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Record W331029664 · doi:10.82308/55464

Nephrin mediated signaling in actin organization of podocyte

2010· dissertation· en· W331029664 on OpenAlexfundno aff
Jian‐Xin Zhu

Bibliographic record

VenueeScholarship@McGill (McGill) · 2010
Typedissertation
Languageen
FieldMedicine
TopicRenal Diseases and Glomerulopathies
Canadian institutionsnot available
FundersCanadian Institutes of Health ResearchKidney Foundation of CanadaFaculty of Medicine, McGill UniversityMcGill University
KeywordsNephrinPodocyteCell biologyActin cytoskeletonSlit diaphragmPhosphorylationPodocinTyrosine phosphorylationActin remodelingCortactinChemistryBiologyCytoskeletonBiochemistryEndocrinologyCellKidney

Abstract

fetched live from OpenAlex

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

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 score0.001
Threshold uncertainty score0.003

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 science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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.

Opus teacher head0.011
GPT teacher head0.247
Teacher spread0.236 · 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
Published2010
Admission routes1
Has abstractyes

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