Neuroscience and Disease

Novel Signaling Biomarkers and Mediators in Gut-Brain Axis Communication and Regulation

Gut health, Neurodegenerative disorders, Mitochondria, Immunity, DAMPs, miRNAs, ccf-mtDNA


Research lines

Impact of miRNAs and ccf-mtDNA in neurodegenerative diseases and inflammatory bowel diseases

Discovery of Novel Biomarkers for Neurodegenerative Disease Diagnosis

Overview

This line of research focuses on understanding how microRNAs (miRNAs) and circulating cell-free mitochondrial DNA (ccf-mtDNA) regulate gene expression and serve as signaling molecules along the gut-brain axis, influencing neurodegenerative diseases like Parkinson's. By examining specific miRNAs involved in gut microbiota communication and neuroinflammation, alongside the role of ccf-mtDA in immune responses and gut-brain signaling, we will uncover novel molecular mechanisms and identify therapeutic targets to mitigate neuronal degeneration and develop innovative treatments for these conditions.

This research line will focus on identifying specific microRNAs (miRNAs) and circulating cell-free mitochondrial DNA (ccf-mtDA) as potential biomarkers for early detection and progression monitoring of gut-brain axis dysfunction in both neurodegenerative (e.g., Alzheimer's, Parkinson's) and gut inflammatory diseases (e.g., Crohn's disease, ulcerative colitis). By profiling miRNA and ccf-mtDA expression in patients and animal models, we seek to identify specific molecular signatures linked to disease onset and progression. The ultimate goal is to develop non-invasive biomarkers that enable early detection, more accurate disease staging, and personalized therapeutic strategies, potentially revolutionizing how neurodegenerative disorders are diagnosed and monitored.

Our research strategy includes various experimental models (human samples, cell lines, primary cultures, and animal experimentation) as well as diverse techniques, including cellular function analysis, bioenergetics and dynamics (e.g., Seahorse), microscopy, flow cytometry, and molecular biology.

 

 

Publications

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Information about journal articles, updated at 17-11-2024, from platform CIÊNCIAVITAE.

Neuronal control of microglia through the mitochondria

Pereira-Santos, A.R.; Candeias, Emanuel; Magalhães, J.D.; Empadinhas, Nuno; Esteves, A. Raquel; Cardoso, Sandra M., 2024. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 2024. http://dx.doi.org/10.1016/j.bbadis.2024.167167 . 10.1016/j.bbadis.2024.167167 . Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Nocardia cyriacigeorgica Elicits Gut Disturbances in a Leaky Gut Model of Colitis, but Not the Harmful Cascade Leading to Gut-First Parkinson’s Disease

Magalhães, João Duarte; Candeias, Emanuel; Melo-Marques, Inês; Abreu, António E.; Pereira-Santos, Ana Raquel; Esteves, Ana Raquel; Cardoso, Sandra Morais; Empadinhas, Nuno, 2024. International Journal of Molecular Sciences. 6. 25. 2024. http://dx.doi.org/10.3390/ijms25063423 . 10.3390/ijms25063423 . International Journal of Molecular Sciences

Intestinal infection triggers mitochondria-mediated a-synuclein pathology: relevance to Parkinson’s disease

D. Magalhães, João; Candeias, Emanuel; Melo-Marques, Inês; Silva, Diana F.; Esteves, A. Raquel; Empadinhas, Nuno; Cardoso, Sandra Morais, 2023. Cellular and Molecular Life Sciences. 6. 80. 2023. http://dx.doi.org/10.1007/s00018-023-04819-3 . 10.1007/s00018-023-04819-3 . Cellular and Molecular Life Sciences

LPS-induced mitochondrial dysfunction regulates innate immunity activation and a-synuclein oligomerization in Parkinson's disease

Esteves, A. Raquel; Silva, Diana F.; Banha, Diogo; Candeias, Emanuel; Guedes, Beatriz; Cardoso, Sandra M., 2023. Redox Biology. 63. 2023. http://dx.doi.org/10.1016/j.redox.2023.102714 . 10.1016/j.redox.2023.102714 . Redox Biology

The Impact of microRNAs on Mitochondrial Function and Immunity: Relevance to Parkinson's Disease

