Authentic Biochemistry

Eur J Endocrinol. 2017 176(5): R235–R246 Molecular Cell Volume 81, Issue 18, 16 September 2021, Pages 3677-3690 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

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 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

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 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

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 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

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 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

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 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

Age Ageing, Volume 48, Issue 6, November 2019, Pages 776–782 Biomedicines. 2020 Aug 6;8(8):277 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

Dr. Guerra authentically arrives at the inveighing cancer paradigm contribution to the sickness unto death. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

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 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

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 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

References Front. Immunol., 29 June 2012  J Immunol 2016;197:3762-3770 Front. Immunol., 03 February 2020 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

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 --- Send in a voice message: https://anchor.fm/dr-daniel-j

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 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

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 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

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. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

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) --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

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 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

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 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

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

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 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message