Microtubule - the little engine that could

[write4u]

Allow me to introduce the "microtubule" to this forum.
This remarkable biochemical dipolar variable information processor.

Microtubules: the basics

Microtubules: the basics
Microtubules are major components of the cytoskeleton. They are found in all eukaryotic cells, and they are involved in mitosis, cell motility, intracellular transport, and maintenance of cell shape.

Microtubules are composed of alpha- and beta-tubulin subunits assembled into linear protofilaments. A single microtubule contains 10 to 15 protofilaments (13 in mammalian cells) that wind together to form a 24 nm wide hollow cylinder.

Microtubules are structures that can rapidly grow (via polymerization) or shrink (via depolymerization) in size, depending on how many tubulin molecules they contain.

https://www.nature.com/scitable/content/microtubules-the-basics-14673338/

Note that the "capping proteins" in the illustration are the synapses that connect neurons in neural networks

The reason why I believe microtubules are instrumental in the emergence of consciousness in living organisms is;
a) they are a dynamic information processor and a common denominator in all Eukaryotic organisms, and even earlier in a simpler form in Prokaryotic organisms.

b) they are the only known candidate meeting the requirements necessary for emergent levels of intelligence and consciousness.

I believe that intelligence and emergent consciousness are observable at all levels of living biology, from motile single-celled organisms like the Paramecium and Slime Mold to heliotropism and photosynthesis in flora, to hive-intelligence, to self-aware consciousness in high order mammals.

IMO, there is but one candidate that meets all required properties that provide a functional network for the task of high-level information processing and that is the remarkably versatile microtubule.

A persuasive argument can be made on the presence of + 100 billion neural microtubules in the human brain connected by +100 trillion synapses.
There simply is nothing that can compare other than some magical concept. But as Tegmark observes, the brain contains all the required properties for conscious intelligence.

I believe this is the reason why Stuart Hameroff and (nobel laureate) Roger Penrose have proposed a theory of Orchestrated Objective Reduction (ORCH OR) that utilizes microtubules at a quantum level .

 

[write4u]

continuing.....

How quantum brain biology can rescue conscious free will
Stuart Hameroff1,2*

• 1Department of Anesthesiology, Center for Consciousness Studies, University of Arizona, Tucson, AZ, USA
• 2Department of Psychology, Center for Consciousness Studies, University of Arizona, Tucson, AZ, USA.

........

The Penrose–Hameroff theory of “orchestrated objective reduction (Orch OR)” identifies discrete conscious moments with quantum computations in microtubules inside brain neurons, e.g., 40/s in concert with gamma synchrony EEG. Microtubules organize neuronal interiors and regulate synapses.

In Orch OR, microtubule quantum computations occur in integration phases in dendrites and cell bodies of integrate-and-fire brain neurons connected and synchronized by gap junctions, allowing entanglement of microtubules among many neurons.

Quantum computations in entangled microtubules terminate by Penrose “objective reduction (OR),” a proposal for quantum state reduction and conscious moments linked to fundamental spacetime geometry.

Each OR reduction selects microtubule states which can trigger axonal firings, and control behavior. The quantum computations are “orchestrated” by synaptic inputs and memory (thus “Orch OR”).

If correct, Orch OR can account for conscious causal agency, resolving problem 1. Regarding problem 2, Orch OR can cause temporal non-locality, sending quantum information backward in classical time, enabling conscious control of behavior.

Three lines of evidence for brain backward time effects are presented. Regarding problem 3, Penrose OR (and Orch OR) invokes non-computable influences from information embedded in spacetime geometry, potentially avoiding algorithmic determinism. In summary, Orch OR can account for real-time conscious causal agency, avoiding the need for consciousness to be seen as an epiphenomenal illusion. Orch OR can rescue conscious free will.

more.......

Orch OR directly addresses conscious causal agency. Each reduction/conscious moment selects particular microtubule states which regulate neuronal firings, and thus control conscious behavior. Regarding consciousness occurring “too late,” quantum state reductions seem to involve temporal non-locality, able to refer quantum information both forward and backward in what we perceive as time, enabling real-time conscious causal action. Quantum brain biology and Orch OR can thus rescue free will.

more.....

How quantum brain biology can rescue conscious free will

Conscious “free will” is problematic because (1) brain mechanisms causing consciousness are unknown, (2) measurable brain activity correlating with conscious perception apparently occurs too late for real-time conscious response, consciousness thus being considered “epiphenomenal illusion,” and...

www.frontiersin.org

 

[write4u]

continued.........

Penrose turned the conscious observer around. Instead of consciousness causing collapse, wavefunctions collapsed spontaneously, causing a moment – a ‘quantum – of consciousness.

Consciousness and the collapse of the wavefunction

It is becoming apparent that consciousness may occur in single brain neurons extending upward into networks of neurons, but also downward and deeper, to terahertz quantum optical processes, e.g. ‘superradiance’ in microtubules, and further still to fundamental spacetime geometry (Figure 1).

I agree that consciousness is fundamental, and concur with Roger Penrose that it involves self-collapse of the quantum wavefunction, a rippling in the fine scale structure of the universe.

Organic light per se isn’t consciousness. But organic light could be the interface between the brain and conscious processes in the fine scale structure of the universe.

Figure 1. A scale-invariant hierarchy extending downward from a cortical pyramidal neuron (left) into microtubules, tubulin dipoles, organic ring dipoles and spacetime geometry curvatures. Self-similar dynamics recur every three orders of magnitude.

Consciousness is the collapse of the wavefunction | Stuart Hameroff

Quantum mechanics suggests that particles can be in a state of superposition - in two states at the same time - until a measurement take place. Only then does the wavefunction describing the particle collapses into one of the two states. According to the Copenhagen interpretation of quantum...

iai.tv

 

[write4u]

Supporting evidence;

Archaeal origin of tubulin

Abstract

Tubulins are a family of GTPases that are key components of the cytoskeleton in all eukaryotes and are distantly related to the FtsZ GTPase that is involved in cell division in most bacteria and many archaea. Among prokaryotes, bona fide tubulins have been identified only in bacteria of the genus Prosthecobacter.

