There are many ongoing studies into fasting, a practice prescribed across many religions. Increasingly, there is evidence to support that intermittent fasting is beneficial to human health.

The opposite of fasting – overeating – has been revealed to be a major culprit in many illnesses, including cancer, obesity, and heart disease. For many years, the medical consensus was that fasting, i.e. prolonged hunger, too, could have deleterious effects on the human body. From kidney failure to loss of muscle, fasting was believed to be harmful – thus calling into question the benefits of this widespread religious commandment.

People of faith – including Muslims – have long believed that God wouldn’t recommend a practice that was harmful to the body. The hardships and troubles that accompany a religious practice are not too extreme for people aware of their servitude to God: they regard their trials as a testament of their faith. Part of that faith is the certainty that God wouldn’t recommend a harmful or unbearable practice.

In this article, we will share with you two unknown benefits of fasting that have been recently discovered.

Regenerating stem cells

There is a substantial body of evidence showing that staying hungry during certain periods of the day heals the body’s metabolism, hastens loss of fat, decreases oxidative stress,* and improves the functions of the tissues that make up various organs including the liver, the intestines, and the brain. The first of the two new discoveries about the underlying processes, however, provides a missing piece of the puzzle by helping us understand the incredible changes hunger triggers in stem cells.

Researchers at MIT, Duke University School of Medicine, and Whitehead Institute for Biomedical Research in Cambridge published an article recently on stem cells, indicating that part of stem cell’s mystery could lie in the oxidation (burning) of fat in the mitochondria [1]. Omer H. Yilmaz and his fellow researchers found that a 24-hour fast hastens fat breakdown in intestinal stem and special progenitor cells of rats.

To run the study, Yilmaz and colleagues let the mice go hungry for 24 hours to study the state of their stem cells. They found that the functions of intestinal stem cells increased, and fat metabolism quickened, in both young and aged mice, even during early periods of hunger. They saw that the body’s tapping into fat for its energy needs maintained the health and strength of the intestinal stem cells. Moreover, they noticed that if the aged mice did not fast, they started to lose their ability to break down and use fats for energy expenditure.

The researchers obtained more interesting results as the studies progressed. It was found that a single period of hunger for 24 hours boosted renewal of intestinal cells – and the stem cell functions increased even more significantly in aged mice. Another interesting finding was that mice with damaged intestines that were fasted recovered faster than those that were fed.

“My lab is really interested in understanding how diet, in general, can be used to improve tissue function,” Yilmaz said. “One of the tissue types I study is the intestine. In my lab we study the intestine because it’s one of the largest organs in the body. It’s also a tissue that experiences rapid cellular turnover.” [2]

The intestine is lined by a single layer of cells, Yilmaz explains, that turns over every 5 to 7 days. The workhorses of the intestinal lining and this cellular turnover are intestinal stem cells. These cells must retain a high level of function or cellular health in order to replenish the intestinal epithelium on a regular basis. Intestinal stem cells are particularly important in terms of repairing intestinal damage caused by gut infections and chemotherapy, for example.

The single layer of epithelial cells needs to be renewed every 5-7 days: the aids and enzymes secreted in the intestine for digestive and absorptive activities damage cells despite the protective mucus layer, and some other cells already burst and die as they empty their secretions. Moreover, some medications, particularly chemotherapy, cause the destruction and breakdown of the epithelial cell layer. However, fast-multiplying stem cells replenish the epithelial cells. Stem cells are very active and young and have the ability to divide and multiply continuously.

Dr. Yilmaz also says:

“As we age, stem cells in the intestine as well as in many other tissues of the body, including in the blood and nervous systems, become less functional. We believe that reduced adult stem cell function contributes to some of the decline of function associated with old age. My lab is very interested in studying low-calorie interventions to delay this decline. As a field, we’ve known for over 100 years that low-calorie states such as fasting or caloric restriction can have positive effects on tissue health and aging. We’ve seen evidence that fasting during times of intestinal infections that lead to diarrhea may promote healing of the intestinal lining, for example.” [2]

This quote emphasizes the importance of the issue. Yilmaz adds that despite all this knowledge, the cellular mechanisms of this renewal have not been discovered, and he and his team are working to find out how fasting and hunger enable this recovery.

Stem cells become happy in fat!

The researchers discovered through the experiments that the stem cell function could be brought about in hungry mice by the burning (oxidation) of fatty acids in intestinal cells. When they stopped the fat metabolism through genetic engineering, they noticed that the benefits of fasting on intestinal stem cells were negligent.

In the present dietary conditions, we obtain nearly 60-70% of our energy from carbohydrates or sugar, 20% from fats and 10% from amino acids. Yet an interesting finding revealed by Dr. Yılmaz and his research team is that we essentially obtain much greater energy from using fats once we fast. According to their experiments on mice, during fasting, the intestinal stem cells in both young and aged mice switch from carbohydrates to fats as the primary source of energy, and this shift enables improvement in stem cell functions.

It is not yet known what underlies the fat metabolism that boosts stem cell functions in response to fasting, but it is observed that stem cells work better when they burn fat. The ability to metabolize fats efficiently decreases with age.

It is likely that this hastened metabolism – encouraged by certain diets, like the keto diet, where the amount of fat ingested is raised to 70% and carbohydrate intake is limited to 5% – helps with epileptic seizures and similar neurological disorders: the ketone bodies generated during metabolism of fats are used as energy sources by the brain.

According to Dr. Yilmaz, if fasting can improve the functions of intestinal stem cells through metabolism of fats, the key is the mitochondria, the powerhouses of the cell responsible for this function. Fat metabolism, or the immediate breaking down or “burning” of the fat entering the cell, is carried out in the mitochondria. Disrupted energy generation associated with aging and decreasing mitochondria can be a reason for the brain’s susceptibility to age-related illnesses. Positive developments in brain functions can therefore be viewed in connection with the correlation between fasting and the oxidation of fatty acids.

Cleaning by fasting

Just like the spring cleaning in our homes, our cells need a thorough cleaning to function properly. Wrongly folded protein particles, remains of damaged organelles, broken molecular pieces, and aged cells that can no longer divide should be disposed out of our cellular structure. Fasting perfectly performs the task of cleaning these wastes and clearing the area in the cell.

“Everything has zakat (a means of cleaning), and the zakat of the body is fasting.” (Ibn-i Majah, Siyam: 44)
“Fasting is a protective shield.” (Bukhari, Sawm: 2)

What is autophagy?

Autophagy is the compound of two ancient Greek words: auto (self) and phagos (eating). What is meant by “self-eating,” is the breaking down and recycling of protein waste and old, impaired molecules by intracellular digestive organelles called lysosomes. In this way, proteins or cellular organelles are digested and taken out of circulation. We can liken autophagy to garbage collection.

Japanese researcher Yoshinori Ohsumi’s study, which brought him the 2016 Nobel Prize for Medicine, found that the autophagy that occurs inside the cell due to fasting or starvation plays an important role in preventing ageing, infections, and tumors. If autophagy breaks down, many illnesses may be triggered, including cancer. Conversely, if autophagy activity is regular, tumors may be suppressed – depending on the stage of development and type of tumor. Cancer research has long focused on channeling these autophagic activities. Restriction of food intake through fasting shows promise: it may protect normal cells while triggering autophagy and thus increasing the effect of cancer treatments. Autophagy might offer solutions or treatment options for other illnesses, too, including inflammatory diseases [3], neurodegeneration [4], metabolic and cardiovascular diseases [5], obesity [6], and metabolic disorders.

Preclinical studies have shown that dietary restrictions by fasting contribute to the increase of a person’s lifespan and slow the development of age-related diseases such as cancer and neurodegenerative and cardiovascular diseases [7].

* Oxidative stress: The damage caused as a result of excessive proliferation of free oxygen radicals released from foods that spike blood sugar (with high glycemic index) as metabolic waste. A good example of oxidative stress is the browning of certain foodstuff such as apples, bananas, etc. sometime after they are peeled.

