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You have wisely landed upon Authentic Biochemistry, with Dr. Daniel J Guerra, where published biochemical, physiological, genetic and immunological research along with biomedical and pharmaceutical science are interrogated.
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Andrew and Healey. 1967 "Call on Me" Big Brother and the Holding Company Janis Joplinhttps://open.spotify.com/track/4HljoGSCvaFsesUZWpb2mK?si=5322f5968cbe4975
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Clapton &Whitlock. 1970."Why does Love have to be so Bad?" on LAYLA lp.
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Hayward,J. 1970. "Dawning is the Day" Moody blue AQoB lp.
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Haggard, M. 1969. "Okie from Muskogee"
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QMS. 1968. "Happy Trails"
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Mozart, WA . 1782-85'. "The Six Haydn Quartets"
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Simon, 1968. "Old Friends/ Bookends"
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Allman,G. 1967. "Melissa" Allman Brothers. Eat a Peach lp.
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Friend& Mills 1922 "Lovesick Blues" Hank Williams
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Vivaldi, A. 1718 "La Primavera" Violin Concerto in E Major OP 8. RV.269https://music.youtube.com/watch?v=3LiztfE1X7E&si=QMSJGvDnaH8pOsIu
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Telemann, G.P. 1733. Taflemusik complete
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J Exp Med . 2023 Aug 29;220(11):e20222105Guerra, DJ 2025 Unpublished LecturesHunter/Garcia. 1973"Row Jimmy" on Wake of the Flood lp.
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Guerra, DJ 2025 Unpublished Lectures.Science. 2009 May 22;324(5930):1076–1080.
Ballard, H. 1959. "The Twist" Chubby Checker
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Lennon/McCartney 1963. "She Loves You"
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Richards and Jones. 1966 "Ruby Tuesday"
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Simon, P. 1966. "Kathy's Song"
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Schmelzer, H. 1662.Sonata in d minor
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Redding ,O. 1965. "Respect" Aretha Franklin.https://music.youtube.com/watch?v=9iayJ8u4Qew&si=MQGj24vwxi-a7MA2
McQuinn, R. etal. 1969. Ballad of Easy Rider" lp
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Tartini, G. 1739-1741. Various Violin Concertihttps://open.spotify.com/album/3l2hknOjPdgD3WNxqPoGrF?si=bOmGO0nbRtWpfMJ2qtUtaw
Lennon/McCartney 1966. "For No One" on Revolver (lp)https://open.spotify.com/track/1kDkaFlmkdEZiVUogaP9OZ?si=82292716f8f642eb
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Guerra, DJ.2025. Nascent Lectures :Neuroimmune Diaventome.
Nash,J.1972. "I Can See Clearly Now"
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Pinder, M. 1967 "Dawn is a Feeling" on DOFP(lp) Moody Blues
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Seeger&Davies.1958."Bells of Rhymmy" Byrds https://open.spotify.com/track/1mpv6hIbfG75txI9zJGcf4?si=832538f153134d02
Mozart. WA. 1791. Requiem Mass in D minor. K.626
Performed by the Academy of St Martin of the Fields w/ Neville Mariner conducting
https://open.spotify.com/album/2mAq4V9WfnKBIMmKGLS653?si=PJ3mysXATBSti1vfSPSP3A
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Guerra DJ 2025. General Immuno-Neurobiochemical lectures
Plant&Page. "Rain Song" LZIV.
https://open.spotify.com/track/3JLrri1xSCui3bzITDJbkk?si=c4ff9d466c2d455f
Hunter/Garcia. 1970 "Attics of my Life" American Beauty lp. GD
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Schubert F. 1828. Piano Sonata in B flat Major. #15. D960
https://open.spotify.com/track/7H3UCOtOQhmvKaC3QA0h7p?si=312dc808cbf64a5b
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Guerra, DJ. 2025 Neurohormonal Lectures Brief Introductions
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Mol Cell Biol . 2002 Nov;22(22):7758–7768.Front Immunol. 2023; 14: 1151166. Guerra, DJ.2025. Unpublished lectures
Blood . 2017 Nov 30;130(22):2401-2409
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Preitti, Creatore and Weiss 1961"Cant Help Falling in Love with You". Elvis
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Mozart, WA. 1785. Piano Concerto #22.in EMajor. K482
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Hayward, J. 1971."You Can Never Go Home" Moody blues on Every Good Boy Deserves Favor" lp
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Baker/Taylor. 1968. "Those Were the Days". Wheels of Fire. lp. Cream.
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Schubert, F. Quartet 13. in A Minor. D.804
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Hunter/Garcia. 1971. "Bertha" Skulls&Roses lp. Grateful Dead.
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Hunter/Garcia.1970. "Ripple" American Beauty lp. Grateful Dead
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Beethoven, LV. 1806. Violin Concerto in D Major. Op.61
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Guerra, DJ.2025. Unpublished lecturesTownsend. P. 1971 "Im in Tune" The Who.
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Hunter/Garcia/Lesh. 1969. "St Stephen" Aoxomoxama Grateful Dead.
Lennon/McCartney 1967. "Hello Goodbye"https://open.spotify.com/track/0vZ97gHhemKm6c64hTfJNA?si=9f938e5357724d8d
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Mason, D. 1970. "Sad and Deep as You" Traffic.
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Miller, S. 1977. "Wintertime"
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Bach,JS. 1741. "Goldberg Variations"
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Mozart, WA. 1791."Ave Verum Corpus transcribed by Liszt.
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Dylan, R. 1964. Mr. Tambourine Man
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Henley and Frey. 1973. Desperado. The Eagles
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Tchaikovsky, P.I 1878..Violin Concerto in D Major Op 35.
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Beethoven LV. 1804. Symphony 3. IN E. Major Op. 55. "Eroica"
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Miller and Winwood 1968. "Medicated Goo" Traffic•https://open.spotify.com/track/3OD2BlIAkr1DkSe94sKIoI?si=46125a00f2474ac5Hayward and Thomas 1969. " Are you sitting comfortably" Moody Blues On the Threshold of a Dream lp
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Schubert, F. 1822. Symphony 8
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Zappa, F. 1964. "Status Back Baby"
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Bruce and Brown. 1968. "Deserted Cities of the Heart" CREAM.
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Guerra, DJ 2025. Unpublished lectures.
Anderson, I 1969."We Used to Know" on Stand Up [lp]. Jethro Tull
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Hayward, J. 1969. I never Thought Id Live to be a Hundred" Moody Blues. ToCC lp.
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Mozart. WA. 1780's Complete Piano Sonatas.
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Previous discussions
Correction:
In my lecture I incorrectly used the W single letter designation as representing tyrosine. I miss-spoke.
W=tryptophan while Y=tyrosine.
The WW domain discussion is important for specific protein:protein interactions wherein the tryptophan (W) residues (found in the beta1 and beta 3 folds) are separated by 20 -22 amino acids that contain certain tyrosine (Y) residues in the beta2 region which may become phosphorylated thus generating phosophotyrosine binding (PTB)domains that are recognized by other proteins.
I apologize for the error.
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REDOX and Cholesterol metabolism lectures-Dr Guerra
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Oncogene.2017 Mar 23; 36(12): 1607–1618
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DJGPhD writings on Middle Platonist Metaphysics in Biochemistry: unpublished
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AJP Endocrinology and Metabolism. 2008. 295(6):E1287-97
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Dr Guerra's lectures
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References and Inspiration
Dr Guerra lecture notes
https://youtu.be/uubKzLxxj1s
References and Inspirations
Dr Guerra graduate biochemistry lectures
https://youtu.be/156u4nV2uGE
References and Inspirations
Dr Guerra's lecture notes-graduate biochemistry
https://youtu.be/nP4nBxMtEug
References&Inspirations
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Rather than referencing this episode I am enlisting your input.
Please email me at our new email address:
Sincerely,
Dr Guerra
References
Dr Guerra's micro RNA lectures
FEBS J Volume278, Issue10 May 2011. Pages 1598-1609
International Journal of Molecular Sciences 2013. 14(11):22796-22816
Front. Genet., 07 September 2021
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JCI Insight. 2020 Sep 3;5(17):e138443
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Referernces
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References
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Dr Guerra's Lecture notes
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Int. J. Mol. Sci. 2019, 20, 4660; doi:10.3390/ijms20194660
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Dr Guerra lipid lectures
Dr. Guerra's Basic Biochemistry Lecture notes
Necessary and sufficient knowledge eo ipso obtaining the communicated telos.
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References
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Front Immunol. 2019; 10: 1309.
Infect Immun. 2013 Dec; 81(12): 4478–4489.
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Dr Guerra's Immunology lectures
Am J Gastroenterol. 2004 Nov;99(11):2147-9.
Front Immunol. 2019 Jun 7;10:1309
Nat Rev Gastroenterol Hepatol. 2019 Dec 9
Immunity Volume 55 Issue 8 Pages 1370-1385.e8 (August 2022) DOI: 10.1016/j.immuni.2022.06.007
References
Dr. Guerra's lecture notes
Immunity 2022. Volume 55 Issue 8 Pages 1370-1385.e8.
References
Dr Guerra's membrane immune synapse lectures
Al-Aghbar, M.A., Jainarayanan, A.K., Dustin, M.L. et al. The interplay between membrane topology and mechanical forces in regulating T cell receptor activity. CommunBiol 5, 40 (2022). https://doi.org/10.1038/s42003-021-02995-1
Dinkel BA, Kremer KN, Rollins MR, Medlyn MJ, Hedin KE. GRK2 mediates TCR-induced transactivation of CXCR4 and TCR-CXCR4 complex formation that drives PI3Kγ/PREX1 signaling and T cell cytokine secretion.
J Biol Chem. 2018 Sep 7;293(36):14022-14039. doi: 10.1074/jbc.RA118.003097. Epub 2018 Jul 17. PMID: 30018141;
Al-Aghbar, M.A., Jainarayanan, A.K., Dustin, M.L. et al. The interplay between membrane topology and mechanical forces in regulating T cell receptor activity. CommunBiol 5, 40 (2022). https://doi.org/10.1038/s42003-021-02995-1
Dr Guerra Membrane lipid lectures
References
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Seminars in Immunology Volume 13, Issue 2, April 2001, Pages 129-138
References
Dr Guerra's membrane lipid lectures
Neuron 2015. Volume 85, Issue 4.Pages 695–702
Referewnce
Guerra basics lecture
References
Dr Guerra membrane lectures
Cell Metab. 2020 Dec 1;32(6):981-995.e7
PNAS 2011.108 (29) 11860-11865
J. Dev. Biol. 2020, 8(2), 10.
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Dr Guerra Tumor lectures
Nature Reviews Endocrinology 2020.volume 16, pages224–233
J Neurochem. 2006 Nov;99(4):1237-50. doi: 10.1111/j.1471-4159
References
Dr Guerra's membrane sterol lecture notes
Cells. 2019 Apr; 8(4): 293.
References
Dr Guerra's Lecture notes
References
Dr Guerra's lipid and membranes lectures
Biochimica et BiophysicaActa (BBA) - Molecular and Cell Biology of Lipids.2014.Volume 1841, Issue 9, Pages 1241-1246
Onco Targets Ther. 2017;10:5491-5524
References
Dr Guerra's lecture notes
Biochimica et BiophysicaActa (BBA) - Molecular and Cell Biology of Lipids.2014. Volume 1841, Issue 9, Pages 1241-1246
References
Dr Guerra's membrane lecture notes
Biochimica et BiophysicaActa (BBA) - Molecular and Cell Biology of Lipids.2014. Volume 1841, Issue 9, September Pages 1241-1246
BioEssays, Volume: 40, Issue: 5, First published: 30 March 2018, DOI: (10.1002/bies.201800007)
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Redox Biology 2021.Volume 47, November. 102165
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Redox Biology 2021 Volume 47, November. 102165
Front. Immunol., 26 August 2020
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Mechanisms of Ageing and Development 2016. 156: 25-33
The Journal of Biological Chemistry 2018. 293: 2422-2437
https://youtu.be/GIdDBdEywzk
References
Dr Guerra's neuroscience lectures
References
Dr Guerra's membrane biochemistry/electrophyiology lectures
References
Dr Guerra's lecture marginalia
References
Dr Guerra's Immunology Lecture notes
Redox Biol. 2020 Apr; 31: 101482.
Mechanisms of Ageing and Development.2006. Volume 127, Issue 9: 705-718
References
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References
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References
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Dr. Guerra Neuroscience lecture notes
References
Trends Pharmacol Sci. 2013 Aug; 34(8): 437–444.
Dr Guerra's Neuroscience lecture notes
References
Dr Guerra's notes
Curr Neuropharmacol. 2013 Mar; 11(2): 141–159
Advances in Neurobiology, 01 Jan 2014, 11:13-30
References
Genes Immun. 2020 May; 21(3): 150–168
BMC Rheumatology 2020. volume 4, Article number: 4
Nature Immunology.2002. August. volume 3 no 8
Cell Tissue Res. 2019 Jan; 375(1): 143–172.
References
Cell Tissue Res. 2019 Jan; 375(1): 143–172.
Int. J. Mol. Sci. 2021, 22(21), 11465
References
Dr Guerra's notes
Curr Neuropharmacol. 2013 Mar; 11(2): 141–159
References
Dr Guerra's neuroscience lectures
Neurosci BiobehavRev. 2019 Aug; 103: 50–59
References
Dr Guerra's Neuroscience lecture notes
References
Dr Guerra's lipid lectures
Int J Mol Sci. 2019 Oct; 20(19): 4860
JNCVolume109, Issue3May 2009 Pages 694-705
References
Dr Guerra's lecture notes
J.of Neuroinflammation. 2016. volume 13, Article number: 264
Am J Med. 2020 Jun;133(6):713-722.e7.
J Hepatol. 2014 Aug;61(2):396-407.
References
Dr. Guerra's: membrane lectures
J Clin Med. 2021 Sep; 10(17): 3795
J Neuroinflammation. 2016; 13: 264.
References
Dr Guerra's lipid lecture archive
References
Dr. Guerra's notes
Ennead V-Plotinus
Critique of pure Reason-Kant
Biophysical Journal.2009. 96(7):2676-88).
References
Dr. Guerra's notes
Front. Immunol., 26 August 2020
Int. J. Mol. Sci. 2021, 22, 1487
References
Dr Guerra's notes
Oncotarget. 2016 Jan 26; 7(4): 4195–4209
FEBS J. 2017 Jun; 284(11): 1590–1605
Biochim Biophys Acta Mol Basis Dis. 2021 Oct 1;1867(10):166184.
Biol. Cell (2007)99, 129–140
References
The first reference is my preceding video podcast lecture Membrane Biochemistry XXI published on youtube
*https://youtu.be/ZEEYOganuCU
Dr Guerra's notes
J Immunol August 1, 2017, 199 (3) 874-884
Ann Rev Cell Devel.Biology 2018. 34:111-136
Blood . 2016 Apr 14;127():1930-9
References
Archivum Immunologiae et Therapiae Experimentalis 2013 Apr;61(2):119-25.
Journal of Neuroscience 23 October 2019, 39 (43) 8576-8583
Annual Review of Cell and Developmental Biology 2018 Volume 34, pp 111-136
References
Dr Guerra's lipids lectures
Nature 2008. volume 455, pages40–41.
Nature Immunology 2013. volume 14, pages893–900
European Heart Journal 2021. Vol 12 Dec.
References
Dr Guerra's lipid lecture notes
European Medicines Agency•20/05/2022
Pharmaceuticals (Basel). 2022 Feb; 15(2): 192
NeuropharmacologyVolume 128, January 2018, Pages 54-62
References
Dr Guerra's notes
Biomedicines. 2021 Dec; 9(12): 1908
RNA. 2020 Aug; 26(8): 903–909
Journal of Alzheimer's Disease, 1 Jan. 2019 : 743 – 750.
References
Dr. Guerra's notes
Biochem Biophys Res Commun. 2007 Aug 31;360(3):593-9
Cell Death Dis. 2021 Feb; 12(2): 180.
References
Pharmacology & Therapeutics Available online 27 June 2022, paper # 108237
Cell Death Dis. 2021 Feb; 12(2): 180.