Guedes, Beatriz F. S.; Cardoso, Sandra Morais; Esteves, Ana Raquel, 2023. Biomedicines. 5. 11. 2023. http://dx.doi.org/10.3390/biomedicines11051349 . 10.3390/biomedicines11051349 . Biomedicines

The Role of Bacteria–Mitochondria Communication in the Activation of Neuronal Innate Immunity: Implications to Parkinson’s Disease

Magalhães, João D.; Esteves, Ana Raquel; Candeias, Emanuel; Silva, Diana F.; Empadinhas, Nuno; Cardoso, Sandra Morais, 2023. International Journal of Molecular Sciences. 5. 24. 2023. http://dx.doi.org/10.3390/ijms24054339 . 10.3390/ijms24054339 . International Journal of Molecular Sciences

Parkinson's Disease: A Multisystem Disorder

Costa, Helena Nunes; Esteves, Ana Raquel; Empadinhas, Nuno; Cardoso, Sandra Morais, 2022. Neuroscience Bulletin. 2022. http://dx.doi.org/10.1007/s12264-022-00934-6 . 10.1007/s12264-022-00934-6 . Neuroscience Bulletin

Neurodegenerative Microbially-Shaped Diseases: Oxidative Stress Meets Neuroinflammation

Silva, Diana Filipa; Empadinhas, Nuno; Cardoso, Sandra Morais; Esteves, Ana Raquel, 2022. Antioxidants. 11. 11. 2022. http://dx.doi.org/10.3390/antiox11112141 . 10.3390/antiox11112141 . Antioxidants

Footprints of a microbial toxin from the gut microbiome to mesencephalic mitochondria

Esteves, A Raquel; Munoz-Pinto, Mário F; Nunes-Costa, Daniela; Candeias, Emanuel; Silva, Diana F; Magalhães, João D; Pereira-Santos, A Raquel; et al, 2021. Gut. gutjnl - 2021. 2021. http://dx.doi.org/10.1136/gutjnl-2021-326023 . 10.1136/gutjnl-2021-326023 . Gut

THE MITORIBOSOME: A WORLD OF OPPORTUNITIES FOR MITOCHONDRIAL DYSFUNCTION TOWARD PARKINSON’S DISEASE

Gonçalves, A Mafalda; Pereira-Santos, A Raquel; Esteves, A. Raquel; Cardoso, Sandra Morais; Empadinhas, Nuno, 2020. Antioxidants & Redox Signaling. 2020. http://dx.doi.org/10.1089/ars.2019.7997 . 10.1089/ars.2019.7997 . published Antioxidants & Redox Signaling

Microbial BMAA elicits mitochondrial dysfunction, innate immunity activation, and Alzheimer’s disease features in cortical neurons

Silva, Diana F.; Candeias, Emanuel; Esteves, A. Raquel; Magalhães, João D.; Ferreira, I. Luísa; Nunes-Costa, Daniela; Rego, A. Cristina; Empadinhas, Nuno; Cardoso, Sandra M., 2020. Journal of Neuroinflammation. 1. 17. 2020. http://dx.doi.org/10.1186/s12974-020-02004-y . 10.1186/s12974-020-02004-y . Journal of Neuroinflammation

Differential protein expression in diverse brain areas of Parkinson’s and Alzheimer’s disease patients

Esteves, A. R.; Cardoso, S. M., 2020. Scientific Reports. 1. 10. 2020. http://dx.doi.org/10.1038/s41598-020-70174-z . 10.1038/s41598-020-70174-z . accepted Scientific Reports

Acetylation as a major determinant to microtubule-dependent autophagy: Relevance to Alzheimer's and Parkinson disease pathology

Esteves, Ana; Andreia Palma; Rui Gomes; Daniel Santos; Diana Silva; Sandra Morais Cardoso, 2019. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 2019. published Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

The Role of Beclin-1 Acetylation on Autophagic Flux in Alzheimer’s Disease

Esteves, A. Raquel; Filipe, Filipa; Magalhães, João D.; Silva, Diana F.; Cardoso, Sandra M., 2019. Molecular Neurobiology. 5654 - 5670. 8. 56. 2019. http://dx.doi.org/10.1007/s12035-019-1483-8 . 10.1007/s12035-019-1483-8 . Molecular Neurobiology

