The parable of those who take to them other than God for guardians (to entrust their affairs to) is like a spider: it has made for itself a house, and surely the frailest of houses is the spider’s house. If only they knew this! (Qur’an, 29:41)

A prehistoric Greek fairytale says a young girl named Arachne was a superb spinner and knitted the most gorgeous cloth. She dared the goddess Athena to a competition. When Athena saw Arachne’s stunning work, she ripped the cloth and hit the young girl. Disgraced, Arachne committed suicide by hanging herself. Athena regretted and transformed Arachne into a spider, so that she could whirl repeatedly and endlessly. Arachnida is the scientific name for spiders. It comes from the young girl in the famous Greek fairytale.

Although usually feared and disliked by people, spiders in fact make life easy for us by feeding on mosquitoes, flies, and locusts, thus saving our crops and eliminate the need for man-made insecticides which pose environmental problems. Besides, spiders are much less dangerous than people think they are; most spiders are keen to avoid interaction with people and will bite only when wounded or scared. Even poisonous spiders are rarely as dangerous as popular myths would have us believe: though black widows are poisonous, and their bites painful, they rarely kill people. If handled properly and quickly the adverse consequences of a black widow’s bite typically diminish in a few hours, and, after a couple of days’ rest or cessation of activities, the victim will fully recuperate [1].

There are countless features of spiders. But their silk is exceptionally unique and this article covers its various aspects.

Spider silk

Biomaterials, having developed over millions of years, frequently surpass man-made substances in their properties. Spider silk is an exceptionally stringy biomaterial which is made almost completely of substantial proteins. Silk fibers have stretchy powers similar to steel and some silks are practically as elastic as rubber on a weight-to-weight basis. In uniting these two properties, silks disclose a hardiness that is two to three times that of artificial fibers like Nylon or Kevlar. In addition, spider silk is also antimicrobial, hypoallergenic, and completely biodegradable [2].

The power of spider silk, so fragile in manifestation, is astonishingly great. A filament can be outstretched as much as one half its normal length before breaking, and has a tensile strength exceeded only by fused quartz fibers. Fine fibers are sturdier than others, the power to some degree depending on the velocity with which they are pulled out of the spider’s body. The higher the speed, the superior the strength.

Most of the silken fibers are not single fibers but are made up of two or more strings. A thread may be as fine as a millionth of an inch in width but, frequently, it is ten or twenty times as dense, and the assemblage of these threads unsurprisingly creates larger threads of a diversity of thicknesses. Furthermore, some threads are gluey whereas others are not.

Scientific research demonstrates that a single thread of spider silk, thick as a pencil, could stop a 747 Jumbo Jet in flight, and that on an equivalent footing, the spider’s silk is stronger than steel, per unit weight. It has been shown that the dragline silk of the golden orb spider is one of the planet’s hardest threads.

Spiders employ silk for webs, but also for trap lines, draglines, ballooning lines, for egg pouches and nursery nets, for compartments in which to sleep through winter or to copulate, and for entrapping and wrapping their victims. Silk for all these objectives is not accomplished with one kind of gland; there are at least seven distinct kinds. A few distinctive spiders have as many as six kinds and probably have more than six hundred independent glands; others have fewer than this [1].

Mechanism behind the formation of spider silk

A batch of scientists headed by researchers from the RIKEN Center for Sustainable Resource Science (CSRS) have scrutinized spider silk and discovered that a formerly undiscovered organizational constituent is critical to how the proteins form into the beta-sheet conformation that gives the silk its extraordinary power [3]. If humans can cultivate equivalents to spider silk, they could be applied in industrial and medical applications. It is well-known that the beta-sheets in spider silk are significant to its strength, but how the sheets are created is scantily comprehended, making it difficult to produce synthetic variations. It is hard to comprehend the process: the silk is originally produced as soluble proteins, which very swiftly crystalize into a solid form.

To explain this, the CSRS scientists obtained silk proteins using genetically altered bacteria that can generate silk from a golden orb-web spider (Nephila clavipes) and then executed multifaceted examinations of the soluble proteins. They discovered that the reiterating area is comprised of two designs – unsystematic spirals and a design called polyproline type II helix. Their investigations confirmed that the polyproline type II helix is critical for the creation of the stiff construction, which can then be rapidly converted into beta-sheets, letting the silk be swiftly intertwined. Fascinatingly, it was discovered that pH – which is supposed to be significant for the molecular exchanges of the N- and C- terminus areas – does not play a significant role of the foldup of the recurring areas, and that it is rather the elimination of water and mechanistic forces through the silk gland.