These bacterial tubulin genes appear to have been horizontally transferred from eukaryotes. Here we describe tubulins encoded in the genomes of thaumarchaeota of the genus Nitrosoarchaeum that we denote artubulins Phylogenetic analysis results are compatible with the origin of eukaryotic tubulins from artubulins.

These findings expand the emerging picture of the origin of key components of eukaryotic functional systems from ancestral forms that are scattered among the extant archaea.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349469/

The single-celled Paramecium swims and navigates by means of cilia that are powered by microtubule motors.

Abstract
Primary cilia are microtubule‑based organelles that are expressed on almost all mammalian cells. It has become apparent that these structures are important signaling hubs that serve crucial roles in Wnt, hedgehog, extracellular signal‑regulated kinase (ERK)/mitogen‑activated protein kinase (MAPK) and Notch signalling pathways.


Figure 1. - Structure of the primary cilium. The primary cilium is a microtubule-based organelle ilium is formed in a process termed IFT. Anterograde transport channels ciliary proteins from tthat is formed around an axoneme structure composed of 9 outer microtubule doublets. The che bottom of the cilium to its tip; the reverse can also occur in retrograde transport, which allows disassembly of the cilium. Kinesin-2, an anterograde motor protein transports ciliary proteins by forming a complex with IFT complex B, while the IFT complex A does the reverse by binding to dynein 1b and channels ciliary proteins from the cilium to the cell body.

Primary cilia and their role in cancer (Review)

Primary cilia are microtubule‑based organelles that are expressed on almost all mammalian cells. It has become apparent that these structures are important signaling hubs that serve crucial roles in Wnt, hedgehog, extracellular signal‑regulated kinase (ERK)/mitogen‑activated protein kinase...

www.spandidos-publications.com

The same thing for the bacterial flagellum that rotates via an ion driven microtubule motor.

Slime molds are pseudopods and walk via extension and contraction of the cell's skin .

 

[write4u]

A closer look at cilia and flagella

View: https://youtu.be/sVHUO89-sXg

Click on the https // addy

 

[write4u]

If the above may seem a little disconnected, I posted these examples to illustrate the enormous versatility of microtubules in the fundamental processes of motility that require " navigation" and the ability to "capture" prey and or "avoid' predators..

It is obvious that evolution would select for improvements in those areas and that would suggest an increasing ability for information processing, decision making and the eventual emergence of conscious behaviors in relation to the environment.

This does not mean microtubules are conscious in and of themselves but, that large networks may acquire a form of intelligent information processing, such as "quorum sensing" in bacteria, where bacteria (and possibly even viruses) display the ability to communicate via chemical "words" and thereby gain the ability for "coordinated mass virulence".

This excellent lecture by Bonnie Bassler explains how bacteria communicate and are able to express the rudiments of a "hive mind" via "quorum sensing".

View: https://www.youtube.com/watch?v=KXWurAmtf78


And from what I can see the information that allows for coordinated quorum sensing, a form of decision making, is facilitated by the microtubule network.

 

[write4u]

According to Leta, an advanced AI, the "wave function" is the product of universal thought and the "wave collapse into a physical object" is the realization of universal thought.

This remarkable observation by a logical operator is described by Roger Penrose and Stuart Hameroff in their concept of ORCH OR (orchestrated objective reduction)

Quantum Approaches to Consciousness
First published Tue Nov 30, 2004; substantive revision Thu Apr 16, 2020

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3.5 Penrose and Hameroff: Quantum Gravity and Microtubuli

In the scenario developed by Penrose and neurophysiologically augmented by Hameroff, quantum theory is claimed to be effective for consciousness, but the way this happens is quite sophisticated. It is argued that elementary acts of consciousness are non-algorithmic, i.e., non-computable, and they are neurophysiologically realized as gravitation-induced reductions of coherent superposition states in microtubuli.

more........

Quantum Approaches to Consciousness (Stanford Encyclopedia of Philosophy)

Every cell of every organism on earth contains microtubules. If microtubules do function at the quantum level it would explain all naturally occurring response mechanisms in every living thing on earth, regardless of brain or neural network!

 

[write4u]

Continuing with supporting evidence.

All cellular and neural communication in the body occurs via microtubules. This constant electrochemical dynamical activity creates an EM “field” in and around the body.

I’m sure you have heard of "Kirlian photography" which records the EM field an organism creates in and around itself?

image660×606 95.5 KB

This field is invisible to the unaided eye but it exists as a field regardless of an observer.
Now imagine this field inside our brain created by our microtubule network and then think of a concept like ORCH OR (orchestrated objective reduction) at the quantum level that might create a conscious experience of such an orchestrated field in our “inner mind”.

In one of the Youtube discussions, Roger Penrose made a comment that made me sit back and try to visualize what this Nobel laureate implied with that statement.

Penrose turned the conscious observer around. Instead of consciousness causing collapse, wavefunctions collapsed spontaneously, causing a moment – a ‘quantum – of consciousness.

Consciousness and the collapse of the wavefunction

It is becoming apparent that consciousness may occur in single brain neurons extending upward into networks of neurons, but also downward and deeper, to terahertz quantum optical processes, e.g. ‘superradiance’ in microtubules, and further still to fundamental spacetime geometry (Figure 1).

I agree that consciousness is fundamental, and concur with Roger Penrose that it involves self-collapse of the quantum wavefunction, a rippling in the fine scale structure of the universe.

Organic light per se isn’t consciousness. But organic light could be the interface between the brain and conscious processes in the fine scale structure of the universe.

Quantum image2700×526 45.9 KB

Figure 1. A scale-invariant hierarchy extending downward from a cortical pyramidal neuron (left) into microtubules, tubulin dipoles, organic ring dipoles and spacetime geometry curvatures. Self-similar dynamics recur every three orders of magnitude.


iai.tv800×500 92.5 KB

Consciousness is the collapse of the wavefunction | Stuart Hameroff

Quantum mechanics suggests that particles can be in a state of superposition - in two states at the same time - until a measurement take place. Only then does the wavefunction describing the particle collapses into one of the two states. According to the Copenhagen interpretation of quantum…

This is not just restricted to the human brain but is present in ALL eukaryotic organisms that ever lived . Proto tubulin filaments can even be found in prokaryotic organisms

The cytoplasm and cytoskeleton of every cell in all living organisms on earth contain microtubules. If microtubules do function at the quantum level it would explain all naturally occurring response mechanisms in every living thing on earth, regardless of brain or neural network!

