User:Etienne Robillard/Notebook/NMDA dependent cell adhesion

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Current revision (20:16, 12 June 2013) (view source)
(For next time!)
 
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* <s>A integrin beta3 mutant polypeptide lacking the PTBP1 gene ?</s>
* <s>A integrin beta3 mutant polypeptide lacking the PTBP1 gene ?</s>
-
* A pyrimidine-rich associated polypeptide complex is best known a protein.  
+
* 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 <font color=red>red</font> <font color=purple>heering</font> in understanding protein over-expression factors in the transcription of mRNA.  
* A e.coli K12 derived auxotrophic restriction enzyme system may be the key <font color=red>red</font> <font color=purple>heering</font> 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...  
+
* '''<font color=purple>Dude where's my calcium?</font>''': Zinc/Leucine/Glycine/Serine  (Rho, GNAT, etc) -> KEY Calcium/Magnesium (Ca2+/Mg2+) mediated cell adhesion amino acids; phosphatase-like (transferase) family members...  
 +
** see also [http://www.brenda-enzymes.org/php/result_flat.php4?ecno=3.4.21.4&Suchword=&organism%5B%5D=Homo+sapiens&show_tm=0 EC 3.4.21.4] - [http://www.genome.jp/kegg-bin/show_pathway?hsa05164+5646 PATHWAY] - [http://www.uniprot.org/uniprot/P35030 UNIPROT]
* 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.
* 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!
* "horn" directed mutagenesis: too difficult to realize in vivo? -- Check this!
Line 20: Line 21:
=== Going a bit further... ===
=== Going a bit further... ===
-
* Explain dna methylation and role of 30C6HSL (exo-genous) promoters in the upregulation of N-Methyl-D-Aspartate receptor and Calcium channel blockers   
+
* Explain dna methylation and role of [[User:Etienne_Robillard/Notebook/30C6HSL|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 <font color=purple>visual signals</font> properly in the fore-brain (ie: hippocampus) through a signal transduction cascade...  
* summarly define how a calcium channel blocker 'block' (disrupt) GABA receptor from processing <font color=purple>visual signals</font> properly in the fore-brain (ie: hippocampus) through a signal transduction cascade...  
* What is primary difference between a putative and non-putative gene?
* 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 <font color=purple>binding (adhesion)</font> variance when information about a system is poor.
 +
** <i>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.</i> http://journals.sfu.ca/coactionbks/index.php/Bindslev/article/viewArticle/14/75
 +
 +
=== Case study: Focus on Hemagglutinin binding factors ===
 +
 +
* Review this Free PMC [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2025700/ 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 [http://www.uniprot.org/uniprot/Q9WFX3 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 <font color="purple">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."</font> [[http://www.uniprot.org/uniprot/Q9WFX3 1]]
 +
** 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 ===
 +
 +
* [http://www.genome.jp/kegg-bin/show_pathway?hsa05010 PATHWAY]
 +
* [http://www.genome.jp/dbget-bin/www_bget?hsa:814+hsa:815+hsa:816+hsa:817+hsa:818 CAMK] -- Alcoholism*, Learning (memory), LTP
 +
* [http://www.genome.jp/dbget-bin/www_bget?hsa:2902+hsa:2903+hsa:2904+hsa:2905+hsa:2906 NMDAR] -- Alcoholism*, Alzheimer, LTP
 +
* NMDAR -> CREB2 http://www.genome.jp/dbget-bin/www_bget?hsa:468
=== References ===
=== References ===
* Proteins and enzymes:
* Proteins and enzymes:
-
# http://www.uniprot.org/uniprot/P20592
+
# cAMP-dependent protein kinase A (C-alpha): http://www.uniprot.org/uniprot/P17612
-
# http://www.uniprot.org/uniprot/P26599
+
# cAMP-dependent protein kinase A (C-beta) : http://www.uniprot.org/uniprot/P22694
# Histone-lysine N-methyltransferase (SETD8) http://www.uniprot.org/uniprot/Q9NQR1 [http://omim.org/entry/607240 OMIM]
# Histone-lysine N-methyltransferase (SETD8) http://www.uniprot.org/uniprot/Q9NQR1 [http://omim.org/entry/607240 OMIM]
# E-cadherin (CDH1) http://www.uniprot.org/uniprot/P12830 [http://omim.org/entry/192090 OMIM]
# E-cadherin (CDH1) http://www.uniprot.org/uniprot/P12830 [http://omim.org/entry/192090 OMIM]
 +
# Wnt3 (<u>also known as the Ca2+ pathway, aka a Voltage-gated ion channel...</u>) http://www.uniprot.org/uniprot/P56703 [http://www.genome.jp/kegg-bin/show_pathway?org_name=hsa&mapno=04310&mapscale=&show_description=hide pathway]
 +
