The Fractalkine/CX3CR1 System Regulates β Cell Function and Insulin Secretion

2 – Retrieved from https://www.cell.com/fulltext/S0092-8674(13)00287-0

Neuroimmune Reactions, Mental Heath & Neurodegenerative Disorders

Metal-based Toxicity

Researchers at Gladstone Institute, have found that calm reduces levels of the protein tau, which is  known for its role in Alzheimer’s disease and other neurodegenerative  conditions, changes excitatory and inhibitory cells in ways that make it  harder for the brain to burst with overexcitation. It also promotes the maintain balance in the brain. Previously they showed in mouse models that reducing tau levels makes the brain more resistant to epilepsy of diverse causes. [Retrieved form https://www.sciencedaily.com/releases/2021/10/211019223309.htm].

” Retrieved from https://www.ncbi.nlm.nih.gov/gene/2904;  https://www.medicalnewstoday.com/articles/260649#link;  https://ww.eurekalert.org/news-releases/675909#.YTTkWdpAnSc.twitter; https://medcraveonline.com/MOJPB/dna-the-phantom-effect-quantum-hologram-and-the-etheric-body;html?fbclid=IwAR199BUqYjWCvNGq2GCgdzl3d0n_lVzu_6na4KVVcYVuBzk-JeiM-CgRyDQ;

• GenBank

Cell–cell interactions (CCIs) are physical interactions  between two or more  cells, which can be mediated by proteins, ligands,  sugars or other  biomolecules. Protein–protein interactions (PPIs) are  physical interaction between two proteins,  often involved in  structural systems, signal transduction or metabolic  processes. Differentially Expressed Genes  are identified as more highly (or lowly)  expressed in one condition  versus the other after comparison of their  expression values between  two conditions. Genes with restricted, constitutive or  unusual pattern of expression are quantified accordingly to their  characteristics to avoid  miscalculation or underestimation of signals.  Operational taxonomic unit—a  definition used to classify groups of closely related organisms. DNA  sequences  can be clustered according to their similarity to one another,  and  operational taxonomic units are defined based on the similarity threshold (usually 97% similarity) set by the researcher. Biomolecules or biological molecule, any of numerous substances that are produced by cells and living organisms. (Retrieved  from https://www.hindawi.com/journals/ijg/2003/393029/; https://www.nature.com/articles/s41576-020-00292-x#Sec22)

Note: Iron molecules are found in a variety of different chemical environments in biology. In addition, iron biomolecules can be divided into those which  utilise iron to effect a biological function (02 transport, electron  shuttling, etc.) and those which transport and store iron. With regards to Parkinson’s Disease, one of the targets that LRRK2 regulates is called Rab8a, a protein  which, along with many others of the Rab family, helps control the  movement or “trafficking” of a wide variety of cellular vesicles  (vesicle is a structure within or outside a cell, membrane-bound subcellular compartments). [Retrieved from https://neurosciencenews.com/parkinsons-diseaseiron-19808/].

Nerve cells in the human brain talk to one another at sites called  synapses, where molecules are released to signal to the next cell. When  people learn or remember things, this signalling is strengthened. When  communication between synapses goes wrong, circuits become broken. The function of nerve cells and synapses depends on proteins that are  made using information encoded in genetic material called RNA. It is  thought that RNAs are located exactly where and when they are needed for  synaptic signalling because some kind of synaptic ‘tag’ labels the  correct active synapse.  Scientists have recently learned that RNA can have a methyl  group/molecule added to one of the RNA bases, which ‘marks’ the RNA  message. Such adding of methyl groups can influence proteins binding to  DNA or RNA and consequently stop proteins being produced.

A new study shows that RNA marking can be reversed at synapses and hence may  act as a ‘synaptic tag’. Synaptic tagging allows the synapse, rather than the nucleus, to be the unit of long-lasting neuronal plasticity. The findings suggest, that if disrupted, this  could cause synapses and nerve cells to malfunction by influencing the  formation of toxic protein clumps [causing brain injury (deficits) such in the case of  Long-Term Potentiation (LTP) and long-term memory (LTM) encoding needed for learning.

The genomic mechanisms involve methyl groups being put on RNA messages  and importantly taken off when a synapse is active. The implications  are very important for normal brain function, but also for reversible  psychiatric mental conditions such as anxiety and addiction disorders  and early-stage neurodegenerative diseases such as dementias.” [Retrieved from https://neurosciencenews.com/synapse-neurotransmission-19501/; https://www.frontiersin.org/articles/10.3389/fnhum.2013.00589/full?utm_source=newsletter&utm_medium=email&utm_campaign=Neuroscience-w41-2013].

Note: Iron is part of the Heme group which plays multiple roles in cellular processes. The strong affinity of heme toward oxygen makes it possible for hemoglobin and myoglobin,  two heme-containing proteins, to function as major oxygen transporters.  Heme also participates in respiration, sensing of diatomic gases, drug detoxification, signal transduction and regulation of transcription, translation, microRNA processing, mitochondrial protein  import, protein stability, and differentiation. While most cells  synthesize heme, differentiating erythrocytes represent the major site  of heme production in humans due to the synthesis of hemoglobin, which  accounts for 85% of the total heme. Malfunction of heme synthesis can lead to disorders such as anemia and porphyrias. [Retrieved from https://www.sciencedirect.com/topics/chemistry/heme].

Also, Note:  Studies have demonstrated that iron can regulate tau.This study examines the levels of total tau, hyperphosphorylation of tau, and SDS- and  β-mercaptoethanol-resistant high molecular weight tau (HMW-tau) in crude  extracts from gray and white matters of AD frontal lobes were analyzed by immuno-blots. They found the seeding potency is markedly higher in gray matter than in white matter such disease that includes Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), and other disease pathologies ..[Retrieved from https://pubmed.ncbi.nlm.nih.gov/33459649/; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108061/].

