8 research outputs found
The translocator protein (TSPO) is prodromal to mitophagy loss in neurotoxicity
- Author
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2021
- Field of study
Dysfunctional mitochondria characterise Parkinson's Disease (PD). Uncovering etiological molecules, which harm the homeostasis of mitochondria in response to pathological cues, is therefore pivotal to inform early diagnosis and therapy in the condition, especially in its idiopathic forms. This study proposes the 18 kDa Translocator Protein (TSPO) to be one of those. Both in vitro and in vivo data show that neurotoxins, which phenotypically mimic PD, increase TSPO to enhance cellular redox-stress, susceptibility to dopamine-induced cell death, and repression of ubiquitin-dependent mitophagy. TSPO amplifies the extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) signalling, forming positive feedback, which represses the transcription factor EB (TFEB) and the controlled production of lysosomes. Finally, genetic variances in the transcriptome confirm that TSPO is required to alter the autophagy-lysosomal pathway during neurotoxicity
Lawson Criterion for Ignition Exceeded in an Inertial Fusion Experiment
- Author
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- Yee B
- Yi S
- Yin L
- Young B
- Young C
- Young P
- Youngblood K
- Zacharias R
- Zagaris G
- Zaitseva N
- Zaka F
- Ze F
- Zeiger B
- Zika M
- Zimmerman G
- Zobrist T
- Zuegel J
- Zylstra A
- Publication venue
- Publication date
- 01/01/2022
- Field of study
Lawson criterion for ignition exceeded in an inertial fusion experiment
- Author
- Abu-Shawareb H
- Acree R
- Adams J
- Adams P
- Addis B
- Aden R
- Adrian P
- Afeyan BB
- Aggleton M
- Aghaian L
- Aguirre A
- Aikens D
- Akre J
- Albert F
- Albrecht M
- Albright BJ
- Albritton J
- Alcala J
- Alday C
- Alessi DA
- Alexander N
- Alfonso J
- Alfonso N
- Alger E
- Ali SJ
- Ali ZA
- Alley WE
- Amala P
- Amendt PA
- Amick P
- Ammula S
- Amorin C
- Ampleford DJ
- Anderson RW
- Anklam T
- Antipa N
- Appelbe B
- Aracne-Ruddle C
- Araya E
- Arend M
- Arnold P
- Arnold T
- Asay J
- Atherton LJ
- Atkinson D
- Atkinson R
- Auerbach JM
- Austin B
- Auyang L
- Awwal AS
- Ayers J
- Ayers S
- Ayers T
- Azevedo S
- Bachmann B
- Back CA
- Bae J
- Bailey DS
- Bailey J
- Baisden T
- Baker KL
- Baldis H
- Barber D
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- Barker D
- Barnes A
- Barnes CW
- Barrios MA
- Barty C
- Bass I
- Batha SH
- Baxamusa SH
- Bazan G
- Beagle JK
- Beale R
- Beck BR
- Beck JB
- Bedzyk M
- Beeler RG
- Beeler RG
- Behrendt W
- Belk L
- Bell P
- Belyaev M
- Benage JF
- Benedetti LR
- Benedict LX
- Bennett G
- Berger R
- Bernat T
- Bernstein LA
- Berry B
- Bertolini L
- Berzak Hopkins L
- Besenbruch G
- Betcher J
- Bettenhausen R
- Betti R
- Bezzerides B
- Bhandarkar SD
- Bickel R
- Biener J
- Biesiada T
- Bigelow K
- Bigelow-Granillo J
- Bigman V
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- Wootton A
- Work K
- Workman JB
- Wright J
- Wu M
- Wuest C
- Wysocki FJ
- Xu H
- Yamaguchi M
- Yang B
- Yang ST
- Yatabe J
- Yeamans CB
- Yee BC
- Yi SA
- Yin L
- Young B
- Young CS
- Young CV
- Young P
- Youngblood K
- Zacharias R
- Zagaris G
- Zaitseva N
- Zaka F
- Ze F
- Zeiger B
- Zika M
- Zimmerman GB
- Zobrist T
- Zuegel JD
- Zylstra AB
- Publication venue
- 'American Physical Society (APS)'
- Publication date
- 06/07/2022
- Field of study
For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion
Lawson Criterion for Ignition Exceeded in an Inertial Fusion Experiment
- Author
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- Publication venue
- 'American Physical Society (APS)'
