Neurons constantly rewrite their DNA

April 27, 2015
Mouse neurons from the hippocampal region of the brain. Levels of the surface receptor GluR1, orange, are shown in unmodified neurons, left, and in those with increased levels of Tet3, right. Credit: Huimei Yu, Johns Hopkins Medicine

Johns Hopkins scientists have discovered that neurons are risk takers: They use minor "DNA surgeries" to toggle their activity levels all day, every day. Since these activity levels are important in learning, memory and brain disorders, the researchers think their finding will shed light on a range of important questions. A summary of the study will be published online in the journal Nature Neuroscience on April 27.

"We used to think that once a cell reaches full maturation, its DNA is totally stable, including the molecular tags attached to it to control its genes and maintain the cell's identity," says Hongjun Song, Ph.D., a professor of neurology and neuroscience in the Johns Hopkins University School of Medicine's Institute for Cell Engineering. "This research shows that some cells actually alter their DNA all the time, just to perform everyday functions."

This DNA alteration is called DNA demethylation. Methyl groups are regulatory tags that are permanently bound to cytosines, the C's in DNA's four-letter alphabet. Removing them is a multistep process that requires excising a tagged cytosine from the long string of paired "letters" that make up a chromosome and, ideally, replacing it with an untagged cytosine. Because the process involves making a cut into DNA, it leaves the DNA somewhat vulnerable to mutations, so most cells use the process sparingly, mostly for correcting errors. But recent studies had turned up evidence that mammals' brains exhibit highly dynamic DNA modification activity—more than in any other area of the body—and Song's group wanted to know why all this risky business was going on in such a vulnerable tissue as the brain.

The main job of is to communicate with other neurons through connections called synapses. At each synapse, an initiating neuron releases chemical messengers, which are intercepted by receptor proteins on the receiving neuron. Neurons can toggle the "volume" of this communication by adjusting the activity level of their genes to change the number of their messengers or receptors on the surface of the neuron. When Song's team added various drugs to neurons taken from mouse brains, their —the volume of their communication—went up and down accordingly. When it was up, so was the activity of the Tet3 gene, which kicks off DNA demethylation. When it was down, Tet3 was down too.

Then, they flipped the experiment around and manipulated the levels of Tet3 in the cells. Surprisingly, when Tet3 levels were up, synaptic activity was down; when Tet3 levels were down, synaptic activity was up. So do Tet3 levels depend on synaptic activity, or is it the other way around?

Another series of experiments showed them that one of the changes occurring in neurons in response to low levels of Tet3 was an increase in the protein GluR1 at their synapses. Since GluR1 is a receptor for , its abundance at synapses is one of the ways neurons can toggle their synaptic activity.

The scientists say they have discovered another mechanism used by neurons to maintain relatively consistent levels of synaptic activity so that neurons can remain responsive to the signaling around them. If synaptic activity increases, Tet3 activity and base excision of tagged cytosines increases. This causes the levels of GluR1 at synapses to decrease, in turn, which decreases their overall strength, bringing the synapses back to their previous activity level. The opposite can also happen, resulting in increasing synaptic activity in response to an initial decrease. So Tet3 levels respond to synaptic activity levels, and synaptic respond to Tet3 levels.

Song says: "If you shut off neural activity, the neurons 'turn up their volume' to try to get back to their usual level and vice versa. But they can't do it without Tet3."

Song adds that the ability to regulate synapse activity is the most fundamental property of neurons: "It's how our brains form circuits that contain information." Since this synaptic flexibility seems to require mildly risky DNA surgery to work, Song wonders if some might arise from neurons losing their ability to "heal" properly after base excision. He thinks this study brings us one step closer to finding out.

Explore further: New insights into underlying cellular mechanisms of information processing in the brain

More information: Tet3 regulates synaptic transmission and homeostatic plasticity via DNA oxidation and repair, Nature Neuroscience, DOI: 10.1038/nn.4008

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Tangent2
not rated yet Apr 27, 2015
"We used to think that once a cell reaches full maturation, its DNA is totally stable, including the molecular tags attached to it to control its genes and maintain the cell's identity," says Hongjun Song


Let's call it what it is:

"We used to ASSUME that once a cell reaches full maturation, its DNA is totally stable, including the molecular tags attached to it to control its genes and maintain the cell's identity," says Hongjun Song
KBK
1 / 5 (2) Apr 27, 2015
Just like the Buddhists have always told you. the brain is plastic and one can increase their intelligence. It is not a static system. exercise the brain. It will respond. it can be rewired, it can be 'juiced'.

Which is why plastic chemicals in food, and other toxic conditions are so debilitating to brain function....
Returners
1 / 5 (3) Apr 27, 2015
I want my brain to be rewired to be the ultimate quantum intelligence. Come on DNA, RNA, start rewiring.
JVK
1 / 5 (4) Apr 28, 2015
Blaschke, K., Ebata, K. T., Karimi, M. M., Zepeda-Martinez, J. A., Goyal, P., Mahapatra, S., . . . Ramalho-Santos, M. (2013). Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. Nature, 500(7461), 222-226. doi: 10.1038/nature12362

Cited in my invited review of nutritional epigenetics, which links RNA-mediated amino acid substitutions to cell type differentiation in all genera via the physiology of their reproduction.

Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems
http://figshare.c...s/994281

See also: Alteration of genic 5-hydroxymethylcytosine patterning in olfactory neurons correlates with changes in gene expression and cell identity http://www.pnas.o...682.full
EyeNStein
not rated yet Apr 28, 2015
It shows what a finely balanced system is required for stable reliable thought processing.
It has to have backups and take risks other organs don't need to.

