α-Tocopherol Protects Against Oxidative Stress in the Fragile X Knockout Mouse: an Experimental Therapeutic Approach for the Fmr1 Deficiency
Open accessAbstract
Fragile X syndrome is the most common genetic cause of mental disability. The mechanisms underlying the pathogenesis remain unclear and specific treatments are still under development. Previous studies have proposed an abnormal hypothalamic-pituitary-adrenal axis and high cortisol levels are demonstrated in the fragile X patients. Additionally, we have previously described that NADPH-oxidase activation leads to oxidative stress in the brain, representing a pathological mechanism in the fragile X mouse model. Fmr1-knockout mice develop an altered free radical production, abnormal glutathione homeostasis, high lipid and protein oxidation, accompanied by stress-dependent behavioral abnormalities and pathological changes in the first months of postnatal life. Chronic pharmacological treatment with alpha-tocopherol reversed pathophysiological hallmarks including free radical overproduction, oxidative stress, Rac1 and alpha-PKC activation, macroorchidism, and also behavior and learning deficits. The restoration of the oxidative status in the fragile X mouse emerges as a new and promising approach for further therapeutic research in fragile X syndrome.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The absence of FMRP, as shown in FMR1-knockout mice, leads to increased oxidative stress (152-154).
“the absence of FMRP, as shown in FMR1-knockout mice, leads to increased oxidative stress (152–154).”
From Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms (2014) · cites this paper as [153]
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302 · see citing works
Physiology and neurobiology of stress and adaptation: central role of the brain
McEwen, B. S. (2007) · Physiological Reviews · doi:10.1152/physrev.00041.2006 · Cited by 4,981 · see citing works
[12] Assays of glutathione peroxidase
Flohé, L., & Günzler, W. A. (1984) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(84)05015-1 · Cited by 4,954 · see citing works
A fluorometric method for determination of oxidized and reduced glutathione in tissues
Hissin, P. J., & Hilf, R. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90326-2 · Cited by 4,116 · see citing works
Verkerk, A. J. M. H., Pieretti, M., Sutcliffe, J. S., Fu, Y.-H., Kuhl, D. P. A., Pizzuti, A., Reiner, O., Richards, S., Victoria, M. F., Zhang, F., et al. (1991) · Cell · doi:10.1016/0092-8674(91)90397-h · Cited by 3,481 · see citing works
[42] Determination of aldehydic lipid peroxidation products: Malonaldehyde and 4-hydroxynonenal
Esterbauer, H., & Cheeseman, K. H. (1990) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(90)86134-h · Cited by 3,365 · see citing works
Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.
Phillips, R. G., & LeDoux, J. E. (1992) · Behavioral Neuroscience · doi:10.1037/0735-7044.106.2.274 · Cited by 3,292 · see citing works
Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.
Phillips, R. G., & LeDoux, J. E. (1992) · Behavioral Neuroscience · doi:10.1037//0735-7044.106.2.274 · Cited by 3,262 · see citing works
NOX enzymes and the biology of reactive oxygen
Lambeth, J. D. (2004) · Nature Reviews Immunology · doi:10.1038/nri1312 · Cited by 3,125 · see citing works
Carlberg, I., & Mannervik, B. (1985) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(85)13062-4 · Cited by 3,009 · see citing works
The use of a plus-maze to measure anxiety in the mouse
Lister, R. G. (1987) · Psychopharmacology · doi:10.1007/bf00177912 · Cited by 2,617 · see citing works
A Controlled Trial of Selegiline, Alpha-Tocopherol, or Both as Treatment for Alzheimer's Disease
