Sphingosine-1-Phosphate Receptors in the Central Nervous and Immune Systems
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Sphingosine-1-phosphate receptor (S1PR) modulators have entered clinical practice as immune-modulators for the treatment of multiple sclerosis (MS). Pharmacologic modulation of S1PR expression on lymphocytes inhibits these cells capacity to respond to the S1P gradient within regional lymph nodes (LNs) (and thymus) that promotes their exit into peripheral circulation. The resultant peripheral blood restricted lymphopenia is considered to underlie the capacity of S1PR modulators to reduce new inflammatory lesion formation in MS in the absence of global immune suppression. These modulators also regulate entry of selective lymphocyte populations and dendritic cells (DCs) into LNs and modulate sphingosine-1-phosphate (S1P) cell signaling networks that govern the generation of specific cell subsets within LNs. S1PR modulators that access the CNS can also have functional effects within this compartment since S1PRs are expressed by cells comprising the blood brain barrier (BBB) and by those within the parenchyma, including neurons, astrocytes, oligodendrocytes and microglia. Absence of S1P1 receptor (S1PR1) on astrocytes reduces disease severity in experimental autoimmune encephalomyelitis (EAE). Even under conditions that inhibit cell responses to the natural ligand, S1PR modulators can continue to induce active signaling responses; such responses may be relevant for promoting neuroprotection and augmenting tissue repair within the CNS.
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.
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it