4 research outputs found
Quantification of interacting cognate odorants with olfactory receptors in nanovesicles
This study aims to improve our understanding of the interaction between olfactory receptors and odorants to develop highly selective biosensing devices. Natural nanovesicles (NVs) from Saccharomyces cerevisiae, ∼100 nm in diameter, carrying either the human OR17-40 or the chimpanzee OR7D4 olfactory receptor (OR) tagged with the c-myc epitope at their N-terminus, are presented as model systems to quantify the interaction between odorant and olfactory receptors. The level of expression of olfactory receptors was determined at individual NVs using a novel competitive ELISA immunoassay comparing the values obtained against those from techniques involving the solubilization of cell membrane proteins and the identification of c-myc-carrying receptors. Surface Plasmon Resonance (SPR) measurements on L1 Biacore chips indicate that cognate odorants bind to their Ors, thereby quantifying the approximate number of odorants that interact with a given olfactory receptor. The selectivity of OR17-40-carrying NVs towards helional and OR7D4-carrying NVs towards androstenone has been proven in cross-check experiments with non-specific odorant molecules (heptanal and pentadecalactone, respectively) and in control receptors. © 2017 The Author(s).This work was supported by the “Nanoscience, nanotechnologies, materials, and new production technologies” programme under the BOND project (228685-2) from the 7th Research Framework Programme of the European Union (PI and AC), by the FIS Project PI10/01171 funded by the Instituto de Salud Carlos III, by the Botin fundation, and by the predoctoral fellowship of the Instituto de Salud Carlos III-Ministry of Science and Innovation (Spain) (MS). The Nb4D group and Nanobioengineering SIC-BIO group are supported by the Commission for Universities and Research of the Department of Innovation, Universities, and Enterprise of the Generalitat de Catalunya (2014 SGR 1442 and 2014 SGR 1484). This work was partially supported by the MINDS project (TEC2015-70104-P), awarded by the Spanish Ministry of Economy and Competitiveness and the CERCA program from Generalitat de Catalunya. CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with support from the European Regional Development Fund. The authors also thank Dr. Marie-Annick Persuy and Dr. Edith Pajot-Augy (NBO, INRA, Université Paris-Saclay) for olfactory receptors expression in yeast cells and yeast membrane material. Dr. José Amable Bernabé (ICMAB/CSIC/CIBER BBN) for his help with Nanosight measurements and Dr. Carmen López (CCiT, UB) for her help with Cryo-EM measurements.Peer reviewe
Primary T-cell immunodeficiency with immunodysregulation caused by autosomal recessive LCK deficiency
International audienceSignals emanating from the antigen T-cell receptor (TCR) are required for T-cell development and function. The T lymphocyte-specific protein tyrosine kinase (Lck) is a key component of the TCR signaling machinery. On the basis of its function, we considered LCK a candidate gene in patients with combined immunodeficiency. Objective: We identify and describe a child with a T-cell immunodeficiency caused by a homozygous missense mutation of the LCK gene (c.1022T>C) resulting from uniparental disomy. Methods: Genetic, molecular, and functional analyses were performed to characterize the Lck deficiency, and the associated clinical and immunologic phenotypes are reported. Results: The mutant LCK protein (p.L341P) was weakly expressed with no kinase activity and failed to reconstitute TCR signaling in LCK-deficient T cells. The patient presented with recurrent respiratory tract infections together with predominant early-onset inflammatory and autoimmune manifestations. The patient displayed CD41 T-cell lymphopenia and low levels of CD4 and CD8 expression on the T-cell surface. The residual T lymphocytes had an oligoclonal T-cell repertoire and exhibited a profound TCR signaling defect, with only weak tyrosine phosphorylation signals and no Ca21 mobilization in response to TCR stimulation. Conclusion: We report a new form of T-cell immunodeficiency caused by a LCK gene defect, highlighting the essential role of Lck in human T-cell development and responses. Our results also point out that defects in the TCR signaling cascade often result in abnormal T-cell differentiation and functions, leading to an important risk factor for inflammation and autoimmunit
Minbar al-Sharq, No.489 (vol. 27, Feb. 13, 1948)
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Language impairment in the genetic forms of behavioural variant frontotemporal dementia
Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.Copyright © The Author(s) 2022. Background:
Behavioural variant fronto-temporal dementia (bvFTD) is characterised by a progressive change in personality in association with atrophy of the frontal and temporal lobes. Whilst language impairment has been described in people with bvFTD, little is currently known about the extent or type of linguistic difficulties that occur, particularly in the genetic forms.
