Soluble membrane-type 3 matrix metalloprioteinase causes changes in gene expression and increased gelatinase activity during Xenopus laevis development
Bibliographic record
Abstract
Matrix metalloproteinases (MMPs) are a family of endopeptidases that cleave and remodel the extracellular matrix (ECM). Membrane-type 3 MMP (MT3-MMP) is a membrane-anchored MMP, which has recently been shown to 'shed' from the cell surface in a soluble form upon proteolytic cleavage. Shed MT-MMPs can activate gelatinase-A in vitro and have been directly linked to the metastatic potential of many cancers. Here we examined the effect of ectopic expression of full-length tethered and shed (soluble) forms of MT3-MMP during Xenopus laevis development. Injection of mRNA coding for full-length tethered MT3-MMP resulted in the delayed onset of gastrulation and subsequent defects. Phenotype severity and the frequency of embryo death were dose-dependent. Dose-dependent defects were also observed with the injection of mRNA of the soluble form, but the phenotypes and frequencies of death were greater. Histological analysis of injected embryos demonstrated defects in the organization of axial structures, such as the neural tube and somites. Embryos injected with full-length MT3-MMP mRNA showed no significant changes in expression levels of the tissue specific genes endodermin, chordin and muscle actin when examined by semi-quantitative RT-PCR. In contrast, embryos injected with the soluble form of MT3-MMP exhibited decreased expression of these same marker genes. In addition, while full-length tethered MT3-MMP failed to alter gelatinase activity, a 50% increase was measured in response to injection of the soluble form, suggesting that the two forms of this protein could play distinct roles during embryogenesis.
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How this classification was reachedexpand
Direct model labels (unvalidated)
Per-model category and study-design labels from the labeling rounds. They are machine output, unvalidated, and the disagreement between models ships as data. No study design here is MEDLINE-validated yet.
| Model arm | Categories | Study design | Confidence |
|---|---|---|---|
| gemma | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Bench or experimental | low |
| gpt | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Bench or experimental | low |
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) | 0.000 | 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) | 0.000 | 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 itClassification
machine, unvalidatedLabeled directly by 2 models reading the full record.
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".