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Parkinson’s disease patient-specific neuronal networks carrying the LRRK2 G2019S mutation unveil early functional alterations that predate neurodegeneration
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Carola, G.; Malagarriga, D.; Calatayud, C.; Pons-Espinal, M.; Blasco-Agell, L.; Richaud-Patin, Y.; Fernández-Carasa, I.; Baruffi, V.; Beltramone, S.; Molina, E.; Dell’Era, P.; Toledo-Aral, Juan José; Tolosa, E.; Muotri , A. R.; García Ojalvo, J.; Soriano, J.; Raya, A.; Consiglio, A.. - : Springer Nature, 2021
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Abstract:
A deeper understanding of early disease mechanisms occurring in Parkinson’s disease (PD) is needed to reveal restorative targets. Here we report that human induced pluripotent stem cell (iPSC)-derived dopaminergic neurons (DAn) obtained from healthy individuals or patients harboring LRRK2 PD-causing mutation can create highly complex networks with evident signs of functional maturation over time. Compared to control neuronal networks, LRRK2 PD patients’ networks displayed an elevated bursting behavior, in the absence of neurodegeneration. By combining functional calcium imaging, biophysical modeling, and DAn-lineage tracing, we found a decrease in DAn neurite density that triggered overall functional alterations in PD neuronal networks. Our data implicate early dysfunction as a prime focus that may contribute to the initiation of downstream degenerative pathways preceding DAn loss in PD, highlighting a potential window of opportunity for pre-symptomatic assessment of chronic degenerative diseases. ; Research from the authors’ laboratories is supported by the European Research Council-ERC (2012-StG-311736-PD-HUMMODEL), the MESOBRAIN project from the European Union’s Horizon 2020 research and innovation (grant agreement No. 713140), the Spanish Ministry of Economy and Competitiveness-MINECO (RTI2018-095377-B-100, FIS2016-78507-C2-2-P, PID2019-108842GB-C21) the Spanish Ministry of Economy and Competitiveness-MINECO/AEI/FEDER, UE (BFU2016-80870-P) and the Spanish Ministry of Economy and Competitiveness- AEI/10.13039/501100011033 (PID2019-108792GB-I00), Instituto de Salud Carlos III-ISCIII/FEDER (Red de Terapia Celular - TerCel RD16/0011/0024 and RD16/0011/0025), AGAUR (2017-SGR-899 and 2017-SGR-1061), and CERCA Program/Generalitat de Catalunya. M.P.E. was partially supported by a Beatriu de Pinós fellowship from the Agency for Management of University and Research Grants (AGAUR) of the Government of Catalonia (2017 BP 00133). L.B. is the recipient of a pre-doctoral fellowship FPI (BES-2017-080579) from the Spanish Ministry of Economy and Competitiveness (MINECO). G.C. was partially supported by pre-doctoral fellowship from Spanish Economy and Competitiveness-MINECO (BES-2014-069603). ; Peer reviewed
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URL: https://doi.org/10.1038/s41531-021-00198-3
http://hdl.handle.net/10261/263923
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| 62 |
Review: The Dura language: Grammar and phylogeny
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In: Himalayan Linguistics, vol 20, iss 1 (2021)
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| 63 |
Learning a weather dictionary of atmospheric patterns using Latent Dirichlet Allocation
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In: https://hal.archives-ouvertes.fr/hal-03258523 ; 2021 (2021)
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Chapter 11. Catalan nativization patterns in the light of weighted scalar constraints
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In: Romance Languages and Linguistic Theory 2018 ; https://hal.archives-ouvertes.fr/hal-03503041 ; Romance Languages and Linguistic Theory 2018, 357, John Benjamins Publishing Company, pp.206-223, 2021, Current Issues in Linguistic Theory, ⟨10.1075/cilt.357.11pon⟩ (2021)
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| 65 |
Circonscrire le discours de haine
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In: université d’automne, Discours de haine, discriminations et inégalités ; https://hal.archives-ouvertes.fr/hal-03554056 ; université d’automne, Discours de haine, discriminations et inégalités, Oct 2021, Pise, Italie (2021)
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| 66 |
Quand la haine fait son genre
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In: La haine en discours ; https://hal.archives-ouvertes.fr/hal-03184258 ; Nolwenn Lorenzi Bailly et Claudine Moïse. La haine en discours, Le Bord de l'eau, pp.73-100, 2021 (2021)
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| 67 |
Refutació dels arguments blaveristes entorn de "Regles de esquivar vocables o mots grossers o pagesívols"
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In: Llengua i Literatura Catalanes (TFG) (2021)
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| 68 |
La vuelta al mundo en 70 años: itinerario de la poética de Julio Cortázar —Arte, fotografía y tecnología urbana—
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In: TDX (Tesis Doctorals en Xarxa) (2021)
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| 69 |
El nomen Pompeius en Hispania
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In: TDX (Tesis Doctorals en Xarxa) (2021)
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| 73 |
De la investigación sobre aproximativos en español a una teoría de la aproximación en la lengua
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| 74 |
The That-Deletion Phenomenon in English and the Restrictions that Constrain its Use
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| 75 |
Descripció microtipològica i anàlisi freqüencial de les obertures en català
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La vuelta al mundo en 70 años: itinerario de la poética de Julio Cortázar —Arte, fotografía y tecnología urbana—
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| 77 |
El procés d'elisió de la /n/ final en síl·laba tònica en català: estat de la qüestió i experiment amb pseudoparaules
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Descripció i anàlisi acústica de les realitzacions de les fricatives labiodentals sordes finals en posició prevocàlica
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Descripció i anàlisi de les realitzacions de vocals mitjanes en manlleus esdrúixols del català de Barcelona
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L’assignació de gènere gramatical en una mostra de manlleus incorporats al català
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