Membrane Lipids Direct Proteins and Proteins Direct Lipids

N0019830 EndocytosisThe largest number of brain molecules are lipids (fats). Unique regulation of brain lipids is complex and contributes to many diseases. Surprisingly, it has been found that membrane lipids direct proteins and proteins direct lipids. 

Previous posts have discussed the importance of lipids in communication between brain cells using vesicles made with fatty membranes. The rapid complex process where lipid covered vesicles transmit neuro transmitters at synapses uses 80% of all of the brain’s energy. Secretory pathways in neurons that form fatty membranes for vesicles are extremely complex. Large complexes of many interlocking proteins are involved assembling machinery for lipid-based processes. The unusual collaboration of unique lipids and proteins in membranes are just being discovered. 

Lipids in the Brain

Lipids in the brain are unusual in that they are insoluble, but at the same time form complex structures in water solution. Brain has more varied lipids than any other organ and elaborate lipids are correlated with higher cognitive ability in primates. Lipids in brains vary at different ages, in different brain regions and with stress and trauma. Changes in lipids are associated with many psychiatric and neurological diseases.

B0004227 Synapse showing neurotransmitter vesiclesVital pre synaptic terminals engage in very rapid and complex remodeling of fatty membranes. Please see the previous post on Mysterious Pre Synaptic Vesicles for a discussion of the complexity of this process. It is still not completely understood.

Membranes are dramatically and very rapidly altered to provide constant release of vesicles filled with neurotransmitter molecules. Vesicles somehow are released from the membrane without making holes and then are recycled and re used milliseconds later. Protein structures build scaffolding for this release in the form of clathrin and SNARE machinery discussed in previous posts.

Chicken and Egg

PD Lipid_raft_organisation_schemeNew research shows lipids regulating all of the complex membrane processes. But, proteins help to rapidly produce unique lipids for each situation. They both direct each other. Another well known chicken and egg conundrum is DNA making proteins and proteins regulating DNA. How do these interactions develop? At synapses, lipids control protein activity and proteins control what types of lipids are produced.

From Mitoribo

From Mitoribo

Lipids do more than provide a barrier. They are uniquely interactive with proteins in all processes. Terminals are extremely efficient at remodeling membranes. Vesicles fuse with membranes in 1 millisecond and can reproduce this process 100 times per second or more.

Vesicles are released from special active zones with elaborate SNARE machinery including many large interacting proteins. Active zones include a large amount of interconnected proteins that prepare and dock vesicles and help to release them. Vesicles are also taken back in to membrane of the synapse. Somehow, membranes are rapidly brought back to the normal state to prepare for the next alteration. If membranes did not go back to the normal state, they would rapidly deteriorate with proteins and lipids in the wrong places.

Special Lipids in Membranes

Lands cycleSynapses contain cholesterol and poly unsaturated fatty acids (PUFAsee post on Polyunsaturated Fatty Acid Signaling in the Brain). Vesicle mechanisms need other particular lipids including phosphatidylinositol phosphates and phosphatidylserin (PtdinsPs and PtdSer). Many different enzymes metabolize lipids in synapses that alter their structures.

PtdinsPs are negatively charged lipids facing the inside of the cell. They are critical in multiple steps of neurotransmission process. Seven different PtdinsPs are used in various phases based on where phosphates are placed on the molecule and how many placements there are. Although there is only a small concentration of each lipid molecule in membranes, many of the proteins in the synaptic machinery have unique interactions with each type. These specific lipid molecules define unique compartments in the membrane.

Special interactions between particular lipid versions and unique proteins are vital where vesicles are released in synapses. Collaborations are necessary for neurotransmitter release. Lipid molecules regulate how pre synaptic vesicles are released by controlling calcium. It has been known for some time that when action potentials arrive at axon terminals, calcium is increased and this somehow triggers release of pre synaptic vesicles filled with neurotransmitters. But, only recently has the direction by lipid molecules been discovered.