- Publication date
- 01/01/2022
- Field of study
Achievement of Target Gain Larger than Unity in an Inertial Fusion Experiment
- Author
- Abu-Shawareb H
- Acree R
- Adams J
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- Addis B
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- Park H
- Pasternak A
- Patankar S
- Patel M
- Patel P
- Patterson R
- Patterson S
- Paul B
- Paul M
- Pauli E
- Pearce O
- Pearcy J
- Pedretti A
- Pedrotti B
- Peer A
- Pelz L
- Penetrante B
- Penner J
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- Pernice E
- Perry T
- Person S
- Petersen D
- Petersen T
- Peterson D
- Peterson E
- Peterson J
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- Petrasso R
- Philippe F
- Phillion D
- Phipps T
- Piceno E
- Pickworth L
- Ping Y
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- Reynolds H
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- Samuelson S
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- Schappert G
- Schiaffino S
- Schlossberg D
- Schmidt D
- Schmit P
- Schneider D
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- Schoff M
- Schollmeier M
- Schrauth S
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- Scott H
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- Shmayda W
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- Simakov A
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- Skupsky S
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- Smeltser R
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- Smith I
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- Sterne P
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- Taranowski M
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- Theobald W
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- Thompson I
- Thongstisubskul A
- Thorsness C
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- Publication venue
- Publication date
- 01/01/2024
- Field of study
Lawson Criterion for Ignition Exceeded in an Inertial Fusion Experiment
- Author
- Abu-Shawareb H
- Acree R
- Adams J
- Adams P
- Addis B
- Aden R
- Adrian P
- Afeyan B
- Aggleton M
- Aghaian L
- Aguirre A
- Aikens D
- Akre J
- Albert F
- Albrecht M
- Albright B
- Albritton J
- Alcala J
- Alday C
- Alessi D
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- Alfonso N
- Alger E
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- Ali Z
- Alley W
- Amala P
- Amendt P
- Amick P
- Ammula S
- Amorin C
- Ampleford D
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- Appelbe B
- Aracne-Ruddle C
- Araya E
- Arend M
- Arnold P
- Arnold T
- Asay J
- Atherton L
- Atkinson D
- Atkinson R
- Auerbach J
- Austin B
- Auyang L
- Awwal A
- Ayers J
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- Azevedo S
- Bachmann B
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- Bae J
- Bailey D
- Bailey J
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- Barnes A
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- Barty C
- Bass I
- Batha S
- Baxamusa S
- Bazan G
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- Bernat T
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- Berry B
- Bertolini L
- Berzak Hopkins L
- Besenbruch G
- Betcher J
- Bettenhausen R
- Betti R
- Bezzerides B
- Bhandarkar S
- Bickel R
- Biener J
- Biesiada T
- Bigelow K
- Bigelow-Granillo J
- Bigman V
- Bionta R
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- Black A
- Bleile R
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- Briggs T
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- Christensen M
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- Crilly A
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- Cross D
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- Cuotts G
- Czajka C
- Czechowicz D
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- Davalos G
- Davidovits S
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- Deeney C
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- Desjarlais M
- Dewald E
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- Dimonte G
- Dittrich T
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- Dixit S
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- Dodd E
- Dolan D
- Donovan A
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- Dorrer C
- Dorsano N
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- Downie J
- Downing E
- Dozieres M
