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Record W4210613299 · doi:10.1073/pnas.2122584119

Cellular itinerary of LDL cholesterol

2022· letter· en· W4210613299 on OpenAlexaff
Jean E. Vance

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2022
Typeletter
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicLipid Membrane Structure and Behavior
Canadian institutionsUniversity of Alberta
Fundersnot available
KeywordsCholesterolLdl cholesterolChemistryBiochemistry

Abstract

fetched live from OpenAlex

Cholesterol is an essential component of eukaryotic cells. This lipid is synthesized on endoplasmic reticulum (ER) membranes and can also be supplied to cells extracellularly via lipoprotein particles such as low-density lipoproteins (LDLs). These cholesterol-carrying LDL particles bind to transmembrane LDL receptors in the plasma membrane (PM) and are internalized into cells via receptor-mediated endocytosis (1). Mutations in the LDL receptor gene cause the human disease familial hypercholesterolemia in which LDL cholesterol accumulates in plasma, thereby promoting atherosclerosis and heart disease (2). The endocytosed LDL particles are delivered to lysosomes where the LDL cholesterol is released and exported to the PM. Subsequently, the cholesterol is transferred from the PM to the ER, the site at which cellular cholesterol content is tightly regulated by genes encoding several membrane-associated proteins (1). When the cholesterol content of the ER exceeds ∼5% of the total lipid mass of the ER, the synthesis of cholesterol and the production of LDL receptors in the ER are down-regulated (3). In addition, excess cholesterol in the ER is esterified to cholesteryl esters for storage in lipid droplets. This stringent regulation of cholesterol homeostasis is essential for normal cell viability and growth. Previous studies by Trinh et al. (4), and from the laboratories of Tontonoz (5) and Saheki (6), have shown that the transport of cholesterol from the PM to the ER in mammalian cells requires the anionic phospholipid phosphatidylserine (PS), as well as the ER- and PM-associated Aster proteins (Fig. 1). However, it was not clear whether PS and the Aster proteins operated together or independently in this pathway. In PNAS, Trinh et al. (7) establish that, although PS and the Aster proteins largely act together in PM-to-ER cholesterol transport, the two factors also partially function independently of one another in this pathway. Fig. 1. Movement of cholesterol from the PM to … [↵][1] 1Email: jean.vance{at}ualberta.ca. [1]: #xref-corresp-1-1

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: Not applicable · Consensus signal: none
GenreCandidate signal: Other · Consensus signal: Other
Teacher disagreement score0.030
Threshold uncertainty score0.102

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.000
Science and technology studies0.0010.000
Scholarly communication0.0020.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0300.042

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 head0.025
GPT teacher head0.275
Teacher spread0.250 · 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 designNot applicable
Domainnot available
GenreOther

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".

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Citations17
Published2022
Admission routes1
Has abstractyes

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