Histological and proteomic analysis of reversible H-Ras V12G expression in transgenic mouse skin
Bibliographic record
Abstract
We have used a two-transgene tetracycline system to reversibly express oncogenic H-Ras(V12G) in mouse skin and primary keratinocytes culture using the bovine keratin 5 promoter. Induction of H-Ras(V12G) expression in skin at 30 days after birth causes epidermal basal cell hyperplasia, an eruption of keratinous cysts and loss of hair follicles by 3 weeks. Subsequent H-Ras(V12G) de-induction for 3 days results in massive apoptosis in the non-H-Ras(V12G)-expressing stroma as well as in the suprabasal cells of the epidermis. Several procaspases such as CASP3, 1alpha, 5 and 12 disappeared, whereas the pro-apoptotic proteins AIF, Bax and Fas ligand were induced in H-Ras(V12G) de-induction skin. This process is followed by a wave of cell division at 14 days as hair follicles regrew, returning to near normal histology and skin appearance by 30 days. Using Kinetworkstrade mark multi-immunoblotting screens, the phosphorylation status of 37 proteins and expression levels of 75 protein kinases in the skin were determined in three samples: (i) wild-type skin, (ii) hyperplastic H-Ras(V12G)-expressing skin and (iii) skin where H-Ras(V12G) expression was suppressed for 7 days. Following H-Ras(V12G) induction, 16 kinases were increased over 2-fold, and 2 kinases were reduced over 50%. This included increased phosphorylation of both known downstream H-Ras(V12G) targets and unknown H-Ras(V12G) targets. After H-Ras(V12G) suppression, many but not all protein changes were reversed. These results from skin and primary keratinocytes are organized to reflect the molecular events that cause the histological changes observed. These proteomic changes identify markers that may mediate the oncogenic addiction paradigm.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".