Embracing ecology to limit antimicrobial resistance
Bibliographic record
Abstract
The immunological synapse (IS) is a specialized membrane domain with localized display of T-cell receptor (TCR) in contact with a similar display of peptide-loaded MHC on antigen presenting cells (APCs). Aberrant IS function is linked to ineffective tumor killing and autoimmunity. Accumulating evidence indicates a key role of endocytic traffic in the generation and maintenance of the IS. The C-terminal Eps-15 Homology Domain-containing proteins (EHD1-4) are essential regulators of endocytic recycling of surface receptors. Yet, nothing is known about their role in immune cell function. EHD-regulated receptors include the MHC-I and MHC-II proteins, and EHDs regulate vesicle budding at neural synapse. Our hypothesis is that EHD-dependent recycling of TCR and accessory receptors on T cells and MHC-II on APCs is required for the formation and stability of the IS. Indeed, using antigen-specific TCR transgenic CD4+ T-cells, we observe an accumulation of EHD proteins at the interface of T cells and APCs. CD4+ T-cells from floxed EHD1,3,4 mice bearing CD4-Cre and an antigen-specific TCR transgene demonstrate reduced antigen-driven proliferation. Further in vitro and in vivo analyses are being carried out to test the idea that endocytic recycling orchestrated by EHD proteins plays an important functional role in the formation and/or maintenance of IS and in T-cell function.
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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 | 0.001 |
| 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 | 0.002 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 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".