NIR: Why do bats fly at dawn?

Why do bats fly at dawn? 

Bats, ounce for ounce are the longest lived of all mammals. A two year old mouse is already a geriatric whereas it takes ten years for a tiny Pipistrel to start to conk out with age and outrageously, it takes 40 years for a 7 gramme Brand's bat to do the same. Even the incredibly tiny Kitti's Hog Nosed bat at 2g (!) lives for 5 years. 

We have a good idea why bats live so long; it's the same reason as do pidgeons and parrots ... they have very good mitochondria. In both (very diverse) genera the mitochondria are smaller, more prolific, energy efficient and produce fewer damaging free radicals than do their counterparts in mice and indeed humans.

In recent time mitochondrial well-being has become the focus of a multitude of anti-aging strategies and increasingly photo-therapy using near infra-red radiation (NIR) has gained in popularity.

This is because NIR can penetrate through the skin ( and clothes or fur) and stimulate mitochondrial proliferation. The mechanism is proposed to involve cytochrome c oxidise acting as the NIR photo-receptor  absorbing it at around 800-850nm and from there a path of retrograde signalling informs the cell about what to do for the best.

In effect, new mitochondria potentially 'rejuvenate' an old cell which will have a significant population of damaged mitochondria. As a result of this knowledge and availability of cheap LEDs there is a good, even an over-supply, of NIR lamps for sale for personal as well as professional use.

If NIR, is truly beneficial to mitochondria ( as seems it is)  then the source of NIR and the mechanism of action must be rather more ancient than NIR LED lamps! Fortunately 54% of incident light on the earth is NIR ( 34% is our 'visible' light th erest UV). This gives animals every chance to soak NIR up. 

The whole 'NIR is good for you' edifice however looked like falling becasue our long-lived super mitochondrial bats are, as everyone knows,  are nocturnal. Worse, they like dark caves and  famously, belfries, during the day.

A quick bit of on-line research turned up two facts One I should have known, the other was new to me. The latter is that the most ( by far) NIR during the day occurs at dawn follwed by the light at dusk.  Bats swarm or just fly about feeding a lot at dawn and dusk. Some like the tiny Kitti's bat only fly at dawn and dusk.

NIR causes apoptosis of vascular smooth muscle cells. This appears to be a good and a bad thing. Remodelling of blood vessels littered with quiescent ( unused ) smooth muscle cells benefit from a clear-out and remodelling. However for diseased vessels and atherosclerotic vessels there can be adverse effects including plaque rupture. 

Fructose makes you very Fat

 Fuctose makes you very Fat

High fructose corn syrups are the principle cause of the First World's obesity epidemic. Many scientists, medics and nutritionalists given a basic understanding of biochemistry have known this for years. 

It's one thing though  to know something and quite another to go up against the food industry whose 'counter-clout' or more explicitly, their ability to destroy you, rivals that of big pharma or, as in the past, the tobacco industry*.

After all isn't obesity caused by taking in too many calories, especially calories 'hidden' in liquid or pre-masticated, semi-digested food products in which lurk fats and sugars? It's simple, isn't it?  And so accordingly foodstuffs are now labelled clearly with nutritional information listing fats, sugars and of course calories to help us controll our intake.

Usually fat in obesity debates gets the lion share of the blame on account of the energy density per gram that fats have. Then comes generic sugars as the new popular villain while more specific types of sugar; like fructose, lactose and oligi sacharrides usually escape scrutiny.

Finally there is a dawning awareness that all calories from whatever source are not equivalent. That is, maybe calories from sugars are not 'one to one 'equivalent to calories from proteins and fats. How can this be? 

Whatever, the situation is multifactorial, complex and a full understanding requires biochemical knowledge of intermediary metabolism outside the scope of nutritionalists and medics in general. 

So, given the above, how can we say fructose, a single sugar, abundant in fruits is alone as the chief driver of obesity?

The answer is simple. 

Anyone with a basic knowledge of intracellular glycolysis and oxidative phosphorylation will tell you that fructose is handled differently to other simple sugars like glucose and galactose. 

Glucose dominates the simple sugars being derived from starches, maltodextrins and other oligosacharrides as well as from 'sugar' sucrose and 'milk-sugar' lactose {sucrose = glucose+fructose, lactose = glucose+galactose}. Unsuprisingly glucose is carefully regulated both outside and inside the cell whether by the insulin system or enzymatic control. Fructose is not.

A paper published in the journal Obesity, elegantly and triumphantly spotted something simple and profound.  They studied animals preparing for hibernation. Naturally animals that do hibernate need to maximise fat reserves for the winter sleep. In order to do this the calories you take in must exceed that calories you expend but what is the best way to prioritise fat storage in the autumnal feeding phase?