Methods:
Participants with genetic bvFTD along with healthy controls were recruited from the international multicentre Genetic FTD Initiative (GENFI). Linguistic symptoms were assessed using items from the Progressive Aphasia Severity Scale (PASS). Additionally, participants undertook the Boston Naming Test (BNT), modified Camel and Cactus Test (mCCT) and a category fluency test. Participants underwent a 3T volumetric T1-weighted MRI, with language network regional brain volumes measured and compared between the genetic groups and controls.
Results:
76% of the genetic bvFTD cohort had impairment in at least one language symptom: 83% C9orf72, 80% MAPT and 56% GRN mutation carriers. All three genetic groups had significantly impaired functional communication, decreased fluency, and impaired sentence comprehension. C9orf72 mutation carriers also had significantly impaired articulation and word retrieval as well as dysgraphia whilst the MAPT mutation group also had impaired word retrieval and single word comprehension. All three groups had difficulties with naming, semantic knowledge and verbal fluency. Atrophy in key left perisylvian language regions differed between the groups, with generalised involvement in the C9orf72 group and more focal temporal and insula involvement in the other groups. Correlates of language symptoms and test scores also differed between the groups.
Conclusions:
Language deficits exist in a substantial proportion of people with familial bvFTD across all three genetic groups. Significant atrophy is seen in the dominant perisylvian language areas and correlates with language impairments within each of the genetic groups. Improved understanding of the language phenotype in the main genetic bvFTD subtypes will be helpful in future studies, particularly in clinical trials where accurate stratification and monitoring of disease progression is required.We thank the research participants and their families for their contribution to the study. Several authors of this publication are members of the European Reference Network for Rare Neurological Diseases—Project ID No 739510. The Dementia Research Centre is supported by Alzheimer’s Research UK, Alzheimer’s Society, Brain Research UK, and The Wolfson Foundation. This work was supported by the NIHR UCL/H Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer’s Research UK. This work was also supported by the JPND GENFI-PROX grant (2019-02248; to JDR, MO, BB, CG, JvS and MS. [latter via DLR/DFG 01ED2008B]). JDR is supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Bluefield Project and the JPND GENFI-PROX grant (2019-02248). Several authors of this publication are members of the European Reference Network for Rare Neurological Diseases—Project ID No 739510. RC/CG are supported by a Frontotemporal Dementia Research Studentships in Memory of David Blechner funded through The National Brain Appeal (RCN 290173). MB is supported by a Fellowship award from the Alzheimer’s Society, UK (AS-JF-19a-004-517). MB’s work is also supported by the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. JCVS was supported by the Dioraphte Foundation grant 09-02-03-00, the Association for Frontotemporal Dementias Research Grant 2009, The Netherlands Organization for Scientific Research (NWO) grant HCMI 056-13-018, ZonMw Memorabel (Deltaplan Dementie, project number 733 051 042), Alzheimer Nederland and the Bluefield project. FM received funding from the Tau Consortium and the Center for Networked Biomedical Research on Neurodegenerative Disease (CIBERNED). RS-V is supported by an Alzheimer’s Research UK Clinical Research Training Fellowship (ARUK-CRF2017B-2), and has received funding from Fundació Marató de TV3, Spain (grant no. 20143810). CG received funding from JPND-Prefrontals VR Dnr 529-2014-7504, VR 2015-02926 and 2018-02754, the Swedish FTD Inititative-Schörling Foundation, Alzheimer Foundation, Brain Foundation and Stockholm County Council ALF. MM has received funding from a Canadian Institute of Health Research operating grant and the Weston Brain Institute and Ontario Brain Institute. JBR has received funding from the Welcome Trust (103838) and is supported by the Cambridge University Centre for Frontotemporal Dementia, the Medical Research Council (SUAG/051 G101400) and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC-1215-20014). EF has received funding from a CIHR grant #327387. DG received support from the EU Joint Programme—Neurodegenerative Disease Research (JPND) and the Italian