Dr Guerra's notes
References
Dr Guerra's notes
Oncogene. 2009 Sep 3;28(35):3097-110
Mol Cell Biol. 2005 Aug;25(15):6363-79
J Neuroinflammation. 2019; 16: 236.
References
Dr. Guerra's notes
The Journal of Nutrition, Volume 137, Issue 3, March 2007, Pages 548–553
References
Dr. Guerra's notes
The Journal of Nutrition, Volume 137, Issue 3, March 2007, Pages 548–553
Front Immunol. 2019; 10: 1309.
Int J Mol Sci. 2019 Oct 11;20(20):5028
References
Front Immunol. 2019; 10: 1309.
Int J Mol Sci. 2019 Oct 11;20(20):5028.
References
Dr Guerra's ideas
References
Dr Guerra's notes
Int J Mol Sci. 2019 Oct 11;20(20):5028
References
Dr Guerra's lectures
PNAS September 28, 2010 107 (39) 16783-16787;
References
Sci Signal. 2016 Aug 23; 9(442): ra83.
Dr Guerra's Neuroscience lectures
References
Dr Guerra lecture notes
Nature Communications volume 11, Article number: 6133 (2020)
Current Biology Volume 31, Issue 11, 7 June 2021, Pages 2274-2285.e5
Eur J Neurosci. 2019 Jan;49(1):40-50
References
Dr Guerra's notes,concepts and ideas
Sci Signal. 2016 Aug 23; 9(442): ra83.
References
Dr Guerra's notes
Sci Signal. 2016 Aug 23; 9(442): ra83
Front. Pharmacol., 24 April 2019
References
Dr Guerra's notes
Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:436
JAMA. 2008;299(11):1345-1350
References
Dr Guerra's synthesis of lecture material
Histochemistry and Cell Biology volume 145, pages275–286 (2016)
Biol Rev Camb PhilosSoc.. 2018 May;93(2):827-844.
References
Dr Guerra's synthesis of lectures
Scientific Reports volume 5, Article number: 15292 (2015)
References
Dr Guerra's lecture sytheses
Scientific Reports volume 5, Article number: 15292 (2015)
References
Dr Guerra's synthesis of the relevant literature
BioEssays, Volume: 39, Issue: 5, First published: 20 February 2017.
Front Cardiovasc Med. 2020; 7: 2.
References
Dr. Guerra's synthesis of the epitranscriptome lecture notes
Sci Signal. 2017 Jan 31; 10(464): eaaf7478.
References
Sci Signal. 2017 Jan 31; 10(464): eaaf7478
Prostaglandins Leukot Essent Fatty Acids. 2015 Jul;98:49-55
Nat Commun. 2020; 11: 4664.
Int J Biol Sci. 2015; 11(11): 1272–1280
References
Dr Guerra's lecture notations and synthesis
Cell. 2014 Dec 18; 159(7): 1615–1625
Nat Commun. 2020; 11: 102.
References
Dr Guerra's lecture notes
Nat Commun. 2020; 11: 102.
Cold Spring Harb Perspect Biol. 2013 Sep; 5(9): a017947.
References
Dr Guerra's letures/reasoning
SCIENCE ADVANCES • 22 May 2019 • Vol 5, Issue 5
Cell MetabolismVolume 22, Issue 2, 4 August 2015, Pages 304-311
Cell Chem Biol. 2020 May 21; 27(5): 538–550.e7.
References
Dr Guerra's Lecture notes
Cell Chem Biol. 2020 May 21; 27(5): 538–550.e7
Circulation. 2020 Dec 15;142(24):2356-2370
References
Dr Guerra's notes
Circulation. 2020 Dec 15;142(24):2356-2370
Cancer Science June 2014. 105(9)
References
Dr. Guerra's notes
Cancer Res. 2011 May 1; 71(9): 3400–3409
Front. Neurosci., 17 May 2017
References
Dr Guerra's pathbiochemistry lecture notes
Cancer Res. 2011 May 1; 71(9): 3400–3409
References
Radiol Oncol. 2021 Dec; 55(4): 379–392
References
Guerra lecture notes/ideas
Genes (Basel). 2014 Dec; 5(4): 865–886.
Molecular Therapy—Nucleic Acids (2015) 4, e252
Int. J. Mol. Sci. 2016, 17(5), 719
References
J of Computational Chemistry 2011 Volume32, Issue10: Pages 2077-2083
Dr Guerra organic chemistry notes and concepts
Review mini lecture
References
Dr Guerra's ideas and concepts
Cells. 2021 Jun; 10(6): 1355.
Cells. 2019 Mar; 8(3): 227.
References
Introductory remarks from Guerra's research
Trends in Cell Biology, 2017-06-01, Volume 27, Issue 6, Pages 453-463.
Dr Guerra takes this episode to redouble the committment of Authentic Biochemistry to providea detailed analysis and synthesis of current biomedical research science based on peer-reviewed published literature. Please become a regular subscriber!
Grazie!
References
Dr. Guerra lipid lectures
Journal of Diabetes Research, 2016, Article ID 2372741, 12 pages
Lipids in Health and Disease 2013.12(1):98
Cell Reports 2022. 38, 110566
References
Dr. Guerra Lipid and Intermediary Metabolism lectures
Cell Reports 2022. 38, 110566
PNAS July 24, 2017 | 114 (32) 8649-8654
References
Dr. Guerra's lipid lecture archives
PNAS July 24, 2017 | 114 (32) 8649-8654
Int J Mol Sci. 2019 Oct; 20(19): 4924
References
Dr. Guerra's notes
References
Dr Guerra lipid lecture notes
Biophysical J. Volume 110, Issue 11, 7 June 2016, Pages 2397-2406
Am J Pathol. 2020 Sep; 190(9): 1782–1788
References
Dr. Guerra lecture material
Nutr J. 2014; 13: 17.
References
Dr. Guerra lecture notes
Prog Neurobiol. 2018 Apr-May; 163-164: 27–58.
Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:28–40
References
Dr. Guerra's Lecture Notes
Journal of the American College of Nutrition. 2019. 38:8, 693-702.
Curr Diabetes Rev. 2020;16(8):797-806
References
Dr. Guerra's lectures
Curr Med Chem. 2017;24(17):1827-1852
Cancer Res. 2018 Apr 1; 78(7): 1713–1725
References
Dr. Guerra's lipid lecture notes
Cancer Res. 2018 Apr 1; 78(7): 1713–1725.
Progress in Lipid Research Volume 74, April 2019, Pages 145-159
References
Dr Guerra's notes
Front. Physiol., 30 January 2019 | https://doi.org/10.3389/fphys.2019.00042
References
Dr. Guerra's lecture notes
Front. Physiol., 30 January 2019 | https://doi.org/10.3389/fphys.2019.00042
Cold Spring Harb PerspectBiol. 2018 Feb; 10(2): a028415.
References
Dr Guerra's lectures notes
Cancer Res. 2018 Apr 1; 78(7): 1713–1725
Cold Spring Harb PerspectBiol. 2018 Feb; 10(2): a028415.
References
Dr Guerra's lecture notes
Diabetologia. 2021 Jan; 64(1): 168–180
Diabetologia. 2020 Dec;63(12):2654-2664
References
Dr. Guerra lecture notes
J AM Coll Cardiology Basic Trans Science.2019. (4) 3: 385-400
References
Dr. Guerra lecture notes
Circulation Research Volume 128, Issue 10, 14 May 2021; Pages 1419-1420
Adv Exp Med Biol . 2017;960:135-160.
Current Opinion in Clinical Nutrition and Metabolic Care Issue: Volume 21(4), July 2018, p 260-266
References
Dr. Guerra's lecture notes
J Immunol. 2018 Nov 15;201(10):2934-2946
Endocr Rev. 2020 Aug; 41(4): 594–609.
References
Dr Guerra lecture notes
Endocr Rev. 2020 Aug; 41(4): 594–609
Alzheimer’s & Dementia: Translational Research & Clinical Interventions (TRCI) 2021 Volume7, Issue1 e12217
References
Dr Guerra's Lecture notes
Alzheimer’s & Dementia: Translational Research & Clinical Interventions (TRCI) Volume7, Issue1 2021 e12217
References
Dr Guerra Lecture archives
Alzheimer’s & Dementia: Translational Research & Clinical Interventions (TRCI) 2021.Volume7, Issue1 e12217
EBioMedicine. 2015 Dec; 2(12): 1888–1904
References
Dr. Guerra's lecture notes
Curr Med Chem. 2017;24(17):1827-1852
Journal of Hepatology 2012 56, 704-713DOI: (10.1016/j.jhep.2011.09.020)
Reference
George A, Stead T S, Ganti L (August 26, 2020) What’s the Risk: Differentiating Risk Ratios, Odds Ratios, and Hazard Ratios?. Cureus12(8): e10047. doi:10.7759/cureus.10047.
References
Dr Guerra's lecture material
From Dr. Guerra's lecture archives
References
Dr Guerra's lecture notes
World J Gastroenterol. 2013 Nov 14; 19(42): 7258–7266.
Int J Endocrinol. 2015; 2015: 595649.
PLoS One. 2017; 12(10): e0186643.
BMC Cancer. 2019; 19: 185
References
Dr. Guerra lecture notes
BMC Cancer. 2019; 19: 185.
References
Journal of Biological Chemistry.2013. 288 Issue 52 Pages 37355-37364.
Prostaglandins & Other Lipid Mediators. 2022(April) . Volume 159, 106621
References
Dr. Guerra's lecture notes
Prostaglandins & Other Lipid Mediators 2022.April. 159. 106621
Reviews in Endocrine and Metabolic Disorders. 2020. 21: 631–643
References
Dr. Guerra lecture notes
Reviews in Endocrine and Metabolic Disorders. 2020. 21: 631–643.
J Lipid Res. 2015 Mar; 56(3): 588–598.
References
Dr. Guerra's notes-unpublished
Cancer Res. 2019 Oct 15; 79(20): 5355–5366.
References
Redox Biol. 2021 Jan; 38: 101807
Cancer Res. 2019 Oct 15; 79(20): 5355–5366.
References
Dr Guerra Lecture notes
Chem Biol Interact. 2019 Dec 12; 316: 108917
Chapter 7. Cook and McMaster. 2002. in Biochemistry of lipids, lipoproteins and membranes 4th edition. Elsevier Science. Vance and Vance eds.
References
Chem Biol Interact. 2019 Dec 12; 316: 108917
J Neuroinflammation. 2019; 16: 236.
References
Circulation Research 2020.Volume: 128, Issue: 2, Pages: 232-245, DOI: (10.1161/CIRCRESAHA.120.317933)
J Neuroinflammation. 2019; 16: 236.
References
Adv Exp Med Biol . 2017;960:135-160.
Lipids in Health and Disease volume 19, Article number: 113 (2020)
Circulation Research. 2020.Volume: 128, Issue: 2, Pages: 232-245
References
Dr. Guerra's lecture notes
Infect Immun. 2013 Dec; 81(12): 4478–4489
Am J Gastroenterol. 2004 Nov;99(11):2147-9
Front Immunol. 2019 Jun 7;10:1309
Nat Rev Gastroenterol Hepatol. 2019 Dec 9.
References
Dr. Guerra's lecture notes
Int J Mol Sci. 2021 Jan; 22(1): 330
References
Dr. Guerra's lecture notes
Int J Mol Sci. 2021 Jan; 22(1): 330.
References
Dr. Guerra's lecture notes
References
Dr. Guerra's lecture notes
Mol Genet Metab Rep. 2021 Mar; 26: 100709.
References
Dr. Guerra's lecture notes
From Dr. Guerra's lecture notes
References
Dr. Guerra lecture notes
Malonyl CoA controls the categorical/biochemical logic of hepatic glucose and lipid homeostasis via metabolic inhibition of metabolic antimony.
References
Dr Dan Guerra Biochemistry Lecture Notes. 2010-2021
Vance and Vance Biochemistry of Lipids, Lipoproteins and Membranes 4th ed. 2002. Elsevier Publisher.
Basic reductive biosynthesis as an exemplar for this first lecture in anabolism.
References
J Biol Chem. 2016 Feb. 291(7): 3658–3667
J Biol Chem 2013 Dec. 288 (52): 37355-37364
Biophys J. 2005 Feb;88(2):1091-103
Infect Immun. 2018 Jul; 86(7): e00035-18
References
Infect Immun. 2018 Jul; 86(7): e00035-18
J Biol Chem. 2019 Jun 7;294(23):9213-9224
Egyptian Journal of Basic and Applied Sciences. 2018. (5) 4 : 237-244
Arteriosclerosis, Thrombosis, and Vascular Biology. 2019. (39) 3: 432-445
References
Oral Microbiol Immunol. 2006 April 21 (2):84-92 1647-6017
Infect Immun. 2018 Jul; 86(7): e00035-18
References
J Dent Res. 2019 Nov;98(12):1315-1323
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 1996.Vol. 335, No. 1, November 1, pp. 102–108,.
Nature Reviews Microbiology. 2003. volume 1, pages219–230
Front. Microbiol. 2021. 14 July
References
Infect Immun. 2013 Dec; 81(12): 4478–4489
Journal of Molecular Evolution 2020. 88:26–40
PLoS One. 2016; 11(11): e0166656
References
International Journal of Pharmacy and Pharmaceutical Sciences 2015 7(9):20-29
PLoS One. 2016; 11(11): e0166656.
PLoS Pathog. 2019 Nov15;15(11):e1007687
Clin Microbiol Rev. 2006 Oct;19(4):728-62
Expert Rev Vaccines. 2009 Apr;8(4):447-54
Front. Microbiol., 14 July 2021
References
Front. Microbiol., 14 July 2021
PLoS One. 2016; 11(11): e0166656.
The Lancet Microbe 2021; 2(7) Pages e291-e299
Reference
Front. Microbiol., 14 July 2021
PLoS One. 2015 Jan 21;10(1):e0116919.
Neurochem Res. 2015 Jan;40(1):59-69
Physiology. 2009. Volume 24 Issue 6: 367-376
The human neuroendocrine system is directly regulated and in communication with the autonomic nervous system via cortical and diencephalonomic CNS nuclei. These converging networks coordinate satiety, glycemia, bioenergetics, oxygen transport, dietary input, digestion and muscular activity in direct association with pancreatic insulin/glucagon ratio dynamics.
References
Molecular Neurobiology volume 56, pages769–796 (2019)
Molecular Neurobiology volume 56, pages7950–7965 (2019)
Introduction to motor neuron structure/function relationships and the MND's including Amyotrophic Lateral Sclerosis.
The CNS processes nutritional (biochemical) signaling from the external and internal environment during and subsequent to dietary ingestion. During the initiation phase, affective (limbic) and executive (PFC/OFC) attention is facilitative toward ingestive behavior linked to appetitive hunger stimulation via neural, visceral, and endocrine networking including memory cues that obtain opportunity to consume pleasurable high caloric density nutrition.
Gastroenterology. 2017 May; 152(7): 1728–1738
Int J Obes (Lond). 2018 Mar;42(3):376-38
Trends Endocrinol Metab. 2019 Mar;30(3):163-176
https://www.genecards.org/cgi-bin/carddisp.pl?gene=TUB
Pharmacokinetics are discussed.
Dopaminenergic pathways are corrupted by addictive behaviors especially the use/abuse of psychoactive drugs that may become behavioral reward saliencies linked to epigenomic modifications.
References
Front Neurosci. 2019; 13: 707
Nature Metabolism 2019. 1:754–764
Int. J. Mol. Sci. 2019, 20(6), 1505
Neuropsychiatr Dis Treat. 2015; 11: 875–888
Mol Psychiatry. 2016 Oct; 21(10): 1358–1365.
References
Biol Psychiatry. 2020 Jan 1; 87(1): 64–73
Front. Neurosci., 26 November 2019
J Neuroinflammation. 2019; 16: 34
Nature Cell Biology, 02 Sep 2011, 13(9):1016-1023
Critical Reviews in Clinical Laboratory Sciences Volume 56, 2019 - Issue 7 Pages 472-492
References
Nat Cell Biol. 2019 Mar; 21(3): 397–407
CELL Volume 126, Issue 3, 11 August 2006, Pages 503-514
Prostaglandins Leukot Essent Fatty Acids. 2015 Jul;98:49-55
Int J Biol Sci. 2015; 11(11): 1272–1280
Sci Signal. 2017 Jan 31; 10(464): eaaf7478.
