write4u Posted February 4, 2023 Author Report Posted February 4, 2023 (edited) On 11/4/2022 at 11:47 PM, JeffreysTubes8 said: This is exactly what concerns me, how can something more complicated be saved and stored as data transfer in something less complicated than itself, such as the coded blueprints of the entire human body in Eukaryotic cells? To discern between the entire neural pathways and how they interact and think wouldn't the dna have to be able to think itself? No, chromosomes don't need to think. And DNA does not store memories of an experiential nature. DNA contains only cell growth instructions and is strictly chemical in function. This is what allows the microtubules to make copies with exquisite fidelity. What does DNA do? The DNA code contains chemical instructions needed to make the proteins and molecules essential for chronological growth, development and health. Quote DNA? provides instructions for making proteins? (as explained by the central dogma?). The sequence of the bases?, A, C, G and T, in DNA determines our unique genetic code and provides the instructions for producing molecules in the body. The cell reads the DNA code in groups of three bases. Each triplet of bases, also called a codon, specifies which amino acid? will be added next during protein synthesis. There are 20 different amino acids, which are the building blocks of proteins. Different proteins are made up of different combinations of amino acids. This gives them their own unique 3D structure and function in the body. Only 61 of the 64 codons are used to specify which of the 20 amino acids is next to be added. There are three codons that don’t code for an amino acid. These codons mark the end of the protein and stop the addition of amino acids to the end of the protein chain. The codon wheel above can be used to translate DNA codons into amino acids. Find the first letter of your sequence in the inner circle and work outwards to see the corresponding amino acid, for example ATG = methionine. Image credit: Genome Research Limited https://www.yourgenome.org/facts/what-does-dna-do/ The role of microtubules in the mitotic spindle is to make exact copies of the chromosomes, so that the exact growth instructions are passed on into the daughter cells. Any copy errors are usually too small to impact the overall construct, but does show up as identifiable differences even between siblings and of course may lead to favorable or unfavorable natural selection along the lifeline of the organism. Memories are stored in the Purkinje neurons in the brain and they much more numerous than all the cells in your body. There are some 14.5 million Purkinje neurons in the cerebellum and a single Purkinje neuron may connect to 100,000 synapses, fed by bundles of neural microtubules. Does that pique your interest?..😲 MTCL1 plays an essential role in maintaining Purkinje neuron axon initial segment, Tomoko SatakeKazunari YamashitaKenji HayashiSatoko MiyatakeMiwa Tamura-NakanoHiroshi DoiYasuhide FurutaGo ShioiEriko MiuraYukari H TakeoKunihiro YoshidaHiroyuki YahikozawaNaomichi MatsumotoMichisuke YuzakiAtsushi Suzuki Abstract Quote The axon initial segment (AIS) is a specialized domain essential for neuronal function, the formation of which begins with localization of an ankyrin-G (AnkG) scaffold. However, the mechanism directing and maintaining AnkG localization is largely unknown. In this study, we demonstrate that in vivo knockdown of microtubule cross-linking factor 1 (MTCL1) in cerebellar Purkinje cells causes loss of axonal polarity coupled with AnkG mislocalization. MTCL1 lacking MT-stabilizing activity failed to restore these defects, and stable MT bundles spanning the AIS were disorganized in knockdown cells. Interestingly, during early postnatal development, colocalization of MTCL1 with these stable MT bundles was observed prominently in the axon hillock and proximal axon. These results indicate that MTCL1-mediated formation of stable MT bundles is crucial for maintenance of AnkG localization. We also demonstrate that Mtcl1 gene disruption results in abnormal motor coordination with Purkinje cell degeneration, and provide evidence suggesting possible involvement of MTCL1 dysfunction in the pathogenesis of spinocerebellar ataxia. https://www.embopress.org/doi/full/10.15252/embj.201695630# <==the paralell fibers are bundled microtubules? microtubuleshttps://www.sciencedirect.com/topics/neuroscience/purkinje-cell# Purkinje Neurons: Development, Morphology, and Function, Tomoo Hirano 1 Abstract Quote Cerebellar Purkinje neurons are arguably some of the most conspicuous neurons in the vertebrate central nervous system. They have characteristic planar fan-shaped dendrites which branch extensively and fill spaces almost completely with little overlap. This dendritic morphology is well suited to receiving a single or a few excitatory synaptic inputs from each of more than 100,000 parallel fibers which run orthogonally to Purkinje cell dendritic trees. In contrast, another type of excitatory input to a Purkinje neuron is provided by a single climbing fiber, which forms some hundreds to thousands of synapses with a Purkinje neuron. This striking contrast between the two types of synaptic inputs to a Purkinje neuron has attracted many neuroscientists. Quote It is also to be noted that Purkinje neurons are the sole neurons sending outputs from the cerebellar cortex. In other words, all computational