Monday, 13 July 2009

Camera Obscura

A refracting lens is a key component of our image-forming camera eye; however, its evolutionary origin is unknown because precursor structures appear absent in non-vertebrates.

Most living vertebrates possess anterior paired eyes, each with a lens. Although anterior photoreceptors are known to have evolved before the radiation of the major lineages of bilaterally symmetrical animals, the vertebrate lens is a more recent innovation that evolved in the vertebrate lineage. Indeed, the accurate vision facilitated by the lens is one of the key adaptations proposed to underlie the evolution of active predation by ancestral vertebrates and the subsequent evolutionary success of vertebrates themselves. The unique structural properties of the lens are due to its very high content of long-lived proteins, the crystallins. These derive predominantly from two gene families, the α-crystallin family and the βγ-crystallin family. The structure of βγ-crystallins has been elucidated and found to have derived from an ancestral protein domain that comprised two symmetrically organized Greek key motifs.

Vertebrates, together with invertebrate urochordates such as the sea squirt Ciona intestinalis, compose phylum Chordata. C. intestinalis larvae share a basic chordate body plan with vertebrates, including the possession of a notochord and dorsal neural tube in which an anterior photoreceptor resides in a small brain. Urochordates are, however, thought to have split from the vertebrate lineage prior to the evolution of the lens and the associated co-option of crystallin genes into the visual system.

In the larval head is a small brain that includes a neuroectodermal sensory vesicle with two sensory organs, the ocellus and the otolith, together thought responsible for controlling larval locomotion in the search for a suitable site for metamorphosis. Once located, the larva adheres to the substratum with secretion from three anterior epidermal palps and subsequently undergoes a radical metamorphosis during which the majority of the brain and tail are reabsorbed. The remaining tissues are extensively remodeled to produce a sedentary adult. The ocellus is a ciliary-based photoreceptor system that includes a single pigmented cell and is considered homologous to the vertebrate retina. In some urochordate larvae, including those of C.intestinalis, three cells lie above the pigment cell, and because light must pass through them to reach the photoreceptors, these are sometimes referred to as lens cells. However, there is no evidence that these cells are homologous to vertebrate lens cells. Similarly, the otolith is not considered homologous to the vertebrate ear.

The two pigmented cells of the ascidian sensory vesicle share a common developmental origin in that they arise from a bilaterally symmetrical pair of cells in the anterior nervous system. These cells have been shown to be initially equivalent, with the potential to form both types of pigment cell. Which forms ocellus and which forms otolith appears to be regulated by Bmp and chordin signaling. Additionally both ocellus and otolith lineages express opsins. Because anterior photosensory structures are primitive for the bilateria, the parsimonious explanation is that both ocellus and otolith evolved from such photosensory structures.

We therefore conclude that the evolution of the lens did not derive from a new association between a visual system regulatory circuit and co-opted lens structural genes but from the reuse of a pre-existing regulatory interaction linking these components in the central nervous system of a primitive chordate.

The brain of the ascidian larva comprises two pigment cells, termed the ocellus melanocyte and the otolith melanocyte. Cell lineage analysis has shown that the two bilateral pigment lineage cells (a-line blastomeres) in the animal hemisphere give rise to these melanocytes in a complementary manner.

...The two bilaterally positioned cells destined to become the pigment cells in the first step are still equipotent at this stage in that they can give rise to either the ocellus or otolith. Thus, they constitute what is termed an "equivalence group." In the second step, the individual fates of the two cells that compose the equivalence group are determined. Namely, one cell develops into an ocellus and the other cell develops into an otolith.

Ocellus noun, plural ocelli, adjective ocellate - from Latin, ocellus, a little eye.

1. Simple eyes, small extra eyes, usually situated on the top of the head. The cuticle covering the eye is thickened like a lens. Below the lens there is a layer of transparent cells, continuous with the adjacent epidermal cells. Most insects with complete metamorphosis (holometabolous) have three ocelli on top of the head, arranged in a triangle.

Dorsal ocelli are light-sensitive organs found on the dorsal (top-most) surface or frontal surface of the head. They tend to be larger and more strongly expressed in flying insects (particularly bees, wasps, dragonflies and locusts), where they are typically found as a triplet.

A dorsal ocellus consists of a lens element (cornea) and a layer of photoreceptors (rod cells). As noted above, ocelli vary widely among insect orders. The ocellar lens may be strongly curved (e.g. bees, locusts, dragonflies) or flat (e.g. cockroaches). The photoreceptor layer may (e.g. locusts) or may not (e.g. blowflies, dragonflies) be separated from the lens by a clear zone (vitreous humour). The number of photoreceptors also varies widely, but may number in the hundreds or thousands for well developed ocelli.