- Draggoo V
- Drake D
- Drake R
- Drake T
- Dreifuerst G
- DuBois D
- DuBois P
- Dunham G
- Dylla-Spears R
- Dymoke-Bradshaw A
- Dzenitis B
- Döppner T
- Ebbers C
- Eckart M
- Eddinger S
- Eder D
- Edgell D
- Edwards M
- Efthimion P
- Eggert J
- Ehrlich B
- Ehrmann P
- Elhadj S
- Ellerbee C
- Elliott N
- Ellison C
- Elsner F
- Emerich M
- Engelhorn K
- England T
- English E
- Epperson P
- Epstein R
- Erbert G
- Erickson M
- Erlandson A
- Erskine D
- Espinosa R
- Estabrook K
- Estes C
- Evans S
- Fabyan A
- Fair J
- Fallejo R
- Farmer N
- Farmer W
- Farrell M
- Fatherley V
- Fedorov M
- Feigenbaum E
- Feit M
- Ferguson W
- Fernandez J
- Fernandez-Panella A
- Fess S
- Field J
- Filip C
- Fincke J
- Finn T
- Finnegan S
- Finucane R
- Fischer M
- Fisher A
- Fisher J
- Fishler B
- Fittinghoff D
- Fitzsimmons P
- Flegel M
- Flippo K
- Florio J
- Folta J
- Folta P
- Fooks J
- Foord M
- Foreman L
- Forrest C
- Forsman A
- Fortner R
- Fournier K
- Fratanduono D
- Frazier N
- Frazier T
- Frederick C
- Freeman M
- Frenje J
- Frey D
- Frieders G
- Friedrich S
- Froula D
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- Gales S
- Gambhir A
- Gao L
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- Gates C
- Gatu Johnson M
- Gaut E
- Gauthier P
- Gavin Z
- Gaylord J
- Geissel M
- Georgeson J
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- Geppert-Kleinrath V
- Gharibyan N
- Gibson C
- Gibson J
- Giraldez E
- Glebov V
- Glendinning S
- Glenn S
- Glenzer S
- Goade S
- Gobby P
- Goldman S
- Golick B
- Gomez M
- Goncharov V
- Goodin D
- Grabowski P
- Grafil E
- Graham P
- Grandy J
- Grasz E
- Graziani F
- Green T
- Greenman G
- Greenough J
- Greenwood A
- Gregori G
- Griego J
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- Gross S
- Guckian J
- Guler N
- Gunney B
- Guss G
- Génin F
- Haan S
- Hackbarth J
- Hackel L
- Hackel R
- Haefner C
- Hagmann C
- Hahn K
- Hahn S
- Haid B
- Haines B
- Hall B
- Hall C
- Hall G
- Hamamoto M
- Hamel S
- Hamilton C
- Hammel B
- Hammer J
- Hampton G
- Hamza A
- Handler A
- Hansen S
- Hanson D
- Haque R
- Harding D
- Harding E
- Hares J
- Harris D
- Harte J
- Hartouni E
- Hatarik R
- Hatchett S
- Hauer A
- Havre M
- Hawley R
- Hayes J
- Hayes S
- Hayes-Sterbenz A
- Haynam C
- Haynes D
- Headley D
- Heal A
- Heebner J
- Heerey S
- Heestand G
- Heeter R
- Hein N
- Heinbockel C
- Hendricks C
- Henesian M
- Heninger J
- Henrikson J
- Henry E
- Herbold E
- Hermann M
- Hermes G
- Hernandez J
- Hernandez V
- Herrera O
- Herrmann H
- Herrmann M
- Hewett D
- Hibbard R
- Hicks D
- Hill D
- Hill K
- Hilsabeck T
- Hinkel D
- Ho D
- Ho V
- Hoffer J
- Hoffman N
- Hohenberger M
- Hohensee M
- Hoke W
- Holdener D
- Holdener F
- Holder J
- Holko B
- Holunga D
- Holzrichter J
- Honig J
- Hoover D
- Hopkins D
- Hoppe M
- Horner J
- Hornung R
- Horsfield C
- Horvath J
- Hotaling D
- House R
- Howell L
- Hsing W
- Hu S
- Huang H
- Huckins J
- Hui H
- Humbird K
- Hund J
- Hunt J
- Hurricane O
- Hutton M
- Huynh K
- Iglesias C
- Igumenshchev I
- Inandan L
- Izumi N
- Jackson J
- Jackson M
- Jacobs S
- James G
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- Jaquez J
- Jarboe J
- Jarrott L
- Jasion D
- Jeet J
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- Jimenez J
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- Jobe D
- Johal Z
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- Johnson M
- Johnson R
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- Johnson T
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- Jones M
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- Jorgenson H
- Julian M
- Jun B
- Jungquist R
- Kaae J
- Kabadi N
- Kaczala D
- Kalantar D
- Kangas K
- Karasiev V
- Karasik M
- Karpenko V
- Kasarky A
- Kasper K
- Kauffman R
- Kaufman M
- Keane C
- Keaty L
- Kegelmeyer L
- Keiter P
- Kellett P
- Kellogg J
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- Kemic S
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- Kershaw D
- Kessler T
- Key M
- Khan S
- Khater H
- Kiikka C
- Kilkenny J
- Kim Y
- Kimko J
- Kimmel M
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- Kirkwood R
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- Knudson M
- Kobs D
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- Kong C
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- Kot L
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- Kozlowski M