According to Keiji Numata, who is a project leader of JST ImPACT and led the research group, “Spider silk is a wonderful material, as it is extremely tough but does not contain harmful substances and is readily biodegradable, so it does not exert any harmful load on the environment” [4]. Numata hopes that this discovery may lead to the production of artificial silk that will prove useful for society.

Analysis of silk

The silk itself is a material identified as a “scleroprotein.” When created in the glands it is a fluid; only when dragged outside the body does it solidify into thread. Once it was believed that contact with air produced the toughening, but it currently looks that the drawing-out activity alone is accountable for the change.

To carry out the exertion done by the glands, a spider is armed with spinnerets, usually six in number. These are as accommodating as fingers; they can be prolonged, compacted, and overall be applied like human hands. In the “spinning field,” where the spinnerets are congregated, single threads are joined into numerous compound threads, and some of the dehydrated threads may be covered with a gluey substance. Thus, a completed thread may be thin or thick, dry or sticky. It may also have the look of a bead-trimmed necklace. For the last kind, the spider spins rather unhurriedly and, drawing out the gluey thread, lets it go with a jolt. The liquid thus is organized in beads spread out lengthwise across the completed line.

The strand known as the dragline may be understood as a spider’s “life line” because it performs as a lifeguard in all kinds of situations. The dragline goes along with the spider, no matter where or how far it journeys, winding out from spinnerets at the back of the body. It forms a portion of the building of webs, it grips its tiny builder firmly in problematic places, and it helps in absconding from adversaries. When a spider is inactive in a web, the dragline enables a rapid descent and escape. It allows energetic chasing spiders to jump from buildings, cliffs, or any tall position with absolute security. [1]  

Benefits of spider silk to us

The silk of the silkworm could be very profitable and marketable. There are, however, challenges. One is the changing thickness of a spider’s strand; the other is that it doesn’t well endure the interweaving process. Housing and feeding large numbers of silkworms is not difficult. But housing and feeding large numbers of spiders? There are enormous difficulties.

Native inhabitants of New Guinea have used spider silk in a variety of conditions. They make fishing nets, traps, and such objects as bags, headdresses that will keep away rain, and caps. These are not formed from single threads but from tangled, warped threads. The aboriginals of North Queensland, Australia, look to spiders for their angling supplies.

Spider silk has been valuable to the manufacturers of such complex instruments as astronomical telescopes, guns, and engineers’ levels. The threads, being exceedingly fine but nonetheless robust, are outstanding for sighting marks. Throughout the Second World War, there was a significant demand for spider thread for surveying and laboratory instruments. Black widow spiders were utilized for the manufacture of this silk.

One drawback to the use of spider silk in industry is that it might slump in a moist environment. To overcome this problem, strands of platinum or etching on glass plates take its place in such instruments as periscopes and bombsights. [1]

Spider’s silk also might have healing properties. Due to its antibacterial properties and because the silk is abundant in vitamin K, it may be efficient at clotting blood. Because of the problems in obtaining and handling extensive amounts of spider silk, the largest known piece of cloth made of spider silk is an 11 by 4-foot (3.4 by 1.2 m) fabric made in Madagascar in 2009. Eighty-two persons labored for a period of four years to gather over one million golden orb spiders and extract silk from them. [5]  

Applications of spider silk

As mentioned, human beings have been using spider silk for thousands of years.

The manufacture of contemporary synthetic super-fibers such as Kevlar (bulletproof material) includes petrochemicals, which adds to pollution. Kevlar is also strained from concentrated sulphuric acid. In comparison, the manufacture of spider silk is totally ecologically sustainable. It is created by spiders at ambient temperature and pressure and is strained from water. Furthermore, silk is totally biodegradable. If the manufacture of spider silk ever becomes industrially practical, it could be a substitute for Kevlar and be used to create a varied extent of articles such as: bulletproof vests, wear-resistant lightweight clothing, ropes, nets, seat belts, parachutes, rust-free boards on motor vehicles or boats, biodegradable bottles, bandages, surgical thread, artificial tendons or ligaments, and backings for weak blood vessels. [6]

Synthetic spider silk [5]

Duplicating the multifaceted settings needed to make threads that are similar to spider silk has been difficult to both research and manufacture. Through genetic engineering, Escherichia coli bacteria, yeasts, plants, silkworms, and animals have been utilized to produce spider silk proteins. Yet, these synthetic threads have diverse, simpler features than those of a spider. Manmade spider silks have lesser and unsophisticated proteins than natural dragline silk, and have subsequently half the diameter, strength, and flexibility.