From Jbryan13

From Jbryan13

Particular neurons that release hormones have special lipids placed in unique places at terminal membranes. They are close to the SNARE machinery and many vesicles docked and ready for release. Proteins (Syntaxin1A) form dense clusters of vesicles ready to be released and these bind to special lipid molecules. Molecular connections occur between vesicles, lipids and proteins that run through the entire membrane, ready to release a vesicle. Each Syntaxin1A binds to five lipid molecules (Ptdins(4,5)P2). Interactions of protein and lipid form special clusters. In studies where these lipids are metabolized, transmission doesn’t occur.

Lipids with negative charge also bind to other proteins in active zones at the same time. These are related to preparing vesicles and their docking sites. Docking sites and vesicles bind together because specific domain structures in active zones are positively charged. Lipids connect docking structures to membrane proteins. Other more abundant negatively charged lipids join in the mechanism. Because membranes are fluid, these many mechanisms are necessary to stabilize the entire operation. Together they release the vesicle.

Lipids Regulate Proteins

From Studentne

From Studentne

The SNARE machinery is very elaborate with many large interacting molecules. These have regions with positive charge. Positively charged regions bind with two negatively charged special lipids. Lipids have the ability to shield other positive charged proteins as they approach the SNARE complex.

Other lipids help in this directed process to bind particularly with SNARE. In fact, enzymes cut different lipids (sphingolipids) processing positively charged lipids to help this complex process of connecting to original negative lipids. Many different lipids control electrostatic charges from all proteins present in complex terminals. In this way, they organize so that the critical negative lipid meets a precise positive domain in the active zone.

action potential - ion channelsPtdinsPs also coordinate ion channels that create electric charge in neuronal membranes. One unique lipid in particular controls the shape of the ion channel, so that only particular combinations of proteins and this particular lipid can allow ion exchange to occur. These have been shown to be critical in potassium channels that maintain axon resting electrical charge. Special lipids again interact strongly with proteins that lie across membranes. Research shows that only with this interaction are channels placed properly in membranes.

As electric potential changes during an action potential, lipids help change shapes of channels for this process. They also help ensure that when not needed, channels are inactive. When action potentials reach the terminal, these same lipids are involved in activation of calcium channels. Calcium is positively charged and neutralize negative lipid charge as part of the mechanism.

Local small regions of special lipids keep correct proteins at sites needed to release pre synaptic vesicles. Lipids provide exact sites where vesicles merge with membranes and are released. They do the same when vesicles are picked up into membranes to be recycled. Lipids also allow placement of vesicles before release and the release mechanism. They regulate ion channels that create electric charge in the axon.

After Release

gr3Just after release of a vesicle, lipids and proteins are grabbed back into the cell in a very short time. This occurs near the edge of an active zone that is preparing for more vesicles to be released. It is much slower to build protein clathrin scaffold structures for the vesicle returning to the cell. They can also come in as a group in another region (bulk endocytosis).

The same negatively charged lipids are necessary for the clathrin process and possibly in other mechanisms. In the same way, negatively charged lipids bind to all necessary proteins in complex ways. Special lipids are necessary for the sites that bring vesicle back in at the periphery of the active zone.

Making Lipids

FEATURE Protein molecule for Complex Neuron MachineryProteins that are critical in all phases recognize only one or a few of these specific lipid molecule variations. Specific lipids are manufactured for particular jobs and define different sites by their ability to bring proteins together. Most is known about how this occurs in the process of vesicle release in the different compartments. Unique lipids define different sub regions.

Even more complex is that unique lipids are altered by particular enzymes (kinases take off phosphates and phosphatases add phosphates) to make different variations. Enzymes alter structures of local machinery by changing lipids that attract different proteins to a region. Many enzymatic changes make the situation much more complex and hard to research. To make this even more complex, several of the enzymes can make multiple different versions of unique lipids.

In the process of bringing back vesicles using protein clathrin coats, enzymes produce many specific lipids. First, one form of lipid is used. Then when other proteins are needed, enzymes alter each lipid to attract other proteins. There appears to be a back and forth interaction between the lipid and protein molecules that regulates the entire process—lipid regulating proteins and protein enzymes regulating lipids.