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- Kraus B
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- Kumbera M
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- Kunimune J
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- Lahmann B
- Lairson B
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- Landen O
- Lane M
- Laney D
- Langdon A
- Langenbrunner J
- Langer S
- Langro A
- Lanier N
- Lanier T
- Larson D
- Lasinski B
- Lassle D
- LaTray D
- Lau G
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- Laumann C
- Laurence A
- Laurence T
- Lawson J
- Le Galloudec B
- Le Galloudec K
- Le H
- Le Pape S
- Leach R
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- Leatherland A
- LeChien K
- Lechleiter B
- Lee A
- Lee M
- Lee T
- Leeper R
- Lefebvre E
- Leidinger J
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- Levedahl K
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- Loucks S
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- Ludwigsen A
- Lundgren E
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- MacDonald M
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- Mackinnon A
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- Manes K
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- Mannion O
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- Mara G
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- Pak A
- Palaniyappan S
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- Patterson S
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- Publication venue
- Publication date
- 01/01/2022
- Field of study
C. Literaturwissenschaft.
- Author
- About Edmond M.
- Ackermann Louise
- Ad
- Adam Juliette J.
- Adhemar J.
- Adler M. J.
- Agoult Marie C.
- Agramonte F.
- Aids Moner R.
- Aineal J.
- Alain Chartier A.
- Albertet J
- Alcobe S.
- Alcoforado Mariana L.
- Alcoforado Mariana L.
- Aleixandre Vicente A
- Alexandru C.
- Alexis Paul
- Alfieri Vittorio A
- Alfons X. A. G.
- Algunas
- Alonso A.
- Amadis
- Amatucci G. A.
- Ambrosio Montesino
- Amunategui Solar D.
- Anagnine E.
- Andry de la Vigne R. E.
- Angles H.
- Anläfsach
- Anläfsach
- Annius de Viterbe II
- AnSiji
- Antero de Quental Tarquinio B.
- Antero de Quental Tarquinio B.
- Antero de Quental Tarquinio L
- Aparicio Bartolomo J. E.
- Apollinaire Guillaume F.
- Araaut Daniel G
- Arboleda S.
- Argensola Bartolomo Leonardo
- Arias A.
- Ariosto Francesco G.
- Arnaut Catalan F.
- Arnaut de Mareill R. C
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- Art
- Asch O.
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- Assaf J. E.
- Aubanel
- Aubanel
- Aubigne Agrippa K.
- Aubigne Agrippa K.
- Audoux Marguerite
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- Austin H. D.
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- Bacchelli Riccardo F.
- Bachet de Meziriac C.
- Baden H. J.
- Badenheusen R.
- Badius Conrad A.
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- Bailly A.
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- Baldacchini Francesco Saverio
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- Bandln M
- Barbosa du Bocage Manoel Maria H.
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- Bell A. F. G.
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- °o
- ·» I
- Publication venue
- 'Walter de Gruyter GmbH'
- Publication date
- 01/01/1940
- Field of study
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HNRNPC haploinsufficiency affects alternative splicing of intellectual disability-associated genes and causes a neurodevelopmental disorder
- Author
- Acosta Maria T.
- Adams David R.
- Admard Jakob
- Afzali Ben
- Allworth Aimee
- Alvarez Raquel L.
- Alvey Justin
- Ambrose J.C.
- Andrews Ashley
- Arumugam P.
- Ashley Euan A.
- Bacino Carlos A.
- Bademci Guney
- Bain Jennifer
- Balasubramanian Meena
- Balasubramanyam Ashok
- Baldridge Dustin
- Bale Jim
- Bamshad Michael
- Banka Siddharth
- Barbouth Deborah
- Bayrak-Toydemir Pinar
- Beck Anita
- Beggs Alan H.
- Behrens Edward
- Bejerano Gill
- Bellen Hugo J.
- Benke Paul J.
- Bennet Jimmy
- Bernstein Jonathan A.
- Berry Gerard T.
- Bertrand Miriam
- Bevers R.
- Bican Anna
- Bivona Stephanie
- Bleda M.
- Blesson Alyssa E.
- Blue Elizabeth
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- Bohnsack John
- Bonner Devon
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- Briere Lauren C.