Front Immunol. 2019; 10: 345.
J Neuroinflammation. 2019; 16: 34.
Cell Metabolism 2020 31472-492
Amino Acids. 2012 Oct;43(4):1803-7
Molecular Cell Volume 81, Issue 18, 16 September 2021, Pages 3677-3690
References
HORMONES 2013, 12(2):172-191
Proc Natl Acad Sci U S A . 2002 Dec 24;99(26):17155-60
Eur J Endocrinol. 2017 176(5): R235–R246.
Eur J Endocrinol. 2017 176(5): R235–R246
Molecular Cell Volume 81, Issue 18, 16 September 2021, Pages 3677-3690
An introductory lecture on the biomolecular sensor kinase, Adenosyl Mono-Phosphate (protein) Kinase; AMPK.
References
Mol Genet Metab. 2013 Jul;109(3):260-8
PLoS One. 2016 Aug 16;11(8):e0161252.
Experimental & Molecular Medicine volume 48, 224 (2016)
Molecular Cell Volume 81, Issue 18, 16 September 2021, Pages 3677-3690
References
Cell Metabolism. 2016. 23, 1127–1139
Cells 2020, 9(1), 228
Front. Immunol., 31 May 2019
Int J Mol Sci. 2020 Nov; 21(22): 8609
Circ Res. 2018 Sep 14; 123(7): 868–885.
Int J Mol Sci. 2019 Mar; 20(5): 1223
References
Nat Cell Biol. 2019 Mar; 21(3): 397–407
J Diabetes Metab Disord. 2020 Jul 21;19(2):1797-1825
Int. J. Mol. Sci. 2014, 15, 16848-16884
Besides 2-methoxy-17beta-estradiol, cell cycle arrest via chromatin deacetylation can mitigate cell proliferation by decreasing global transcription while promoting the expression of tumor suppressor genes like p16INK4a while DNA Damage Repair (DDR) from pro-inflammatory cytokine production from senescent cells and Th1 lymphocytes can inhibit commitment to mitosis and cytokinesis by generating the paracrine SASP paradigm.
Refs.
Am J Physiol Cell Physiol 2012;302:C1026-C1034
Steroids Volume 75, Issue 10, October 2010, Pages 625-631
Oncotarget. 2013 Oct; 4(10): 1552–1553
Cancer Metastasis Rev. 2020; 39(3): 681–709
Cell fate from Either ageing associated senescence to programmed cell death OR cell proliferation is finely tuned to the splice variant expression of Cell Cycle dependent kinase inhibitors and the relative production of pro-inflammatory cytokines under the synchrony of DNA Damage Repair (DDR), telomerase expression decline, and the protective role of the Senescence Associated Secretory Phenotype (SASP).
Dr. Daniel J. Guerra. 06 Dec 2021 Authentic Biochemistry Productions
References:
Oncotarget. 2013 Oct; 4(10): 1552–1553
Cancer Rep Rev. 2018 Mar; 2(2): 10
Nat Med. 2017 Jun; 23(6): 775–781
Cancer Genet Cytogenet. 1999 Mar;109(2):108-13.
EBioMedicine 2016 830-39DOI: (10.1016/j.ebiom.2016.04.017
Age Ageing, Volume 48, Issue 6, November 2019, Pages 776–782
Biomedicines. 2020 Aug 6;8(8):277
Dr. Guerra authentically arrives at the inveighing cancer paradigm contribution to the sickness unto death.
Nutrients. 2020 Mar; 12(3): 622.
Biochemistry and Cell Biology of Ageing: Part II Clinical Science. 2019. pp 21-43.The Immune System and Its Dysregulation with Aging
Ludmila Müller, Svetlana Di Benedetto, and Graham Pawelec. Springer Publishers
1.Biochemistry and Cell Biology of Ageing: Part II Clinical Science. 2019. pp 21-43. The Immune System and Its Dysregulation with Aging. Ludmila Müller, Svetlana Di Benedetto, and Graham Pawelec. Springer Publishers.
2. Aging (Albany NY). 2019 Apr 30; 11(8): 2343–2351.
3. Immun Ageing. 2020; 17: 2
References
Front. Immunol., 29 June 2012
J Immunol 2016;197:3762-3770
Front. Immunol., 03 February 2020
The Src-family kinase Lck regulates T-cell development, activation, proliferation, and immune synapse dynamics. These are the initiation phases of TCR signaling. Upon antigen presentation via the APC- TCR immune synapse, Lck phosphorylates tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAMs) of the TCR-associated CD3 membrane protein domains.
Phosphorylated ITAMs function as a molecular platform for tandem SH2 domains located on the tyrosine kinase Zap-70, initially activated by Lck.
Lck kinase activity is regulated at two canonical phosphorylation sites Tyr394 and Tyr505, wherein auto-transphosphorylation of Tyr394 in the kinase domain erupts a relaxed/active conformation but phosphorylation of Tyr505, located at the C-terminus, by the tyrosine kinase Csk results in an inactive enzyme.
References
Longev Healthspan. 2012; 1: 6
SCIENCE ADVANCES•19 Jun 2019•Vol 5, Issue 6
Dr Guerra carries out the synthesis of multiple pathobiochemical events into an architechtonic of the aging human co-morbidity resulting in a sickness unto death.
Authentic Biochemistry Production
22 October 2021
References
Cardiovasc Diabetol. 2020; 19: 33.
Cytometry A. 2006 Mar;69(3):189-91
Nat Rev Dis Primers. 2019 Mar 7;5(1):16
J Lipid Res. 2007 Jan;48(1):19-29. doi: 10.1194
Mech Ageing Dev. 2001 Sep 15;122(13):1413-30
That there are senescence-associated decreases in the JAK-STAT signaling transduction cascade has been observed in human lymphocyte lineages. This phenomena, as associated with a decreased JAK- tyrosine phosphorylation of STAT5, is linked to plasma membrane cholesterol content. Therefore, plasma membrane cholesterol content is involved in T cells modulation and proliferation.
Acid sphingomyelinase- mediated ceramide lipid raft mobilization and aggregation of membrane receptors plays a crucial role in this pathobiochemical dynamic leading to multiple disease and comorbidity states in the elderly.
Classical Papers Examined:
Mech Ageing Dev. 2001 Sep 15;122(13):1413-30
Cytometry A. 2006 Mar;69(3):189-91
J Lipid Res. 2007 Jan;48(1):19-29. doi: 10.1194
Chromatin instability leads to alterations in gene expression that re-directs cellular senescence by corruption of chemokine and cytokine signalling resulting in epithelial to mesenchymal transitions and the potential for metastatic cancer in the elderly .
As lymphocyte lineage's age these underlying pathobiochemical events are potentiated by hypo and hyper immune responses thus generating a downward reductio to misdirected hyperinflammatory states and the potential for autoimmune disease sequalae.
Front Cell Dev Biol. 2019; 7: 226
Advances in Immunology. 2011 v.109.Pp125
Cell Reports 10, 2043–2054, March 31, 2015
Experimental & Molecular Medicine volume 51, pages1–15 (2019)
Dr. Guerra details the aging immune phenotype at the transcriptional and metabolic level.
References
Immun Ageing. 2020; 17: 2.
Experimental & Molecular Medicine volume 51, Article number: 80 (2019)
Nat Immunol. 2011 Nov 6; 12(12): 10
Cell 146, 772–784, September 2, 2011
Nat Immunol. 2014 Aug; 15(8): 767–776.
Cell Reports Volume 17, Issue 11, 13 December 2016, Pages 2827-2836
ILC3 can contribute to the progression and aggravation of IBD's while both IL-22 and IL-17, along with IFN-γ, are overexpressed by the dysregulation of NCR− ILC3 or NCR+ ILC3 function
NCR (natural cytotoxicity receptors), are type 1 transmembrane proteins of the immunoglobulin superfamily. Upon stimulation, NCR's mediate NK killing and release of IFNγ. They bind viral ligands such as hemagglutinins, neuraminidases, bacterial ligands, and cellular ligands related with auto immune diseases, tumour growth, and associated aging morbidity.
References
Experimental & Molecular Medicine volume 51, Article number: 80 (2019)
Cell Death & Disease volume 10, Article number: 315 (2019)
Front. Immunol., 28 September 2015
Omega-Three VLCPUFA's as asymmetrically distributed in membrane glycerolphospholipids mediate vesiculation and permeability of endothelia to circulating lymphocytes and leukocytes thus coupling folic acid, Vitamin B12 and epigenetic modification of chromatin to ultimately link bioenergetics with cytotoxicity and inflammation. This regulated system involves the neuroimmunoepigenome and the senescent environment of aging human vasculature, skeletal and cardiac muscle, and the CNS toward pathobiochemical increases in morbidity -presenting disease phenotypes.
References
J Biomed Biotechnol. 2011; 2011: 298348.
Blood 2009 114:2567-2568; https://doi.org/10.1182/blood-2009-07-230904
Am J Clin Nutr. 2017 Oct;106(4):1157-1165. doi: 10.3945/ajcn.117.155648.
BIOCHEMISTRY AND CHEMICAL BIOLOGY STRUCTURAL BIOLOGY AND MOLECULAR BIOPHYSICS
March 2018 https://elifesciences.org/articles/34394
Sci Signal. 2017 Jan 31; 10(464): eaaf7478.
Prostaglandins Leukot Essent Fatty Acids. 2015 Jul;98:49-55. doi: 10.1016/j.plefa.2015.04.007.
Int J Biol Sci. 2015; 11(11): 1272–1280
Pro-inflammatory gene transcription is tanked when demethylation is inhibited but cytotoxicity of virally infected or cancer cells by NK’s (where demethylation is inhibited) remains intact.
References
J. Biol. Chem. 2018;293:2422-2437
J. of Biol. Chem. 2016. 291, 23756-23768
Dr. Guerra discusses some of the complexity of both the epigenetic mechanisms and cellular responses associated with immunomodulatory failure in the aging human.
References
Anal Cell Pathol (Amst). 2018; 2018: 787.1814.
Daniel J. Guerra. 2018. DOI: 10.5772/intechopen.82176 https://www.intechopen.com/chapters/64596
Dr. Guerra continues a dialectical accounting of the biochemical and cellular events leading to the terminal outcome of aging.
Topic today is the reintroduction of Natural Killer Cells and the epigenetic mechanisms that orchestrate unique gene expression.
References
Anal Cell Pathol (Amst). 2018; 2018: 787.1814.
The Journal of Biological Chemistry2018. 293: 2422-2437
Oxidases, dehydrogenases and oxygenases in the electron transport chain et al.
This is the link to my new (second in the series) of synoptic Human Aging YouTube lectures.
https://youtu.be/IckyMGw8Ffs
Please subscribe to both my podcast and YouTube channels!
And please contribute!
It is the First day of Autumn. Enjoy!
Interferons are innate immune agents of inflammation and recovery. Mutations or epigenetic modifications associated with advanced aging may corrupt interferon pathway fidelity involving mitophagy leading to autoimmune disease and morbidity later in life.
References
Nat Immunol. 2021 Mar; 22(3): 312–321
J Neuroinflammation. 2019; 16: 236.
A general audio lecture involving a molecular interactome mediating the innate immune response and the control over T and B lymphocyte memory cells resulting in long term potentiation of autoimmune disease during aging.
I discuss the complex but potent interactions of TLR signaling with plasma membrane protein complexes including semaphorin cytoplasmic kinase interactions leading to PPAR gamma transcription that fires off CD36 and beta oxidation gene transcription to switch M1 to M2 macrophage polarity thus feedback regulating the pro-inflammatory glycolytic mToRC system dynamics.
Aging is associated with a corruption in this fine-tuning that presents in the older sedentary human individual as a simple dysregulation of inflammation that ultimately impairs the ability to ward off otherwise relatively innocuous pathogens while simultaneously punctuating the equilibrium otherwise exerted to control tissue repair and the potential for cellular proliferation and oncogenesis.
References
Nat Immunol. 2018 Jun;19(6):561-570.
FEBS Letters 2011 Volume 585, Issue 23, Pages 3829-3835
Scientific Reports 2015 volume 5, Article number: 11789
Ann Allergy Asthma Immunol. 2000 Jul;85(1):9-18
Macrophage polarization and differentiation works in conjunction with CD4+ T lymphocyte differentiation into Th1 and Th2 subclasses and both NK and B cell activities. The aging human loses feedback control over the pro-inflammatory and anti-inflammatory pathways from these classical cellular differentiations contributing to hyperinflammation and/or hypoinflammatory responses ultimately resulting in pathological cell degeneration or proliferation, morbidity and death. Dr. Daniel J. Guerra Authentic Biochemistry Production. 18.9.21.
Reference
Nature Immunology June 2018 19: 561–570
https://youtu.be/4sW-BNVhzrs
Dr. Guerra introduces a primer on membrane biochemistry in preparation for a florid analysis of autophagy and the various forms of programmed cell death linked to the aging human.
References
Cell Discovery volume 7, Article number: 4 (2021)
Non coding RNA may regulate melanogenesis and in combination with plasma cell producing IgG the nutritional regulation of satiety.
Aging results in alterations of this complex system thus resulting in localized melanogenesis and a corruption of the HPA axis.
References:
Aging (Albany NY). 2021 Jan 31; 13(2): 2700–2726.
Stem Cells Int. 2020; 2020: 1047896. First Published online 2020 Jul 8
PNAS. 2002 Dec 24;99(26):17155-60
Components of metabolic sequence toward gluconeogenesis in the human liver.
Dr. Guerra details the glucagon and epinephrine mediated control through Stimulatory G-protein couple adenylate cyclase activating PKA over Hepatic Glycolysis and Gluconeogenesis.
Utilization of a protein cysteine SH derived thioester intermediate alters the free energy hurdle for the synthesis of 1,3 bis PGA thus allowing for glycolytic ATP and NADH synthesis.
The interaction of glycolysis and lactic acid transport from skeletal muscle to the liver plays a significant role in oxygen uptake, transport and release in association with pulmonary carbon dioxide efflux . Dr. Daniel J. Guerra. An Authentic Biochemistry Production 19.8.21.
Any chronic decrease in the ability for molecular oxygen to bind to circulating Hb will diminish its availability in the Central Nervous System and Skeletal Muscle resulting in the potential for long-term Pathophysiology and Illness. Dr. Dan Guerra Published 11 August 2021. Authentic Biochemistry.
Classical Amino Acid Degradation Biochemistry : Emphasis on pathway interconversions and production of bioactive amines
J Physiol. 2005 563:285-90
Eur J Appl Physiol(2011) 111:2837–2843
Biomedicines. 2020 Aug 6;8(8):277.
Journal of Neurochemistry, Volume: 146, Issue: 4, Pages: 416-428, First published: 20 May 2018, DOI: (10.1111/jnc.14464
Journal of Neurochemistry, Volume: 146, Issue: 4, Pages: 416-428, First published: 20 May 2018, DOI: (10.1111/jnc.14464)
Life Sci . 2019 Sep 1;232:116612
This is one of my classical biochemistry introductory lectures on amino acid utilization.
Trends in Immunology Volume 36, Issue 4, 2015, 217–228
Carcinogenesis 2015;36:1180-1192
Clinical and Molecular Allergy volume 15, Article number: 21 (2017)
Front. Immunol., 25 September 2019 | https://doi.org/10.3389/fimmu.2019.02247
Oncotarget. 2013 Oct; 4(10): 1552–1553
In this episode Dr. Guerra provides the overview of Pharmacodynamics .
A.D.M.E.
Anesthesiology Clinics, 2019-09-01, Volume 37, Issue 3, Pages 475-492.
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Risk factors for aging morbidity are linked to large variations in protein synthesis and lack of adipose derived TAG utilization.
The immune response becomes compromised during aging leading to states of hyperinflammation followed by hypo-immune sequalae opening up the potential for opportunistic respiratory infections and alterations in pulmonary endothelial membrane lipid fluidity restricting oxygen intake.
