Authentic Biochemistry

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 neurops...

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...

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 proce...

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 ST...

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 Dysfunc...

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...

• 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. d...

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 t...

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 o...

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...

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 di...

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 phosphorylat...

 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 r...

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 fla...

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...

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...

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...

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...

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 stimulatio...

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 mechan...

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 cellula...

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 Cel...

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 fa...

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 vol...