References

1. Yilmaz, Omer H. et al. 2018. “Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging.” Cell Stem Cell, Vol. 22, Issue 5, May 3, pp. 769–778.
2. Paige Brown Jarreau. 2018. “Eating (Or rather, Fasting) Our Way to Rejuvenated Stem Cells?” in Life and Tech @ LifeOmic. June 7. A Medium Corporation.
3. Cadwell K. 2016. “Crosstalk between autophagy and inflammatory signaling pathways: balancing defence and homeostasis.” Nat Rev Immunol.16 (11): 661–75.
4. Menzies FM, Fleming A, Caricasole A, Bento CF, Andrews SP, Ashkenazi A et al. 2017. “Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities.” Neuron. 93 (5):1015–34.
5. Bravo-San Pedro JM, Kroemer G, Galluzzi L. 2017. “Autophagy and Mitophagy in Cardiovascular Disease.” Circ Res. 120((11)):1812–24.
6. Lavallard VJ, Meijer AJ, Codogno P, Gual P. 2012: “Autophagy, signaling and obesity.” Pharmacol Res. 66 (6):513–25.
7. O’Flanagan CH, Smith LA, McDonell SB, Hursting SD. 2017. “When less may be more: calorie restriction and response to cancer therapy.” BMC Med. 15(1):106.

Fear of obesity may sometimes lead people to an extreme diet, and this may cause a deadly disease: anorexia nervosa. The sufferer initially tries to lose weight by going on a diet, but the illness soon reaches the point of no return as the result of extreme dieting. At this point, weight loss cannot be stopped; the person can no longer eat, even if he or she may want to. If they do manage to eat a little food, they throw it up. This disease and many other health conditions are connected with how our bodily functions like appetite are regulated with the secretions in our brain.

Discovered in 1998, orexin is a neuropeptide, or protein-like substance secreted by the brain. It is responsible for regulating states like wakefulness, appetite, and arousal. There are tens of thousands of neurons in the lateral hypothalamus of the human brain that secrete orexin. It was first discovered to increase appetite, but later other functions – especially in relation internal organs – were identified, including regulating the body’s energy use.

Orexins play very important roles in the development and maturation of the brown adipose tissue, which is especially important for infants. The fats in this tissue are directly converted into heat. It is the duty of the adipose tissue to protect the body from illnesses in cold weather. Experiments on lab rats have revealed that body temperature decreases in animals without orexin in their body, and they fail to consume fats. The conclusion is that orexins help boost energy consumption, protect the body from cold-related illnesses by raising the body temperature, and prevent obesity.

Orexins also help regulate metabolic activity and its speed. They are also responsible for regulating the circadian rhythm, or the daily sleep-wake cycle, especially by helping us stay awake. Orexins help increase the secretion of dopamine, norepinephrin, histamine, and acetylcholine hormones, which are in charge of the proper functioning of the daily sleep-wake cycle. All these hormones are substances that increase wakefulness.

The destruction of neurons responsible for producing orexin leads to a severe illness called narcolepsy, which is a serious sleep disorder. Patients suffer from sudden fits of involuntary and extreme sleepiness, irregular nighttime sleep, sleep apnea, various hallucinations, and muscular paralysis called cataplexy. They may suddenly fall into REM asleep while driving and watching television. The muscular paralysis accompanied by REM sleep makes sufferers collapse wherever they may be. They sometimes cannot move and remain motionless, even when they wake up. The fits of sleep strike with or without forewarning and make the need for sleep impossible to fight off. Since frequent uncontrollable collapses may cause injury, narcoleptics know they have to take precautions when they perform daily tasks. Generally appearing in a person’s twenties, the disorder may result from organic factors such as inflammation or a tumor in the brain or other underlying hostile causes.

Narcolepsy is untreatable. It can sever patients from real life and incapacitate them, leaving them unable to perform routine daily tasks. Treatments that are available can only make patients’ lives bearable.

Cataplexy is a condition in which muscles become dysfunctional, speech becomes incomprehensible, and the body collapses due to loss of strength in the neck or knees. Fits may also appear in the form of emotional responses such as excessive laughter, anger, or fear. The duration of cataplexy may last from a few seconds to a few minutes. Patients do not become unconscious during the attack; they just lose control of their physical functions. More often than not, people who have a cataplexy attack in public places seem to be under the influence of alcohol or drugs. They can see and hear others, but they cannot respond.

Sleep paralysis is a temporary state of inability to speak or move during sleep. Although it may look frightening, it is in fact not dangerous. Hypnotic hallucinations, on the other hand, are extremely vivid and frightening dream-like states experienced when falling asleep or waking. An extreme tendency for daytime sleep and hypnotic hallucinations are consequences suffered by people who have not had enough sleep, whereas cataplexy is unique to narcoleptic patients.

Orexins are also responsible for increasing the amount of nutrition a body consumes. This duty is not about meeting the body’s daily diet. Orexins tend to increase appetite, even when the body does not need feeding. They suppress the feeling of satiety, causing the person to continue eating. The willpower should kick in at this point, and the person should use it to stop eating.

The secretion of orexin is influenced by two opposite hormones. The first is leptin, secreted in obese people. Leptin’s duty is to prevent the person from overeating by reducing orexin secretion. The second is ghrelin, a digestive hormone secreted when the stomach is empty. Ghrelin increases orexin secretion, causing an increase in appetite.

It has also been discovered that orexins are connected with smoking and drug addiction. Medicines that reduce orexin secretion are used in addiction treatment. Orexins stimulate the neurons of pleasure in the brain, the reward centers, and impact a person’s happiness or sadness. A reduction in orexin secretion leads to unhappiness and sadness.

References

• Herring W. J. et al. “Orexin receptor antagonists for the treatment of insomnia and potential treatment of other neuropsychiatric indications”, J Sleep Res., 2018; e12782. doi.org/10.1111/jsr.12782.
• Kaushik, M. K. et al. “Continuous intrathecal orexin delivery inhibits cataplexy in a murine model of narcolepsy”, PNAS, June 5, 2018 115 (23) 6046–605.
• Zhou, W. et al. “Activation of orexin system facilitates anesthesia emergence and pain control”, PNAS, November 6, 2018 115 (45) E10740–E10747.

In our previous article where we discussed the mind-boggling complexity of our eyes’ retinas. We learned about the ten separate layers of cells, but we did not elaborate on the intricacies of their creation. We also learned how the substance in the cone cells, called rhodopsin, is destroyed on exposure to light and then regenerated in the dark. We thus touched on the wisdom behind the existence of both night and day.

The destruction of rhodopsin is caused by the generation of electricity after its contact with light. This electric impulse is transmitted from cones and rods to either horizontal or bipolar (having two poles) cells. The section between these two different layers of cells is called the outer plexiform layer, where horizontal cells receive electric impulses from rods and cones, and carry them to neighboring bipolar cells. The horizontal cells are also charged with transmitting electricity horizontally between rod and cone cells. The signals make it possible for shapes to be carried to the central nervous system in an appropriate contrast. Other signals are blocked so that the borders of the place of contact with light can be clarified in the brain, which does not receive an excessive load of signals. If it were not for these cells, it would be harder to perceive borders because the line of difference between two different colors would not become clear.

Bipolar cells have two opposite poles. They are created as one of two types, in accordance with their functions: one amplifies generated electric impulses, while the other inhibits the transmission of excessive impulses from around the perceived object to the brain. Bipolar cells provide the contrast necessary for making borders clear. They make clear vision possible, and yet most people have never heard of this wondrous gift inside their retinas!

How is contrast enabled?

Thanks to an innate ability, our brain does not occupy itself with regions that have the same color or the same light. It will not be stimulated much if, for example, a wall is completely white or a car is bright red all over. If, however, there are other colors on the wall, say, a white moon or star on a red background, then there will be more stimulation in the brain. Suppose we place the shape of a crescent on the wall. The stimulated parts of the brain will lie along the sharp ends of the crescent, not in the inside or outside of it. The stimulation in the brain is less associated with non-contrasting regions than contrasts in view. The higher the contrast, i.e. the greater the difference between light and dark areas, the greater the degree of stimulation.

Amacrine cells in the inner plexiform layer of the retina enable horizontal transmission. There are up to 30 different types of these cells, and they carry out at least five to six functions. For instance, one type of Amacrine cell transmits electric impulses from cones and rods to bipolar cells, then to other Amacrine cells, then to ganglion cells, and finally to the brain.

Another type of Amacrine cell responds strongly to the onset of the visual signal, while another to its completion. One other type reveals the difference in light intensity regardless of direction, while still others respond to the movement of a light point in a certain direction in the retina, causing a perception in the brain as to the direction of the light.

Further research may reveal yet more functions. Amacrine cells might have such functions as regulating the intensity of electric impulses specific to each wavelength and generating different levels of impulses for moving or stationary objects.

