P3–419: Identification of presenilin–associated proteins and potential regulators of the gamma–secretase complex
Bibliographic record
Abstract
The presenilins, NCT, aph–1 and pen–2 form a series of high molecular weight complexes that are necessary for gamma– and epsilon–secretase cleavage of selected Type 1 transmembrane proteins, including APP, Notch and cadherins. However, questions concerning the biology of the presenilin complexes remain to be resolved. These include how their activity is modulated in terms of substrate specificity, what are the relative activities of the gamma– and epsilon–sites, and whether or not additional proteins in the presenilin complexes might subsume these putative regulatory functions. To investigate the possible presence of additional co–factors, we sought to apply an in situ cross–linking method that maintains the microenvironment of the presenilin complex. PS1 immuno–affinity purification using a novel in vivo formaldehyde cross–linked has been used in wild–type and PS1/ PS2 double knockout blastocyst–derived cells. This has revealed that all four known constituents of the presenilin complex (nicastrin, aph–1, pen–2 and PS1) were present as shown by mass spectrometry. A few other possible candidates were also identified in the immunoprecipitates from wild–type cells. We are following up on that the confirmation experiments on their interaction with presenilin complex by co–immunoprecipitation, glycerol velocity gradients and on native/2D gel chromatography. This has been complemented by functional examination of gamma–secretase activity by determination of Abeta and ICD production in whole cells and cell–free gamma–secretase assays. This has led to the identification of several potential modulators of the presenilin complex that may have functional significance.
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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 | 0.000 | 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) | 0.003 | 0.002 |
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".