Ministry of Health (PreFrontALS) grant 733051042. RV has received funding from the Mady Browaeys Fund for Research into Frontotemporal Dementia. MO has received funding from BMBF (FTLDc). JL received funding for this work by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy—ID 390857198). Group authorship for the Genetic FTD Initiative (GENFI): Annabel Nelson: Department of Neurodegenerative Disease, Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK. David L Thomas: Neuroimaging Analysis Centre, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, Queen Square, London, UK. Emily Todd: Department of Neurodegenerative Disease, Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK. Hanya Benotmane: UK Dementia Research Institute at University College London, UCL Queen Square Institute of Neurology, London, UK. Jennifer Nicholas: Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK. Rachelle Shafei: Department of Neurodegenerative Disease, Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK. Carolyn Timberlake: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK. Thomas Cope: Department of Clinical Neuroscience, University of Cambridge, Cambridge, UK. Timothy Rittman: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK. Alberto Benussi: Centre for Neurodegenerative Disorders, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy. Enrico Premi: Stroke Unit, ASST Brescia Hospital, Brescia, Italy. Roberto Gasparotti: Neuroradiology Unit, University of Brescia, Brescia, Italy. Silvana Archetti: Biotechnology Laboratory, Department of Diagnostics, ASST Brescia Hospital, Brescia, Italy. Stefano Gazzina: Neurology, ASST Brescia Hospital, Brescia, Italy. Valentina Cantoni: Centre for Neurodegenerative Disorders, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy. Andrea Arighi: Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Neurodegenerative Diseases Unit, Milan, Italy; University of Milan, Centro Dino Ferrari, Milan, Italy. Chiara Fenoglio: Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Neurodegenerative Diseases Unit, Milan, Italy; University of Milan, Centro Dino Ferrari, Milan, Italy. Elio Scarpini: Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Neurodegenerative Diseases Unit, Milan, Italy; University of Milan, Centro Dino Ferrari, Milan, Italy. Giorgio Fumagalli: Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Neurodegenerative Diseases Unit, Milan, Italy; University of Milan, Centro Dino Ferrari, Milan, Italy. Vittoria Borracci: Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Neurodegenerative Diseases Unit, Milan, Italy; University of Milan, Centro Dino Ferrari, Milan, Italy. Giacomina Rossi: Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy. Giorgio Giaccone: Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy. Giuseppe Di Fede: Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy. Paola Caroppo: Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy. Pietro Tiraboschi: Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy. Sara Prioni: Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy. Veronica Redaelli: Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy. David Tang-Wai: The University Health Network, Krembil Research Institute, Toronto, Canada. Ekaterina Rogaeva: Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada. Miguel Castelo-Branco: Faculty of Medicine, University of Coimbra, Coimbra, Portugal. Morris Freedman: Baycrest Health Sciences, Rotman Research Institute, University of Toronto, Toronto, Canada. Ron Keren: The University Health Network, Toronto Rehabilitation Institute, Toronto, Canada. Sandra Black: Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Toronto, Canada. Sara Mitchell: Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Toronto, Canada. Christen Shoesmith: Department of Clinical Neurological Sciences, University of Western Ontario, London, Ontario, Canada. Robart Bartha: Department of Medical Biophysics, The University of Western Ontario, London, Ontario, Canada; Centre for Functional and Metabolic Mapping, Robarts Research Institute, The University of Western Ontario, London, Ontario, Canada. Rosa Rademakers: Center for Molecular Neurology, University of Antwerp. Jackie Poos: Department of Neurology, Erasmus Medical Center, Rotterdam, Netherlands. Janne M. Papma: Department of Neurology, Erasmus Medical Center, Rotterdam, Netherlands. Lucia Giannini: Department of Neurology, Erasmus Medical Center, Rotterdam, Netherlands. Rick van