Diseases From Altered Enzymes

N0021139 Illustration; the pathology of Alzheimer's DiseaseIf these enzymes are altered by mutations, diseases occur in brain and elsewhere. Gene mutations can affect either kinases or phosphatases. Another enzyme that helps originally produce lipids can have mutations as well. This later mutation affects spinal cord anterior horn cells causing a debilitating syndrome with joint contraction, loss of muscle and nerves that affect breathing. There are other versions of this severe deadly syndrome.

Many diseases are caused by various different mechanisms. Alterations in lipid metabolism causes Friedrich’s ataxia, a more common disease with progressive loss of nerves connecting cerebellum and spinal cord. Another mutation can cause a very early version of Parkinson’s disease and epilepsy. This latter mutation stops activity of Ptdins3Ps and PtdinsPs involved in synaptic vesicles and in lysosomes (vital vesicles that clean cellular debris and microbes). These lipids are also part of Down’s syndrome and the Alzheimer’s version of Down’s syndrome. The risk factor for the more common Alzheimer’s involves APOE4, which lowers these lipids.

Membrane Characteristics

PD Cone shaped lipidsShapes and flexibility of membranes are crucial to their functions. These same unique lipids contribute to thickness of membranes and its ability to form curves. The amount of particular lipids with cone shapes determines whether membranes can effectively form a curve, which is necessary for all round vesicles and for fusion with membranes and vesicles. Spherical vesicles are the most difficult of all membrane curves to keep stable.

Local amounts of these special lipids allow for correct bending. Sometimes, specific lipids are produced and replace others for rapid bending needs. The amount of fatty acids and cholesterol affects flexibility. Placement of these particular lipids at the exact timing of a bend is vital to the entire vesicle process.

Cone Shaped Lipids

PD cone shaped lipids 2Cone shaped lipids are necessary for curves and bending. They are part of the fusion processes and alter amounts of energy needed to make curves. Special lipids promote positive and negative curves. Ceremide, phosphatidic acid (PA), diacylglycerol (DAG) and lysophospholipids cause negative curvature in sphere. They are found near SNARE machinery in the active zones.

Cone shaped lipids on the inner half of membranes (cytoplasmic leaflet) cause fusion with vesicles. Inverse cones on outer leaflets can do the same. Therefore, there are many options for membranes that are fusing with vesicles for exocytosis and endocytosis. Calcium can trigger these particular lipids with an enzyme called lipase. Lipases make the appropriate lipids for neurotransmission.

Enzyme remodeling of lipids is vital for all aspects of synapse activity. Alterations in enzymes produce many different severe neurodegenerative diseases. Different diseases have various mutations of a gene for phospholipase. How these mechanisms operate has not been figured out yet. Very specific lipid functions are vital to function of the brain. Many other types of enzymes related to general lipid metabolism also produce specific neurological diseases.

Lipids have Water Loving Sections

PD Omega 6Many different kinds of fatty acids vary in length and chemical characteristics. They have many different relations with water solutions. Synapses have a large number of different PUFAs (polyunsaturated fatty acidssee post on PUFA signaling). PUFAs help synapse machinery because they strengthen regions of membranes that stay away from interactions with water. They are also more flexible. Mechanisms that alter membrane shapes to produce vesicle fusions are greatly helped by PUFAs. They also avoid any chance of very curved membranes to allow interactions with water and possible membrane breaks. The curve of a vesicle is the sharpest curve of all organelles.

Large amounts of cholesterol in synapse membranes affect lipid structures and flexibility. Cholesterol is necessary for synaptic vesicles. Cholesterol can move from inner to outer leaflets of membranes relaxing stress by filling in space between lipid molecules in very curved membrane. Cholesterol also defines specific compartments of membranes and SNARE machinery.

From Materialscientist

From Materialscientist

Structures that make membranes more flexible and strong control protein shapes in membranes and their activity. Flexible PUFAs are necessary for functional protein shape changes such as channels. Vision requires PUFAs in rats and non-human primates. It helps in two ways, increasing membrane flexibility and increases lateral diffusion of elements for signaling.