# c-Src proto-oncogene: http://www.uniprot.org/uniprot/P12931
* By organism:
* By organism:
-
# H. sapiens (EC 2.7.11.1) (PTEN-Induced Putative Kinase 1) http://www.genome.jp/dbget-bin/www_bget?hsa:65018 [http://brenda-enzymes.org/php/result_flat.php4?ecno=2.7.11.1&Suchword=&organism%5B%5D=Homo+sapiens&show_tm=0 BRENDA]
+
# H. sapiens (EC 2.7.11.1, PTEN-Induced Putative Kinase 1) http://www.genome.jp/dbget-bin/www_bget?hsa:65018 [http://brenda-enzymes.org/php/result_flat.php4?ecno=2.7.11.1&Suchword=&organism%5B%5D=Homo+sapiens&show_tm=0 BRENDA]
-
# H. sapiens (EC 2.1.1.43) (SETD8) http://www.genome.jp/dbget-bin/www_bget?hsa:387893
+
# '''H. sapiens (EC 2.7.11.17, CaM kinase II, CamKII)''' http://www.genome.jp/dbget-bin/www_bget?ec:2.7.11.17
-
# H. sapiens ('''ITGB2''') http://www.genome.jp/dbget-bin/www_bget?hsa:3689 [http://omim.org/entry/600065 OMIM] (note the chromosome location and the annotated phenotype)
+
# H. sapiens (EC 2.1.1.43, SETD8) http://www.genome.jp/dbget-bin/www_bget?hsa:387893
 +
#<s> H. sapiens ('''ITGB2''') : http://www.genome.jp/dbget-bin/www_bget?hsa:3689 [http://omim.org/entry/600065 OMIM] (note the chromosome location and the annotated phenotype)</s>
 +
# H. sapiens ('''NMDAR1''') : http://www.genome.jp/dbget-bin/www_bget?hsa:2902
=== Keywords ===
=== Keywords ===
-
* Integrins, pyrimidine, glutamine, NMDA, hippocampus, calmodulin, PTBP1, neuropeptides, b-secretase (BACE)
+
* <s>Integrins</s> (Ketamine), S1P, pyrimidine (?), calcium, glutamine, NMDA, hippocampus, calmodulin, PTBP1, neuropeptides, b-secretase (BACE), NMDAR, NMDAR1
=== For next time! ===
=== For next time! ===
-
* Review and complete wiki class page on [[Integrase]].
+
* Review Calcium and [[User:Etienne_Robillard/Notebook/GABA|GABA]] signaling?  
-
* Review Calcium and GABA signaling? (Hint: Wet blanket for Calcium-mediated glutamine excitoxicity!)
+
** IFP as a flow calibration mesure to visualize the impact of Ketamine on neurocognitive functions via Remote triggered smart phones (iphone4 type tablets)
-
* 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 ? -[[User:Etienne_Robillard|ER]]
+
* Ketamine (Arylcyclohexylamine) induced beta-amyloids APP (Alzheimer Disease) plaque aggregation 
-
* 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 ? -[[User:Etienne_Robillard|ER]]
+
** [[User:Etienne_Robillard/Notebook/Arylcyclohexylamines/2013/05/24|Lab notebook 2013/05/24]]
-
** '''Important Note: Back in World-war 2, Ziklon-b pellets (Auschwitz) were found to dispense the deadly compound to the prisoneers from the <font color=red>outside</font> 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 ? -[[User:Etienne_Robillard|ER]]
+
** Review this paper [http://aizenmanlab.neurobio.pitt.edu/aizenman_position_files/pdf/ardenkcn.pdf here] about the DNA methylation of neuropeptides with cyanide affects the NMDA receptor. [yet more NMDAR stuff]
-
** 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  ?  -[[User:Etienne_Robillard|ER]]
+
* Review role of [http://web.campbell.edu/faculty/nemecz/323_lect/cofactors/pyridoxal_1.html PLP] (pyridoxal-5-phosphate) in the intermediate synthesis of [[User:Etienne_Robillard/Notebook/Schiff_base|Schiff bases]] (pKa='''11''').
-
* Review this paper [http://aizenmanlab.neurobio.pitt.edu/aizenman_position_files/pdf/ardenkcn.pdf here] about the DNA methylation of neuropeptides with cyanide affects the NMDA receptor.
+
** Notice the presence of ketimine in the reaction and the '''-rC=N''' alpha-hydrogen bond. [http://www.chem.ucalgary.ca/courses/350/Carey5th/Ch21/ch21-2.html Review acidity of alpha-Hydrogens bonds here]
-
** For Acetonitrile based cyanolation reagents, see: [[Acetonitrile]]
+
** [[User:Etienne_Robillard/Notebook/Arylcyclohexylamines/2013/05/23|Lab notebook 2013/05/23]]
-
** For simple alcohol-based polypeptide cross-linker reagents (dA), see: [[PVA]] and [[Isopropanol]]
+
** [http://web.campbell.edu/faculty/nemecz/323_lect/cofactors/pyridoxal_2.html PLP metabolic regulation notes part two].
=== See also... ===
=== See also... ===
Line 54: Line 76:
* c-Src specialized kinase (SH2/SH3 domain, PH domain, 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: [[User:Etienne_Robillard/Notebook/EGFR|EGFR]]
* MAPK <-> c-Src domain interactions and cross-talk, ie integrins mediated cross-talking, see: [[User:Etienne_Robillard/Notebook/EGFR|EGFR]]
-
 
