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F/N: Six-bit storage of information in BOTH D/RNA codons and CaMKII-Micro Tubule “bytes”? Coincidence?

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A few days back, Dr Hunter highlighted here and at his own blog, a suggestion in PLoS that CaMKII-MT “bytes” are used in neurons to store six-bit coded information. (BTW, “byte” can be used for short bit arrays, not just eight-bit ones.)

Let’s look at an illustration:

Craddock et al, Figure 1. The CaMKII holoenzyme. Top - Face View, Bottom - Side View. (A) Not activated. Yellow/Green - Kinase domains, Purple - Association domain, Brown –Autoregulatory domain, Black – Linker domain. (B) Activated, (C) Electrostatic map: Blue +0.5 kT/e, Red −0.5 kT/e. Scale bar 5 nm. doi:10.1371/journal.pcbi.1002421.g001 (NB: A 20 nanometre storage unit compares well with our own IC ckts, too,)


Clipping the Author Summary of the PLoS article by Travis J. A. Craddock1*, Jack A. Tuszynski1,2, & Stuart Hameroff:

Memory is understood as strengthened synaptic connections among neurons. Paradoxically components of synaptic membranes are relatively short-lived and frequently re-cycled while memories can last a lifetime. This suggests synaptic information is encoded at a deeper, finer-grained scale of molecular information within post-synaptic neurons. Long-term memory requires genetic expression, protein synthesis, and delivery of new synaptic components. How are these changes guided on the molecular level? The calcium-calmodulin dependent protein kinase II (CaMKII) has been heavily implicated in the strengthening of active neural connections. CaMKII interacts with various substrates including microtubules (MTs). MTs maintain cellular structure, and facilitate cellular cargo transport, effectively controlling neural architecture. Memory formation requires reorientation of this network. Could CaMKII-MT interactions be the molecular level encoding required to orchestrate neural plasticity? Using molecular modeling and electrostatic profiling, we show a precise matching between the spatial dimensions, geometry and electrostatics of CaMKII and MTs, and calculate the potential information capacity and bio-energetic parameters of such interactions. Results suggest signaling and encoding in MTs offers rapid, robust information processing with a large potential for memory storage, reflecting a general code for MT-based memory in neurons and other eukaryotic cells.

[“Cytoskeletal Signaling: Is Memory Encoded in Microtubule Lattices by CaMKII Phosphorylation?” Link. PLoS Computational Biology, March 2012]

In effect, on this model:

In long-term potentiation (LTP), a cellular and molecular model for memory, post-synaptic calcium ion (Ca2+) flux activates the hexagonal Ca2+-calmodulin dependent kinase II (CaMKII), a dodacameric holoenzyme containing 2 hexagonal sets of 6 kinase domains. Each kinase domain can either phosphorylate substrate proteins, or not (i.e. encoding one bit). Thus each set of extended CaMKII kinases can potentially encode synaptic Ca2+ information via phosphorylation as ordered arrays of binary ‘bits’. Candidate sites for CaMKII phosphorylation-encoded molecular memory include microtubules (MTs), cylindrical organelles whose surfaces represent a regular lattice with a pattern of hexagonal polymers of the protein tubulin. Using molecular mechanics modeling and electrostatic profiling, we find that spatial dimensions and geometry of the extended CaMKII kinase domains precisely match those of MT hexagonal lattices. This suggests sets of six CaMKII kinase domains phosphorylate hexagonal MT lattice neighborhoods collectively, e.g. conveying synaptic information as ordered arrays of six “bits”, and thus “bytes”, with 64 to 5,281 possible bit states per CaMKII-MT byte. Signaling and encoding in MTs and other cytoskeletal structures offer rapid, robust solid-state information processing which may reflect a general code for MT-based memory and information processing within neurons and other eukaryotic cells.

Six-bit hexagonal ring arrays of proteins being used to store six bits based on phosphoryllation or not? Quite interesting. And, six bits per unit rings a bell.

Oddly enough, the three-letter codons in D/RNA, with four states per digit are also six-bit units.