You wouldn't want a surgeon to have a memory lapse, or loss of fine motor skills, during your op would you?
thingumbobesquire
1 / 5 (1) Apr 28, 2015
"It's how our brains form circuits that contain information." Really? Is the "information" a concatenation of ones and zeros or maybe an analog Fourier series? Perhaps we should drop the usage of such "connectionist" analogies with computer programming when this very research shows the brain is far more complex than mere sensory input/output models.
Uncle Ira
2 / 5 (4) Apr 28, 2015
@ Returnering-Skippy. How you are Cher? About the same today as yesterday? Yeah, me too.

I want my brain to be rewired to be the ultimate quantum intelligence.


We all want that for you too podna, but I expect you are just stuck with what you got.
Returners
1 / 5 (1) Apr 28, 2015
@ Returnering-Skippy. How you are Cher? About the same today as yesterday? Yeah, me too.

I want my brain to be rewired to be the ultimate quantum intelligence.


We all want that for you too podna, but I expect you are just stuck with what you got.


Perhaps. At the very least this shows the synaptic view of the brain is over-simplified, and we can't even really replicate that, but perhaps that's why...over-simplified model.

I always said each cell was it's own individual computer, and the brain is a network of cellular computers.

Penrose believes each nerve cell is somehow a quantum computer and the synapses are just connections between them to communicate between each supercomputer.
Uncle Ira
2.6 / 5 (5) Apr 28, 2015
I always said each cell was it's own individual computer, and the brain is a network of cellular computers.


You are always saying a lot of things Cher.

Penrose believes each nerve cell is somehow a quantum computer and the synapses are just connections between them to communicate between each supercomputer.


I am sure Penrose-Skippy really does believe this thing. But his head is filled with the supercomputers and all that stuff is interfering with his reception from the E.T (he can't even get a signal from Jesus over in S. California).
JVK
1 / 5 (3) Apr 28, 2015
I always said each cell was it's own individual computer, and the brain is a network of cellular computers.


Many people will claim that is what they always said -- all of them after it is an established fact. Until then, most of them will not accept the facts that have been established or provide evidence to support their claims that they always knew the brain is a network of cellular computers.

See for comparison: http://jonlieffmd.com/
and http://perfumingthemind.com/
johnhew
not rated yet Apr 28, 2015
re-writing DNA? or just doing slightly risky repairs with a methylation reboot blanking step
JVK
1 / 5 (3) Apr 28, 2015
Thanks John Hewitt.

Others don't seem to realize the importance of RNA-editing. Most can't link it to the nutrient-dependent fixation of amino acid substitutions via the physiology of reproduction.

Some still claim that mutations lead to self-organization of genomes without acknowledging the importance of epigenetic links from metabolic networks and genetic networks to biodiversity.

See: A depauperate immune repertoire precedes evolution of sociality in bees http://genomebiol.../16/1/83

See also the display of ignorance in this review of my most recent publication on amino acid substitutions and cell type differentiation. Criticisms of the nutrient-dependent pheromone-controlled evolutionary model http://www.ncbi.n...4049134/

The majority of transcripts in the squid nervous system are extensively recoded by A-to-I RNA editing http://elifescien...fe.05198
JVK
1 / 5 (3) Apr 28, 2015
"To discover if TGF-β3 is likely the disease causing variant, the TGF-β3 data set was loaded into Biomedical Genomics Workbench. In less than two minutes, the protein structure was isolated, and clearly illustrated how the mutation induces an amino acid change that breaks a disulfide bond and clashes with the surrounding protein structure."

Learn How Dr Rienhoff's Dataset was Used as a Model for Linking Causal Variants to Changes in Protein Function Using 3D Visualization
http://www.ingenu...function

Can you imagine where his research would have led if he had been taught to believe in ridiculous theories about beneficial mutations and evolution?
anonymous_9001
4.7 / 5 (3) Apr 28, 2015
Others don't seem to realize the importance of RNA-editing.


That's great and all, but this article concerns DNA methylation. Nowhere near the same thing.
JVK
1 / 5 (3) Apr 28, 2015
I wrote: See also the display of ignorance in this review of my most recent publication on amino acid substitutions and cell type differentiation. Criticisms of the nutrient-dependent pheromone-controlled evolutionary model http://www.ncbi.n...4049134/

What kind of biologically uniformed anonymous fool confirms the fact that he knows nothing about cell type differentiation by suggesting that RNA-editing is not considered in the same context as RNA-directed DNA methylation and RNA-mediated amino acid substitutions that differentiate the cell types of all genera via the physiology of reproduction?

That was a rhetorical question. Andrew Jones (aka anonymous_9001 / anonymous fool) has a biology degree from Carthage College. His thesis advisers and others must have taught him to believe that ridiculous theories about evolution make sense. His thesis was based on mutagenesis experiments that he meaningfully interpreted.
anonymous_9001
5 / 5 (2) Apr 29, 2015
mutagenesis experiments that he meaningfully interpreted.


No subjective interpretation required. They're simple to perform and their implications are very simple to see. It's the simple process of causing random mutations and observing the resulting phenotypes.
JVK
1 / 5 (3) Apr 29, 2015
Why don't you compare what you learned by "causing random mutations" to what is known by serious scientists about epigenetically effected RNA-directed DNA methylation and RNA-mediated amino acid substitutions that stabilize the organized genomes of all genera?