Sano, M., Ernesto, C., Thomas, R. G., Klauber, M. R., Schafer, K., Grundman, M., Woodbury, P., Growdon, J., Cotman, C. W., Pfeiffer, E., et al. (1997) · New England Journal of Medicine · doi:10.1056/nejm199704243361704 · Cited by 2,380 · see citing works
Neurocircuitry of stress: central control of the hypothalamo–pituitary–adrenocortical axis
Herman, J. P., & Cullinan, W. E. (1997) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)10069-2 · Cited by 2,270 · see citing works
Biochemistry and pathology of radical-mediated protein oxidation
Dean, R. T., Fu, S., Stocker, R., & Davies, M. J. (1997) · Biochemical Journal · doi:10.1042/bj3240001 · Cited by 1,678 · see citing works
Brown, V., Jin, P., Ceman, S., Darnell, J. C., O'Donnell, W. T., Tenenbaum, S. A., Jin, X., Feng, Y., Wilkinson, K. D., Keene, J. D., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00568-2 · Cited by 1,109 · see citing works
Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE
Wautier, M., Chappey, O., Corda, S., Stern, D. M., Schmidt, A. M., & Wautier, J. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.280.5.e685 · Cited by 1,076 · see citing works
Fmr1 knockout mice: A model to study fragile X mental retardation
THEDUTCHBELGIANFRAGILEXCONSOR (1994) · Cell · doi:10.1016/0092-8674(94)90569-x · Cited by 1,075 · see citing works
Correction of Fragile X Syndrome in Mice
Dölen, G., Osterweil, E., Rao, B. S. S., Smith, G. B., Auerbach, B. D., Chattarji, S., & Bear, M. F. (2007) · Neuron · doi:10.1016/j.neuron.2007.12.001 · Cited by 979 · see citing works
Protein carbonylation in human diseases
Dalle-Donne, I., Giustarini, D., Colombo, R., Rossi, R., & Milzani, A. (2003) · Trends in Molecular Medicine · doi:10.1016/s1471-4914(03)00031-5 · Cited by 961 · see citing works
Magarin˜os, A. M., & McEwen, B. S. (1995) · Neuroscience · doi:10.1016/0306-4522(95)00259-l · Cited by 863 · see citing works
Morris, M. C. (2002) · JAMA · doi:10.1001/jama.287.24.3230 · Cited by 678 · see citing works
Levine, R. L. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)00765-7 · Cited by 657 · see citing works
Chauhan, A., & Chauhan, V. (2006) · Pathophysiology · doi:10.1016/j.pathophys.2006.05.007 · Cited by 656 · see citing works
Weiler, I. J., Irwin, S. A., Klintsova, A. Y., Spencer, C. M., Brazelton, A. D., Miyashiro, K., Comery, T. A., Patel, B., Eberwine, J., & Greenough, W. T. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.10.5395 · Cited by 644 · see citing works
Floyd, R. A., & Carney, J. M. (1992) · Annals of Neurology · doi:10.1002/ana.410320706 · Cited by 541 · see citing works
Li, Y., Zhu, H., Kuppusamy, P., Roubaud, V., Zweier, J. L., & Trush, M. A. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.4.2015 · Cited by 526 · see citing works
Suppression of two major Fragile X Syndrome mouse model phenotypes by the mGluR5 antagonist MPEP
Yan, Q. J., Rammal, M., Tranfaglia, M., & Bauchwitz, R. P. (2005) · Neuropharmacology · doi:10.1016/j.neuropharm.2005.06.004 · Cited by 521 · see citing works
Glyoxalase 1 and glutathione reductase 1 regulate anxiety in mice
Hovatta, I., Tennant, R. S., Helton, R., Marr, R. A., Singer, O., Redwine, J. M., Ellison, J. A., Schadt, E. E., Verma, I. M., Lockhart, D. J., et al. (2005) · Nature · doi:10.1038/nature04250 · Cited by 498 · see citing works
RNA cargoes associating with FMRP reveal deficits in cellular functioning in Fmr1 null mice
Miyashiro, K. Y., Beckel-Mitchener, A., Purk, T. P., Becker, K. G., Barret, T., Liu, L., Carbonetto, S., Weiler, I. J., Greenough, W. T., & Eberwine, J. (2003) · Neuron · doi:10.1016/s0896-6273(03)00034-5 · Cited by 495 · see citing works
Regulation of reactive-oxygen-species generation in fibroblasts by Rac 1
Sundaresan, M., Yu, Z., Ferrans, V. J., Sulciner, D. J., Gutkind, J. S., Irani, K., Goldschmidt‐Clermont, P. J., & Finkel, T. (1996) · Biochemical Journal · doi:10.1042/bj3180379 · Cited by 486 · see citing works
