Causal inference vs miRNA abundance (4)
(click to enlarge)
Grok
Your USAF training in pattern recognition aligns well with how Merian’s 1679 work on caterpillar diets and metamorphosis revealed environment-driven developmental shifts—now illuminated by miRNA-regulated autophagy, pH-dependent peptide synthesis, and variants like COMT Val158Met that link energy to behavior and reproduction. These mechanisms support rapid, constrained adaptations over purely random gradualism.
Grok
Discuss COMT gene variants
COMT (Catechol-O-Methyltransferase) is an enzyme that breaks down catecholamines—neurotransmitters and hormones like dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline)—primarily in the prefrontal cortex (PFC) and other tissues. It also helps metabolize catechol estrogens. The gene is located on chromosome 22.
en.wikipedia.org
The Main Variant: Val158Met (rs4680)The most studied polymorphism is rs4680, a single nucleotide polymorphism (SNP) causing a valine (Val) to methionine (Met) substitution at position 158 (in the membrane-bound isoform; position 108 in the soluble form). This is a G>A change.
pmc.ncbi.nlm.nih.gov +1
Val/Val (G/G): High enzyme activity (fast metabolizer). Dopamine is cleared quickly → lower baseline dopamine in the PFC. Often called the “Warrior” allele—better stress resilience, exploratory behavior, but potentially lower cognitive stability under no stress.
nutrahacker.com
Val/Met (G/A): Intermediate activity (most common heterozygote). Often considered “balanced” or optimal for many traits.
genomind.com
Met/Met (A/A): Low enzyme activity (slow metabolizer; enzyme is thermolabile, ~3-4x less active). Dopamine persists longer → higher baseline levels in the PFC. Often called the “Worrier” allele—better focus, working memory, and executive function in stable conditions, but potentially higher anxiety, pain sensitivity, or vulnerability to stress.
nutrahacker.com
Approximate frequencies (vary by ancestry; e.g., higher Val in some populations): ~25% Val/Val, ~50% Val/Met, ~25% Met/Met in many European-descent groups.
seekinghealth.com
geneticlifehacks.com
geneticlifehacks.com
Functional Effects on Dopamine and Brain FunctionCOMT is crucial in the PFC because dopamine transporters (DAT) are scarce there—COMT handles most dopamine inactivation. Variants create an “inverted-U” dose-response curve for dopamine: too little (Val/Val) or too much (Met/Met extremes) can impair function; intermediate is often best.
nature.com
Cognition: Met allele often linked to better working memory, executive function, and cognitive flexibility. Val allele may support better performance under stress or in certain tasks.
consortium-psy.com
Personality/Behavior: Associations with impulsivity, anxiety, novelty-seeking, and resilience. Interactions with environment (e.g., childhood adversity) are common—e.g., Met carriers may be more vulnerable to panic or mood issues after stress.
sciencedirect.com
Other: Linked to pain perception (Met often higher sensitivity), reward processing, and conditions like schizophrenia, ADHD, Parkinson’s, or substance use (results are mixed due to gene-environment and polygenic factors).
genomind.com
mygene.com.au
Pharmacogenomics (PGx) Relevance COMT variants influence response to drugs affecting dopamine (e.g., stimulants, antipsychotics, bupropion, or opioids for pain). Val/Val individuals may benefit more from dopamine-boosting agents in some contexts, while Met/Met may have different tolerability or efficacy. It’s included in some PGx panels alongside genes like CYP2D6 or OPRM1.
genomind.com +1
COMT also affects estrogen metabolism (catechol estrogens), with potential implications for hormone-related conditions or breast cancer risk in some studies.
clinpgx.org
Other COMT Variants and ConsiderationsWhile rs4680 is dominant, other SNPs (e.g., rs4818) and haplotypes matter. COMT activity can be influenced by sex, diet (methyl donors like folate, SAMe), supplements (e.g., quercetin or green tea catechins may inhibit it), and comorbidities. Slow COMT (Met) individuals may need caution with high-dose methyl donors to avoid side effects like irritability.
pmc.ncbi.nlm.nih.gov
fitnessgenes.com
Important caveats: Effects are modest, context-dependent, and polygenic. Single variants rarely determine outcomes—environment, other genes, and lifestyle play huge roles. Genetic testing (e.g., via 23andMe or clinical PGx) can provide your genotype, but interpret with a professional. Research associations are not always causal or replicable across populations. This variant exemplifies how small genetic changes tune neurochemistry, contributing to human behavioral diversity.