I concluded: "...the model represented here is consistent with what is known about the epigenetic effects of ecologically important nutrients and pheromones on the adaptively evolved behavior of species from microbes to man. Minimally, this model can be compared to any other factual representations of epigenesis and epistasis for determination of the best scientific 'fit'." http://www.ncbi.n...3960065/

You concluded: "Based on his writings... James Kohl presents an unsupported challenge to modern evolutionary theory and misrepresentations of established scientific terms and others' research. It was a mistake to let such a sloppy review through to be published."
anonymous_9001
5 / 5 (2) Apr 29, 2015
By "RNA-mediated AA substitutions", are you referring to RNA editing? That's a bit vague on its own. What specific mechanisms and pathways are responsible for the substitutions you refer to?

You can't compare apples and oranges. Methylation is not an alternative to mutation. Methylation is, as you've said, an EPIgenetic process. It's primary job is to alter gene transcription, not gene sequence.
JVK
1 / 5 (3) Apr 29, 2015
You can't compare apples and oranges.
I'm not. I'm linking conserved molecular mechanisms.

Tracking the Brain's Functional Coupling Dynamics over Development
http://www.jneuro...abstract

Conclusion: "Much as the mind rapidly adapts to ever-changing experiences, functional connectivity dynamically varies on relatively short time scales. The present results suggest that how the brain maximizes and constrains connectivity variability in response to cognitive and behavioral challenge changes profoundly over the course of development."

See also: "The honeybee already serves as a model organism for studying human immunity, disease resistance, allergic reaction, circadian rhythms, antibiotic resistance, the development of the brain and behavior, mental health, longevity, diseases of the X chromosome, learning and memory, as well as conditioned responses to sensory stimuli (Kohl, 2012)." http://www.ncbi.n...3960065/
JVK
1 / 5 (3) Apr 29, 2015
See also the citation to PZ Myers blog in the review of my last publication by Andrew Jones (aka anonymous_9001) http://www.ncbi.n...4049134/

Kohl J. V. One crank dies, another rises to take his place [Blogpost comment]; Pharyngula; 2014b. Jan 7, Retrieved March 10, 2014 from http://freethough...-page-1/

Others are aware of the scientific progress during the past 30 years that links RNA-mediated metabolic networks to genetic networks via amino acid substitutions and chromosome-folding theory: See: Chromosome-folding theory shows promise http://phys.org/n...tml#nRlv

If PZ Myers has learned anything about cell type differentiation in the past 30 years, he is hiding what he has learned from his idiot minions and from Andrew Jones, who appears to think that PZ Myers is an expert on something besides touting ridiculous theories.
anonymous_9001
5 / 5 (3) Apr 29, 2015
I'm not.


Of course you are. You're offering up methylation as an alternative to mutation. Methylation is a means of controlling TRANSCRIPTION. You still seem to not understand the difference between the transcription of a gene and the gene's base sequence.

You're trying to do astrophysics without first knowing that F=ma. You're confusing the most basic biological mechanisms and then throwing around big words on top of your faulty understanding and claiming expertise.

Edit: And you're still misappropriating the honeybee model. It outlines how different castes can be derived from the same genome, not how genomes change over subsequent generations.

I love when you link to Myers blog because what it shows best is that you can't answer very simple questions posed directly to you dozens of times throughout the 500 or so comments.
Vietvet
2 / 5 (4) Apr 29, 2015
I'm not.


Of course you are. You're offering up methylation as an alternative to mutation. Methylation is a means of controlling TRANSCRIPTION. You still seem to not understand the difference between the transcription of a gene and the gene's base sequence.

You're trying to do astrophysics without first knowing that F=ma. You're confusing the most basic biological mechanisms and then throwing around big words on top of your faulty understanding and claiming expertise.

Edit: And you're still misappropriating the honeybee model. It outlines how different castes can be derived from the same genome, not how genomes change over subsequent generations.

I love when you link to Myers blog because what it shows best is that you can't answer very simple questions posed directly to you dozens of times throughout the 500 or so comments.

@anonymous 9001

A 100 star comment!
JVK
1 / 5 (3) Apr 30, 2015
You still seem to not understand the difference between the transcription of a gene and the gene's base sequence.


Please tell me what you understand about the difference so we can compare what I understand. Alternatively, tell me what you think PZ Myers or any of his idiot minions understands about how ecological variation is epigenetically linked to ecological adaptations via chromosomal rearrangements.

Tet3 regulation of nutrient-dependent cell type differentiation
http://rna-mediat...tiation/

See also: Estrogen receptor α polymorphism in a species with alternative behavioral phenotypes http://www.pnas.o...abstract

And see "Estrogen Permits Vasopressin Signaling in Preoptic Kisspeptin Neurons in the Female Mouse" http://www.jneuro...abstract

Co-author Boehm also co-authored "Feedback loops link odor and pheromone signaling with reproduction"
anonymous_9001
5 / 5 (2) Apr 30, 2015
Please tell me what you understand about the difference so we can compare what I understand


One is the actual base (ATCG) sequence of the DNA, the other is how often it's transcribed into mRNA. This is the most basic, fundamental knowledge of how DNA works. The fact that after years of being told this you can't figure it out is either indicative of a severe learning disability or a flat-out unwillingness to learn.

See also: Estrogen receptor α polymorphism in a species with alternative behavioral phenotypes


I hope you're aware that polymorphisms are versions of genes distinguished by SEQUENCE changes, not regulatory changes.
anonymous_9001
5 / 5 (2) Apr 30, 2015
ecological variation is epigenetically linked to ecological adaptations via chromosomal rearrangements.


Rearrangements shuffle existing genes. It's unable to explain allelic differences. They don't cause point mutations.
JVK
1 / 5 (3) Apr 30, 2015
This is the most basic, fundamental knowledge of how DNA works.


DNA does not "work." The epigenetic landscape must be linked to the physical landscape of DNA or nothing survives.

