S4 old Q Flashcards
Production and assembly of collagen fibrils by local cells
syn of pro alpha chain
hydroxylation of lysine and prolines and self assembly of the B pro alpha chains with H bonds for stability
procollagen triple helix formation
packing of pro collagen in to secretory vessicle and secrtion
cleavage of propeptides and to collegen molecules and self assembly into fibreils
how does increase in lox expression in cancer cells contribute to cancer progression
Lox catalyzes aldehyde formation on lysine residues of collagen precursors
highly reactive so forms linkages with eachother and corsslinks collagen to increase stiffeness of ECM which makes cancer cells escape and metastizie
integrin receptor structure and activation
transmembrane heterodimers composed of alpha and beta subunits with ligand bindng, head, and tail domains
outside in activation
inside out activation
outside in activation of integrin
ligan binds to outside on head domain of hterodimers in ecm
conformational change that exposes talin binding site (beta subunit) talin binds and actin assembles
inside out activation of integrins
talin activated by PIP2 intracellularly
talin binds to beta subunit
confromational change
RTK +GPCR extracellular signals
how do integrin recpetors generate signaling complexes that regulate cell functions
through the outside in method of activation talin becomes bound
talin exposes FAK binding site
FAK recruited, clusters and cross phosphorylate each other at Tyr residues
phosphorylated FAK generates phosphorylated binding sites for other signaling molecuels
signaling cascades for cell survival, growth, organization
2 biological functions of basement membrane
mechanical support: connects epidermis to dermis
Selective Filter: prevents fibroblasts from contacting epithelial cells but allows immune/nerve cells access
in vivo stem cell experimetn
Cre to study SC lineage Rosa26-stop-lacz BSC-GFP-CRE cross above BSC will express GFP/Lacz cell tracked and imaged from liverr in immuno prep
Advantages of patient iPS cells
autologous so no rejection
no ethical concerns
disadvantages of patient iPS cells
low efficacy
concern for tumors
incomplete programming
two critical tests showing that cells are ready for transplantation in vitro
cell sort to see if youre getting cells
screen for tumor forming
critical and efficacy data that you need to provide the FDA
saftety data: mortatlity rate, severe bodily effects on organs/fucntions
efficacy data: any off target side effects, how the effective treatment was at improving the number of insulincytes or diabetic symptoms (dose dependence)
phase 1 trial primary and secondary measures
primary is saftety of transplant in patient
secondary is efficacy as a treatment and off target effects
2 diffferences btwn phase 2 and phase 3
phase II uses larger group than PI but PIII useus massive group from larger area
P2 is looking at general efficacy of the treatment, but phase III looks at collective efficacy and safety in a large population
For BTK why would only the A form of G6PD be expressed in B cells
BTK gene is specific for B cell maturation and a defect in BTK will result specifically in B cell development arrest