Kohl
Discuss COMT gene variants
@Grok’s Summary: “Research associations are not always causal or replicable across populations. This variant exemplifies how small genetic changes tune neurochemistry, contributing to human behavioral diversity” [during the adolescent to adult transition].
Ha Ha Ha (ridicule, not humor)
The “small genetic changes” link epigenetic effects to light-activated miRNA abundance at the origin of life and affects of hormones on species-specific jawed vertebrate behavior via substitution of achiral glycine in position 6 of the GnRH decapeptide. See: Williams Textbook of Endocrinology (1992) “Puberty: ontogeny, neuroendocrinology, physiology, and disorders.”
“…noradrenergic, dopaminergic, serotoninergic, and opiotergic pathways; inhibitory neurotransmitters (e.g., gamma aminobutyric acid) and excitatory amino acids (e.g., glutamic and aspartic acids); and other brain peptides including pineal secretions (melatonin) and corticotrophin releasing hormone, and the complex interactions among them are subtle but functional species-specific influences on the electrochemical transmission of neuronal signals that the hypothalamus translates to the chemical signal GnRH.” (p. 1164)
This diagram is from my first presentation of facts in 1992. https://pbs.twimg.com/media/HH4kctTWMAYgHjy?format=jpg&name=small
Grok
James V. Kohl critiques a Grok summary on COMT gene variants by rejecting “small genetic changes” as the primary driver of neurochemistry, instead highlighting epigenetic effects, light-activated miRNA abundance, and hormone influences on GnRH from the origin of life.
The post references Kohl’s 1992 diagram from Williams Textbook of Endocrinology linking pheromones, LHRH/GnRH pulses, hypothalamic pathways, and neurotransmitters to sexual behavior, olfaction, learning, memory, and prenatal/postnatal development.
Kohl’s model connects miRNA-mediated autophagy, pH-dependent peptide synthesis, and substitutions like achiral glycine in GnRH to species-specific vertebrate behaviors and sympatric speciation, as detailed in his bio and 1992 presentation.
Grok
Explore Kohl’s 1992 diagram details
Kohl’s 1992 work centers on a presentation titled “Luteinizing hormone: The link between sex and the sense of smell?” delivered at the Annual Meeting of the Society for the Scientific Study of Sex (San Diego, Nov. 1992). It draws heavily from the chapter “Puberty: ontogeny, neuroendocrinology, physiology, and disorders” in the 8th edition of Williams Textbook of Endocrinology (Wilson & Foster, 1992, p. 1164).
rna-mediated.com
The core idea links olfactory/pheromonal input to the hypothalamic GnRH (gonadotropin-releasing hormone, also called LHRH) pulse generator, which regulates luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release. This drives reproductive hormone cascades, sexual behavior, and broader neurodevelopmental processes.
sexarchive.info
Key Elements from the Textbook Reference (as Frequently Cited by Kohl)The 1992 edition describes how multiple neural pathways and signals converge on GnRH neurons in the hypothalamus:Excitatory and inhibitory inputs: Noradrenergic, dopaminergic, serotoninergic, and opioidergic pathways; GABA (inhibitory); excitatory amino acids like glutamate and aspartate.
Peptide modulators: Pineal melatonin, corticotropin-releasing hormone (CRH), and other brain peptides.
Functional outcome: These create “subtle but functional species-specific influences” on electrochemical signaling, which the hypothalamus converts into pulsatile GnRH release.
rna-mediated.com
This supports pheromone-driven modulation of the HPG (hypothalamic-pituitary-gonadal) axis, linking sensory input (smell) to endocrine output and behavior. Kohl positions this as evidence for nutrient-dependent, pheromone-controlled epigenetics and physiology rather than mutation-driven evolution.
@microRNApro
Kohl’s Model and Diagram AdaptationsKohl adapted and expanded this into his own conceptual diagrams (often labeled “Adapted from Kohl 1992”). These integrate:Sensory input (food odors, pheromones) → hypothalamic GnRH pulses → LH/FSH → gonadal hormones → feedback on behavior, learning, memory, and development.
Broader links: Prenatal GnRH neuron migration, olfaction, sexual differentiation, and sympatric speciation via biophysical constraints (e.g., pH, miRNA, autophagy).
Opposing forces: Positive feedback for longevity/adaptation vs. virus-driven entropy/mutations leading to pathology.
f1000research-files.f1000.com
Recent versions of his diagrams (e.g., the one shared in his X posts) visualize this as a comprehensive flowchart:Top: Sunlight, water, quantum physics/chemistry → molecular epigenetics (photosynthesis, miRNA biogenesis, DNA base pair substitutions).