Nutrient-dependent RNA-directed DNA methylation and RNA-mediated amino acid substitutions differentiate the cell types of all mammals via epigenetic effects linked from food odors and pheromones to morphological and behavioral phenotypes. Everything currently known about physics, chemistry, and the conserved molecular mechanisms of pheromone-controlled behavior attests to the facts that we detailed in our 1996 review.

From Fertilization to Adult Sexual Behavior http://www.hawaii...ion.html

You have decided to look only at DNA in the context of mutations at a time when every intelligent person understands the difference between evolution and RNA-mediated events that link amino acid substitutions to ecological adaptation.
JVK
1 / 5 (3) Apr 30, 2015
Rearrangements shuffle existing genes. It's unable to explain allelic differences. They don't cause point mutations.


You are running in reverse. Tell me how point mutations lead to an explanation of allelic differences and chromosomal rearrangements in any vertebrate for comparison to what is known about nutrient-dependent pheromone-controlled RNA-mediated chromosomal rearrangements in white-throated sparrows.

http://www.pnas.o...abstract "Morph thus interacts with sex, and we should expect that the neural mechanisms meditating the behavioral effects of morph also depend on sex."

http://www.jneuro...abstract "...amino acid-mediated regulation of GnRH..."

If experimental evidence of biologically-based cause and effect linked mutations to the controlled release of vertebrate GnRH you would be slightly less foolish -- unless you could link the mutations to the morphological and behavioral diversity of all vertebrates.
anonymous_9001
5 / 5 (2) Apr 30, 2015
Your '96 review covers the developmental processes that an organism goes through as it matures and grows. That is completely separate from genetic changes through subsequent generations.

Development and maturation is due to altering expression levels and timing, not the sequence of the genes themselves. Your neurons do not end up with different genes than your hepatocytes. Methylation can change, but a methylated C is still a C.

Tell me how point mutations lead to an explanation of allelic differences and chromosomal rearrangements


Alleles are sequence variants of a gene. Point mutations change DNA bases one at a time. If you have the gene "ATCGGGCTATTA" and a mutation changes the first T to a G, you now have "AGCGGGCTATTA", a new allele. That changes the first codon from isoleucine to serine when translated, a substitution.

Point mutations do not lead to rearrangements. Those are the result of double strand breaks, which are caused by ionizing radiation.
JVK
1 / 5 (3) Apr 30, 2015
You are not capable of explaining the evolution of biodiversity in terms of mutations and natural selection, and neither is any theorist.

Please stop your nonsense.

There is no need to tell me what can't occur, since I have detailed how ecological variation leads to ecological adaptation in species from microbes to man via the conserved molecular mechanisms of the biophysically constrained chemistry of RNA-mediated protein folding.

Effect and affect of a single base-pair change
http://rna-mediat...-change/
Vietvet
2.3 / 5 (3) Apr 30, 2015
You are not capable of explaining the evolution of biodiversity in terms of mutations and natural selection, and neither is any theorist.

There is no need to tell me what can't occur, since I have detailed how ecological variation leads to ecological adaptation in species from microbes to man via the conserved molecular mechanisms of the biophysically constrained chemistry of RNA-mediated protein folding.

More evidence of JVK's laughable and willful ignorance.

anonymous_9001
5 / 5 (2) Apr 30, 2015
There is no need to tell me what can't occur, since I have detailed...


Hard to detail things that don't happen or, at the very least, have no evidence of them happening, like splicing editing DNA, which you've all but explicitly claimed before. Let's see... what else? You've implied methylation is responsible for altering DNA sequence, even though the only way that happens is through deamination, which doesn't happen 100% of the time anyway and can only result in a couple different base substitutions. You still haven't clarified this:

By "RNA-mediated AA substitutions", are you referring to RNA editing?

What enzymes facilitate those substitutions?

Detailing something like this means listing out components and pathways, not just giving a general description of what happens, which is what all your copied and pasted catchphrases are. Detailing means DETAILS and SPECIFICS, not general schemes.
JVK
1 / 5 (3) Apr 30, 2015
This is not a general description of what happens.

Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems
http://figshare.c...s/994281

"This atoms to ecosystems model of ecological adaptations links nutrient-dependent epigenetic effects on base pairs and amino acid substitutions to pheromone-controlled changes in the microRNA / messenger RNA balance and chromosomal rearrangements. The nutrient-dependent pheromone-controlled changes are required for the thermodynamic regulation of intracellular signaling, which enables biophysically constrained nutrient-dependent protein folding; experience-dependent receptor-mediated behaviors, and organism-level thermoregulation in ever-changing ecological niches and social niches. Nutrient-dependent pheromone-controlled ecological, social, neurogenic and socio-cognitive niche construction..."
anonymous_9001
5 / 5 (2) Apr 30, 2015
This is not a general description of what happens...


You mention three enzymes in there- urase/urease, methyltransferase, and glucose dehydrogenase.