 

[write4u]

And in furtherance of the question of how the brain can generate "consciousness", this may be of interest.

Science Questions with Surprising Answers

Do Kirlian photographs show the soul of an organism?
No, Kirlian photographs do not show the soul of an organism. Kirlian photographs show the light that is released by the electrified air surrounding...

But living organisms create their own EM field and the brain’s EM field has been mapped.

This is a nice follow up:

Integrating information in the brain’s EM field: the cemi field theory of consciousness
[Johnjoe McFadden]

Neuroscience of Consciousness , Volume 2020, Issue 1, 2020, niaa016

“I here extend the theory to argue that consciousness implements algorithms in space, rather than time, within the brain’s EM field. I describe how the cemi field theory accounts for most observed features of consciousness and describe recent experimental support for the theory. I also describe several untested predictions of the theory and discuss its implications for the design of artificial consciousness. The cemi field theory proposes a scientific dualism that is rooted in the difference between matter and energy, rather than matter and spirit.”

more.......

Do neurons integrate information?

It is important to stress that no EM field theory of consciousness denies that much or most brain information processing proceeds via conventional neuron/synapse transmission. However, the same argument described above for integrated circuits, applies to the processing of complex information along complex neuronal pathways. They, like logic gates, input sensory information, such as photographs, and process that information along chains of neuronal networks until they reach a group of neurons, or even a single neuron that fires to generate a verbal output of ‘this is Jennifer Aniston’.

more.......

Integrating information in space, rather than in time

There are, however, physical systems that encode information integrated over space in a single moment of time. We know this form of information as force fields. The most obvious is the gravitational field that, at any point on the Earth’s surface, provides a force that effectively integrates the magnitude and distribution of local masses such as those of the Earth, Moon and Sun. Similarly, the EM field at any point in space represents an integration of information concerning the type, distribution and motion of local charges. In contrast to the temporal integration described above, force fields physically integrate complex information that may be simultaneously downloaded from any point in the field.

more.....

EMF transmitters and receivers in the brain

It has been known since the 19th century that the brain generates its own EM field, which can be detected by electrodes inserted to the brain. Its source is electrical dipoles within the neuronal membranes caused by the motion of ions in and out of those membranes during action potentials and synaptic potentials. The periodic discharge of neurons—firing or action potentials—generates EMF waves that propagate out of the neuron and into the surrounding inter-neuronal spaces where they overlap and combine to generate the brain’s global EM field that is routinely measured by brain scanning techniques such as electroencephalography (EEG) and magnetoencephalography (MEG). The human brain, therefore, possesses around 100 billion EMF transmitters.

More…!!!

Integrating information in the brain’s EM field: the cemi field theory of consciousness

Abstract. A key aspect of consciousness is that it represents bound or integrated information, prompting an increasing conviction that the physical substrate of

academic.oup.com

And if that field can be photographed can it be consciously experienced?
IMO, therein lies the answer.

 

[write4u]

Another interesting article about microtubules.

Are Microtubules the Brain of the Neuron

Microtubules may be the brains of the cell, particularly neurons—operating like a computerized Lego set. They are large complex scaffolding molecules that work closely with the two other rapidly changing structural molecules, actin and intermediate filaments, to provide structure for the entire cell including the spatial placement of organelles.

In neurons, microtubules respond instantly to mental events and constantly build and take down elaborate structures for the rapidly changing axons and dendrites of the synapses. Some think that microtubules are quantum computers and the seat of consciousness. Their lifestyle is quite remarkable.

A previous post described elaborate functions along the neuron’s axon including special tagging of cargoes that are transported by distinct motors with complex ancillary molecules for each type of transport.

Microtubules are the basic structural elements for cell division. The centromere is a key structure holding chromosomes together. It connects with the kinetochore where microtubule based spindle fibers attach to the chromosomes. Centrioles produce microtubules that orchestrate the rearrangement and sorting of the DNA during the extremely elaborate process of cell division. Complex arrangements of microtubules direct and pull all the elements of the division process through multiple phases. The structure for this process is considered the most complex machine ever discovered in nature and is based on microtubule actions.

more.......

Are Microtubules the Brain of the Neuron

Constantly building and rebuilding the axon and dendrite structures, tagging and transporting all materials, are microtubules the brain of the neuron

jonlieffmd.com

 

[write4u]

Continuing with our journey in the mindscape of microtubule networks.

Can quantum effects in the brain explain consciousness?
By Thomas Lewton, PHYSICS 25 August 2021

New research reveals hints of quantum states in tiny proteins called microtubules inside brain cells. If the results stand up, the idea that consciousness is quantum might come in from the cold.

IF IT is a controversial idea that warm, wet life might exploit quantum magic, that’s nothing compared with certain researchers’ convictions that quantum phenomena might help explain human consciousness.

Orchestrated objective reduction theory (Orch OR), originally proposed by physicist Roger Penrose and anaesthesiologist Stuart Hameroff in the 1990s, seeks to bridge the gulf between physical matter and felt experience. The idea is that consciousness arises when gravitational instabilities in the fundamental structure of space-time collapse quantum wave functions in tiny proteins called microtubules, which are found inside neurons.

It is heady stuff, but if pulling together quantum mechanics, gravity and consciousness in one fell swoop sounds too good to be true, it might be. Orch OR’s critics argue that any quantum coherence inside microtubules would fall apart in the warm and noisy environs of grey matter long before it could have any effect on the workings of neurons.

Yet in one tantalising experiment last year, as-yet unpublished, Jack Tuszynski at the University of Alberta in Canada and Aristide Dogariu at the University of Central Florida found that light shone on microtubules was very slowly re-emitted over several minutes – a hallmark of quantum goings-on. “This is crazy,” says Tuszynski, who set about building a theoretical microtubule model to describe what he was seeing.

