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Record W3015055090 · doi:10.1101/2020.04.01.020768

Gene deletion studies reveal a critical role for prostamide/prostaglandin F <sub>2α</sub> synthase in prostamide F <sub>2α</sub> formation

2020· preprint· en· W3015055090 on OpenAlexaff
Jacques Bertrand, David F. Woodward, Joseph M. Sherwood, Alice Spenlehauer, Cristoforo Silvestri, Fabiana Piscitelli, Vincenzo Di Marzo, Maya Yamazaki, Kenji Sakimura, Kikuko Watanabe, Darryl R. Overby

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2020
Typepreprint
Languageen
FieldMedicine
TopicGlaucoma and retinal disorders
Canadian institutionsUniversité Laval
FundersJapan Society for the Promotion of ScienceAllergan
KeywordsProstaglandinProstanoidIntraocular pressureThromboxane-A synthaseChemistryInternal medicineEndocrinologyATP synthaseEnzymeBiochemistryBiologyMedicineOphthalmologyArachidonic acid

Abstract

fetched live from OpenAlex

Abstract Prostamide / prostaglandin F synthase (PM/PGFS) is an enzyme with very narrow substrate specificity and is dedicated to the biosynthesis of prostamide and prostaglandin F 2α. The importance of this enzyme, relative to the aldoketoreductase (AKR) series, in providing functional tissue prostamide F 2α levels was determined by creating a line of PM/PGFS gene deleted mice. Deletion of the gene encoding PM/PGFS (fam213b) was accomplished by a two exon disruption. Prostamide F 2α levels in WT and PM/PGFS KO mice were determined by LC/MS/MS. Intraocular pressure was measured by tonometry and outflow facility was measured by the iPerfusion method in enucleated mouse eyes. Deletion of fam213b had no observed effect on behavior, appetite, or fertility. Intraocular pressure was significantly elevated by approximately 4 mmHg in PM/PGFS KO mice compared to littermate WT mice. No effect on pressure dependent outflow facility occurred, which is consistent with the typically reported prostanoid effect of increasing outflow through the unconventional pathway. The elevation of intraocular pressure caused by deletion of the gene encoding the PM/PGFS enzyme likely results from a diversion of the endoperoxide precursor pathway to provide increased levels of those prostanoids that raise intraocular pressure, namely prostaglandin D 2 (PGD 2 ), thromboxane A 2 (TxA 2 ). It follows that PM/PGFS may serve an important regulatory role in the eye by providing PGF 2α and prostamide F 2α to constrain the influence of those prostanoids that raise intraocular pressure.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

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)0.0020.001

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 head0.021
GPT teacher head0.263
Teacher spread0.242 · 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 source (direct Gemma or distilled Codex), 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

Citations0
Published2020
Admission routes1
Has abstractyes

Explore more

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