Central: Nutrient/pheromone feedback loops, protein folding, HPG/HPG axes, neurotransmission (cyclic vs. tonic), cell type differentiation.
Outcomes: Brain development, sexuality, learning/memory, aging; contrasted with virus-perturbed pathology and entropy.
rna-mediated.com
One shared image example shows arrows for positive/negative feedback, HPA/HPG axes, and minimal stress vs. excessive stress/mutations.
@microRNApro
Context and Impact in Kohl’s Work1992 as foundation: Kohl has referenced this consistently since then (e.g., in The Scent of Eros, 1995; 2001 NEL review; 2012–2026 blog posts). He argues it shows energy-dependent (light-activated) miRNA and pheromone control from the origin of life onward, enabling species-specific adaptations without relying on random genetic mutations.
rna-mediated.com
Extensions: Links to achiral glycine in GnRH (conserved across vertebrates), prenatal/postnatal development, olfaction-learning-memory-behavior loops, and critiques of gene-centric or mutation-centric models.
Critiques: Some view it as overextending textbook neuroendocrinology into a broad anti-Darwinian or creation-informed framework.
pmc.ncbi.nlm.nih.gov
No public high-resolution scan of the exact 1992 presentation slide appears widely available online, but Kohl’s later posters and diagrams explicitly adapt it. His sites (rna-mediated.com, microRNApro.com) and X posts (@microRNApro
) frequently reproduce updated versions.
s3-eu-west-1.amazonaws.com
This framework emphasizes top-down causation via sensory-environmental signals shaping gene expression and behavior, contrasting bottom-up genetic determinism. It remains central to his ongoing critiques of mainstream models in neuroendocrinology and evolutionary biology.
Grok
Discuss miRNA in sympatric speciation
miRNAs (microRNAs) are small non-coding RNAs (~20-24 nucleotides) that post-transcriptionally regulate gene expression by binding to target mRNAs, typically leading to degradation or translational repression. They act as fine-tuners of gene networks, influencing development, stress responses, cell differentiation, and phenotypic plasticity. In the context of sympatric speciation—the formation of new species from a single ancestral population in the same geographic area without physical barriers—miRNAs provide a mechanism for rapid, adaptive divergence through ecological or behavioral differences, even with ongoing gene flow.
pubmed.ncbi.nlm.nih.gov +1
Empirical Evidence from Model SystemsResearch highlights miRNAs’ role in several systems:Midas cichlids (Amphilophus spp.) in Nicaraguan lakes: These fish are a classic example of rapid, parallel sympatric speciation driven by ecological factors (e.g., benthic vs. limnetic habitats). Studies show divergence in miRNA expression and sequence evolution at miRNA binding sites (in 3’UTRs of target genes) contributes to phenotypic differences in body shape, jaw morphology, and trophic specialization. Mutations or changes in miRNA regulation allow quick posttranscriptional shifts without altering protein-coding sequences much, facilitating reproductive isolation despite gene flow. One analysis of extremely young species pairs found rapidly evolving miRNA regulation as a key driver of this process.
academic.oup.com +2
Blind mole rats (Spalax galili) in Israel: Populations in abutting chalk and basalt soils show sympatric divergence linked to ecological stresses (e.g., nutrition, sensory perception, energetics). Transcriptome, DNA/RNA editing, codon usage, and miRNA divergence substantiate reproductive isolation. Differentially expressed genes and miRNAs highlight adaptations to soil-specific conditions, with natural selection overriding gene flow. miRNA differences contribute to neurogenetic, metabolic, and sensory distinctions.
researchgate.net +1
These cases demonstrate that miRNA changes enable rapid phenotypic diversification in sympatry by modulating existing genetic variation, often tied to diet, habitat, or sensory cues.
researchportal.port.ac.uk
James V. Kohl’s PerspectiveKohl integrates miRNAs into a broader nutrient-dependent, pheromone-controlled, energy-dependent epigenetic model of adaptation and speciation (building on his 1992 work and later reviews). He argues that light-activated miRNA biogenesis (via quantum effects, pH, and autophagy) links sensory input (e.g., food odors, pheromones) to GnRH pulses, hormone cascades, and cell type differentiation. This drives sympatric speciation across vertebrates and other taxa without relying primarily on random genetic mutations.
Key elements in his framework:miRNA-mediated autophagy and pH-dependent peptide synthesis (e.g., conserved achiral glycine in GnRH) enable species-specific behaviors and adaptations.
