ERB

Resting potential (Inactive state)

• 평소엔
  • All Na v-gated channels are closed
  • Most K v-gated channels are closed
  • Na/K pumps are open
    • Na⁺/K⁺-ATPase (sodium-potassium pump) transports 2 potassium ions inside and 3 sodium ions outside at the cost of 1 ATP molecule.
      • Thus , within a cell
        • K high
        • Na low (Na 를 계속 cell 밖으로 내보내고 있으므로)
• the respective reversal potentials (equilibrium) are +60 mV for sodium (E_Na) and −80 mV for potassium (E_K).
  In a healthy animal cell Na⁺ permeability is about 5% of the K⁺ permeability or even less,
  Thus, the cell’s resting potential will be about −73 mV.

Process

	Presynaptic cell	Synaptic cleft	Postsynaptic cell
평조 (resting potential)			sodium-potassium pump 보다는 diffusion through Leakage channels 이 역할이 크고, 또 이중 K 의 (나가기만 하는) 비중이 크기 때문에 negative charge	결국 : 평소엔 K 이 drive 하고, Action potential 은 Na 이 주로 drive 하는 것이구나.
Action potential	(Action potential 이 presynaptic terminal 에 도착하면 →) presynaptic terminal 에서 ca influx ↑ → vesicle 내의 neurotransmitter 가 released →	Neurotransmitter from presynaptic cell bind the receptors on the postsynaptic cell → ion channels open 되면서 action potential	Synaptic input to a cell → ↑ memb potential ('depolarization') → 일부 Na channels open / ↑ Na influx, 직후 K channels open / ↑ K outflux → −55 mV (threshold potential) 도달하면 → 모든 Na channels open / ↑ Na influx → at the peak of memb potential, Na channels close while K 은 계속 나가고 있고 → {Zampese 2022} in SN DA neurons, ↑ caldium entry through Cav1 channels → calcium release from ER → mitochondrial oxidative phosphorylation) → ↓ memb potential ('repolarization') and K channels open → ↑ K outflux 시작 → (아마도 어느 ion 의 channel 이 open 되느냐에 따라) ↑ Memb potential (depolarization) : 이 경우가 excitatory ↓ Memb potential (hyperpolarization) : 이 경우가 inhibitory → 두 경우 모두, propagates to neuboring region in the membrane	근데 heart 에선 Na 후에 Ca 의 주가적인 역할이 있구나 (m contraction 하려고, & 그래서 AP 길어짐)
			Action potential 시 Na 이 확 들어오므로 (through Na channel) 확 postiive 로 (depolarization ) Peak 에서부터는 Na 진입이 막히고 K 진줄만 있으므로, 전압 내려감 (repolarization)

상기 과정이 보통 neuron 에서 10-100/sec

• 양이온 나감은 negative 쪽으로 작용
• 양이온 들어옴은 positive 쪽으로 작용
• 핵심:

	Resting potential 에 이 둘이 상보적으로 작용함.	Action potential 에 작용
	Na⁺/K⁺-ATPase (sodium-potassium pump)	Leakage channels (ie simple diffusion)	Voltage-gated channels
Na	내보냄	→ 들여옴	들여옴
K	들여옴 (이래서 K 가 cell 내 많아지므로)	→ 내보냄	내보냄

voltage-dependent ion channels

• i.e. The transition between conformations (closed, open & deactivated) is influenced by the membrane potential
• Na_v, Ca_v

ERB

BUSC	Tsho	R&D Ethics and Compliance department	Tbos
	portal: Shonan Biosafety Portal dates in 2022 (deadline 4/11→) 5/9, (deadline 5/27→) 6/13, (deadline ?→) 7/11, 8/8, 9/12, 10/17, 11/14, 12/12 secretariat: Ootani, Yoshikazu EC is held in every other months Required documents Protocol Protocols must be created and submitted in CLIMSON. Template of Informed Consent Form and Consent Document (draft is accepted) (If any) Joint research contract (draft is acceptable ) (If any) Certificate of approval of ethics review at a joint research institution Mandatory if a fast review is required. In many cases, ethics reviews at Takeda and a joint research institution for the joint research takes place simultaneously.	Missy Heidelberg, Global Bioethics Lead (Kathleen Stern who was the head of bioethics, left Takeda. )	Searching "bioethics" in Workday I got only one hit: Missy Heidelberg, in Jenny Colombo's group below. I would start with her and move up her line if she can't answer.

Endoplasmic Reticulum (ER)

		FUNCTION
Rough	ribosomes attached to its outer (cytoplasmic) surface.	Rough ER lies immediately adjacent to the cell nucleus, and its membrane is continuous with the outer membrane of the nuclear envelope. The ribosomes on rough ER specialize in the synthesis of proteins that possess a signal sequence that directs them specifically to the ER for processing.
Smooth	not associated with ribosome	The smooth ER is involved in the synthesis of lipids, including cholesterol and phospholipids, which are used in the production of new cellular membrane.

4 Exosome

• Exosomes are small extracellular vesicles with a diameter of 30 to 150 nm derived from the membranes of various cell types, including microglia and neurons (He et al., 2018).
• [JF PDRx 20240501]
  • 5% of plasma aSyn is in the EV fractions
  • Phosp aSyn is enriched in EVs (plasma)
  • aSyn in CSF EVs was below LOD for half of the control samples

Function

• the transmission of biomacromolecules.
• Since exosomes are membrane-permeable and have low immunogenicity, these nanoparticles have been extensively used as biological carriers to deliver multiple therapeutic compounds that could avoid phagocytosis and bypass lysosomal engulfment

limitation of exosome

• Lack of validation of the cellular orginin of the exosomes.
  • contamination 도 rule out 해야 함
  • peripheral origin 도 rule out 해야 함.
  • 다른 tissue 도 rule out 해야 함.
• Pituitary
  • Pituitary gland is outside of the BBB!
• Skeletal m
  • skm

Process

• Exosome Diagnostics, Inc (exosomedx) :
  • Exosome Dx Depletion Enrichment (EDDE)
    • The patented EDDE platform can select exosomes derived from a specific tissue type,
      • Depletion: of non-relevant exosomes &
      • → Enrichment: of specific target you want (어떤 방법으로 Depletion & Enrichment 하는지는 비밀이겠다)
      • → RNASeq → mapping → analysis
        • biotype distribution
        • correlation

Uncertain Spans

location	transcription	uncertainty
Process / 평조	left column reads 평조 (sic, single Korean glyph likely intended as 평소); preserved verbatim.	source typo.