Proteins sitting in membranes are affected by rigidity and thickness. Gamma secretase enzymes cut APP molecules to make amyloid plaques in Alzheimer’s. Cholesterol modulates effects of secretase by keeping it in certain positions, cutting APP in thicker deeper membranes. Deeper membrane cuts are more likely to make plaques. When certain fatty acids are in membranes, less toxic types are produced. Different membrane thicknesses from special lipids affect properties related to interactions with water. These changes in relation to water alter how cuts are made. This is not fully understood, but there are many other lipids that interact in Alzheimer’s.

Lipids and Proteins Cooperate in Membranes

From Studentne

From Studentne

All of these membrane characteristics occur at the same time, such as flexibility, positive and negative charges, and thickness. Proteins influenced by lipids are all affecting lipid structures as well. Proteins are also critical in stabilizing membrane curves. Proteins sense differences in lipid structures. Sections of proteins have different interactions with lipid and water. When membranes are highly curved, proteins can stabilize by inserting strands into lipids.

Negatively charged PtdinsPs attract special proteins to unique regions in the membrane structure. These create stresses in various places and help form vesicles in multiple different parts of the process. They help make pits, control their size, form vesicle structures and help membranes break away from the membrane after fusion. These proteins change characteristics and can be soluble and can then change and be part of lipid non-soluble membranes. Multiple different strands and sub domains on proteins can interact with many different situations. Some even become links to specific cargoes.

Lipid protein interactions are highly complex and alter membranes and also attract necessary cargoes and machinery to make more vesicles. α-synuclein is a prominent synaptic protein that also has domains that bind lipids in membranes. Abnormal α-synuclein causes Parkinson’s disease. It becomes insoluble and produces Lewy bodies. What α-synuclein does in normal membranes is not clear, but it is one of the important proteins for presynaptic membrane remodeling. Lipids control different shapes of α-synuclein molecules. Abnormal types form beta sheets.

Membrane Lipids Direct Proteins and Proteins Direct Lipids

From Dr jrf

From Dr jrf

Interaction of lipids and proteins are very complex and are just being researched. Presynaptic release of neurotransmitters is extremely efficient and rapid. Every step is very complex including altering the membrane to start the process, fusion of vesicles with membrane, sorting material afterward and fission or taking the vesicle out of membranes.

To accomplish each step, very specific lipids create sub domains in the membranes attracting and working closely with many kinds proteins. Unique lipids determine the various complex structures in membranes needed for all aspects of vesicle release. This includes production and docking of a large amounts of vesicle ready to be used. Lipids direct all the many proteins involved all of these phases of synaptic transmission.

But, proteins produce many variations of the lipids for each use with many different enzymes. In one case, lipids and proteins regulate enzymes that metabolize lipids changing the membrane composition. In many other cases enzymes determine how the special lipids are produced.

In one of the notable chicken and egg phenomenon in biology (such as DNA making protein and protein regulating DNA), membrane lipids regulate proteins and proteins regulate and modify lipids. It is very hard to research lipids in a membrane, so this story is just beginning.

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  • I hope you will comment on this link from energy-dependent metabolic networks to genetic networks in all genera, and place it into the context of your claims. The story seems to be ending with links from quantum physics to niche construction via alternative RNA splicings, which take us back to your post from 2012.

    Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disordershttp://www.ebiomedicine.com/article/S2352-3964%2816%2930143-8/fulltext

    • Roy Niles

      Kohl, explain what you mean by “links from quantum physics to niche construction via alternative RNA splicing” if you can. I propose that you can’t.

      • Nothing can be explained to you, Roy Niles. You have no understanding of any aspect that serious scientists have used to link top-down causation from the sun’s anti-entropic virucidal energy force to RNA-mediated cell type differentiation in all living genera via the innate immune system, alternative RNA splicings, amino acid substitutions, and supercoiled DNA.

        When you see a “quantum cat” you know only that it is something that — along with everything else — emerged and evolved from nothing sometime after the “big bang.”
        Others are linking my model from Einstein’s, Schrodinger’s, and Dobzhansky’s claims to all morphological and behavioral phenotypes of all organisms on Earth.

        See: Scientists take next step towards observing quantum physics in real life http://phys.org/news/2016-04-scientists-quantum-physics-real-life.html

        Excerpt: “Experimentally demonstrating a proverbial cat that is simultaneously dead and alive at ambient temperatures is still an open question in quantum mechanics. The steps taken in this research might allow to eventually observe ‘quantum cats’ on everyday life scales and temperatures.”