The function of the ganglion cells in the innermost layer of the retina is to help ensure that the electric impulse generated and corrected in the retina is eventually transmitted to the brain. Three distinct ganglion cells are identified in the retina. These cells are represented with the letters W, X, and Y. W cells are assigned the task of transmitting signals from rod cells, which produce black and white visual signals in the dark. Making up about 40 percent of all ganglion cells, they have diameters of less than 10 micrometers and transmit signals at a speed of 8 m/sec. It is evident that these cells are assigned the task of perceiving objects in the dark as rough, vague shapes.

X cells, on the other hand, transmit electric impulses to the brain, creating precise color pictures of objects. Making up 55 percent of ganglion cells, they have midsize diameters (10-15 micrometers) and transmit signals at a speed of 14 m/sec.

The largest of ganglion cells (with diameters as long as 35 micrometers), Y cells are assigned the task of transmitting instant changes in sight. Making up only 5 percent of ganglion cells, they send signals at speeds of 50 m/sec.

Sending intense signals in split seconds, Y cells inform the central nervous system immediately in case of a threat or an unusual encounter. When our body or eyes face a threat, these cells help protect us by warning the brain to move away from the threat or close our eyelids rapidly. If it were not for these cells, we would not be able to reflexively close our eyes and thus protect them. It’s incredible to ponder how complex these systems are – and how perfectly they’ve been created.

Between layers of cells there also lie layers of network that house neurons and their connections (synapses). These cells too have subgroups trained to carry out specific tasks. All of these cells are built according to certain specifications so that they can transmit stimuli to the brain when they receive light. Extremely severe visual problems develop when even a single layer of these types of cells is missing. Every one of the layers in our eyes is immensely special, and it is hard to imagine them to have been randomly placed there. It should be born in mind that this article simply skipped numerous elements of the retina and their chemical functions. Taking the precise measurements and mechanisms into account, we can only feel greater awe and love in the face of the incredible art devoted to the creation.

The first article can be found at https://fountainmagazine.com/2018/issue-126-november-december-2018/retina-the-mind-boggler

The human cerebrum is divided into two hemispheres, the right and left. These sides are not identical to one another in structure or function. The right hemisphere is in charge of coordinating functions related to the left side of the body, and the left part of the brain controls the right side of the body. To date, science hasn’t been able to explain the reason for this split.

There are other differences between the hemispheres, including functions like speech and motor skills. For example, in 90% of people, speech and hand skills are centered in the left hemisphere. However, skills such as drawing, architecture, or sense of perspective – skills that are spatial and dimensional – are dominated by the right hemisphere. While the two hemispheres are employed for various tasks, they communicate with each other. For this to happen, a structure called the corpus callosum, which contains only axons as nerve extensions, is placed between the two hemispheres and enables the transfer of information. For instance, if a needle sticks your left hand, this is perceived by the right hemisphere. In patients where the corpus callosum is missing or disconnected, when an image of a red apple is shown with the left eye closed and again with the right eye shut, the patient will report having seen no apple.

The lack of a corpus callosum is rarely encountered as a birth defect (corpus callosum agenesis). In this instance, there is rarely a deficiency when it comes to movements and sensory receptions. Activities such as speaking, standing, balancing, walking and running are almost similar to normal levels.

In the case of epilepsy, an abnormal electric current is observed in the cerebrum. The corpus callosum can be cut by surgery, disconnecting the two hemispheres in order to prevent the dispersal and transfer of abnormal electricity to the other hemisphere of the brain.

These days, this surgery is not implemented unless necessary. Obviously, performing this surgery means communication between the two hemispheres is interrupted; the tasks that are assigned to the right brain remain only in the right and the ones assigned to the left brain stay in the left. This can complicate basic motor skills. For instance, if a person wants to write or throw a ball with two hands, this task is first planned in the left hemisphere, then it is transferred to the motor-skill regions found in both hemispheres via the corpus callosum. These skills are developed via both sides of the brain and our hands, and usually one hand is better in these skills than the other. Because the left brain is usually dominant, most people are right handed.

Schizophrenia is a permanent psychiatric disease that affects a person’s emotions, thoughts, and behaviors. It means being split-minded, or the separation of the mind (in Greek, schizo means split, or divided, and phrenos means mind). In schizophrenia, the coordination between the hemispheres is disrupted and the two hemispheres intervene simultaneously to solve the same problem. Briefly, it may not cause a problem if a specific task requires only one hemisphere to be in charge; however, complications arise when both hemispheres try to solve the same job. In schizophrenic patients, it has been reported that a problem exists in the corpus callosum; therefore, communications are hindered between them. This results in a disruption.

At this point, some questions may arise. Why is our body controlled by two brain regions that have different jobs? Why do these two hemispheres communicate? What would happen if our brain was not built in two parts?

It’s hard to give answers to these questions. Sometimes, we end up with nothing to say but, “if God creates in this way, then it must be in the most beautiful form.” There is nothing useless, extra and unnecessary in the human body. But the following can be hypothesized regarding the two sided functioning of the brain: cerebral hemorrhages always occur in only one side of the brain. Speech is lost if the left side is injured, and spatial and geometrical skills are lost when the right side is injured. Therefore, maybe while a function is lost on one side, the functions of the other side are conserved.

Though the different hemispheres of the brain are in charge of different functions, they successfully fulfill their duty to activate our bodily functions through constant communication. Despite continuing clinical studies, the full extent of the brain’s power remains mysterious. Its incredible design, which allows the body to function so perfectly, is a sign of humanity’s remarkable architecture.

Various studies exist about these compartments – which controls the expression of the soul through the body, which is responsible for memory, intelligence, belief, hatred and love. The brain’s two hemispheres have different functions and specialize in different areas. For example, linguistic abilities and tongue functions are usually controlled by the left hemisphere, while musical abilities and the ability to comment and analyze complex images are controlled by the right hemisphere. However, it is not possible to state that the forebrain functions independently from the hemispheres of the brain. The Wernicke’s area, located on the upper tail of the temporal lobe, is responsible for language comprehension, and the Angular Gyrus that is a mediator between sound and vision, is responsible for linguistic and mathematical operations. For this reason, the Angular Gyrus is accepted to be related with superior consciousness and intelligence. Scientists have proven that intelligence and consciousness decrease more dramatically upon the destruction of these areas when compared to the destruction of the forebrain. Therefore, for the spiritual functions to be able to operate in the body, it’s essential that these areas of the brain function.

The more accepted view, at least today, is that spiritual characteristics and personality function independent of the brain. A convincing proof disregarding this view is that during many tumor surgeries, even though the body’s vital activities remain intact, after removing tissue from the brain, spiritual characteristics sometimes degrade. Another proof is the surgery performed to remove the forebrain of depressed patients (a prefrontal lobotomy). The patients vital activities were not disrupted upon surgery and their mood improved for a while. For a short amount of time, patients stopped suffering from serious neurological and psychiatric disturbances. However, when the patients were observed several years after the surgery, it was concluded that the patients lacked the functions of the forebrain and these surgeries were abandoned. The most prevalent side effects related to the removal of the forebrain were:

• Loss of the ability to solve complex social problems,
• Loss of the ability to take sequential steps in order to resolve a complex problem,
• Loss of the ability to multitask,
• Loss of determination, effort and desire to do activities,
• Loss of the ability for a community response when faced with a problem,
• Loss of ethical values and the feeling of shame,
• Loss of coherent thought even though the ability to speak and understand what is said is not lost,
• Instant emotional changes: from kindness to frustration, passion, violence and insanity,
• Inability to use artistic or naturally existing talents for the sake of a purpose.

These dysfunctions made it apparent that there was a correlation between the forebrain and spiritual characteristics.

Single neurons, not from the human brain, were inoculated in the lab and an experiment was carried out.. Studies showed that these neurons were not a means to highly intellectual capabilities, such as intelligence; whereas when neurons taken from the forebrain were inoculated and experimented on, it was found that they were a means to uniquely human capabilities like intelligence. Complex problem solving and the capacity to make discoveries were found to be correlated with the forebrain. It is not possible to explain such a fact without taking the soul into consideration. Spiritual characteristics such as sadness, happiness, joy, peace, patience, compassion, and love are all the results of complex interactions within the brain. However, it is not convincing to say that they are only results of electrical or chemical interactions within the brain.

The prefrontal area is where all thoughts coming from lower brain areas (such as sight, hearing, and feeling cortex areas, and the thalamus and hypothalamus) are gathered and processed to be enriched. Many information and memories gathered from different parts of the brain come together in the prefrontal area to be synthesized into deeper thoughts. Active memory is when different pieces of information are synthesized together and form a thought; and this thought is later acted upon. This allows to accurately surmise future events, and to plan for them.