The “otolithic organs,” as they are known, are a pair of sensors—the utricle and the saccule—nestled in the labyrinthine architecture of the inner ear.

Grossly speaking, each consists of a bunch of tiny pebbles (of the white rock known as calcium carbonate) embedded in a gooey wad that sits atop a carpet of delicate hairs. The saccule is roughly vertical in our heads, and the utricle more or less horizontal. Together they orient us in the world, since they work as tiny inertial references: raise your head suddenly (or get in a jerky elevator), and the pebbles of the saccule get momentarily left behind as your skull starts upward; this bends down the hairs against which those pebbles lay, and the sensitive hairs function like switches, sending signals to your brain that you register as a feeling of ascent. The utricle does the same work for motion from side to side, and between them these tiny organs generate the neurological data that give us our normal sense of being in the world. What would it feel like not to have those pebbles? Delete them from a mouse and it spends a lot of time falling over.

Both the utricle and the saccule contain what I have called “pebbles,” but they are little more than mineral crystals really, microscopic sand bound together into a mass by a matrix of protein. Not so the homologous structures in fish, our evolutionary ancestors. They retain, inside their skulls, quite clearly defined, and nearly always large enough to see (and sometimes as large as marbles), healthy little rocks known as otoliths, or “ear stones.” The minute pebbles of our otolithic organs would appear to be the powdered remains of these ancestral lithic pips.

Fish otoliths are among the strangest and most wonderful bits of vertebrate anatomy. They are strikingly sculptural, and their clean surfaces tend to display an alluring opalescent sheen. No one is absolutely sure about all their functions (which would seem to vary from species to species), but it is safe to say that they generally serve in a sensory system very much like the saccule/utricle: they sit atop a mat of sensitive hairs and their sloshing around gives the fish information about its movement in space. Fish that have to deal with complicated spatial environments (reefs, kelp beds) usually have bigger otoliths; those open water predators that stick to swimming fast in straight lines (tuna, billfish) tend to have relatively small ones.

Otoliths also seem to play a role in underwater hearing in many species: because they are stone (and therefore of a different specific gravity than the rest of the fish), their vibrations in response to sound waves are out of phase with those of the animal’s body; these differences can be translated into acoustic information. (Interestingly, although hearing in mammals is now handled by a very different system, it has recently been shown that human beings can “hear” very high frequency sounds by means of their otolithic organs, which appear to retain some acoustic sensitivity, despite having been converted almost entirely into sensors for movement and orientation).

...About thirty years ago a curious geologist, tinkering with an otolith (it was a rock, after all), made the truly shocking discovery that those annual layers can be further resolved, microscopically, down to daily layers, layers that contain, in their chemical composition and size, information about the temperature and the salinity of the water through which the fish moved, the food that it ate, and various environmental contaminants it encountered. The result is a stratigraphy unprecedented in the organic world: the diligent student can peruse the otolith of a long-lived deep sea fish, and reconstruct not merely its age, but (and I am barely exaggerating) what it had for breakfast on 6 March 1964...

Apart from the obvious detection of sounds, the inner ear also helps the fish to orient itself in three dimensional space, giving it a feeling of bottom (gravity) and direction.

As sound waves reach a fish, the whole fish moves with the waves, as water is non-compressible. The otoliths, being more dense than the rest of the fish (3X) lag behind the rest of the fish. The otoliths are suspended in liquid and are surrounded by ciliary bundles located on the ends of sensory hair cells. The differential movement of the otoliths bends some of these cilia, which deforms the hair cells, which stimulates neural transmission to the auditory centers of the brain.

With higher frequency sounds, the amplitude of fish displacement is much less and more energy is needed for otolith stimulation. Some fishes have adaptations to increase the sensitivity of their hearing. The gas bubble of the swimbladder of some bony fishes can serve as a sort of amplifier. As gas is more compressible than water, the bladder will pulsate more than the rest of the fish when encountering sound waves. This vibrates the tissues around the bladder, providing the necessary additional movement for auditory nerve stimulation.

As with most vertebrates, the eye is the primary site of photoreception. However, the pineal organ also is photosensitive and is especially important in maintaining circadian (day-night, seasonal) rhythms.