The animal is active during this phase, very active foraging, so it does not want to use a gramme of its fat reserves as energy. Fortunately at this time sugars but especially fructose in fruit is abundant. They found that fructose did two jobs, these were, a) putting on fat and b) conserving exsiting fat deposits.

The biochemical explanations were not in the scope of the paper but they are very clear from a metabolic control point of view. Fructose 'screams' unregulated through the pathway known as glycolysis. Glycolysis is used to break down glucose to provide the simple molecular 'food' for mitochondria which they then fully oxidise to generate energy and biosynthetic power.

The problem is that mitcondria cannot handle unlimited amounts of their molecular food known as 'acetyl' a simple two carbon atom molecule combined with hydrogen and oxygen. They can only process a limited amount and even this depends on the level of demand created by activity of the cell and the animal that it belongs to. In order to stop a catastrophic build up of acetyl it is turned into fat which can be safely ( from a biochemical perspective) stored in adipose tissue. 

Clearly in a fructose rich environment one can easily visualise evey last gram of ingested fructose going straight to fat.

So, what of humans rather than hiberanting mammals? Well, due to our lifetsyles being so inactive many of the mitochondria especially in muscle will already be down-regulated, some will be nearly dormant. Now, add a fructose rich diet, eg high-fructose syrups in biscuits, cakes, candy and fruit-rich products like juices and yoghurts and the mitochondria will be 'maxed out' quite quickly. 

Now, and here's the key, and the one made clear by the authors in Obesity: add a modest amount of any other foodstuff to the diet: lean meat, fish, bread, whatever and the calories are not going anywhere .. except as fat storage.

This means that with high fructose diets, the total calorie count means less than the composition of the diet. You can reduce your calorie intake substantially and yet get very much fatter ... how cruel but how obvious when you look around you.

1) The fructose survival hypothesis as a mechanism for unifying the various obesity hypotheses

Richard J. Johnson, Laura G. Sánchez-Lozada, Miguel A. Lanaspa

First published: 17 October 2023 https://doi.org/10.1002/oby.23920

*the vape nicotine comeback is pretty impressive so don't count themm out.

The most unhealthy meal ever?

 

It’s holiday time and so to explore the most unhealthy meal ever?

Forget UPFs this is serious.

(in case anyone reads this I am being ironic..the food IS healthy)

 

Imagine you are in a nice holiday restaurant,

say on one of the countries bordering the Mediterranean sea.

On the table are some fresh olives and wild mushrooms in an extra-virgin olive oil

vinegar, garlic and thyme vinaigrette and some fresh cod-roe taramasalata too.

You choose the clams in white wine and parsley as a starter  and the grilled sardine for your main meal

All served with fresh flatbreads and ad-libitum green salad .. and of course, naturally, some wine to wash it down.

OMG! ( does anyone say that nowadays?) are you mad? You are signing your own death warrant, think about your cholesterol levels, after all that's why you are on statins.

Yes, I choose this particular meal for a reason:

Firstly it is an exemplar of the ‘healthy’ med-diet and it is a meal that I could plausibly present as an exemplar. It has oily fish, extra virgin olive oil, is high in protein and low in carbs. No animal fats and no processed foods. Plus green veg and wine!

Secondly I choose it as a meal as high in cholesterol and cholesterogenic foodstuffs that I could imagine without becoming taste-wise implausible.

Basically, oily fish, fish eggs and seafood such as prawns, mussels, clams, calamari are  the top three foods for the levels of cholesterol. Also, (sorry vegans) extra virgin olive oil and mushrooms contain squalene and ergosterol respectively which are quickly converted to cholesterol by the body  ( = cholesterogenic) .

So, healthy or deadly?

Luckily you are on holiday somewhere sunny so some of this circulating cholesterol in your bloodstream is being converted to vitamin D by the action of sunlight on your reddening skin and equally luckily you take statins to lower blood cholesterol.

Pity those poor locals who don’t know what risks they are taking.Enjoy

ps Don't get me started on that lamb's liver and wild mushroom casserole on the Autumn menu.

 

 

 

 

 

 

 

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.

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 though less so today due to the cost of hormone treatment which is largelyy replaced by fast growing breed giorged on soya. 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

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

Decline and Fall of Homo Sapiens

Decline and Fall of Homo Sapiens

Sub-title: How capitalism regained its grip in the 21st century but failed to spot it wasn't in the 19th Century anymore.

Many of the problems that beset us in the 21st Century arise from the rapid increase in global population over the last century. Increases in wealth and improvements in health accounted for an increase in childhood survival and, average age of death, which in turn fuelled a Malthusian increase in population numbers globally. 

