The Size of the Unbranched Aliphatic Chain Determines the Immunomodulatory Potency of Short and Long Chain n-Alkanols
Bibliographic record
Abstract
Aliphatic n -alkanols are a family of ubiquitous substances that display general anesthetic properties in accordance to their degree of hydrophobicity. In addition, the immunomodulatory activity of one of its members, ethanol, has long been recognized. We reasoned that because unbranched aliphatic n -alkanols are structurally very similar they might have an immunological impact that mirrors their anesthetic potency. We report the impact of the homologous C 1 –C 12 alcohol series on the ability of activated primary human lymphocytes to produce IFN-γ. Methanol enhanced IFN-γ production whereas C 2 –C 10 alcohols reduced the release of this cytokine. The activity of the n -alkanol series was observed within a wide concentration window ranging from millimolar levels for short chain alcohols to micromolar amounts for C 7 –C 10 alcohols. There was a clear correlation between immunomodulatory activity and hydrophobicity of the compounds, but a cutoff effect was evident at C 11 . n -Alkanols were shown to act downstream of the cell membrane because T cell receptor early signaling was preserved. The activation of the nuclear factor of activated T cells (NFAT) was down-regulated progressively in accordance to the size of the n -alkanol aliphatic chains with a clear downward trend that was interrupted at C 11 . The nuclear factor-κB (NF-κB) signaling was also compromised, but the cutoff appeared earlier at C 10 . The pattern of immunomodulation and transcriptional dysregulation induced by the n -alkanol series suggested the existence of interaction pockets of defined dimensions within intracellular targets that compromise the activation of NFAT and NF-κB transcription factors and ultimately modulate the effector function of the T lymphocyte. Background: Aliphatic n -alkanols have multiple biological effects not yet completely characterized. Results: n -Alkanols are immunomodulators that act downstream of the cell membrane by dysregulating the activation of the NFAT and NF-κB transcription factors. Conclusion: There is a correlation between the immunomodulatory capacity of the homologous series of n -alkanols and the size of the aliphatic chain/hydrophobicity. Significance: This work contributes to the understanding of the biological activity of ubiquitous n -alkanols.
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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".