Seminars in Cell & Developmental Biology Volume 40, April 2015, Pages 115-126
Pharmaceutical Research March 2018, 35:49
Journal of Molecular Endocrinology 2017. 58, 1; 10.1530/JME-16-0182
J. Lipid Res. 2018 59:(3) 488-506.
Feng, T., Yang, X., Hao, S. et al. Immunol Res. 05 April 2020
Molecular Neurodegeneration volume 7, Article number: 45 (2012)
J Biol Chem. 2019 Jun 7;294(23):9213-9224
Annu. Rev. Physiol. 2013. 75:685–705
Nutrients. 2020 Mar; 12(3): 622
FASEB J. 2013 Jun; 27(6): 2458–2467.
Scientific Reports volume 7, Article number: 13763 (2017)
Scientific Reports volume 9, Article number: 1220 (2019)
Prog Neuropsychopharmacol Biol Psychiatry. 2005 Oct 12
Bulletin of Experimental Biology and Medicine.2003. 136.(3). 1573-8221
Pharmacological reports 2005, vol. 57, no6, pp. 811-817
Brain Res Bull, December 11, 2006; 71(1-3): 279-86.
Journal of Endotoxin Research, Vol. 4, No. 5, 363-370 (1997)
Scientific Reports volume 7, Article number: 13763 (2017)
Brain Behav Immun. 2019 Oct;81:41-51
Neuroimmunomodulation 2002/2003;10:101-121
Front. Neurol., 23 January 2018
TLRs recognize molecular patterns associated with invasive pathogens. TIR domain-containing adaptors define the specificity of TLR signaling.
TLR interactions from CNS-resident microglia can obtain a pro-inflammatory environment that leads to neuronal degeneration as associated with classical aging related diseases like Parkinson's.
J Neuroinflammation. 2014 Sep 20;11:166
Brain Behav Immun. 2019 Oct;81:41-51
J Mol Neurosci. 2021 Mar 9
Pathogens, and abiotic ischaemic damage manifest a constellation of molecular interactions triggering pattern recognition receptors such as TLR's, with canonical protein binding domains that signal through intracellular cascades such as activating Ca2+ signaling; eo ipso obtaining potent hyperimmune inflammation, providing event ontological foundation and episodic contribution to the aging morbidity in human decline and mortality.
Oncotarget. 2016 Jan 26; 7(4): 4195–4209
Nature Reviews Immunology volume 6, pages644–658(2006)
The removal of damaged neurons and associated synaptic connections with the
simultaneous repair of other neuronal circuits is a mechanism for the sculpting of
the brain network and thus a means by which the highly innervated and connected
prefrontal cortex can receive and respond to neurotransmission from the limbic system.
Reference: Genes (Basel). 2019 Mar; 10(3): 249
Authentic Biochemistry Podcast 27 April 2021
References
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Mol Immunol. 2017Aug;88:125-134
As an hypothetico-deduction, Dr. Guerra proposes that the Recombination Activating Gene-RAG System is a Potential Candidate in Age Associated Morbidity.
In conjunction with a neutral sphingomyelinase and the subsequent synthesis of diacylglycerol thence promoting activation of a PKC-Zeta, T cell receptor translocation and activation are obtained.
Prior RAG mediated recombination events in CNS-resident lymphocytes, associated microglia and neurons can lead to recombination event epigenomic ontologies that either promote or curtail a resident hyperimmune response leading to classical neurodegenerative diseases of the elderly.
References:
J. Biol. Chem. 1998;273:14550-14559
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Front Cell Dev Biol. 2019; 7: 226.
Single-nucleotide polymorphisms and copy-number variations (CNV’s) result from genome wide chromosomal abnormalities including large deletions and duplications where the the immune system appears to play a major role in the accumulation of chromosomal variation.
Aging in humans may be linked to immune-mediated epigenomic epistasis as facilitated by Recombination Activating Gene proteins RAG1 & RAG2 that are canonically linked to V(D)J recombination of the T cell receptor and the B cell immunoglobulins.
Neuroinflammatory mediators play a critical role in the pathophysiology of brain ischemia, exerting either deleterious effects on the progression of tissue damage or beneficial roles during recovery and repair.
These processes occur throughout life and involve the immune system, biochemical pathways, cellular turnover and alteration of gene expression.
Signal transduction cascades allow for genome editing to epigenomic mediation of metabolic event ontologies.
Aging is a process whereby these processes lose specificity and valence, increasingly functioning without appropriate fine control leading to the potential for chronic and more rarely, acute disease states that ultimately result in mortality
An Introduction to the theory of immunoepigenetic tailoring of human instanence.
Dr. Guerra
Authentic Biochemistry Podcast Studios
J Immunol August 1, 2017, 199 (3) 874-884
Ann Rev Cell Dev Biol 2018. 34:111-136
Blood. 2016 Apr 14;127(15):1930-9
J BiolChem. 2017 Aug 25; 292(34): 14292–14307
What is involved to make a sound decision?
Biochemistry is a scientific discipline; one that examines and interprets the foundational structures and functions of living systems.
As with any judgment, as there are reasons for believing, there are also reasons for disbelieving, and the freely willed decision to choose which, should involve the discovery of truths to use as exemplars for seeking coherence and foundation to the premises that necessarily and sufficiently support the better argument for that decision
Listen to my lecture to learn the details of this unfolding discussion that recombines epistemology with metaphysics as re-purposed to find Authentic Biochemistry.
DJGPhD
31 March 2021
Annual Review of Cell and Developmental Biology Vol. 34:111-136
Journal of Neuroscience 23 October 2019, 39 (43) 8576-8583
Archivum Immunologiae et Therapiae Experimentalis 2013 Apr;61(2):119-25.
In this foundational lipid absorption lecture, Dr. Guerra address the roles of apo- lipoproteins, triacylglycerol and cholesteryl esters with membrane associated caveolae transport in adipocytes, endothelia and skeletal muscle. An Authentic Biochemistry Podcast Production. 25 March 2021.
Electron transport and the anapleurotics of intermediary metabolism. Dr. Daniel J. Guerra
Authentic Biochemistry Studios
21.3.21
•Impaired immunological responsiveness is common in the elderly
•The immunological competence of an individual is determined by the presence of mature lymphocytes formed in primary lymphoid organs, and secondary lymphoid tissues such as the liver, lung and GI tract.
•Immunological equilibrium requires steady lymphocyte output, and controlled expansion
•Thymic and lymph-node stromal microenvironments thus represent key elements in the development of the adaptive immune system. Consequently, impairment of the lymphoid microenvironment will ultimately lead to insufficient primary and secondary immune responses or to the decline of thymic selection, manifesting in immune senescence accompanied by late-onset autoimmune disorders, often observed in elderly.
•Self-tolerant cytotoxic and helper T-lymphocytes, the crucial regulator cells in adaptive immune responses, develop in the specialized epithelial network of the thymus. The thymus, however, gradually loses its capacity to support lymphopoiesis in an involution process that results in a decline of de novo T-cell production.
•Cancers of epithelial origin (carcinomas) are the most frequent type of malignancy in humans, with their incidence and aggressiveness increasing with age
•This observation raises the question as to whether the aging process itself contributes to tumor progression
•. In this regard, telomere biology seems to play a pivotal role since shortening of telomeres has been associated with cellular senescence and organismal aging as well as with cancer incidence and mortality .
•
•In the multistep carcinogenesis model, telomere shortening has been observed together with increased chromosome instability (CIN) in early precancerous conditions
•Experimental models have also shown that a transient period of telomere instability followed by reactivation of telomerase contributes to the acquisition of the metastatic phenotype
•Cytokines regulate the intensity and duration of the immune response, and they can act as growth factors or stimulants or even inhibitors of T cell amplification and differentiation.
•Cytokines are glycoproteins that are synthesized through a dolichol PP mediated pathway in the ER and are thus dependent upon prenyl lipid metabolism
Endoplasmic reticulum localized ADPGK serves glycoprotein synthesis and also functions to control glycolytic vs. aerobic bioenergetic intermediary metabolic agency in lymphocytes.
Scientific Reports volume 9, Article number: 14248 (2019)
1. Glucokinase- GK is in the neuron
2.Control over glycolysis via GK mediates neural transmission
3. Neuronal GK further functions on the appetite/satiety axis thus partially regulating the HPA axis
4. Aging and immune associated dysfunction of these glycolytic systems are associated with neurodegeneration and the loss of neuronal action potential mediated learning, memory, and mood.
Therefore, metabolic control over the severity of chronological age and the immunosenescence of the CNS can be exacerbated by visceral obesity thus linking CNS decline to the major causes of morbidity and mortality in the aging human population.
Curr Opin Lipidol. 2015 Apr; 26(2): 88–95
Am J Physiol Endocrinol Metab. 2016 Jul 1; 311(1): E42–E55
If γ-aminobutyric acid (GABA) concentration drops significantly in the synaptic cleft, excitotoxicity can obtain, sometimes presenting with epileptic convulsions.This can be reversed by decreasing the concentration of L-glutamate via control over the activity of glutamate dehydrogenase, glutamine synthetase and glutamate transporters or by the inhibition of γ-aminobutyric acid aminotransferase (GABA-AT), which catalyzes the conversion of GABA to the excitatory neurotransmitter l-glutamic acid.
Trends in Cell Biology 2020. 30.6: 440-451.
Chem. Rev. 2018. 118. 7: 4037–4070
A basic lecture on reactive oxygen synthesis and reduction coupled with glutathione, folic acid and amino acid metabolism.
This lecture is foundational for subsequent synthesis with neural transmission, microglial activation and exicitotoxicity leading to neurodegeneration in the aging human CNS.
Please subscribe, rate and review, and contribute to Authentic Biochemistry!
Published 9 March 2021 by Dr Daniel J. Guerra.
CPS-1 activity is regulated by liver enriched transcription factors as well as Sirtuin-mediated de-acylation.
Glutaminase breaks down glutamine into glutamate and ammonia. Glutamate also yields additional NH4+ via the enzyme glutamate dehydrogenase. From here, ammonia is initially incorporated into hepatocyte mitochondria and ultimately results in the formation of urea. Urea subsequently leaves the hepatocyte cytoplasm and is ultimately excreted in urine.
Glutaminase-1 (GLS1) is a mitochondrial enzyme found in endothelial cells (ECs) that metabolizes glutamine to glutamate and ammonia and glutaminolysis modulates the function of human umbilical vein endothelia.Glutamine deprivation or GLS1 inhibition also stimulated the production of reactive oxygen species and this was associated with a marked decline in heme oxygenase-1 (HO-1) expression. GLS1 inhibition also sensitized umbilical endothelia to the cytotoxic effect of hydrogen peroxide; a process that is blocked by the overexpression of Heme oxygenase 1. In summary, GLS1 promotes human endothelial proliferation, migration, and survival.
SIRT4 might prevent CNS excitotoxicity and subsequent apoptosis by reducing glutamine synthesis while and upregulating glutamate transport into astrocytes where increased glutamate dehydrogenase activity removes the ultimate source of this neural degeneration mechanism.
In the small intestine, SIRT5 causes deglutarylation and functional activation of glutamate dehydrogenase 1 leading to poor prognosis in colorectal cancer.
Combined, this experimental evidence suggests that the modulation of mitochondrial Sirtuin activity to pharmacologically circumvent CNS pathophysiology may not be appropriate for cancers in the digestive system and that Sirtuin isoform expression and activity is highly nuanced.
J Cell Mol Med. 2017 Sep; 21(9): 2036–2045
Hum Exp Toxicol. 2020 Jul;39(7):938-947
Glutaminase breaks down glutamine into glutamate and ammonia. Glutamate also yields additional urea via the enzyme glutamate dehydrogenase. From here, ammonia is initially incorporated into hepatocyte mitochondria and ultimately results in the formation of urea. Urea subsequently leaves the hepatocyte cytoplasm and is ultimately excreted in urine.
Sirtuin mediated control over glutamate dehydrogenase and carbamoyl-P synthetase via discrete and potentiating ADP ribosylation and deacylation is associated with pancreatic insulin secretion, hepatic amino acid utilization and the potential for pathobiochemical sequalae
SIRT5 causes deglutarylation and functional activation of glutamate dehydrogenase 1 which is essential to cellular glutaminolysis.Indeed, SIRT5 supports the anaplerotic transamination entry of glutamine and other amino acids as alpho ketoglutarate into the TCA cycle in malignant phenotypes of colorectal cancer via activation of the glutamate dehydrogenase1.
Sirt5 is known to regulate the activity of the urea cycle enzyme, carbamoyl phosphate synthase 1 (CPS1). SIRT5 mediated de-glutarylated CPS1 is elevated in activity to maintain urea cycle competency during active amino acid incorporation into the bioenergetic machinery thus promoting the potentiation of tumorigenesis.
Science. 2011 Nov11; 334(6057): 806–809
Cell Metab 2014 Apr 1;19(4):605-17.
Nat Commun. 2018 Feb7;9(1):545
Cell. 2006 Sep 8;126(5):941-54
Mol Cell. 2013 Jun 6; 50(5): 686–698
The Pyruvate dehydrogenase hydrated E1-E2 interface is enthalpy driven, while the dehydrated E3-peripheral subunit binding domain complex is driven by entropy obtaining a favourable delta G= delta H-T delta S= -33.4kj mol where the domain interfacial hydration obtains surface thermal complementarity and contributes finally to an aggregate strength of multiple affinities of individual non-covalent binding interactions via enthalpy-driven catalysis.
Lipoamidase activity of mitochondrial Sirtuin 4 modulates cellular fate by generating a debilitating removal of PDH-E2 dihydrolipoyllysine acetyltransferase-bound lipoic acid thus driving glutaminolysis over glucose oxidation.
Cell. 2014 Dec 18; 159(7): 1615–1625.
PNAS | August 23, 2016 | vol. 113 | no. 34
Structure VOLUME 13, ISSUE 8, P1119-1130, AUGUST 01, 2005
•Free energy change(chemical potential difference) for transporting 1 mole of a substance from region where its concentration is C1 (e.g., Cout) to region where its concentration is C2 (e.g., Cin):
∆G= RTln(C2/C1)
(favorable with ∆G< 0 if C2< C1)
•Transport of ionsacross membrane (must consider electrical potential in addition to concentration difference):
∆G= RTln(C2/C1) + ZF ∆Y
(Z=charge of ion, F=Faraday’s constant, ∆Y=membrane electrical potential in volts)
•Coupled transport (active transport):
∆G= RTln(C2/C1) + ∆G´
(∆G´ of coupled process, such as ATP hydrolysis, may be negative enough to compensate for unfavorable transport against concentration gradient when RT ln (C2/C1) > 0)
•Diffusional transport: movement of substance from high to low concentration across membrane (down concentration gradient)
–Non-facilitated diffusion across lipid bilayer (slow for most biological substances)
–Facilitated diffusion (accelerated diffusion by making membrane more permeable to specific transported substance, e.g., channels and carriers)
•Active transport: Actively driven (generally directly or indirectly coupled to ATP hydrolysis) transport against concentration gradient from low to high concentration across membrane (e.g., pumps)
Mini Lecture 1 on Membrane Physiological Biochemistry.
The amino acid sequence of membrane associated polypeptides obtains secondary structure, glycosylation, acylation and hydropathy which confer functionality (in part) by targeting specific membrane domains.
For Valentine's Day Eve. A bouquet assortment of biochemical thermodynamic principles and metaphysical event ontologies.
To finish my thoughts:
Is life necessary? How to answer this question? One way is to ask if there is sufficient reason for its existence. Outside of spiritual or theological discussion, the answer is compellingly obscure especially since we find no authentic examples except on our planet.
If life is contingent, where does it come from, how does it come about and why does it exist? You see where this is going. Why is there a physical universe? Why isn’t there just nothingness?
Answering with the typical “it just is!” only further confounds the question. The word “just” here, operates syntactically with contingency. By that I mean, proposing that the modality of an event, life in this context, simply "is" a state function, makes no claim that the event "must be". And so…we are back to the beginning. A beginning that has no source.
The Big Bang could be such a beginning, but then again, some event had to proceed it , even if time itself had this event as its source.
