Bibliographic record
Abstract
Podocytes are highly differentiated epithelial cells that contribute to the selective filtration barrier of the renal glomerulus. The actin-based podocyte foot processes possess a subplasmalemmal actin network and a central core of actin filament bundles. The dynamic regulation of the podocyte actin cytoskeleton is vital to kidney function. Nephrin, identified as a slit diaphragm protein, connects foot processes from adjacent podocytes, which is critical for the structural and functional integrity of podocytes. It has been reported that tyrosine phosphorylation of nephrin was responsible for its interaction with PI3-kinase and Nck. PI3-kinase and Nck-Pak signalings are well known regulators of actin dynamics. Therefore, we studied the role of PI3-kinase and Nck-Pak signalings activated via the tyrosine phosphorylation of nephrin, in actin cytoskeleton organization of cultured podocytes. We identified that Y1152 of rat nephrin was responsible for nephrin -PI3K interaction. Stable transfection of rat nephrin in the podocytes with podocin led to nephrin tyrosine phosphorylation, PI3K-dependent phosphorylation of Akt, increased Rac1 and Pak activity, and actin cytoskeleton reorganization with decreased stress fiber and increased lamellipodia. These actin cytoskeleton changes were reversed with an inhibitor of PI3K and not seen when the nephrin mutant Y1152F replaced wild type nephrin. Pak was coimmunoprecipitated with nephrin and Nck in vitro and in vivo. The nephrin increased Pak phosphorylation was completely abolished by a nephrin mutantY1208/1224F (fail to bind Nck), but not affected by the Rac1 inhibitor. Dominant negative Nck constructs blocked Pak1 phosphorylation induced by antibody-mediated cross-linking of nephrin. Transient transfection of constitutively kinase active Pak1 into differentiated mouse podocytes decreased stress fibers and increased cortical F-actin, while kinase-dead mutant, kinase inhibitory construct, and Pak2 knockdown by shRNA had the op
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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) | 0.001 | 0.000 |
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.
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".