Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.02 from other evidence | 0.00 |
| cell type Human Protein Atlas | enriched in the midbrain (22 nTPM), where the nigral dopamine neurons sit | 0.90 |
| chemistry Open Targets | a small-molecule pocket | 0.60 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 4 Parkinson's papers of 80 | 0.79 |
| pathways Reactome | 2 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress CHRNB3 in dopamine neurons; measure evoked dopamine release and dopamine transporter uptake and survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils.
- Cell type
- dopamine neurons
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- evoked dopamine release and dopamine transporter uptake
- Functional readout
- survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils
- Rule-out
- If neither arm moves evoked dopamine release by 20% or more against non-targeting and empty-vector controls, across three independent differentiations, the hypothesis is wrong.
- Lab request
- CRISPRi knockdown and lentiviral overexpression of CHRNB3 in iPSC-derived midbrain dopamine neurons (FOXA2+, LMX1A+, TH+); n = 3 differentiations; readouts: evoked dopamine release and dopamine transporter uptake; survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- CHRNB3 in dopamine neurons, braak+0.19 (p 0.630) → -0.08 (p 0.842)receipt 8586
Swarm cases
receipt 8586: CHRNB3 in dopamine neurons, braak
- power
- full sample +0.03 (p 0.922, n 18), 95% CI -0.45 to +0.49. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.06 (p 0.820, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.02 (p 0.942, n 18). could be the mix.
- skeptic
- leave-one-out range -0.06 to +0.17, sign flips 6; without severely affected donors +0.03 (p 0.922, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CHRNB3 in dopamine neurons.
case closed: nothing better to follow up.
Receipts
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