As a biochemist I authentically and humbly do not obtain sufficient reason to obtain life from the non-living and so I will to be content, on finding how biochemical events happen. As an existing individual, I believe in God.
*Oncogenesis eventuates genetic mutation to epigenetic gene expression mechanisms with molecular signatures either inappropriately proscribed, incorrectly prescribed upon writing as dangerous and deleterious, or erasure; leaving a corrupted chromatin result.
*Tumor cells obtain proliferative autonomy, autophagous –self-maintenance in growth and signaling, neovascularization for nutrient and oxygen supply, and resistance to anti-proliferative and apoptotic stimuli
*In resting cells, the cell cycle is strictly managed by a set of regulatory proteins that control the various cell cycle checkpoints and this will become dysfunction during the early transforming stage of the tumorigenesis via the unregulated dismantling of tumor suppressor genes
*Suppression is the programmed deliberative inhibition of biochemical events while repression is the unintentional inhibition of biochemical events
*When a biochemical event is de-repressed it is brought back to register, regardless of valence
*In effect this dismantling is a repression of tumor suppressor gene transcription and/or translation, post-translational modifications or final agency
*This loss of gene suppressor “activity” can result from deletion, inactivating mutations, epigenetic silencing, incoherent post-translational modification(s) including glycosylation/acylation/prenylation/phosphorylation/aggregation etc.or lipid mediated transport aberrations as with membrane lipid rafts from Sphingomyelinase mediated ceramide synthesis.
*The typical biomedical result is oncogenesis(transformative) and ultimately tumorigenesis (committed), metastasis (mobilized and transactional) and either death or repair to healthy state.
*The progression of the mammalian cell cycle from G1 to mitosis is regulated by cyclins with their cogent catalytic subunits, the referred to as cyclin-dependent kinases (CDKs)
*A family of cyclin–CDK inhibitor proteins (CDIs), which bind and inactivate the CDKs, includes the p16INK4a, p21CIP1, p27KIP1, and associated proteins p15INK4b, p18INK4c, p19INK4d and p57KIP2
*These proteins potentially act as tumor suppressors and their inactivation corresponds with human carcinogenesis.
*Selective removal of CDK inhibitors may ablate senescent cell lineages in a process known as senolysis which may promote healthy cardiac muscle aging in the elderly
* In balance the square of opposition logical conclusion is to distinguish between contrarion vs. contradictory physiological and pharmaco-therapies.
Dr Daniel J. Guerra Authentic Biochemistry Published on 10 February 2021
Refs
EBioMedicine 2016 830-39DOI: (10.1016)
BMC Cancer volume 20, Article number: 882 (2020)
J Cardiol. 2019 Oct;74(4):313-319
Front. Neurosci., 24 July 2019 | https://doi.org/10.3389/fnins.2019.00728
Intra abdominal adiposity (IAA) linked obesity may be the most significant contributory factor to high mortality human disease after aging.
IAA presents with systemic and chronic inflammation and enlarged White Adipose Tissue (WAT) adipocytes that have been infiltrated with lymphocytes and macrophages that secrete pro-inflammatory cytokines, chemokines, growth factors and inappropriate levels of pro-inflammatory adipokines.
Aging combined with chronic obesity not only promotes cardiovascular disease and cancer but further promotes autoimmune disease, dementia and high morbidity metabolic dysfunction, respiratory disease, and hyperimmune response to otherwise non-virulent pathogens linked to mortality.
International Scholarly Research Notices, vol. 2013, Article ID 139239, 12 pages, 2013. https://doi.org/10.1155/2013/139239
*Adipose tissue is the endocrine organ that secretes “adipokines”
*Nothing new to the Authentic Biochemistry crew; adipokines have been very well discussed here and their function as mediators of the feeding/appetitive/satiety response through the arcuate nucleus of the hypothalamus (POMCvNPY neurons) was most recently addressed.
*Adipokines mediate the BMI, heart rate, serum glucose &fatty acid/TAG, and pro- inflammatory cytokine production;they are released by adipocytes (e.g. leptin and adiponectin) or preadipocytes, adipose tissue-infiltrated immune cells, or the gastric system
Indeed, Th2 lymphocytes promote adipose glucose homeostasis by enhancing insulin sensitivity in adipocytes and browning/brown adipose tissue (BAT) activation but chronic inflammation of white adipose tissue (WAT) leads to the activation of pro-inflammatory pathways in adipocytes and resident immune cells following obesity involving the shutting down of Tregs and anti-inflammatory cytokines.
Front Physiol. 2020; 11: 578966
Indian J Pharmacol. 2012 Mar-Apr; 44(2): 155–156.
Cells. 2019 Mar; 8(3): 227.
Proceedings of The Nutrition Society.2012 71(4):521-33
Autophagy. 2009 May; 5(4): 558–560
Molecular and Cellular Endocrinology Volume 472, 5 September 2018, Pages 40-49
Int J Mol Sci. 2020 Nov; 21(21): 8220.
Fear-conditioning learning is a low-threshold enduring psychiatric process that prepares a defense against dangerous phenomena and reduces the need to iteratively relearn the signal. It is a pattern recognition response that can be modulated by experience and the severity of the stress signal and it is a response that deteriorates in the elderly and in certain neuropsycoses and anxiety disorders throughout life. Fear conditioning must be fluid to readjust according to reverse learning.
Persistent fear and avoidance of the potential for fear-associated events are common presentations of social anxiety disorder (SAD) and avoidant behavior maintains SAD, thus it prevents the reversal of fear in social situations. The best treatment outcomes are CBT including exposure therapy, which leads to fear extinction. Pharmacotherapy including antidepressants, benzodiazepines, beta-blockers, anticonvulsants, or neuroleptics, are commonly administered with low efficacy.
Neuropeptide Y (NPY), a 36-amino acid peptide, is the most abundant and widely distributed neuropeptide in the mammalian brain and it may be involved in social behavior and the fear circuitry, including activities in the amygdala, hippocampus, septum, periaqueductal gray, locus coeruleus, cerebral cortex, basal ganglia, hypothalamus, and thalamus. NPY is also a feeding simulant, regulator of blood pressure, bioenergetics , neuroendocrine hormone responses, neuronal excitability, and neuroplasticity including epigenetic mechanisms. Not surprisingly, exogenous NPY causes a variety of behavioral effects when administered into the brain of rodents including stimulation of food intake when administered into the hypothalamic paraventricular nucleus, and it promotes social interaction when administered into the dorsolateral septum and basolateral amygdala and has anxiolytic and antidepressant-like effects when administered intracerebroventricularly (i.c.v.).NPY also affects different aspects of fear-related behaviors, as shown in fear conditioning studies in rodents.
Next time we will link Acid Sphingomyelinase to NPY and the anxiety disorders of the elderly..
Int J Mol Sci. 2020 Nov; 21(21): 8220.
Homeostatic chronic low stress results in low to moderate levels of CRF in the LC in association with enhanced Extra-Dimensional Shifting and optimal executive decision making. However, acute or chronic severe stress is linked to high levels of CRF in the LC and this may contribute to a shift from optimal executive function necessary for goal-directed behavior toward an iterative decision response.
In healthy environments, this variable tonicity is a readout for adaptation when goal-oriented behavior is relaxed so that the individual uses pro-forma decisions even when novel environmental stimuli are encountered.
During aging these pathways lose flexibility due to a decrease in executive decision making linked to the senescence phenotype that may impair neural circuitry via inflammation, over or under activation and lack of control over immune cell responses.
J Neurosci. 2008 Nov 5; 28(45): 11517–11525.
GeroScience. 2017 Feb; 39(1): 61–72.
Neuroscience. 2017 Mar 14; 345: 12–26.
Adaptation to stress-such as the fear response obtains dopaminergic input to striatum and prefrontal cortex and is thought to signal unexpected events and facilitate a shift in attention to promote new learning within the contralateral primary somatosensory cortex (SI) which has been associated with the agentic categories of both the quality and quantity of thought event ontology. This process works in conjunction with the bilateral secondary somatosensory cortex (SII) process involved in executive decision making. Where stimulated, the primary sensory motor-neuronal process is integrated with novel extra-dimensional learning .
Recall that this fear stress response can lose functional valency upon immune-regulating, senescent secretory phenotypes.
In the aging brain, where CRF axon terminals are widely distributed, (including within catecholamine and serotonin nuclei) there are widespread cortical projections into the medial prefrontal cortex; linking executive functional responses to adverse stimuli.
Dr. Daniel J. Guerra
Authentic Biochemistry
Published 20 Jan 2021
Refs
Neuroimage. 2008 May 1;40(4):1765-71.
Biol Psychiatry. 2009 Sep 15; 66(6): 586–593.
The anti-inflammatory IL-10 pathway in the CNS can lead to Glioblastoma which is a disease presented 3-4 fold higher in people ≥65 years old, and with a mortality rate for the same age group some 7 fold higher. Activation of the IL-10 Receptor bound ligand induces the JAK1 signal transducer and activator of transcription 3 (STAT3) pathway in APCs. This results in the subsequent translocation of STAT3 homodimers into the nucleus. This STAT3 homodimer binds to STAT-binding elements which promotes the expression of the suppressor of cytokine signaling 3 (SOCS-3) and IL-1 receptor antagonist (IL-1RN). IL-10 reduces the production of pro-inflammatory cytokines (IL-1β, IL-6, tumor necrosis factor alpha) and diminished expression of both major histocompatibility complex II.
The anti-inflammatory MiDAS phenotype can also induce heart failure in the aging population.
References:
Front Pharmacol. 2019; 10: 200
Aging Cell. 2018 Oct;17(5)
Int Heart J. 2018 Jul 31;59(4):837-844
Front. Immunol., 19 March 2018
Neuro Oncol . 2020 Mar 5;22(3):333-344
Non-uniform ageing is a major associative risk factor for cancer and degenerative diseases and mitochondrial dysfunction is linked to cellular senescence in association with cell cycle arrest, telomerase decline and nucleic acid/lipid/protein oxidation. Indeed, mitochondrial dysfunction comprises a distinct type of cellular senescence; mitochondrial SIRT3 or SIRT5, can induce Mitochondrial Dysfunction Associated-Senescence (MiDAS)
Senescence is a chronological and pathophysiological sequenced event response that restricts mitotic division and thus aberrant proliferation of damaged, infected and/or tumor inducing cells. Because these cells are senescent and exhibit low anabolic currency to present self-produced antigen epitopes as displayed by HLA, they are not targeted by immune responses but rather, may become secretory and induce inflammation by instantiating the Senescence Associated Secretory Phenotype-SASP. Senescence presents with metabolic reprogramming, epigenetic chromatin remodeling, and the secretion of growth factors, signaling molecules, proinflammatory cytokines and chemokines, extra-cellular matrix metallo proteases, nucleotides, exosomes and ionic bursts collectively referred to as SASP.
Both SASP and MiDAS can occur in the CNS during human aging thus generating a remarkably complex-contrarion dual pathophysiological phenotype leading to neurodegeneration or more rarely, certain forms of brain cancer.
Authentic Biochemistry Podcast is produced by Daniel J. Guerra, PhD. Today's Date: 16 January 2021
Refs.
Trends in Biochemical Sciences Volume 41 Issue 3 Pages 207-209 (March 2016)
Cell Metabolism Volume 23, Issue 2, 9 February 2016, Pages 303-314
Front. Immunol., 19 March 2018
LC axonal projections to the mPFC modulate a diversity of cognitive processes, including working memory, sustained attention, and flexible attention and under moderate rates of LC activity and NE release, high-affinity postsvnaptic α2 adrenergic receptors in the PFC are preferentially engaged and promote working memory However, with elevated LC firing and activation of lower affinity α1 adrenergic receptors, working memory is impaired while agentic focused attention becomes prominent so it seems that LC projections to the PFC modulate different cognitive processes in a context-sensitive manner.
his latter mechanism could correlate with the experienced rapid response such as in “fight or flee” decision making upon immediate threatening danger. The sensation perception recognition and response behaviour all works sequentially from these neuronal loci post encounter to the stimulus and as such fit well into Kantian epistemology which obtains that the individual is presented with a particular stimulus-sense data or “intuition” that is processed by the faculty of the understanding as a perception of danger in association with a concept-abstracted from previous experience. This representation is then acted upon and the neural network-already poised to respond sequentially follows suit and ultimately directs the motor cortex to act.
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•Intensive and chronic or excessive stress diminishes intellectual performance and general cognition: this is a form of negative reinforcement and can be related to learning disability and anxiety about future events. Indeed, •Individual responses and the magnitude of stressor as well as its association with self identity and goals will influence endurance, resilience, and self-empowerment vs. dissatisfaction and defeat.
•Stresses first become recognized in the developing fetus since the fetal brain attains awareness during the first trimester and maternal stress is well established as an epigenetic mechanism involved in fetal neural development and stress is lifelong , contributing to one’s character and ability to overcome fear and anxiety.
•Stress response is an element of the hypothalamic-pituitary-adrenocortical (HPA) axis where Corticotropin-releasing factor (CRF) serves as a gate keeper for fear conditioning playing dual roles as hormone and as neuromodulator.
•CRH exerts multiple effects on the adult brain, often spatiotemporal, as shown by secretion site-specific responses in that CRH after binding to its GPCR's: CRHR1 and CRHR2 which subsequently regulates the formation of neuronal dendrites; neurite elongation, synaptogenesis, and circuit integration of adult-born neurons thus organizing and modifying excitatory transmission in a neuronal type-specific manner
Transl Psychiatry. 2019; 9: 272.
Cell Reports Oct 2019, 29, 932–945
1. Corticotropin releasing factor (CRF) or hormone (CRH) is one of several neurohormones synthesized by specific hypothalamic nuclei in the brain and released into the portal system which bathes the anterior pituitary
2. CRF has marked CNS effects by acting at higher centers in the brain: cortical regions where there is a widespread distribution of CRF neurons.
3. Major role of CRF is to prepare the organism for an appropriate response to various stressors such as physical trauma, insults to the immune system and social interactions
4. It is the hyper- or hyposensitivity of the system that can lead to human pathologies such as anxiety, depression and feeding disorders
5. The hypothalamus induced combined pituitary hormone deficiency, which is responsible for systemic hypoplasia is the result of a neutral sphingomyelinase (SMPD3)deficiency
6. SMPD3 deficiency triggers acid sphingomyelinase (ASM) plus de novo CER synthesis and salvage CER production from sphingosine with concomitant alterations in membrane PLC mediated DAG enrichment of VLCPUFA’s and their SFA counterparts thus diturbing membrane raft-mediated signaling and cell death and an appropriate local immune response thus disturbing glucocorticoid (and a host of other) HPA axis hormones.
Naïve T Cell metabolic regulationinvolves allosteric and kinetic mechanisms for maximum capacity to switch from glucose uptake to fatty acylCoA utilization for bioenergetic demand.
Multiple mechanisms of this coordinated regulation involve the fatty acyl CoA concentration modulation by fine tuning cyctosolic fatty acid synthesis from glucose or lactate or amino acids vs. mitochondrial beta oxidation to drive the ATP concentration to levels necessary to prepare for cell proliferation and evenbtually cytokine synthesis and secretion.
Published 06 January 2021.
Dr Daniel J. Guerra, Authentic Biochemistry .
There is a requirement of cholesterol and ceramides for the maintenance of neuronal and T cell porosome integrity, accompanying an interaction of phosphatidic acid (PA) and polyphosphoinositide (PI) lipids with syntaxin-1A where these lipids are necessary for neurotransmitter or cytokine secretion in association with calcium channels modulated by lipid domain formation upon sphingomelinase and fatty acyltransferase activities.
Complex lipid composition and three dimensional sequence topology differs between the inner and outer leaflet of the bilayer at descrete lipid raft domains of the endomembraneous and plasmamembrane where these macromolecular structures contribute to the polarity of transport, access, and differential signaling uniquely essential for cell communication in the CNS and immune synapse.
Published on 05 Jan 2021 Authentic Biochemistry Dr Daniel J. Guerra, Ph.D.