The choroid coat lies under the retina and serves to supply the retinal cells with nutrients and oxygen. Fishes that are heavily vision-dependant have the best developed choroid retina and the highest oxygen concentrations in the vitreous humor of the eye.

Teleosts living below 500m have been found to have a different pigment (chryopsin), this pigment absorbs mainly in the blue region of the spectrum, which is the spectral range of light found in deeper waters.

In the frog, light-sensitive pigment cells in the skin and iris, as well as hypothalamic neurones involved in the control of circadian rhythms, express a chromophore—melanopsin. The impact of a photon on melanopsin induces conformational changes in a seven-membrane G-coupled receptor that is subsequently regenerated in neighbouring cells. Invertebrate photoreceptor cells behave similarly, except that the properties of a different G protein allow the chromophore to be regenerated and available within the same cell. This feature reflects the dispersed nature of photoreceptors in invertebrates—the specialized cell-packed structures that allow functional specialization in eyes do not exist.

Invertebrate-type opsins may have survived in vertebrate skin to provide light sensitivity in tissues remote from the eye, but light-dependent intracellular pigment redistribution may also have evolved for thermoregulation and photoprotection. Arnheiter thinks that pigment cells may have been the evolutionary precursors of photoreceptor cells, since the role of pigment cells in eyes is to act as a screen blocking access of light to one side of a receptor cell to endow it with directional sensitivity. Although photoreception has developed along a number of evolutionary pathways, it seems probable that the starting point was always a rhodopsin-expressing pigment cell in the skin.

For equilibrium control in man, the inner ear contains some tiny 'stones' called otoliths (from the Greek: otos=ear andlithos=stone). In fact these stones are crystals of minerals like calcium carbonate. The stones are inside three semi-circular canals, each one working in one of the three dimensions. As these stones are mineral, they are heavier than surrounding biological tissues: when they move they push on ciliated cells which produce a nervous stimulation, which is used by the brain to compute our body position. Another ear part called the vestibule, is used to detect rotation and acceleration movements by using a similar principle.

It's surprising to find such a sophisticated process in other creatures, but particularly in marine zooplankton, including the larval stages of primitive animals. Some examples are described below.

Equilibrium organs are called statocysts. They contain statoliths (stones) made with dense material such as calcium or magnesium salts crystals which are in contact with specialized cells. Many research studies are in progress on this topic and a hypothesis would be that actin fibers connect the statoliths to the cells.

Many experiments of seed growing in micro-gravity have been made during space flights of the American Shuttle and in this case roots are observed to grow in any direction. (Sorry, I have been unable to rent the Shuttle to try this experiment myself!)

I guess by now you are getting a good idea of how my brain works. I tend to try and find a relationship between various bits of information, and then keep on leap-frogging from source to source from there on in.

Some things will catch my eye. Sometimes things will really stand-out for me. I'm not sure why, but some things will just feel right. I had previously published a small extract from a paper on statoliths in Phycomyces, which right now, feels like it belongs here too:

Statoliths in Phycomyces: Characterization of octahedral protein crystals.

The crystals, which are present throughout the central vacuoles of the sporangiophore, function as statoliths.

Absorption spectra of isolated crystals and in situabsorption spectra of growing zones indicate the presence of chromophores, probably oxidized and reduced flavins. The flavin nature of the chromophores is also indicated by their fluorescence properties. It appears likely that the chromophores represent an essential part of the statoliths and thus the gravitropic transduction chain.

The common origin (monophyly) of all animal eyes is now widely accepted as fact based on shared anatomical and genetic features of all eyes; that is, all modern eyes, varied as they are, have their origins in a proto-eye believed to have evolved some 540 million years ago.

As the eye ages certain changes occur that can be attributed solely to the aging process. Most of these anatomic and physiologic processes follow a gradual decline.

With aging a prominent white ring develops in the periphery of the cornea- called arcus senilis. Aging causes laxity and downward shift of eyelid tissues and atrophy of the orbital fat. These changes contribute to the etiology of several eyelid disorders such as ectropion, entropion, dermatochalasis , and ptosis. The vitreous gel undergoes liquefaction (posterios vitreous detachment or PVD) and its opacities — visible as floaters — gradually increase in number.

Vertebrates have evolved two types of eyes; the lateral eyes (paired eyes) and the median eyes (pineal or parietal eyes). The urochordate ascidian larva has an eye-spot (ocellus) in its brain. Putative photoreceptor organs have also been reported in adult ascidians. Understanding evolutionary relationships between the ascidian photoreceptors and the vertebrate eyes is a key to uncover the origin and evolution of the vertebrate eyes. In C. intestinalis, we have characterized and examined expression patterns of homologues of genes involved in function or development of the vertebrate eyes.

