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Record W7132868767

NoncanonicalTransmission of Biological Information and Master-regulation of Signaling by the Zinc Finger Proteins MSTR-1 and MSTR-2

2022· dissertation· W7132868767 on OpenAlexaff
Matthew Emre Eroglu

Bibliographic record

VenueTSpace · 2022
Typedissertation
Language
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetics, Aging, and Longevity in Model Organisms
Canadian institutionsAmgen (Canada)
Fundersnot available
KeywordsGermlineZinc fingerTranscription factorGerm cellEpigeneticsPiwi-interacting RNASignal transductionTranscription (linguistics)Gene silencingRegulation of gene expression
DOInot available

Abstract

fetched live from OpenAlex

Heritable information is encoded in nucleic acids and transmitted by an immortal germ lineage. Failure of germ cells to clear DNA damage or maintain small RNA expression leads to progressive sterility (germline mortality) over multiple generations due to accumulation of defects such as telomere erosion or transposon mobilization. Here, I show that solid-phase protein amyloids, which I propose to term ‘fluorosomes’ for their intrinsic fluorescence, are inherited transgenerationally and transmit the epigenetic information required for proper germ cell sex determination and germline immortality. I identify two genes, which I term multigenerational sterility and temperature regulated (F22D6.2/mstr-1 and F56F3.4/mstr-2), that when ablated lead to transgenerational accumulation of these fluorosomes and progressive transformation of germ cells from spermatogenic to oogenic fates. Among its key targets, MSTR-1 restricts expression of the sex determinant GLD-1 from spermatogenic cells, whereas in mstr mutants GLD-1 protein but not mRNA accumulates ectopically over several generations, transforming sperm-fated germ cells to oocytes. I further chronicle the discovery of these genes and the work that led to them, from investigation of their roles in cell signaling to the serendipitous discovery of their roles in germline function. Briefly, I show that insulin-like growth factor receptor DAF-2 signaling regulates DAF-16/FOXO dependent and independent networks to modulate LET-60/Ras function in the soma. The FOXO independent mechanism relies on the transcription factor PQM1, which is regulated by the SGK-1 kinase. The transcriptional target of PQM-1, mstr-1, regulates diverse cell signalling pathways important for multiple developmental processes, including vulval cell fate specification, germline proliferation, and longevity. Overall, my work reveals a post-transcriptional transgenerational epigenetic mechanism of trait transmission and demonstrates that germline immortality can be lost independently of DNA or RNA maintenance.

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 score0.005

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 science0.0000.001
Research integrity0.0000.001
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 head0.014
GPT teacher head0.268
Teacher spread0.253 · 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
Published2022
Admission routes1
Has abstractyes

Explore more

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