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- Burke Elizabeth A.
- Burrage Lindsay C.
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- Byrd William E.
- Carey John
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- Cassini Thomas
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- Chang Ta Chen
- Chanprasert Sirisak
- Chao Hsiao-Tuan
- Chinn Ivan
- Clark Gary D.
- Clayton-Smith Jill
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- Cobban Laurel A.
- Cogan Joy D.
- Coggins Matthew
- Cole F. Sessions
- Colley Heather A.
- Cope Heidi
- Corona Rosario
- Craigen William J.
- Crouse Andrew B.
- Cunningham Michael
- D'Souza Precilla
- Dai Hongzheng
- Dasari Surendra
- Davis Joie
- Dayal Jyoti G.
- Delgado Margaret
- Dell'Angelica Esteban C.
- Dipple Katrina
- Doherty Daniel
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- Gahl William A.
- Genomics England Research Consortium
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- Hom Jason
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- Introne Wendy
- Isasi Rosario
- Izumi Kosuke
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- Jain Mahim
- Jarvik Gail P.
- Jarvik Jeffrey
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- Jean-Marie Orpa
- Jobanputra Vaidehi
- Jones L.J.
- Kaitryn Emerald
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- Kayikci M.
- Ketkar Shamika
- Kiley Dana
- Kilich Gonench
- Kobren Shilpa N.
- Kohane Isaac S.
- Kohler Jennefer N.
- Korrick Susan
- Kousathanas A.
- Krakow Deborah
- Krantz Ian
- Krasnewich Donna M.
- Kravets Elijah
- Lahnstein L.
- Lakey A.
- Lalani Seema R.
- Lam Byron
- Lam Christina
- Lanpher Brendan C.
- Lanza Ian R.
- LeBlanc Kimberly
- Lee Brendan H.
- Leigh S.E.A.
- Leong I.U.S.
- Levitt Roy
- Lewis Richard A.
- Liu Pengfei
- Liu Xue Zhong
- Longo Nicola
- Loo Sandra K.
- Lopez F.J.
- Loscalzo Joseph
- Luu Sharon M.
- Maas Richard L.
- Macnamara Ellen F.
- MacRae Calum A.
- Maduro Valerie V.
- Maghiro AudreyStephannie
- Mahoney Rachel
- Maleady-Crowe F.
- Malicdan May Christine
- Mamounas Laura A.
- Manolio Teri A.
- Mao Rong
- Marom Ronit
- Marth Gabor
- Martin Beth A.
- Martin Martin G.
- Martínez-Agosto Julian A.
- Marwaha Shruti
- McCauley Jacob
- McConkie-Rosell Allyn
- McCray Alexa T.
- McEntagart M.
- McGee Elisabeth
- McPheron Molly
- Might Matthew
- Miller Danny
- Minneci F.
- Mirzaa Ghayda
- Mitchell J.
- Morava Eva
- Moretti Paolo
- Morimoto Marie
- Moutsianas L.
- Mueller M.
- Mulvihill John J.
- Murugaesu N.
- Muss Candace L.
- Nakano-Okuno Mariko
- Need A.C.
- Nelson Stanley F.
- Nieves-Rodriguez Shirley
- Niggl Eva
- Novacic Donna
- Odhams C.A.
- Oglesbee Devin
- Orengo James P.
- O‘Donovan P.
- Pace Laura
- Pak Stephen
- Pallais J. Carl
- Papp Jeanette C.
- Park Joohyun
- Parker Neil H.
- Patch C.
- Pereira M.B.
- Perez-Gil D.
- Petcharet Leoyklang
- Phillips John A.
- Posey Jennifer E.
- Potocki Lorraine
- Pullinger J.
- Quinlan Aaron
- Rahim T.
- Raible Sarah E.
- Rao Deepak A.
- Raper Anna
- Raskind Wendy
- Rendon A.
- Renteria Genecee
- Reuter Chloe
- Rives Lynette
- Robertson Amy K.
- Robin Nathaniel H.
- Rodan Lance H.
- Rogers T.
- Rosenfeld Jill A.
- Rosenthal Elizabeth
- Rossignol Francis
- Ruzhnikov Maura
- Sabaii Marla
- Sacco Ralph
- Sampson Jacinda B.
- Saporta Mario
- Savage K.
