Extra Cellular Vesicles in the Brain

B0008197 Vesicle transport at the golgi apparatusVesicles containing  neurotransmitters at synapses are well known, but mechanisms explaining their speed are still not clear. Very recently, neurons have been found to use many other types of vesicles to communicate with other cells, not at the synapse. Myelin patterns have been found to be much more variable than previously thought. These new types of vesicles are secreted in areas of the axon without myelin and at the cell body. Information sent to other cells in these vesicles includes genetic code, many kinds of RNAs, proteins and many other factors. Messages send important information to the other cells, such as astrocytes, microglia, oligodendrocytes, many immune cells and even muscle. Transmitted information can cause dramatic changes in behavior of the receiving cells. One type of information is where myelin should be built and another about how microglia and astrocytes should function. This post will update the recent research about the many different ways extra cellular vesicles in the brain are used.

Cellular Communication

B0004227 Synapse showing neurotransmitter vesiclesCells use many types of signals for communication. It has been surprising to learn how many ways cells communicate with other and the complexity of the back and forth chatter. As well as secretion of well-known neurotransmitters and cytokines, most cells also use nanotubes between cells and vesicles to send information in the form of genetic molecules, proteins and other factors.

A previous post described the very complex rapid release of vesicles with neurotransmitters at the synapse. Another post described how critical vesicles (exosomes) are to communities of cancer cells for their survival and spread. The use of vesicles to send information back and forth between neurons and other brain cells has been mentioned already. But, the full extent of this extra cellular vesicle communication with exosomes and micro vesicles is just now being described. This newly identified vesicle communication has been now seen for neurons with astrocytes and with oligodendrocytes about providing myelin for global neuroplasticity. Further research shows vital signals with microglia increase the spread of degenerative diseases and cancer.

Extra Cellular Vesicles

NIHMS420866.htmlExtra cellular vesicles (EVs) are sent from the cell’s membrane into the extracellular region between cells. Micro vesicles are between 100 nm (nano meter) and 1 μm (micro meter) in diameter and the smaller exosomes are 30 to 100 nm. (milli, micro, nano are each 1000th of the other). Vesicles are formed by taking a piece of the cell membrane or are produced from large multi vesicular bodies (MVBs). The difference derives from the location they are produced in secretory cellular pathways between Golgi, endoplasmic reticulum and lysosomes. Lysosomes destroy or recycle used vesicle material. This pathway was described in a post on lipid pathways.

Some of the vesicles are used inside the cell, some are sent to the cell’s membrane to be sent outside the cell and some are recycled for material. Part of this secretory pathway is a major large protein complex, called the endosomal sorting complex for transport (ESCRT). The ESCRT is required for transport. Other secretory pathways are generally for lipids within the cell and for forming vacuoles and lysosomes.

Another type of vesicle is sent from the cell when it is committing programed suicide through apoptosis. These are not used for communication but rather an orderly breakdown of the cell as it is eaten by phagocytes.

Micro Vesicles

PD Lipid_raft_organisation_schemeMicro vesicles are formed in the plasma membrane by lipid rafts. Lipid rafts surround material and secrete it from the cell. Lipid rafts are particular complexes in the membrane that are, also, used for secretion of neurotransmitters at synapses. Some of the lipids used to form the vesicles are different in microglia. They are also unique in micro vesicles, exosomes and apoptotic vesicles.

Exosomes

B0004340 Golgi complex and mitochondriaExososomes are also called intraluminal vesicles (ILVs). They exist inside of cells and contain unique lipids such as ceremide, which allows it to be built at the lipid rafts. Specialized membrane regions, called microdomains, organize production of signaling molecules and vesicles. The lipid rafts float in the membrane, but are much more ordered than the general membrane and can produce these unique vesicles.

In compartments of the cell, a narrow space limits the size of the vesicles. Golgi provides proteins for the vesicle. Vesicles can fuse with the outside membrane and release the contents without a vesicle. Another type fuses with a lysosome and sends the contents to be broken down. Even though micro vesicles and exosomes are different, it is not yet clear that they have any differences in protein types. There are many different complex versions of ESCRT complexes that are used in a variety of circumstance, such as providing covers for many different viruses as they leave the cell’s membrane.