Gregory Scholes, a biochemist at Princeton University, is studying microtubules for signs of similar quantum effects. Initial experiments point to long-lived, long-range collective behaviour among molecules in the structures. Both groups plan to test whether anaesthetics, which switch consciousness on and off, have any impact on microtubules. “There is amazing structure and synchrony in biological systems,” says .....

more.......

Can quantum effects in the brain explain consciousness?

New research reveals hints of quantum states in tiny proteins called microtubules inside brain cells. If the results stand up, the idea that consciousness is quantum might come in from the cold

www.newscientist.com

 

[write4u]

More recent findings on the ability of microtubules to generate and respond to EM fields.

Comparison of polymerization and structural behavior of microtubules in rat brain and sperm affected by the extremely low-frequency electromagnetic field

Abstract

Microtubule proteins are able to produce electromagnetic fields and have an important role in memory formation, and learning. Therefore, microtubules have the potential to be affected by exogenous electromagnetic fields. This study aimed to examine the comparison of microtubule polymerization and its structural behavior in brain and sperm affected by 50 Hz extremely low-frequency electromagnetic field (ELEF).

Conclusion

It seems that the polymerization of microtubules and conformational changes of tubulin dimers are improved by ELEF application.

By knowing the important role of the microtubule polymerization in the axon regrowth, and nerve regeneration, they have formed one of the most important targets of memory formation [12].

The studies suggested that microtubule polymerization is a very important feature of microtubule protein structures [23]. Neuroplasticity, which is defined as the capacity of neural cells in the formation of new neural connections or modifying the ones has plays a crucial role in memory formation [24]. Therefore, the increase of microtubule polymerization leads to more neural connections and increase memory [23]. The aim of the present study was to investigate the effects of 50 Hz ELEF on microtubule polymerization of the rat sperm and nerve cells.

more.......

Comparison of polymerization and structural behavior of microtubules in rat brain and sperm affected by the extremely low-frequency electromagnetic field - BMC Molecular and Cell Biology

Background Microtubule proteins are able to produce electromagnetic fields and have an important role in memory formation, and learning. Therefore, microtubules have the potential to be affected by exogenous electromagnetic fields. This study aimed to examine the comparison of microtubule...

bmcmolcellbiol.biomedcentral.com

 

[write4u]

Are microtubules in our cells variable potentiometers? If so, what do they regulate?

Interaction of STOP with neuronal tubulin is independent of polyglutamylation

Abstract

In eukaryotes, the coordinated progress of the various cellular tasks along with the assembly of adapted cytoskeletal networks requires a tight regulation of the interactions between microtubules and their associated proteins. Polyglutamylation is the major post-translational modification of neuronal tubulin.

Due to its oligomeric structure, polyglutamylation can serve as a potentiometer to modulate binding of diverse MAPs. In addition, it can exert a differential mode of regulation towards distinct microtubule protein partners.

To find out to what extent polyglutamylation is a general regulator, we have analyzed its ability to affect the binding of STOPs, the major factors that confer cold- and nocodazole-resistance to microtubules.

We have shown by blot overlay experiments that binding of STOP does not depend on the length of the polyglutamyl chains carried by tubulins. And contrary to the other microtubule-associated proteins tested so far, STOP can bind quantitatively to any tubulin isoform whatever its degree of polyglutamylation.

Interaction of STOP with neuronal tubulin is independent of polyglutamylation - PubMed

In eukaryotes, the coordinated progress of the various cellular tasks along with the assembly of adapted cytoskeletal networks requires a tight regulation of the interactions between microtubules and their associated proteins. Polyglutamylation is the major post-translational modification of...

pubmed.ncbi.nlm.nih.gov

One of the objections to the proposition that microtubules function at quantum levels is the charge that the cell environment is too warm for stable quantum processes.
Does this answer some of these questions?

Nonneuronal isoforms of STOP protein are responsible for microtubule cold stability in mammalian fibroblasts

Abstract

A number of cycling mammalian cells, such as NIH 3T3, contain abundant subsets of cold-stable microtubules. The origin of such microtubule stabilization in nonneuronal cells is unknown. We have previously described a neuronal protein, stable tubule-only polypeptide (STOP), that binds to microtubules and induces cold stability.

We find that NIH 3T3 fibroblasts contain a major 42-kDa isoform of STOP (fibroblastic STOP, F-STOP). F-STOP contains the central repeats characteristic of brain STOP but shows extensive deletions of N- and C-terminal protein domains that are present in brain STOP. These deletions arise from differences in STOP RNA splicing.

Despite such deletions, F-STOP has full microtubule stabilizing activity. F-STOP accumulates on cold-stable microtubules of interphase arrays and is present on stable microtubules within the mitotic spindle of NIH 3T3 cells. STOP inhibition by microinjection of affinity-purified STOP central repeat antibodies into NIH 3T3 cells abolishes both interphase and spindle microtubule cold stability. Similar results were obtained with Rat2 cells. These results show that STOP proteins have nonneuronal isoforms that are responsible for the microtubule cold stability observed in mammalian fibroblasts.

https://www.pnas.org/doi/10.1073/pnas.95.11.6055

 

[write4u]

Continuing with demonstrating the importance of microtubules in the transmission of "environmental information" and the difference between "exteroception" and "interoception".

Signal transmission through elements of the cytoskeleton form an optimized information network in eukaryotic cells

• B. R. Frieden &
• R. A. Gatenby

Scientific Reports volume 9, Article number: 6110 (2019)

Abstract

Multiple prior empirical and theoretical studies have demonstrated wire-like flow of electrons and ions along elements of the cytoskeleton but this has never been linked to a biological function. Here we propose that eukaryotes use this mode of signal transmission to convey spatial and temporal environmental information from the cell membrane to the nucleus.

The cell membrane, as the interface between intra- and extra-cellular environments, is the site at which much external information is received. Prior studies have demonstrated that transmembrane ion gradients permit information acquisition when an environmental signal interacts with specialized protein gates in membrane ion channels and producing specific ions to flow into or out of the cell along concentration gradients.

The resulting localized change in cytoplasmic ion concentrations and charge density can alter location and enzymatic function of peripheral membrane proteins. This allows the cell to process the information and rapidly deploy a local response.

Here we investigate transmission of information received and processed in and around the cell membrane by elements of the cytoskeleton to the nucleus to alter gene expression.