        • Donald Cameron

          Life is bottom up not top down.
          Correlation is metaphoric.
          Causation has to be derived or extrapolated.- courts of law, courts of scientific consensus, experimentation ….
          Cause is defined as difference opened.
          http://blog.rationalmechanisms.com/#Cause

          • What kind of biologically uninformed science idiot joins Roy Niles as another antagonist more than 4 years after this was published?

            Top-down causation: an integrating theme within and across the sciences?
            http://rsfs.royalsocietypublishing.org/content/2/1/1.abstract

          • Donald Cameron

            I don’t have to read biology to understand complexity.
            I grew up in the 60’s a child of the 50’s with Scientific American magazine editions all over the house.
            I stopped reading Sciam when it went all humanities around the time of omni magazine.
            Then I got caught up in the late 80’s with Object Oriented software Design. Then became intrigued by Booch and “The Five Attributes of Complex Systems”.
            Top-down has no meaning in a universe of inward and outward flow.- complexity obviates the concept of force and time.
            In science there is a presumption that mass is the source of gravity. In complexity, gravity gives rise to mass.

          • Do you have a model of biologically-based cause and effect that you would like to compare to my model of top-down causation?

            Nutrient-dependent/pheromone-controlled adaptive evolution: a model. http://www.ncbi.nlm.nih.gov/pubmed/24693353

          • Donald Cameron

            Not until we publicly flesh it out. Please be careful with what you “understand” or “infer” from the lexicon and the aphorisms. The lexicon is to be taken literally or at face value.
            Thank you for showing interest.

          • Do you have a model of biologically-based cause and effect that you would like to compare to my model of top-down causation?

            Nutrient-dependent/pheromone-controlled adaptive evolution: a model. http://www.ncbi.nlm.nih.gov/pubmed/24693353

        • Roy Niles

          Hey, Kohl, I see that Donald Cameron has already given you a lesson in causation that beats what I was about to say. And I see that you’ve reverted to the “others are linking my model” claim that implies that actual scientists are somewhere in line out there waiting to back your “all things are caused by their connected links” theorizing up. So far, no scientist has ever responded to your clarion calls. But hope does spring from the eternal quanta.

          • Eugene Daev and Anna Di Cosmo are among those who have cited my reviews, more than a decade after others cited

            From Fertilization to Adult Sexual Behavior http://www.hawaii.edu/PCSS/biblio/articles/1961to1999/1996-from-fertilization.html

          • Roy Niles

            That was not a paper that resulted from the author’s scientific experiments, it was a review of other papers from which these rather amateurish “scientists” drew their own unsupported opinions, and consequently allowed you to use your review as a legitimate example, not realizing that you were even less of a reputable scientific source that they were. Unfortunately you can fool some of the people some of the time, but when it comes to the Shapiros who are much harder to be made a fool of, instead of learning from them and trying to correct your mistakes, you rant and rave that they’re the incompetents, and you’re the founder of the quanta biological resurrection.

          • Roy Niles

            I’ve found instances where you’ve claimed their material supported yours, but nothing where they’ve claimed your material supported theirs.

          • Why do you think they cited my work if it did not support their works?

          • Roy Niles

            I haven’t found any evidence that they cited your work – only the opposite. And if they did, it would be because you fooled them by pretending, as usual, you were a bona fide scientist and could be trusted.

  • Donald Cameron

    Metabolisms are Complex Mechanisms.
    “Complex Mechanism : any given aggregate of Machines that implements its Acquisition through its Expression and implements its Expression through its Acquisition.”
    http://blog.rationalmechanisms.com/#Complex_Mechanism

  • Roy Niles

    What’s pitiful is that we have here another well prepared post from Dr. Lieff about the complex interactions between lipids and proteins, and Kohl immediately derails any interaction from the comment gallery by his bassackwards assertions regarding quanta that have miraculously evolved from nothing. And I must confess that I have been remiss myself in failing to disregard his rants and raves. Worse, I’ve been egging him on!
    It’s fun, but it would be more fun to ignore him and read some intelligent comments from those who have actually read and had something interesting to say about these rather remarkable posts from Dr. Lieff.