It also allows for a rapid, appropriate response to the signals gathered by the five sensory channels. It allows for predicting the consequences of actions before performing them and for resolving problems of a complex medical, mathematical, ethical, moral, or philosophical basis. It can also postpone emotional responses for an appropriate time, measure the consequences of verbal and physical communications, use will power to measure the ethical and moral consequences of actions, and use information gathered from all channels to diagnose a problem. People who have damaged prefrontal cortexes, have serious difficulty synthesizing information and processing it to form coherent thoughts (active memory). This situation shows us that the prefrontal cortex enables consciousness and highly intellectual actions.

Another function of the prefrontal cortex is to enable focus about a specific topic. Taking this into consideration, the prefrontal cortex is semi related to attention. An existing proof for this is that people with damaged prefrontal cortexes are unable to concentrate and their focus is easily disturbed. Individuals whose prefrontal cortex has been removed or damaged can acquire a spiritual consciousness; however due to their handicap, they are unable to express their thoughts in a serial and sensible fashion for more than a minute. They can be easily distracted from the original subject. The prefrontal cortex allows an individual to accomplish a process of thought despite distractions, and allows for communication between the soul and the mind.

To sum it up, the prefrontal cortex is correlated with intellectual characteristics such as consciousness, intelligence, and self control, and also relates to how well we perform our moral values. For example, if the prefrontal cortex is unable to function, the individual does not feel shame anymore. This makes people believe shame is related only to the prefrontal cortex. However, the brain is merely a bridge between the body and the soul. Our brain is a bridge and curtain for our soul, which is the source of our spiritual characteristics. When we physically have a problem with our brain, the soul carries on its existence as before, however it is unable to express its consciousness, intellect, and will power in this material world.

The first is the preservation of characteristic, long term data imprints that describes the development of an organism in the stable DNA sequences.

Second is the storage of medium term epigenetically featured data that is carried a couple of generations further down the cellular level. Epigenetic information is not stored within nucleotide sequences but in the chemical modifications of these sequences (like the methylation of repeated strings of GC dinucleotide).

Third is the storage of data generated as a result of dynamic interactions between proteins, RNA and DNA in order to adapt to the events and changes during cellular life cycle in the form of nucleoprotein or DNA-protein complexes.

The data generation and storage capacity of DNA in three different hierarchical levels and time periods demonstrates that genome plays a plethora of roles in cellular activities and heredity. Formatting of genome for its generation and storage of data is carried out via DNA sequences of various features. Genomic system is composed of repeating DNA sequences. DNA sequences (satellite) function as a marker as they repeat numerous times in various frequencies. Genome includes genomic folders similar to that of computer systems. These genomic folders, also known as the epigenetic index of genomes, are responsible for the remodeling of chromatin and the coordinated control of genomic functions. Repeating DNA sequences play a critical role in replication of genome (making a copy of DNA), dispersal of copied DNA into daughter cells and construction of support systems that enable organization of chromatins.

It is possible to better understand genomic functions in relation to examples such as memory sticks and hard drives that are used in electronic information systems. The difference between a genome as a basic data-information storage medium from a hard disc is that it can be replicated as required by its nature and these replicas can be transferred to daughter cells. Following examples could be given to illustrate that a genome gains function only when it interacts with various data processing modules in the cell.

1. A copy of genome is produced by cellular DNA replication system
2. Correct localization of each genome copy towards daughter cells is only possible when chromosome segregation system works (the centrosomes and microtubules)
3. The central transcription system is responsible for the copy of data from DNA to RNA. Different gene expression patterns are developed via regulation of transcription time and level with the help of transcription factors and a web of cell signalization.

Very intricately organized genomic system structures are designed through the successive combination of protein encoding sequences, signals distributed in various places and repeating DNA sequences. Formatting of genome resembles formatting of computer programs. Various repeated serial commands of computer software are used to allocate addresses to files independent of the original data contained; different computer systems use different signals and structures to manage programs. In a similar fashion, diverse living species often utilize repeating DNA sequences and chromosomal structures to organize the encoded information and to format their genomes.

Diversity and variation of repeating DNA sequences are building blocks that are constructed into different genomic system structures. Genomes of different organisms bear characteristic system morphology just like computers with various operating systems and hardware. For instance, animal cells are created as a good model to take and incorporate foreign DNA into their genomes. Genetic data transfer among organisms of the same kind is referred to as “vertical gene transfer” whereas transfers between different species, genuses and classes are called “horizontal gene transfer.” Mobile DNA sequences like transposons are very effective horizontal gene transfer agents.

Cellular differentiation and morphogenesis (formation of tissue and organ from cell) is not programmed completely in the primary structure of the DNA sequence. Components of modular programs are encoded in a flexible way and a continuous renewed and recombined arrangement is enabled when needed.

The reason behind creation of different organisms from a single genome is this utilization of such genomic structure. Metamorphosis, that is the development of different organisms like invertebrates such as a caterpillar and a butterfly, is a good example of this feature.

Two organisms from the perspective of the same genomic protein and RNA codes can be considered as two different species. Different genomic structures and repetition of sequences among different organisms are distinctive criteria for the identification of species since these features can lead to mismatch of reproductive cells, different expression patterns of genetic code sequences, and may cause ecological diversity as well. That is why repeated DNA sequences are very important in studying parental relationships. Today, microsatellite DNA as repeated DNA sequences are used to configure biological relations among individuals in forensic sciences. Plant species vary in respect to the repeated sequences in centromeres in their chromosomes; these variations are used for identification of species. Main determinants of genomic system structure are diversity, frequency, and genomic localization of repeated DNA sequences. To explain this with examples, we could say that successively repeated sequences at centromeres, telomere repetitions and transcription, packing of chromatin, repeated sequences that are spread throughout genome in charge of cellular functions like nucleus localization are the main elements of the genome system structure. Genome is a single integrated system that is controlled closely and remotely via communication webs that use repeated sequences.

While explaining the Qur’anic concept of the Manifest Record (36:12) Bediuzzaman Said Nursi, the great renovator of Islamic thought in Turkey in the twentieth century, wrote that the Manifest Record expresses one aspect of Divine knowledge that is related “more to the past and future than to the present. It is a book of Divine Destiny that contains the origins, roots, and seeds of things, rather than their flourishing forms in their visible existence” (30th Word, Second Aim).

Inspired from this view, a seed can be considered as a tiny adorned form of Divinely creative command as programs and indexes and as a determinant for those programs and indexes in the organization of an entire tree. Since the Manifest Record book, as a title of Divine knowledge and command, observes the past and the future rather than the present, the genome of a grain or a seed acts like a library and an archive in which the future and past of an organism is written.

Sequences encoding different information in DNA

Different information types corresponding with various DNA sequences exist in the genome. These DNA sequences that were considered junk for a long time because they were not coding proteins, have in fact been found to be responsible for an amazing array of functions in genomic structure. Some of these sequences include:

1. Group determining sequences that enable coordinated or successive expression of genes,
2. Sequences acting as a marker in charge of initiation and termination during transcription of DNA to RNA ,
3. Signal sequences responsible for conversion of primary immature RNA, sequences into smaller functional RNA molecules,
4. Transcription control sequences that determine the expression frequency of genes,
5. Sequences that identify and mark the initiation regions for intensification and remodeling of chromatins,
6. Sequences that make binding regions which affect the relocation of genome in nucleus or nucleolus,
7. Sequences that target regions where covalent DNA modification (methylation) with functional groups like methyl takes place,
8. Sequences that control and identify the regions responsible for initiation of DNA replication,
9. Sequences that make the structures which enable completion of replication at terminal ends,
10. Sequences at the segregation points that enable equal distribution of copied DNA molecules into daughter cells and centromere sequences,
11. Sequences responsible for guidance during repair of DNA bound errors and damages,
12. Start point sequences used for repackaging of genomes,

Recurring sequences exist in the genomes of many organisms and shows great structural diversity. Recurring elements function as an initiator or terminator for heterochromatin regions. Furthermore they form an important scaffold and binding spots for folding of DNA structure. As if they carry out the job of an architectural mold in specific shaping of genome to be packed into a very limited area. The ratio of repeating sequences in genome (60-90%) is much more than sequences that are encoding proteins and RNA (10-40%). To explain it with an example, chromosomes in human genome are made up of packages of protein-DNA such as heterochromatin and euchromatin. Heterochromatin regions usually make up the regions with no transcription whereas euchromatin regions feature DNA transcription.