Iron  chelation therapy, either subcutaneous or orally administered, has been  used successfully in various clinical conditions. The removal of excess  iron from various tissues, e.g., the liver spleen, heart, and the  pituitary, in beta thalassemia patients, has become an essential therapy  to prolong life. More recently, the use of deferiprone to chelate iron  from various brain regions in Parkinson’s Disease and Friederich’s  Ataxia has yielded encouraging results, although the side effects, in  <2% of Parkinson’s Disease(PD) patients, have limited its long-term  use. A new class of hydroxpyridinones has recently been synthesised,  which showed no adverse effects in preliminary trials. A vital question  remaining is whether inflammation may influence chelation efficacy, with  a recent study suggesting that high levels of inflammation may diminish  the ability of the chelator to bind the excess iron. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789569/; https://pubmed.ncbi.nlm.nih.gov/33805195/; https://pubmed.ncbi.nlm.nih.gov/12127956/; https://www.verywellhealth.com/what-is-iron-chelation-4103177:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486448/;https://ashpublications.org/blood/article/116/21/2064/111868/Combination-of-Two-Orally-Active-Iron-Chelating].

Synergism

Synergism represents an efficient means of increasing the amplitude of cellular responses induced by low levels of stimulation. Recently, several kinetic and physicochemical models have been developed to describe and predict synergistic responses. Synergy mainly results from mutations in functionally related genes. In one study, on the etiology of the prevalent defects found with Antiphospholipid Syndrome (APS), a systemic autoimmune disease which has cognitive effects,  the synergism between aPL and anti-NMDA antibodies were explored and found a direct effect of anti-PL on neuronal cells. [Retrieved from https://pubmed.ncbi.nlm.nih.gov/19665253/;  https://www.frontiersin.org/articles/10.3389/fimmu.2016.00005/full]. Note: physicochemical models include physicochemical stress(es) comprises environmental factors in the form of  food/nutrition, noise, pollution, metabolic disorder, infection, and  inflammation. [Retrieved from https://www.frontiersin.org/research-topics/5755/stress-and-immunity].

In recent years, large genome-wide association studies have been  extremely helpful to identify new genetic risks of psychiatric diseases  (e.g. PTSD, SCZ, BP, MDD), and genetic overlapping risks among these  disorders and other medical diseases, and traits. A more comprehensive  understanding of the genetic overlapping among these disorders is needed  to clarify common pathways among diseases, or specific genes (see The Thymus below) uniquely  implicated in each disorder. [Retrieved from https://www.frontiersin.org/research-topics/15833/shared-genetic-risk-factors-among-psychiatric-diseases-and-other-medical-diseases-and-traits]

Biological scientists often want to determine whether two agents or   events, for example, extracellular stimuli and/or intracellular signaling pathways, act synergistically when eliciting a biological  response. Similarly, the nervous system is highly vulnerable to various internal and external  factors which could lead to acute or chronic neurodegeneration. The  morphological basis of dysfunction after injury involves loss of  integrity of the extracellular matrix, neuronal circuitry, and synaptic  activity and plasticity (see Thymus below).

“Light Of The Soul”

The primary injury  enables a huge variety of developmentally-related biomolecules (carbohydrates, lipids, nucleic acids, and proteins) to  stimulate the process of regeneration. Extracellular proteins, cell  adhesion molecules, neurotrophic factors as well as different organic  and inorganic compounds of the nervous tissue are necessary for recovery  after injury. However, the secondary injury as well as further  degeneration of the surrounding tissue, could be prevented by  reactivation and recruitment of a plethora of cell signals, such as  growth factors, neurotransmitters, extracellular matrix (see thymus below) proteases, cell  adhesion and recognition molecules (search  Agents for Metal-Based Drugs and Chelating  metal-based therapies for tauopathies for Neurodegenerative Diseases; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821171/). [Retrieved from https://www.frontiersin.org/research-topics/12990/morphogenic-cascades-underlying-regeneration-and-plasticity-after-nervous-system-injury; https://www.sciencedirect.com/science/article/abs/pii/S0022282898906551; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514778/].

One category of signaling cascade includes receptors to receive  signals, kinases (serine/threonine/tyrosine) that phosphorylate  proteins, adaptor proteins that bring kinases and substrates together,  and transcription factors that alter gene expression as a response to  stimuli.  Other signaling cascades depend on hormone signaling and their cognate receptors that function as transcriptional regulators. The pathways described here are a small example of how inter- and  intracellular signaling is important for development of an organism,  sustaining cellular homeostasis, and how aberrations in these pathways  can lead to disease. [Retrieved from https://www.sciencedirect.com/science/article/pii/B9780128179277000090].

Note: 15- PCSK6 Chromosome This gene encodes a member of the subtilisin-like proprotein convertase  family, which includes proteases that process protein and peptide  precursors trafficking through regulated or constitutive branches of the  secretory pathway. The encoded protein undergoes an initial  autocatalytic processing event in the ER to generate a heterodimer which  exits the ER and sorts to the trans-Golgi network where a second  autocatalytic event takes place and the catalytic activity is acquired.  The encoded protease is constitutively secreted into the extracellular  matrix and expressed in many tissues, including neuroendocrine, liver,  gut, and brain (see Thymus, Brain & Testes). This gene encodes one of the seven basic amino  acid-specific members which cleave their substrates at single or paired  basic residues. Some of its substrates include transforming growth  factor beta related proteins, proalbumin, and von Willebrand factor.  This gene is thought to play a role in tumor progression and left-right  patterning.

Likewise, 7- RELN This gene encodes a large secreted extracellular matrix protein thought  to control cell-cell interactions critical for cell positioning and  neuronal migration during brain development. This protein may be  involved in schizophrenia, autism, bipolar disorder, major depression  and in migration defects associated with temporal lobe epilepsy.  Mutations of this gene are associated with autosomal recessive  lissencephaly with cerebellar hypoplasia. Two transcript variants  encoding distinct forms have been identified for this gene. Other  transcript variants have been described, but their full-length nature has  not been determined. [Retrieved from https://www.ncbi.nlm.nih.gov/gene/5649].  Note: Cerebellar hypoplasia can sometimes present alongside hypoplasia of the corpus callosum or pons. [Retrieved from https://medlineplus.gov/genetics/condition/pontocerebellar-hypoplasia/].