results within the cortex are transmitted by Purkinje cell axons, which inhibit neurons in the cerebellar or vestibular nucleus. Notably, Purkinje neurons show several forms of synaptic plasticity. Among them, long-term depression (LTD) at parallel fiber synapses has been regarded as a putatively essential mechanism for cerebellum-dependent learning. In this special issue on Purkinje neurons, you will find informative reviews and original papers on the development, characteristics and functions of Purkinje neurons, or related themes contributed by outstanding researchers. https://pubmed.ncbi.nlm.nih.gov/30284678/ And it appears that it is the Purkinje neurons that store memories and like the Pyramidal neurons are actively involved in processing sensory stimulation and processing of input data against prior memorized experiential data in a constant feed-back loop that produces cognition and triggers action potentials in response. Is this the point where consciousness emerges? Edited February 15, 2023 by write4u identification Quote
write4u Posted February 4, 2023 Author Report Posted February 4, 2023 (edited) Stepping back for a moment to a simpler example of "problem solving" abilities in brainless (non-neural) organisms such as the slime-mold. Please note that any reference to the plasmodial cytoskeleton actually addresses microtubules and related filaments. Quote cy·to·skel·e·ton noun BIOLOGY a microscopic network of protein filaments and tubules in the cytoplasm of many living cells, giving them shape and coherence. But that is just the beginning of what microtubules do. On the role of the plasmodial cytoskeleton in facilitating intelligent behavior in slime mold Physarum polycephalum, Richard Mayne,* Andrew Adamatzky, and Jeff Jones* Outsourcing computation to the cytoskeleton Quote Let us apply paradigms of morphological computation (see Introduction) to a hypothetical slime mold under the assumption that the cytoskeleton functions as a data network. Stimulation of surface receptors, e.g., by detection of a chemical gradient, may prompt the signal to be transduced as electrical potential/quantum events/molecule transport (or any combination of these) through the cytoskeletal proteins coupled to the receptor. Quote The frequency (and also possibly the magnitude) of incident signals are proportional to the degree of stimulation, but are transduced in an unambiguous, statistically repeatable format, and are then transmitted to the parts of the organism which receive and act upon such information (here assumed to be the nuclei). It is assumed that when the hypothetical signal reaches a branch in the cytoskeletal network, it may propagate down multiple branches, depending on its ‘pattern’ (encompassing data type, frequency and possibly magnitude), thereby amplifying the signal to inform multiple nuclei. Hence, data has been converted into a format the slime mold can ‘understand’ and broadcast to multiple nuclei, despite the process requiring no control from the slime mold: these tasks can therefore be said to have been outsourced to the morphology, in that they occurred automatically as a consequence of the physical properties of the cytoskeleton. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594612/ And is this where consciousness began to evolve? Edited February 4, 2023 by write4u Quote
write4u Posted February 5, 2023 Author Report Posted February 5, 2023 (edited) Quote JeffreysTubes8 said; 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 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. Edited February 5, 2023 by write4u Quote
write4u Posted February 5, 2023 Author Report Posted February 5, 2023 (edited) 15 hours ago, JeffreysTubes8 said: It's all in the blood. The brain actually can make changes to cells using blood flow. Understanding how oxygen, ions, biolelectricity, and the salty synapses between neurons and nerve endings talk to the brain as a whole and the specific regions responsible for these cellular modifying functions (connected more to the endocrine system than the CNS I would imagine) can help us create nanotechnology that can truly modify genes by talking to the brain the way I suspect red blood cells do. I don't think so. Blood delivers oxygen to the cells, and also removes toxic materials, such as carbon dioxide from cells, but it has little to do with carrying electrochemical information. Microtubules inform the individual cells and networked cells of the status and control of health and functional sensory acuteness. They began by controlling very early after the first Eukaryotic organism began to populate earth. The basic "fight or flight" response system (pattern) has undergone an evolutionary journey from purely chemical responses to controlled reactions to external and/or internal stressors. Microtubules do the sorting (a process) of incoming information for consideration by the brain and the production and release of "action potentials" to deal with potential problems. Figure 11.44 Organization of microtubules in nerve cells Quote Two distinct types of processes extend from the cell body of nerve cells (neurons). Dendrites are short processes that receive stimuli from other nerve cells. The single long axon then carries impulses from the cell body to other cells, which may be either other neurons or an effector cell, such as a muscle. Stable microtubules in both axons and dendrites terminate in the cytoplasm rather than being anchored in the centrosome. In dendrites, microtubules are oriented in both directions, with their plus ends pointing both toward and away from the cell body. In contrast, all of the axon microtubules are oriented with their plus ends pointing toward the tip of the axon. https://www.ncbi.nlm.nih.gov/books/NBK9932/# Edited February 6, 2023 by write4u Quote
