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Record W4367556811 · doi:10.1101/2023.04.29.538807

Astroglial <i>Hmgb1</i> regulates postnatal astrocyte morphogenesis and cerebrovascular maturation

2023· preprint· en· W4367556811 on OpenAlexafffund
Moises Freitas‐Andrade, César H. Comin, Peter Van Dyken, Julie Ouellette, Joanna Raman‐Nair, Nicole Blakeley, Qing Yan Liu, Sonia Leclerc, Youlian Pan, Ziying Liu, Micaël Carrier, Karan Thakur, Alexandre Savard, Gareth M. Rurak, Marie‐Ève Tremblay, Natalina Salmaso, Luciano da Fontoura Costa, Gianfilippo Coppola, Baptiste Lacoste

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2023
Typepreprint
Languageen
FieldNeuroscience
TopicBarrier Structure and Function Studies
Canadian institutionsCarleton UniversityUniversity of VictoriaNational Research Council CanadaUniversity of OttawaOttawa Hospital
FundersFundação de Amparo à Pesquisa do Estado de São PauloCanadian Institutes of Health ResearchConselho Nacional de Desenvolvimento Científico e TecnológicoUniversity of Ottawa
KeywordsAstrocyteHMGB1BiologyAquaporin 4NeuroscienceCell biologyAngiogenesisEndocrinologyInternal medicineAnatomyPathologyMedicineCentral nervous systemImmunologyInflammationCancer research

Abstract

fetched live from OpenAlex

Abstract Astrocytes are intimately linked with brain vessels, a relationship that is critical for neuronal health and function. However, astroglial factors driving these physical and functional associations during postnatal brain development have yet to be identified. We characterized structural and transcriptional changes in mouse cortical astrocytes and microvessels during the first two postnatal weeks and found that high-mobility group box 1 ( Hmgb1 ), normally upregulated with injury and involved in adult cerebrovascular repair, was highly expressed in astrocytes at birth and then decreased rapidly. Astrocyte-selective ablation of Hmgb1 at birth affected astrocyte morphology and endfoot placement, altered distribution of endfoot proteins connexin43 and aquaporin-4, induced transcriptional changes in astrocytes related to cytoskeleton remodeling, and profoundly disrupted endothelial ultrastructure. While lack of astroglial Hmgb1 did not affect the blood-brain barrier or angiogenesis postnatally, it impaired neurovascular coupling and behavior in adult mice. These findings identify astroglial Hmgb1 as a key player in postnatal gliovascular maturation.

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 categoriesMeta-epidemiology (narrow)
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 score0.146
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0000.001
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 head0.019
GPT teacher head0.211
Teacher spread0.191 · 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.

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

Citations1
Published2023
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicBarrier Structure and Function StudiesFrench-language works237,207