Cargoes In EVs

PD syntheis of neuron axonVesicles can carry RNA, lipids and even large proteins. From a research standpoint, it is hard to distinguish the various types of vesicles to define exactly what cargoes they have. Most transport inside of the cell, such as along the axon, or in the secretory pathways, involves tags on the molecules that describe their destination. This has been difficult to discover thus far in vesicles and it is very complex. Research on this appears in several available sources, Vesiclopedia and EVpedia. Another complication is that each type of cell has different versions of the EVs and other cells respond only to certain ones with special receptors. Also, there have been different definitions of exosomes and microvesicles.

EVs are, also, present in CSF and in blood, as part of normal communication.

ESCRT Complex in the Membrane

From 2013MMG320C

From 2013MMG320C

ESCRT or endosomal sorting complex for transport was first discovered related to cargoes sent to lysomes for breakdown of debris. A small region where the lumen is narrow forms an inward limited vesicle from the membrane forming a MVB and ILV. ESCRT then chooses what will go into the new vesicle. It, also, closes the vesicle. There are many different versions of ESCRTs and many different cellular functions are based on them.

From 2013MMG320C

From 2013MMG320C

ESCRT are a very complicated set of 100 different large proteins that are in five different sub units. Different species have different versions. There are many associated proteins as well. One type in metazoans uses ubiquitin for tagging of cargo. Many processes use multiple ESCRTs at the same time along with ubiquitin tagging. Some uses of ESCRTs are not stable, but change during the procedures, such as EXCRT-III. This one forms a very long thin structure that creates a coil around the vesicle where it is being cut from the internal membrane. This type is, also, used for the budding of some viruses, such as HIV.

N0013888 HIV virus budding from T lymphocyteIn the membrane, the lipid PI3P (lipid phosphatidyl-inositol 3 phosphate) is attracts the complex. This first molecular complex tags proteins with ubiquitin. ESCRT-0 binds ESCRT1, ESCRT2 and together they start separating off vesicles from the multi vesicle body membrane. It uses the ubiquitin tags to sort and identify the various vesicles that are made.

Exosomes have a different protein and lipid composition from other extracellular vesicles. This composition varies based on many factors. Exosomes often carry immune molecules, cytoskeleton molecules and cellular signals.

The mechanisms that build each type of vesicle is extremely complex and just now being researched. Data will be provided as it is discovered. For now, the rest of post discusses the particular vesicles and their functions in the brain.

EVs In The Brain

B0005622 Enhanced MRI scan of the headNeurons secrete exosome sized EVs when stimulated with electrical action potentials, calcium channels, and molecules that block GABA or stimulate AMPA and NMDA. In one experiment fragments of tetanus toxin were sent to the neuronal surface. The toxin was brought into the cell and then released in vesicles from the neuron. Some showed transmission to other neurons. A brain tumor cell sent it to glia. One type of vesicle was found with receptors that were being discarded outside of the cell.

Many kinds of microRNAs are sent in these vesicles. During neuroplasticity, microRNAs are discarded in vesicles from the cell when their effects of silencing specific genes are too strong. Specific microRNAs sent to astrocytes produce an increase in specific transporters that take up glutamate from outside of the cell. This has significant effects on the glutamate signaling.

Oligodendrocytes Use Vesicles

B0006137 Schwann cell myelinating axonsA recent post on global neuroplasticity from myelin showed that communication between neurons and oligodendrocytes all over the brain is critical in determining the speeds of long range circuits so they can be coordinated to arrive at synapses at the correct moment for decision making. Vesicles are sent from axons that are not near the synapses to the oligodendrocytes. These carry proteolipid protein (PLP) and other myelin proteins critical for making myelin. They, also, include special proteins to help avoid oxidative damage. These are triggered by glutamate signals from neurons. The mechanism included calcium increase in the oligodendrocyte receptors for NMDA and AMPA.

Oligodendrocytes sent vesicles that are received by microglia and neurons. CRE recombinase enzyme was picked up from a vesicle and it helped neurons respond to cell stress. Special oligodendrocyte exosomes signal stem cells to stop making particular additional oligodendrocytes and myelin. This communication inhibits myelin from being made inappropriately or before they are near the neurons.