write4u Posted February 7, 2023 Author Report Posted February 7, 2023 This may be of help in visualizing how the brain processes information. I believe that the microtubule network patterns allow for the processes that are being discussed. Quote
write4u Posted February 8, 2023 Author Report Posted February 8, 2023 (edited) 2 hours ago, JeffreysTubes8 said: Well, you're sort of biased towards MTs because that's what this thread is about. But before you can't get microtubules out of your head, consider how sensitive the brain's release of hunger hormones is to blood sugar. So blood really does transmit electrochemical signals to the brain. Please don't misunderstand. I recognize that blood is essential for homeostatic processes that do not necessarily involve neurons and the brain . Blood keeps the body alive. Quote It is therefore not surprising that the arterial blood supply to the human brain ... The total length of capillaries in the human brain is ~400 miles [11]. https://www.ncbi.nlm.nih.gov/books/NBK53086/ Quote The hemoglobin is the only organ that permeates and flows through every organ in the body, every cell of the body gets contacted by the hemoglobin, it is the perfect instrument for synaptic monitoring even over microtubule cells. Are you aware that microtubules are not cells but are nano-sized dipolar tubulin coils inside cells by the hundreds. There are many more microtubules than cells in your body Note : this is a single celled Paramecium. The hairlike cilia are made up from microtubules and associated filaments. Components of the eukaryotic cytoskeleton. Actin filaments are shown in red, microtubules are in green, and the nuclei are in blue. The cytoskeleton provides the cell with an inner framework and enables it to move and change shape. And that is just the cytoskeleton in every cell, including the axons of neural cells that connect microtubule bundles over long distances. The brain alone has some 100 billion neurons connected by some 1000 trillion synapses. Note that synapses are the terminal ends of microtubules and is the area where "action potentials" are created and transmitted. Neurons allow us to think and evaluate sensory experiences and also form the mitotic spindle for cell division, a dynamic copying process. Blood provides the energy, neuronal network provides control, both conscious and unconscious. Edited February 8, 2023 by write4u Quote
write4u Posted February 15, 2023 Author Report Posted February 15, 2023 (edited) On 2/8/2023 at 10:20 AM, JeffreysTubes8 said: So blood really does transmit electrochemical signals to the brain. The hemoglobin is the only organ that permeates and flows through every organ in the body, every cell of the body gets contacted by the hemoglobin, it is the perfect instrument for synaptic monitoring even over microtubule cells. I'd like to revisit this. I believe you have this backwards. a) hemoglobin is the oxygen transport system and consists of a molecule containing iron as the oxygen carrier. Not all animals have hemoglobin as the oxygen carrier in their blood. Crustaceans and mollusks (Octopuses) have hemocyanin in their blood which makes it blue/green instead of red, but works better under extreme cold. A beautiful example of natural selection for survival advantage. But where I believe you may be in error is that blood does not pass through cells but delivers its oxygen content to individual cells via a process of diffusion. And here is where I believe microtubules play a role, perhaps even in several ways. . THEORY OF OXYGEN TRANSPORT TO TISSUE Quote In mammals, oxygen is extracted from the atmospheric air in the lungs, and carried by the bloodstream through the circulation to the tissue, where it is utilized mainly within the mitochondria. Behind this simple picture lie many questions concerning physical mechanisms of transport in different parts of the pathway. Is oxygen transported in blood mainly by pure convection, and what are the roles of diffusion and chemical kinetics? How important are the resistances to transport provided by various membranes (red blood cell, endothelial cell, parenchymal cell) along the pathway? Does oxygen cross these membranes by pure diffusion, or is the diffusion facilitated by a carrier? more...... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5445261/ This article is a little dated and was published before the study of microtubules at nano scale could be performed. However it does mention that the oxygen is primarily used by the mitochondria that distributes energy throughout the cell. It is now known that mitochondria is intimately connected to microtubule function. From a more recent article: Microtubules Are Essential for Mitochondrial Dynamics–Fission, Fusion, and Motility–in Dictyostelium discoideum Quote Mitochondrial function is dependent upon mitochondrial structure which is in turn dependent upon mitochondrial dynamics, including fission, fusion, and motility. Here we examined the relationship between mitochondrial dynamics and the cytoskeleton in Dictyostelium discoideum. Quote Using time-lapse analysis, we quantified mitochondrial fission, fusion, and motility in the presence of cytoskeleton disrupting pharmaceuticals and the absence of the potential mitochondria-cytoskeleton linker protein, CluA. Our results indicate that microtubules are essential for mitochondrial movement, as well as fission and fusion more.... