User:Etienne Robillard/Notebook/NMDA dependent cell adhesion
Mo calcium, mo visual hallucinations
An essay on the role of the Integrin beta-3 protein (ITGB3) in Ca2+-dependent orthogonal riboswitches.
In the study of calcium-mediated (Ca2+) neuronal receptors (NMDA and GABA mostly), the relevance of Ca2+-dependent ligands (ie: calmodulin) may hold important factors in the morphogenesis of psychological brain disorders and the pathogenesis of the Alzheimer disease, a important phenotype in the understanding of GPCR-mediated brain mutations. Hence a proper understanding of the polypyrimidine tract binding protein-1 (PTBP1) dependent signaling pathway may reveal new insights in the functions and features of the integrin beta-3 protein as a cell-adhesive (and voltage-gated!) neural substrate for long-term axon and neuronal growth. 
A integrin beta3 mutant polypeptide lacking the PTBP1 gene ?
- A pyrimidine-rich associated polypeptide complex is best known as a "protein".
- A e.coli K12 derived auxotrophic restriction enzyme system may be the key red heering in understanding protein over-expression factors in the transcription of mRNA.
- Dude where's my calcium?: Zinc/Leucine/Glycine/Serine (Rho, GNAT, etc) -> KEY Calcium/Magnesium (Ca2+/Mg2+) mediated cell adhesion amino acids; phosphatase-like (transferase) family members...
- Neural (Voltage-gated) ligand expression possible side-effect may include novel psychotic behavior, especially if remotely activated with electromagnetic (RF) signals under 2.45 GHz ? -- Check this.
- "horn" directed mutagenesis: too difficult to realize in vivo? -- Check this!
Going a bit further...
- Explain dna methylation and role of 30C6HSL, a keto-ester, in the upregulation of N-Methyl-D-Aspartate receptor and Calcium channel blockers
- summarly define how a calcium channel blocker 'block' (disrupt) GABA receptor from processing visual signals properly in the fore-brain (ie: hippocampus) through a signal transduction cascade...
- What is primary difference between a putative and non-putative gene?
- Erbb Signaling Pathway: http://www.genome.jp/dbget-bin/www_bget?pathway:map04012 Look for "CAMK" on this map and which conclusions may you draw from its interactions (Cross-talking) with erbb2? Is erbb2 a promoter or a repressor of Calcium-dependent adhesion (and why)?
- On Hill coefficient (Kd) measurement and analysis:
- In short, the Hill coefficient is a statistical tool (function) to measure binding (adhesion) variance when information about a system is poor.
- As pointed out by Cornish-Bowden and Koshland (1975), the ‘logit’ plot in pharmacology is a plot identical to the Hill plot, and formally equivalent to Nernst's plot of redox electrochemistry (Reed & Berkson 1929, their example 5; Malmstrom 1974). The logit plot is also equivalent to the gating transitions of voltage dependent ion channels (Yifrach 2004). See Section 10.3.9 for more on the relationship between the Nernst and the Hill equations. http://journals.sfu.ca/coactionbks/index.php/Bindslev/article/viewArticle/14/75
Case study: Focus on Hemagglutinin binding factors
- Review this Free PMC here. Can you identify the factors which makes the HA protein clump or can you postulate the role and significance of Ca2+ signaling pathway in the viral coating of the H. influenza virus ? Recall that the Hemagglutinin protein is solely required for the H. influenza virus to attach into its host and begin an unwary invasion on the immune system.
- Note 1 (HA cleaving factors): "The extent of infection into host organism is determined by HA. Influenza viruses bud from the apical surface of polarized epithelial cells (e.g. bronchial epithelial cells) into lumen of lungs and are therefore usually pneumotropic. The reason is that HA is cleaved by tryptase clara which is restricted to lungs. However, HAs of H5 and H7 pantropic avian viruses subtypes can be cleaved by furin and subtilisin-type enzymes, allowing the virus to grow in other organs than lungs." 
- Based on this comment above, can you postulate how unwary HA infections may silently avoid immune-specific detection by the host ??