Minkelen: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, Netherlands. Yolande Pijnenburg: Amsterdam University Medical Centre, Amsterdam VUmc, Amsterdam, Netherlands. Benedetta Nacmias: Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy. Camilla Ferrari: Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy. Cristina Polito: Department of Biomedical, Experimental and Clinical Sciences “Mario Serio”, Nuclear Medicine Unit, University of Florence, Florence, Italy. Gemma Lombardi: Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy. Valentina Bessi: Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy. Michele Veldsman: Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, UK. Christin Andersson: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. Hakan Thonberg: Center for Alzheimer Research, Division of Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden. Linn Öijerstedt: Center for Alzheimer Research, Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Bioclinicum, Karolinska Institutet, Solna, Sweden; Unit for Hereditary Dementias, Theme Aging, Karolinska University Hospital, Solna, Sweden. Vesna Jelic: Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden. Paul Thompson: Division of Neuroscience and Experimental Psychology, Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK. Tobias Langheinrich: Division of Neuroscience and Experimental Psychology, Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK; Manchester Centre for Clinical Neurosciences, Department of Neurology, Salford Royal NHS Foundation Trust, Manchester, UK. Albert Lladó: Alzheimer’s disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Barcelona, Spain. Anna Antonell: Alzheimer’s disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Barcelona, Spain. Jaume Olives: Alzheimer’s disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Barcelona, Spain. Mircea Balasa: Alzheimer’s disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Barcelona, Spain. Nuria Bargalló: Imaging Diagnostic Center, Hospital Clínic, Barcelona, Spain. Sergi Borrego-Ecija: Alzheimer’s disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Barcelona, Spain. Ana Verdelho: Department of Neurosciences and Mental Health, Centro Hospitalar Lisboa Norte—Hospital de Santa Maria & Faculty of Medicine, University of Lisbon, Lisbon, Portugal. Carolina Maruta: Laboratory of Language Research, Centro de Estudos Egas Moniz, Faculty of Medicine, University of Lisbon, Lisbon, Portugal. Catarina B. Ferreira: Laboratory of Neurosciences, Faculty of Medicine, University of Lisbon, Lisbon, Portugal. Gabriel Miltenberger: Faculty of Medicine, University of Lisbon, Lisbon, Portugal. Frederico Simões do Couto: Faculdade de Medicina, Universidade Católica Portuguesa. Alazne Gabilondo: Cognitive Disorders Unit, Department of Neurology, Donostia University Hospital, San Sebastian, Gipuzkoa, Spain; Neuroscience Area, Biodonostia Health Research Insitute, San Sebastian, Gipuzkoa, Spain. Ana Gorostidi: Neuroscience Area, Biodonostia Health Research Insitute, San Sebastian, Gipuzkoa, Spain. Jorge Villanua: OSATEK, University of Donostia, San Sebastian, Gipuzkoa, Spain. Marta Cañada: CITA Alzheimer, San Sebastian, Gipuzkoa, Spain. Mikel Tainta: Neuroscience Area, Biodonostia Health Research Insitute, San Sebastian, Gipuzkoa, Spain. Miren Zulaica: Neuroscience Area, Biodonostia Health Research Insitute, San Sebastian, Gipuzkoa, Spain. Myriam Barandiaran: Cognitive Disorders Unit, Department of Neurology, Donostia University Hospital, San Sebastian, Gipuzkoa, Spain; Neuroscience Area, Biodonostia Health Research Insitute, San Sebastian, Gipuzkoa, Spain. Patricia Alves: Neuroscience Area, Biodonostia Health Research Insitute, San Sebastian, Gipuzkoa, Spain; Department of Educational Psychology and Psychobiology, Faculty of Education, International University of La Rioja, Logroño, Spain. Benjamin Bender: Department of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany. Carlo Wilke: Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany; Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany. Lisa Graf: Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany. Annick Vogels: Department of Human Genetics, KU Leuven, Leuven, Belgium. Mathieu Vandenbulcke: Geriatric Psychiatry Service, University Hospitals Leuven, Belgium; Neuropsychiatry, Department of Neurosciences, KU Leuven, Leuven, Belgium. Philip Van Damme: Neurology Service, University Hospitals Leuven, Belgium; Laboratory for Neurobiology, VIB-KU Leuven Centre for Brain Research, Leuven, Belgium. Rose