(2013 Kordower) ,

Mean MDS-UPDRS part I score, Mean MDS-UPDRS part II score, Mean MDS-UPDRS part III score

(2006 Sato Movement Disorders Vol. 21, No. 9, 2006, pp. 1384–1395)

• 발병은 대개 70세 이전임.
• 병 진행 속도는 개인차가 대단히 크다.
• 그럼에도 불구하고 굳이 평균을 내보자면, 발병부터 3기로 가는데, 평균 10년이 걸림
• 발병부터 4기, 혹은 5기로 가는데는, 평균 16-20년 이상이 걸림 (4,5기까지 가는 환자들이 소수라는 것이 실제적인 의미임)
• 발병 10년 후 보면, 28% 환자가 4혹은 5기, 15년 후엔 41% 환자가 4혹은 5기

HA-tag

• Definition of HA
  • Hemmaglutinin이 aa sequence 를 갖는 작은 peptide (aa 10개 정도?)
• Protein-HA construct
  • Eg: TOM20-HA

A. AAV - mitoTag construct: Nho I — Tomm20 — E — F — 3xHA — Asc I (linker: gaa-GAA-TTC-tac)

• Detection of protein-HA CONstruct
  • WB
    • Protein-HA construct 는 protein alone에 비해 Molecular weight 증가하는 듯

WB conditions: pAAV-mitoTag (−, +, −, +) × AAV-Cre (+, +, −, −); IB: HA shows TOM20-HA band; IB: TOM20 shows TOM20-HA upper band and TOM20 lower band.

• Staining: protein 까지 염색하면 endogenous 와 구분이 안되므로, 당연히 HA 만 염색하겠지.

HA / DAPI fluorescence microscopy image (red HA puncta with blue DAPI nuclei).

Hearing loss

	Sensorineural	conductive	mixed
	Most common
	the inner ear nerves and hair cells are damaged	typically the result of obstructions in the outer or middle ear — perhaps due to fluid, tumors, earwax or even ear formation
Tx	cannot be corrected medically or surgically, but can be treated and helped with the use of hearing aids	can often be treated surgically or with medicine
	hair cell (sensory receptors) (detecting movement in fluid) in within the spiral organ of Corti on the Healthy inner ear schematic: Semicircular canals (Balance), Vestibular nerve, Auditory nerve, Cochlea (Hearing), Endolymphatic sac. thin basilar membrane in the cochlea of the inner ear. inner ear hair cells cannot regenerate, this damage is permanent.[5] Ear drum→ bones (malleus/incus/stapes) → Hair cell (detect vibrations in the fluids of the cochlea into electrical signals by following steps: ion rush into the hair cells → neurotransmitter release Sensorineural Hearing Loss schematic: Outer Ear (green check) → Middle Ear (green check) → Inner Ear (red X). from the hair cells) → auditory nerve → to the auditory brainstem → the auditory cortex
	BLB: at the luminal surface of inner ear capillaries restricts entry of most blood-borne compounds into inner ear tissues, In the inner ear, the term blood labyrinthine barrier (BLB) refers to the barrier between the vasculature and the inner ear fluids, either endolymph or perilymph

Nigrosome1 MRI

Their flagship technology is nigrosome1 MRI. Nigrosome1 is a small structure in the midbrain and PD its intensity in MRI is changed due to the loss of melanin-containing neurons. Its quantitiation is somewhat challenging to standardize and they are using AI to distinguish PD patients from normal people. They are now trying to validate this with clinically-based PD diagnosis by a clinical study (N=221). However, at this stage, I doubt its utility for our translational or clinical works since we already have good clinical imaging modalities that have good diagnostic power and longitudinal effect size when they have been assessed longitudinally.

Nigrosome1 MRI

• Cross-sectional

Uncertain Spans

location	transcription	uncertainty
AAV-mitoTag schematic / Nho I, gaa-GAA-TTC-tac, Asc I	linker site labels read Nho I (likely Nhe I) and Asc I flanking Tomm20 - E - F - 3xHA; preserved verbatim.	low confidence on Nho vs Nhe.
Nigrosome1 MRI / Their flagship technology paragraph	the paragraph is one long sentence with multiple commas and an opening clipped header ron (the prior heading was truncated at the left edge, likely iron or part of a larger word); preserved verbatim.	low confidence on parent heading text.