The results suggest that ascidians have photoreceptor systems more similar to those of vertebrates than to those of other invertebrates. The larval ocellus expresses a vertebrate-type opsin gene and the surrounding brain cells express visual cycle genes similar to those found in the retinal pigment epithelium of vertebrates. A number of genes related to eye function and development are also expressed in part of the primordial pharynx and atrial primordia, suggesting that adult photoreceptors develop in these regions, possibly oral and atrial siphons.

Based on comparisons of the developmental origins, gene expression patterns, and functions of eyes between vertebrates and ascidians, we propose a hypothesis that the larval ocellus and the adult anterior photoreceptors (of the oral siphon) are homologous to the vertebrate median eye and lateral eyes, respectively. The last common ancestor of urochordates and vertebrates may have possessed distinct precursors of the lateral eyes and the median eye of vertebrates.

Another interesting modification in the larval nervous system in ascidians is found in the diversity of the brain sensory organs. The larval brain of Ciona and Halocynthia contains two sensory organs, the otolith (gravity-sense organ) and the ocellus (photoreceptor organ). In some ascidian species, such as those in the genus Molgula, however, the brain contains only the otolith. On the other hand, other species, including Botryllus schlosseri, have a single sensory organ, the photolith, responding to both gravity and light. We intend to compare development of the brain sensory organ in these species with that of Ciona. This study will contribute to our understanding how developmental pathways can be modified during evolution.

The tuatara is a reptile endemic to New Zealand which, though it resembles most lizards, is actually part of a distinct lineage, order Sphenodontia. The two species of tuatara are the only surviving members of its order, which flourished around 200 million years ago. Their most recent common ancestor with any other extant group is with the squamates (lizards and snakes). For this reason, tuatara are of great interest in the study of the evolution of lizards and snakes, and for the reconstruction of the appearance and habits of the earliest diapsids (the group that also includes birds and crocodiles).

The tuatara has a third eye on the top of its head called the parietal eye. It has its own lens, cornea, retina with rod-like structures, and degenerated nerve connection to the brain, suggesting it evolved from a real eye. The parietal eye is only visible in hatchlings, which have a translucent patch at the top centre of the skull. After four to six months it becomes covered with opaque scales and pigment. Its purpose is unknown, but it may be useful in absorbing ultraviolet rays to manufacture vitamin D, as well as to determine light/dark cycles, and help with thermoregulation. Of all extant tetrapods, the parietal eye is most pronounced in the tuatara. The parietal eye is part of the pineal complex, another part of which is the pineal gland, which in tuatara secretes melatonin at night. It has been shown that some salamanders use their pineal body to perceive polarised light, and thus determine the position of the sun, even under cloud cover, aiding navigation.

Together with turtles, the tuatara has the most primitive hearing organs among the amniotes. There is no eardrum and no earhole, and the middle ear cavity is filled with loose tissue, mostly adipose tissue. The stapes comes into contact with the quadrate (which is immovable) as well as the hyoid and squamosal. The hair cells are unspecialized, innervated by both afferent and efferent nerve fibres, and respond only to low frequencies. Even though the hearing organs are poorly developed and primitive with no visible external ears, they can still show a frequency response from 100-800 Hz, with peak sensitivity of 40 dB at 200 Hz.

Tuatara probably have the slowest growth rates of any reptile, continuing to grow larger for the first 35 years of their lives. The average lifespan is about 60 years, but they can live to be well over 100 years old. Some experts believe that captive tuatara could live as long as 200 years

The pineal gland or epiphysis synthesizes and secretes melatonin, a structurally simple hormone that communicates information about environmental lighting to various parts of the body. Ultimately, melatonin has the ability to entrain biological rhythms and has important effects on reproductive function of many animals. The light-transducing ability of the pineal gland has led some to call the pineal the "third eye".

The pineal gland is a small organ shaped like a pine cone (hence its name). It is located on the midline, attached to the posterior end of the roof of the third ventricle in the brain. The pineal varies in size among species; in humans it is roughly 1 cm in length, whereas in dogs it is only about 1 mm long. To observe the pineal, reflect the cerebral hemispheres laterally and look for a small grayish bump in front of the cerebellum. The images below shows the pineal gland of a horse in relation to the brain.