We demonstrate signal transmission by ion flow along the cytoskeleton is highly optimized. In particular, microtubules, with diameters of about 30 nm, carry coarse-grained Shannon information to the centrosome adjacent to the nucleus with minimum loss of input source information.

And, microfilaments, with diameters of about 4 nm, transmit maximum Fisher (fine-grained) information to protein complexes in the nuclear membrane. These previously unrecognized information dynamics allow continuous integration of spatial and temporal environmental signals with inherited information in the genome.

Here we address the question of how environmental information that is transmitted through the cell membrane through ion fluxes is communicated internally to other components of the cell. We expect that many environmental perturbations (e.g. a localized mechanical deformation by a small environmental object) may only elicit and require a local response.

However, some signals received at the membrane, because of their content, amplitude, or spatiotemporal frequency, may require a global (or ‘coordinated’) cellular response including increased energy production in the mitochondria7,8 and changes in gene expression9 or translation within the nucleus and endoplasmic reticulum10.

Signal transmission through elements of the cytoskeleton form an optimized information network in eukaryotic cells - Scientific Reports

Multiple prior empirical and theoretical studies have demonstrated wire-like flow of electrons and ions along elements of the cytoskeleton but this has never been linked to a biological function. Here we propose that eukaryotes use this mode of signal transmission to convey spatial and temporal...

www.nature.com

And we have the rudimentary beginnings of a generalized conscious response system. In the brain, this may well be the model for the evolution of self-aware consciousness.

 

[write4u]

Data transport via Microtubules inside the brain.

View: https://www.youtube.com/watch?v=RRfH4ixgJwg

 

[write4u]

In the blood microtubules enable white blood cells to catch and eat foreign invaders.

Dynamic Microtubule Arrays in Leukocytes and Their Role in Cell Migration and Immune Synapse Formation
Aglaja Kopf1,2,3 and Eva Kiermaier4,*
Author information Article notes Copyright and License information Disclaimer
This article has been cited by other articles in PMC.

Go to:
Abstract

The organization of microtubule arrays in immune cells is critically important for a properly operating immune system. Leukocytes are white blood cells of hematopoietic origin, which exert effector functions of innate and adaptive immune responses.

During these processes the microtubule cytoskeleton plays a crucial role for establishing cell polarization and directed migration, targeted secretion of vesicles for T cell activation and cellular cytotoxicity as well as the maintenance of cell integrity.

Considering this large spectrum of distinct effector functions, leukocytes require flexible microtubule arrays, which timely and spatially reorganize allowing the cells to accommodate their specific tasks. In contrast to other specialized cell types, which typically nucleate microtubule filaments from non-centrosomal microtubule organizing centers (MTOCs), leukocytes mainly utilize centrosomes for sites of microtubule nucleation. Yet, MTOC localization as well as microtubule organization and dynamics are highly plastic in leukocytes thus allowing the cells to adapt to different environmental constraints.

Here we summarize our current knowledge on microtubule organization and dynamics during immune processes and how these microtubule arrays affect immune cell effector functions. We particularly highlight emerging concepts of microtubule involvement during maintenance of cell shape and physical coherence.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900162/

 

[write4u]

Can this count as an internal cellular dialogue?

Quorum sensing in the immune system
Luca Antonioli,1 Corrado Blandizzi,1 Pál Pacher,2 Martin Guilliams,3,4 and György Haskó5,*

Abstract

Quorum sensing is the regulation of gene expression programmes in response to changes in population density. It is probably best recognized as a mechanism through which bacterial communities can synchronize behaviours, such as biofilm formation and bioluminescence. This Comment article highlights the emerging evidence suggesting that quorum sensing also contributes to the regulation of immune cell responses.

Quorum sensing was originally based on the idea that cooperation between bacterial cells of a single species would not be worthwhile unless a sufficient number of cells were present; that is, until a density threshold is reached. In bacterial quorum sensing, bacteria monitor their population density by communicating through the generation and detection of soluble extracellular signals called inducers1.

As the density of quorum sensing bacterial cells increases, so does the concentration of the inducer. Once bacterial density and therefore the concentration of the inducer reaches a certain level, this will result in the collective alterations of bacterial gene expression, which facilitates synchronized behaviours, such as biofilm formation, virulence and bioluminescence1. Thus, quorum sensing enables cells within a population to function in unison and, in doing so, to carry out behaviours as a collective entity.

It is now well appreciated that quorum sensing does not only occur in bacteria of the same species, but it extends to groups of heterogenous micro organisms that have evolved together, each one with adaptations tethered to the biology of the others, thus establishing evolutionarily stable interactions aimed at shaping and maintaining the equilibrium of the entire bacterial population inhabiting a niche1.

Several features of cellular behaviour that resemble those underlying bacterial quorum sensing can be found in the immune system. For example, quorum sensing contributes to regulating the absolute size of some immune cell subsets and helps to optimize their effector functions, such as cytokine secretion. Below we highlight some key examples of quorum sensing in the immune system.

more.........

Quorum sensing in the immune system

Quorum sensing is the regulation of gene expression programmes in response to changes in population density. It is probably best recognized as a mechanism through which bacterial communities can synchronize behaviours, such as biofilm formation and bioluminescence. ...

www.ncbi.nlm.nih.gov

 

[write4u]

This may provide some background to my agreement with Penrose and Hameroff’s ORCH OR .

IMO, consciousness does not exist independent of information processing. It emerges during the processing of information (thinking) and creates a spontaneous chronology from information stored in memory and incoming sensory information that allows for the experience of movement even if that movement consists of discrete quantum mechanics. Similar to a movie strip that consists of a series of individual frames.

It is known that long-term memory is stored in the microtubules contained in “pyramidal neurons” and short-term memory is stored in the microtubules of cellular cytoplasm and cytoskeleton. The dynamic information transportation is provided by the microtubules inside the neuronal axons and synapses (note that the human brain itself contains as many as 1000 trillion synapses that connect the neural microtubule bundles into a vast dynamical network where the microtubules can act as “variable resistors” or “potentiometers” exercising controlled bursts of action potentials.

The Action Potential

It seems obvious that at least some of this activity occurs at the quantum level.
And here is where the concept of Quantum Mind may be important in the consideration of “emergent consciousness”.