Bruffaerts: Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Biomedical Research Institute, Hasselt University, 3500 Hasselt, Belgium. Koen Poesen: Laboratory for Molecular Neurobiomarker Research, KU Leuven, Leuven, Belgium. Pedro Rosa-Neto: Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, McGill University, Montreal, Québec, Canada. Serge Gauthier: Alzheimer Disease Research Unit, McGill Centre for Studies in Aging, Department of Neurology & Neurosurgery, McGill University, Montreal, Québec, Canada. Agnès Camuzat: Sorbonne Université, Paris Brain Institute—Institut du Cerveau—ICM, Inserm U1127, CNRS UMR 7225, AP-HP—Hôpital Pitié-Salpêtrière, Paris, France. Alexis Brice: Sorbonne Université, Paris Brain Institute—Institut du Cerveau—ICM, Inserm U1127, CNRS UMR 7225, AP-HP—Hôpital Pitié-Salpêtrière, Paris, France; Reference Network for Rare Neurological Diseases (ERN-RND). Anne Bertrand: Sorbonne Université, Paris Brain Institute—Institut du Cerveau—ICM, Inserm U1127, CNRS UMR 7225, AP-HP—Hôpital Pitié-Salpêtrière, Paris, France; Inria, Aramis project-team, F-75013, Paris, France; Centre pour l'Acquisition et le Traitement des Images, Institut du Cerveau et la Moelle, Paris, France. Aurélie Funkiewiez: Centre de référence des démences rares ou précoces, IM2A, Département de Neurologie, AP-HP—Hôpital Pitié-Salpêtrière, Paris, France; Sorbonne Université, Paris Brain Institute – Institut du Cerveau—ICM, Inserm U1127, CNRS UMR 7225, AP-HP—Hôpital Pitié-Salpêtrière, Paris, France. Daisy Rinaldi: Centre de référence des démences rares ou précoces, IM2A, Département de Neurologie, AP-HP—Hôpital Pitié-Salpêtrière, Paris, France; Sorbonne Université, Paris Brain Institute—Institut du Cerveau—ICM, Inserm U1127, CNRS UMR 7225, AP-HP—Hôpital Pitié-Salpêtrière, Paris, France; Département de Neurologie, AP-HP—Hôpital Pitié-Salpêtrière, Paris, France. Dario Saracino: Sorbonne Université, Paris Brain Institute – Institut du Cerveau—ICM, Inserm U1127, CNRS UMR 7225, AP-HP—Hôpital Pitié-Salpêtrière, Paris, France; Inria, Aramis project-team, F-75013, Paris, France; Centre de référence des démences rares ou précoces, IM2A, Département de Neurologie, AP-HP—Hôpital Pitié-Salpêtrière, Paris, France. Olivier Colliot: Sorbonne Université, Paris Brain Institute—Institut du Cerveau—ICM, Inserm U1127, CNRS UMR 7225, AP-HP—Hôpital Pitié-Salpêtrière, Paris, France; Inria, Aramis project-team, F-75013, Paris, France; Centre pour l'Acquisition et le Traitement des Images, Institut du Cerveau et la Moelle, Paris, France. Sabrina Sayah: Sorbonne Université, Paris Brain Institute—Institut du Cerveau—ICM, Inserm U1127, CNRS UMR 7225, AP-HP—Hôpital Pitié-Salpêtrière, Paris, France. Catharina Prix: Neurologische Klinik, Ludwig-Maximilians-Universität München, Munich, Germany. Elisabeth Wlasich: Neurologische Klinik, Ludwig-Maximilians-Universität München, Munich, Germany. Olivia Wagemann: Neurologische Klinik, Ludwig-Maximilians-Universität München, Munich, Germany. Sandra Loosli: Neurologische Klinik, Ludwig-Maximilians-Universität München, Munich, Germany. Sonja Schönecker: Neurologische Klinik, Ludwig-Maximilians-Universität München, Munich, Germany. Tobias Hoegen: Neurologische Klinik, Ludwig-Maximilians-Universität München, Munich, Germany. Jolina Lombardi: Department of Neurology, University of Ulm, Ulm. Sarah Anderl-Straub: Department of Neurology, University of Ulm, Ulm, Germany. Adeline Rollin: CHU, CNR-MAJ, Labex Distalz, LiCEND Lille, France. Gregory Kuchcinski: Univ Lille, France; Inserm 1172, Lille, France; CHU, CNR-MAJ, Labex Distalz, LiCEND Lille, France. Maxime Bertoux: Inserm 1172, Lille, France; CHU, CNR-MAJ, Labex Distalz, LiCEND Lille, France. Thibaud Lebouvier: Univ Lille, France; Inserm 1172, Lille, France; CHU, CNR-MAJ, Labex Distalz, LiCEND Lille, France. Vincent Deramecourt: Univ Lille, France; Inserm 1172, Lille, France; CHU, CNR-MAJ, Labex Distalz, LiCEND Lille, France. Beatriz Santiago: Neurology Department, Centro Hospitalar e Universitario de Coimbra, Coimbra, Portugal. Diana Duro: Faculty of Medicine, University of Coimbra, Coimbra, Portugal. Maria João Leitão: Centre of Neurosciences and Cell Biology, Universidade de Coimbra, Coimbra, Portugal. Maria Rosario Almeida: Faculty of Medicine, University of Coimbra, Coimbra, Portugal. Miguel Tábuas-Pereira: Neurology Department, Centro Hospitalar e Universitario de Coimbra, Coimbra, Portugal. Sónia Afonso: Instituto Ciencias Nucleares Aplicadas a Saude, Universidade de Coimbra, Coimbra, Portugal
