Preliminary investigation of caspase6 cleavage of HTT and HTT-HAP40 2019/07/15
Bibliographic record
Abstract
Project: Structural and functional analysis of huntingtin protein Experiment: Preliminary investigation of caspase6 cleavage of HTT and HTT-HAP40 Date: 2019/07/15 Background: HTT is cleaved by numerous enzymes to generate protein fragments, many of which have implications for disease pathogenesis (reviewed by Saudou et al (2016) Neuron). However, very few of these proteases have been assessed for their cleavage of purified HTT protein or HTT-HAP40 protein samples. Caspase-6 cleavage of HTT has been reported to generate a aa. 1-586 fragment. However, it is not clear how HAP40 binding of HTT might affect cleavage by caspase-6 or release of this fragment from the complex structure. The caspase-6 cleavage site is in the intrinsically disordered region, distal from the globular structure. How cleavage might release a 1-586 fragment from the remainder of the structure remains incompletely understood. Rationale: In this experiments I am aiming to optimise conditions for caspase-6 cleavage to test how proteolytic cleavage of HTT affects “pathogenic” fragment formation for apo vs HAP40-bound HTT.
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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 | 0.001 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.042 | 0.029 |
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".