Archives for: October 2012
Major news about one of my favorite molecules, l-fucose. In addition to being part of the antigenic structure of the H antigen found in blood group O, fucose is now garnering attention as an important component in learning. Although neurophysiology spends quite a bit of time looking at the neurosynaptic junction (the gap between two nerve cells, where nerve conduction occurs) most of the emphasis is on the neurotransmitters (such as serotonin and dopamine) that can jump the gap.
However, what goes into holding the synapse together may be as important a factor in cognition and learning as what jumps across the synapse. And that appears to be lectin-like receptors on one side of the nerve synapse which bind to fucose as a ligand on the other.
In other words your nerves have a sweet tooth for fucose.
Reaction in the brain involving fucose skyrocket during periods of intense learning. And human milk is a very rich source of the sugar, with amounts far higher than all other species. The sugar content of human milk varies by ABO blood type and secretor status which makes me want to do a study looking at learning differences along blood group and secretor status in breast fed and bottle fed children.
The fucosyltransferase enzymes FUT1, FUT2 and FUT3 are very intimately involved in determining ABO, secretor and Lewis blood types and recent research has linked serum B12 levels (another important player in proper nerve function) to the FUT2 (secretor) gene.
Fucose and fucosylation have a big role in ontogeny (the origin and the development of an organism from the fertilized egg to its mature form) via it's role in the development of the Lewis X antigen (FUT9) which supports cell-to-cell-adhesion in embryos. Lewis X expression in the brain is in turn controlled by the PAX6 gene, which regulates many elements of nerve growth in addition to forming the architecture of the iris.
The link between PAX6 and Lewis X (FUT9) may explain why a recent study showed that at least some aspects of personality were determined by the genetics of iris formation. Close-up pictures were taken of the study participants' irises, and they also filled out a questionnaire about their personalities. The researchers looked at crypts (pits) and contraction furrows (lines curving around the outer edge of the iris), which are formed when pupils dilate. It was found that those with more crypts were likely to be tender, warm and trusting, while those with more furrows were more likely to be neurotic, impulsive and give in to cravings.
PAX6 is gene that helps regulate embryonic differentiation. PAX6 also has some interesting effects on adrenal and pancreatic function as well as norepinephrine expression in the gut via the enteric nervous system. Maybe there's a future in medicine for the iris after all.
Going forward, I predict that soon the best thing to use in kids who are learning-challenged will not be the usual suspects like Ritalin or SSRIs, but rather glycomic agents from the diet that enhance fucosylation. These drugs do enhance the function or persistence of neurotransmitters, but fucosylation enhancers seem to enhance the stability of the entire neural network. It makes no sense to up-regulate neurotransmitters if you haven't insured that the nerves are holding to each other in the first place.
Of course, most of the old blood typers know that Bladderwrack (Fucus vesiculosis) is a decent source of fucose.
Schizophrenia, gluten, and low-carbohydrate, ketogenic diets
We report the unexpected resolution of longstanding schizophrenic symptoms after starting a low-carbohydrate, ketogenic diet. After a review of the literature, possible reasons for this include the metabolic consequences from the elimination of gluten from the diet, and the modulation of the disease of schizophrenia at the cellular level.
Previously, Dohan (Acta Psych Scand 1966, 42(2):125-152) observed a decrease in hospital admissions for schizophrenia in countries that had limited bread consumption during World War II, which suggested a possible relationship between bread and schizophrenia. Early work with lectins clearly showed that the brains of schizophrenics bind lectins differently than the brain tissue of non-schizophrenics, which appears to make sense in that the carbohydrate content of schizophrenic brain tissue (in addition to dementia and a few other illnesses) revealed the existence of spherical deposits in the inner and middle molecular layers of the dentate gyrus in the hippocampal formation which contained fucose, galactose, N-acetyl galactosamine, N-acetyl glucosamine, sialic acid, mannose and chondroitin sulfate; many of these blood group active carbohydrates with known lectin binding affinities (link).
Over the years some of the most stirring letters I've received from book readers have centered around improvements in family members with schizophrenia. Almost all of these letters have been from or about blood type O schizophrenics, which may mean that the nutritional approach to schizophrenia might necessarily differ by foods and blood type. We are now only beginning to understand the effects of tissue glycosylation on the development and maintenance of brain neural networks.
Henry Ford, it is said, commissioned a survey of the car scrap yards of America to find out if there were parts of the Model T Ford which never failed. His inspectors came back with reports of almost every kind of breakdown: axles, brakes, pistons -- all were liable to go wrong. But they drew attention to one notable exception, the kingpins of the scrapped cars invariably had years of life left in them. With ruthless logic Ford concluded that the kingpins on the Model T were too good for their job and ordered that in future they should be made to an inferior specification.
For the automotively challenged, the kingpin is the main pivot in the steering mechanism of a car or other vehicle. Originally this was literally a steel pin on which the moveable, steerable wheel was mounted to the suspension. It is usually made out of metal.
This story, well-known on the internet, was originally told by Nicholas Humphrey in 1976, and often referred to by other biologists including Jared Diamond and Richard Dawkins, the latter recounting the story in what is, by far, the most pessimistic chapter ("God's Utility Function") in his book River Out of Eden.
John Hawks, who has an interesting anthropology weblog takes a look at the Henry Ford story, and why evolutionary biologists seem to love it so:
Of course, the truth is natural selection doesn't cut back the quality of functional parts easily, either. Selection also has to overcome fixed costs in order to change populations: costs stemming from pleiotropy, epistasis, and coevolution with other kinds of organisms (e.g. predator-prey relationships, mutualisms, and mimicry). How much selective advantage can come from reducing femur diameter a smidgeon? It can't be very much, and it might easily be outweighed by the manifold costs of changing osteoblast function to accomplish it. In other words, adaptation is constrained by the same sorts of problems that constrain industry. Ruthless efficiency can rarely be maintained in biology or in manufacturing.
But then again, was the story even true?
Barbara Mikkelson over at the Urban Legends website thinks not, but offers an additional insight:
Though the legend is almost always positioned as a "let's screw the consumers" tale, on rare occasion it has been presented as an example of intelligent design."*
It all reminds me of the Edward de Bono books I read as a kid.
* She includes a similar type of anecdote about another engineering triumph, from WWII:
"A proposal was made to armour bombers in the places where the returning planes showed most damage from anti-aircraft fire. One young analyst suggested that instead, the planes should be armoured where the returning bombers showed no damage. He inferred that the planes that did not return were being damaged in the places that the returning planes were not. His suggestion was implemented and an X% reduction in lost planes resulted."