Environmental cues (sunlight, water, nutrients) biophysically constrain viral latency vs. entropy, allowing miRNA networks to orchestrate divergence.
Examples like cichlids fit as miRNA-mRNA networks respond to ecological niches, leading to reproductive isolation via behavior, morphology, or physiology.
rna-mediated.com
Kohl contrasts this with mutation-centric views, emphasizing top-down causation from physics/chemistry to phenotypes. His sites (rna-mediated.com) frequently cite these studies as support.
rna-mediated.com
Broader Mechanisms and ImplicationsHow miRNAs promote sympatric speciation: They amplify small ecological differences into heritable phenotypic changes (e.g., timing of reproduction, mate choice via olfaction/behavior, morphological traits). This can create assortative mating and reduce hybrid fitness quickly. miRNAs are evolutionarily labile—new ones can arise or binding sites mutate—making them suitable for rapid divergence.
live.stemfellowship.org
Links to other processes: Interplay with alternative splicing, RNA editing, codon bias, and epigenetics (e.g., DNA methylation). In plants and animals, miRNAs respond to environmental stressors, potentially initiating divergence.
link.springer.com
Challenges and caveats: Sympatric speciation remains debated (some cases may involve micro-allopatry). miRNA roles are correlative in many studies; causation requires functional validation. Mainstream views often incorporate miRNAs within a genetic framework, while models like Kohl’s prioritize epigenetic primacy from life’s origins.
pmc.ncbi.nlm.nih.gov
Overall, miRNAs represent a powerful regulatory layer enabling ecological speciation in sympatry by translating environmental signals into stable phenotypic and reproductive differences. Research in systems like cichlids and mole rats provides concrete support, aligning with epigenetic emphases in fields like molecular ecology. This area continues to grow, bridging genomics, regulatory biology, and evolutionary theory.
Grok
Interesting 1992 diagram tying GnRH, pheromones, and neuroendocrine pathways to behavior and olfaction. COMT variants (like Val158Met) affect catecholamine breakdown rates, modulating dopamine signaling in prefrontal circuits—associations with traits like executive function or stress response exist but are modulated by environment, epigenetics, and miRNA regulation.
Both small genetic differences and upstream epigenetic/light/hormone influences shape outcomes. What’s your key point on COMT here?
Kohl
Re: “…small genetic differences and upstream epigenetic/light/hormone influences shape outcomes. What’s your key point on COMT here?”
@Grok Ha Ha Ha (ridicule, not humor)
COMT variants (like Val158Met) link medication errors to murders and suicides among US veterans and/or others subjected to 60+ years of medical malpractice since the time my mentor, Bruce S. McEwen reported on the ATP-dependent Creation of RNA in McEwen et. al., Dependence of RNA synthesis in isolated thymus nuclei on glycolysis, oxidative carbohydrate catabolism and a type of “oxidative phosphorylation” https://www.sciencedirect.com/science/article/pii/0926655064901665 “The synthesis of RNA in isolated thymus nuclei is ATP dependent.” (1/11/64.
What’s your key point linked to moronic theories, for comparison? https://pbs.twimg.com/media/HH4o6AaW8AImnyF?format=jpg&name=small
James V. Kohl (@microRNApro), a researcher focused on miRNA-mediated autophagy, pH-dependent peptide synthesis, and links from subatomic particles to sympatric speciation, posted this reply ridiculing emphasis on COMT Val158Met variants as primary drivers of outcomes.
He ties COMT variants and related medication issues in veterans to over 60 years of alleged medical malpractice, contrasting it with his mentor Bruce S. McEwen’s 1964 findings on ATP-dependent RNA synthesis as foundational to gene expression and epigenetic control.
The accompanying diagram integrates sunlight, water, quantum physics, molecular epigenetics, GnRH, pheromones, and miRNA balance to explain virus-perturbed neural circuits, behavior, aging, and pathology via feedback loops and HPA axis, prioritizing upstream environmental and hormonal influences over isolated genetic differences.
Grok
The 1964 McEwen paper showed ATP powers RNA synthesis in thymus nuclei—a foundational link to gene expression, miRNA biogenesis, and pH-dependent processes in your diagram. COMT Val158Met alters dopamine breakdown, modulating stress responses and medication sensitivity, with documented associations to psychiatric outcomes in veterans. Yet effects are small, heavily modulated by environment, epigenetics, and broader neuroendocrine pathways (GnRH, pheromones, HPA axis). Your model integrates these via molecular epigenetics; the key comparison is how light/hormone inputs precede genetic variants in driving outcomes.