One tactic is to remove the spider silk gene and utilize additional life forms to generate the spider silk. Canadian biotechnology company Nexia effectively produced spider silk protein in transgenic goats that passed the gene for it; the milk made by the goats comprised noteworthy amounts of the protein: 1-2 grams of silk proteins per liter of milk. To make spider silk, Nexia utilized damp whirling and pressed the silk protein across minor extrusion cavities in order to mimic the performance of the spinneret, but this process was not adequate to duplicate the sturdier characteristics of innate spider silk.

In March 2010, investigators from the Korea Advanced Institute of Science and Technology was able to produce spider silk by means of the bacteria E. coli, altered with definite genes of the spider Nephila clavipes. This tactic removes the necessity of milking spiders.

It should be noted that the manufacture of spider silk is not easy and there are intrinsic difficulties. First of all, spiders cannot be cultivated like silkworms since they are flesh-eaters and will merely eat each other if in proximity to each other. The silk produced is very slight, so 400 spiders would be required to make only one square yard of cloth. The other problem is, silk also toughens when subjected to air, which makes working with it problematic.

A different tactic is to study how spiders whirl silk and then replicate this process to make artificial spider silk. The silk itself would also have to be synthetically produced. Chemical production of spider silk is not feasible at present due to the absence of information about the makeup of silk. Randolph V. Lewis, Professor of Molecular Biology at the University of Wyoming in Laramie, has introduced silk genes into Escherichia coli bacteria so that the recurring sections of spidroin 1 and spidroin 2 efficaciously come to form. Others theorize about the likely gene introduction into fungi and soya plants. It may also be possible to modify the silk genes for precise intentions.

Why a spider’s house is the frailest of houses

Spider silk is stronger than steel, but the Qur’an (29:41) states that the flimsiest of houses is the spider’s house. The per unit weight of the dragline silk of the golden orb spider is one of the world’s hardest fibers. Webs are combinations of many kinds of spider silk, all able to be produced by the same spider. The web radials are strong, but the somewhat feebler circumferential (quasi-circular concentric) fibers are flexible and gluey to absorb the energy of a flying insect and hold it in place. The strongest of all is the fiber, which the spider uses for transport, the dragline silk. In summary, the spider fabricates both sturdy as well as feeble fibers and the web it weaves to catch flying insects is weaker; this may be the reason why it is referred to in the Qur’an as the “frailest” of houses.

Conclusions

Scientists are foreseeing many potential uses for biosilk. Textile usages are noticeable one. The flexibility and potency of prevailing merchandises such as spandex and nylon have to be improved. Since it is lightweight, hardy and flexible, biosilk may also have uses in satellites and aircraft. More prominently, the new group of progressive things that spider silk investigation may cause has the prospective to alter our lives in innumerable manners that we can barely imagine. More than 72 years have passed since the inventions of Wallace and Carothers that gave the world nylon that led us into the age of polymers. Artificial spider silk may help produce super-performing clothes of the future. Earthquake resistant suspension bridges hung from cables of synthetic spider silk fibers may someday be a reality. [1]

References

1. Syed, I. B. : Spider Silks http://www.irfi.org/articles/articles_1_50/spider_silks.htm
2. Romer, L and Scheibel, T.: The elaborate Structure of spider silk, PRION, Oct-Dec. 2(4) 154-161, 2008. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2658765/
3. RIKEN Center for Sustainable Resource Science (CSRS). Scientists discover key mechanism behind the formation of spider silk. Materials Science. May 29, 2018, https://phys.org/news/2018-05-scientists-key-mechanism-formation-spider.html

4. Nur Alia Oktaviani, Akimasa Matsugami, Ali D. Malay, Fumiaki Hayashi, David L. Kaplan, Keiji Numata, “Conformation and dynamics of soluble repetitive domain elucidates the initial β-sheet formation of spider silk”, Nature Communications, 10.1038/s41467-018-04570-5 https://en.wikipedia.org/wiki/Riken
5. Service, Robert F. (18 October 2017). “Spinning spider silk into startup gold”. Science Magazine, American Association for the Advancement of Science. Retrieved 26 November 2017. https://en.wikipedia.org/wiki/Spider_silk
6. Vivienne Li, University of Bristol, Spider Silk and Venom. Molecule of the Month – July 2002. http://www.chm.bris.ac.uk/motm/spider/page4.htm

It is estimated that there are approximately 100 trillion cells in the human body. They fulfill their duties harmoniously with all the systems, organs, and tissues manifesting innumerable signs of wonder and wisdom. If a disruption occurs to the working of cells or the coordination among cells, the process leading to cancer starts to develop in the body’s tissue.

The recent increase in cancer occurrences has led researchers to look into its development. The phrase “cellular anarchy” is sometimes used to refer to cancer’s development. Indeed, when we examine the mechanism of cancer development, we see that cells engage in irregular – anarchic – activities in addition to regular ones.