A human with a particularly high measure of SPS is considered to have “hypersensitivity”, or be a highly sensitive person (HSP).[2][3]   See The Theory of Positive Disintegration- those with mental  issues as sick (neurosis, anxiety, etc. see original Dabrowski works for  an extensive list), the theory proposes that it is the very persons who  show those symptoms who have the highest potential for growth and personality development. The strengths of the TPD clearly lie in the  different view it gives of certain mental health symptoms. [Retrieved from https://www.frontiersin.org/articles/10.3389/fpsyg.2019.01291/full?fbclid=IwAR2MAZ7N-rhfJAV5DD2TmefvuDc8QBtOZs1_b9wFYSuh9rIPh9EiVVjUZSE].

GenBank Overview

What is GenBank?

GenBank ® is the NIH genetic sequence database, an annotated collection of all publicly available DNA sequences:

-Learning Disabilities: https://www.ncbi.nlm.nih.gov/gene/?term=Homo+sapies+learning+disabilities

Note: COMT- 22 Catechol-O-methyltransferase catalyzes the transfer of a methyl group  from S-adenosylmethionine to catecholamines, including the  neurotransmitters’ dopamine, epinephrine, and norepinephrine.  Furthermore, Catechol-O-methyltransferase (COMT-22), an enzyme that is involved in the degradation of catecholamine neurotransmitters  (e.g., dopamine, epinephrine, and norepinephrine), can affect executive  functions involved in cognitive flexibility, impulse control, abstract  thought, and the ability to follow instructions (1, 2, 3) -(COMT-22 also in addictions and ADHD below).

Note: 17- lNF1 provided by HGNC gene product appears to function as a negative regulator of the RAS signal transduction of the pathways that control such processes as actin cytoskeleton integrity, cell  proliferation, cell differentiation, cell adhesion, apoptosis, and cell  migration (Read About RAS and Cerebral Cortex  BELOW). The cytoskeleton provides structural integrity and determines localization of proteins and organelles throughout the cell [aka cell health]. The cytoskeleton is a structure that helps cells maintain their shape and internal organization, and it also provides mechanical support that enables cells to carry (see 7 under learning disabilites, gifted and talented and 2e & cell health below) out essential functions like division and movement [Retrieved from https://www.cell.com/neuron/pdf/S0896-6273%2812%2901034-3.pdf; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728923/].

Can we turn off this production with Epigenetics?? Holistic, Alternative, Natural means? I say…YES

-Dyslexia: https://www.ncbi.nlm.nih.gov/gene/?term=Homo+sapiens+dyslexia+susceptibility+1

Note: 15- DNAAF4 provided by HGNC  gene encodes a tetratricopeptide [The tetratricopeptide repeat (TPR) is a structural motif.  It consists of a degenerate 34 amino acid tandem repeat identified in a  wide variety of proteins] repeat domain-containing protein.  The encoded protein interacts with estrogen receptors and the heat shock  proteins, Hsp70 and Hsp90. An homologous protein in rat has been shown  to function in neuronal migration in the developing neocortex [read more below]. A  chromosomal translocation involving this gene is associated with a  susceptibility to developmental dyslexia. Mutations in this gene are associated with deficits in reading and spelling.

Note:  6- KIAA0319 provided by HGNC  gene for kidney disease (PKD) domains. The encoded protein may play a role in the development of the cerebral cortex by regulating neuronal migration and cell adhesion. Single nucleotide polymorphisms in this gene are associated with dyslexia. (see the Thymus-  It plays a role in immunity, autoimmunity,  and aging. This gene encodes a doublecortin domain-containing family member. The  doublecortin domain has been demonstrated to bind tubulin and enhance  microtubule polymerization. This family member is thought to function in  neuronal migration where it may affect the signaling of primary cilia.  Mutations in this gene have been associated with reading disability (RD)  type 2, also referred to as developmental dyslexia.  6-DCDC2 This gene encodes a doublecortin domain-containing family member. The  doublecortin domain has been demonstrated to bind tubulin and enhance  microtubule polymerization. This family member is thought to function in  neuronal migration, where it may affect the signaling of primary cilia.  Mutations in this gene have been associated with reading disability (RD)  type 2, also referred to as developmental dyslexia.

Can we turn off developmental dyslexia with Epigenetics?? Holistic, Alternative, Natural means? I say…YES

-Autism: https://www.ncbi.nlm.nih.gov/gene/?term=Homo+sapies+autism

Note: 7- AUTS2 provided by HGNC gene has been implicated in neurodevelopment and as a candidate  gene for numerous neurological disorders, including autism spectrum  disorders, intellectual disability, and developmental delay. Mutations  in this gene have also been associated with non-neurological disorders,  such as acute lymphoblastic leukemia, aging of the skin, early-onset  androgenetic alopecia, and certain cancers [see thymus below].  7-also in high levels (chemical base in DNA such as thymine) in mammalian postmitotic central nervous system neurons, functions in diverse processes such as synaptic plasticity and neuronal migration through phosphorylation of proteins required for cytoskeletal organization, endocytosis and exocytosis, and apoptosis.

