Tuesday, June 20, 2023

Cheddar Man: a black man in a cold climate

 Cheddar Man: a black man in a cold climate


Cheddar man was a genetically and phenotypically typical western europe hunter-gatherer who lived in Britain in the mesolithic period about 10,000 years ago.



The reconstructed face shown above from the British Museum was created from DNA sequencing and the bone structure of a skeleton found in Cheddar GB. With very dark brown skin, black hair and blue/blue-green eyes it was in many ways shocking to the now mostly white population. Cheddar man disappeared and was replaced by lighter skinned farmers originating from Turkey and they in turn were replaced by even paler and taller people originating from the Eastern steppes. This post is not about human evolution but about Vitamin D.


Quite simply, farming brought about a diet containing domesticated cereals, legumes and pulses and a more indoor lifetsye. Vitamin D is low in diets that have these foods at  their core. Fortunately we can make Vitamin D from cholesterol in the blood through the action of sunlight. It is a well regulated system whereby the skin darkens due to the sun-blocking pigment melanin which is produced through the stimulation of sunlight ( sun-tan). The brighter the sun the darker the skin and vice-versa.


The near translucent pale skins of say the Northern Irish where light levels are low compared to the near black skins of bush Australian aborigines who are exposed to the most intense light on the planet illustrates the point clearly. Different light intensity, siiar Vit D production.

Both populations are by the way geneticay classified as Caucasian!


Cheddar Man is therefore an anomaly, especially as he had good, solid bones. His dark sunlight-blocking skin  has a range of explanations: the sun was brighter in the UK 10,000 years ago; unlike later farmers he spent a lot more time outside; he and his population were recent immigrants from southern climes or he had  high levels of dietary Vitamin D ( which promotes melanisation).


The sun wasn’t brighter, he wasn’t a southern immigrant but he would have spent a lot of time outside. Recent immigrants to the UK from the Asian subcontinents with darkskins, eating traditional diets, and avoiding sun-bathing are very vulnerable to Vitamin D deficiency. They may even develop a Vitamin D-deficiency bone-disease rickets. Not so Cheddar Man


Cheddar Man most likely then ate a diet high in Vitamin D and/or rich in pro-vitamin D substrates.

The latter are cholesterol, ergocholesteol and squalene.


To, so to speak, ‘max-out’ on the above he would need to eat the following



Seafood ( mussels, urchins, clams, oysters, crayfish, crabs)

Oily fish ( sprats, sardines, rays, salmon, trout)

Eggs ( bird’s eggs, especially from large colonies say of fulmar, puffin)

Fungi (field mushrooms)

Offal (liver, brain, kidney)


In all likelihood these are exactly the foods he would have easiest access to: shores, rivers, cliffs and woods. No dangerous technical hunting needed, trapping and netting would suffice and nor would cooking  be really necessary. 


So, in short, Cheddar Man’s high cholesterol diet and outdoor ife style allowed him to stay safely black.


Monday, June 05, 2023

The future is trans.

 

The future is trans?  

Testosterone, oestrogen, and progesterone are  sex hormones naturally produced by our gonads, (otherwise known as testes and ovaries). Together with epigenetic signals (eg cultural signals)  these hormones determine our phenotype,, typically in binary form, ie as male or female. Puberty, when gonads are particularly active, is a significant and to an extent irreversible developmental step influenced by these hormones.Today, in western societies ‘non-binary’ is a phrase increasingly used to describe gender identity and the issue of artificially ‘transitioning’ from one gender to another using synthetic hormones is a  hotly discussed topic.  My impression is that gender is not what it was. The question is, is the change  real or imagined?

I think the change is real.

6o+ years of ingesting  sex hormones have altered societies across the globe in a way never seen before. 

Ingesting sex hormones? Yes, we, or rather the pharmaceutical industry, have been synthesising sex hormones on a grand scale for a very long time.. 

Sex hormones are part of the generic class of chemicals derived from cholesterol-like molecules called steroids and these have many profound effects on the body:  doping with male steroids, androgens like testosterone, has been part of elite  and now ‘gym’ male sports culture for 70 years and (banned and tested for with greater or lesser success)  whereas female sex hormones are used for contraception  and even more extremely to transition from a male phenotype to female. has been effected by administration of oestrogens. 

Changes in bodily appearance brought about by sex hormones are obvious but what is less obvious is that there is a psychological change.Changing levels of sex hormones always produce psychological changes. The paragraph above is mostly about extremes, what about every day sex hormone ingestion?

In the middle, so to speak and much more importantly are ‘us’..(well not me I am a biochemist).

If you are female you may have been ingesting the hormonal oral contraceptive, maybe for years.

If you eat poultry and cattle meat, oh and dairy, you  will have ingested some of the female sex hormones used in promoting their growth. If you ingest soya ( in bread and most bakery products as well in ‘milks’ protein shakes and others) you will ingest phyto-oestrogens. If you are a gym bunny and maybe you want to lose some fat and gain some lean then testosterone is for you.

The point is, ingesting (eating) sex hormones will change you, physically and psychologically, and that’s what we do now. Sometimes it is elective: contraception, gender phenotype, sport performance but often it is in  a form now near ubiquitous in foodstuffs. And whilst on the subject of foodstuffs, morbid obesity increases the production of oestrogen in males as well as females. The important wor din this paragraph is ‘psychologically’. Changes in mind appear long before phenotype changes are noticeable.


If you accept the premises above then what should we see in the population around us. Well, everything from ultra-agressive males (roiders) to an increase in gender disphoria, decrease in binary gender identity, intersex ‘podgy’male phenotypes, reduced fertlity and reluctance to reproduce. In other words the folk of any city high street in the UK.