McBride, S. M. J., Choi, C. H., Wang, Y., Liebelt, D. A., Braunstein, E. M., Ferreiro, D., Sehgal, A., Siwicki, K. K., Dockendorff, T. C., Nguyen, H. T., et al. (2005) · Neuron · doi:10.1016/j.neuron.2005.01.038 · Cited by 473 · see citing works
Immobilization stress causes oxidative damage to lipid, protein, and DNA in the brain of rats
Liu, J., Wang, X., Shigenaga, M. K., Yeo, H. C. H., Mori, A., & Ames, B. N. (1996) · The FASEB Journal · doi:10.1096/fasebj.10.13.8940299 · Cited by 383 · see citing works
Non-Antioxidant Activities of Vitamin E
Zingg, J.-M. A., & Azzi, A. (2004) · Current Medicinal Chemistry · doi:10.2174/0929867043365332 · Cited by 377 · see citing works
A new function for the fragile X mental retardation protein in regulation of PSD-95 mRNA stability
Zalfa, F., Eleuteri, B., Dickson, K. S., Mercaldo, V., Rubeis, S. D., di Penta, A., Tabolacci, E., Chiurazzi, P., Neri, G., Grant, S. G. N., et al. (2007) · Nature Neuroscience · doi:10.1038/nn1893 · Cited by 364 · see citing works
Virgin, C. E., Ha, T. P., Packan, D. R., Tombaugh, G. C., Yang, S. H., Homer, H. C., & Sapolsky, R. M. (1991) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1991.tb08309.x · Cited by 358 · see citing works
Singh, L. K., Pang, X., Alexacos, N., Létourneau, R., & Theoharides, T. C. (1999) · Brain Behavior and Immunity · doi:10.1006/brbi.1998.0541 · Cited by 346 · see citing works
(Over)correction of FMR1 deficiency with YAC transgenics: behavioral and physical features
Peier, A. M. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.8.1145 · Cited by 285 · see citing works
Inhibition of p21-activated kinase rescues symptoms of fragile X syndrome in mice
Hayashi, M. L., Rao, B. S. S., Seo, J.-S., Choi, H.-S., Dolan, B. M., Choi, S.-Y., Chattarji, S., & Tonegawa, S. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705003104 · Cited by 281 · see citing works
[62] Glutathione transferases from human liver
Warholm, M., Guthenberg, C., von Bahr, C., & Mannervik, B. (1985) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(85)13065-x · Cited by 278 · see citing works
Sensorimotor gating abnormalities in young males with fragile X syndrome and Fmr1-knockout mice.
Frankland, P. W., Wang, Y., Rosner, B., Shimizu, T., Balleine, B. W., Dykens, E. M., Ornitz, E. M., & Silva, A. J. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001432 · Cited by 275 · see citing works
Brain-Derived Neurotrophic Factor Rescues Synaptic Plasticity in a Mouse Model of Fragile X Syndrome
Lauterborn, J. C., Rex, C. S., Kramár, E. A., Chen, L. Y., Pandyarajan, V., LYNCH, G. S., & Gall, C. M. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2624-07.2007 · Cited by 241 · see citing works
Lee, A., Li, W., Xu, K., Bogert, B. A., Su, K., & Gao, F. (2003) · Development · doi:10.1242/dev.00792 · Cited by 229 · see citing works
Grossman, A. W., Elisseou, N. M., McKinney, B. C., & Greenough, W. T. (2006) · Brain Research · doi:10.1016/j.brainres.2006.02.044 · Cited by 204 · see citing works
Prevention of PC12 Cell Death byN-Acetylcysteine Requires Activation of the Ras Pathway
Yan, C. Y. I., & Greene, L. A. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-11-04042.1998 · Cited by 162 · see citing works
Transport of Fragile X Mental Retardation Protein via Granules in Neurites of PC12 Cells
de Diego‐Otero, Y., Severijnen, L.-A. W. F. M., van Cappellen, G. W. A., Schrier, M., Oostra, B. A., & Willemsen, R. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.23.8332-8341.2002 · Cited by 149 · see citing works
Cortisol and behavior in fragile X syndrome
Hessl, D., Glaser, B., Dyer-Friedman, J., Blasey, C., Hastie, T., Gunnar, M., & Reiss, A. L. (2002) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(01)00087-7 · Cited by 115 · see citing works
Rac1 Induces the Clustering of AMPA Receptors during Spinogenesis