The ratio of protein encoding sequences to the entire human DNA is approximately 1.2%. Around 43% of euchromatin regions are composed of recurring and mobile DNA elements. 18% of heterochromatin region is also made of satellite (dense repeating sequences) and mobile DNA elements. Therefore almost 50% of human genomic DNA is composed of these repeating DNA sequences. In bacteria however, these only make up around 5-10% of the genome. These sequences were described as parasitic and junk individual DNA structures up until today and still continues to be described thus by many researchers and scientist. Nevertheless, even today, mobile DNA elements and repeating sequences are accepted as genomic parasites. Recent advances in the last ten years that have demonstrated this is not true, have instead revealed the vital importance of repeating sequences in genomic functions.

Repeating DNA sequences affect chromatin (dense pack of DNA and protein) structure in two ways. Irregular repeating DNA sequence copies contain binding regions for proteins that organize DNA. Heterochromatin (darker since it is densely packed chromatin) inhibits transcription and recombination, delays replication, and generally blocks the reading of information in DNA sequences that contain genetic coding. Heterochromatin regions are distributed throughout the chromosome. Because of this, presence of regions with coupled successive repeated sequences triggers heterochromatin formation.

In fruit flies, placement of protein encoding loci required for eye pigmentation near the heterochromatin blocks in centromeres (phenomenon of position effect) is provided via organization of chromosomes and thus, formation of phenotypic characters are inhibited. The “phenomenon of position effect” is convincing evidence that genome is a major system which is integrated with composition of partially repeating DNA sequences. When heterochromatin amount is increased in XYY male fruit flies, reorganized pigmentation of eye expression decreases. In XO males, when heterochromatin amount decreases, inhibition becomes severe. Changes in levels of protein which binds to special heterochromatin specific DNA regions generate opposite effects. Decrease in these proteins reduces or suppresses “phenomenon of position effect.” Surplus synthesis of these proteins also enriches this effect.

Repeating DNA sequences play an important role in the transfer of genome into daughter cells. For instance, they function in formation of the centromeres as chromosomal binding regions for microtubules, during gamete formation as linear terminals of chromosomes are replicated, and during chromosomal matching. Distribution of repeating sequences plays a major role in configuration of genomic functions. Each genome has genomic system structure that is shaped dependent on the amount of repeating DNA sequences to a major extent.

Going back to Nursi’s explanation of the Manifest Record, we can draw a parallelism between the book of the universe and the book of revelation, the first of which shows us that certain sequences in the genome are repeated for significance and necessity, just as many verses are repeated frequently in the Qur’an with nuances to refer to different meanings, benefits, and purposes, opening a wider space for many interpretations.

A genome is not only a book that contains protein and RNA codes, but also has a complex system structure with many functions for cellular vitality. The most needed sequences are those that are repeated more frequently. They are not pieces of junk DNA as predicted, they are jewels Divinely constructed.

References

• Shapiro J. A. 2001. “Genome Formatting for Computation and Function :Genome Organization and Reorganization in Evolution: Formatting for Computation and Function.” Presented at a symposium on “Contextualizing the Genome,” Ghent University, Belgium, November 25 – 28, 2001 (Ann. N.Y. Acad. Sci., in press)
• Shapiro, J.A. 2005. “A 21st century view of evolution: genome system architecture, repetitive DNA, and natural genetic engineering.” Gene 345, pp: 91–100.
• Shapiro J. A. and Sternberg R. V. 2005. “Why repetitive DNA is essential to genome function.” Biol. Rev., 80, pp. 1–24. Cambridge Philosophical Society.

The cell is the structural, functional, and biological unit of all organisms. All information needed for numerous processes in a cell, including repair and division, is contained in DNA (Deoxyribonucleic acid). DNA is a huge single molecule with intriguing features. How can a single molecule have such a dominant role in preserving information essential for the continuation of life? What are the mechanisms and levels of organization during its function? What does DNA mean for a single cell or for a human being? It’s impossible to answer these great questions in a single article; however, understanding the ways DNA exerts its role, DNA’s impact on multiple levels ranging from a single cell to an organism, and coordination between various levels, can potentially open up new frontiers in our mind and in our perception of life.

“Double helix” architecture of DNA DNA has an elegant structure that forms the basis for all of its functions. DNA is a repeating structure of nucleotides. Each nucleotide is formed of a phosphate group, 5-carbon sugar (deoxyribose) and a nitrogen-containing base attached to the sugar from outside to inside (See Figure 1a for a schematic view of DNA). There are four types of nucleotides in DNA, differing only in bases. We can consider bases as the identity of nucleotides. These four nucleotides are shown with letters A (adenine), T (thymine), G (guanine) and C (cytosine). Thousands of nucleotides bound with sugar-phosphate covalent bonds come together to form long strings. The sugar-phosphate backbone can be imagined as the steelwork of a skyscraper. The nice thing about nucleotides is their specific match to each other in double helix. A forms a base pair with only T, and G forms a base pair with only C. These pairs are bound to each other with hydrogen bonds. This feature is the key that makes DNA a double ladder. Two strings of nucleotides form a double helix by selective interactions of As with Ts, and Gs with Cs (See Figure 1b for 3-D structure of DNA). In DNA structure, hydrophobic bases tend to stay inside of double helix and hydrophilic sugar-phosphates stay outside interacting with water in nucleus. This feature helps DNA to form a double ladder. The length of the sugar-phosphate backbone is more than the bases. To compensate for the length difference, the sugar-phosphate backbone wraps around the bases inside, as a road wraps around a mountain to climb to the top. This simple difference is the main reason for DNA to form a helix.

The double-stranded nature of DNA with specific base pairing is one of its key features as genetic material. DNA is replicated using one strand as a template. Replication machinery reads one strand of DNA and builds the second strand by putting As against Ts and Gs against Cs. If a mutation occurs in one strand, it can be repaired using the second strand. This system is like photocopying DNA from itself instead of building it from scratch every time. That is why specific base pairing of nucleotides in the double helix makes it possible to replicate DNA through generations, protecting its integrity and information content. The code of DNA, an alphabet with four letters DNA contains the information to produce nano-sized cellular machineries called proteins. We mentioned that there are four types of nucleotides. Nucleotides are like letters in DNA, three of them are code for one amino acid of protein. We can make it more understandable by giving an example: “ATG-GCC-CTG-TGG-ATG” as a nucleotide sequence of DNA corresponds to the first five amino acids of a protein called insulin (a hormone regulating blood glucose level that is important in diabetes) and amino acid sequence is methionine-alanine-leucine-tryptophan-methionine. The code is so sensitive that even a single mistake in the sequence of DNA can cause serious diseases in humans such as sickle-cell disease or cystic fibrosis. With all these nucleotides, DNA can be thought of as a book containing amino acid sequence information for thousands of proteins (about 30,000 in humans). The amount of information contained in DNA is incredible: a typical human cell contains 2 meters of DNA that is tightly packed by proteins in the nucleus. If we tried to write the information from DNA into books, the book would contain over one billion words and 1,500,000 pages. DNA-protein interdependency and the cell as a micro-factory DNA can be thought of as an instruction manual that stores information for proteins and RNAs. Proteins, as molecular machines, perform particular tasks such as energy production and synthesis of DNA and RNA (See Figure 2 for the structure of proteins). Certain proteins read the information on DNA and make a transient copy of certain regions of DNA. These copies are called messenger-RNAs (mRNAs) and mRNAs are transported from nucleus to cytoplasm (See Figure 3 for representation of mRNA production from DNA by proteins). In cytoplasm, the information on mRNAs is read by protein complexes called ribosome. Ribosomes produce new proteins processing the data from mRNAs. This information flow from DNA to proteins is called central dogma in molecular biology (Figure 4). The data that is encoded in DNA can be read, translated, and put into the form of product only by proteins. We can conclude that for a protein to be produced, DNA is essential; for DNA regions to be read into proteins, proteins are essential. So, there is interdependency between proteins and DNA. Proteins without DNA have no future and no ability to regenerate and DNA without proteins is just like an instruction and manufacture manual of a computer without the user and computer itself. We can imagine the cell as a sophisticated factory, and proteins as the machines of the factory. DNA includes the instructions for the factory to be rebuilt and for itself to be rewritten for every new factory. It has instructions on how to build every machine in the factory. It has also codes for when and how much of these machines should be produced (we will discuss more about these codes on DNA in the next section). On the other hand, the timing and control of all these productions also depend on machines in the factory. Some of these machineries read and decode the instruction manual, some of them produce new machines by reading the decoded copies of the instruction manual, some of them act as sensors for the signals, some of them transmit signals to other machines, some of them produce signals by measuring the levels of materials in the factory, some of them function in communication with other factories, and so on. As we can see, DNA and proteins are meaningful for life only when they are together in the excellent cell context. This is a perfect example of the principle that the whole is bigger than the sum of its parts, because each element of the cell system has limited potential, until it comes together with the others to blossom into life.