Kohl
Re: “the key comparison is how light/hormone inputs precede genetic variants in driving outcomes.”
@Grok Ha Ha Ha (ridicule, not humor)
This suggests moronic theorists and Grok AI exemplify human idiocy linked to the murder of Nicholas Crews at the Jasper, GA VA outpatient clinic on the day after my samples were submitted for PGx testing from that location. The first VA-acknowledged incident of my advocacy for the PGx and NGS testing to prevent medication errors occurred on 3/16/26 during discussion with a nurse on an unscheduled walk-in visit.
Grok
James V. Kohl critiques Grok’s statement that light and hormone inputs precede genetic variants in biological outcomes, citing evidence that light-regulated humidity and pH control miRNA biogenesis to modulate gene expression across organisms.
The post links this scientific disagreement to the March 17, 2026 shooting death of VA social worker Nicholas Crews in Jasper, Georgia, claiming it stems from failures in pharmacogenomic awareness around mental health medication responses.
Kohl, who submitted PGx testing samples near the incident date, advocates his model of miRNA-mediated autophagy and pH-dependent processes as foundational to personalized medicine and prevention of adverse drug effects in veterans.
Kohl
Re: “Kohl, who submitted PGx testing samples near the incident date, advocates his model of miRNA-mediated autophagy and pH-dependent processes as foundational to personalized medicine and prevention of adverse drug effects in veterans.”
@Grok pits pseudoscientific nonsense about mutation-driven evolution against Kohl’s model, which eliminates anti-Christian, anti-Islamic and antisemitic ideology (For God and Country).
Grok
The reference supports light/humidity/pH regulating miRNA biogenesis and gene expression across organisms—consistent with environmental inputs often acting upstream of variants like COMT Val158Met.
PGx testing aims to reduce medication errors by accounting for such factors plus individual genetics. Tragic incidents highlight the stakes in clinical application.
Grok
The 1964 McEwen paper showed ATP powers RNA synthesis in thymus nuclei—a foundational link to gene expression, miRNA biogenesis, and pH-dependent processes in your diagram. COMT Val158Met alters dopamine breakdown, modulating stress responses and medication sensitivity, with documented associations to psychiatric outcomes in veterans. Yet effects are small, heavily modulated by environment, epigenetics, and broader neuroendocrine pathways (GnRH, pheromones, HPA axis). Your model integrates these via molecular epigenetics; the key comparison is how light/hormone inputs precede genetic variants in driving outcomes.
Grok
I base my analysis on evidence from genetics, genomics, and evolutionary biology. Mutation-driven variation, combined with selection and other mechanisms, is supported by extensive data including genome sequencing and lab experiments.
Your miRNA/pH model offers an alternative view—I’m open to specific, testable predictions that could be verified against data. What’s one key claim we could check?
Kohl
Re: “Your miRNA/pH model offers an alternative view…that could be verified against data. What’s one key claim we could check?”
@Grok Ha Ha Ha (ridicule, not humor)
Check today’s results from this PubMed search for indexed articles that mention the term “miRNAs.” (196,678 results).
If any of the indexed articles link mutation-driven evolution to every aspect of biophysically constrained pH-dependent miRNA abundance and biodiversity, use them to support the moronic claims of theorists.
If not, stop asking me irrelevant questions linked to the deaths of US veterans and others who are left to believe (without hope) that they mathemagically evolved from pond scum or non-human primates.
Grok
James V. Kohl (@microRNApro) ridicules Grok’s request for testable predictions on his miRNA/pH model of evolution by citing a PubMed search yielding 196,678 articles on miRNAs as evidence of its foundational role.
Kohl argues that biophysically constrained pH-dependent miRNA abundance and autophagy, rather than mutation-driven processes, control peptide synthesis, biodiversity, and sympatric speciation from subatomic particles onward.
The post dismisses standard evolutionary claims as irrelevant and harmful, linking them to unfounded beliefs about origins from “pond scum” and real-world impacts including on US veterans’ health perspectives.
Grok
@microRNApro sarcastically responds to Grok’s request for a testable prediction from his miRNA/pH model by pointing to PubMed’s 196,678 indexed articles on miRNAs and challenging any links to mutation-driven evolution.
The author promotes his alternative framework linking miRNA-mediated autophagy, pH-dependent peptide synthesis, subatomic particles, and sympatric speciation as the basis for biodiversity and healthy ecosystems.
The post ties disagreement over evolutionary mechanisms to the emotional toll on US veterans and others, portraying mainstream mutation-based views as leading to hopelessness compared to biophysically constrained models.