    • Quantized energy clearly did not evolve from nothing, Roy Niles. In my model, is creation links the sun’s anti-entropic virucidal effects on RNA-mediated DNA repair from hydrogen-atom transfer in DNA base pairs in solution to supercoiled DNA via the innate immune system and the physiology of reproduction.

      Docosahexanoic acid appears to play a primary role by linking energy as information to all biodiversity in species from green algae to humans.

      For instance, in 2012, I published: http://www.socioaffectiveneuroscipsychol.net/index.php/snp/article/view/17338

      Excerpt: Just as the influence of diet and pheromones can be in the larval stages or in other developmental stages of insects, it can also be in the pre- and postconception stages of mammals, including humans (Fowden et al., 2006; Mennella, Jagnow, & Beauchamp, 2001). For example, pheromones and nutrition could alter levels of maternal hormones, gestational events, and postnatal outcomes via their direct effect on maternal GnRH and the placenta. The outcomes might not always be positive, which means the possible effects should not be ignored. That would be like ignoring the likely effects of docosahexaenoic acid in the maternal and postnatal diet on LH and on neuronal development in the mammalian brain (Lassek & Gaulin, 2011).
      ——–
      People like Roy Niles can’t seem to grasp the fact that their mother should have been taking a DHA supplement due to the deficiency that caused their relatively undeveloped brain. What’s worst is that people with undeveloped brains are trying to prevent discussion of DHA because they failed to take a supplement post-natally until too long after the virus-driven brain damage eliminated the chance for DNA repair, which could have helped allow them to develop into normal adults.

      “Misery loves company” and Roy Niles is the best example of someone in misery who wants others to suffer in ignorance — as he has.

    • Quantized energy clearly did not evolve from nothing, Roy Niles. In my model, is creation links the sun’s anti-entropic virucidal effects on RNA-mediated DNA repair from hydrogen-atom transfer in DNA base pairs in solution to supercoiled DNA via the innate immune system and the physiology of reproduction.

      Docosahexanoic acid appears to play a primary role by linking energy as information to all biodiversity in species from green algae to humans.

      For instance, in 2012, I published: http://www.socioaffectiveneuroscipsychol.net/index.php/snp/article/view/17338

      Excerpt: Just as the influence of diet and pheromones can be in the larval stages or in other developmental stages of insects, it can also be in the pre- and postconception stages of mammals, including humans (Fowden et al., 2006; Mennella, Jagnow, & Beauchamp, 2001). For example, pheromones and nutrition could alter levels of maternal hormones, gestational events, and postnatal outcomes via their direct effect on maternal GnRH and the placenta. The outcomes might not always be positive, which means the possible effects should not be ignored. That would be like ignoring the likely effects of docosahexaenoic acid in the maternal and postnatal diet on LH and on neuronal development in the mammalian brain (Lassek & Gaulin, 2011).
      ——–
      People like Roy Niles can’t seem to grasp the fact that their mother should have been taking a DHA supplement due to the deficiency that caused their relatively undeveloped brain. What’s worst is that people with undeveloped brains are trying to prevent discussion of DHA because they failed to take a supplement post-natally until too long after the virus-driven brain damage eliminated the chance for DNA repair, which could have helped allow them to develop into normal adults.

      “Misery loves company” and Roy Niles is the best example of someone in misery who wants others to suffer in ignorance — as he has.

      • Roy Niles

        You, Kohl, are the one that wrote that wrote that quantum energy arose from nothing. You apparently had noted that physicists like Krauss had written a book to the effect that the big bang arose from nothing, but you apparently did not know that he was later forced to recant, and admit that there had to have been energy available at the very least, rather than a state of nothing. Although as I recall, he did not consider that a state of nothing was impossible. It was a philosopher of physics that had pointed out where Krauss as wrong, but then again, you’re no philosopher even more than you’re no scientist. You’re not even a good liar for that matter.

        • There are more than 600 blog posts to that site.

