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Record W4400684810 · doi:10.1016/j.xcrm.2024.101647

Dysregulation of FLVCR1a-dependent mitochondrial calcium handling in neural progenitors causes congenital hydrocephalus

2024· article· en· W4400684810 on OpenAlexaff
Francesca Bertino, Dibyanti Mukherjee, Massimo Bonora, Christoph P. Bagowski, Jeannette Nardelli, Livia Metani, Diletta Isabella Zanin Venturini, Diego Chianese, Nicolás Santander, Iris C. Salaroglio, Andreas Hentschel, Elisa Quarta, Tullio Genova, Arpana Arjun McKinney, Anna Lucia Allocco, Veronica Fiorito, Sara Petrillo, Giorgia Ammirata, Francesco De Giorgio, Evan Dennis, Garrett Allington, Felicitas Maier, Moneef Shoukier, Karl-Philipp Gloning, Luca Munaron, Federico Mussano, Ettore Salsano, Davide Pareyson, Maja Di Rocco, Fiorella Altruda, Georgia Panagiotakos, Kristopher T. Kahle, Pierre Gressèns, Chiara Riganti, Paolo Pinton, Andreas Roos, Thomas D. Arnold, Emanuela Tolosano, Deborah Chiabrando

Bibliographic record

VenueCell Reports Medicine · 2024
Typearticle
Languageen
FieldMedicine
TopicFetal and Pediatric Neurological Disorders
Canadian institutionsChildren's Hospital of Eastern Ontario
FundersMinistero dell'Istruzione e del MeritoNational Institute of Neurological Disorders and StrokeNational Institute of Mental HealthEuropean Regional Development FundUniversity of California, San FranciscoFondazione TelethonSandler FoundationCompagnia di San PaoloNational Institutes of HealthUniversità degli Studi di Torino
KeywordsNeurogenesisMitochondrionBiologyNeural stem cellCalciumProgenitor cellCell biologyCalcium signalingVentricleNeuroscienceStem cellInternal medicineSignal transductionMedicine

Abstract

fetched live from OpenAlex

Congenital hydrocephalus (CH), occurring in approximately 1/1,000 live births, represents an important clinical challenge due to the limited knowledge of underlying molecular mechanisms. The discovery of novel CH genes is thus essential to shed light on the intricate processes responsible for ventricular dilatation in CH. Here, we identify FLVCR1 (feline leukemia virus subgroup C receptor 1) as a gene responsible for a severe form of CH in humans and mice. Mechanistically, our data reveal that the full-length isoform encoded by the FLVCR1 gene, FLVCR1a, interacts with the IP3R3-VDAC complex located on mitochondria-associated membranes (MAMs) that controls mitochondrial calcium handling. Loss of Flvcr1a in mouse neural progenitor cells (NPCs) affects mitochondrial calcium levels and energy metabolism, leading to defective cortical neurogenesis and brain ventricle enlargement. These data point to defective NPCs calcium handling and metabolic activity as one of the pathogenetic mechanisms driving CH.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.320
Threshold uncertainty score0.624

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.022
GPT teacher head0.279
Teacher spread0.256 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations7
Published2024
Admission routes1
Has abstractyes

Explore more

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