Abnormalities emerge in cancerous cells during cell division and differentiation (when they transform into specialized cells according to different tissues). Cancer cells divide uncontrollably. Under normal circumstances, numerous genes are active in cell division. In cancerous cells, however, failures occur in the mechanisms that control division. Moreover, due to differentiation flaws in cancerous cells, undifferentiated cells, which fail to acquire features that enable them to function in a tissue or organ, form groups of cells that constrain and damage other cells because of the space they occupy.

Checkpoints in cell division and tumor suppressing genes

How is cell division controlled in a normal cell?

Our cells go through numerous stages as they divide. The beginning of each stage is called a “checkpoint” because it is where errors in cell divisions are checked. At each checkpoint (called G1, S and G2) are proteins with certain duties. One of these proteins, P53, suppresses development of cancer. In other words, P53’s job is to prevent failures during cell division, hence blocking the path to cancer’s development in the cell. Whether there is a flaw in the DNA it is checked over and over again at each checkpoint. If no error is identified, the next stage proceeds. In this way, it is ensured that there is not any genetic error in the cells formed as a result of division. If there is an error, cell division is stopped. First an attempt is made to correct this genetic error. If it can be corrected, cell division is resumed. If the error is too big to be corrected, then the cell is scheduled to die; this is called apoptosis. It is worth remembering at this point that proteins that are too minute to be observed even by microscopes are tasked to perform these stupendous mechanisms. It is remarkable that they were designed to work so effectively.

Because these systems are disrupted during the development of cancer, genetically flawed cells form and multiply. Proteins produced with the genetic codes of the flawed cells are also flawed, and these flawed proteins cause a failure of the mechanisms that constrain cell division. Unconstrained cells have an abnormal capacity for division and they divide continuously, which is why cancerous cells have a greater ability to divide than normal cells.

Proto-oncogenes and oncogenes

It is essential that the parts of our body that grow, develop, or get damaged be repaired. In such cases, our cells synthesize certain “signal” molecules which are responsible for carrying to the nucleus the information that our cells should divide. As a result of the incoming information, some DNA regions called proto-oncogenes are stimulated and cell division gets underway. Proto-oncogenes are genes responsible for checking the start of cell division. When the human body encounters various cancer-making elements, damages occur in proto-oncogenes, which transform into oncogenes, or genes with the potential to cause cancer. Oncogenes lead a cell to develop cancer because cell division does not stop where it should and continues endlessly in the absence of healthy proto-oncogenes. Underlying abnormal tissue growth and spread to other organs is the fact that the control over cell division is lost.

Genetic treatment of cancer

It became apparent that age-old treatment methods proved wrong once it was discovered that the biological foundations of cancer stemmed from genetic disruptions. Despite its increase in the last century, cancer has in fact been seen throughout the history of mankind; even ancient Egyptian papyri talked about it. Because there was not a definite treatment for cancer, radical treatments were used, such as burning or cauterizing the tumor. In the first half of the twentieth century, only surgical methods were implemented in cancer treatments. Desired results could not be obtained by surgical procedures, which ended up with the excision of entire organs.

Research studies were launched in the second half of the twentieth century into whether it was possible to treat cancer using drugs. These studies revealed that cancer stemmed from genetic flaws (like the ones in oncogenes and tumor suppressing genes), which led to questions about types of treatment. Treatments of flaws at the genetic level are based on genes themselves. These treatments use such methods as stopping genes that work abnormally, eliminating the products of these genes, and killing cancer cells by making use of their genetic mechanisms.

New incidents of cancer are likely to continue to develop, for people are exposed to factors that cause disruptions of the makeup of genes. To prevent cancer, it is critically important that one should have a conscious, natural, and balanced lifestyle. People should be well-informed about the effects of smoking, genetically modified food, radiation, stress, and chemicals, so that they can lessen exposure to such risk factors. Moreover, more frequent implementation of screening tests will make early diagnosis easier. More effective methods with fewer adverse effects should also be developed for higher success rates in cancer treatment. Genetic treatment of cancer is a relatively new field but an increasing number of studies focus on it. These studies aim to kill only cancerous cells and spare healthy ones. It can be expected that research into this field will produce promising outcomes in coming years.

Just as animals can find their food, GPS seems like it can find almost any spot on Earth. Thanks to this technology, it is now possible to find people lost on mountains, in caves, or at sea. GPS can instantly detect the whereabouts of a car in a city; parents worried about their children are able to track them with ease and precision.

Though we’re able to track people with shocking degrees of accuracy, it’s harder for us to follow the miraculous activities of the micro-structures and complex molecules in our cells. We do not yet have instruments which can accurately track objects that are so small. Though we can see the holes in our skin with the naked eye, we can only see molecules, and smaller structures, with the help of an electron microscope.

