QUANTUM ENGINEERING #2: THE ELEPHANT MAN

Organisms follow the cycle of the day, even at the cellular level, creating an internal clock. Humans' biology will follow this circadian rhythm even when external stimuli like light or temperature changes don't occur. Researchers have now used a fruit fly model to identify a role for a gene called neurofibromin (NF1) in the regulation of the circadian rhythm. Mutations in Nf1 were believed to be the cause the disease neurofibromatosis, which leads to tumor growth in the nervous system. Paradoxically, sleep disturbances are also known to be a symptom of neurofibromatosis.  

The Nf1 gene expression fluctuates according to the sleep-wake phases of the organism: its expression increases when the are awake and stimulates growth, while it decreases during their sleep.  Neurofibromatosis (NF) causes tumors to grow on nerves.

There are two main types of NF, as well as a third and very rare type called schwannomatosis.  

Neurofibromatosis type I

NF type 1 is the most common type of neurofibromatosis, NF1 and can cause a wide range of symptoms that can impact skin pigmentation (melanin), the nervous system, bones, and normal development.  Tissue tied to the neuroectoderm seem to have alter circadian clock mechanism that lead to disease manifestation.  

One of the first signs of NF1 are cafe-au-lait macules (CALMs), or cafe-au-lait spots. These are darkened areas of skin that resemble birthmarks. In some cases, they are present at birth. In other cases, they may appear during childhood or puberty. While harmless, having six or more CALMs can be a sign of NF1. Freckles in the underarms or groin are another skin pigmentation abnormality seen in people with NF1. Like CALMs, freckles are not harmful.

Neurofibromas are another common manifestation of NF1. These are benign tumors that form on the nerves. Most occur near the surface of the body and can be felt as lumps underneath the skin. Others occur deeper within the body. Neurofibromas may put pressure on nerves, causing symptoms like pain, numbness, and tingling. People with NF1 can also develop benign tumors in the eyes and along the optic nerve, which can impair vision. 

Lisch nodules. These are deposits of pigment in the iris of the eye called melanotic hamartomas. They are associated with NF1 and do not cause any problems or symptoms.  You can view them here. 

Glioma. This is a type of nerve tumor that occurs in the glial cells in the brain and spinal cord. Gliomas are more common in people with NF1, particularly optic pathway gliomas (OPGs), which occur in the nerves that connect the eyes and brain. OPGs can cause visual impairment.  You can view images here.  

Plexiform neurofibromas are larger tumors that affect multiple nerves and lead to disfigurement. While the majority of tumors that develop as a result of NF1 are benign, people with NF1 are at an increased risk of several types of cancer, including leukemia, brain tumors, breast cancer, malignant peripheral nerve sheath tumors, and others.  This implies that all these disease must also be related to circadian clock dysfunction at some level.  I have had an extensive experience with all of these tumors in my career.  Many often forget that nnEMF light blue light liberate Vitamin A (retinol) to cause many sleep disturbances.  It appears that the free retinol might have larger implications for the clock mechanisms in neuroectodermal derivatives.  

Other signs and symptoms associated with NF1 include scoliosis (lateral curvature of the spine), a larger than normal head circumference, smaller stature, bone abnormalities, early or late onset of puberty, high blood pressure, and learning disabilities.  The disfigurement can be quite shocking in these disease due to the damage to the clock mechanism. 

NF1 symptoms and the severity of those symptoms can vary greatly from person to person.  The paper below is hinting to us that the amount of dysfunction of the clock mechanism is key to the expression of the disease.  

Neurofibromatosis type 2
Neurofibromatosis type 2 (NF2) is caused by a mutation of the gene neurofibromin 2. As with NF1, the mutation that causes NF2 can be spontaneous or inherited. Whereas the onset of NF1 symptoms are observable at birth or during early childhood, NF2 usually has a later onset—the first symptoms typically appear during puberty or early adulthood. People with NF2 also have CALMs, but typically fewer CALMs than people with NF1.

People with NF2 develop tumors called vestibular schwannomas on cranial nerve #8. These benign tumors form on one or both auditory nerves, which connect the ears to the brain. These tumors can impact the functioning of the auditory nerves, causing hearing loss, tinnitus (ringing in the ears), and problems with balance.

Tumors may also form along other nerves, which can result in a variety of neurological symptoms—impaired speech, muscle weakness, pain, numbness, facial drop, difficulty swallowing, headaches, seizures, and problems with vision, including cataracts.  This also implies all these associated disease are affected by circadian clock dysfunction.  

Schwannomatosis
This rare type of neurofibromatosis is caused by mutations to the tumor suppressing genes SMARCB1 and LZTR1.  The benign tumors that occur with schwannomatosis are called schwannomas. These are the same type of tumor that occur with NF2. However, with schwannomatosis, these tumors do not involve the auditory nerves. Instead, these tumors develop on the peripheral nerves, brain, and/or along the spinal cord. Depending on the nerves that are impacted, symptoms can include chronic pain, numbness, and loss of muscle. Onset typically occurs during early adulthood.  These tumors are seen by neurosurgeon.  

What did the researchers find out about this disease recently?  

The researchers determined that the NF1 gene in the animals they studied had chronically low Nf1 expression levels had aberrant sleep cycles. These animals were totally dysregulated and had many more sleep phases than they should have had.  This told the researchers that this disease had to be related to a defective clock mechanism and not a defective gene.  

Recall that excessive blue light exposure and nnEMF at night alter calcium flows and free radicals in cells. (above)

In the new research cited below the scientists analyzed gene expression in neurons that are part of a region of the zebrafish brain that's involved in learning and sleep, known as mushroom bodies because of their shape. 

This was done for both healthy, normal fruit flies and flies with a dysregulated sleep-wake cycle.

Neurons in the mushroom bodies are activated by calcium release, and the NF1 protein is known to be upstream of that process in research animals. When the protein of the NF1 gene is expressed, neurons in the mushroom body are more active, promoting wakefulness during the daytime. The expression level is reduced at night.  The absence of light and a lower temperature (melatonin) turn off the expression of the protein from the NF1 gene.  This implies the gene always stays on and leads to the disease phenotype.  Most physicians were taught in medical school that neurofibromatosis is a strict genetic disease with no circadian cause.  We now know it is light and dark and temperature in the brain that lead to this disease and has little to do with a defective gene.  This is a torpedo to neo-Darwinist beliefs.   

In humans, the NF1 protein suppresses tumor growth in the nervous system (by regulating the activity of the p21 oncoprotein Ras). Mutations in the Nf1 gene have been believed to be the cause neurofibromatosis but now we have to question this belief.  This explains the range of symptoms that can include sleep disturbances and growth of tumors in nerve sheaths all over the body.  

CITES

https://www.nature.com/articles/s41467-021-26031-2