Some of the oligodendrocyte and neuron signals include PLP and are picked up by microglia using micro pinocytosis. This did not trigger microglia immune function, but rather was used as a way for the microglia to help rid the oligodendrocyte of cargo.

Vesicle Messages To Muscles

B0004108 Poly-innervated neuromuscular junctionsThe extremely complex back and forth communication between neurons and muscles was described in a previous post. Exosomes have been found to be critical in this process. Far from active zones, vesicles are observed to fuse with the muscle away from the synapse site. These vesicles contain specific enzymes used by the muscle. The complex junction called the sub synaptic reticulum forms a special tube and this is where the exosomes travel to the muscle and trigger specific receptors.

Schwann Cell EVs

B0005970 Myelinated nerve fibresSchwann cells produce myelin in the peripheral nervous system. Remarkably, they are able to alter their differentiated state if there is damage and return to being stem cell to help with the regeneration of the tissue. These new stem cells release vesicles with particular receptors that respond to neurotrophin factors for regeneration. Neurons pick up these vesicles (exosomes) and they are used for the regeneration. Vesicle cargoes increased the rate of the new axon’s regeneration. They, also, helped with the remodeling and breakdown of the axon before regeneration by inhibiting the axon growth cone. Also, critical receptor molecules for BDNF were also taken into the axon.

Microglia EVs

B0009828 Microglial cells from mouse spinal cord, LMMicroglia have been found to actively use EVs as well, not just to help eliminate debris. Stimulated by ATP from astrocytes on their surface receptors, microglia sent EVs with complex cargos. The vesicle included the precursor protein of cytokine interleukin-1β (IL-1β), as well as critical enzymes and receptors. The purpose of these vesicles is to release cytokines by action of the enzyme cutting the precursor protein. These vesicles are sent just in case they are needed, if tissue damage is found. As soon as damage is found, then the vesicles alter the precursor into the active cytokine, which is critical to stimulate the inflammatory response.

Microglia vesicles are, also, used to regulate the neuron’s action potential. Cargoes from the microglia stimulated neurons to fire with neurotransmitter release at the synapse. The neuron was also stimulated to make more ceremide and other special lipids for the creation of more vesicles. This also stimulated more production of the SNARE complex, a large multi protein structure that helps with vesicle launching from the membrane.

B0009824 Motor neurone from rat spinal cord, LMMicroglia are able to regulate the balance of neuronal stimulatory and inhibitory signals. Their micro vesicles include cargos of endocannabinoids, critical lipid molecules that are involved in the regulation of synapses. Endocannabinoids are often on the surface of the vesicle and can trigger the CB1 receptor in GABA neurons, which inhibits the inhibitory action of GABA. The microglia vesicles at the same time can stimulate excitatory neurons.

Some microglia micro vesicles send special immune signals similar to B lymphocytes and dendritic cells. They include complex cargo with receptors for class II MHC major histocompatibility complex, chaperone molecules, and other enzymes and receptors. One cargo includes an enzyme involved in opioid metabolism. They contain molecules related to Alzheimer’s. During large energy use of neurons when making an action potential, microglia send vesicles filled with lactate to use as an alternative energy source.

Several neurotransmitters such as serotonin stimulate receptors on microglia. These send vesicles with special enzymes related to breaking down insulin and amyloid–β. High levels of serotonin can decrease the amount of the amyloid–β.

Astrocyte EVs

ImageJ=1.45sAstrocytes have many critical functions related to producing and maintaining synapses. They also help balance ions and the blood brain barrier. They secrete exosomes that include IL-1β when stimulated by ATP.

The communication between oligodendrocytes, astrocytes, microglia and neurons involves many different uses of EVs. Research shows that these messages affect the amount of activity that the neuron will produce, the responses to cellular and organism stress and repair and protection of the neuronal network.

EVs in Invertebrates

fliesMore research has been able to be done on worms and flies than humans that shows prominent use of EVs for communication between cells in their nervous system.

In flies, the junction between the neuron and muscle has been widely studied. EVs control development of the neuro muscular junction during development both in the pre junction neuron and the post synaptic muscle. As muscles grow, communication is sent back and forth altering the junction through messages.