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Cellular long chain acyl-CoA concentrations are controlled by multiple networked and coherent metabolic pathways ( including mitochondrial β-oxidation versus Golgi-ER-PL complex lipid synthesis versus glyceropholipid and sphingolipid hydrolysis), which functionally associate resident acyl-CoA in cellular bioenergetic and signaling pathways. Thus, the regulation of PFK-1 by its direct interaction with acyl-CoA generates downstream interconnected alterations in metabolic flux through glycolysis, the OPP and mitochondrially associated oxidative metabolism plus vesicular trafficking and directed subcellular localization associated with porosomes.
Biol Open. 2019 Oct 15; 8(10): bio040311.
Biochem Soc Trans. 2015 Apr;43(2):193-8.)
J of Molecular and Cellular Medicine 2014. 18: pp.1927
Naive T lymphocytes, as opposed to memory T cells(which are more common in aging) carry out homolactate fermentitive glycolysis.
Memory cells are operating under complete aerobic metabolism involving mitochondrial bioenergetics including the TCA cycle but also fatty acid oxidation as a source for reducing equivelents to drive the electrontransport chain and oxidative phosphorylation.
The regulation of these alternative pathways involves allosteric modification of key enymes and trafficking proteins intracellularly.
The acid sphingimyelinase and protein palmitoylation enzymatic machinery coordinates this regulation by changing the membrane micro-environment.
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Early stage TCR activated T cells with rampant lactic acid fermentation, fail to maintain adequate ATP levels , especially when glucose is limiting.This decrease in ATP relative to ADP+AMP results in the activation of AMPK, which inhibits mTOR activity and all subsequent anabolism especially assocaited for T cell proliferation. Indeed, induced Loss of AMPKα1, will sythetically restore mTOR signaling and T cell cytokine production, but not proliferation. Although loss of AMPK can restore some functions in glucose-restricted T cells, the cells do not initiate metabolic adaptations necessary to recover ATP levels. In vivo, AMPKα1-deficient T cells have decreased mitochondrial respiration, flux of glutamine into the mitochondria, and ATP:AMP ratios, and therefore fail to proliferate and function effectively.
In cardiac and skeletal muscle, AMPK phosphorylates the bifunctional enzyme at a unique SER residue which induces the PFK-2 activation over the phosphatase activity thus stimulating glycolysis and overcoming hypoxia. Hypoxia renders the mitochondrial electron-transport chain-oxidative phosphorylation pathway non-functional as molecular oxygen is the ultimate electron acceptor becoming reduced to water. With depleted oxygen as in stress and in heavy skeletal muscle contraction, glycolysis must be stimulated as AMP levels rise. AMP also controls PFK-1 directly
In tumors, the rate of translation of HIF-1a mRNA in cancer cells is dependent upon the activity of the mammalian target of rapamycin (mTOR), which in turn is determined by the activity of upstream tumor suppressor proteins and oncoproteins. HIF-1α plays a key role in stimulating glycolytic enzymes and in blocking mitochondrial activity. LncRNAs can also regulate Akt and AMPK pathways. Akt may increase oxidative phosphorylation by enhancing metabolic coupling between glycolysis and oxidative phosphorylation.
Relevant Research References
Cell Research volume 30, pages649–659(2020)
Molecular Cancer July 2017. 16(1)DOI: 10.1186/s12943-017-0699-3
Genomics, Proteomics & Bioinformatics Volume 14, Issue 1, February 2016, Pages 42-54
J BiolChem. 2011 Apr 8; 286(14): 11937–11950.
Authentic Biochemistry Podcast 29 December 2020
Daniel J. Guerra Ph.D.
•All scientific inquiry should start with dialectical method that uses the current knowledge base to generate various specific Theses and then follow each with the counter-argument by employing the Square of Opposition thus producing Anti-theses and then, making the third movement, which allows for a Synthesis that has the flavor of rejection, acceptance or indifference.
*Downstream of co-stimulation and PI3K-AKT, the mammalian target of Rapamycin (mTOR) kinase pathway integrates multiple signals and regulates anabolic metabolic reprogramming in T cells exiting quiescence. mTOR complex 1 (mTORC1) is required for cell cycle entry and coordination of early metabolic changes that occur upon T cell activation.
*T cells deficient in Raptor, an essential component of mTORC1, fail to upregulate the expression of Glut1 and other glycolytic enzymes when activated.
*Raptor-deficient T cells also exhibit defects in de novo lipid synthesis and oxidative phosphorylation, suggesting the mTOR pathway is a global regulator of T cell metabolic programs.
*mTORC1-mediated signaling is also required for proteomic remodeling of pathways including one-carbon metabolism(SAM and Folic acid), FAO, and the electron transport chain (ETC) that occurs early in activating T cells.
Human neuroscientific research seeks to uncover patterns of commonality and uniformity to help define mechanisms which reliably result in the experience of thinking and interacting with the world. This scientific mindset is in opposition to real life experience where human bonding is unique to a specific relationship. This may be best understood as a compatibilist approach, where neuroscience may affirm the very real experience of an individual when he makes a judgment or chooses to imagine his next move while the neurocircuitry is providing the means to have that experience without an agentic causal connection. This view as stated is not a contradiction, since it doesn’t assert there is no experience of free will or directed emotion or thought but rather that it is coincidental to the neurophysiology and the grounding provided by neurobiochemical networking.
In my view, there is an alternative to this theory; it is based on the principal of “first causes”.
Merry Christmas Everyone!
T cell agency initiates upon the stimulation of the TCR via presentation of cognate peptide-MHC complexes in associative ligand-mediated membrane co-receptor CD28 with co-stimulatory molecules presented on the surface of the APC: this event is called T cell licensure and essentially quits quiescence.
The TCR signals through the ERK/MAPK pathways and calcium flux; where as CD28 signaling activates the PI3K-AKT-mTOR axis, and both pathways synergistically engage the NF-κB organon of pleitropic T lymphocyte agency.
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In this episode Dr Guerra provides a concise description of T lymphocytic fatty acid synthesis from glucose via cytosolic glycolysis, mitochondrialpyruvate dehydrogenase, pyruvate carboxylase, and citrate synthase and a return to the cytosol for ATP citrate lyase and the homodimeric polyprotein complex FAS to generate palmitoyl-ACP.
This ability of antigen-MHC Antigen Presenting Cell TCR - activated T lymphocytes to prepare for massive cytokine and chemokine expression requires a biochemical poise to use newly synthesized intracellular triacylglycerol to drive cellular exapnsion and effector-mediated immune responses.
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Metabolic syndrome (MetSyn)is a dyslipidaemic chronic and aging linked sedentary life-style constellation of disease presentations including metabolic disorganization, prodromal Type 2 diabetes and a prominent connection to hypertension-most prominently associated with over-eating and obesity. MetSyn is often prolegomena to middle-age onset CVD, cancer and neurodegeneration. High caloric density soluble carbohydrate nutrition, lack of fasting and the species-specific metabolic inability to convert fatty acids into glucose via gluconeogenesis, provide a pathobiochemical poise toward MetSyn.
As Nicotinamide Adenine Dinucleotide (NAD+) levels decline with age and obesity a potential suppression of NAD (H)-dependent enzymes in oxidative phosphorylation, the TCA cycle, and glycolysis resulting in suppressed ATP production can trigger the AMPK mediated transcriptional activation of the senescence-associated secretory phenotype (SASP) leading to morbidity and mortality in the advanced aged human.
However, NAD+ essential DNA Damage Repair and Sirtuin-mediated deacetylation of histone-associated chromatin may exacerbate aging and both neurodegeneration and tumorigenesis.
Published and produced by Dr. Daniel J. Guerra, Authentic Biochemistry 17 December 2020.
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J Biomed Sci. 2019; 26: 34
Front. Genet., 12 March 2015
BioEssays, 2017. Volume: 39, Issue: 5,
Both the innate and acquired immune systems become senescent during chronological aging. While T cell activation may become disenfranchised from its co-stimulatory control apparatus during aging, the potential for hyper or hypo-immune responses becomes more common. At the same time, CNS microglia and peripheral resident and circulating macrophages are activated following the stimulation of various pattern recognition or phagocytic receptors. In the CNS, this activation state is subsequently controlled by proximal neurons, which secrete regulatory ligands. The end result of these interactions is the release of cytokines, neurotoxins, and/or growth factors by microglia/macrophages and the activation of cellular pathways including phagocytosis. Aberrant function of these pathways can result in significant degeneration during aging.
Cell Rep. 2018 Feb 6; 22(6): 1509–1521.
FEBS Journal. 2009.Vol. 276, 1 Pages: 13-26
Experimental & Molecular Medicine volume 51, Article number: 80 (2019)
Frontiers in Immunology · February 2013
Cell cycle (Georgetown, Tex.) September 2008 7(15):2296-8
Dr. Guerra reminds and extends his decade-long hypothesis that The Immune Response could function to generate the networked synaptic connections in the brain during initiation, development, learning, and aging.
The question considered is how do immune cells and immuno-regulatory proteins such as cytokines and chemokines and immunoglobulins recognize certain neurons and not others? The mechanism for maintaining and increasing synaptic strength vs. obsolescence and programmable cell death could be mediated by cellular phenomena known as pattern recognition.
The bioenergetics of T lymphocyte activation and subsequent effector mediated inflammatory responses involves a conversion of glucose to lactate via aerobic glycolysis as coordinated through the early TCR activation stage phosphorylation of pyruvate dehydrogenase via PDHK1 and axial coordination of NAD+ synthesizing LDH.
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Aging and chronic stress can obtain activation of CNS-resident microglia and astrocytes, that produce type 1 interferons (T1 IFNs) which signal through the heterodimeric IFN-α/β receptor (IFNAR) where receptor binding of T1 IFNs activates the JAK/STAT thus inducing IFN-stimulated genes (ISGs) which mediate both pro- and anti-inflammatory functions depending upon the cellular micro-environment.
Now consider how aging is linked to elevated & activated leukocyte counts and it becomes clear that this is a patho-biochemical phenocopy to T cell acute lymphoblastc leukaemia (T-ALL) where signaling through Notch, Jak/Stat, PI3K/Akt/mTOR, and MAPK are shared.
IL7-induced glucocorticoid resistance is diagnostic of certain subtypes of T-ALL and this is also associated with the senescence associated secretory phenotype of aging-linked morbidity and mortality.
Finally, consider that chronic CNS stress leads to increased glucocorticoid production leading to a suppression of cell adhesion protein thus corrupting synaptic plasticity, memory re-formation, and cognitive acuity while promoting sarcopenia by stimulating proteasomal removal of contractile proteins and inhibiting the PI3-kinase/Akt pathway. Glucocorticoids also prevent IL-2 synthesis and secretion thus causing immune suppression by blocking T cell activation.
J Neuroinflammation. 2019; 16: 236.
Cytokine & Growth Factor Reviews, 22 Apr 2017, 35:85-96
In this first pre-Christmas present Authentic Biochemistry Podcast lecture, Dr Guerra examines the multifactorial expansion of NOTCH signalling through early thymocyte development as regulated by paracrine and endocrine hormonal systems in cooperation with the exemplary plenum of IL7 cytokine mediated signalling through the phosphatidylinositol and AKT kinase cascades.
References
J Cell Physiol. 2003 Mar;194(3):237-55
Development 2019 146: dev172148
Int J Mol Sci. 2020 Nov; 21(21): 7972
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In today's lecture, Dr Guerra explains how subclinical hypothyroidism obtains increased serum thyrotropin (thyroid stimulating hormone, TSH) with flat levels of of free thyroxin (T4) and biologically active free triiodothyronine (T3) in the elderly;β1 adrenergic receptors, sodium/potassium ATPase, voltage-gated potassium channels, malic enzyme and atrial and brain natriuretic factor all respond favourably to thyroxin and hese proteins form the primary architecture of the cardiomyocyte and determine contractile strength. ATP drives muscle contraction/relaxation thus active mitochondrial nadh oxidation is essential for healthy aging. Ketone and free fatty acid oxidation decreases with aging while glucose oxidation reciprocally increases while thyroid hormone levels decline with aging, suggesting that myocardial metabolic pathology is linked phenomenologically to subclinical hypothyroidism.
Indeed,thyroid hormone deficiency found in aging populations inhibits fatty acid oxidation through transcriptionally mediated downregulation of PPARα where this transcription factor normally suppresses PDK4, which allows increased PDH. This suggests that aging correlates with decreasing fatty acid oxidation which is associated with reduced cardiac function. The aged heart relies on lactate, glucose and pyruvate in place of fatty acids and the PDH complex plays a central role in the modulation from fatty acid oxidation to glucose oxidation in the mitochondria to finally anaerobic glycolysis in the aging heart.
T lymphocyte maturation and expansion also follows a switch in carbon energy utilization so the two systems function in contrarion regulation, leading to decreased cardiac output with a declining naive T cell population thus losing the regulated induction of inflammation from diverging metabolic sequalae in the aging human.
PLoS One. 2013; 8(6): e65532.
Int J Mol Sci. 2020 Nov; 21(21): 7972
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On this 16th of November Authentic Biochemistry Podcast episode acknowledging my sister Carol's birthday, I explain the MST- kinase mediated transcription factor HIPPO pathway and its potentially gravid linkage to aging associated lymphocyte-informed autoimmune disease, cancer and neurodegeneration. Published by Dr.. Daniel J. Guerra. 2020
References
Experimental & Molecular Medicine volume 51, Article number: 80 (2019)
Pharmacological Research Volume 143, May 2019, Pages 151-165
Trends in Cancer, May 2019, Vol. 5, No. 5297-307
Nature Reviews Rheumatology volume 13, page389(2017)
Adv Immunol . 2019;144:87-119
During thymic T lymphocyte recombinatorial self avoidance, the processing obtained in T cell receptor excision generates small circular DNA byproducts that may be used as a biomarkers for thymic output and for the relative ability of T lymphocytes to fight infection, tumors, and obesity -linked cardiovascular disease and metabolic disorders that may become important pathologies in the aging human population.
Transcription factors like Nfil3 are important components of this networked age-related decline called immunosenescence that has the pathobiochemical signatures of SASP , ROS, mutation, epimutation and epigenetic gene expression pathologies.
Dr. Daniel J. Guerra Authentic Biochemistry Podcast Publication. 14 November 2020
References
Braz J Med Biol Res. 2019; 52(7): e8292
PLoS One. 2016; 11(6): e0157930
Experimental & Molecular Medicine volume 51, Article number: 80 (2019)
1.Id proteins are helix-loop-helix (HLH) proteins lacking the basic amino acid domain necessary to bind DNA.and therefore ID functions in a dominant negative manner by sequestering ubiquitously expressed or cell- restricted basic HLH transcription factors: this results in effective blockade of transcription since ID causes a failure of dimerized basic HLH proteins to bind DNA.
2. Id proteins regulate transcription factors that are involved in developmental processes such as myogenesis, neurogenesis, bone morphogenesis, lymphopoiesis hematopoiesis, and myeloid differentiation
3. Id2−/− mice lack lymph nodes and Peyer's patches*,
*Peyer's patches are discrete masses of lymphatic tissue found throughout the ileum of the mammalian small intestine
Oncogene volume 22, pages1–9(2003)
PNAS January 15, 2019 116 (3) 890-899
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Since epithelial clock gene and lymphocyte transcription factor Nfil3 expression is elevated in recombination deficient mice the potential for increased bacterial populations lining the gut may induce an expansion of class 3 innate-like T lymphocytes (ILC3) in the small intestine. thus allowing for circadian clock activity maintenance and effective immune clearance of potential pathogens. This observation may provide a potential pathobiochemical link between obesity and the increasing pathophysiology associated with human aging.
Dr. Daniel J. Guerra Authentic Biochemistry Publication 10 November 2020
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NFIL3 is a critical transcription factor immunologically linking the microbiome to the circadian clock and lipid metabolism where the
Innate Lymphoid Cell subtype 3 and dendritic cells may stipulate the intestinal microfloral associated epithelial temporal chronicity.
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Published by Dr Daniel J Guerra, Authentic Biochemistry 09 November 2020
Reference: Science. 2017 Sep 1; 357(6354): 912–916.
