MD‐1 is a Critical Part of the Mechanism Causing Th1‐Cytokine‐Triggered Murine Fetal Loss Syndrome
Bibliographic record
Abstract
PROBLEM: Fetal loss syndrome (abortion/resorption) occurring on or after gestation day (gd) 9.5 in CBA/JxDBA/2 matings is dependent upon presence of TNF-alpha + IFN-gamma, which act by increasing expression of fg12 prothrombinase at the feto-maternal interface. The magnitude by which the abortion rate can be boosted by an injection of these cytokines on gd 7.5 depends on endogenous rate of loss, and appears to depend on microbial flora. Is cytokine-triggered abortion dependent upon a third signaling pathway that senses 'danger'? METHODS: Female CBA/J were mated to DBA/2 males and, C57B1/6 and C57B1/6 TNFalphaR1-/-Mak were mated to C57B1/6 control or TNFalphaR1-/-Mak males. LPS from Escherichia coli and Salmonella enteritidis, or the combination of TNF-alpha + IFN-gamma, was injected to stimulate abortions. The effect of anti-MD-1, which interferes with expression of CD14 and, hence, with signaling by LPS via the CD14-tlr4 complex, on TNF-alpha + IFN-gamma was tested. The presence of MD-1 in the uterus was evaluated by in situ hybridization, and effect of lipopolysaccharide (LPS) on mice lacking TNF-alphaR1 was tested. RESULTS: Anti-MD-1 completely abrogated TNF-alpha + IFN-gamma-induced abortions. MD-1 was expressed on trophoblast and in deciduas on gd 8.5 but LPS could not abort mice that lacked the type 1 receptor for TNF-alpha. Pregnant CBA/J females had classical resorptions (abortions) countable on gd 13.5-14.5 in response to LPS from E. coli or S. enteritidis, but C57B1/6 strain mice resorbed only in response to the latter, and E. coli LPS appeared to induce 'occult' losses. 'Occult' loss did not require TNF-alphaR1. CONCLUSIONS: TNF-alpha + IFN-gamma could not induce murine abortions without co-presence of a 'danger' signal such as LPS acting via CD14 on toll receptors, and LPS could not act without co-signaling by TNF-alpha. Classical resorptions/abortions and 'occult' losses have a different mechanism in these models as reflected in type of endotoxin and requirement for TNF-alphaR1 signaling.
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 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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".