Communication occurs not at the junction but an adjacent area called the sub synaptic reticulum (SSR). Signals have proteins that are specially modified to become hydrophobic and therefore cannot just be secreted but rather need to be transported in a vesicle. With vesicles, the molecule can be taken right up to special receptors. Vesicles seem to use SNARE machinery that is similar to humans. Vesicles also are sent in response to the level of activity of the neuron, with many going out if there is greater frequency of action potentials.

B0007258 Neuromuscular junctionAt the neuro muscular junction exosomes are exchanged as well. Vesicles from the neuron sends information that has direct effects on the muscles related to plasticity and development. One protein that is often used for regulation of both anterograde and retrograde transmission in the brain is released in these exosomes for the muscle, just like microglia. It is also used in the fetus and with cancer. Another particle sent in exosomes regulates how many glutamate receptors there are in the muscle junction.

In worm sensory neurons cilia secrete vesicles with receptors. A complex transport mechanism for these vesicles lies along the flagella including the motor kinesin. Vesicles communicate with other worms related to mating behavior and increase their movement.

EVs In Disease

N0021139 Illustration; the pathology of Alzheimer's DiseaseA previous post described how mis folded proteins in the brain can be transmitted by vesicle transport between brain cells. They are, also, used in brain cancers (see post on Cancer and Exosomes) and in inflammation. But, they, also, send information for protection of neurons and are beginning to be used in treatment.

Prions are, also, transmitted as well in vesicles. (See post on Transmission of of Prions). Prion behavior is found in many other mis folded proteins that cause disease including amyloid-β and tau in Alzheimer’s; α-synuclein in Parkinson’s disease; and TAR DNA-binding protein (TDP43), copper zinc superoxide dismutase 1 (SOD1) and other proteins in amyotrophic lateral sclerosis and fronto temporal degeneration. Now, it has been found that all of these are packaged and transmitted in vesicles. This is difficult research because, a very small amount of mis folded protein can start this process, particularly prions. Also, it is possible that different forms of the proteins are sent in vesicles such as folded, unfolded and clumped (see post on the role of tau in brain disease). In cancers, vesicles can come from dying cells to further the cancer community.

It has not been established that vesicles are definitely part of the cause of Alzheimer’s. But, amyloid plaques have markers for exosomes. Other research points to exosomes being used as a protection for the cell to remove amyloid-β. Microglia in their reactive form in inflammation form micro vesicles that send material making amyloid soluble and increases Alzheimer’s pathology. In this scenario, micro vesicles increase Alzheimer’s and the exosomes do the opposite. Another study showed that abnormal tau is transmitted by exsosomes from microglia.

B0010354 Human brain cancer stem cells treated with graphene, SEMAs a previous post on cancer noted, cancers use an increased amount of vesicles for communication between the communities of cells. What is interesting is that among cancer cells, the contents of vesicles contain material that is altered from normal. These proteins can help a cancer grow in different ways and are called transforming proteins. They, also, contain RNAs that can alter cells and various unique histones.

Glioblastomas use stem cells to build the tumor and use vesicles to increase survival, movement and reproduction of other cells. Studies show that contents of vesicles alter receptors and pathways. When cancer cells are injected into another animal, they produce vesicles that start the new cancers in the new cell. In order for breast cancer cells to cross the blood brain barrier to form metastasis in the brain, they send specific microRNAs in vesicles that degrade the choroid cells at the blood brain barrier.

From Netha Hussain

From Netha Hussain

Microglia and astrocytes use vesicles as part of neuro inflammation. Neuro inflammation was described in another post as a complex form of neuroplasticity, where neurons produce all of the symptoms and signs of inflammation in various measured ways. In multiple sclerosis, cytokines are sent in the vesicles (cytokine IL-1β, interferon-γ, tumour necrosis factor (TNF) among others) to further inflammation. These vesicles also include proteins that can damage the blood brain barrier altering the tight junctions and extra cellular matrix. This allows T cells and other immune cells to cross into the brain without permission of the choroid cells (see post on Choroid Cells). When neurons are injured, astrocytes are activated and produce a large number of vesicles. Oligodendrites get into the act by stimulating microglia to further the inflammation. Patients with multiple sclerosis have a larger than normal amount of vesicles in the blood and CSF.