16- HP restricted to liver. This gene encodes a preproprotein, which is processed to yield both  alpha and beta chains, which subsequently combine as a tetramer to  produce haptoglobin. Haptoglobin functions to bind free plasma  hemoglobin, which allows degradative enzymes to gain access to the  hemoglobin, while at the same time preventing loss of iron through the  kidneys and protecting the kidneys from damage by hemoglobin. Mutations  in this gene and/or its regulatory regions cause ahaptoglobinemia or  hypohaptoglobinemia. This gene has also been linked to diabetic  nephropathy, the incidence of coronary artery disease in type 1  diabetes, Crohn’s disease, inflammatory disease behavior, primary  sclerosing cholangitis, susceptibility to idiopathic Parkinson’s  disease, and a reduced incidence of Plasmodium falciparum malaria. The  protein encoded also exhibits antimicrobial activity against bacteria. A  similar duplicated gene is located next to this gene on chromosome 16.  Multiple transcript variants encoding different isoforms have been found  for this gene.

Note: In a 2018 study, They found that greater  changes in gene expression in the upper layers 2/3 neurons and microglia  predicted worse behavioral deficits. These results lend support to  previous research suggesting that changes in neurons, as well as  non-neuronal cells such as microglia, may be involved in autism. (Retrieved from https://www.autismbrainnet.org/2019/07/10/single-cell-study-identifies-brain-cell-types-linked-to-autism/) Note:

Can we turn off immense anger/hatred and shame/grief with Epigenetics?? Holistic, Alternative, Natural means? I say…YES

Schizophrenia  & Psychological Disorders

-11 DRD2 This gene encodes the D2 subtype of the dopamine receptor. This  G-protein coupled receptor inhibits adenylyl cyclase activity. A  missense mutation in this gene causes myoclonus dystonia; other  mutations have been associated with schizophrenia. Alternative splicing  of this gene results in two transcript variants encoding different  isoforms. A third variant has been described, but it has not been  determined whether this form is normal or due to aberrant splicing.

Note: Gene Methylation in Specific Brain Regions involves the biological processes associated with neuronal axon  development, intercellular adhesion, and cell morphology changes and,  specifically, in PI3K-Akt, AMPK, and MAPK signaling pathways. AMPK activation has also recently been linked to circadian clock  regulation, which couples daily light and dark cycles to control of  physiology in a wide variety of tissues through tightly coordinated  transcriptional programs84. (see Thymus Below, Testes) (Retrieved from https://www.hindawi.com/journals/bmri/2020/8047146/; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249400/.)

Can we turn off (DOC) Disorders of Conscious with Epigenetics?? Holistic, Alternative, Natural means? I say…YES

-Borderline Personality Disorder (BPD) another name Emotionally Intense or Sensitive: https://www.ncbi.nlm.nih.gov/gene/?term=borderline+personality+disorder+homo+sapiens

Note: Gene 17- This gene encodes an integral membrane protein that transports the  neurotransmitter serotonin from synaptic spaces into presynaptic  neurons. The encoded protein terminates the action of serotonin and  recycles it in a sodium-dependent manner. This protein is a target of  psychomotor stimulants, such as amphetamines and cocaine, and is a  member of the sodium: neurotransmitter symporter family.

Note: A polymorphism is when there are two or more possibilities of a trait on a gene. A repeat length  polymorphism in the promoter of this gene has been shown to affect the  rate of serotonin uptake. There have been conflicting results in the  literature about the possible effect, if any, that this polymorphism may play in behavior [learning] and depression. [provided by RefSeq, May 2019] (see Gifted & Talented, 2e w/ Dyslexia). [Retrieved from https://www.ncbi.nlm.nih.gov/gene/?term=borderline+personality+disorder+homo+sapiens].

Note: Developmental  factors, including problems with emotional attunement [shame] between a  developing child and caregivers, seem to play a role, as do physical or  sexual abuse, or emotional neglect (stems from temperament and trauma, triggered by Events such as Abandonment). [See List Of Characteristics-Retrieved from https://healthmatters.nyp.org/understanding-difference-bipolar-borderline-personality-disorder/; https://healthmatters.nyp.org/understanding-difference-bipolar-borderline-personality-disorder/?fbclid=IwAR0wDlXw9oH6Dr2Ezvi-w4U5bIFjOACgugstR4KN93cAOPBBbOmKMuNCxno].

-Depression: https://www.ncbi.nlm.nih.gov/gene/?term=Homo+sapies+depression

Note: 6- KIAA0319 provided by HGNC gene encodes a multifunctional proinflammatory cytokine that  belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions  through, its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine  is involved in the regulation of a wide spectrum of biological processes  including cell proliferation, differentiation, apoptosis, lipid  metabolism, and coagulation. This cytokine has been implicated in a  variety of diseases, including autoimmune diseases, insulin resistance,  psoriasis, rheumatoid arthritis ankylosing spondylitis, tuberculosis,  autosomal dominant polycystic kidney disease, and cancer. Mutations in  this gene affect susceptibility to cerebral malaria, septic shock, and  Alzheimer disease [see RAS/pons/thymus, hippocamp and insensitivity and depression below].

Can we turn off Neurodevelopmental disorders with Epigenetics?? Holistic, Alternative, Natural means? I say…YES

-ADHD: https://www.ncbi.nlm.nih.gov/gene/?term=Homo+sapies+adhd

Note: COMT-22 Catechol-O-methyltransferase catalyzes the  transfer of a methyl group  from S-adenosylmethionine to catecholamines,  including the  neurotransmitters’ dopamine, epinephrine, and  norepinephrine.  Furthermore, Catechol-O-methyltransferase (COMT-22), an enzyme that is involved in the degradation of catecholamine neurotransmitters  (e.g., dopamine,  epinephrine, and norepinephrine), can affect executive  functions  involved in cognitive flexibility, impulse control, abstract  thought,  and the ability to follow instructions (1, 2, 3)-(COMT-22 also in addictions and learning disabilities).

Note: a number of genes associated with ADHD, which has a heritability of 71-90%, are also linked to dopamine transporter dysfunction (3). Dopamine imbalance has also been implicated in other conditions,  including autism spectrum disorder, Tourette’s syndrome, and dyspraxia. [Retrieved from https://www.psychologytoday.com/gb/blog/pathways-progress/202108/is-there-link-between-neurodiversity-and-mental-health].