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801864/# The same mechanism that allows for inter-cellular communication may well be used to uptake the diffusion of oxygen from the blood in capillaries and transport it to the mitochondria. Heuristic consequences of a load of oxygen in microtubules Quote Abstract The current cell oxygen paradigm shows some major gaps that have not yet been resolved. Something seems to be lacking for the comprehensive statement of the oxygen distribution in the cell, especially the low cytoplasmic oxygen level. Quote The entrapment of oxygen in microtubules (MTs) resolves the latter observation, as well as the occurrence of an extensive cytoplasmic foam formation. It leads to a novel oxygen paradigm for cells. During the steady-state treadmilling, the mobile cavity would absorb oxygenated cytoplasm forward, entrap gas nuclei and concentrate them. A fluorescence method is described to confirm the in vitro load of oxygen in MTs during their periodic growths and shrinkages. The latter operating mechanism is called the gas dynamic instability (GDI) of MTs. Quote Several known biosystems could rest on the GDI. (1) The GTP-cap is linked with the gas meniscus encountered in a tube filled with gas. The GTP hydrolysis is linked to the conformational change of the GTPase domain according to the bubble pressure, and to the shaking of protofilaments with gas particles (soliton-like waves). (2) The GDI provides a free energy water pump because water molecules have to escape from MT pores when foam concentrates within the MT. Quote Beside ATP hydrolysis in motor proteins, the GDI provides an additional driving force in intracellular transport of cargo. The water streams flowing from the MT through slits organize themselves as water layers between the cargo and the MT surface, and break ionic bridges. It makes the cargo glide over a water rail. (3) The GDI provides a universal motor for chromosome segregation because the depolymerization of kinetochorial MTs is expected to generate a strong cytoplasmic foam. Chromosomes are sucked up according to the pressure difference (or density difference) applied to opposite sides of the kinetochore, which is in agreement with Archimedes' principle of buoyancy. Non-kinetochorial MTs reabsorb foam during GDI. more.... https://pubmed.ncbi.nlm.nih.gov/24525190/ Note that blood cells themselves have microtubules. A comparative study of microtubules of disk-shaped blood cells Quote Experiments were performed on the disk-shaped nucleated erythrocytes of the frog and the chick, chick thrombocytes, and blood platelets of rat and man to test (a) whether the microtubules of the marginal bundles showed a similar response to different treatments and (b) whether there was any correlation between the integrity of the marginal bundle and cell shape. https://www.sciencedirect.com/science/article/abs/pii/S0022532070901450 While this article does not specifically mention any potential role microtubules in bloodcells may have in oxygenation diffusion, this may be due to the known role iron plays in oxygen uptake, but of which little is actually known about the actual mechanics. This may lead to some clarity. What Does Iron Do for Your Body What Does Iron Do for Your Body Quote Just as iron is essential in the production of steel, it is also essential to human life. About 70% of the iron in your body can be found in a protein in red blood cells called hemoglobin. Iron is essential in making hemoglobin, a protein in red blood cells. These red blood cells help carry oxygen throughout your body. Six percent of iron can also be found in other essential proteins and another 25% is stored in your body in a blood protein called ferritin. Iron is also vital for a fully functioning immune system. If your iron levels are too high or too low, they can cause serious health problems. What Is Ferritin? and what does ferritin do? Ferritin forms dynamic oligomers to associate with microtubules in vivo: implication for the role of microtubules in iron metabolism Quote Ferritin is a protein in the body that stores iron and releases it when needed. A ferritin test can determine how much iron your body has stored. On average, adult males have about 1,000 mg of stored iron (enough for about three years), and adult women have about 300 mg (enough for about six months). When iron intake is chronically low, these stores can become depleted, resulting in lower-than-normal ferritin levels and decreased hemoglobin. more... https://pubmed.ncbi.nlm.nih.gov/16603154/# It appears then that blood is the bulk oxygen carrier, but when diffusion into cells takes place this process may well be controlled and/or facilitated by microtubules. These little nano scale dipolar coils are everywhere and play a role in electro-chemical information control and distribution. I believe we haven't even begun to discover what these little data processors can do. But there is a healthy interest and research underway. Edited February 15, 2023 by write4u editing Quote
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