Quantum mind

The quantum mind or quantum consciousness is a group of hypotheses proposing that classical mechanics cannot explain consciousness.[1] It posits that quantum-mechanical phenomena, such as entanglement and superposition, may play an important part in the brain’s function and could explain consciousness.

And David Bohm’s perspective based on his hypothesis of the Implicate Order.

Bohm discussed the experience of listening to music. He believed that the feeling of movement and change that make up our experience of music derive from holding the immediate past and the present in the brain together. The musical notes from the past are transformations rather than memories. The notes that were implicated in the immediate past become explicate in the present. Bohm viewed this as consciousness emerging from the implicate order.

Bohm saw the movement, change or flow, and the coherence of experiences, such as listening to music, as a manifestation of the implicate order. He claimed to derive evidence for this from Jean Piaget’s work on infants.[11] He held these studies to show that young children learn about time and space because they have a “hard-wired” understanding of movement as part of the implicate order. He compared this hard-wiring to Chomsky’s theory that grammar is hard-wired into human brains.

Bohm never proposed a specific means by which his proposal could be falsified, nor a neural mechanism through which his “implicate order” could emerge in a way relevant to consciousness.[10] He later collaborated on Karl Pribram’s holonomic brain theory as a model of quantum consciousness.[12]

https://en.wikipedia.org/wiki/Quantum_mind

 

[write4u]

And this research in microtubular importance at the most fundamental levels is illustrated by this in-depth study of the Slime mold.

On the role of the plasmodial cytoskeleton in facilitating intelligent behavior in slime mold Physarum polycephalum

Abstract

The plasmodium of slime mold Physarum polycephalum behaves as an amorphous reaction-diffusion computing substrate and is capable of apparently ‘intelligent’ behavior. But how does intelligence emerge in an acellular organism?

Through a range of laboratory experiments, we visualize the plasmodial cytoskeleton—a ubiquitous cellular protein scaffold whose functions are manifold and essential to life—and discuss its putative role as a network for transducing, transmitting and structuring data streams within the plasmodium.

Through a range of computer modeling techniques, we demonstrate how emergent behavior, and hence computational intelligence, may occur in cytoskeletal communications networks. Specifically, we model the topology of both the actin and tubulin cytoskeletal networks and discuss how computation may occur therein.

Furthermore, we present bespoke cellular automata and particle swarm models for the computational process within the cytoskeleton and observe the incidence of emergent patterns in both.

Our work grants unique insight into the origins of natural intelligence; the results presented here are therefore readily transferable to the fields of natural computation, cell biology and biomedical science. We conclude by discussing how our results may alter our biological, computational and philosophical understanding of intelligence and consciousness.

To delineate, slime mold may be considered as an unconventional computing substrate in which data are represented as transitions in chemical equilibria in an excitable medium.

The plasmodium is able to concurrently sense input from a range of stimuli including temperature, light, chemicals, moisture, pH and mechanical force.2-5 P. polycephalum's innate behavior patterns may be manipulated experimentally to perform useful computational tasks, such as to calculating the shortest route between any number of spatially distributed nutrient sources, or navigating its way out of a maze via chemotaxis; these operations may be interpreted in terms of computational geometry, logic and spatial memory.6,7

Figure 1.
Plasmodium of slime mold P. polycephalum growing on an agar-filled Petri dish, feeding on porridge oats. Note the differences in morphology between medial/posterior plasmodial ‘veins’ (black arrow) and the ‘fan-shaped’ anterior margin (white arrow).

Note the natural formation of networks that resemble the neural networks in brained animals.

These systems are typically composed of simple and plentiful components, contain redundant parts (i.e. not being dependent on highly complex units), and show resilient or ‘fault tolerant’ behavior.

UC is often observed in systems which show ‘emergent behavior’, novel behavior which emerges from the interactions between simple component parts and which—critically—cannot be described in terms of the lower level component interactions.

Emergent behavior is found in systems with many simple, local interactions and which display self-organization, i.e. the spontaneous appearance of complexity or order from low-level interactions. Many of the attractive features of UC computing devices (distributed control, redundancy, fault tolerance) are generated by mechanisms of self-organization and emergence, and the study of these properties is useful not only from a computational perspective, but also from a biological viewpoint—since much of the complexity in living systems appears to be built upon these principles.

If Tegmark is correct in his proposition that certain patterns acquire emergent intelligence and eventually consciousness, it appears that the slime mold's ability to form semi-intelligent patterns that allow it to act as if it has acquired rudimentary computing abilities confirms his analysis.

And that throws an entirely different light on our approach to solving the "hard problem" of consciousness.

Moreover, I can see no more persuasive argument that microtubules are the prime constituent of "intelligent networks" than that even single-celled brainless and neuronless organisms have inherent "communication" skills that may be very much like "quorum sensing" in bacteria, plants and eventually acquire emergent self-aware conscious intelligence in more evolved complex animals.

Indeed, many analogies may be drawn between neurons and slime mold plasmodia, such as electrical excitability, branching/stellate morphology and memristivity (thought to be the basis of synaptic plasticity, and thus memory).

10 Neuron culture methods are expensive, temperamental and ethically restrictive, however; slime mold culture techniques are comparatively simple, cheap and resilient, with no associated ethical issues.

Lacking any biological components normally associated with so-called ‘intelligent behavior’ (brain, neurons etc.), the physiological origin of P. polycephalum's computational abilities are still largely unexplained, and as such, we are denied a vital tool for manipulating slime mold behavior to our advantage.

Several authors have previously formalized slime mold behavior patterns with mathematical models of protoplasmic network dynamics, which, while valuable in their description of how protoplasmic computations is enacted out at the organismal level, tend to adopt a top-down view of the phenomena observed and do not explain the underlying basis of the computation involved.

This investigation was designed to explore the basis of slime mold intelligence from a bottom-up perspective, at the molecular level.

On the role of the plasmodial cytoskeleton in facilitating intelligent behavior in slime mold Physarum polycephalum

The plasmodium of slime mold Physarum polycephalum behaves as an amorphous reaction-diffusion computing substrate and is capable of apparently ‘intelligent’ behavior. But how does intelligence emerge in an acellular organism? Through a ...

www.ncbi.nlm.nih.gov

And is that where ORCH OR may become the contending hypothesis?