Technology has largely met the increase in the consumption of energy to feed, warm and transport the populations. But with  catastrophic environmental consequences. This much is all so well known and a path so well trodden that it hardly needs to be restated here.

What is gradually dawning on the world however is that humans may be dying out, just like any organism that explodes into profusion exhausts its environment and declines. Below without any supplementary, exhaustive referencing are some facts easily gleaned from a thousand  official websites

 Global Population Decline is due to:

1) Birth rate decline

            a) declining sperm count

                i) increased oestrogen and phyto oestrogens in diet

            b) older first time mothers

                    i) daughters of older mothers have none or fewer children

            c) gender disphoria/identity/sexual orientation

                    i) change in male-epigenetic signalling

                    ii) changes in female epigenetic signalling

                    iii) homosexual partnership increase

                    iv) low reproduction in LBGTQ+ individuals*

2) Elective smaller families

        a) increased access to contraception

        b) increased access to abortion

        c) reduced authority of religious/societal mandating access to sex only through mariage

3) Mortality increase

           a) pension age increase

           b) increase in type 2 diabetes

           c) reduced health care access

            d) pandemics

Add, them up, no one factor is deciding the issue and there is no escape, humans are not reproducing at anywhere near replacement levels from Dublin to Bejiing ( India is still increasing but it is due to reduced infant mortality which will level out).

The interesting thing from my point of view is, how was the Malthusian nightmare avoided? Malthus himself formulated his over-population 'expansion to crisis' model in the mid 18th century, having witnessed first hand pre-famine Ireland where the newly-acclimatised carbohydrate rich potato, combined with a religious imperative to procreate, created a population boom which was accompanied by incredible, epic poverty amongst the poor.

Here is how I think we were saved, or will be saved from overpopulation and then  doomed by depopulation: Economics, in this case Capitalism.

The logic is simple. Children have always been a blessing and a burden. To support dependent children in a capitalist society you need your own money. If you  procreate beyond your means to support your progeny, you will be poor, or very poor and may have to give up children to illness, realtives or strangers.

Population control, that is intercourse without procreation, could be achieved in the past by abstinence, coitus interuptus, good menstrual cycle timing and  use of condoms (from mid 19th century). Unless of course  particular religious practices forbade these already unreliably methods. Finally , abortion was available at great personal risk and with universal condemnation from most societies.

Once  hormonal contraeptive pills became available and chemical or physical abortion became safer, the game changed completely. 

A family of one child or two has more disposable income than one with more children. Modern living, the good life, from London to Moscow to Delhi to Bejing depends upon disposable income in order to buy goods and services which define the good life and keep the people 'happy'. Most countries, with exceptions like North Korea, prefer the capitalist 'carrot' to the socialist stick to keep the population quiet.

Capitalism produces near unlimited wealth for the few and  minor aspirational wealth for the many. In the latter instance it is obvious that having fewer to no children will maximise personal wealth. With contraception readily available and with dimished authority of religious demands to reproduce it is obvious that the number of children will reduce.

Logically if you want to be maximally wealthy in a capitalist society then no-children is the answer.

Second best is one maybe two children conceived as late in life as passible.

Population decline means labour shortages. Once again technology can solve the probllem. Automation which started seriously in the period called the Industrial Revolution has developed markedly into the era of autonomous robotics and AI. A cycle is generated, fewer workers means more automation: more automation means fewer people are needed. Simply put, if  birth rates recovered what on earth would you do with the people? Meta-work, the work that occurs in offices and meeting rooms as opposed to productive work still convinces most people that it is  meaningful mostly becasue their time is well compensated but the illusion will vanish inevitably thereby generating an existentail crisis.

Terminal capitalism therefore, like terminal popultion growth is not far away. The means of production will no longer depend on labour and so compensation for labour beomes meaningless for the majority. The rich will pay the remaining people to simply to consume or the whole cycle of manufacture fails. 

As Margeret Thatcher onced observed  in a monetarist pure-capitalism,along the lines that 'there is no such thing as society': well, it'll have to be re-invented, and quickly, if we are to survive.

*LBGTQ+: Less than 20% of same sex couples have any off-spring, under 50% of women identifying as bisexual have given birth and transgender pregnancy is in laboratory stage so is numerically effectively zero. 

post script:

It is worth noting that Sapiens is the only surviving species of  the once quite diverse Homo genus. It is not unlikely in my opinion that the Neandethals and Denisovans to name two species simply died out because they stopped reproducing in sufficient for existentail reasons rather than environmental. Consciousness has a price.