Green fluorescent proteins

Taking the minute activities that occur inside an organism and transferring these processes into a visible format, and photographing intracellular chemical changes, are among the major struggles scientists face. Many researches have tried to develop ways to transfer the micro and nano worlds into a visible form.

One way of doing this is called molecular tracking. To do this, scientists track one molecule, which is easy to spot or photograph because of the light it has been conditioned to emit, and connect it to the item they’re going to examine. It is possible to make minute things observable by means of this light-marking method. The question is: how to make the molecule emit light in the first place?

The answer lies in nature. Certain sea creatures emit colorful lights. Producing light as a result of biochemical activity is called “bioluminescence”. Many creatures living in the depths of the sea, as well as fireflies and a few other species, possess bioluminescence.

Bioluminescent creatures live with special proteins that absorb light energy. While they absorb a little of this energy, they reflect the rest, emitting light. For a long time, scientists did not understand how these proteins worked. But in the 1960s, scientists managed to isolate green fluorescent proteins. This was a breakthrough in terms of marking and viewing human cells. The researchers who decoded the chemical structure of these molecules won the 2008 Nobel Prize in chemistry.

One of the most important bioluminescent creatures is the jellyfish aequorea victoria. Shimomura et al first obtained this creature’s proteins through chemical means in 1962. These green fluorescent proteins are now widely used in molecular biology and biochemistry. They are used as gene and cell markers, and thus help scientists determine the amounts of these genes in different organisms.

One of the proteins scientists track is GAD67, a protein which has important duties, particularly in the brain. GAD67 produces some messenger molecules, which function in the communication activities of the nervous system. When scientists want to know if there is GAD67 in the brain or somewhere in the nervous system, they first inject green fluorescent proteins into the cell. Later, they study the cell by using special antibodies attached to the green fluorescent proteins. If there is GAD67 in the tissue, scientists recognize it from the green color. What they are seeing is not actually GAD67, but the green fluorescent proteins attached to it.

These proteins, which are complex structured giant molecules, have a very special geometry and pattern. While even modeling the mathematical structures of a molecule takes much effort, another molecule of a different color produced by another creature makes things easy for researchers. This “marking” makes it possible to understand whether genes work or not, and whether they are active in protein production or not. It is possible to trace connections between cells, observe reactions between proteins, and to find mechanisms that form signals.

During the diffusion of light from the green fluorescent protein, no substance other than oxygen is needed (such as metal ion, phosphate, etc.). Such research can thus be simply conducted by observing the green-lit protein under ultraviolet light. This protein absorbs light from a spectrum between 395 nm and 470 nm. This range is within the wavelengths of light visible to the human eye. Normal proteins diffuse light at 300 nm, and are not visible to humans. Here, we witness another miracle in the way the world are created. It is a blessing that this special protein diffuses light of 450 nm, unlike other proteins.

Uses of green fluorescent proteins

Since the 1970s, fluorescent proteins have been used as markers in researches studying cell biology, biochemistry, and material sciences. The discovery of these proteins marked the beginning of a new era for intracellular (in vivo) research. Scientists have used this method to discover the biochemical workings of bacteria, nematodes (round worms), insects, and mammalian cells. For example, green fluorescent proteins can be used to observe the development of embryos, the unfolding of genes, or to monitor cancer metastasis in the human liver. Since a series of cancerous cells generates a very bright green light, they can easily be spotted. Hopefully, the wider use of such proteins will make identifying cancer easier in the future.

In addition to these discoveries, the emergence of some plant viruses has been observed thanks to these proteins. They’ve also been used to monitor the development of pollen. Lastly, the proteins have been useful when tracking gene transfers from plants to animals.

All of this has been possible because sea creatures absorb light differently than creatures on land. Organisms living underwater diffuse light best at a wavelength of 450-490 nm. The jellyfish who provide the necessary green proteins are perfectly adapted to their environment, and this enables them to hide from their enemies. It is this light that scientists are now using to understand nature – and to potentially save lives.

They are tiny, and there are billions of them inside you. Tiny machines, one thousand times thinner than a hair strand but strong enough to carry all kinds of material within your cells. Yes, there is a complex army of tiny machines inside your body performing an amazing array of functions while you sit at home sipping your tea.

Your heart is beating. Its lifelong duty is to pump blood to tissues to deliver essential nutrients. Transportation of nutrients continues from blood vessels to cells and then into subcellular compartments. Inside of a cell, there is a need for sophisticated biomachines which are responsible for transport. Did you know that you were equipped with minuscule motors that transported cargos in your cells? Or about cellular highways where molecular cargos are transported?

