaki
- & Ran Darshan
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Article
| Open AccessFixational eye movements enhance the precision of visual information transmitted by the primate retina
The visual signals transmitted by the retina to the brain are affected by random drift in eye position, but the impact of this on visual capabilities is not clear. Here, the authors show that the decoding of images from evoked spike trains recorded in the macaque retina improves with fixational eye movements, even when the eye position is unknown.
- Eric G. Wu
- , Nora Brackbill
- & E. J. Chichilnisky
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Matters Arising
| Open AccessInterindividual differences in pain can be explained by fMRI, sociodemographic, and psychological factors
- Suhwan Gim
- , Dong Hee Lee
- & Choong-Wan Woo
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Matters Arising
| Open AccessReply to: Interindividual differences in pain can be explained by fMRI, sociodemographic, and psychological factors
- M. E. Hoeppli
- , H. Nahman-Averbuch
- & R. C. Coghill
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Article
| Open AccessLOXHD1 is indispensable for maintaining TMC1 auditory mechanosensitive channels at the site of force transmission
The Grillet lab identified an additional component of the auditory mechanotransduction Machinery, the protein LOXHD1, which is indispensable to keep the ion channel subunit TMC1 next to the tip-link, where the force induced-by sound is transmitted.
- Pei Wang
- , Katharine K. Miller
- & Nicolas Grillet
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Article
| Open AccessA distinct neuronal ensemble of prelimbic cortex mediates spontaneous pain in rats with peripheral inflammation
Neural mechanisms underlying spontaneous pain are not fully understood. Here authors identify a unique neuronal ensemble in the PL of rats with chronic inflammation, encoding spontaneous pain independently. Activating this ensemble triggers pain-like behaviors, while inhibiting it alleviates pain and accelerates recovery.
- Longyu Ma
- , Lupeng Yue
- & Ming Yi
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Article
| Open AccessEntorhinal cortex vulnerability to human APP expression promotes hyperexcitability and tau pathology
In this study using an adult-onset mouse model of Alzheimer’s pathology, we uncovered a neuron-type-specific mechanism responsible for region-specific circuit dysfunction. Short-term expression of human amyloid precursor protein (hAPP) led to hyperexcitability in the entorhinal cortex, but not in isocortex, due to a distinct vulnerability of PV interneurons in the entorhinal region.
- Annie M. Goettemoeller
- , Emmie Banks
- & Matthew J. M. Rowan
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Article
| Open AccessSUB-immunogold-SEM reveals nanoscale distribution of submembranous epitopes
Nanoscale protein localisation by immunogold-scanning electron microscopy has been restricted to extracellular epitopes. Here, the authors extend this method to sub-membranous epitopes, revealing how transmembrane and cytoplasmic proteins distribute along the surfaces of exposed cells.
- Katharine K. Miller
- , Pei Wang
- & Nicolas Grillet
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Article
| Open AccessConcept and location neurons in the human brain provide the ‘what’ and ‘where’ in memory formation
Whether specialized neuronal firing in the human MTL predicts successful memory encoding remains unknown. Here, the authors find this to be the case for two distinct populations of single neurons responding to items and locations, respectively.
- Sina Mackay
- , Thomas P. Reber
- & Florian Mormann
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Article
| Open AccessARViS: a bleed-free multi-site automated injection robot for accurate, fast, and dense delivery of virus to mouse and marmoset cerebral cortex
To express a biosensor in primate cortex, multiple injections of virus carrying the sensor gene are necessary. Here, the authors develop an automated robotic system for multiple, safe injections.
- Shinnosuke Nomura
- , Shin-Ichiro Terada
- & Masanori Matsuzaki
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Article
| Open AccessDeep intravital brain tumor imaging enabled by tailored three-photon microscopy and analysis
Observation of glioblastoma invasion in subcortical brain regions is challenging. Here the authors develop a Deep3P workflow to enable longitudinal deep imaging of glioblastoma and its microenvironment by combining three-photon microscopy and deep learning-based analysis, unraveling the invasion routes of these tumor cells into and within the white matter.
- Marc Cicero Schubert
- , Stella Judith Soyka
- & Varun Venkataramani
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Article
| Open AccessVariants in LRRC7 lead to intellectual disability, autism, aggression and abnormal eating behaviors
Here the authors identify 33 individuals with a dominant neurodevelopmental disorder due to heterozygous missense or loss-of-function variants in the gene encoding Densin-180, a scaffold protein present at postsynaptic sites in neurons of the central nervous system.
- Jana Willim
- , Daniel Woike
- & Hans-Jürgen Kreienkamp
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Article
| Open AccessPropofol disrupts the functional core-matrix architecture of the thalamus in humans
Anesthesia alters thalamocortical circuits, causing a shift from unimodal-transmodal functional geometry to a transmodal-deficient pattern. This change is associated with disrupted matrix cell connectivity, suggesting a mechanism for unconsciousness.
- Zirui Huang
- , George A. Mashour
- & Anthony G. Hudetz
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Article
| Open AccessGenetic, transcriptomic, histological, and biochemical analysis of progressive supranuclear palsy implicates glial activation and novel risk genes
The authors present the largest genome-wide association study to date for a rare Parkinsonian disorder, progressive supranuclear palsy (PSP). They include follow-up investigations of the identified susceptibility loci, functional consequences, and cell-specific pathologies, providing insights into genetic and molecular mechanisms underlying PSP.
- Kurt Farrell
- , Jack Humphrey
- & Adam Naj
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Article
| Open AccessHuman cell surface-AAV interactomes identify LRP6 as blood-brain barrier transcytosis receptor and immune cytokine IL3 as AAV9 binder
Engineered adeno-associated viruses (AAVs) aim to improve safety and potency for use in gene therapy but mechanisms underlying these features are poorly understood. Here, authors use unbiased screens to identify an interaction with the human immune system and a determinant of enhanced brain potency.