The famous term “Gene” We can think of genes as functional units of DNA. A gene has the information content for at least one protein. Humans have about 20,500 genes that are read by protein machineries to produce proteins. Special proteins read the information on genes and make a transient copy of these certain regions of DNA. The process of making a copy of a gene as an mRNA is called transcription.

Genes don’t only store information; they have an intrinsic architecture of design to coordinate transcription utilizing three main components: promoter, coding region, and terminator. The promoter is the gene region that signals for the start of transcription. Protein machineries bind to the promoter and activate transcription. The coding region has the information for the amino acid sequence of the protein. The terminator region gives the stop signal for transcription. There are different functional regions on DNA located between separate genes such as enhancer regions that are platforms for binding regulatory proteins to tune the transcription.

The coding region of genes has multiple reading blocks for amino acid sequences and these reading blocks are called as exons. For some genes, different combinations of exons can be put together to give rise to different proteins. This mechanism allows one gene to be able to produce multiple proteins, increasing the efficiency of genetic material. A similar mechanism is used to produce antibodies (proteins recognizing foreign antigens) by the immune system. Different regional genes come together by a mechanism of DNA rearrangement (V(D)J recombination) and their differential combinations form many different antibodies. For example, a part of the antibody that is called a heavy chain is produced by a DNA region containing 65 variable (V) genes plus 27 diversity (D) genes and 6 joining (J) genes (5, 6). This produces a combination of 65 V genes x 27 D genes x 6 J genes = 10,530 heavy chains. There is a similar mechanism of rearrangement for light chain and variable region of antibodies, which result in millions of different antibodies for host antigens. A single example in the immune system shows us that DNA not only has a decent design for the coding system, but it also has ingenious and creative mechanisms to maximize its potential.

Gene expression is orchestrated during development and formation of organs The human body which consists of more than 1013 (ten trillion) cells is generated from a single cell called the zygote (see Figure 5). This tells us that, in a single cell, all the information and instructions to build and coordinate the systems of human body is encoded. Different tissues and organs including muscles, nerve cells, connective tissue, and eyes are fruits of one single cell. They all contain the same genetic information. Then what makes them different?

Promoters, enhancers, and repressors located in and nearby genes are important in spatial and temporal control of gene expression in different cell types of the body. Each cell type in our organs expresses a different subset of genes; this is what gives a cell its identity. For example, in muscles, myosin is expressed and in the eye’s retina, rhodopsin is expressed. Myosin functions in contraction and rhodopsin functions in vision. What determines the expression of rhodopsin in the eye but not in a muscle? The determination process occurs during development by programmed interactions of specific proteins called transcription factors, and restricted regions of DNA including promoters and enhancers. During development, certain regulatory proteins in a specific cell type, bind to DNA regions of only some genes (for example, in future retinal cells of the eye, rhodopsin gene would be activated but not myosin) and this predetermination orchestrates differential expression of genes to give rise to hundreds of different types of cells.

Different layers of complexity and organization related to DNA

There are different layers of function for DNA—each subtitle of this article tries to focus on a certain layer of function. DNA as a molecule has a double helix structure and is replicated through generations to preserve genetic information. It stores genetic information and has a four-letter alphabet for the expression of proteins. In the second layer, DNA has an informational unit called gene and thousands of genes are encoded in DNA to contain information for proteins. Each gene is controlled individually by making use of promoters and enhancers. In the third layer, all processes in the cell micro-factory as an entity are performed through interactions of DNA and proteins with each other and among themselves. Proteins read DNA code and work as cellular nano-machineries. In another layer, temporal and spatial expression of genes on DNA are orchestrated and different subsets of genes give rise to different cell types and organs. Organs communicate with each other to function properly and keep the balance and homeostasis of the body. The information stored in DNA not only coordinates highly sophisticated processes of a single cell, it simultaneously projects the whole body system of a human being, which is billions times bigger than a single cell.

DNA functions in all these different layers and keeps a great harmony in coordination between various layers of function. After grasping this complexity, organization and communication from a single molecule, to proteins, to a single cell, to tissues and organs, and to a human being by utilization of DNA, should not we ask ourselves, “can these elements come into existence by random forces and collisions?

References

1. Calladine, C. R. et al. 2004. Understanding DNA: The Molecule and How It Works, Academic Press

2. http://www.genome.gov

3. Li A, Rue M, Zhou J, et al. 2004. “Utilization of Ig heavy chain variable, diversity, and joining gene segments in children with B-lineage acute lymphoblastic leukemia: implications for the mechanisms of VDJ recombination and for pathogenesis.” Blood 103 June (12): 4602–9.

All the organs functioning in your body have a direct or indirect relationship with me. I can be compared to a kind of “chemical brain.” All metabolic activities are among my duties, including the control of excretions, digestion, and the composition of blood. You would be stupefied if I listed every single function I carry out, but let me tell you this much: biochemists have discovered that I am directly included in more than 80 different activities and related to more than 5,000 chemical reactions taking place in your body. Surprised? But this is only what they’ve learned so far; you do not know me in detail yet. My plain appearance is in contrast with my numerous functions. My size is about one-tenth of the body of a six-month-old fetus; now that you have become a young man, I weigh about one fiftieth of your body weight. Since I am the largest excretory organ in your body, I am firmly strapped with mesentery so you can run, jump, and make other movements without trouble.

Most people see me merely as a bile-producing organ, which happens to be among the simplest of my duties. Let me explain it another way: the heat I produce while working is equal to one-third of the heat your body produces while resting. I have a special circulatory system. Since I am located at a “junction,” the blood coming from the intestines which bear nutrient molecules come to my vein first together with the blood from the spleen, before joining the rest of the bloodstream. It can be compared to an obligatory customs check. The amount of blood I supervise within 24 hours is about 2,000 liters. With every heartbeat, almost 28 percent of the blood being pumped passes through me.

I adjust the level of blood sugar in a very sensitive balance. If you eat desserts or pastries I convert excess sugar into glycogen (animal starch) and store it. If your blood sugar decreases from hunger, I break down glycogen into sugar (glucose) and come to your help so that you do not come to a halt, like a car out of fuel.

I use various protein molecules to synthesize numerous enzymes. I also play a role in blood coagulation, red blood cell production, and storing the iron you need. You know, nothing is wasted in the divine system of nature. So how can I waste anything? When the aged red blood cells die, I help the spleen to break them down and store the iron they contain. My job in fat metabolism is no less important. Thanks to the bile I produce, the fatty food you eat is broken down to smaller molecules to be absorbed in a way similar to detergents remove oily remnants from dishes. Naturally, the fat-soluble vitamins (A, D, E, K) are also absorbed along the process. I store the excess of both these vitamins and fats. Fats are an important fuel particularly for your heart muscles. I excrete an average of 600–700 grams of bile a day. Two minutes after oily foods pass to duodenum the walls of my gallbladder are operated. Through contractions of 2–6 times a minute and a pressure of 25–30 mmHg, the bile is passed to duodenum in a time span of 15 to 90 minutes. What gives bile its yellowish-green color is the substance named bilirubin, which appears with the breaking down of the old red blood cells and disposed of through the bowels.

The Kuppffer cells—as you name them—have the duty of checking out newly produced blood cells one by one in addition to producing antibodies against germs. If any ill-formed blood cells come up, I must detect and destroy them. Otherwise they corrupt your blood. Thanks to the Kuppffer cells, the ill-formed blood cells are destroyed as soon as they are detected.

The average longevity of my cells varies between 150-180 days (220 days maximum). New cells are produced immediately to replace the dying ones and the system works smoothly. In each of these cells there are 1,000-3,000 mitochondria and millions of ribosome. An average of 180 new ribosome are produced every second. Although none of my cells have consciousness or intelligence, thousands of them come together to form little lobes resembling hexagons. The number of these lobes varies between 50,000 to 100,000.