Case study: Focus on Alzheimer phenotype
- CAMK -- Alcoholism*, Learning (memory), LTP
- NMDAR -- Alcoholism*, Alzheimer, LTP
- NMDAR -> CREB2 http://www.genome.jp/dbget-bin/www_bget?hsa:468
- Proteins and enzymes:
- cAMP-dependent protein kinase A (C-alpha): http://www.uniprot.org/uniprot/P17612
- cAMP-dependent protein kinase A (C-beta) : http://www.uniprot.org/uniprot/P22694
- Histone-lysine N-methyltransferase (SETD8) http://www.uniprot.org/uniprot/Q9NQR1 OMIM
- E-cadherin (CDH1) http://www.uniprot.org/uniprot/P12830 OMIM
- Wnt3 (also known as the Ca2+ pathway, aka a Voltage-gated ion channel...) http://www.uniprot.org/uniprot/P56703 pathway
- c-Src proto-oncogene: http://www.uniprot.org/uniprot/P12931
- By organism:
- H. sapiens (EC 22.214.171.124, PTEN-Induced Putative Kinase 1) http://www.genome.jp/dbget-bin/www_bget?hsa:65018 BRENDA
- H. sapiens (CaM kinase II, CamKII) http://www.genome.jp/dbget-bin/www_bget?ec:126.96.36.199
- H. sapiens (EC 188.8.131.52, SETD8) http://www.genome.jp/dbget-bin/www_bget?hsa:387893
- H. sapiens (ITGB2) : http://www.genome.jp/dbget-bin/www_bget?hsa:3689 OMIM (note the chromosome location and the annotated phenotype)
- H. sapiens (NMDAR1) : http://www.genome.jp/dbget-bin/www_bget?hsa:2902
- Integrins, pyrimidine, glutamine, NMDA, hippocampus, calmodulin, PTBP1, neuropeptides, b-secretase (BACE), NMDAR, NMDAR1
For next time!
- Review and complete wiki class page on Integrase.
- Review Calcium and GABA signaling? (Hint: Wet blanket for Calcium-mediated glutamine excitoxicity!)
- beta-amyloids APP - In the synthesis of 1,2,3,4-tetrahydroisoquinolines derivatives via asymmetric PS synthesis, how is beta-linked amyloids (note: For the Alzheimer precursor protein type "APP" on uniprot) responding to 2.45 GHz electromagnetic waves (2.450 GHz is a typical radio-frequency (RF) signal used in portable human wireless devices; Iphone4-type device; etc) for horn-directed mutagenesis of neuronal X-linked polypeptides/ligands ? -ER
- Moreover assuming the psychochemical media require a ultra-sound frequency (ie: 2.450 GHz) to INDUCE mRNA-activated polypeptide alkane isomerisation of the PTBP1 genes, how mentally retarded do you estimate a human-made decision must be (IQ) to allow and implement the forced installation of such biological assault devices without the consent and informed judgement into the homes and residences of civilians ? -ER
- Important Note: Back in World-war 2, Ziklon-b pellets (Auschwitz) were found to dispense the deadly compound to the prisoneers from the outside of the concentration camps. Based on theses evidences, which experimental protocol may you use to measure and verify the risks and effects of cumulative exposure to 1,2,3,4-tetrahydroisoquinolines derivatives ? -ER
- Furthermore, based on the evidences correlated to the implementation of such potentially harmful and intrusive technology into unprotected homes (non-ionising EM waves) to human health, do you believe the idea/concept of "smart metering" is an affront to human dignity and thus in direct conflict with the principle of saving lifes ? -ER
- Review this paper here about the DNA methylation of neuropeptides with cyanide affects the NMDA receptor. [yet more NMDAR stuff]
- Rhodopsin - Rho/GTPase specific AI inducers: Rhodopsin etc.
- c-Src specialized kinase (SH2/SH3 domain, PH domain, etc)
- MAPK <-> c-Src domain interactions and cross-talk, ie integrins mediated cross-talking, see: EGFR
"Courage is resistance to fear, mastery of fear, not absence of fear." -Mark Twain
"You will never do anything in this world without courage. It is the greatest quality of the mind next to honor." - Aristotle
"Success is not final, failure is not fatal: it is the courage to continue that counts." -Winston Churchill