Note: 11- DRD2 provided by HGNC  neuronal survival gene in the adult brain; Alzheimer’s, Parkinson’s, and Huntington’s; stress response and in the biology of mood disorders.

The CDC reports  that as of 2016, almost 10% of children were estimated to have ADHD,  with boys twice as likely to be diagnosed than girls. [Retrieved from https://www.psychologytoday.com/gb/blog/psychiatry-the-people/202110/how-mindfulness-tunes-function-in-4-key-adhd-brain-circuits].

Note: No one knows exactly what causes a person to have ADHD, but some  researchers have looked at a neurotransmitter called dopamine as a  possible contributor to ADHD. Dopamine allows us to regulate emotional  responses and take action to achieve specific rewards. It’s responsible  for feelings of pleasure and reward. Dopamine (DA) is a key brain neurotransmitter that contributes to  control of different functions, such as cognition, motivation and  rewards, as well as locomotion [1–3]. Alterations in dopaminergic function represent a hallmark in numerous mental diseases, including schizophrenia. [Retrieved from https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00034/full]

The anterior insular cortex is a region of the brain that plays a  critical role in motivation. A set of neurons that activate a gene  called Fezf2(Fezf2 neurons) in this area are active  when mice are doing both physical and cognitive tasks. Li and his lab  hypothesized that these neurons do not affect the mouse’s ability to do  the task; rather, the brain cells influence the mouse’s motivational  drive. [Retrieved from https://neurosciencenews-com.cdn.ampproject.org/c/s/neurosciencenews.com/fezf2-motivation-19778/amp/?fbclid=IwAR0CEbUqdyGzTxr38GPai6p_G2nyBMFTiEnnYg2ZoGr4TOk-lg3fiSJ-wqU].

Another study found, dopaminergic pathways, [enables several species] to coordinate influence both ongoing and future behavior. [Retrieved from https://neurosciencenews.com/dopamines-motivation-learning-19564/?fbclid=IwAR10PI7VmMbVQNrKEEZUzm3AvcUIR4MkDp2ZCk481aLbDU6Him4cxK2gitM].

Note: brain, adrenal, thyroid below

Focus…on Healing

What are mitochondria?

Mitochondria are  compartmentalized, dual-membrane organelles that are responsible for  most energy production in the cell. Mitochondria contain their own DNA  and ribosomes (RNA).  Their primary function is to convert energy from glucose into ATP via oxidative phosphorylation. Mitochondria also play an  important role in the cellular stress response through processes such as  autophagy, apoptosis, and hypoxia. Mitochondrial dysfunction is implicated in many human diseases including cancer, metabolic syndrome  & neurodegenerative disorders, ex. Alzheimer’s Disease (AD) (Retrieved from https://www.novusbio.com/research-areas/cellular-markers/mitochondrial-markers.html; https://www.frontiersin.org/articles/10.3389/fnmol.2018.00393/full).

Mitochondria have been increasing recognized as important players in the  aging process. Most aging related diseases and particularly  neurodegenerative diseases have mitochondrial involvement. Co-activation- brings the neurons to activation and stimulation of mitochondrial production within the cells which  helps build more efficient, proactive neuronal networks and plasticity.  Mitochondria are the principal synergetic energy generators of cells, and neurons are cells that require a lot of energy. People with depression have fewer mitochondria in their neurons and people with untreated depression have lower levels of protein produced by mitochondria. These proteins help maintain optimal energy production as well as structural integrity and optimal numbers of mitochondria. [Retrieved from https://www.mdpi.com/journal/biology/special_issues/Mitochondria; https://neurosciencenews.com/mitochondira-depression-19710/; https://www.frontiersin.org/articles/10.3389/fnins.2018.00386/full].

Mitochondrial Toxicity or Corosion- A goal of the Tox21 program is to transit toxicity testing from traditional in vivo models to in vitro assays that assess how chemicals affect cellular responses and toxicity pathways. This comprehensive approach allows for evaluation of thousands of  environmental chemicals for mitochondrial toxicity and identification of  possible MOAs. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154066/].

Please Note: A new NIH grant will allow Virginia Tech researchers to explore the mechanisms of social memory in the hippocampus. “Impaired social memory is a phenotype of numerous neurological  disorders, ranging from autism spectrum disorder to schizophrenia and  Alzheimer’s disease,” Farris said. “By unraveling the molecular nuances  underlying healthy memory storage, we aim to pinpoint a host of  potential interventional targets for neurodevelopmental, neurocognitive  and neurodegenerative disease. She [Farris] hypothesizes that these unusual mitochondrial characteristics may be  influencing this brain region’s plasticity – or ability to rapidly  modify synapses, neurochemical portals that mediate communication  between neurons.” [Retrieved from https://neurosciencenews.com/mitochondria-social-memory-19623/].

Ribosomal  RNA is the predominant form of RNA found in most cells; it makes up  about 80% of cellular RNA despite never being translated into proteins  itself. Ribosomes are composed of approximately 60% rRNA and 40%  ribosomal proteins by mass. [Retrieved from https://en.wikipedia.org/wiki/Ribosomal_RNA]

What is Proteomics?

Proteomics is the large-scale study of proteomes.  A proteome is a set of proteins produced in an organism, system, or  biological context. … Proteomics is used to investigate: when and  where proteins are expressed also the rates of protein production, degradation,  and steady-state abundance.

Think about mitochondria and cell health? Also, on a cellular level, think about the Epigenetics Modulators?

3 – Retrieved fom https://www.researchgate.net/figure/a-The-three-main-components-of-the-cytoskeleton-actin-microtubules-and-intermediate_fig2_345153653

Epigenetic modulators thus serve to transduce signals from environmental agents, injury, inflammation, aging  and other cellular stressors towards modifiers to alter the chromatin states of tumor suppressors or oncogenes and to promote epigenetic flexibility and the acquisition of stem-like features early during:

• Epigenetic mechanisms form a layer of control within a cell that regulates gene expression and silencing. …
• Three different epigenetic mechanisms have been identified: DNA methylation,  histone modification, and non-coding RNA (ncRNA)-associated gene  silencing (“turning off dyslexia”).