Wiens, K. M., Lin, H., & Liao, D. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.1947-05.2005 · Cited by 111 · see citing works
A Rho-related GTPase Is Involved in Ca2+-dependent Neurotransmitter Exocytosis
Doussau, F., Gasman, S., Humeau, Y., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.11.7764 · Cited by 109 · see citing works
Hippocampal mossy fiber distribution covaries with open-field habituation in the mouse
Crusio, W. E., & Schwegler, H. (1987) · Behavioural Brain Research · doi:10.1016/0166-4328(87)90163-x · Cited by 102 · see citing works
Vitamin E therapy in Parkinson's disease
Fariss, M. W. (2003) · Toxicology · doi:10.1016/s0300-483x(03)00158-6 · Cited by 100 · see citing works
The fragile X syndrome: exploring its molecular basis and seeking a treatment
Bardoni, B., Davidovic, L., Bensaid, M., & Khandjian, É. W. (2006) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399406010751 · Cited by 100 · see citing works
Oxidative stress and neural dysfunction in Down Syndrome
Iannello, R. C., Crack, P. J., de Haan, J. B., & Kola, I. (1999) · Springer eBooks · doi:10.1007/978-3-7091-6380-1_17 · Cited by 89 · see citing works
Irreversible Inactivation of Protein Kinase C by Glutathione
Ward, N. E., Pierce, D. S., Chung, S. E., et al. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.20.12558 · Cited by 89 · see citing works
Guo, L., Wang, L. H., Sun, B., Yang, J., Zhao, Y. Q., Dong, Y. X., Spranger, M. I., & Wu, C. F. (2007) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf070440a · Cited by 86 · see citing works
El Bekay, R., Romero‐Zerbo, Y., Decara, J., Sanchez‐Salido, L., Del Arco‐Herrera, I., Rodríguez‐de Fonseca, F., & De Diego‐Otero, Y. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05939.x · Cited by 85 · see citing works
Self-citationNeuroprotective effects of α-tocopherol on oxidative stress in rat striatal cultures
Osakada, F., Hashino, A., Kume, T., et al. (2003) · European Journal of Pharmacology · doi:10.1016/s0014-2999(03)01495-x · Cited by 74 · see citing works
Vitamin E in the Genesis and Prevention of Cancer a Review
Das, S. (1994) · Acta Oncologica · doi:10.3109/02841869409121771 · Cited by 65 · see citing works
Final common pathways in neurodegenerative diseases: regulatory role of the glutathione cycle
Weber, G. F. (1999) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(99)00041-x · Cited by 61 · see citing works
Facilitation of Ca2+‐dependent exocytosis by Rac1‐GTPase in bovine chromaffin cells
Li, Q., Ho, C. S., Marinescu, V., et al. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.039073 · Cited by 56 · see citing works
del Arco, I., Muñoz, R. M., de Fonseca, F. R., Escudero, L., Martı́n-Calderón, J. L., Navarro, M., & Villanúa, M. Á. (1999) · NeuroImmunoModulation · doi:10.1159/000026416 · Cited by 46 · see citing works
Self-citationGruss, M. (2004) · Neurochemistry International · doi:10.1016/j.neuint.2003.12.001 · Cited by 40 · see citing works
Fragile X Syndrome: A Model of Gene-Brain-Behavior Relationships
Hagerman, R. J., & Hagerman, P. J. (2001) · Molecular Genetics and Metabolism · doi:10.1006/mgme.2001.3225 · Cited by 33 · see citing works
Translocation and activation of Rac in the hippocampus during associative contextual fear learning
Martinez, L. A., Klann, E., & Tejada-Simon, M. V. (2007) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2007.01.008 · Cited by 31 · see citing works
Understanding the biological underpinnings of fragile X syndrome
Chiurazzi, P., Neri, G., & Oostra, B. A. (2003) · Current Opinion in Pediatrics · doi:10.1097/00008480-200312000-00003 · Cited by 29 · see citing works
Ainsah, O., Nabishah, B. M., Osman, C., et al. (2009) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0029-1212139 · Cited by 15 · see citing works