64 possibilities per codon unit:

Genetic code (RNA form) showing a START (AUG) in codon 1, courtesy Wiki



Sure would be convenient, though.

But at any rate, we see here a candidate for binary coded storage in our nerve cells, that would control microtubules, which in turn govern synaptic behaviour, which is known to be connected with memory and learning, given the processing power of neural networks to drive outputs based on nested weighted sums of inputs; making them great for pattern-recognition and decision-making. Clipping Wiki for a handy 101:

Simplified model of a neural network

The term neural network was traditionally used to refer to a network or circuit of biological neurons.[1] The modern usage of the term often refers to artificial neural networks, which are composed of artificial neurons or nodes. Thus the term has two distinct usages:

  1. Biological neural networks are made up of real biological neurons that are connected or functionally related in a nervous system. In the field of neuroscience, they are often identified as groups of neurons that perform a specific physiological function in laboratory analysis.
  2. Artificial neural networks are composed of interconnecting artificial neurons (programming constructs that mimic the properties of biological neurons). Artificial neural networks may either be used to gain an understanding of biological neural networks, or for solving artificial intelligence problems without necessarily creating a model of a real biological system. The real, biological nervous system is highly complex: artificial neural network algorithms attempt to abstract this complexity and focus on what may hypothetically matter most from an information processing point of view . . . .

A biological neural network is composed of a group or groups of chemically connected or functionally associated neurons. A single neuron may be connected to many other neurons and the total number of neurons and connections in a network may be extensive. Connections, called synapses, are usually formed from axons to dendrites, though dendrodendritic microcircuits[2] and other connections are possible. Apart from the electrical signaling, there are other forms of signaling that arise from neurotransmitter diffusion.

So, we have an interesting set of suggestions.

(Please note the use of question marks. That is almost always a sign of guessing, or suggesting, in a scientific context.)

In any case, the astonishing, co-ordinated and integrated, functionally specific, information-rich  complexity involved in biological systems is further underscored.

Cue the “just because it is complex, co-ordinated and functionally specific does not mean it was designed” objection in 5, 4, 3, 2 . . . seconds.