“Cells are continuously dying in our body due to infections, cell turnover, developmental processes, and other extrinsic stress…”: In these chromosomes…most present in neurodiversity; we are needing to examine cell health (avoid cytotoxicity) such as:

17  (cell gene– lNF1 provided by HGNC also ACTL6A ) Remember- meaning- knowledge (RAS- see also 11 below/ARAS-Thymus), Engagement with the learning task

22 (connection gene– COMT 22 provided by HGNC ) Recall- motivation- wisdom (Pons), Strategies to process that information

11 (neuronal survival cell gene– DRD2 provided by HGNC ) Recognize- meaning & motivation-understanding (see 17 also ARAS//Thymus/Testes), Recognition of the information to be learned

Intercellular Interactions For Gene Expression

Signalling pathways include the network of biomolecules that serve to transmit  signals and induce cellular responses. Post-translational modification  of proteins is the most common way signals are propagated. See thymus discussion below, to learn more about the intercellular signalling pathways that has become a common analysis performed across diverse disciplines. (Retrieved from Cell death: From its Induction to the Removal of Dying Cells! https://www.frontiersin.org/research-topics/27626; https://www.ncbi.nlm.nih.gov/books/NBK532999/; https://www.nature.com/articles/s41576-020-00292-x].

“Moreover, numerical and functional deficiencies and phenotypic alterations of CD56+ immune cells have been reported in patients with various infectious, autoimmune or malignant diseases (Table 1).” [Retrieved from https://www.frontiersin.org/articles/10.3389/fimmu.2017.00892/full].

Cellular Senescence in Learning Disabilities and Neurodegenerative Disorders

Although several factors can induce senescence, DNA damage, oxidative  stress, neuroinflammation, and altered proteostasis have been shown to  play a role in its onset.  (Retrieved from Cellular Senescence in Neurodegenerative Diseases https://www.frontiersin.org/article/10.3389/fncel.2020.00016; https://downloads.hindawi.com/journals/omcl/2017/7280690.pdf; https://www.sciencedaily.com/releases/2020/01/200129174540.htm).

A slew of 17 studies reveals the first comprehensive list of all cell types in the primary motor complex,  offering “a starting point for tracing cellular networks to understand  how they control our body and mind and how they are disrupted in mental  and physical disorders,” reports ScienceDaily. From the report:    The 17 studies, appearing online Oct. 6 in the journal Nature,  are the result of five years of work by a huge consortium of  researchers supported by the National Institutes of Health’s Brain  Research Through Advancing Innovative Neurotechnologies (BRAIN)  Initiative to identify the myriad of different cell types in one portion  of the brain. It is the first step in a long-term project to generate  an atlas of the entire brain to help understand how the neural networks  in our head control our body and mind and how they are disrupted in  cases of mental and physical problems. While researchers have discovered numerous cell types in the brain, this  atlas of all cell types in one area — the primary

— is  the first comprehensive list and a starting point for tracing cellular  networks to understand how they control our body and mind and how they  are disrupted in mental and physical disorders. (Retrieved from https://science.slashdot.org/story/21/10/08/223218/neuroscientists-roll-out-first-comprehensive-atlas-of-brain-cells; https://www.nature.com/articles/s41586-021-03950-0).

Three Potential Mechanisms of Transcranial Photobiomodulation (tPBM):

First, by direct stimulation, where photobiomodulation is applied directly on the distressed neurons themselves, activates mitochondrial function that then increases both adenosine triphosphate energy and the expression of stimulatory and/or protective genes.

Second, by indirect stimulation, where photobiomodulation triggers recruitment of a “middle man”, such as cells of the immune and/or stem cell systems. These activated cells may swarm to the region of distressed neurons and helps them survive and function, by potentially increasing the expression of anti-inflammatory cytokines while decreasing the pro-inflammatory ones.

Third, rather than acting on the distressed neurons through either a direct or indirect stimulation as described above, photobiomodulation may act on other brain regions, for example motor cortex, that then stimulate the neural networks that underpin the behavioural improvements. [Retrieved from https://www.nrronline.org/article.asp?issn=1673-5374;year=2018;volume=13;issue=10;spage=1738;epage=1740;aulast=Hamilton].

1. *10- Thymus, see brain and testes association HERE. TBATA provided by HGNC gene encodes a protein that regulates thymic epithelial cell proliferation and thymus size. It has been identified as a ligand for  the class I human leukocyte antigen (HLA-I) in thymus. Studies of the orthologous mouse protein suggest that it may also play a role in  spermatid differentiation, as well as in neuronal morphogenesis [a class of large neurons present in the peripheral nervous system below] and synaptic plasticity. As well, the energy cycles which are known as circadian rhythms, which were popularized by  Nobel Prize-winning researchers Jeffrey Hall, Michael Rosbash, and  Michael Young. They highlighted that every cell in the body is set to  follow this biological clock which determines your sleep, appetite,  hormone releases, and energy levels. Polymorphisms in this gene are associated with  susceptibility for multiple sclerosis (MS). Alternative splicing results  in multiple transcript variants (see Thymus below). “The circadian rhythm of about 24 hours is a fundamental physiological function observed in almost all organisms, from prokaryotes to humans. Identification of clock genes has allowed us to study the molecular bases for circadian behaviors and temporal physiological processes such as hormonal secretion, and has prompted the idea that molecular clocks reside not only in a central pacemaker, the suprachiasmatic nuclei (SCN) of hypothalamus in mammals, but also in peripheral tissues, even in immortalized cells.” Furthermore …(See RAS, Pons, Thymus  below, and see brain and testes association HERE-Retrieved from Thymus Function and Aging: A Focus on Thymic Epithelial Cells https://www.frontiersin.org/research-topics/24158 https://pubmed.ncbi.nlm.nih.gov/15834108/; https://link.springer.com/article/10.1186/1471-2199-5-18).