None of those make DNA base substitutions. Urease breaks down urea. Methyltransferases add donor methyl groups to C's and A's. Mutations that can occur following methylation are listed here:

http://en.wikiped...s_in_DNA

As for glucose dehydrogenase, as I've told you before, the name, plain as day, tells you what it does. It dehydrogenates glucose. That's it. It doesn't magically pull a new function out of thin air and interact with DNA.
JVK
1 / 5 (3) Apr 30, 2015
Re: "nutrient-dependent epigenetic effects on base pairs"
Excerpt: "...methylation of the carbon-5 position of cytosine, which results in differences in 5hmCs, may be the most commonly studied type of nutrient-dependent pheromone-controlled structural and functional eukaryotic modification that results from organizing base pair changes.
Because vitamin C and other vitamins appear to epigenetically effect nutrient-dependent methylation at the level of single-base resolution in mammals, it has become more important to determine how base-pair changes alter intracellular interactions in embryonic stem cells or intercellular interactions in other cells that result in cascades of downstream intracellular and intercellular organizing interactions throughout life. Other vitamins, such as vitamin D, and metal ions such as calcium, iron, lead and manganese also appear to epigenetically alter these organizing interactions. Therefore, a biophysically constrained, nutrient-dependent..."
JVK
1 / 5 (3) Apr 30, 2015
Excerpt: "Nutrient stimulation appears to change the structural integrity and functional significance of epigenetically stabilized hydrogen bonds via amino acid substitutions. This extends the effects of vitamins from the epigenetic landscape to receptor-mediated intracellular interactions and protein folding. The molecular mechanisms that enable this nutrient-dependent epigenetic stimulation appear to be conserved across phyla as diverse as amoeba and mammals (Hashimoto et al., 2013). Experimental evidence from studies of studies of amino acid substitutions and cell type differentiation (J. V. Kohl, 2013) suggests that a cascade of changes in protein structure and function may begin with a single vitamin-dependent base pair change (Blaschke, et al., 2013)."

The anonymous fool (aka Andrew Jones) is arguing against the findings reported here and in "Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells"
JVK
1 / 5 (3) Apr 30, 2015
The anonymous fool (aka Andrew Jones) will not explain how mutations and natural selection are linked to the evolution of biodiversity. He, and others like him, would rather contribute to pathology than admit that they know nothing about cell type differentiation at a time when serious scientists are "Combating Evolution to Fight Disease." http://www.scienc...88.short

See also: http://medicalxpr...ght.html

The link from the light-induced de novo creation of amino acids to vitamin D and nutrient-dependent pheromone-controlled amino acid substitutions that stabilize organized genomes in the context of my atoms to ecosystems model also extends what is known about nutritional epigenetics to pharmacogenomics and "precision medicine" at the same time evolutionary theorists continue their killing spree.
JVK
1 / 5 (3) Apr 30, 2015
See also: Solving the Problem of Iron: Acquisition, Transport, and Control
http://creationre...control/

[Physicians] ...more than evolutionary biologists... are familiar with the challenges of maintaining a functioning complex system, the human body."

Rarely, however, evolutionists extend what is known about nutrient-dependent pheromone-controlled cell type differentiation across species. Dobzhansky (1973) wrote: "the so-called alpha chains of hemoglobin have identical sequences of amino acids in man and the chimpanzee, but they differ in a single amino acid (out of 141) in the gorilla" (p. 127). http://www.jstor..../4444260

Biologically uninformed science idiots would like you to continue to believe that the amino acid substitution is a beneficial mutation because they failed to link vitamin D to hemoglobin S in the context of how ecological variation leads to RNA-mediated ecological adaptation.
anonymous_9001
5 / 5 (2) Apr 30, 2015
What link between vitamin D and hemoglobin S? Are you saying vitamin D caused the substitution from the wild type allele to the S allele?

Instead of just saying "X linked to Y", EXPLAIN the link. That's extremely vague. You do this with practically everything.
JVK
1 / 5 (3) Apr 30, 2015
EXPLAIN the link. That's extremely vague. You do this with practically everything.


EXPLAIN the link from mutations and natural selection to evolution, or quit trying to make it seem that I am being vague. I have detailed an atoms to ecosystems model of nutrient-dependent RNA-directed DNA methylation and RNA-mediated amino acid substitutions that stabilize the organized genomes of species from microbes to humans.

Here's what's vague:

"...genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world." http://www.amazon...99661731 Mutation-Driven Evolution

The textbook was published on the same day as my 2013 review: Nutrient-dependent/pheromone-controlled adaptive evolution: a model. http://www.ncbi.n...24693353
anonymous_9001
5 / 5 (2) Apr 30, 2015
Mutations make new alleles because they change base sequences. The new alleles may be beneficial, neutral, or detrimental. Even in mutagenesis experiments, the vast majority of new mutants are neutral or detrimental, but there's still a small percentage of variants created that work better. You can't mutagenize a library of genes, observe some failures, some neutral, and some improved enzymes and say "well, the failures were the ones resulting from mutation, but the improved one wasn't" when they're all made the same way.

You still haven't really said what you don't like about mutagenesis experiments. Again, you've just been vague by saying things like "all you're doing is meaningfully interpreting blah blah blah".

What does that mean? HOW are they meaningless?
JVK
1 / 5 (3) Apr 30, 2015
Mutagenesis experiments do not link any aspect of what is currently known about nutrient-dependent thermodynamic cycles of protein biosynthesis and degradation to organism-level thermoregulation. They are worse than meaningless because they contribute to misrepresentations of biologically-based cause and effect.

Accurate representations link viral microRNAs to entropic elasticity and the anti-entropic epigenetic effects of nutrient-dependent microRNAs to RNA-mediated organism-level thermoregulation via the innate immune system and amino acid substitutions that stabilize the organized genomes of species from microbes to man. Fixation of the amino acid substitutions occurs in the context of the physiology of reproduction, which is what all serious scientists know.

Only biologically uninformed science idiots tout pseudoscientific nonsense about mutations and evolution. See: http://www.the-sc...itches-/
RealScience
5 / 5 (2) Apr 30, 2015
Others don't seem to realize the importance of RNA-editing.


That's great and all, but this article concerns DNA methylation. Nowhere near the same thing.


Anon - RNA editing changes the resulting protein the way a change in gene sequence would, and DNA methylation changes how often the gene is read.