Dear Peter, you intake various toxic substances together with the foods you eat. You don’t even realize that food has been corrupted by bacteria and fungi until its taste changes. Frankly, you should not have lived very long with so much toxic intake; Providence has given me an important duty to protect you from such harm. I capture these toxic compounds released into your bloodstream and neutralize them. The same goes for different medicines you take; I try to neutralize their toxic effects as well. But I have my own limits of tolerance; if I am faced with more toxic substances than I can handle, then I give signals of danger. You wonder how. Well, I shout “help” through red spots in your hands and itchy spots on your skin. You should be more careful about what goes down your throat.

Given that I fulfill various important functions, the littlest failure in me reveals itself as a health problem immediately. Hepatitis is among the common diseases heralding my failure. Excessive increase of bilirubin in your blood causes the white of your eye and your skin to turn yellow. I fear viruses most. Particularly hepatitis B and C viruses destroy my tissue. And alcohol, as you know, is my sworn enemy. I have to exert myself to neutralize even a tiny amount of alcohol. And if the hepatitis virus is added, I become knocked down and contract cirrhosis. It does not happen suddenly, though. Along the process which you know as liver failure I give various signals: skin eruption, digestion problems, sleepiness, and headache after meals, and so on. Since these symptoms are not serious problems, most people ignore these signals I give. Due to my various functions, the lab tests about me are more than a hundred.

Talking about my enemies may have upset you a bit, but it’s not all doom and gloom. After all, I am the organ with the highest capacity to renew itself. Sounds good, right? Otherwise I would have been finished off long ago, so this ability is a real blessing. Let me give you an example: although 90 percent of my cells are destroyed during hepatitis, I can help you survive with the remaining 10 percent if you rest well and control what you eat. If you ignore the disease, it might lead you and me to the grave. Do not ever believe those who take this lightly and say: “This doctor says that a small amount of alcohol is good for health.” Tell it to the marines. Those who say that should visit hospitals first. I’m sorry, Peter, but it really gets on my nerves. If they could only appreciate a work of art like me. Anyway, that’s all for now, please take good care of me.

Decisions within the cell: mathematical and algorithmic character

In order to enable Escherichia coli bacteria to use lactose (disaccharide), the genetic information of the enzymes that have role in transporting the lactose into the cell and converting it into glucose is coded in the bacteria’s genome. The binding and decoding structure which enables the genes to be transcribed at the right time in the appropriate amount is called the operon. The operons are model mechanisms which work on the synthesis or destruction of every chemical molecule (metabolite). One of these, lactose operon, is a good example that demonstrates how the decoding information contained in DNA is regulated and controlled in the bacteria. E. Coli is equipped with a system that distinguishes lactose and glucose when they are combined and this system functions perfectly. Primarily, all of the existing glucose is consumed before the start of the production of those enzymes that splits lactose into glucose and galactose. It has been discovered that this operation in the bacteria is followed by an interaction between DNA sequences located on the upper part of the lactose gene and various molecules. The DNA sequences on the upper part of the gene are the signals that format DNA for transcription. These signals cause the decoding of the genes that interact with the transcription factors. While some of the signals in the relevant region of the genes are common in most genes, some others are specific.

The most basic interaction system of the genome-proteome (all proteins in cell) is the suppression of the lactose operon that is observed in E. Coli. This process depends on DNA-protein interactions which are based on a mutual relationship and it requires the existence of repeated DNA sequences. Tetramer lac1 protein control the lac operon binds to four repeating binding regions on the DNA. Since one dimer can be connected to one operator sequence, two dimers are connected to two operator region units, and as a result the result is a loop formation in the DNA structure. Consequently, because of the access of RNA polymerase to the promoter region, the pre-coding process of genes is hindered. If the hindering protein is in the form of a monomer, the operator displays a weak interaction with half of the sequence. In the dimer form there is a stable binding. For this reason, many procedures in the cell occur by working together and making a union of molecules. Since the loop shape of DNA stabilizes the structure, it prevents the RNA polymerase from being connected to the promoter region. In order to eliminate the blockage on the lac operon, the mutual relationship must be prevented by stimulatory molecules, such as lactose.

There is metabolic information in cells that measure and control the physiological condition. The sequences on the regulatory region of the lactose operator and the data concerning the physiological condition of the lactose and glucose metabolisms are analyzed in the cell which perceives the presence and the amount of glucose through the changes in the system that transports the glucose into the cell. The molecule that announces the presence of glucose in E.coli is cyclic-AMP and concentration of this molecule in the cell is inversely proportional to glucose. The level of this signal affects both the coding and regulation of genomic information. The protein that transports glucose into the cell contains a phosphate group; as it transports glucose into the cell, this carrier protein phosphorylates the glucose molecule thereby loosing its phosphate group. As a result, the proportion phosphorylated transport protein and those without phosphate provides information about the glucose level in the cell. The phosphorylated form of the carrier protein activates the adenosine cyclase enzyme. Through this enzyme, ATP is converted into cyclic-AMP. The cyclic-AMP level increases in the cell. Consequently, the situation that concerns the increasing concentration of the phosphorylated transfer protein and the cyclic-AMP is interpreted as non-existence of glucose in the cell. The CRP protein that binds to regulatory region of the lactose can only bind to this region in the presence of cyclic-AMP. The cyclic-AMP-CRP complex which is tied to the promoter region of the lactose gene speeds up the transcription of the lactose operon. Transcription rarely happens when there is no lactose. This is because the lactose repressor protein lacI, hinders the RNA polymerase reaching the lactose promoter region by binding to the operator of regulating region. The cell can sense the existence of lactose in a circuitous manner. Low levels of coded Permease enzyme on the lacY region transfer some lactose into the cell. The coded beta galactosidase on the lac Z region alters them into a sugar called allolactose. The allolactose is bound to the lacI repressor protein and changes its conformation. The allolactose –lacI repressor complex can not bind to the operator region. The promoter region, called LacP, of Lactose operon is set free for transcription. In fact, every one of these molecular interactions is an incident of information being transferred. All these incidents demonstrate that an algorithm (If there is no glucose and only lactose exists, then transcribe the lacZYA enzyme) that is able to distinguish the difference between two sugars exists in bacteria cells and that it functions perfectly.

In short, the signal transfer in lactose operon occurs with the activation of chemical molecules that represent the experimental data pertaining to the physiological environment of the cells. For example, the levels of cyclic-AMP, allolactose and protein phosphorylation indicate the existence of glucose and lactose. The regulating network system, on the other hand, combines many aspects of cell activity (transport, enzymology, energy metabolism) in order to make the transcription decision. Briefly, it is impossible to show that arranging the order of the genome in any cell occurs independently from physiological or biochemical processes.

The principle of “using combinations in the arrangement of specific binding regions” is commonly used in metabolic signal networks that control cell physiology and the differentiation of cell (morphogenesis) that are oriented towards tissue formation. Such an interaction takes place on these network paths between proteins and DNA sequences to ensure that the cell is allowed to process molecular information and to calculate whether it will transcribe a specific genetic sequence. The common binding regions on DNA have vital roles in the coordinated control of various genetic loci, and it is then that the decoding of genes in a harmonious (symphonic) manner becomes possible. Various combinations of these regions are also used in making more complex decisions. As an example, protein-binding regions that are involved in the lowest level of genomic indicators have a role in decoding genes. The proteins that bind to these DNA sequences can become active when they form a group that has an interaction with more than one protein molecule. For instance, each one of the lacO and CRP regions on the lactose operon shows a palindromic sequence structure (the DNA sequence remains the same when the sequence is read from either end). Similarly, the lacP region has two lower regions that are appropriate for the binding of RNA polymerase and are separated from each other by a 16–17 base pair. In all living beings, the proteins and DNA sequences interact with each other. For example, the LacI repressor, which is in charge of controlling the lactose operon,has separate regions for not only binding the DNA region, but also for creating protein-protein binding as well as the binding of allolactose stimulator. The unique combinations of this region on the genome sequence result in a unique protein synthesis.