Beskow, A. H., Emahazion, T., Prince, J. A., Angelini, C. I., & Brookes, A. J. (2000) · Gene Function & Disease · doi:10.1002/1438-826x(200005)1:1
Flagged first, then by citations
Cited by
Sorted by citations
Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms
Tordjman, S., Somogyi, E., Coulon, N., Kermarrec, S., Cohen, D., Bronsard, G., Bonnot, O., Weismann-Arcache, C., Botbol, M., Lauth, B., et al. (2014) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2014.00053 · Cited by 283 · see citing works
A novel function for fragile X mental retardation protein in translational activation
Bechara, E. G., Didiot, M. C., Melko, M., Davidovic, L., Bensaid, M., Martin, P., Castets, M., Pognonec, P., Khandjian, E. W., Moine, H., et al. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000016 · Cited by 206 · see citing works
From Chronic Cerebral Hypoperfusion to Alzheimer-Like Brain Pathology and Neurodegeneration
Zhao, Y., & Gong, C.-X. (2015) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-014-0127-9 · Cited by 180 · see citing works
McLennan, Y., Polussa, J., Tassone, F., & Hagerman, R. (2011) · Current Genomics · doi:10.2174/138920211795677886 · Cited by 160 · see citing works
Pyronneau, A., He, Q., Hwang, J.-Y., Porch, M., Contractor, A., & Zukin, R. S. (2017) · Science Signaling · doi:10.1126/scisignal.aan0852 · Cited by 122 · see citing works
Utari, A., Chonchaiya, W., Rivera, S. M., Schneider, A., Hagerman, R. J., Faradz, S. M. H., Ethell, I. M., & Nguyen, D. V. (2010) · American Journal on Intellectual and Developmental Disabilities · doi:10.1352/1944-7558-115.5.433 · Cited by 105 · see citing works
FMR1 premutation and full mutation molecular mechanisms related to autism
Hagerman, R., Au, J., & Hagerman, P. (2011) · Journal of Neurodevelopmental Disorders · doi:10.1007/s11689-011-9084-5 · Cited by 85 · see citing works
Brief Report: Acamprosate in Fragile X Syndrome
Erickson, C. A., Mullett, J. E., & McDougle, C. J. (2010) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-010-0988-9 · Cited by 67 · see citing works
Biologic stress, oxidative stress, and resistance to drugs: what is hidden behind
Pantelidou, M., Tsiakitzis, K., Rekka, E., & Kourounakis, P. (2017) · Molecules · doi:10.3390/molecules22020307 · Cited by 7 · see citing works
- Authors
- de Diego-Otero, Y., Romero-Zerbo, Y., Bekay, R. E., Decara, J., Sanchez, L., Fonseca, F. R.-D., & Arco-Herrera, I. D.
- Affiliations
- Instituto de Salud Carlos III (ES)
- Venue
- Neuropsychopharmacology
- Published
- 2008-10-08
- Volume
- 34
- Issue
- 4
- Pages
- 1011-1026
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- OpenAlex
- W2012355507
- Cited by
- 133
- References
- 66
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 5 · 2023: 3 · 2022: 3 · 2021: 8 · 2020: 5 · 2019: 4 · 2018: 7 · 2017: 9 · 2016: 11 · 2015: 13 · 2014: 19 · 2013: 11 · 2012: 11
- FWCI
- 4.00
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Repositorio Institucional de la Universidad de Málaga (University of Málaga) (submittedVersion, cc-by)
- Funders
- Erasmus Medisch Centrum
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Keywords
- fragile X syndrome, alpha-tocopherol, oxidative stress, Fmr1 knockout mice, NADPH oxidase, glutathione homeostasis, lipid peroxidation, protein oxidation, Rac1, macroorchidism, learning deficits, antioxidant therapy
- MeSH terms
- Acetylcysteine, Aging, Animals, Antioxidants, Behavior, Animal, Conditioning, Psychological, Dose-Response Relationship, Drug, Enzyme Activation, Exploratory Behavior, Fear, Fragile X Syndrome, Free Radicals, Male, Neuropeptides, Phenotype, Stress, Psychological, Mice, Knockout, Oxidative Stress, rac GTP-Binding Proteins, rac1 GTP-Binding Protein, alpha-Tocopherol, Mice, Protein Kinase C-alpha, Fragile X Mental Retardation Protein, Fragile X Messenger Ribonucleoprotein 1, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