‘A man’s mind plans his way [as he journeys through life], But the Lord directs his steps and establishes them [anchor or standby]. ‘  Proverbs 16:9 AMP

An autoimmune disease is a condition that affects your hormones and immune system which mistakenly attacks your body.  The immune system normally guards against germs like bacteria and  viruses. When it senses these foreign invaders, it sends out an army of  fighter cells to attack them. There are more than 100 autoimmune diseases,  including conditions such as celiac disease, type 1 diabetes, and  psoriasis. These occur when the immune system mistakenly attacks parts  of the human body. This statistic comes from the American Autoimmune  Related Diseases Association. [Retrieved from https://www.medicalnewstoday.com/articles/list-of-autoimmune-diseases].

The vitamin D Receptor and T cell function

4 – Retrieved from https://upload.wikimedia.org/wikipedia/commons/7/7c/Renin-angiotensin_system_in_man_sh adow.svg

Where is the vitamin D receptor?

In humans, the vitamin D receptor is encoded by the VDR gene located on chromosome 12q13. 11.  Like the iNKT cells, there are also fewer CD8αα/TCRαβ precursors in the thymus of VDR-KO animals. Moreover, to complete development CD8αα/TCRαβ  cells must travel from the thymus to the gastrointestinal tract where  IL-15 induces proliferation and upregulation of CD8αα. Due to decreased  levels of IL-15 receptor expression VDR-KO CD8αα/TCRαβ cells proliferate  poorly, resulting in a diminished mature CD8αα/TCRαβ population in the  VDR-KO gut (Yu et al., 2008; Bruce and Cantorna, 2011; Ooi et al., 2012).  These data illustrate that in contrast to conventional T cells, VDR  expression is mandatory for development of both iNKT cells and  CD8αα/TCRαβ T cells. VDR is expressed in most tissues of the body, and regulates  transcription of  about 900 genes involved in intestinal and renal transport of  calcium and other minerals.  In a study by Patel et al. (1995)  plasma toxins from uremic patients was shown to bind to the patient’s  VDR, thereby disrupting binding of VDR-RXR to DNA resulting in a  diminished VDR response. It so appears that post-translational  modifications of VDR adjust VDR activity in both health and disease. [Retrieved from https://www.frontiersin.org/articles/10.3389/fimmu.2013.00148/full].

Note: In humans, the vitamin D receptor is encoded by the VDR gene located on chromosome 12q13. 11.   VDR is expressed in most tissues of the body, and regulates   transcription of genes involved in intestinal and renal transport of  calcium and other minerals (See asc, adhd, epilipsry and schzophrinia & Chromosome 12 above).

Similarly,  early last year, researchers from institutes in Germany and Greece  reported a mechanism in the brain’s outer cortical cells that produces a  novel ‘graded’ signal all on its own, one that could provide individual  neurons with another way to carry out their logical functions. By  measuring the electrical activity in sections of tissue removed during  surgery on epileptic patients and analyzing their structure using  fluorescent microscopy, the neurologists found individual cells in the  cortex used not just the usual sodium ions to ‘fire’, but calcium as  well. [Retrieved from https://www.sciencealert.com/a-never-before-seen-type-of-signal-has-been-detected-in-the-human-brain?fbclid=IwAR3sZiK3xsrIVnHirG-RjcIKY9NW5czdUk3iPK8dURZnz-qXaKsXJwE6sDs].

Thymic involution, probably through the hormonal turmoil and cell health, provoke many of our learning and memory problems. -Tricia Cook

5 – Elements of the figure were generated using Biorender.com.

Endogenous regeneration in the brain is the ability of cells to engage in the repair  and regeneration process. … Another benefit that can be achieved by  using endogenous regeneration could be avoiding an immune response from  the host. There are therapeutic approaches for boosting thymus function. Likewise, the causes age-related thymic involution have been suggested along with several possible mechanisms identified including blockages of T-cell receptor gene rearrangement, decreased self-peptide MHC molecules, and depletion of T-cell progenitors [Retrieved from  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837659/; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2750859/;

979-020-0173-8].

Note: In the brain, hormones alter or change the production of gene products  that participate in synaptic neurotransmission as well as affect the structure of brain cells. As a result, the circuitry of the brain and  its capacity for neurotransmission.  I give natural and holistic ways to improve your thymic hormone function and cell-mediated immunity… “Although epigenetic modulators that control effector status in Th17 cells have been identified 15, 21, the TF regulators that globally program the capacity of CD4+ T cells to dynamically control their functional identity in response to changing contexts are mostly undefined.”  Retrieved from cell gene and https://www.pnas.org/content/115/8/1883 (see HPA & Pineal Body, Pituitary & Adrenal Glands below).

Supplementation with these nutrients has been shown to improve thymic  hormone function and cell-mediated immunity such as…Zinc,  vitamin B6, and vitamin C are perhaps the most critical.  Zinc may be the critical  mineral involved in thymus gland function and thymus hormone action. Hematite worn around the neck brings balance to both the etheric body and the  physical body. Due to its magnetic nature and our ying-yang  energies, it’s nature is to bring us back to equilibrium. Plus, Note: I go much deeper than supplements like neurometric education (read below) to avoid early thymic involution and/or dysfunction, imbalance, etc. ….   (Retrieved from https://www.frontiersin.org/articles/10.3389/fimmu.2020.01745/full; https://www.frontiersin.org/research-topics/11340/new-insights-into-thymic-functions-during-stress-aging-and-in-disease-settings).