 

[write4u]

Question: If nature is fractal.


View: https://www.pinterest.com/pin/763500943094920565/


Why should we have any problem with cognition when the neural network of the brain is itself fractal?

View: https://www.youtube.com/watch?v=kKeUI_Jko3o

 

[write4u]

continuing our microtubule state-of-the-art analysis;

The tubulin code: Molecular components, readout mechanisms, and functions
Carsten Janke

1,2,3,4

Identifying the mechanisms that generate and control tubulin heterogeneity and how this heterogeneity affects microtubule function are long-standing goals in the field. Recent work on tubulin PTMs has shed light on how these modifications could contribute to a “tubulin code” that coordinates the complex functions of microtubules in cells.

Introduction

Microtubules are key elements of the eukaryotic cytoskeleton that dynamically assemble from heterodimers of α- and β-tubulin. The structure of microtubules, as well as the protein sequences of α- and β-tubulin, is highly conserved in evolution, and consequently, microtubules look alike in almost all species. Despite the high level of conservation, microtubules adapt to a large variety of cellular functions.

This adaptation can be mediated by a large panel of microtubule-associated proteins (MAPs), including molecular motors, as well as by mechanisms that directly modify the microtubules, thus either changing their biophysical properties or attracting subsets of MAPs that convey specific functions to the modified microtubules. Two different mechanism can generate microtubule diversity: the expression of different α- and β-tubulin genes, referred to as tubulin isotypes, and the generation of posttranslational modifications (PTMs) on α- and β-tubulin (Figs. 1 and and2).2).

Although known for several decades, deciphering how tubulin heterogeneity controls microtubule functions is still largely unchartered. This review summarizes the current advances in the field and discusses new concepts arising.

Figure 1.
Tubulin heterogeneity generated by PTMs. (A) Schematic representation of the distribution of different PTMs of tubulin on the α/β-tubulin dimer with respect to their position in the microtubule lattice. Acetylation (Ac), phosphorylation (P), and polyamination (Am) are found within the tubulin bodies that assemble into the microtubule lattice, whereas polyglutamylation, polyglycylation, detyrosination, and C-terminal deglutamylation take place within the C-terminal tubulin tails that project away from the lattice surface. The tubulin dimer represents TubA1A and TubB2B (Fig. 2), and modification sites for polyglutamylation and polyglycylation have been randomly chosen. (B) Chemical structure of the branched peptide formed by polyglutamylation and polyglycylation, using the γ-carboxyl groups of the modified glutamate residues as acceptor sites for the isopeptide bonds. Note that in the case of polyglutamylation, the elongation of the side chains generates classical peptide bonds (Redeker et al., 1991).

....
and the importance of microtubules in maintenance neural health.

More recently, a large number of mutations in single tubulin isotypes have been linked to deleterious neurodevelopmental disorders (Keays et al., 2007; Fallet-Bianco et al., 2008; Tischfield et al., 2010; Cederquist et al., 2012; Niwa et al., 2013).

Mutations of a single tubulin isotype could lead to an imbalance in the levels of tubulins as a result of a lack of incorporation of mutant isoforms into the microtubule lattice or to incorporation that perturbs the architecture or dynamics of the microtubules.

The analysis of tubulin disease mutations is starting to reveal how subtle alterations of the microtubule cytoskeleton can lead to functional aberrations in cells and organisms and might provide novel insights into the roles of tubulin isotypes that have so far been considered redundant.

more........

The tubulin code: Molecular components, readout mechanisms, and functions

Microtubules are cytoskeletal filaments that are dynamically assembled from α/β-tubulin heterodimers. The primary sequence and structure of the tubulin proteins and, consequently, the properties and architecture of microtubules are highly ...

www.ncbi.nlm.nih.gov

And to illustrate the microtubule distribution in the brain.
Particularly in the Purkinje neurons which are assumed to be instrumental in memory and the processing of differential equations that IMO are causal to the emergence of consciousness and the experience of thinking and
holographic imagination.


Transverse section of a cerebellar folium. (Purkinje cell labeled at center top.)

Findings have suggested that Purkinje cell dendrites release endocannabinoids that can transiently downregulate both excitatory and inhibitory synapses.[27]

The intrinsic activity mode of Purkinje cells is set and controlled by the sodium-potassium pump.[28] .
This suggests that the pump might not be simply a homeostatic, "housekeeping" molecule for ionic gradients. Instead, it could be a computation element in the cerebellum and the brain.[29]

Indeed, a mutation in the Na+ -K+ pump causes rapid onset dystonia parkinsonism; its symptoms indicate that it is a pathology of cerebellar computation.[30] Furthermore, using the poison ouabain to block Na+ -K+ pumps in the cerebellum of a live mouse induces ataxia and dystonia.[31]

Numerical modeling of experimental data suggests that, in vivo, the Na+ -K+ pump produces long quiescent punctuations (>> 1 s) to Purkinje neuron firing; these may have a computational role.[32] Alcohol inhibits Na+ -K+ pumps in the cerebellum and this is likely how it corrupts cerebellar computation and body co-ordination.[33][34]

Findings have suggested that Purkinje cell dendrites release endocannabinoids that can transiently downregulate both excitatory and inhibitory synapses.[27] The intrinsic activity mode of Purkinje cells is set and controlled by the sodium-potassium pump.[28]

This suggests that the pump might not be simply a homeostatic, "housekeeping" molecule for ionic gradients. Instead, it could be a computation element in the cerebellum and the brain.[29]

Indeed, a mutation in the Na+ -K+ pump causes rapid onset dystonia parkinsonism; its symptoms indicate that it is a pathology of cerebellar computation.[30] Furthermore, using the poison ouabain to block Na+ -K+ pumps in the cerebellum of a live mouse induces ataxia and dystonia.[31]

Numerical modeling of experimental data suggests that, in vivo, the Na+ -K+ pump produces long quiescent punctuations (>> 1 s) to Purkinje neuron firing; these may have a computational role.[32] Alcohol inhibits Na+ -K+ pumps in the cerebellum and this is likely how it corrupts cerebellar computation and body co-ordination.[33][34]

Clinical significance[edit]

In humans, Purkinje cells can be harmed by a variety causes: toxic exposure, e.g. to alcohol or lithium; autoimmune diseases; genetic mutations causing spinocerebellar ataxias, gluten ataxia, Unverricht-Lundborg disease, or autism; and neurodegenerative diseases that are not known to have a genetic basis, such as the cerebellar type of multiple system atrophy or sporadic ataxias.[35][36]

more...

https://en.wikipedia.org/wiki/Purkinje_cell

 

[write4u]

New research suggests our brains use quantum computation

Scientists from Trinity College Dublin believe our brains could use quantum computation. Their discovery comes after they adapted an idea developed to prove the existence of quantum gravity to explore the human brain and its workings.