- Sawant K.
- Schaechter Judy
- Schedl Timothy
- Schoch Kelly
- Scott Daryl A.
- Scott R.H.
- Seto Elaine
- Sharma Prashant
- Shashi Vandana
- Shelkowitz Emily
- Sheppeard Sam
- Shin Jimann
- Siddiq A.
- Sieghart A.
- Silverman Edwin
- Sinsheimer Janet
- Sisco Kathy
- Smith Edward
- Smith Kevin
- Smith S.C.
- Solnica-Krezel Lilianna
- Solomon Ben
- Sosinsky A.
- Spiller Michael
- Spillmann Rebecca
- Starling Susan
- Stergachis Andrew
- Stoler Joan
- Stuckey A.
- Sullivan Jennifer
- Sullivan Kathleen
- Sutton Shirley
- Sweetser David A.
- Sweetser David A.
- Swerdzewski Barbara N.
- Sybert Virginia
- Tabor Holly K.
- Tan Amelia L.
- Tan Queenie K.-G.
- Tanguy M.
- Tarakad Arjun
- Taylor Tavares A.L.
- Tekin Mustafa
- Telischi Fred
- Thiffault Isabelle
- Thomas E.R.A.
- Thompson S.R.
- Thorson Willa
- Tifft Cynthia
- Toro Camilo
- Tran Alyssa A.
- Tucci A.
- Ungar Rachel A.
- Urv Tiina K.
- van Esbroeck Annelot C.M.
- Vanderver Adeline
- Velinder Matt
- Vetrini Francesco
- Viskochil Dave
- Vogel Tiphanie P.
- Wahl Colleen E.
- Walker Melissa
- Wallaard Ilse
- Walley Nicole M.
- Wambach Jennifer
- Wan Jijun
- Wang Lee-kai
- Wangler Michael F.
- Ward Patricia A.
- Wegner Daniel
- Weisz Monika
- Welland M.J.
- Wener Mark
- Wenger Tara
- Westerfield Monte
- Wheeler Matthew T.
- Whitlock Jordan
- Wilke Martina
- Williams E.
- Witkowska K.
- Witt Dennis
- Wolfe Lynne A.
- Wood S.M.
- Woods Emily
- Yamamoto Shinya
- Zarowiecki M.
- Zhang Zhe
- Zhou Dihong
- Zuchner Stephan
- Publication venue
- Elsevier Inc
- Publication date
- 03/08/2023
- Field of study
Heterogeneous nuclear ribonucleoprotein C (HNRNPC) is an essential, ubiquitously abundant protein involved in mRNA processing. Genetic variants in other members of the HNRNP family have been associated with neurodevelopmental disorders. Here, we describe 13 individuals with global developmental delay, intellectual disability, behavioral abnormalities, and subtle facial dysmorphology with heterozygous HNRNPC germline variants. Five of them bear an identical in-frame deletion of nine amino acids in the extreme C terminus. To study the effect of this recurrent variant as well as HNRNPC haploinsufficiency, we used induced pluripotent stem cells (iPSCs) and fibroblasts obtained from affected individuals. While protein localization and oligomerization were unaffected by the recurrent C-terminal deletion variant, total HNRNPC levels were decreased. Previously, reduced HNRNPC levels have been associated with changes in alternative splicing. Therefore, we performed a meta-analysis on published RNA-seq datasets of three different cell lines to identify a ubiquitous HNRNPC-dependent signature of alternative spliced exons. The identified signature was not only confirmed in fibroblasts obtained from an affected individual but also showed a significant enrichment for genes associated with intellectual disability. Hence, we assessed the effect of decreased and increased levels of HNRNPC on neuronal arborization and neuronal migration and found that either condition affects neuronal function. Taken together, our data indicate that HNRNPC haploinsufficiency affects alternative splicing of multiple intellectual disability-associated genes and that the developing brain is sensitive to aberrant levels of HNRNPC. Hence, our data strongly support the inclusion of HNRNPC to the family of HNRNP-related neurodevelopmental disorders.
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We identified genetic variants of HNRNPC in 13 individuals with intellectual disability and global developmental delay. Through a meta-analysis of multiple cell types, we found that loss of HNRNPC affects alternative splicing, in particular of intellectual disability-associated genes. In vivo assays confirmed that neurodevelopment was affected by aberrant HNRNPC levels