Okay, folks, just for fun. END

Enjoy the Easter weekend. kairosfocus
Indeed, the language of digital logic is present throughout living systems! I like the way Averick summarizes Meyer's point using his very appropriate magnetic letters example. I have to chuckle every time some news article links "biological building blocks" with the OOL problem, as if the presence of nucleotides and/or amino acids gets us close to solving the problem. It's all about SEQUENCE SPECIFICITY, the line item that's absent in the pop-media's accounting of OOL scenarios. Thanks for the link to the Abel paper. I'm going to try and read it over the weekend. Cheers! material.infantacy
Hi MI: The cumulative weight of evidence regarding where C-chemistry, aqueous medium, organised informational macromolecule cell based life comes from is indeed getting heavier and heavier. In this case, things are a bit speculative on the case of the 6-bit storage rings that are a candidate to regulate the synapses in neural networks, but a very interesting suggestion indeed. That lo and behold we are looking at a 6-bit unit, the same size as the well-known D/RNA codon, is highly suggestive too. While I am at it let me clip Reb Averick [HT, News] on the way such codons store info, they are not chemically constrained (which would frustrate info storage):
The double-helix structure of DNA is composed of two parallel “backbones” winding one around the other consisting of identical sugar and phosphate molecules. In between the sugar-phosphate backbones are the four nucleobases: (A) Adenine, (T) Thymine, (C) Cytosine, and (G) Guanine. On the inner edges of the backbones one of these four bases are linked to the respective sugar-phosphate molecules by a chemical bond called an “N-glycosidic” bond. Spanning the gap between the two strands, (A) always bonds with a (T) on the other side and (C) always bonds with (G). Horizontally then, the DNA molecule consists of a phosphate + sugar + N-glycosidic bond + (A) (T) or (C) (G) + N-glycosidic bond + sugar + phosphate. The information used for protein construction, however, resides in the vertical or longitudinal order of the nucleobases. The order in which the hundreds of thousands of nucleobases are arranged vertically code for particular sequences of amino acids which if arranged correctly, will produce functional proteins that are used by the cell. Meyer points out a rather astonishing fact – about which there is no scientific controversy – regarding the arrangements of the nucleobases in DNA. There are absolutely no chemical affinities or preferences for which nucleobases bond with any particular phosphate and sugar molecule. The N-glycosidic bond works equally well with (A), (T), (G), or (C). And secondly, there are also no chemical bonds in the vertical axis between the nucleobases. What this means is that there are no forces of physical/chemical attraction and no chemical or physical law that dictates the order of the nucleobases; they can be arranged in a nearly infinite amount of different sequences. Meyer gives an easy to understand illustration: Imagine a series of magnetic letters on the metal door of a refrigerator. All the letters are attached to the door by the same bond, namely a magnetic attraction. However, while the magnetic attraction is identical, there is nothing at all about the structure of any particular letter, or the magnetic bond, that would determine a preference for the order in which the letters are arranged on the door. If the letter G must always follow L which must always follow C, etc, then all you would get would be an endlessly repeating pattern of C, L, G etc., and no information could be conveyed. In fact, it is this very indeterminate nature of the arrangements of letters which allows them to convey functional information. Similarly, the arrangement of letters on a printed page has nothing at all to do with the chemical composition of the ink or paper. Meyer shows that the same applies to the arrangement of the letters of the genetic text. What allows the storage of encyclopedic amounts of information in DNA is the very indeterminate nature of the arrangements of the nucleobases, which are the “letters” of the genetic text. Meyer makes this point in critique of what are called “self-organizational scenarios,” one of the main naturalisitc approaches to explaining the origin of life and the ultimate origin of biological information. These theories attempt precisely to explain the ultimate origin of biological information by refernce to chemical bonding affinities or some physical or chemical law. Meyer demonstrates decisively why these theories cannot work; they fail to explain the basic facts of DNA chemistry and they fail to appreciate the non-redundant, non-repeating nature of functionally specified information. As he explains, laws by definition describe repeating patterns of redundant order. They do not describe aperiodic information-rich complex sequences. Yet, as he notes, the base sequences in functional sections of DNA are not highly repetitive. DNA contains a set of functional biochemical instructions, not an endlessly repeating mantra. A law might generate the latter, but can’t accurately describe or explain the former.
