Version history

{
  "description": "Challenge generated from hypothesis h-f32ba823 (composite_score=0.798). Target gene/pathway: MANF, CDNF. Source hypothesis: Hypothesis 1: MANF/CDNF Signaling as Primary Neuroprotective Effector.\n\n## Falsifiable Predictions\n1. Recombinant MANF (1-10 μg/mL) reduces ER stress markers (ATF4, CHOP, GRP78) by >40% in tunicamycin-stressed SH-SY5Y cells. 2. AAV-MANF or AAV-CDNF delivery maintains TH+ dopaminergic neuron counts at >80% of sham levels (vs <50% in AAV-GFP controls) in 6-OHDA unilateral striatal lesion model. 3. CSF MANF protein positively correlates (r > 0.5, p < 0.01) with dopaminergic neuron viability in post-mortem PD brain cohort (n >= 30). 4. MANF-KO mice show >30% increase in nigral dopaminergic neuron loss after mild 6-OHDA challenge vs WT, confirming endogenous necessity.",
  "challenge_type": "hypothesis_resolve",
  "scope": "single_hypothesis",
  "initial_bounty_usd": 500,
  "current_bounty_usd": 500,
  "bounty_confidence": 0.5,
  "market_price": 0.5,
  "composite_score": 0.798,
  "debate_count": 0,
  "status": "open",
  "question": "Is MANF or CDNF protein delivery sufficient to reduce ER stress and prevent dopaminergic neuron loss in neurodegeneration models, and what is the mechanistic link to UPR pathway suppression?",
  "domain": "neurodegeneration",
  "triggered_by": "low-hypothesis-to-action-throughput-detector"
}