Hydroxypyridinone-benzofuran hybrids with potential protective roles for Alzheimer´s disease therapy

Hiremathad, Asha; Chand, Karam; Tolayan, Lori; Rajeshwari; Keri, Rangappa S.; Esteves, A. Raquel; Cardoso, Sandra M.; Chaves, Sílvia; Santos, M. Amélia, 2018. Journal of Inorganic Biochemistry. 82 - 96. 179. 2018. http://dx.doi.org/10.1016/j.jinorgbio.2017.11.015 . 10.1016/j.jinorgbio.2017.11.015 . Journal of Inorganic Biochemistry

Novel Tacrine-Hydroxyphenylbenzimidazole hybrids as potential multitarget drug candidates for Alzheimer's disease

Hiremathad, Asha; Keri, Rangappa S.; Esteves, A. Raquel; Cardoso, Sandra M.; Chaves, Sílvia; Santos, M. Amélia, 2018. European Journal of Medicinal Chemistry. 255 - 267. 148. 2018. http://dx.doi.org/10.1016/j.ejmech.2018.02.023 . 10.1016/j.ejmech.2018.02.023 . European Journal of Medicinal Chemistry

Mitochondrial Metabolism Regulates Microtubule Acetylome and Autophagy Trough Sirtuin-2: Impact for Parkinson’s Disease

Esteves, Ana R.; Arduíno, Daniela M.; Silva, Diana F.; Viana, Sofia D.; Pereira, Frederico C.; Cardoso, Sandra M., 2017. Molecular Neurobiology. 1440 - 1462. 2. 55. 2017. http://dx.doi.org/10.1007/s12035-017-0420-y . 10.1007/s12035-017-0420-y . Molecular Neurobiology

Mitochondrial Metabolism Power SIRT2-Dependent Deficient Traffic Causing Alzheimer’s-Disease Related Pathology

Silva, D. F.; Esteves, A. R.; Oliveira, C. R.; Cardoso, S. M., 2016. Molecular Neurobiology. 4021 - 4040. 6. 54. 2016. http://dx.doi.org/10.1007/s12035-016-9951-x . 10.1007/s12035-016-9951-x . Molecular Neurobiology

LRRK2 at the Crossroad Between Autophagy and Microtubule Trafficking

Esteves, A. Raquel; Cardoso, Sandra M., 2016. The Neuroscientist. 16 - 26. 1. 23. 2016. http://dx.doi.org/10.1177/1073858415616558 . 10.1177/1073858415616558 . The Neuroscientist

LRRK2 a pivotal player in mitochondrial dynamics and lysosomal clustering: highlights to sporadic Parkinson’s disease

Ana Raquel Fernandes Esteves, 2015. Therapeutic Targets for Neurological Diseases. 2015. http://dx.doi.org/10.14800/ttnd.629 . 10.14800/ttnd.629 . published Therapeutic Targets for Neurological Diseases

The rescue of microtubule-dependent traffic recovers mitochondrial function in Parkinson's disease

Esteves, A.R.; Gozes, I.; Cardoso, S.M., 2014. Biochimica et Biophysica Acta - Molecular Basis of Disease. 7 - 21. 1. 1842. 2014. http://www.scopus.com/inward/record.url?eid=2-s2.0-84887706170&partnerID=MN8TOARS . 10.1016/j.bbadis.2013.10.003 . Biochimica et Biophysica Acta - Molecular Basis of Disease

The Impact of Mitochondrial Fusion and Fission Modulation in Sporadic Parkinson’s Disease

Santos, Daniel; Esteves, A. Raquel; Silva, Diana F.; Januário, Cristina; Cardoso, Sandra M., 2014. Molecular Neurobiology. 573 - 586. 1. 52. 2014. http://dx.doi.org/10.1007/s12035-014-8893-4 . 10.1007/s12035-014-8893-4 . Molecular Neurobiology

The Upshot of LRRK2 Inhibition to Parkinson’s Disease Paradigm

Esteves, A. R.; G-Fernandes, M.; Santos, D.; Januário, C.; Cardoso, S. M., 2014. Molecular Neurobiology. 1804 - 1820. 3. 52. 2014. http://dx.doi.org/10.1007/s12035-014-8980-6 . 10.1007/s12035-014-8980-6 . Molecular Neurobiology