Histologically, the pineal is composed of "pinealocytes" and glial cells. In older animals, the pineal often is contains calcium deposits ("brain sand").

The gland will sometimes shrink and then fill up with specific types of mineral salts that are referred to as "brain sand." The condition has been traced directly to poor nutrition. When this condition exists in the pineal gland, thinking and sexual processes are affected. The pineal gland will respond quickly to proper nutrition even after being "starved" and degeneration has begun. The pineal contains more lecithin than any other body part.

The pineal isn't an actual gland; it's a neuroendocrine transducer: meaning it converts incoming nerve impulses into outgoing hormones. Most glands are triggered by changes in the body or hormones secreted by other glands. The pineal gland releases hormones in response to bioelectrical messages from the outside environment received through the eyes. The optic nerve sends information to the visual portion of the brain through nerve fibers. The impulses from the brain are carried to the superior cervical ganglia (a cluster of nerve cells) in the upper part of the neck by smaller nerve fibers. From there the autonomic nervous system relays the information to the pineal.

In some lower vertebrates, the Epiphysis Cerebri - Pineal Gland, has a well developed eye - like structure; in others, though not organized as an eye, it functions as a light receptor. In lower vertebrates, the pineal gland has an eye like structure and it functions as a light receptor and also is considered by some, to be the evolutionary forerunner of the modern eye.

The human pineal gland, in the centre of the brain, has been found to contain large numbers of calcite micro-crystals that “bear a striking resemblance” to calcite crystals found in the inner ear. The ones found in the inner ear have been shown to exhibit the quality of piezoelectricity. If those found in the pineal gland also have this quality then this would provide a means whereby an external electromagnetic field might directly influence the brain.

It’s interesting to note, though, that paragraph 18 does refer to a suggestion by Frohlich that a biological system might behave in some way like a radio receiver, amplifying a very small signal through a process of resonance; this idea is dismissed due to the unlikelihood of biological material resonating in this way – but of course one of the earliest types of radio was the ‘crystal set’, in which a mineral crystal was made to resonate (by tuning with a ‘cats whisker’) with an incoming radio wave, which is simply an electromagnetic wave of rather lower frequency than microwaves. The conclusion of this section was that “…there is little evidence to support resonant behaviour…”. The existence in the pineal gland of crystals which may prove to exhibit piezoelectric properties puts the whole issue in a totally different light – particularly in a scenario where the absolute requirement is to ‘play it safe’ (Stewart’s ‘Precautionary Principle’).

The organ where calcification is so widely accepted that it is almost considered a natural consequence of aging, is the pineal gland. In Japan, a study of 2877 people of all ages, after pathological cases were excluded, showed a 81% pineal calcification rate in people between 70 and 79 year old. The youngest person they found to have calcification of the pineal gland was 8 years old. They found that calcification increased with age. Another Japanese study of 450 subjects, found a 70% pineal calcification rate in people over 30 years, and also found the rate of calcification was proportional to increase in age. A German study focused on pineal calcification in 1044 children found calcification in 3% of children under 1 year, rising gradually to 7% at 10 years of age, and 33% by 18 years of age.

The composition of the calcification in the pineal gland has been shown to have calcium and phosphorus as the major elements and accumulations of calcium associated with phosphorus have been localized in vesicles,vacuales, lipid droplets, lipopigments, and mitochondria of dark pinealocytes.

There is also one bacteria that deserves special attention, due to its role in calcification. In 1998, Drs. O Kajander and N Ciftcioglu came across a very slow growing bacteria, which they called nanobacteria sanguineum, while they were researching something else. This bacteria, so small that it needs highly specialized instruments for it to be detected, protects itself by building a calcium shell around itself. It has been implicated in the plaque that forms on artery walls, and has been found in kidney stones and implicated in polycystic kidney disease.

“We can’t publish this. It’s too small to be alive. It must be a contaminant”

The turbidity in Kajander and Ciftcioglu’s culture flask turned out to be biofilm, elaborated by a previously undescribed bacterial species, which they named Nanobacterium sanguineum.

Nanobacteria readily bind to mammalian cells, trick the cells into internalizing them, and then trigger target cell apoptosis - including killing those cells responsible for our natural defenses like T-Lymphocytes (fig1-Nanobacteria killing a T6 Lymphocyte). N. sanguineum demonstrates unique radioresistance, related to its unique nucleic acid makeup and low division rate.