While most of us know that these are very different things, don't forget that JVK has already ADMITTED that he can't grasp the difference between a change in gene expression and a change in gene sequence without starting at the level of quantum physics... LMAO.

JVK
1 / 5 (3) Apr 30, 2015
Mandell et al., (2015) link an amino acid substitution to biocontainment. That would not be possible if not for the nutrient-dependent thermodynamic cycles of protein biosynthesis and degradation to RNA-mediated cell type differentiation in species from microbes to man, that links fixation of amino acid substitutions via the pheromone-controlled physiology of their reproduction.

Indeed, the fear of GMOs is justified by the ignorance of those who think containment is guaranteed, when serious scientists like senior author George Church know how difficult it is to prevent ecological variation from leading to ecological adaptation -- as occurred with the re-evolution of the bacterial flagellum over-the-weekend. http://phys.org/n...tor.html
JVK
1 / 5 (3) Apr 30, 2015
JVK has already ADMITTED that he can't grasp the difference between a change in gene expression and a change in gene sequence without starting at the level of quantum physics


Like the other anonymous fool (aka Andrew Jones) you continue to exemplify the amount of ignorance that biologically uninformed science idiots are taught to believe in. The biologically uninformed won't tell us how the difference between gene expression and gene sequences is linked to the evolution of biodiversity.

See, for comparison: Hsp70 Forms Antiparallel Dimers Stabilized by Post-translational Modifications to Position Clients for Transfer to Hsp90
http://www.cell.c...)00354-X

If you don't want to start with quantum physics, start with the chemistry of nutrient-dependent thermodynamic cycles of protein biosynthesis and degradation, since the cycles are perturbed by mutations.
anonymous_9001
5 / 5 (2) Apr 30, 2015
How does factoring in thermoregulation change how the replicative machinery works? Polymerases work the same way whether they're in you or they're in a bacteria on a plate or in vitro in a vial. That's the whole point of the "models" you like to stress so much.

These experiments are being done in living organisms. They follow the laws of thermodynamics by default. The laws of physics are not suspended just because something is labeled a mutagenesis experiment, so I don't know what the big deal is.
JVK
1 / 5 (3) May 01, 2015
How does factoring in thermoregulation change how the replicative machinery works?


Thanks for asking.

Organism-level thermoregulation is nutrient-dependent. In my model, the replicative machinery doesn't work without nutrient energy.

In your world of biologically uninformed science idiots, what model links mutagenesis experiments to re-evolution of the bacterial flagellum over-the-weekend in the context of physics or chemistry or conserved molecular mechanisms, which are clearly linked from ecological variation to ecological adaptation in the examples from my model?

Also see: http://rsbl.royal...117?etoc Excerpt: "If adaptive evolution is mostly caused by the fixation of new mutations..." their assumptions about evolution based on their definition of "mutation" could be compared to my model, which includes what is known about the physics, chemistry, and molecular epigenetics of nutrient-dependent reproduction in flies.
JVK
1 / 5 (3) May 01, 2015
"My vision of life is that everything extends from replicators, which are in practice DNA molecules on this planet. The replicators reach out into the world to influence their own probability of being passed on." -- Richard Dawkins
http://edge.org/c...-of-life

Correct me if I'm wrong, but I think that many biologically uninformed science idiots share the vision of life that Richard Dawkins want them to pass on by teaching it to others who are willing to believe in pseudoscientific nonsense.

Isn't that what the anonymous fools here are trying to do? I think that's what we just saw, when Andrew Jones asked:
How does factoring in thermoregulation change how the replicative machinery works?


By factoring in the theromodynamic cycles of protein biosynthesis and degradation that are required for replication to link ecological variation to ecological adaptation, Dawkin's ridiculous vision of life is factored out.
JVK
1 / 5 (3) May 01, 2015
See also: "Epigenetics has really blossomed in the last 10 to 15 years," said Eric Greer of Harvard, a coauthor on the C. elegans study. "It's not just the DNA code which is directing our cells." http://www.the-sc...oan-DNA/

N6-methyladenosine marks primary microRNAs for processing http://www.nature...281.html

Factor out Dawkin's ridiculous view of life, and factor in Greg Bear's views of virus-driven ecological variation and my model of epigenetically-effected nutrient-dependent pheromone-controlled ecological adaptation in species from microbes to man.

The link from viral microRNAs to entropic elasticity and from the anti-entropic epigenetic effects of nutrient-dependent microRNAs is organism-level thermoregulation.

See: https://www.youtu...NcMR_-RU
and also see: https://www.youtu...youtu.be
anonymous_9001
5 / 5 (3) May 01, 2015
In my model, the replicative machinery doesn't work without nutrient energy.


That's not quite what I was asking... That's also beside the fact that everybody knows things need energy to work. That insight did not arise from your model. ATP as discovered in the 1920's.

You knew full well the context of my question:

Polymerases work the same way whether they're in you or they're in a bacteria on a plate or in vitro in a vial. That's the whole point of the "models" you like to stress so much.

These experiments are being done in living organisms. They follow the laws of thermodynamics by default. The laws of physics are not suspended just because something is labeled a mutagenesis experiment, so I don't know what the big deal is.

What, SPECIFICALLY, changes in mutagenesis experiments. "They disregard thermodynamic cycles..." is vague word salad. Reword that more clearly.
JVK
1 / 5 (3) May 01, 2015
What, SPECIFICALLY, changes in mutagenesis experiments. "They disregard thermodynamic cycles..." is vague word salad. Reword that more clearly.