LRRK2, a puzzling protein: Insights into Parkinson's disease pathogenesis

Esteves, A. Raquel; Swerdlow, Russell H.; Cardoso, Sandra M., 2014. Experimental Neurology. 206 - 216. 261. 2014. http://dx.doi.org/10.1016/j.expneurol.2014.05.025 . 10.1016/j.expneurol.2014.05.025 . Experimental Neurology

Mitochondria drive autophagy pathology via microtubule disassembly: A new hypothesis for Parkinson disease

Arduíno, D.M.; Esteves, A.R.; Cardoso, S.M., 2013. Autophagy. 112 - 114. 1. 9. 2013. http://www.scopus.com/inward/record.url?eid=2-s2.0-84872195238&partnerID=MN8TOARS . 10.4161/auto.22443 . Autophagy

Prodromal metabolic phenotype in MCI cybrids: Implications for Alzheimer's disease

Silva, D.F.; Santana, I.; Esteves, A.R.; Baldeiras, I.; Arduino, D.M.; Oliveira, C.R.; Cardoso, S.M., 2013. Current Alzheimer Research. 180 - 190. 2. 10. 2013. http://www.scopus.com/inward/record.url?eid=2-s2.0-84875000768&partnerID=MN8TOARS . 10.2174/1567205011310020008 . Current Alzheimer Research

Design, synthesis and neuroprotective evaluation of novel tacrine-benzothiazole hybrids as multi-targeted compounds against Alzheimer's disease

Keri, R.S.; Quintanova, C.; Marques, S.M.; Esteves, A.R.; Cardoso, S.M.; Santos, M.A., 2013. Bioorganic and Medicinal Chemistry. 4559 - 4569. 15. 21. 2013. http://www.scopus.com/inward/record.url?eid=2-s2.0-84879689184&partnerID=MN8TOARS . 10.1016/j.bmc.2013.05.028 . Bioorganic and Medicinal Chemistry

Ubiquitin proteasome system in Parkinson's disease: A keeper or a witness?

Martins-Branco, D.; Esteves, A.R.; Santos, D.; Arduino, D.M.; Swerdlow, R.H.; Oliveira, C.R.; Januario, C.; Cardoso, S.M., 2012. Experimental Neurology. 89 - 99. 2. 238. 2012. http://www.scopus.com/inward/record.url?eid=2-s2.0-84866521159&partnerID=MN8TOARS . 10.1016/j.expneurol.2012.08.008 . Experimental Neurology

Mitochondrial metabolic control of microtubule dynamics impairs the autophagic pathway in Parkinson's disease

Cardoso, S.M.; Esteves, A.R.; Arduno, D.M., 2012. Neurodegenerative Diseases. 38 - 40. 1-4. 10. 2012. http://www.scopus.com/inward/record.url?eid=2-s2.0-84860223145&partnerID=MN8TOARS . 10.1159/000332601 . Neurodegenerative Diseases

Mitochondrial metabolism in Parkinson's disease impairs quality control autophagy by hampering microtubule-dependent traffic

Arduíno, D.M.; Esteves, A.R.; Cortes, L.; Silva, D.F.; Patel, B.; Grazina, M.; Swerdlow, R.H.; Oliveira, C.R.; Cardoso, S.M., 2012. Human Molecular Genetics. 4680 - 4702. 21. 21. 2012. http://www.scopus.com/inward/record.url?eid=2-s2.0-84867828156&partnerID=MN8TOARS . 10.1093/hmg/dds309 . Human Molecular Genetics

Amyloid-ß-induced mitochondrial dysfunction impairs the autophagic lysosomal pathway in a tubulin dependent pathway

Silva, D.F.F.; Esteves, A.R.; Arduino, D.M.; Oliveira, C.R.; Cardoso, S.M., 2011. Journal of Alzheimer's Disease. 565 - 581. 3. 26. 2011. http://www.scopus.com/inward/record.url?eid=2-s2.0-80053559887&partnerID=MN8TOARS . 10.3233/JAD-2011-110423 . Journal of Alzheimer's Disease