- Timothy F. Shay
- , Seongmin Jang
- & Viviana Gradinaru
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Article
| Open AccessNetwork state changes in sensory thalamus represent learned outcomes
The computational role of individual sensory thalamic nuclei in flexible encoding during adaptive behaviors is not fully understood. Here authors, using longitudinal deep brain two-photon calcium imaging, show that changes in mouse auditory thalamus single cell and neuronal population dynamics are predictive of task outcome in cross-modal associative learning.
- Masashi Hasegawa
- , Ziyan Huang
- & Jan Gründemann
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Article
| Open AccessOptimal level of human intracranial theta activity for behavioral switching in the subthalamo-medio-prefrontal circuit
Direct electrophysiological recordings in the human prefronto-subthalamic circuit show that behavioral switching requires an optimal level of theta activity to be successful, which is well accounted for by a negative modulation of a drift-diffusion model starting point.
- Maëva Laquitaine
- , Mircea Polosan
- & Julien Bastin
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Article
| Open AccessWide-field calcium imaging of cortical activation and functional connectivity in externally- and internally-driven locomotion
How the cerebral cortex controls internally- versus sensory-driven movements remains unclear. Here the authors show that the differences in these two classes of movements are represented in cortex-wide activation and functional connectivity patterns.
- Sarah L. West
- , Morgan L. Gerhart
- & Timothy J. Ebner
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Article
| Open AccessAstrocyte-derived clusterin disrupts glial physiology to obstruct remyelination in mouse models of demyelinating diseases
Glia abnormalities drive the progression of demyelinating diseases. Here, the authors show that reactivated astrocytes secrete clusterin to impede remyelination by blocking astrocytic removal of myelin debris and oligodendrocyte precursor cell differentiation in mouse models of demyelination.
- Chen Chen
- , Yaqing Shu
- & Wei Qiu
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Article
| Open AccessGlutathione peroxidase 3 is a potential biomarker for konzo
The search for biomarkers associated with konzo disease has been a long-standing question within the research community. Here, the authors have uncovered a potential biomarker for konzo that is associated with the ability to manage oxidative damage.
- Matthew S. Bramble
- , Victor Fourcassié
- & Arnaud Droit
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Article
| Open AccessCognitive processing speed and accuracy are intrinsically different in genetic architecture and brain phenotypes
Here, the authors investigate the genetic architecture and neuroimaging signatures of cognitive processing speed and accuracy, two fundamental dimensions underlying cognitive abilities. They also identify links between these two factors and lifestyle, mental health and cognitive development.
- Mingyang Li
- , Xixi Dang
- & Dan Wu
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Article
| Open AccessHyperscanning shows friends explore and strangers converge in conversation
People employ different conversational strategies to establish social connection. Here, the authors use fMRI hyperscanning to track neural and linguistic trajectories during naturalistic conversation to show that friends diverge, exploring new ground, while strangers converge, seeking common ground.
- Sebastian P. H. Speer
- , Laetitia Mwilambwe-Tshilobo
- & Diana I. Tamir
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Article
| Open AccessHypothalamic-hindbrain circuit for consumption-induced fear regulation
Nutrient intake and threat avoidance interact adaptively. Here, authors show a molecularly defined hypothalamus-to-hindbrain circuit responsible for the regulation of fear by feeding in male mice, representing a novel coordination mechanism.
- Qin Wang
- , Rui-Yue Sun
- & Xiao-Ming Li
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Article
| Open AccessSex differences in functional cortical organization reflect differences in network topology rather than cortical morphometry
Here, the authors show sex differences in the functional sensory-association axis are associated with differences in functional connectivity profiles and network topology rather than reflecting differences in brain size, microstructural organization, or geodesic distance.
- Bianca Serio
- , Meike D. Hettwer
- & Sofie L. Valk
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Article
| Open AccessCannabidiol ameliorates mitochondrial disease via PPARγ activation in preclinical models
Mutations in mitochondrial genes cause untreatable diseases such as Leigh syndrome (LS). Here, authors show that cannabidiol (CBD) administration can extend lifespan and improves pathology in LS mouse models, mediated by PPARγ.
- Emma Puighermanal
- , Marta Luna-Sánchez
- & Albert Quintana
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Article
| Open AccessBase excision repair and double strand break repair cooperate to modulate the formation of unrepaired double strand breaks in mouse brain
DNA damage is observed in the brain. Here the authors show that high base excision repair (BER) and low double strand break repair (DSBR) in neurons facilitate reversible single strand break to double strand break conversion in response to oxidative stress.
- Aris A. Polyzos
- , Ana Cheong
- & Cynthia T. McMurray
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Comment
| Open AccessNeurovascular coupling during hypercapnia in cerebral blood flow regulation
Neuronal activity consumes cellular energy and generates carbon dioxide (CO2). To counter this metabolic challenge, synaptic signalling communicates with nearby microvasculature to increase local blood flow. Is this process solely based on feedforward synaptic signalling, or is the generated CO2 also involved? This question was addressed in mice in a new Nature Communications publication by Tournissac and colleagues where they showed that neurovascular coupling is not affected by exogenous CO2 or its associated acidification.
- Grant R. Gordon
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Article
| Open AccessNeurovascular coupling and CO2 interrogate distinct vascular regulations
A remerging hypothesis suggests that CO2 generated by neuronal metabolism contributes to neurovascular coupling (NVC). Here, the authors show that NVC is unaffected by the acidification of the entire arteriolar column during cerebrovascular reactivity to CO2, demonstrating that CO2 is not a mediator of NVC.
- Marine Tournissac
- , Emmanuelle Chaigneau
- & Serge Charpak
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