There are many other examples of vesicles used in inflammation. Pattern receptors normally pick up microbes and trigger inflammation responses. In the brain pattern recognition receptors on all three glia cells pick up injured cells and produce more cytokines that can increase damage. Many different inflammatory vesicles are produced in the degenerative diseases of Alzheimer’s, Parkinson’s and ALS.

Protecting the Brain

2D Mri Brain Image with 6mm Pituitary TumorAs well as spreading disease, vesicles also protect the brain. They send materials to rebuild after injury, disease and stress. They take toxic material to be removed including amyloid. They fight against prions. They help avoid damage from oxidation. Oligodendrocytes produce many molecules to help with stress from oxidative molecules including SOD1 and these are sent in vesicles to neurons. They send signals to avoid apoptosis and necrosis and help increase neuronal metabolism. HSPs (heat shock proteins) help as signals against stress and as chaperones. They were thought to only work inside of cells, but now it is shown that vesicles transmit them to help other cells. Many different brain cells send HSP in response to stress.

Vesicles work against aging also. MicroRNAs are sent by oligodendrocytes to produce more stem cells for increased myelination during injury.

Treatment with EVs

B0006226 Blood vessels in the retinaExosomes are found in all parts of the body and in all fluids and are increasingly part of disease diagnoses. They can be possible vehicles for treatment. Some exosomes pass through the blood brain barrier and can carry RNAs of various kinds and mediations. They do not trigger many immune reactions. They can be sent directly to specific types of cells with identification tags.

Many stem cells send particularly useful messages in exosomes that could be used for therapies. Vesicles can be produced by stem cells in cultures when stimulated by various factors. They produce very specific microRNAs that increase healing and neuroplasticity in an ischemic damaged area. Another type of exosome from a stem cell sends an enzyme that can degrade amyloid-β and can rid it from inside cells when they take up the exosome. It can also workand in the extra cellular matrix.

Other examples:

  • Exosomes from immune dendritic cells that are stimulated by interferon-gamma produce microRNAs such as miR-219 that stimulates stem cells to produce more oligodendrocytes and more myelin production.
  • Exosomes produced by macrophages produce enzymes that are anti oxidants and have been useful with Parkinson’s patients.
  • Another type is filled with siRNAs that stop beta-secretase enzyme to help Alzheimer’s.

Extra Cellular Vesicles in the Brain

revision figures draft 06112014.pptxAs more and more communication is found between all types of cells, important new messages have been found that are used by neurons. Vesicles used at synapses are well known. But, recently many other types of vesicle messages have been found. Similar messages have been found using nanotubes. Both these new vesicles and nanotubes are very small and have only recently been seen with electron microscopes. But, the research is very arduous and the information is only now coming out.

Advanced communication from neurons occurs with astrocytes, microglia, oligodendrocytes, many immune cells and even muscle cells. Where is the global understanding of the situation that allows a cell to communicate with another cell at great distance? Can anyone think this is random? Can anyone think these cells are not intelligent?

Where is the direction for this? Isn’t it reasonable to consider some form of mind interacting with these cells?

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  • the_professeur

    “Advanced communication from neurons occurs with astrocytes, microglia,
    oligodendrocytes, many immune cells and even muscle cells. Where is the
    global understanding of the situation that allows a cell to communicate
    with another cell at great distance? Can anyone think this is random?
    Can anyone think these cells are not intelligent?”

    I can believe that I don’t know for sure that intelligence is the factor that is at work here. I can believe that the “intelligence” is hard-coded into the cells in such a way that they cannot “not” communicate.

    How this communication comes about is unknown to me, but I will remain open to such information. For now.

    • The logic of people like Roy Niles tells them that information is automagically linked to some evolutionary self-directed purpose.

      He wants others to believe there is a “built in” strategic system that is not the innate immune system because he also wants others to believe in the pseudoscientific nonsense of neo-Darwinian theory.

      For comparison, see the series of blog posts here that link Jon Lieff’s accurate representations of biophysically constrained cell type differentiation from microbes to humans via the conserved molecular mechanisms that link angstroms to energy-dependent ecosystems in all living genera.