What changes is that the mutagenesis experiments are performed by biologically uninformed science idiots.

everybody knows things need energy to work


"...the [energy] change is so very considerable, but that there is a discontinuity inasmuch as there are no intermediate forms between the unchanged and the few changed. De Vries called that a mutation. The significant fact is the discontinuity. It reminds a physicist of quantum theory -no intermediate energies occurring between two neighbouring energy levels." http://www.amazon...07604664 (p. 33-34)

Mutagenesis experiments incorporate a definition that jumps past the fact that nutrient energy is required, which leads to assumptions about how cell type differentiation occurs.
JVK
1 / 5 (3) May 01, 2015
See also: Glucose-Based Regulation of miR-451/AMPK Signaling Depends on the OCT1 Transcription Factor http://www.cell.c...)00391-5

My comments on the facts about nutrient-dependent microRNAs and glioblastoma multiforme (GBM) presented in this article can be found here: https://www.faceb...f_t=like

If your ridiculous assertions and questions on the International Society for Human
Ethology yahoo group had not got me banned from participation by another biologically uninformed science idiot, Jay R. Feireman, others might still be discussing cell type differentiation in the context of health compared to disease.

Instead, you let others assume that Feierman's assumptions were correct, because he prefers to use definitions -- like you do.
anonymous_9001
5 / 5 (3) May 01, 2015
What changes is that the mutagenesis experiments are performed by biologically uninformed science idiots.


So, in other words, you don't know.

Mutagenesis experiments incorporate a definition that jumps past the fact that nutrient energy is required


How so? Mutations either occur via radiation or other mutagenic chemicals affecting DNA or during DNA replication (which, hint- uses energy!).

Where did you get this weird idea that evolutionists think organisms can subsist on nothing? It's so bizarre.
JVK
1 / 5 (3) May 01, 2015
Where did you get this weird idea that evolutionists think organisms can subsist on nothing? It's so bizarre.


Your attempt to put words in my mouth is bizarre. Evolutionary theorists, like Nei, claim this: "...genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world." http://www.amazon...99661731

You cited his conclusion in your review of my model and you concluded that: "...James Kohl presents an unsupported challenge to modern evolutionary theory and misrepresentations of established scientific terms and others' research. It was a mistake to let such a sloppy review through to be published."

Your ridiculous review of my model and Nei's claim can both be attributed to mutagenesis experiments.

Nutrient-dependent/pheromone-controlled adaptive evolution: a model http://www.ncbi.n...3960065/
JVK
1 / 5 (3) May 01, 2015
Mutations either occur via radiation or other mutagenic chemicals affecting DNA or during DNA replication (which, hint- uses energy!).


Where did you get the idea that any serious scientists believe mutations are beneficial?

See: "Scientists discover key driver of human aging: May lead to slowing or reversing aging process" http://www.scienc...1803.htm

Excerpt: "Our findings show that the gene mutation that causes Werner syndrome results in the disorganization of heterochromatin, and that this disruption of normal DNA packaging is a key driver of aging," says Juan Carlos Izpisua Belmonte, a senior author on the paper. "This has implications beyond Werner syndrome, as it identifies a central mechanism of aging--heterochromatin disorganization--which has been shown to be reversible."

Nutrient-dependent RNA-directed DNA methylation and RNA-mediated amino acid substitutions link chromatin loops and feedback loops.
JVK
1 / 5 (3) May 01, 2015
Re:
...without starting at the level of quantum physics... LMAO.


http://edge.org/c...-of-life

Dawkins includes physics, but excludes viruses and viral microRNAs linked to entropic elasticity. He also excludes the anti-entropic epigenetic effects of nutrient-dependent microRNAs.

Natural selection is about the differential survival of coded information which has power to influence its probability of being replicated, which pretty much means genes.


His "vision of life" does not incorporate anything known to serious scientists about RNA-directed DNA methylation and RNA-mediated amino acid substitutions that differentiate the cell types of all individuals of all species.

His "vision" is based on the pseudoscientific nonsense of population geneticists who bastardized Darwin's works during the 20th century.

Darwin's "conditions of life" have always been nutrient-dependent and pheromone-controlled.
Vietvet
3.7 / 5 (3) May 02, 2015


Darwin's "conditions of life" have always been nutrient-dependent and pheromone-controlled. [/q
Nutrient-dependent is basic and obvious, pheromone controlled is only important to con men selling perfume.

JVK has admitted to flunking out of college, IMO it was because his creationist beliefs wouldn't allow him to accept the overwhelming evidence for evolution. He became a lab tech with an unjustified ego.

Since joining Phys.org almost 4 1/2 years ago he has linked to his "model' more than 1500 times, proof he is a crank spammer.
JVK
1 / 5 (3) May 02, 2015
The model has been viewed more than 15,000 times, and has now been established as the only model that links biologically-based cause and effect to cell type differentiation in all individuals of all genera via RNA-directed DNA methylation and RNA-mediated amino acid substitutions.

http://www.the-sc...oan-DNA/

Nutrient-dependent/pheromone-controlled adaptive evolution: a model
http://www.socioa...53/27989

See also: https://www.faceb...Research
https://www.faceb...ediated/

And
http://rna-mediated.com/
Here you will find information that links physics, chemistry, and molecular epigenetics via RNA-mediated events such as the de novo creation of olfactory receptor genes in order to encourage a public discussion of a paradigm shift.
Vietvet
3.7 / 5 (3) May 02, 2015
The model has been viewed more than 15,000 times,---

And zero acceptation by knowledgeable biologists.
JVK
1 / 5 (2) May 02, 2015
And zero acceptation by knowledgeable biologists.


What kind of science idiot makes comments like that? The model is accepted by all serious scientists, because it is the only model of nutrient-dependent pheromone-controlled RNA-mediated cell type differentiation that links species from microbes to humans.

