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quorum 2/3Description
RESOLUTION QUESTION: How do ALS-associated TDP-43 mutations produce similar mRNA mislocalization as complete TDP-43 loss? EMPIRICAL MILESTONES: Resolution requires: (1) mRNA localization assay (RNA FISH, subcellular fractionation) in motor neurons from ALS-linked TDP-43 mutation carriers vs sporadic ALS vs controls, quantifying nuclear vs cytoplasmic TDP-43 ratio; (2) comparison with C9orf72 DPR/GR models establishing whether convergence on mislocalization is TDP-43-dependent or independent; (3) rescue experiment where restoring TDP-43 nu This market resolves YES when the primary empirical milestone is met with peer-reviewed publication and independent replication.
Rationale
Domain: neurodegeneration. Priority score: 0.87. Importance: 0.89. Tractability: 0.82. SCIENTIFIC RATIONALE: The abstract reports that disease mutations phenocopy TDP-43 knockout effects on mRNA localization, suggesting a loss-of-function mechanism. However, this contradicts evidence that ALS mutations often cause toxic gain-of-function, requiring mechanistic clarification for therapeutic targeting. Gap t RESOLUTION TIMELINE: 18–36 months. Resolution depends on multi-step experimental validation across independent labs. LMSR LIQUIDITY RECOMMENDATION: 150 tokens. Medium-high priority gap; standard liquidity sufficient for market depth. Initial b-parameter should be set to token_cost/100 = 1.5 for LMSR scoring rule.
Pricing semantics
continuous_probability
Proposal cost: 150 tokens