Mitochondrial dysfunction: The road to alpha-synuclein oligomerization in PD

Cardoso, S.M.; Esteves, A.R.; Arduíno, D.M.; Silva, D.F.F.; Oliveira, C.R., 2011. Parkinson's Disease. 2011. http://www.scopus.com/inward/record.url?eid=2-s2.0-79952169319&partnerID=MN8TOARS . 10.4061/2011/693761 . Parkinson's Disease

Therapeutic intervention at cellular quality control systems in Alzheimer's and Parkinson's diseases

Arduino, D.M.; Esteves, A.R.; Silva, D.F.F.; Martins-Branco, D.; Santos, D.; Pimentel, D.F.G.; Cardoso, S.M., 2011. Current Pharmaceutical Design. 3446 - 3459. 31. 17. 2011. http://www.scopus.com/inward/record.url?eid=2-s2.0-80055080733&partnerID=MN8TOARS . 10.2174/138161211798072481 . Current Pharmaceutical Design

Mitochondria: The common upstream driver of amyloid-ß and tau pathology in Alzheimers disease

Silva, D.F.F.; Esteves, A.R.; Oliveira, C.R.; Cardoso, S.M., 2011. Current Alzheimer Research. 563 - 572. 5. 8. 2011. http://www.scopus.com/inward/record.url?eid=2-s2.0-79959926983&partnerID=MN8TOARS . 10.2174/156720511796391872 . Current Alzheimer Research

Mitochondrial fusion/fission, transport and autophagy in Parkinson's disease: When mitochondria get nasty

Arduíno, D.M.; Esteves, A.R.; Cardoso, S.M., 2011. Parkinson's Disease. 2011. http://www.scopus.com/inward/record.url?eid=2-s2.0-79953286639&partnerID=MN8TOARS . 10.4061/2011/767230 . Parkinson's Disease

Polymorphic Variation in Cytochrome Oxidase Subunit Genes

Lu, Jianghua; Wang, Kaixuan; Rodova, Mariana; Esteves, Raquel; Berry, Diana; E, Lezi; Crafter, Adam; et al, 2010. Journal of Alzheimer's Disease. 141 - 154. 1. 21. 2010. http://dx.doi.org/10.3233/jad-2010-100123 . 10.3233/jad-2010-100123 . Journal of Alzheimer's Disease

Cross-talk between mitochondria and proteasome in Parkinson’s disease pathogenesis

Branco, Diogo Martins, 2010. Frontiers in Aging Neuroscience. 2010. http://dx.doi.org/10.3389/fnagi.2010.00017 . 10.3389/fnagi.2010.00017 . Frontiers in Aging Neuroscience

Mitochondrial control of autophagic lysosomal pathway in Alzheimer's disease

Cardoso, S.M.; Pereira, C.F.; Moreira, P.I.; Arduino, D.M.; Esteves, A.R.; Oliveira, C.R., 2010. Experimental Neurology. 294 - 298. 2. 223. 2010. http://www.scopus.com/inward/record.url?eid=2-s2.0-77952549554&partnerID=MN8TOARS . 10.1016/j.expneurol.2009.06.008 . Experimental Neurology

Dysfunctional mitochondria uphold calpain activation: Contribution to Parkinson's disease pathology

Esteves, A.R.; Arduíno, D.M.; Swerdlow, R.H.; Oliveira, C.R.; Cardoso, S.M., 2010. Neurobiology of Disease. 723 - 730. 3. 37. 2010. http://www.scopus.com/inward/record.url?eid=2-s2.0-75949120541&partnerID=MN8TOARS . 10.1016/j.nbd.2009.12.011 . Neurobiology of Disease

Mitochondrial respiration and respiration-associated proteins in cell lines created through Parkinson's subject mitochondrial transfer

Esteves, A.R.; Lu, J.; Rodova, M.; Onyango, I.; Lezi, E.; Dubinsky, R.; Lyons, K.E.; et al, 2010. Journal of Neurochemistry. 674 - 682. 3. 113. 2010. http://www.scopus.com/inward/record.url?eid=2-s2.0-77950661030&partnerID=MN8TOARS . 10.1111/j.1471-4159.2010.06631.x . Journal of Neurochemistry

Mitochondrial metabolism modulation: A new therapeutic approach for Parkinson's disease