The genetic engineering procedures in cells

Some of the genetic engineering procedures that take place in the cells are as follows: Recombination systems (mutual material exchange) that are observed in homologous chromosomes (the chromosome pair derived from each parent), recombination specific to a particular region; separation of DNA sequences specific to those regions (fusion of gene pieces, VDJ recombination of genes as appointed in the immune system); the existence of systems that combine end points in non-homologous chromosomes (the binding of broken DNA parts, the formation of new genetic fusion, the formation of sequences that are open to hyper mutations); DNA transposons (DNA sequences that can insert themselves into different DNA sequences or can copy themselves there and leave a copy); the RNA sector that can control the transcription and signals that are responsible for the maturing transcription; the signal sequences that cause the rearrangement of neighboring DNA sequences (such as amplification, deletion, and inversion); and finally, controlling the transcription with micro RNAs.

None of the above phenomena which cause in-cell changes are random. Each of the genetic engineering functions is planned in a way that makes specific changes and arrangements. In the processes of insertion, i.e. when a specific amount of DNA is added to a different region of the genome, or deletion, i.e. when a specific amount of DNA is severed, there should be arranging, cutting and coding sequences that will bind the cut part to its new place in an appropriate way. On the genome, special regions that are suitable to mutation are created in order to produce variety and to respond to adaptation. When all these molecular engineering functions are thoroughly analyzed, it can be seen that even the point mutations, which up until now were thought to have happened by chance, are not coincidence; rather, they occur through the divinely designed genetic engineering functions. Most of the mutations that are thought to occur by chance in the cell have been removed by the repair systems and fault correction functions in the cell. Thus, the changeability and variety in DNA sequences are shaped by the power and will of God the Almighty according to a planned, programmed genetic schedule.

The R&D department of the genome

Depending on the stimulation received, God-given genetic engineering functions are arranged in the cells and a decision is made about which parts of the genome should be changed. Some of the changes inside the cell appear on a large scale. Inside the genome, different and far removed regions can be rearranged. The changes are related to one another and are in no way disconnected. One mechanism can produce more than one change. The reconstruction of changes in some organisms is a part of the normal life cycle. In the Cornelius protozoan, the embryonic genome is regularly decomposed to a thousand slices. Then, through processing and rearranging in the cells, a functional genome with a distinct system structure is created.

While the genome is reshaped, there is the production of new different sequences rather than the sequences that they regulate and which have the code for the continuity of existing phenotype features. The organization of the genome along the system base emerges with the functions of the genetic molecules, such as cut-paste-rearrange. For example, in immune system cells, there is a planned disposition to mutation and the specific antibodies are rearranged to recognize an infinite number of different antigens. The life cycles of lymphocytes demonstrates both the control of the DNA rearrangement improvements and the specificity of mutations. It is estimated that the new sequences which do not change the existing structure operate like a research center for the genome.

The God-given genetic engineering systems imposed in the cells, when analyzed from the perspective of the population, are molecular mechanisms that carry out basic changes to ensure adaptation. The duty of reconstructing the genome during adaptation has been assigned to the divine genetic engineering functions imposed in the cell. The divine genetic engineering tools and mechanisms, which are placed in the cell with active nucleic acid elements that carry information, change the genome in parallel to the changes in both the inner and outer environment; this change occurs not only on one point of the genome, but rather on every point of genome. The functions of the DNA elements, which allow for the exchange of genetic information (both horizontally and vertically, in species and between species, between types and classes), are arranged by domestic cell signal transfer and data process networks. The signal network systems that are in charge of rearranging and controlling in-cell procedures not only control when the genome is rearranged, at the same time it decides where these rearrangements take place inside the genome. The selection of the target is planned, it is not random. For instance, R1 and R2 retrotransposons which are established in the DNA region that codes 28S ribosomal RNA have specific recognition regions and the information of endonuclease cutting DNA region on specific points that it had settled down. Eukaryotic cells have more complex decision making systems. The cells continuously create responses in response to DNA damage, cell physiology and outer-cell reproduction factors. One of the critical questions and answers is whether the damage will be repaired or whether programmed death will take place. If the cell avoids giving an answer, then genetic indecisiveness appears and abnormal cell reproduction, i.e., cancer, begins. From this perspective, cancer is a result of pathology in the signal and information process in the cell. The changes in gene expression without any changes in the DNA sequence (epigenetic) as well as the divine genetic engineering functions are clear proof demonstrating that every single action in the cell occurs with a certain aim that is based on knowledge and calculations.

Hamza Aydin holds a PhD in biology.

References

• Shapiro J. A.(2001). “Genome Formatting for Computation and Function: Genome Organization and Reorganization in Evolution: Formatting for Computation and Function.” Presented at the “Contextualizing the Genome” symposium, Ghent University, Belgium, November 25–28, 2001 (Ann. N.Y. Acad. Sci., in press).
• –. (2005). “A 21st century view of evolution: genome system architecture, repetitive DNA, and natural genetic engineering.” Gene 345 (2005) pp. 91–100.
• Shapiro J. A. and Sternberg R V (2005). “Why repetitive DNA is essential to genome function.” Biol. Rev. (2005), 80, pp. 1–24. Cambridge Philosophical Society. DOI: 10.1017/S1464793104006657.

Open heart surgery is performed after putting the patient to sleep under a general anesthetic. The chest is then opened by the surgeon, and the heart is temporarily bypassed or deactivated for the duration of surgery (although in some new techniques like beating heart surgery or minimal invasion heart surgery, the operation is possible without deactivation of the heart) During this period the functions of the heart are performed by an artificial lung mechanism called the heart-lung machine (cardiopulmonary bypass machine). Performing surgery on a working heart cases where there is no facility for beating heart surgery would be like trying to repair the engine of a car while it is in motion. This is why it is necessary to temporarily prevent the functions of the heart during the operation, which requires great care and accuracy.

Stopping the heart

During this procedure the patient is connected to the machine, thin pipes called cannulae are inserted into the main veins which lead to the heart, and thus the blood which goes to the heart is directed into the heart-lung pump, fed with oxygen, and then redirected into the body. Preventing the function of the heart is not a very difficult process. When the heart-lung machine is activated and the blood is cooled and redirected into the blood vessels, the body temperature is reduced to below 30°C, and this lowers the heart rate and assists the heart to stop functioning. The actual stopping of the heart is performed by feeding a serum containing a concentrated solution of potassium ions into the coronary artery, which feeds the heart muscle. Potassium ions are normally found in the human body but in a fixed proportion; potassium is an electrolyte which, if increased, causes a defect in the heart’s rhythm and can lead to ceasing of the heart function. Feeding the coronary artery rapidly with a rich potassium solution causes the heart to stop within a few seconds and allows the surgeon to perform the operation on a non-functioning, motionless heart.

The heart should not be stopped from functioning for a long period, even if the heart-lung pump is performing the function of the heart successfully. Under normal conditions the pump cannot perform the whole duty of the actual heart and lungs. When the body temperature is reduced, there is a reduction of functioning in many organs of the body to such an extent that they almost stop working, especially the brain. This means that every organ freezes and if the patient’s pulse were taken within this period, they would be assessed as dead.

Restarting the heart

To restart the heart following the operation a reversal of the procedure performed at the beginning of surgery is necessary; the temperature of the body is increased to 36.5–37°C again with the help of the heart-lung pump, and at the same time the amount of potassium in the blood is reduced to a normal level. This is usually executed by ensuring the normal function of the kidneys which discard the potassium from the body. This is when the function of the heart is monitored closely because there is a reversal in the process of inducing low body temperature and the excess of potassium which caused the heart to stop. In other words, the barrier which stopped the flowing river is removed; therefore, according to the laws of physics, the trapped fluid should flow again at great speed, and although following surgery the majority of hearts do begin to function again when these procedures are performed, there is unfortunately no actual guarantee. There may be certain complications or even causes which we have not yet discovered, in which case an electric shock of 10–20 joules is delivered directly to the heart muscle to encourage it to function normally. If this is unsuccessful, medication such as adrenalin, which induces the functioning of the heart, is given to the patient. If, following these repeated procedures, there is no effect, and, regardless of all the effort, the heart does not function, then everything is performed again from the beginning, including the operation. But there is always the possibility that the desired result may not be achieved. Human beings always face the prospect of death in daily life, and although there is a very slim chance of death, with such a big operation there is always the possibility.

The result

We are normally totally unaware of the rhythmic incidents, a combination of great harmony, occurring within our bodies. Even breathing, a necessity for every living creature to stay alive, is not an action which we activate and continue of our own will. Sight, hearing, hunger and senses are acts of nature over which we have little direct will or power. Nevertheless, they are all events which we can only describe as divine miracles and what a great blessing it is that none of these complex functions of our bodies have been left to us humans.