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Record W2908658437 · doi:10.3389/fnmol.2018.00480

PKR: A Kinase to Remember

2019· review· en· W2908658437 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueFrontiers in Molecular Neuroscience · 2019
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA regulation and disease
Canadian institutionsnot available
FundersMinistry of Health, State of IsraelMinistry of Science and Technology, IsraelAzrieli FoundationIsrael Science FoundationInternational Development Research CentreCanadian Institutes of Health ResearchEU Joint Programme – Neurodegenerative Disease Research
KeywordsProtein kinase RNeurodegenerationBiologyKinaseCellular stress responseCell biologyProtein kinase ARegulatorSignal transductionFunction (biology)EIF-2 kinaseNeuroscienceBioinformaticsMedicineGeneticsFight-or-flight responseDiseaseMitogen-activated protein kinase kinaseCyclin-dependent kinase 2GeneInternal medicine

Abstract

fetched live from OpenAlex

Aging is a major risk factor for many diseases including metabolic syndrome, cancer, inflammation, and neurodegeneration. Identifying mechanistic common denominators underlying the impact of aging is essential for our fundamental understanding of age-related diseases and the possibility to propose new ways to fight them. One can define aging biochemically as prolonged metabolic stress, the innate cellular and molecular programs responding to it, and the new stable or unstable state of equilibrium between the two. A candidate to play a role in the process is protein kinase R (PKR), first identified as a cellular protector against viral infection and today known as a major regulator of central cellular processes including mRNA translation, transcriptional control, regulation of apoptosis, and cell proliferation. Prolonged imbalance in PKR activation is both affected by biochemical and metabolic parameters and affects them in turn to create a feedforward loop. Here, we portray the central role of PKR in transferring metabolic information and regulating cellular function with a focus on cancer, inflammation, and brain function. Later, we integrate information from open data sources and discuss current knowledge and gaps in the literature about the signaling cascades upstream and downstream of PKR in different cell types and function. Finally, we summarize current major points and biological means to manipulate PKR expression and/or activation and propose PKR as a therapeutic target to shift age/metabolic-dependent undesired steady states.

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.

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: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.904
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
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 head0.025
GPT teacher head0.312
Teacher spread0.287 · 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