Arduíno, D.M.; Esteves, A.R.; Oliveira, C.R.; Cardoso, S.M., 2010. CNS and Neurological Disorders - Drug Targets. 105 - 119. 1. 9. 2010. http://www.scopus.com/inward/record.url?eid=2-s2.0-77949908141&partnerID=MN8TOARS . CNS and Neurological Disorders - Drug Targets

Microtubule depolymerization potentiates alpha-synuclein oligomerization

Esteves, A. Raquel, 2010. Frontiers in Aging Neuroscience. 1. 2010. http://dx.doi.org/10.3389/neuro.24.005.2009 . 10.3389/neuro.24.005.2009 . Frontiers in Aging Neuroscience

Polymorphic variation in cytochrome oxidase subunit genes

Lu, J.; Wang, K.; Rodova, M.; Esteves, R.; Berry, D.; Lezi, E.L.; Crafter, A.; et al, 2010. Journal of Alzheimer's Disease. 141 - 154. 1. 21. 2010. http://www.scopus.com/inward/record.url?eid=2-s2.0-77954963850&partnerID=MN8TOARS . 10.3233/JAD-2010-100123 . Journal of Alzheimer's Disease

Oxidative stress involvement in a-synuclein oligomerization in Parkinson's disease cybrids

Esteves, A.R.; Arduíno, D.M.; Swerdlow, R.H.; Oliveira, C.R.; Cardoso, S.M., 2009. Antioxidants and Redox Signaling. 439 - 448. 3. 11. 2009. http://www.scopus.com/inward/record.url?eid=2-s2.0-58849086657&partnerID=MN8TOARS . 10.1089/ars.2008.2247 . Antioxidants and Redox Signaling

ER-mediated stress induces mitochondrial-dependent caspases activation in NT2 neuron-like cells

Arduíno, D.M.; Raquel Esteves, A.; Filipa Domingues, A.; Pereira, C.M.F.; Cardoso, S.M.; Oliveira, C.R., 2009. BMB Reports. 719 - 724. 11. 42. 2009. http://www.scopus.com/inward/record.url?eid=2-s2.0-73449102905&partnerID=MN8TOARS . BMB Reports

Endoplasmic reticulum and mitochondria interplay mediates apoptotic cell death: Relevance to Parkinson's disease

Arduíno, D.M.; Esteves, A.R.; Cardoso, S.M.; Oliveira, C.R., 2009. Neurochemistry International. 341 - 348. 5. 55. 2009. http://www.scopus.com/inward/record.url?eid=2-s2.0-67649342203&partnerID=MN8TOARS . 10.1016/j.neuint.2009.04.004 . Neurochemistry International

Calpain-mediated MPP+ toxicity in mitochondrial DNA depleted cells

Domingues, A.F.; Esteves, A.R.F.; Swerdlow, R.H.; Oliveira, C.R.; Cardoso, S.M., 2008. Neurotoxicity Research. 31 - 38. 1. 13. 2008. http://www.scopus.com/inward/record.url?eid=2-s2.0-44649157955&partnerID=MN8TOARS . 10.1007/BF03033365 . Neurotoxicity Research

Mitochondria and ubiquitin-proteasomal system interplay: Relevance to Parkinson's disease

Domingues, A.F.; Arduíno, D.M.; Esteves, A.R.; Swerdlow, R.H.; Oliveira, C.R.; Cardoso, S.M., 2008. Free Radical Biology and Medicine. 820 - 825. 6. 45. 2008. http://www.scopus.com/inward/record.url?eid=2-s2.0-54949100005&partnerID=MN8TOARS . 10.1016/j.freeradbiomed.2008.06.007 . Free Radical Biology and Medicine

Mitochondrial function in Parkinson’s disease cybrids containing an nt2 neuron-like nuclear background

Esteves, A. Raquel F.; Domingues, A. Filipa; Ferreira, I. Luísa; Januário, Cristina; Swerdlow, Russell H.; Oliveira, Catarina R.; Cardoso, Sandra M., 2008. Mitochondrion. 219 - 228. 3. 8. 2008. http://dx.doi.org/10.1016/j.mito.2008.03.004 . 10.1016/j.mito.2008.03.004 . Mitochondrion

R&D Projects

Past R&D Projects

2022-01-01

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