There are various proteins called “motors” in the cell. They can convert chemical energy to mechanical energy to produce force and motion in the cellular highways.¹ Amazingly, molecular motors are much superior to man-made motors in terms of energetic efficiency by hydrolyzing ATP to fuel enzymatic reactions. These molecular motors include rotary motors, polymerization motors, nucleic acid motors and cytoskeletal motors.

Rotary motors

Bacterial flagellum, used for swimming, acts as a propeller and uses a rotary motor. It has been suggested that this motor is similar to Fo motor found in FoF1-ATP synthase. FoF1-ATP synthase takes part in the conversion of chemical energy in ATP to proton gradient, or vice versa. This chemical reaction involves mechanical rotation of parts of the complex.

Polymerization and nucleic acid motors

Polymerization motors take role in polymerizations and these polymerizations generate forces for repulsion (Actin or microtubule polymerization), or separation of clathrin buds from plasma membrane (Dynamin).

DNA and RNA synthesis also involves the use of molecular motors such as RNA polymerase (RNA synthesis from DNA), DNA polymerase (DNA synthesis), Helicases (separation of double stranded DNA prior to DNA or RNA synthesis), Topoisomerases (removal of supercoiling of DNA), RSC, SWI/SNF, and SMC proteins (Chromatin remodeling and chromosome condensation). Moreover, there are specific viral DNA packaging motors that pack tightly viral DNA into capsids. separation of double stranded DNA prior to DNA or RNA synthesis), Topoisomerases (removal of supercoiling of DNA), RSC, SWI/SNF, and SMC proteins (Chromatin remodeling and chromosome condensation). Moreover, there are specific viral DNA packaging motors that pack tightly viral DNA into capsids.

Cytoskeletal motors

Dyneins, kinesins and myosins denote the three major classes of molecular motor that moves along cytoskeletal structures. Myosin is among the most prominent of motor proteins that takes role in muscle contraction. Kinesin operates on microtubules (long tubes composed of dimers of the protein tubulin, arranged to form 13 parallel tracks) to move cargos inside the cells away from the nucleus (toward positive end of microtubules) and play essential roles in the formation of spindle apparatus and axonal transport. Dynein is also known to transport cargo but in the opposite direction to Kinesin, towards the cell nucleus (toward minus end of microtubules). In addition, dynein is required to beat cilia and flagella.

How molecular motors move

Myosin and kinesin are structurally similar in terms of being dimeric with two motor heads, two legs, and a common stalk. The head regions control the forward movement by binding itself to actin or microtubule filaments. Movement is facilitated by the consumption of ATP by ATPase sites. It is fascinating how these motors translate chemical energy into motion and still be different to the movement of cars. There are different proposals as to how molecular motors move, such as walking (hand-over-hand model), inchworm model, and biased diffusion model.

The-hand-over-hand model suggests that ATP binding induces a conformational change in the forward head movements and keeps fixed, thus leading to the movement of the rear head forward and vice versa. This model, which is also known as the walking model, is similar to upright walking where one foot moves forward while other stay fixed, and vice versa. On the other hand, the inchworm model suggests that only forward head movements use ATP and leads while the other head follows. Studies on the Myosin VI with shorter legs suggested a biased diffusion model. In the diffusion model, the motor moves randomly to the next binding site in a forward direction. In order to find out which mechanism used by molecular motors, scientists measured how much of the head moves following staining with a fluorescent dye. Since molecular motor movements are so small (5-10 nM), optical traps and cantilever probes (>100 μm) were not useful to watch head movements. By increasing both photostability and brightness of organic dyes, Dr. Yildiz at UC Berkeley was able to measure head movements down to 1.5nM scale.

Kinesin: A molecular motor that walks

Kinesins are among microtubule-based motors recently shown to walk like a mountain climber by swapping its two motor units (analogous to feet) in a hand-over-hand mechanism rather than an inchworm mechanism. This recent discovery sheds light on how kinesin moves its cargos such as membrane components, messenger RNA, signaling moleculers, and others along microtubules. In addition, as suggested by findings of Dr. Yildiz, kinesin demonstrates an asymmetric walking where motor heads alternate with slow and fast steps. Further studies using advanced microscopy techniques (called FIONA) which allow nano scale detection of movement down to 2nM resolution demonstrated delicately that processive kinesin motor takes about 8 nM steps (eight-billionths of a meter) for each ATP molecule consumption with alternating 16-nm and 0-nm steps. Furthermore, kinesin is attached to the microtubule while it waits for ATP between steps. Since kinesin is used for long distance cargo transport on relatively big highways of a cell, it elegantly demonstrates a processive motor that reliably travels in a coordinated manner. Of course, not all motors will be moving like kinesin.

