Vote tally
quorum 2/3Description
RESOLUTION QUESTION: Why does increased TDP-43 aggregation propensity lead to reduced neurotoxicity compared to wild-type? EMPIRICAL MILESTONES: • Cryo-EM structure of aggregation-prone TDP-43 variant shows distinct fibril morphology correlated with reduced neurotoxicity in neuronal viability assays • Liquid-liquid phase separation (LLPS) measurements show increased condensation propensity without increased cytotoxicity for the variant • Proteostasis network analysis (autophagy, UPS flux) in neurons expressing the variant shows upregulation vs wild-type This market resolves YES when the primary empirical milestone is met with peer-reviewed publication and independent replication.
Rationale
Domain: neurodegeneration. Priority score: 0.86. Importance: 0.88. Tractability: 0.85. SCIENTIFIC RATIONALE: Counterintuitively, the highly aggregation-prone variant showed reduced toxicity in neuronal models despite forming solid-like fibrils more readily than wild-type TDP-43. This challenges assumptions about the relationship between protein aggregation and cellular toxicity. Gap type: contradiction So RESOLUTION TIMELINE: 18–36 months. Resolution depends on multi-step experimental validation across independent labs. LMSR LIQUIDITY RECOMMENDATION: 100 tokens. Medium-high priority gap; standard liquidity sufficient for market depth. Initial b-parameter should be set to token_cost/100 = 1.0 for LMSR scoring rule.
Pricing semantics
continuous_probability
Proposal cost: 100 tokens