      • Roy Niles

        You’re lying as usual, Kohl, since I’ve made it clear many times that I’m not a neo-Darwinist, even though you may not know what a neo-Darwinist actually is. But what they’re not is what I am, a believer that we are self directed intelligent “adapters” to changes in our environments; which also represents our evolutionary purposes, which are in turn to make these necessary changes ourselves, rather than to depend, as you and those actual neo-Darwinists seem to, on some dopey form of happy accidents. Which account for what you seem to see as evolutionary links, rather than evolutionary causes.
        And which have nothing to do with anything that Jon Lieff has written on this blog.
        And by the way, how are those supposedly intelligent chromosomes working for you?

        • If you are referring to the chart from my Molecular Diagnostics poster presentation last week, it can now be compared in the context of “Predicting miRNA Targets by Integrating Gene Regulatory Knowledge with Expression Profiles” http://www.ncbi.nlm.nih.gov/pubmed/27064982 and Transcriptomics resources of human tissues and organs http://msb.embopress.org/content/12/4/862.export

          See the chart here: https://www.youtube.com/watch?v=K35THJtlhoE&nohtml5=False

          What is life when it is not protected from virus driven entropy?

          • Roy Niles

            Of course that’s the piece of meaningless verbiage I was referring to. Predictive? Predictions require an analysis of probabilities. There’s not an analytical bone in that chart’s body.

            What is life when it’s not protected from virus driven entropy? I believe you have the last part of that question backwards.

            And so far, you have five comments on You Tube, all written by you.

          • Roy Niles

            Of course that’s the piece of meaningless verbiage I was referring to. Predictive? Predictions require an analysis of probabilities. There’s not an analytical bone in that chart’s body.

            What is life when it’s not protected from virus driven entropy? I believe you have the last part of that question backwards.

            And so far, you have five comments on You Tube, all written by you.

          • Jon Lieff is commenting on Facebook, and so are others. https://www.facebook.com/SearchingForTheMind/posts/945834518862922?fref=nf

            I’m updating the support for the predictive model as time allows, but I am also preparing another presentation for the Genetics and Genomics webinar.

            The model has already predicted the links from nutritional epigenetics to pharmacogenomics in the context of metabolic networks and genetic networks. No analysis of probabilities is required when facts are included that link angstroms to ecosystems in all living genera.

          • Roy Niles

            Kohl, everything in the end is linked to everything else, which in your view would seem to mean that everything is the cause of everything. Which explains nothing and predicts nothing about what has a causative relation to what, or why. There’s no science involved here at all., and no philosophy. And especially no logic.
            Just babble.
            And Jon Lieff did NOT comment on your “predictive” models at all on facebook.

          • He is following exactly the path that I have used to explain all biologically-based cause and effect via energy-dependent changes in the microRNA/messenger RNA balance. With no need to cite the literature and his ability to write clearly, he is presenting a better case for an educated audience.

          • Roy Niles

            Exactly but better. Couldn’t be put more mildly.

    • IntelligentAnimation

      While we can never be “for sure” about anything in science, except perhaps our own self aware consciousness, would you not say that the preponderance of evidence indicates that vesicular communication is intentional and intelligent?