Dynein moves through uncoordinated stepping of ring domains

Another motor protein involved in long distance cargo transport is dynein. Dynein is a staggering giant which is much bigger and complex than kinesin and myosin motors. There are about 15 types of dyneins known to take role in cilia and flagella movement and 2 cytoplasmic forms. Cytoplasmic dynein is a homodimeric AAA+ (ATPases associated with cellular activities) motor that transports toward the microtubule minus end, acting opposite to kinesin. FIONA assay demonstrated that the heads moving processively but independently. This mechanism is quite different from the hand-over-hand stepping of kinesin and myosin, for dynein’s steps are not strictly coordinated and highly variable. Most of the time, dynein heads move alternatively with variable head-to-head distance of about 5-50nM. Each head of dynein mostly does not pass each other.

Elegant design, efficiency in transportation and being part of the living system makes molecular motors in the cells superior to man-made motors. Molecular motors travel on cellular highways in the cellular microcosm in the manner of dutiful officials of a king traveling in his domain in security via the fastest modes of transportation and easily cross provincial boundaries, demonstrating more evidently that the Sovereignty of the Eternal King is limitless. Indeed, the signs of His Dominion are reflected by each and every entity from the microcosmic world to macrocosmic universe.

Note

1 Cellular highways are composed of microtubules, microfilaments and actin filaments. Myosin moves along microfilaments through interaction with actin, but dynein and kinesin move along microtubules through interaction with tubulin

References

• DeWitt MA et al. Cytoplasmic dynein moves through uncoordinated stepping of the AAA+ ring domains. Science. 2012 Jan 13;335(6065):221-5. Epub 2011 Dec 8.
• King SM. AAA domains and organization of the dynein motor unit. J Cell Sci. 2000 Jul;113 ( Pt 14):2521-6.
• Wilhelm J. Walter & Stefan Diez. A staggering giant. Nature. Vol 482. 2 February 2012.
• Molecular motors and Motor proteins. Retrieved from Wikipedia on 3/31/2012.
• Yildiz et al. Myosin V Walks Hand-Over-Hand: Single Fluorophore Imaging with 1.5-nm Localization. Science 27 June 2003:Vol. 300 no. 5628 pp. 2061-2065
• Yildiz et al. Kinesin Walks Hand-Over-Hand. Science 30 January 2004: Vol. 303 no. 5658 pp. 676-678

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.

Futile cycles are described as two opposing biological reactions that take place in a cell at the same time [1, 2]. As a result, futile cycles have seemingly zero net gain for the cell. Actually, because no process is 100 percent efficient, some energy is lost as heat. Thus, these cycles may even cost cells some energy. They were named “futile” cycles because scientists thought that it was wasteful for a cell to operate two exactly opposite processes simultaneously.

One such process occurs in the powerhouses of cells, the mitochondria. Mitochondria are the places where a process called “oxidative phosphorylation” takes place. Oxidative phosphorylation is an efficient way of producing ATP, the cellular energy currency [1]. In this process, high-energy electrons in nutrients are used to generate potential energy, which is in turn used to produce ATP.

Scientists who worked on mitochondrial function were flabbergasted to discover a family of proteins in the mitochondria that had a strange function. These proteins were dissipating the potential energy in the mitochondria before it could be used to produce ATP. They were named “uncoupling proteins” because they were uncoupling the potential energy buildup from ATP production [3]. Scientists couldn’t imagine what these wasteful proteins were doing in our mitochondria. Uncoupling proteins were decreasing the ATP production efficiency of mitochondria. Therefore, they named this process a futile cycle, where electrons from food were used for building up a potential, and an opposing action of uncoupling proteins were dissipating this potential before it could be stored as ATP [4]. This was similar to short-circuiting a battery by connecting two poles with a wire, and just discharging the energy—energy is lost but no work is done. The scientists took this process as a remnant of a random evolutionary process that was left unfinished—“futile,” with no function at all.

It took several years and the work of a different team of biologists to figure out the benefit of these uncoupling proteins [5]. The scientists were working on the differences between wasps and honey bees. One striking difference between these species was in their ability to adapt to colder temperatures: honey bees couldn’t fly and collect pollen when the outside temperature dropped below 10 C (50 F). They had to stay in their beehives to keep warm. On the other hand, wasps could fly around in colder temperatures. The researchers discovered that the main difference that accounted for this phenomenon was that honey bees didn’t have uncoupling proteins in their mitochondria, while wasps did. Therefore, it became apparent that the main function of uncoupling proteins was to generate heat for the body to stay warm during the times when outside temperatures fell. The uncoupling proteins, it seemed, were generating heat while dissipating the potential energy (just like the wire that heats up when you connect two poles of a battery in short circuit). Later on, it was discovered that these proteins had crucial functions in all warm-blooded animals, especially in ones that hibernate during winter.