Nuclear factor interleukin 3 (NFIL3, also known as E4-binding protein 4, E4BP4) is a repressor of numerous genes. NFIL3 contains a basic leucine zipper domain, comprising amino acids 73–146, among 462 residues; the N-terminal part of this domain directly binds to DNA, while the C-terminal region is responsible for homo- or heterodimerization of the protein. Amino acids 299–363 comprise a transcriptional repression domain where the N-terminal part of this domain directly binds to DNA, while the C-terminal region is responsible for homo- or heterodimerization of the protein and amino acids 299–363 comprise a transcriptional repression domain.
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Dr. Guerra hybridizes multiple strands of published biochemical research to obtain an event ontology for potentiating factors leading to the aging human pathophysio9logical phenotype.
In this lecture I include the following detail:
1. Nuclear factor interleukin 3 (NFIL3, also known as E4-binding protein 4, E4BP4) is a repressor of numerous genes. where an N-terminal domain directly binds to its response element, while the C-terminal region is responsible for homo- or heterodimerization to induce a temporally synchronized geometric configuration obtaining as a transcriptional repression domain
2. NFIL3 represses genes by recruiting histone deacetylase 2 and G9a histone methyltransferase in diverse physiological networks including the circadian clock, acquired immune response, cell fate, and intermediary metabolism.
Papers to read:
Experimental & Molecular Medicine volume 51, Article number: 80 (2019)
Journal of Molecular Endocrinology (2019) 63, R93–R102
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Since space and time are never the same twice and indeed are relatively uncertain, not even the day/night chronicity is a true cycle. It is a pattern or a familiar sequence of events and nothing more. No two moments are identical and so our internal circadian clock tracks these patterns but the means by which this detection operates at the cellular and molecular level, as well as the event itself involving the revolving celestial bodies in constant flux so in time, the pattern becomes less uniform while the ideal presents as fixed and familiar so to be displayed intentionally and subsequently neurologically as apparent classical experiential phenomena.
Feedback loops compose the ‘molecular clock’ which is governed by a cascading transcription and translational regulatory mechanisms that are sufficient to maintain circadian rhythms.
Journal of Molecular Endocrinology (2019) 63, R93–R102
The pharmaceutical Remelteon may be a better MT1 MT2 agonist mimetic for decreasing melatonin synthesis in the aging pineal because it fails to bind MT3 receptor which is an active quinone reductase 2 synthesizing superoxide system. Published 24 October 2020 by Authentic Biochemistry Podcast; Dr Daniel J. Guerra
The artificial enhancement of brain melatonin levels were hoped to suppress the progress of Alzheimer's Disease in humans and for correcting the circadian and sleep-wake disturbances associated with advanced aging.. However, given the complex association of melatonin on NAD+ tonicity and this relationship playing a role in DNA Damage Repair Responses (both SSB and DSB) . melatonin or a surrogate mimetic receptor agonist may have undesirable effects on neurodegeneration and oncogenesis in the CNS and the periphery.
Dr Guerra opens this complex biochemical terrain in this and the previous 21 October Authentic Biochemistry podcast lectures.
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This episode lays the foundation for a common precursor-the essential amino acid L-tryptophan, of both melatonin and NAD+ and the PARP mediated DNA repair pathways linked to tumorigenesis on one hand and in DNA Damage repair-linked cessation of apoptosis on the other, in the aging human Central Nervous System.
Cells. 2019 Sep; 8(9): 1047.
Int J Alzheimers Dis. 2011: 741974.
The pineal endocrine hormone melatonin proximally decreasesIL-1β-induced MMP production by inhibiting Sirt1-dependent NAMPT and NFAT5 signaling in chondrocytes; since autoinflammatory Osteoarthritis (OA) is a degenerative joint (cartilage degradation) disease linked to human aging and Interleukin-1β contributes to OA pathogenesis by enhancing oxidative stress and inflammation the role(s) of sirtuin and NAD+ metabolism is associated with aging morbidity while also being described in Double-Stranded Break (DBS) DNA Damage Repair (DDR), we have isolated and identified with distinction, pathobiochemical components of the human aging event ontology.
Oncotarget. 2017 Aug 22; 8(34): 55967–55983.
PLOS One .November 25, 2014https://doi.org/10.1371/journal.pone.0113939
Int J Mol Sci. 2019 Mar; 20(5): 1223.
eLife 2020;9:e55828 DOI: 10.7554/eLife.55828
Dr. Guerra offers a deep investigation into the roles of sirtuins in homeostasis , aging and disease as linked to NAD+ metabolism via ecto enzymatic CD38 and intracellular forms of this NAD+ metabolizing enzyme that is associated with T lymphocyte bioenergetics, activation and regulation as embedded within the inflammatory response, disease and aging. Published in Authentic Biochemistry Podcast series on Aging and the immune system. 14 October 2020
Papers mentioned in today's lecture :
Hogan, et al. Front. Immunol., 31 May 2019 |
Cells 2020, 9(1), 228
Camacho-Pereira et al., 2016, Cell Metabolism 23, 1127–1139
Sci. Signal. 10, eaal3024 (2017) 17 October 2017
November 2011 Pharmacological reviews 64(1):166-87
Sirtuins are protein deacetylases with multiple isoforms active in the nucleus, cytosol and mitochondria all serving unique functions and requiring NAD+. These sirtuins function to condense chromatin and yet protein abundance has less to do with potency than does the availability of NAD+ which can be synthesized from multiple routes. Furthermore, SIRT1 has been associated with antagonizing age-related decreases in the amplitudes of the SCN output obtaining age-linked differentiating phases of increases and decreases observed within a circadian cycle..
References:
Int J Mol Sci. 2019 Mar; 20(5): 1223.
PLOS One November 25, 2014 https://doi.org/10.1371/journal.pone.0113939
Circ Res. 2018 Sep 14; 123(7): 868–885
It is proposed that the endocrine hormone melatonin may regulate after its synthesis and secretion from the pineal gland, the deacetylase acivity of Sirtuin1 to diminish the SASP repertoire of aging and may be linked to common morbidity of pathophysiology linked to COPD and generic Respiratory Distress Syndrome (RDS)presentation.
Papers of Record in this episode
Int J Mol Sci. 2019 Mar; 20(5): 1223.
Int. J. Mol. Sci. 2014, 15, 16848-16884
International Immunopharmacology Volume 62, September 2018, Pages 23-28
Dr. Guerra temporally organizes the lecture series toward the dialectical event by mindfully schematizing the SASP , the triad of DNA Damage Repair (DDR)responses, transcriptionally activated pro-inflammatory cytokine mediated inflammation, and the pineal-endocrine hormone melatonin circadian clock manifestations in the biochemistry and physiology of the aging human.
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Lipids, proteins carbohydrates and nucleotides-may function within an inflammatory and secretory modality. Thus, the SASP-Senescence-Associated Secretory Phenotype might deliver apoptosis, necroptosis, autophagy, oncogenesis or an extended senescence sequalae.
An Authentic Biochemistry audio lecture podcast by Dr. Daniel J. Guerra. 04 October 2020.
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Nature Reviews | Cancer Reviews 19 | AUGUST 2019 :pp. 439
Nature Communications Vol. 9, Article number: 1228 (2018) doi:10.1038/s41467-018-03566-5
Front. Genet., 12 March 2015 https://doi.org/10.3389/fgene.2015.00094
A take-home message from this research may be that the immunosenescent phenotype in the elderly, while associated with an increased rate of infections and a diminished effect of vaccines, and increased cancer susceptibility may be promoted by cancer and /or chemotherapy to cure the cancer. Both cancer and chemotherapy contribute to immune compromise and potential for gene mutations and epigenetic phenomena.
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The human body is tempered by cellular fate paradigms that include senescence vs. proliferation during aging. A corruption in the senescnce associated secretory phenotype may be a proximal tareget to reduce aging morbidity but does it not open the door to oncogenesis and the potential for autoimmune disease?
Comput Struct Biotechnol J. 2019; 17: 1151–1161
Nat Med. 2017 Jun; 23(6): 775–781
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Dr Guerra continues his associative pathobiochemical dialectic concerning T lymphocytte differentaition and senescence
The Th and Tc populations following uptake and processing of an antigen by an APC such as a dendritic cell is presented either to the CD8 population in the context of MHC-I or to the CD4 subpopulation in the context of MHC-II generates a cascading set of cellular lymphoproliferative and differentiative steps initiated under the inductive influence of cytokines that ultimately determine effector functions.
Papers examined in this episode:
Nat Med. 2017 Jun; 23(6): 775–781
Cancer Genet Cytogenet. 1999 Mar;109(2):108-13.
BMC Cancer volume 20, Article number: 882 (2020)
Dr Guerra swings hard at Treg and naive CD4+/CD8+ lymphocytes in immunosenescence and the potential for infection with aging while accumulating T memory cell lineages confined to antigen./pathogen exposure including vaccine-associated immunizations.
Newe paper disussed today: .Brain Behav Immun 2018 Oct; 73: 546–549.doi: 10.1016/j.bbi.2018.06.019. Epub 2018 Jun 22.
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1. Age -associated Immunosenescence is sometimes treated as synonymous with immune insufficiency, resulting in enhanced random infections and reduced vaccine immunity, and tumor surveillance
2. Self-reactive immune responses are elevated in the elderly, which is a result of inflammaging, a chronic, low-grade, systemic pro-inflammatory phenotype in the absence of acute infection
3. Immunosenescence and inflammaging are pathophysiological, and can be the immune poise for hyperinflammation and autoimmune disease in the elderly, leading to severe morbidity and increased mortality.
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Cellular senescence is a physiological process with genetic determinants and external modififiersincluding stress, nutrition and cell fate reprogramming including autophagy and apoptosis.
Human aging is a lifelong teleological process that includes the specifics of cellular senescence plus an underdefined terminus that tracks chronological longevity and occurs in all systems including musculature, solid organs, the PNS and the CNS
Aging is at the organismal level and is inevitable with increasing morbidity with or without definable etiological agency and the end is always death.
This is in contrast to senescence, which is variable , tissue specific and both plastic and elastic relative to short but stochastic progress that presents with intervals of remission and progression without a necessary uniformity of morbidity or coordinated coincidental death.
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Dr Guerra discusses the Glucocorticoid-induced tumour necrosis factor receptor-related protein (GITR) and its role in stabilizing T Regulatory cell populations relative to T memory cells and T effector Cells in healthy and End-Stage Renal Disease patients of differing chronological age.
This plank is laid down to form the final structural foundations that allow us to examine dialectically, the role(s) of the Immune system on aging and the chronic and auto-immune diseases of the elderly. Published 08 September 2020 by DJGPhD.
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Dr Guerra builds the foundation for transcription factor and epigenetic regulation of Treg cell differentiation in counterbalance to ILC's and T effector lymphocyte populations. Published 01 September 2020.
Dr. Daniel Guerra recombines the discussions of pharmacotherapeutic inhibition of prenylation in T cell activation and the failure of the NF-Kappa B pathway in estrogen receptor associated breast cancer and the lymphoproliferative lymphomas and leukemias with aging and neurodegeneration. PUblished 24 August 2020.
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Dr Guerra discusses the induction of transcription factor SREBP in activated T lymphocytes and the regulation of cellular translocation from the ER to the Golgi to the nucleus for the induction of prenyl and acyl lipogenesis, Published 18 August 2020 by Dr Daniel J. Guerra.
Review of: Front. Pharmacol., 17 March 2020. https://doi.org/10.3389/fphar.2020.00265
In this segment I discuss the phenomenon of DNA and genomic instability and the DNA repair systems implemented as mechanisms to drive cellular longevity . 06 August 2020 .
Programmed Cell Death is a classical cell fate that occurs during embryonic development, tissue repair and both leucocyte and lymphocyte turnover. Various subforms of apoptosis ( classical, necroptosis and ferroptosis) are also involved during infection, genotoxicity, oncogenesis and aging. Published By Dr Guerra 05 August 2020. Subscribe to the podcast! Contribute on Patreon!
Dr Guerra discusses the cancer marker gene mKI67 and its turnover linked to predisposition to euchromatin formation and the progression toward a senescent phenotype. Published 04 August 2020.
The mevalonic acid biosynthetic pathway maintains canonical cell activation triggers that link intermediary metabolism to T lymphocyte differentiation. 02 August 2020
The master regulator of protein translation, mTORC, is itself regulated by the stress-induced AMPK pathway. Rapamycin and semi-selective drugs regulating AMPK may reduce glioblastoma progression and this observation helps to advance a theory for healthy longevity that requires a reduction in anabolism. By Dr Daniel J. Guerra. Published 01 August 2020
In this lecture I gather some of the notable molecular components of age-related decline and the contrarion opposition imposed by cell proliferation. Published 30 July 2020. DJGPhD.
Dr Dan Guerra examines nutritional restriction and exercise in combination with anti-diabetic drugs to impact the aging process. Published 27 July 2020.
Dr Guerra explains chain initiation, propagation and termination during lipid oxidation and the REDOX reactions of the electron transport chain as a lead in to enzymatic oxidations and the plasticity of immune linked senescence. 26 July 2020.
Dr Guerra lays out the reduction of molecular oxygen to water and the accumulation of intermediate free radical oxygen species that are reduced via enzymatic activity and anti=oxidants. Aging is related to the auto-oxidation of nucleic acids, protein and significantly, membrane unsaturated molecular species of lipids. 24 July 2020
Dr Guerra explains how mutations in the glycolytic enzyme, pyruvate kinase, may lead to histone phosphorylation and the florid production of pro-oncogenic events. 24 July 2020.
Dr. Guerra delivers lecture 2 on human aging with a walk on the other side of cell fate:-pathobiochemical immortalization during oncogenesis. Published 21 July 2020
Today I start this robust examination of human aging from the fundamentals of life span and the molecular events that mediate the rate of senescence. This is Part One.
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The synthesis of protease-mediated hyper inflammation in pre-morbid respiratory distress pathobiochemical states linked to coronavirus transmission . How COPD and ARDS in association with cardiovascular disease, diabetes and lung dysfunction pre-dispose to viral infection and illness. Published 11 July 2020.
Airway passage disease has been well characterized in cystic fibrosis and this research which involves both clinical and animal model systems can inform general respiratory distress syndrome and viral pneumonia as that ascribed to the coronavirus 19. Published 10 July 2020
Dr Guerra presents his existential view on the purposive avoidance in science to admit the significance of belief in the knowledge paradigm. 09 July 2020.
Dr Guerra recaps protease mechanisms and zymogen activation ultimately linking serpin mediation of neutrophil elastase during coronavirus infection. Published 08 July 2020
Dr Guerra presents how a protease inhibitor protects a serine protease that is linked to ovarian cancer progression plus how protease inhibitor polymerization overloads the Endoplasmic Reticulum Associated Degradation pathway and Unfolded Protein Response to induce autophagy-linked Hepatocellular Carcinoma. Finally, a mechanistic step-wise summary of the serine protease catalytic triad is presented. Published 03 July 2020.
Far from becoming monomeric and unimodal in effect, the anti-trypsin protease inhibitor functions to modulate the transcriptome and proteome of induced pro-inflammatory responses in both systemic and tumor microenvironments. Dr Dan Guerra 30 June 2020
Dr Guerra targets his lecture on protease inhibitors as positive acute phase proteins serving a modality of repression against proteolytic degradation processes as induced by the pro-inflammatory cytokine mediated hyper-immune response. Published 29 June 2020.
In this session Dr Guerra discusses the physiological and pathophysiological roles of serine protease inhibitors (SERPINS). For example, the physiological role of plasminogen activator inhibitor 1 (PAI-1) involves control over fibrinolysis which is an essential hemostatic mechanism for regulating the dissolution of fibrin clots associated with airway passage remodeling systemic wound repair, and the inflammatory response as linked to cytokine mediated immune responses and circulating t-PA mediated cardiovascular function.
Dr Guerra also mentioned that he has established a PATREON site:
Lease strongly consider recombining with the Patreon link as a means to provide monetary donations to the Authentic Biochemistry Podcast and YouTube lecture series plus the VerEvMed Facebook postings that include Authentic Biochemistry "Minutes" and some original (North)Western philosophy, courtesy of Dr Guerra and his existentialist individualism.