At the moment I'm a sucker for the word "turbid". We have not only turbid waters and turbid skies, but also turbid amber, and turbid urine. Cloudy, murky, or turbid (muddy) urine is characteristic of a urinary tract infection, which may also have an offensive smell. Turbidity is also sometimes applied to describe cataracts in the eye.

The word cataract comes from the Greek meaning "waterfall". Until the mid 1700s, it was thought that a cataract was formed by opaque material flowing, like a waterfall, into the eye.

Cataracts are a common occurrence, often in the elderly, where the lens of the eye loses its transparency and becomes turbid. Cataracts usually occur in one eye first, followed by the other later. Cataracts are protein crystals which grow in the lens of the eye. They begin very small and grow until they obstruct vision; if untreated they can cause blindness.

Think of your eyeball as a balloon full of water, but instead of being rubber, it is a protein membrane. Optical tissue normally allows fluids to flow through the membrane wall which acts like a filter, cleaning out harmful particles, keeping your eyes clear and your vision good as it allows nutrients to permeate. But should the membranes become tough like leather, the fluids are trapped and particles begin to accumulate. If this buildup continues, your vision will seem as if you're looking through frosted glass, a condition known as cataracts.

It all started when NASA senior scientist Rafat Ansari developed a low-powered laser light device to help astronauts with experiments growing crystals in space.

Ansari, with NASA's John Glenn Research Center in Cleveland, knew physics, not medicine. Then his father developed cataracts, where the eye's normally clear lens becomes permanently clouded. Surgery to replace the lens is the only fix.

Surprised at the lack of options, Ansari read up on cataracts and learned the lens is largely made up of proteins and water. One type of protein, called alpha-crystallin, is key to keeping it transparent. When other proteins get damaged — by the sun's UV radiation or cigarette smoke or aging — alpha-crystallins literally scoop them up before they can stick together and clog the lens. But we're born with a certain amount of alpha-crystallin. Once the supply's gone, cataracts can form.

Nanobacterium Sanguineum is a Nanobacteria that is approximately 10,000 times smaller than regular bacteria. It replicates from 1000 to 10,000 times slower than regular bacteria as well. It grows in the human system in blood, and has been found by various medical researchers and scientists to cause many human problems.

Some of the various diseases that it has either been implicated to be involved with or to cause are: calcification in atherosclerotic plaque, kidney stones, calcification in the lenses of eyes that ultimately causes "cataracts", soft tissue calcification in scleroderma, calcification in tumors, calcification in arthritis or osteoarthritis and other pathological disease states in humans. These nanobacteria colonize and secrete a "biofilm" over themselves that causes them to be covered by a calcium "shell". These nanobacteria are implicated to be the cause of all calcification in the human system that you were not born with, that you subsequently develop as you age. These nanobacteria are also implicated in causing some forms of cancer and "apoptosis" or cell death.

We're all a little weary of a new darnfangled disease, aren't we? Does this new research carry any weight? I think that there could be some very exciting ground to be covered in the future regarding nanobacteria. I'm fascinated by the role nanobacteria might play in cataracts.

And here's a thing. I thought I had tonsilitis a few days back. I had found tiny greenish lumps on my tonsils. I had had a funny taste in my mouth, especially when swallowing food, for a good month or so. It was not a pleasant taste - almost rancid. Well, I looked it up on the web and found they were called tonsil stones, and that they are not so much an infection, but are more related to dental plaque. Nanobacteria has been implied in the formation of dental plaque. Am I growing a culture of nanobacteria at the back of my throat? Further still, after describing all these ailments to my wife, I remain unsure to whether she will ever kiss me again.

A role for Melatonin in the regulation of energy production and tissue calcification has been proposed: When Melatonin is plentiful, it is easy to incorporate phosphorus into ATP, and cellular energy is plentiful. When Melatonin is in short supply, ATP production is blunted. The phosphorus will then be incorporated into calcium pyrophosphate, and the mitochondria will begin to calcify. This process occurs first in energy intensive organs, such as the heart, the kidney, and the pineal gland itself. As the pineal begins to calcify, its output of Melatonin falls off further, so pineal and extra-pineal calcification will progress. The Pineal gland appears to be the first organ to calcify in man – the beginning of the end.

Could it be that N. sanguineum puts a brake on human longevity, or that impaired immune function or recurrent Nanobacteremia leads to organ system dysfunction and premature senescence, via the mechanism of Pineal Gland calcification? Could they be everywhere? Rather, why wouldn’t we assume that they are everywhere in our tissues?

Many thanks:

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