Pow, four runs, don't even bother chasing the ball, it is moving that fast for the boundary rope! And Abel et al hit another six cross the long boundary and out into the car park, with their discussion of functional and prescriptive info here, just published in Theoret Bio and Med Modelling. (Remember that silly old taunt about how design thinkers publish no peer reviewed papers? The latest wrinkle now seems to be that 99% of peer reviewed papers are rubbish, tolerated to get the 1% of gold. To which I retort, that what is well warrantred is well warranted, whether or no it is reviewed and signed off by a panel of the approved new Magisterium.) Those who have spent ever so much time and rhetoric on trying to dismiss the idea of functionally specific complex organisation and associated info and its empirically and analytically warranted source, are looking ever more like those who have chosen to follow a reductio ad absurdum to the bitter end. KF kairosfocus
Hi KF, yes it just gets increasingly staggering with more things considered. The impotence of purposeless causes, to produce anything of note with regard to the configured/crafted systems that we observe as a matter of first hand experience, is on display. Appeals to the system in question will just not do as a theory of how novelty arises via material causes. Even as it becomes clearer how (and to what degree) intra-cellular systems reconfigure themselves to express change throughout lineages, we will not have gained an ounce of knowledge about how such marvels arise unaided. The bootstrapping problem here is supremely troublesome to material origins stories. material.infantacy
MI: Protein sequences and regulatory ones too. KF kairosfocus
'“Natural selection” and “evolution” are no more than increasingly conjectural “descriptions” of putative processes. Nor ever could be, for that matter.'
I agree, and I've tried to communicate a similar idea in a few recent posts, perhaps inarticulately -- that evolution is no more a force than natural selection is, but rather a description of an observation. Without a verifiable mechanism for generating novel complexity, 'evolution' is no more than that which we observe as a matter of our first hand experience with the physical expression of living systems, from parent to progeny. Even invoking RV+NS as a causal mechanism requires a system capable of stable reproduction with heritable variation, and these features depend on a host of carefully crafted, purposefully coordinated subsystems. In addition, NS requires RV to do its work first, and RV is a random process, which can only implement a blind search. Blind searches are ineffective tools with which to discover function in the spaces where it would need to be found, namely protein sequences. So definitions of evolution which step outside the realm of description and intend to suggest the presence of a mechanism, 1) presuppose vast amounts of purposefully configured, coordinated systems to be already present and functioning, in order for heritable variation to take place; 2) propose an extrinsic force of change that is wholly impotent to do that which it's credited with doing; that is, stumbling upon novel functions which can be submitted to NS for vetting. In addition, if random changes introduced along the lines of reproduction do much of anything, they do it because they occur within the context of a system which is tolerant to faults, another feature likely to require a host of systems in order to implement that degree of robustness. material.infantacy
F/N: The interested may wish to cf CARM and AiG on the much disputed Lady Hope story. His agnosticism is well documented, and he was invariably polite to inquirers. That may have produced various divergent understandings of his views. Certainly, the Free Thinkers tried to claim him for their own, but were contradicted by the same son, Francis, who underscored agnosticism not atheism. As to a conversion at the very end, there is too much in dispute to be certain or even highly confident. KF kairosfocus
As regards Lady Hope, bankrupting one's family in favour of gifts to the destitute, does not strike one as indicative of dishonesty, does it. She was clearly neither a modern-day American evangelical scam-artist nor a blasphemous Prosperity Gospeller. Axel
Axel: You are right that the search challenge to blind chance and mechanical necessity is being ducked. Seriously ducked, for something that was highlighted in principle by newton in his General Scholium to Principia. Something that was old in the days of Plato for that matter, from The Laws, Bk X. That same dodgem game lies behind the "open systems can do anything" talking point used in reply to raising issues connected to the laws of thermodynamics and the underlying statistics of large numbers of atoms and molecules etc. So, the naturalistic evolutionists have a serious problem getting to first life in Darwin's warm little pond or similar proposed environments. Then, when it comes to starting from established cell based life, they have taken a mechanism that can partially explain specialisation to niches and adaptations to adverse environments -- usually by simply breaking things that are otherwise useful but in particular cases are gateways for attack -- and bodly extrapolated it into an engine of body plan innovation. Have they got any actual observations? Nope, just extrapolations, vague ambiguities in language and ideological imposition of interdicts against what IS empirically well warranted: functionally specific complex organisation and information have just one observed and well warranted source: design. And the sort of needle in the haystack search space challenge that the million monkeys challenge shows up so well gives us an easy way to see the problem, especially when we are dealing with complex, coded algorithmic information. What is the only empirically warranted source for algorithms, codes and