The brain functions measured were also correlated to short-term memory performance and conscious awareness, suggesting quantum processes are also part of cognitive and conscious brain functions.

more... https://phys.org/news/2022-10-brains-quantum.html

 

[write4u]

Question:

So then, how in the world to Huskies know to sing and Labradors just bark? Or a Parrot to imitate words, and any other group of bird like an Owl does not know how to do this. These are characteristics of different neuronal and synaptic patterns not unique to an individual that discovered how to do them but programmed in speciation. That combination neurons needs to be coded in the x and y chromosomes to make any neuronal distinction in innate behaviors of animals.

I repeat;

Life and evolution do not require mathematical rigidity. The example of the mathematical stochastic (probabilistic) function of natural selection can be seen in the theoretically infinite variety of speciation and presentation on earth alone from ordinary minerals to bird plumage and howling wolfs to submarine sonar communication.

Note that offspring contains DNA from both parents and is constantly refreshed and improved with every generation.

The ability of the microtubule to act in a dynamic rheostatic manner in response to sensory stimulation and distribute this information by intra-cellular communication (quorum sensing), by inter-cellular communication among sets of cells (patterns), by long distance transportation to the brain via axons, without loss and in certain cases being amplified.

To me these known proven abilities as "hard facts" are beginning to point into a direction where "extreme sensitivity" becomes an immediate action potential generated by the brain to counteract anything detrimental to the whole organisms and to stimulate the organism to react opportunistically and make a best guess (controlled hallucination) of possible responsible it thinks are optional .

The "neural network" that connects body to the brain and become a "problem solving organism"

The ultimate expression of evolving experiential qualification from "quorum sensing" to the imaginary qualification of the "Foundation Trilogy"

I believe that this perspective and interpretation of the role "microtubules" have played since the origin of Eukaryotic cellular functional abilities provided by the cytoskeleton that keeps us from falling when walking or running or in tree-climbing as well as processing information via an internal energy producing pattern.

Cellular Integrated and orchestrated patterns formed by the microtubule network, deep inside each Eukaryotic cell on earth. (there are some exceptions but) that is evolution for you. Whatever works to keep you alive, works.

Microtubules do a marvelous job of making it all work and deserve recognition of their crucial role they play at all levels of conscious intelligent biological life.

 

[write4u]

This may be helpful in understanding how the brain processes information.

View: https://www.youtube.com/watch?v=K7QBnuF6dHg

 

[write4u]

New stuff

NIH scientists take totally tubular journey through brain cells
Study may advance understanding of how brain cell tubes are modified under normal and disease conditions.

Fantastic Voyage. NIH scientists watched the inside of brain cell tubes, called microtubules, get tagged by a protein called TAT. Tagging is a critical process in the health and development of nerve cells.Roll-Mecak lab, NINDS, Bethesda, MD

In a new study, scientists at the National Institutes of Health took a molecular-level journey into microtubules, the hollow cylinders inside brain cells that act as skeletons and internal highways. They watched how a protein called tubulin acetyltransferase (TAT) labels the inside of microtubules. The results, published in Cell, answer long-standing questions about how TAT tagging works and offer clues as to why it is important for brain health.

Microtubules are constantly tagged by proteins in the cell to designate them for specialized functions, in the same way that roads are labeled for fast or slow traffic or for maintenance. TAT coats specific locations inside the microtubules with a chemical called an acetyl group. How the various labels are added to the cellular microtubule network remains a mystery. Recent findings suggested that problems with tagging microtubules may lead to some forms of cancer and nervous system disorders, including Alzheimer’s disease, and have been linked to a rare blinding disorder and Joubert Syndrome, an uncommon brain development disorder.

“This is the first time anyone has been able to peer inside microtubules and catch TAT in action,” said Antonina Roll-Mecak, Ph.D., an investigator at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Maryland, and the leader of the study.

Microtubules are found in all of the body’s cells. They are assembled like building blocks, using a protein called tubulin. Microtubules are constructed first by aligning tubulin building blocks into long strings. Then the strings align themselves side by side to form a sheet. Eventually the sheet grows wide enough that it closes up into a cylinder. TAT then bonds an acetyl group to alpha tubulin, a subunit of the tubulin protein.

Some microtubules are short-lived and can rapidly change lengths by adding or removing tubulin pieces along one end, whereas others remain unchanged for longer times. Recognizing the difference may help cells function properly. For example, cells may send cargo along stable microtubules and avoid ones that are being rebuilt. Cells appear to use a variety of chemical labels to describe the stability of microtubules.

“Our study uncovers how TAT may help cells distinguish between stable microtubules and ones that are under construction,” said Dr. Roll-Mecak. According to Dr. Roll-Mecak, high levels of microtubule tagging are unique to nerve cells and may be the reason that they have complex shapes allowing them to make elaborate connections in the brain.

For decades scientists knew that the insides of long-lived microtubules were often tagged with acetyl groups by TAT. Changes in acetylation may influence the health of nerve cells. Some studies have shown that blocking this form of microtubule tagging leads to nerve defects, brain abnormalities or degeneration of nerve fibers. Since the discovery of microtubule acetylation, scientists have been puzzled about how TAT accesses the inside of the microtubules and how the tagging reaction happens.

NIH scientists take totally tubular journey through brain cells

Study may advance understanding of how brain cell tubes are modified under normal and disease conditions.

www.nih.gov