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Record W4220768785 · doi:10.1126/sciadv.abm1444

Novel oxygen sensing mechanism in the spinal cord involved in cardiorespiratory responses to hypoxia

2022· article· en· W4220768785 on OpenAlexaff
Nicole O. Barioni, Fatemeh Derakhshan, Luana Tenorio Lopes, Hiroshi Onimaru, Arijit Roy, Fiona B. McDonald, Erika Scheibli, Mufaddal I. Baghdadwala, Negar Heidari, Manisha Bharadia, Keiko Ikeda, Itaru Yazawa, Yasumasa Okada, Michael B. Harris, Mathias Dutschmann, Richard J. A. Wilson

Bibliographic record

VenueScience Advances · 2022
Typearticle
Languageen
FieldNeuroscience
TopicNeuroscience of respiration and sleep
Canadian institutionsAlberta Children's HospitalUniversity of Calgary
FundersNational Institute of General Medical SciencesNational Heart, Lung, and Blood Institute
KeywordsHyperoxiaNicotinamide adenine dinucleotide phosphateHypoxia (environmental)NADPH oxidaseCardiorespiratory fitnessHypoxic ventilatory responseSpinal cordChemistryOxygenNeuroscienceReactive oxygen speciesBiologyEndocrinologyMedicineInternal medicineRespiratory systemOxidase testLungBiochemistry

Abstract

fetched live from OpenAlex

As blood oxygenation decreases (hypoxemia), mammals mount cardiorespiratory responses, increasing oxygen to vital organs. The carotid bodies are the primary oxygen chemoreceptors for breathing, but sympathetic-mediated cardiovascular responses to hypoxia persist in their absence, suggesting additional high-fidelity oxygen sensors. We show that spinal thoracic sympathetic preganglionic neurons are excited by hypoxia and silenced by hyperoxia, independent of surrounding astrocytes. These spinal oxygen sensors (SOS) enhance sympatho-respiratory activity induced by CNS asphyxia-like stimuli, suggesting they bestow a life-or-death advantage. Our data suggest the SOS use a mechanism involving neuronal nitric oxide synthase 1 (NOS1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX). We propose NOS1 serves as an oxygen-dependent sink for NADPH in hyperoxia. In hypoxia, NADPH catabolism by NOS1 decreases, increasing availability of NADPH to NOX and launching reactive oxygen species-dependent processes, including transient receptor potential channel activation. Equipped with this mechanism, SOS are likely broadly important for physiological regulation in chronic disease, spinal cord injury, and cardiorespiratory crisis.

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)0.004
metaresearch head score (Gemma)0.003
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 score0.089
Threshold uncertainty score0.812

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0040.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.005
Science and technology studies0.0010.001
Scholarly communication0.0000.001
Open science0.0020.000
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 head0.069
GPT teacher head0.332
Teacher spread0.262 · 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

Citations22
Published2022
Admission routes1
Has abstractyes

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