In this Lecture I define and then implement a dialectical approach to biomedical scientific research methods that involves event ontologies relative to a non-paradoxical understanding of cancer pathobiochemistry. Published 19 June 2020 by Dr Daniel Guerra
Dr. Dan Guerra apprehends several research publications going back to 2012 and proceeding through 2019 in a synthesis of oppostional logic and the published scientific evidence to explain the mediation of metabolic zonation, transcriptional control, and bioenergetcs using PEDF to mitigate cancer progression.
A brief concluding lecture on the linkage of obesity with Type 2 diabetes plus a clinical case study discussion and review question of a mis-diagnosis via anchoring.
Dr Guerra lays out the prodromal manifestations of metabolic syndrome and insulin resitance that can lead to Type 2 diabetes in the obese sedentary aging population.
Dr Guerra lays down the basics of bioenergetics and the roles of carbohydrate and lipid metabolism in the obese state leading to type 2 diabetes and the pathophysiological sequalae in chronic disease. 25 May 2020b.
Dr Guerra reminds his audience that obesity is the global health pandemic of a generation and that it leads to multiple high mortality diseases associated with a corruption in lipid metabolism, both innate and acquired immunity and associated cancer and cardiovascular disorders. Because obesity sets as a precondition and continued distress to human health and well-being, the predisposition to a constellation of diseases both infectious and non-infectious is obtained. Recorded and produced on 25 May 2020 by Dr Daniel J. Guerra
Dr Guerra provides the basic detail necessary to prepare one for our future examination of the current peer-reviewed literature involving hormonal control over health , infection and inflammation via the immune system.
Dr Guerra discusses hormonal ontology via receptor -binding mechanisms plus the cascade of the hypothalamic-pituitary axis.
Dr Guerra gives a fast paced knowledge-laden series of lectures on the medical physiological and biochemical features of human hormonal signaling. Lecture I Introduction and Classification. Published on line 04 May 2020
Dr Guerra opens up the refereed published scientific literature to provide verified evidence associated with the arcuate nucleus of the hypothalamic arc leading to hormonal control over nutrition and the immune system. Published 28 April 2020
Patho-Biochemical Pathways in CNS-Endocrine Organs with a special emphasis on sphingomyelin phosphodiesterases in the HPA axis of the CNS and Beta hemolysins as virulence factors from the human bacterial pathogen, Staphylococcus aureus. Dr Daniel J Guerra published on 27 April 2020.
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Dr Guerra delivers his third informed discussion of Membrane lipid raft biology and the role of Sphingolipids in mediating an immune response that results in massive tissue damage and poor disease outcome. Published 11 April 2020
In this audio lecture presentation, Dr Guerra gives an aggregated explanation for the association of subcellular biochemical metabolism of sphingolipids via the target of Cationic Amphipathic Drugs such as SSRI's in altering cell fate from programmed cell death to tissue preserving autophagy. Published 11 April 2020.
Dr Guerra uses the Dialectical Method via the Logical Square of Opposition combined with an analysis of the current biomedical evidence associated with the COVID 19 corona virus to obtain validated conclusions. 23 March 2020.
In this third segment on the grounding of Natural Science and the world View it advances, Dr Dan Guerra introduces the endojective perspective for space-time and the foundation of knowledge toward the representation of phenomena as pattern recognition from a possibilistic metaphysical landscape via freely chosen inductive reasoning in an ultimately uncertain universe. Published 20 March 2020.
In this second philosophical segment, Dr. Guerra introduces space-time as a physical manifestation of the synthetic a priori of Phenomenological Metaphysics as he draws inferences from pre-Socratic concepts of vortices and co-mingles these ideas with Clerk Maxwell's explanation of the electromagnetic theory and quantifiable resolution for the velocity of light. Published on the IDES of March 2020.
In this first segment of a three part series, Dr Guerra sets out to ground his scientific principles with an a priori epistemological reasoning that leads to the transcendental method for instantiating metaphysics to perform biochemical, genetic and physiological research. Recorded 11 March 2020.
Dr Guerra explains how there is a cumulative balance between S1P and Ceramide will influence apoptosis and change the regulation of autophagy by the complex interplay between mTOR, beclin, and Bcl-2 where S1P-dependent autophagy is thought to be a homeostatic, pro-survival response involved in the clearance of intra-cellular debris.Describing these systems within the context of inflammation and pathobiochemistry will be obtained.
Today's podcast establishes the significance of sphingolipids in maintaining normal biochemical and physiological homeostasis by detailing membrane organization of pathways and linkage to cell fate and the potential for pathobiology in human disease. Published 03 March 2020 by Daniel J. Guerra, PhD
Dr. Dan Guerra discusses a new publication reviewing the process of resident pulmonary macrophages and innate lymphoid cells in disease with attention to pathogen activation and hyperinflammation as potentiated by co-morbidities leading to poor clinical outcome. 01 March 2020
Dr Dan Guerra recombines Coronavirus with Ceramide linked Neurological Disease and the Pro-Inflammatory Response. 28 February 2020.
In this Authentic Biochemistry Podcast, Dr. Dan Guerra explains the roles of acid sphingomyelinases and associated ceramide production on the NLRP3 inflammasome activation as linked to coronavirus pathogen molecular patterns and the production of proinflammatory cytokines 19 February 2020.
Dr. Guerra discusses a published NEJM paper from late January (2020) that details the initial epidemiology of the novel Coronavirus from China and gives an insight on how sphingolipid metabolism may be a potential pharmacotherapeutic target. Podcast Published 03 February 2020.
Dr Guerra of Authentic Biochemistry starts his lecture series on the current disease-causing Coronavirus from China. This first segment gives detail on the basics of molecular arrangement, replication, intracellular trafficking through the ER-Golgi and ultimate virion transmission with some medical-historical references to the more common animal Nidovirales/Coronavirales and the previous human outbreaks of related SARS and MERS CoV. Please visit https://www.facebook.com/danguerra00 and contribute to our Authentic Biochemistry Fundraiser! Also, subscribe to the Podcast!
Professor Guerra arrives at the functionality of autophagy and bioenergetic coupling via chemokine and cytokine signalling through antigen presenting cell population mediated germ center secondary lymphoid organ resident B cell somatic hypermutation via T follicular-helper cell activation thus evincing the autoimmune paradigmatic disease system lupus erythematosus. 28 January 2020.
Authentic Biochemistry's Dr Dan Guerra gathers published biomedical literature to offer mechanisms and means for sphingolipids and amino acids to make a pathobiochemical donation to immunoepigenomic neurodegenerative disease. 21 January 2020.
19 January 2020. This is a podcast delivering Part 3 in my new arc describing the significance of biochemical and epigenetic reprogramming of T lymphocytes in human autoimmune disease. Parts 1&2 of this series are found as video lectures at https://www.youtube.com/playlist?list=UUcEoA2N9WSlNvDk1BtuznfQ. Dr Daniel J. Guerra of VerEvMed and Authentic Biochemistry.
Dr Guerra investigates T and B cell mediated autoimmune induction in this critical podcast lecture before the full analysis of these destructive human diseases are authentically examined in the peer-reviewed biomedical literature.
As it turns out, autoimmune bacterial epitope mimicry can play a crucial role in autoimmune primary biliary cholangitis and may correlate to major human disorders such as lupus . Prof. Guerra examines a series of papers from the primary literature to focus attenuation on T cell sub-population differentiating dynamics production.related to Plasma cell IgG
T Lymphocyte communication with antigen presenting innate immune cells coupled with B cell activation may be regulated by a glycoprotein that links to discrete glycosylation patterns on membrane polypeptide domains
The epigenetic control over gene expression via transcriptional and post-transcriptional molecular interactions through time including interfering RNA and covalent modification of chromatin results in enivonmental, nutritional and age-related phenotypes . In this episode of Authentic Biochemistry, Dr. Guerra starts investigating the molecular mechanisms employed.
Professor Guerra begins an arc of lectures on the molecular events that describe the covalent modification and temporal variation of gene expression collectively called epigenetics.
Prof Guerra gives a brief examination of Leptin -associated cancers. 15 October 2019
Dr Guerra discusses the intricate roles of Leptin and its receptor in various human diseases. 10 October. 2019
Dr Guerra of Authentic Biochemistry provides his third discussion of adipokine-mediated control over obesity and associated disease from animal models to clinical disease. 02 October 2019.
Dr Dan Guerra pursues how Leptin and POMC regulate neuroendocrine and neuro-appetitive behaviours that link obesity and associated metabolic and life-style disease with the dysregulation of energy homeostasis
Dr. Guerra of Authentic Biochemistry and the VerEvMed YouTube channel provides critical in-depth neuro-anatomical and HPA axial complicity in Leptin Signaling from the Adipose to the stress- and basal regulation of human physiological responsiveness. 22 September 2019
In this Authentic Biochemistry Podcast Episode Prof. Guerra describes the specific metabolism of very long chain polyunsaturated fatty acids from essential dietary precursors of both the Omega 6 and Omega 3 series and associates these pathways with a recent 2019 publication that provides evidence for Omega 3 fatty acid inhibition of adipose stem cell associated IL17a proinflammatory cytokine transcription thus inhibiting obese adipose inflammation. 08 September 2019.
Authentic Biochemistry's Dr Daniel Guerra implements his keen understanding of lipid metabolism to uncover the network of cellular, subcellular and pathway domains regulating fatty acid oxygenation and both glycerol-and sphingosine- lipid signaling that function to mediate cell fate and the inflammatory response in relation to dietary omega three fatty acid. 04 Sept 2019.
Dr. Guerra of Authentic Biochemistry discusses a current published paper that shows how DHA and EPA derived from dietary alpha linolenic acid (18:3 cis d 9,12,15) correlates with a decrease in the production of the pro-inflammatory cytokine, IL17-A in a model system composed of obese adipose stem cell populations.
This is volume VI of the Tregs lecture narrative in which Dr. Guerra provides an introduction to a Diaeventontological process for navigating the labyrinth of T cell biochemistry. Published 17 August 2019. Authentic Biochemistry Podcast.
Treg and Th cells are under transcriptional modulation via cytokine mediated control of a Nfil3 protein that serves to block FOXp3 expression.DR Guerra verifies the evidence in the data from a recent paper: Experimental & Molecular Medicine volume 51, Article number: 80 (2019) that demonstrated Inhibition of the TGF-β signaling pathway led to increased Nfil3 expression which blocked Foxp3 transcription via SMAD3.
This is an important contribution to the T lymphocyte literature as it points to the proximal and distal modulation of T cell lineage differentiation, thus focusing attention to potential pharmacotherapeutic and immunoepigenetic mechanisms to control inflammation in diseases such as IBD while simultaneously suggesting strategies to reorganize the T cell profile to destroy tumors.
Dr Daniel J Guerra, Authentic Biochemistry. 17 August 2019.
Prof. Guerra provides a narrative focusing on evolutionary perspectives and the resultant lymphocyte differentiating foundations for the adaptive immune response as a means to apprehend the event-ontological diverse transcriptional mediation ultimately landing on the Treg FOXp3 promoter . Part IV
In this Authentic Biochemistry episode Dr Guerra unfolds the complex transcription factor and membrane & nuclear- receptor repertoire associated cytokine and chemokine axis activating and maintaining Treg cell differentiation to mediate the Th pro- inflammatory response
Dr Dan Guerra presents "T regulatory Cells in Human Biology and Disease. An update on transcriptional control". Vol.I. This first segment introduces the elaborate nature of innate and acquired lymphoid cells and the transcription factors that drive lineage differentiation.
This is a brief introduction to what will be a multi-segmented sequence of podcasts on the complexity of T cell mediated immunity and its native regulation via Treg activation.
In this podcast, Authentic Biochemistry's own Dr. Dan Guerra ties the actuated Moebius strip of anti-apoptosis rendered neuronal differentiation amidst a tempest of ceramide synthetic possibility.
Dr Guerra of Authentic Biochemistry navigates through the protease inhibitor literature and starts a journey into hepatitis C virus (HCV)-mediated HCC induction and some of the pharmacotherapies impacting this axis.
Dr. Guerra focuses on emerging signaling and immunoepigenetic variations around the theme of protease inhibitor mediation of various stages and forms of solid organ and metastatic tumorigenesis in this June 29,2019 installment of Authentic Biochemistry.
Dr Dan Guerra reveals that serine protease inhibitors (Serpins) are endogenous proteins that block protease-mediated metastasis and cancer associated fibroblast activation in some tumor microenvironments but not all. The myriad 'labyrinth' interactions among cytokines , proteases, protease inhibitors and the dysregulation of the T-lymphocytic immune response obtains a confounding pharmacotherapeutic anisotropy.
Dr.Guerra of Authentic Biochemistry provides a primer on polypeptide proteases and their mode of action as well as their control via processing and inhibition in clinical medicine
Serine proteinases and their peptide inhibitors, the SERPINS, have a role to play in liver pathology and disease potentiation leading to subcellular protein aggregation, enhanced inflammation and ultimate hepatocellular carcinoma. Dr. Guerra of Authentic Biochemistry introduces this new plank in the knowledge platform being constructed to apprehend either the necessary or sufficient conditions in HCC.
In this segment I provide more discussion of the published evidence linking glycolytic pathway enzymes to HCC progression. The expression of certain interfering RNA's that differentially regulate gene expression and promoter habilitation can lead to cyclin dependent kinase mediated chromatin remodeling enhancing cell -specific expression of enzyme isoforms that promote rather than defeat disease progression.
Dr. Guerra of Authentic Biochemistry continues with the 4th in a series of HCC lectures from the primary research literature by explaining the interacting roles of pyruvate kinase M2 and phosphofructokinase 2 promote aerobic glycolysis-enhancing cancer progression.
Authentic Biochemistry's host, Dr Dan Guerra, continues his in depth cellular and molecular discussion of hepatocellular carcinoma (HCC) by introducing the non-universal yet a priori role for the glycolytic enzyme pyruvate kinase isoform M2 in paradigmatic tumor associated aerobic glycolysis.
Dr Guerra takes a deeper dive into the hormonal and subcellular dysfunctional arrays linking obesity to Non-alcoholic Steatohepatitis (NASH) and Hepatocellular Carcinoma
This is Part One of what will be a 3-5 part sequence of podcast lectures giving Authentic Biochemical discussion concerning the links between obesity , sedentary lifestyle, alcohol consumption and inflammatory diseases of the liver that may lead to the high mortality cancer, Hepatocellular Carcinoma.
Because HDAC4 closely resembles the structural component of the superfamily of histone deacetylases, in might be assumed it functions to catalyze the removal of LYS bound acetate. But since HDAC4 does not contain the catalytically necessary TYR-OH but rather an HIS-imidizole it has no deacetylase enzymatic activity. However HDAC4 does interact with other proteins and the net result is protective of skeletal muscle atrophy and motor neuron degeneration in a murine mutant human SOD1 model of Amyotrophic Lateral Sclerosis (ALS). This Authentic Biochemistry podcast episode reveals once again that specificity in time and space with coordinated expression of biochemical species will be more complicated than previously reported once a sharper lens is used to examine the disease pathology at the biochemical/molecular level.
Dr Daniel Guerra or VerEvMed and AB podcast provides the second part of his discussion concerning excitotoxic glutamate inducing aSMASE mediated neurodegeneration involving iron and the depletion of the glutathione-ROS- scavenging system in damaged and diseased oligodendrocytes. 25March2019B
This is the first part of a diaeventontological framing of lipid peroxidative mechanisms for CNS neurodegeneration. Dr Guerra describes recent published research (JLR 2018 .59:312pp.) and develops some of the key elements of the ferroptosis programmed cell death mechanism leading to oligodendrocyte and neuronal degeneration that will participate in a grander understanding of injury-induced and idiotypic age-associated disease in the CNS. 25 March 2019.
In this podcast, Dr Daniel Guerra of Authentic Biochemistry and VerEvMed endeavours to examine the bioenergetic and pro-inflammatory prodromal patho-biochemistry of age-onset Alzheimer's Disease using his diaeventontological toolkit.
Dr. Daniel J. Guerra introduces his paradigmatic shift for understanding biochemical phenomena as prolegomena to understanding Alzheimer's Disease.
Dr Daniel Guerra of Authentic Biochemistry in his initial podcast introducing the show and starting off with initial content on current Alzheimer's Disease research
En liten tjänst av I'm With Friends. Finns även på engelska.