So may be the future really is trans























Thursday, June 01, 2023

Capacitance and the Origin of Life

 Capacitance and the Origin of Life

Over 65 years have elapsed since Peter Mitchell published his chemiosmotic hypothesis1  in which he described how chemical free-energy from the oxidation of substrates such as glucose could be coupled to biosynthetic chemistry using energy stored in an electrochemical potential created  across phospholipid bilayers. Most of this potential, electrochemical energy, was manifested or ‘contained’ in proton gradients, that is in a difference in positive charge form H+ ( hydrogen ions, protons) either side of a non-conductive lipid membrane. It was given the short-hand symbol ΔpH. Chemiosmotic theory is fully accepted today as the prime generator of free chemical energy usually in the form of ATP or  powerful reducing agents such as NADH2  used in cellular growth, maintenance and reproduction…all overwhelmingly endothermic, and entropically negative.

Unsurprisingly, given the above, speculations on the origins of life; the proto-cell, focuses around naturally occurring pH gradients, (either from photo-chemical reactions or from those found in alkaline sub-ocean vents) coupled with lipid bilayers. Bilayers, in turn formed  from simple lipids ,default into vesicles, simple spheres and are well known to exist in primordial ‘soups’2.  And here it rests: a pH gradient and a dielectric barrier in the form of a vesicle..but this is not a viable proto-cell however you argue it.

Modern bioenergetic organelles such as mitochondria or chloroplasts have vast surface areas of membranes and sophisticated regulation of electrical potentials through arrays of proton pumps and controlled depolarisation. 

A mere 40 years ago my PhD3 thesis contained a chapter which focussed on the capacitance of mitochondria as they aged and as their internal membrane area (cristae) decreased (as shown on electron micrographs). The assertion was that although membrane potential was being maintained at levels essential for normal cell function, the capacitance or reservoir of charge was diminishing thereby bringing the ageing organism closer to an energetic ‘cliff-edge’, which if crossed possibly initiating failure and apoptosis.


Capacitance, is a term so intrinsic to electronics that even the most elementary of courses would expect an understanding of the role and mechanism of capacitors in circuitry whether electrolytic or solid state capacitors. Capacitors store charge, they store energy, they are used as reservoirs to smoothing current flows and maintaining voltages during times of energy draw off through demand or natural leakage. In electronic circuits they are ubiquitous.

In my assertion here, the capacitance of electrochemical organelles matters and that it plays a similar buffering/storage role in organelles as it does in electronics. One has only to see an electron micrograph of so called reticulate mitochondria wrapping themselves around a nucleus during mitosis to appreciate they are acting as a huge ‘battery’ of stored charge for a temporarily biochemically semi-dormant cell but one with still with a lot of energetic  work to do to bring about cell division.

Thus, in the speculations about proto-life I think capacitance matters here too. Imperfect evolving systems invoking early proton-pumps, or any other charge separating mechanisms including natural pH gradients all need a reliable store of potential energy to keep the chemical wheels rolling in the same direction for decent periods of time.

Most proto-life theories focus on the formation of natural lipid vesicles. Lipid bilayers will always default to simple vesicles with single membranes as exemplified by the fate of complex membranous structures in cells following homogenisation! But, vesicles have very little capacitance, something with a greater surface area is needed.

Two recent articles have delighted me. The first4 reports that lipid sponge-droplets can be simply formed. The investigators are attempting to create artificial organelles  and have succeeded not in producing sophisticated folded mitochondria full of cristae folded like net curtains but spongy lipid droplets.

No matter, sponges have large surface area and so potentially large capacitance.

The second article5 is from the electronics world where the researchers are attempting to produce nano-super-capacitors and yes, you guessed it, they have produced devices and from their structure are called sponge capacitors.

Sponges like all foam structures have large surface areas compared to their volume. In fact the surface area can be incredibly larger than the volume. A sponge chemiosmotic capacitor would be a potentially very significant reservoir of free energy in the form of a charge distributed across a very large surface.

So, in short, my guess for the proto-cell will involve a sponge-lipid with alkaline and relatively acidic lacunae generating a mesh of charged membranes which contain enough capacitance energy, (charge), to drive endothermic synthetic processes for substantial, crucially continuous periods. To use an analogy from chemistry: driving an endothermic reaction with a heat source, say a Bunsen burner, will not be successful if the burner is turned off for a period every few seconds or so. Biosynthesis requires a consistent if not constant input of free energy and only charge storage provides the possibility of a gradually evolving molecular refinement of the process. 


Capacitance, charge storage, is in my opinion, crucial to  all proto-life theories as, ironically  much as it is crucial now for the electricity-driven green revolution. 


1. Mitchell, P. (1966). "Chemiosmotic Coupling in Oxidative and Photosynthetic Phosphorylation". Biological Reviews. 41 (3): 445–502. doi:10.1111/j.1469-185X.1966.tb01501.x. PMID 5329743. S2CID 2073366.

1a.^ Mitchell, P. (1972). "Chemiosmotic coupling in energy transduction: A logical development of biochemical knowledge". Journal of Bioenergetics. 3 (1): 5–24. doi:10.1007/BF01515993. PMID 4263930. S2CID 20251582

2.https://ecoevocommunity.nature.com/posts/55368-protocells-in-deep-sea-hydrothermal-vents-another-piece-of-the-origin-of-life-puzzle 

3. John A Spencer Biochemistry of Ageing; Birmingham University 1980 Ph.D

4.https://www.pnas.org/doi/10.1073/pnas.2004408117 lipid sponges

5.https://pubs.acs.org/doi/10.1021/nl2023433 sponge capacitors