*ACE- (aka Anger Enzyme) Angiotensin-converting enzyme (EC 3.4.15.1),  is a central component of the renin–angiotensin system (ras), which controls blood pressure by regulating the volume of fluids in the body (See Gut-brain axis and Neurotoxicity).  Corticotropin-releasing hormone (see hypothalamus below)- Stress induces  the hypothalamic production and release of CRH, which then causes the  activation of the CRH receptor (CRHR) type 1 (CRHR-1) in the anterior  pituitary (see HPA below) to stimulate ACTH release, as well as proopiomelanocortin  (POMC) expression and processing. Rationale: The corticotropin-releasing hormone (CRH) stimulation test has been used as a diagnostic test in both adrenal insufficiency and Cushing syndrome. Glucocorticoids are essential steroid hormones secreted from the adrenal gland in response to stress. (Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1819560/; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1819560/; https://www.frontiersin.org/research-topics/7323/involvement-of-neuro-immune-mechanism-and-brain-gut-axis-in-pathophysiology-of-mood-disorders#articles).

A growing body of evidence suggests that chronic anger can take a daily toll  on your cardiovascular health and immune system. Letting go of the  bitterness you feel toward another person can lower your anxiety, which directly impacts both your mental and physical health. Basically, feeling bad is bad for you—especially if those feelings are due to bitter or traumatic memories that frequently come to mind unbidden. [Retrieved from https://getpocket.com/explore/item/forgiving-people-is-good-for-your-health-here-s-how-to-do-it?utm_source=pocket-newtab]. Note: If something confounds you, as well could make someone angry, it makes you feel surprised and confused, often because it does not meet your predefined expectations (perceptions).

THE GIFT OF DYSLEXIA & OTHER LEARNING DIFFERENCES

There’s a lot to be said for Maria Montessori’s observations of trusting the universe along with ‘the child’. If we love and trust our children, this becomes their inner thoughts, ideas, and perspectives. When they trust their own brain [and heart], they can experience the “gifts of dyslexia” and learn anything the way they learn best.

People with dyslexia have a sound and language processing problems. They will struggle to connect letters to sounds and, mainly problems identifying speech sounds and learning how they relate to letters and words; as well, those with visual processing problems struggle to understand visual information such as letters, shapes, or objects and, mainly problems processing graphic symbols. Related to the absorption and processing of sounds [sounds especially can be omitted from words by the student], students with dyslexia most commonly omit letter sounds, words, phrases in the middle position, then the end, and least commonly the beginning. When they omit, they might do sound confusions such as repetition(s), substitution(s), addition(s) or delete altogether, on the other hand; transversal and reversal are more common in students with a visual processing problem-have them remember: if it doesn’t look or sound right reread or rewrite till you’re brain feels like “it’s just right” [trust your brain-you are smart, you can do it, and you are love].

People with dyslexia also have a high coexistence of ADHD (3 types). People with ADHD and Dyslexia have difficulty processing the  basic sounds of language (phonemes) and graphic symbols causing fluency struggles. They “stumble over words” due to reading and processing too fast/slow; mainly, in the beginning-ending of word, sentence, paragraph, passage– rest of the time not too fast/slow sometimes it’s “just right” (I call this “varied reading rate”). If varied prosody, reading rate, and expression/intonation objective aren’t met and they still don’t seem to comprehend; mainly, in the beginning-ending of paragraph, passage, etc. have them remember: if it sounds or looks too fast or slow, or robotic, then adjust your prosody and reading rate by rereading so it will be “just right” [trust your brain- you are smart, you can do it, and you are love].

Both, people with just dyslexia and dyslexia along with ADHD are notoriously known for “guessing at words” and stories meaning despite having average/high IQ due to the dyslexia and ADHD tendencies! They both are having natural universal emotions of learning (such as anger, shame which need to be replace with strength and empathy, as well as, remembering calm). The tendencies change according to the reading, hour day, week, etc.. Also, the tendencies way heavily on if they are sick, hungry, tired, or stressed. Reading can make them feel ill with headaches, stomach aches/knots, tight shoulders/neck and even dizzy.

People with dyslexia, can also be neurodivergent (think differently and view the world with a different lens). Also, seeking out endeavors of creative, imaginative, visual, artistic, and visionary skills while taking on inventing, and innovating pursuits. Lastly, excelling at thinking of “outside the box” solutions, seeing a problem from many different sides (average/higher IQ), and strong spatial relationships along with the ability to think in three dimensions.

My Story

Those that read my story and struggle with learning need to remember the story of Brunette-locks and the Three Doors know what they are and how they are made is “Just Right” and as God had planned!

In this story, Nettie Fermeracle discovers the veil of being imperfect was her ego’s illusion. She experienced the heartache and troubling mind of having a learning difference. Yet, she finds courage and compassion that she needed to when the last door was opened; she gladly accepted the loving invitation of salvation.

Nettie, the girl in my story, is myself…Patricia Flotte Cook. I am not simple nor slow but rather complex and SAVED- thanks to these life lessons, experiences, and trauma including all the antagonist involved; Thanks to God, my protagonist. I just won’t define by my dyslexia and ADHD [undiagnosed Twice Exceptionality] nor as a Southern-Christian lady, Teacher/Tutor, Educational Consultant, and Mom/Wife; I concentrate in serving others through Him by mainly using my gifts of dyslexia which are “getting the whole picture” which includes deep and holistic, list-form thinking, problem-solving, building/constructing abilities, computer skills, gaming strategies, and emotional/intellectual sensitivities.

https://atomic-temporary-173470897.wpcomstaging.com/my-story/#.Ych64FlMGic

Written by -Tricia Cook, MEd., RSP, AOG; https://linktr.ee/tcooktutor

Humbled by His Faith for to Conquer Pride by: ‘Do not be afraid and anxious, little flock, for it is your Father’s good pleasure to give you the kingdom. But [strive for and actively] seek His kingdom, and these things will be given to you as well. ‘ Luke 12:31-32

To learn more: https://sway.office.com/FP5HpTc6qPsIEcsH?ref=Link

Dedicated To: God, my friend and honorable

brother who has saved so many lives,

thanks…Ted, and to the rest of my family

and friends whom love and support me

always!!

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