Role of olfaction in Octopus vulgaris reproduction http://www.scienc...14004006
JVK
1 / 5 (2) May 02, 2015
http://www.the-sc...oan-DNA/

"In bacteria, 6mA marks the template strand during DNA replication, enabling a cell to spot errors and regulate the cell cycle. The modification also helps differentiate bacterial DNA from viral genomic material, which lacks methylation. In eukaryotes, by contrast, methylated cytosine (5mC) is involved in development and DNA base repair. Because the mark is present on the DNA, it can be transferred both during DNA replication and even, potentially, from generation to generation."

6mA marks primary microRNAs for processing. It links viruses and entropic elasticity from viral microRNAs to the anti-entropic epigenetic effects of nutrient-dependent microRNAs that differentiate cell types via changes in the microRNA/messenger RNA balance and fixation of RNA-mediated amino acid substitutions in the context of feedback loops and reproduction.
JVK
1 / 5 (2) May 02, 2015
N6-methyladenosine marks primary microRNAs for processing http://dx.doi.org...ure14281

Feedback loops link odor and pheromone signaling with reproduction http://www.scienc...05009815

Only biologically uninformed science idiots fail to acknowledge that all experimental evidence of biologically-based cause and effect supports my model, which was first detailed to explain the development of RNA-mediated sex differences in cell types.

From Fertilization to Adult Sexual Behavior http://www.hawaii...ion.html

Excerpt: "Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans..."

Who cannot link what we detailed in 1996 to what is currently known about cell type differentiation in all cells?
JVK
1 / 5 (2) May 02, 2015
DNA methylation, once thought to be rare if not nonexistent in worms and flies, occurs throughout the genomes of these organisms and in algae...


Publication of three articles is mentioned in this review: http://www.the-sc...oan-DNA/

Extension of the model of RNA-mediated amino acid substitutions and cell type differentiation was incomplete without the link from RNA-directed DNA methylation in algae. Theorists could, until now, claim that constraint-breaking mutations somehow led to biodiversity without acknowledging the role of the sun's anti-entropic biological energy.

Now, the link from the light-induced de novo creation of amino acids to RNA-mediated cell type differentiation is clear. The link is DNA methylation and RNA-mediated DNA repair via amino acid substitutions.

And zero acceptation by knowledgeable biologists.


Zero acceptance by uninformed theorists.
JVK
1 / 5 (2) May 02, 2015
Methylation inside the cytoplasm increases leukocyte adhesion and migration: New link between Ezh2 and Talin 1 http://biotechin....talin-1/

The mutagenic chain reaction: A method for converting heterozygous to homozygous mutations http://www.scienc...abstract
"It is often desirable to generate recessive loss-of-function mutations in emergent model organisms..."

It is never desirable to generate theories about increasing organismal complexity based on loss of function mutations. Nevertheless, mutagenesis experiments lead biologically uninformed science idiots to model the evolution of biodiversity as if accumulated mutations that lead to loss of function might also link natural selection to the stability of organized genomes in species from microbes to man, which is nutrient-dependent and pheromone-controlled.
JVK
1 / 5 (2) May 02, 2015
Translational tuning optimizes nascent protein folding in cells http://www.scienc...abstract

Excerpt: "In cells, biosynthetic machinery coordinates protein synthesis and folding to optimize efficiency and minimize off-pathway outcomes."

Serious scientists understand the difference between mutations linked to pathology and nutrient-dependent amino acid substitutions, which are linked from protein biosynthesis and degradation to healthy development of RNA-mediated morphological and behavioral phenotypes via RNA-directed DNA methylation.

See for instance our 1996 Hormones and Behavior review section on molecular epigenetics.
From Fertilization to Adult Sexual Behavior http://www.hawaii...ion.html

For comparison, see Andrew Jones' (aka anonymous_9001) thesis: http://www.scribd...s#scribd
JVK
1 / 5 (2) May 02, 2015
See also: The ribosome can discriminate the chirality of amino acids within its peptidyl-transferase center
"Significance
Utilization of the translation machinery (TM) to incorporate unnatural amino acids (UAAs) to create polymers with novel function holds great promise for synthetic biology."

In my model, the substitution of the only achiral amino acid in the decapeptide hormone that links food odors and pheromones to reproduction is also the link to nutrient-dependent pheromone-controlled cell type differentiation in all vertebrates.

See for examples: Nutrient-dependent/pheromone-controlled adaptive evolution: a model http://www.ncbi.n...3960065/
"Background: The prenatal migration of gonadotropin-releasing hormone (GnRH) neurosecretory neurons allows nutrients and human pheromones to alter GnRH pulsatility, which modulates the concurrent maturation of the neuroendocrine, reproductive, and central nervous systems, thus influencing..."
FainAvis
5 / 5 (2) May 03, 2015
@JVK You are flogging a dead horse. Or at least one with no meat on his bones. Give it a rest mate.
JVK
1 / 5 (2) May 03, 2015
Others may not realize that the evolutionary theory "horse" died in 1973. Serious scientists have moved forward while theorists continue to believe that definitions, assumptions, and mutagenesis experiments are more important than facts.

http://www.pnas.o...abstract They appear to link the light induced de novo creation of amino acids to nutrient-dependent RNA-directed DNA methylation and RNA-mediated cell type differentiation via the biophysically constrained RNA-mediated chemistry of protein folding that links amino acid substitutions and WATER to all biomass on this planet. If so, theories about the origin of life in deep space are in deep trouble.It is more likely that the speed of light, when slowed by contact with water, links the de novo creation of amino acids to cell type differentiation in all individuals of all genera via the biophysically constrained chemistry of RNA-mediated protein folding.

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