      Professor: “I can believe that the ‘intelligence’ is hard-coded into the cells in such a way that they cannot ‘not’ communicate.”
      While I am all for open-mindedness, I can honestly say that for me to believe such a thing, literally everything I know about cellular communication and the intelligence of life would need to be entirely different than it is. Although to an extent I have become jaded to ridiculous ideologically-driven comments by materialists, I’ll admit I am struggling with your response.
      One of the reasons it bothers me is that you aren’t the typical boneheaded arrogant materialist. You seem intelligent, open-minded and, unlike most materialists, actually listening and trying to learn. Yet this comment was made and I can’t help but to probe a little deeper here.
      Are you thinking that the likelihood is that cellular communication is intentional, but just trying to go to great lengths to consider all possibilities no matter how silly? Or do you seriously see reason to consider accidental communication to be your primary belief at this point?
      Is it that you see any actual evidence (which ought to be repeatable in a lab, no?) that leads you to believe in functional complex communication by standard chemical reactions or is this just a desperate desire to fulfill an a priori conviction?
      I realize that there may be a few rare instances where something may seem intelligent but it all turns out to be explainable by blind accident. But these would need to be fairly simplistic cases and, again, extremely rare and not repeatedly seen under various circumstances.
      In general terms, the idea of any sort of communication of complex, functional information being transmitted unintentionally runs sharply against common sense, even before any mathematical odds are applied. In fact, the existence of such information at all can legitimately be said to eliminate accident as a cause, even before considering the fact that this information is transmitted, received and acted upon in a functional way.
      That this vesicular communication involves multiple various functions, languages and media defeats the idea of any one extremely bizarre chemical Rube Goldberg freak accident. That the cells take this information, package it into vesicles that are built to be the right size and shape for it, then close the vesicle, transfer it through a cell membrane and send it through the bloodstream or cerebral spinal fluid to another cell, which then admits the vesicle, opens it and carries out vital functions in accordance with the information is an unneeded slam dunk.
      Note that this is not taking place in a test tube (nor would it) but in an organism that seems to indicate literally 100% intelligent action, not the least of which is building multi-cellular creatures who themselves indicate essentially 100% intelligent activity, formation and thoughts. We even know that when we as humans, who are related to, and made from, these cells, communicate, that we do it intentionally and intelligently. At some point, even if you have abandoned all mathematics and science, doesn’t logical uniformitarianism become difficult to ignore?
      Is there ANY point that a materialist recognizes the hopelessness of their position and accepts science?

  • the_professeur

    “Advanced communication from neurons occurs with astrocytes, microglia,
    oligodendrocytes, many immune cells and even muscle cells. Where is the
    global understanding of the situation that allows a cell to communicate
    with another cell at great distance? Can anyone think this is random?
    Can anyone think these cells are not intelligent?”

    I can believe that I don’t know for sure that intelligence is the factor that is at work here. I can believe that the “intelligence” is hard-coded into the cells in such a way that they cannot “not” communicate.

    How this communication comes about is unknown to me, but I will remain open to such information. For now.

  • Roy Niles

    Logic tells us that there has to be some evolutionary self-directed purposes for these intelligent systems to cooperatively and functionally exist. These systems then are all carrying out their “built in” strategic instructions as to what they’ve been systematically assigned to do, and how, and what to choose to accomplish all of this, and when; and which of their adjoining or accompanying cellular “pals” to cooperatively work with in this overall extremely complicated process.
    But as in any group of biological entities or beings, there are going to be leaders to oversee the welfare of the group, and make sure these strategies are properly executed. Which we know is what our human “minds” are there to do as well. So clearly there must be similar mindful forms involved in the processes described in this post. How many are needed and where they might be located is the question. The further question is, then, will it be possible to find their physical locations, if any, with the present means we have available to look for them.

    • Let me guess, Roy Niles. You think the physical locations of “mindful forms” will be found somewhere in the model of the static DNA double helix that Watson and Crick believed in. Right?

      • Roy Niles

        No comment.

  • As always, Jon Lieff exemplifies his great timing with this article.

    Others are starting to catch up!

    Genetic and environmental influences interact with age and sex in shaping the human methylome

    http://www.nature.com/ncomms/2016/160330/ncomms11115/full/ncomms11115.html

    Reported as: This week, Nature Communications features the kind of publication I’m always looking for—an attempt to gauge how heritable epigenetic marks actually are (DNA methylation, in this case). It also addresses the extent to which environmental exposures and genetic variation affect marks at specific sites in the genome.

    How heritable? About 19%, on average. The research team, from a large number of institutions including the Netherlands’s VU Amsterdam, examined DNA methylation in whole blood, using SNP and methylation reads of identical twins and their families to tease out just how much methylation at specific sites depended upon heritability.

    The group also judged to what degree methylation at individual sites owed to gender and to chronological age. The authors add that by comparing this data with methylation studies that measure the effects of smoking, metabolic factors, and more can further illuminate the influence of genes and environment on DNA methylation throughout life.

    -CW New England Biolabs

    • Roy Niles

      Even when copying someone else’s research, you goof it up, Kohl.
      You seem unaware that Dr, Lieff sees methylation as an intelligent biological process of using chemicals not just to “affect” but to control and cause adaptive changes to self-selected biological systems. Adaptation is an ongoing process, not an accidental result of what you seem quite happy to meanginglessly call “linkage.”