          Search Results for ‘Hydrogen-atom transfer in DNA base pairs’ http://rna-mediated.com/?s=Hydrogen-atom+transfer+in+DNA+base+pairs

          “Hydrogen-atom transfer in DNA base pairs” is delivered in 7 parts and linked from the energy-dependent de novo creation of nucleic acids to RNA-mediated cell type differentiation in all living genera in the context of our 1996 Hormones and Behavior review with its section on molecular epigenetics.

          • Roy Niles

            Same old, same old “linkage in the context of” your meaningless babble. And with stuff coming “from nothing to life and death everywhere,” even though you insisted earlier that “Quantized energy clearly did not evolve from nothing, Roy Niles.”
            And of course you’re right that you were wrong when you said it did.

          • Roy Niles

            See my review of Kohl’s review here: (Stolen from http://www.songsforteaching.co…)

            The toe bone’s connected to the foot bone,

            The foot bone’s connected to the ankle bone,

            The ankle bone’s connected to the leg bone,

            The leg bone’s connected to the knee bone,

            The knee bone’s connected to the thigh bone,

            The thigh bone’s connected to the hip bone,

            The hip bone’s connected to the back bone

            The back bone’s connected to the neck bone,

            The neck bone’s connected to the head bone,

            The finger bone’s connected to the hand bone,

            The hand bone’s connected to the arm bone,

            The arm bone’s connected to the shoulder bone,

            Delivered in 12 parts and linked from the energy-dependent de novo creation of the nothing that came before the something.

          • Roy Niles

            OK, so I tried to move the first post of this “review” and then after copying it down here, couldn’t erase the original. This Kohl confusialism is catching.

          • Roy Niles

            See my review here: http://www.songsforteaching.com/folk/
            The toe bone’s connected to the foot bone,
            The foot bone’s connected to the ankle bone,
            The ankle bone’s connected to the leg bone,
            The leg bone’s connected to the knee bone,
            The knee bone’s connected to the thigh bone,
            The thigh bone’s connected to the hip bone,
            The hip bone’s connected to the back bone
            The back bone’s connected to the neck bone,
            The neck bone’s connected to the head bone,
            The finger bone’s connected to the hand bone,
            The hand bone’s connected to the arm bone,
            The arm bone’s connected to the shoulder bone,

            Delivered in 12 parts and linked from the energy-dependent de novo creation of the nothing that came before the something.

          • Roy Niles

            See my review here: http://www.songsforteaching.com/folk/
            The toe bone’s connected to the foot bone,
            The foot bone’s connected to the ankle bone,
            The ankle bone’s connected to the leg bone,
            The leg bone’s connected to the knee bone,
            The knee bone’s connected to the thigh bone,
            The thigh bone’s connected to the hip bone,
            The hip bone’s connected to the back bone
            The back bone’s connected to the neck bone,
            The neck bone’s connected to the head bone,
            The finger bone’s connected to the hand bone,
            The hand bone’s connected to the arm bone,
            The arm bone’s connected to the shoulder bone,

            Delivered in 12 parts and linked from the energy-dependent de novo creation of the nothing that came before the something.

        • There are more than 600 blog posts to that site.

          Search Results for ‘Hydrogen-atom transfer in DNA base pairs’ http://rna-mediated.com/?s=Hydrogen-atom+transfer+in+DNA+base+pairs

          “Hydrogen-atom transfer in DNA base pairs” is delivered in 7 parts and linked from the energy-dependent de novo creation of nucleic acids to RNA-mediated cell type differentiation in all living genera in the context of our 1996 Hormones and Behavior review with its section on molecular epigenetics.

  • Roy Niles

    What’s pitiful is that we have here another well prepared post from Dr. Lieff about the complex interactions between lipids and proteins, and Kohl immediately derails any interaction from the comment gallery by his bassackwards assertions regarding quanta that have miraculously evolved from nothing. And I must confess that I have been remiss myself in failing to disregard his rants and raves. Worse, I’ve been egging him on!
    It’s fun, but it would be more fun to ignore him and read some intelligent comments from those who have actually read and had something interesting to say about these rather remarkable posts from Dr. Lieff.