executing machines to effect same, again? Design. We have whole industries to that effect. Given what needle in the haystack analyses tell us, no surprise. And of course that is what the original post is about: our brains are processors that work based on neural networks, and it is now on the table that we may well have a storage mechanism to code for the variable strength of links from one stage to the next that is the key to neural network architecture. Turns out, if true, it is using 6-bit words, i.e. that would be the same framing pattern as the known case of D/RNA. Biology as 6-bit word based computing systems? Well, arguably, we are in that world once the 3-letter 4-state per letter codon pattern was discovered. Biology as a digitally based system. But even if the coding of neural links CaMKII-MT is not so, we are looking at some pretty serious evidence of digitally coded FSCO/I in life forms already. Take off the materialism blinkers, and ask, what does this point to. Can the materialists explain, on empirical evidence, what we see without recourse to design? I.e. on blind chance plus necessity? Nope. Not if they have to stand up tot he empirical evidence. Do you see why the core point of ID -- which the materialists are so often ever so eager to bury under an avalanche of rabble-rousing, scare mongering, scapegoating rhetoric and strawmen about "creationism in a cheap tuxedo" --is that there are empirically credible signs of design, and these are abundant in the world of life, so it is a reasonable, empirically based, scientific view that life is designed. I guess I am just a tad annoyed this morning because I did my "every so often" look-see at the penumbra of hate sites. I think we are dealing with a lot of no-broughtupcy people who are a lot less bright than they think they are, and who in any case are so blinded by rage and animosity that hey cannot seem to think straight. Never mind seeing themselves bound by duties of care of civility and concern to be fair to others. For instance, *****, you should know by now that Plato in The Laws Bk X exposes that evolutionary materialism is an ancient philosophical view, not a scientific one. It simply posits that all that counts is matter shaped by chance and necessity, whether 400 BC, or 2012 AD. Under the false colours of knowledge, brightness, education and science, it has been imposed on science in our time. But that does not change its absurdities that were evident to Plato, on reflecting on the disasters brought to Athens by spoiled brat manipulators like Alcibiades and co. It has never had an adequate account for the credibility of our minds as being able to objectively know or reason. It has in it no worldview foundational IS that can bear the weight of OUGHT -- so, it is never able to have an objective basis for ought, and those indoctrinated in it are often indoctrinated in one version or another of the idea that might and manipulation make "right." From Alcibiades to today's rage-fuelled new atheists, the result has consistently been that the rise of such an ideology opens the door to nihilistic factions, and if such succeed, onwards to misanthropic tyranny. There is a LOT of history on that. One of the scapegoating talking points seems to be to accuse the undersigned of being a "homophobe," and "liar," with the inference being that to object to the rise of homosexual behaviour and ideology is irrational and hateful. In fact, it is not hard to show that homosexual attraction and behavioural habituation are objectively disordered and harmful to individuals so caught up -- who need our help not either blindly scornful rage or a moral inversion that foolishly encourages such self-destructive and socially- destructive behaviour -- and to society if it spreads across it; so it falls afoul of say Kantian analysis of what is morally sound. So, it cannot be a "right" (and the notion that it is scientifically shown to be genetically determined is yet another case of ideological agenda wrapping itself in a lab coat), and it is possible to have a principled, reasonable objection to such behaviour and the ideology that promotes it. And one may have such a principled objection to behaviour while receiving person and reaching out with concern to help. (I do not approve of the murder and mutilation of the corpse of his victim carried out by a certain Mr X, which has landed him in gaol on a life sentence; the death by hanging having been commuted on order of Her majesty being sick of executions being carried out in her name, I gather, while they were actually practising on the assembled Gallows outside the window of his cell . . . ; but that does not mean that I have an excuse to revile or refuse to reach out to X to help him. The Book of Jonah is all about that, once we know that the Assyrians were ruthless, mass murdering conquerors so Jonah's reluctance to reach out to them and attitude problems are very understandable. I cite this biblical example to make the point clear that when Bible-believing Christians speak of disapproving sin but reaching out to sinners to help, they do so on clear Biblical mandates. On exactly the sort of major OT texts that those ever so eager to paint the God of the OT in the most lurid and hateful strawman colours, consistently do NOT refer to.) But, as the previously linked shows, those who are caught up in such behaviour, can often be helped, by the same sort of approaches that often successfully help those caught up in other life dominating habit forming behaviousr, like alcohol etc. Also, the road to rescue is not an easy one and