+
* http://www.alzforum.org/new/detail.asp?id=2070
----
----

Current revision

Mo calcium, mo visual hallucinations

Contents

Abstract

An essay on the role of the Integrin beta-3 protein (ITGB3) in Ca2+-dependent orthogonal riboswitches.

Introduction

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. [1]

Notes

  • 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." [1]
    • 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

References

  • Proteins and enzymes:
  1. cAMP-dependent protein kinase A (C-alpha): http://www.uniprot.org/uniprot/P17612
  2. cAMP-dependent protein kinase A (C-beta) : http://www.uniprot.org/uniprot/P22694
  3. Histone-lysine N-methyltransferase (SETD8) http://www.uniprot.org/uniprot/Q9NQR1 OMIM
  4. E-cadherin (CDH1) http://www.uniprot.org/uniprot/P12830 OMIM
  5. Wnt3 (also known as the Ca2+ pathway, aka a Voltage-gated ion channel...) http://www.uniprot.org/uniprot/P56703 pathway
  6. c-Src proto-oncogene: http://www.uniprot.org/uniprot/P12931
  • By organism:
  1. H. sapiens (EC 2.7.11.1, PTEN-Induced Putative Kinase 1) http://www.genome.jp/dbget-bin/www_bget?hsa:65018 BRENDA
  2. H. sapiens (EC 2.7.11.17, CaM kinase II, CamKII) http://www.genome.jp/dbget-bin/www_bget?ec:2.7.11.17
  3. H. sapiens (EC 2.1.1.43, SETD8) http://www.genome.jp/dbget-bin/www_bget?hsa:387893
  4. H. sapiens (ITGB2) : http://www.genome.jp/dbget-bin/www_bget?hsa:3689 OMIM (note the chromosome location and the annotated phenotype)
  5. H. sapiens (NMDAR1) : http://www.genome.jp/dbget-bin/www_bget?hsa:2902

Keywords

  • Integrins (Ketamine), S1P, pyrimidine (?), calcium, glutamine, NMDA, hippocampus, calmodulin, PTBP1, neuropeptides, b-secretase (BACE), NMDAR, NMDAR1

For next time!

See also...


"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

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