Authentic Biochemistry

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 i...

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 D...

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 poten...

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. Subscribe to my Podcast and donate! Published by Dr Daniel J Guerra, Authentic Biochemistry 09 Novemb...

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 transcrip...

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 bin...

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...

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) . melatoni...

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...

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 se...

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  antagoni...

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...

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. Please...

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. Please SUBSCRIBE , check...

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...

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 Support...

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 lymphoproli...

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. PLeasse donate to Authentic Bioc...

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. Immunosene...

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,...

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 rol...

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. Please join our Patreon and contribute to Authentic Biochemistry today!