Authentic Biochemistry

Dr Daniel J. Guerra

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Nov 9, 2021 · 29 min
Fine detail of Treg cell control over inflammation suppression via FoxP3 transcriptional modulation. Aging and Obesity will limit this control leading to hyperinflammation. DJGPhD. 08Nov2021
References Front. Immunol., 29 June 2012 J Immunol 2016;197:3762-3770 Front. Immunol., 03 February 2020
Oct 27, 2021 · 29 min
T cell receptor signaling kinase dynamics after APC activation. Co-activating CD28 becomes deficient via immunosenescence thus corrupting T cell efficiency in the elderly. 26.10.2021 DJGPhD.
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
Oct 22, 2021 · 29 min
Indeed oxysterol LDL , circulating hepatic-derived convertase, T lymphocyte differentiation and macrophage to foam cell degeneration obtain the aging cardiovascular/pulmonary pathophysiological state.
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
Oct 20, 2021 · 29 min
How Oxysterol LDL associates with macrophage and T lymphocyte infiltration during aging to generate the hyperinflammatory atherosclerotic plaque. DJGPhD. 19.10.21. Authentic Biochemistry.
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
Oct 16, 2021 · 29 min
Aging results in corruption of T lymphocyte differentiation associated with chromatin instability and epithelial to mesenchymal transitions leading to the pre-cancerous state. DJGPhD 16.10.21
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.
Oct 14, 2021 · 29 min
Lymphocyte maturation and the special Innate like Lymphocyte Subclass including Natural Killer and other ILC lineages. DJGPhD.14.10.21. Authentic Biochemistry
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)
Oct 5, 2021 · 30 min
Immunosenescence and Inflammaging via thymic Involution and comorbid pathophysiology of obesity and aging present a chronic inflammatory phenotype prone to morbidity. DJGPhD. Oct.04,2021. Authentic BC
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
Oct 4, 2021 · 29 min
Natural cytotoxicity receptors (NCR's) within group 3 innate lymphoid cells (ILC3): an association of transcription factors in IBD's and aging. DJGPhD. 03.10.21 Authentic Biochemistry.
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
Sep 29, 2021 · 29 min
Omega three fatty acids and PE N-methyl transferase are associated with methylation and acetylation patterning in NK cells via AMPK and stress.DJGPhD. 29 September 2021.
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
Sep 28, 2021 · 29 min
Natural Killer Cell switching via demethylation of Histone 3 LYS may correlate with the human aging phenotypic hyper-inflammatory state. DJGPhD. 28.9.21
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
Sep 28, 2021 · 30 min
The Genome and the Immunoepigenome interact across a three-way trigonal planar field with the Environment to Obtain the Aging Phenomena. DJGPhD.27.9.21
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
Sep 26, 2021 · 29 min
Natural Killer cells and the epigenomics of gene expression: implications for the aging -senescent human. DJGPhD. 26 .9.21. Authentic Biochemistry
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
Sep 24, 2021 · 28 min
REDOX Biochemistry Primer . DJGPhD Authentic Biochemistry . 24.9.21
Oxidases, dehydrogenases and oxygenases in the electron transport chain et al.
Sep 23, 2021 · 5 min
Video Lecture Announcement. Please Listen to this audio! Grazie, Dr. Daniel J. Guerra 22.9.21
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!
Sep 22, 2021 · 30 min
The Interferon I role in autoimmune disease and the corruption of mechanisms that lead to age-related morbidity and mortality.DJGPhD. 22.9.21
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.
Sep 20, 2021 · 30 min
The Aging Immune Response and Cellular Differentiation are characterized by Apoptosis vs. Necroptosis Mechanisms. DJGPhD. 20.9.21.Authentic Biochemistry Productions.
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.
Sep 19, 2021 · 29 min
Semaphorin works through mToR and thus the abl and AKT kinases in Macrophage reverse switching from lipogenesis to fatty acid oxidation. DJGPhD 18.9.21.
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
Sep 18, 2021 · 29 min
Macrophage and T lymphocyte Inclusion to the Aging Human Pathobiochemical Phenotype. DJGPhD.Authentic Biochemistry 18.9.21
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
Sep 17, 2021 · 2 min
Invitation to Watch my Youtube lecture I on the Aging Human Dialectic. Link found in the show notes. DJGPhD 16.9.21
https://youtu.be/4sW-BNVhzrs
Sep 13, 2021 · 29 min
Membrane Biochemistry Primer and Introduction to Aging. Dr. Daniel J. Guerra. Authentic Biochemistry Productions. 13.9.21
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)