if you do not nibble, you cannot be hooked. In short, what is pretty clear is that the scientific evidence and principles of inductive inference -- apart from a priori imposition of materialism -- strongly support design as best explanation for what we see in teh world of life (and in the cosmos too). But there IS a problem of such ideological imposition, and in absence of a good case on merits, a bad one has been presented on strawmen. Indeed, the subject has been changed to politics and Christian-bashing. Which is exactly the sort of polarising factionalism that Plato warned against. Bu then, the key lessons of history are that if we refuse to learn from it, we are doomed to repeat it, and by and large we refuse to learn from it. Will we wise up this time around, before we pay a terrible price for refusing to learn in good time to avert preventable disaster? One thing I know, the sort of rage-driven blindness we have been seeing is precisely not the sort of mood that lends itself to learning and acting wisely in good time. When I get a moment, I think I need to make some remarks on what happened at the Rock beyond Belief flopped new atheism event at Ft Bragg of Saturday last -- expected 5,000, apparently 200 or so showed up, mostly "civilians." GEM of TKI PS: On Darwin in his last days, kindly cf here on. kairosfocus
For the materialist, in the matter of natural selection, a description of the conjectured process implicitly includes the dynamism that impels it. The process of manufacturing any car would be articulated in some manual in whatever form. However, it would be risibly irrational to assume that such processes are self-powered. Likewise, with regard to their running, they may be called, "automobiles" in the US, but obviously they are not self-started and self-propelled. Intelligent input is required. Not even monkeys will serve, still less random chance. So why do materialists impute self-generation as implicitly integral to the mere processes of Natural Selection and Evolution, as conjectured? It is clearly an abuse of logic at the "a priori" level of language, itself. Axel
In fact Darwin wasn't even "entirely silent", on occasions invoking the Creator in some of his works. "Natural selection" and "evolution" are no more than increasingly conjectural "descriptions" of putative processes. Nor ever could be, for that matter. Axel
In the latest article in UD Feedburner, entitled, Seeking an Official Definition of "Randomness": A Reply to Jay Richards, the author, I believe, unnnamed, states: "First, as far as I can see, the only place where this question of guideness vs. unguidedness arises is with respect to the claim that what drives the process of descent with modification is natural selection operating on genetic mutations, where the genetic mutations are said to be random." This ascription of the process of natural selection as the "driving" force behind the process of descent seems to me a major mischaracterisation, made again and again by IDers, as well as evolutionists, seemingly in subliminal deference to the tribe of "just so" scientismificists, who currently misrule the scientific community. The term, "driving", used here as a metaphor, is, itself, ambiguous at the very point of most seminal contention, What I mean is that it gives the evolutionists a "free pass", by allowing them to confuse description of the process with an actual force, actually driving it: on the subject of which Darwin is entirely silent. This is not so surprising, since, despite his vacillations under spiritual trials, seemingly dating from his daughter's premature death, Darwin himself denied that he was an atheist, if my memory serves. What is certain, in any case, is that a recently found log of the Missionary Society shows that he contributed to the missions until the month of his death. And I find nothing concerning Lady Hope's account of Darwin's last prayerful days, or her explanation of the topography of his house and garden, to persuade me that she was mendacious. Far more likely, it seems to me, is that Darwin's wife and daughter rather enjoyed the way in which he was being lionised by the frustrated atheists of his day, and were, to their immense shame, themselves "economical with the truth". Axel
Perhaps, they have in mind an unintelligently-designed complexity, produced by random (clumsy, 'uncoordinated', and 'non functionally-specific' by definition) chance, an endless stream of entirely fortuitous coincidences. Does the term, 'aleatory' still have its original meaning in scientific research - or have abiogenesis and cosmology 'knocked that on the head', too, rendering it void of meaning, or perverting its meaning all together? Never was acknowledgement of the synonymity of 'meaning' and 'sense' more important, more primordially proper to meaning and (good) sense - than now, after materialists have been confusing chaos with order and random chance with functonally-specific design, without let or hindrance by the scientific establishment. Once words, themselves, are assigned an alien meaning for emotional doctrinaire purposes, there really is not much hope of eliciting any kind of sense from those responsible. Nor is a comparison of their intelligence with that of infant-school children, hyperbolical, still less, fair to the latter. Axel
“'....just because it is complex, co-ordinated and functionally specific does not mean it was designed' objection." I wonder how they would define the prefatory word, 'just', in this context - and justify its use. Axel

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