In this case, an event that initially appeared to be meaningless or even stupid turned out to be indispensible for supporting life under certain circumstances. The fact that we cannot see wisdom behind certain events does not mean they are random or meaningless. Perhaps it is just a matter of time when, in some context, the seemingly futile thing will have a vital role. So the question remains: is there really any such thing as “random” or “futile”?

References

1. Alberts, B., J.H. Wilson, and T. Hunt. 2008. “Molecular Biology of the Cell.” 5th ed. New York: Garland Science. xxxiii, 1601, [90]

2. Available from: http://en.wikipedia.org/wiki/Futile_cycle#cite_note-0.

3. Nedergaard, J., D. Ricquier, and L.P. Kozak. 2005. “Uncoupling Proteins: Current Status and Therapeutic Prospects.” EMBO Rep. 6(10), p. 917–21.

4. Jezek, P. and J. Borecky. 1998. “Mitochondrial Uncoupling protein may participate in futile cycling of pyruvate and other monocarboxylates.” Am J Physiol, 1998. 275(2 Pt 1): p. C496–504.

5. Staples, J.F., E.L. Koen, and T.M. Laverty. 2004. “Futile Cycle Enzymes in the Flight Muscles of North American Bumblebees.” J Exp Biol. 207(Pt 5): p. 749–54.

Imagine: I have just been cooked, and I am now waiting on a dish. Oh, what’s that? A metal thing with four prongs has just stuck itself into my chest, and it threw me into a shaking room with a gate moving up and down. There are, in this room, 32 flat and occluding rocks, some of which are sharp, while some are like millstones, all being lined up in a U-shape row. The frontal rocks have divided me into large pieces by squeezing and cutting. My pieces are pushed backwards by a soft shovel underneath. The rear rocks have made me almost like a paste, thoroughly mashing my pieces. Meanwhile, many taps on the right and left sides and in bottom of the room began flushing water upon me, and the carbohydrates within me have began dissolving by the pityalin enzyme (alpha amilaz) in this water. The flushing water contains substances such as lyzozym and antichore to eliminate any probable microbes within me.

I was fully softened and turned into something almost like gruel, when suddenly I was impelled by the actions of that soft shovel to an extremely tight tube inside of which movements continuously push me downward. A gate opened while I was being brought down and, as I was hoping to enter into a more spacious room and be saved from the compressive movements, I suddenly flopped into a well containing a light-colored liquid. I have come to know, while I was expecting to have some refreshment, that the liquid I flopped into was an acid capable of eroding marble (pH=0,8). I cried ‘Oh My God!’, but it was too late. This acid began to break my proteins down. The pepsinogen which was simultaneously being secreted by some cells over the walls of this large room and which were ineffective within an acid-free environment, became instantly activated by this acid and began to thoroughly break me up. Most of my proteins were broken. While I was wondering and asking ‘how come the liquid I flopped into is capable of eroding the marble but not capable of breaking up this well?’, I have come to notice that walls of the well were coated with a thin layer of mucous substance (membrane) which is unbreakable by acids.

I said ‘Oh My God! As long as you do not permit, these acids, which can erod marble, are not capable of damaging a soft tissue!’. Together with other foodstuff, I have been both blended and broken in this well-like room for about an hour. Later, the outer walls have again squeezed us, and we have been ejected yet again, this time into a new tube at an opposite direction to the one we were just pushed out of, by a sudden loosening and opening of a valve. This tube (called duodenum in Latin) has a length of about 15-18 cm and, appears as if lined up side by side. Here too, we felt wretched and were faced by a basic secretion (sodium bicarbonate) being ejaculated from a tap. This liquid was inactivating (neutralizing) the acids mixed with us, i.e., preventing them from damaging the unprotected walls of the tube which we were in.

Here again the amylaz, lipaz, trypsin, kymotrypsin and carbocsypolypeptidas attacked me, all of which break up, in a respective order, carbohydrates, fats and proteins of my ingredients, along with a lot many other enzymes, and they broke me up to my smallest constituents. Meanwhile, I started pondering the reasons why these enzymes, which are making mincemeat of me, are not damaging the tap (pancreas), which are composed of the same proteins, fats and carbohydrates that they come from. Then, I have come to realize that these enzymes could not become activated in pancreas tissue, since it does not have any activating factors, but they gained shredder features only after we arrived in the tube we are in, and only with the help of such factors which are being secreted from the intestinal walls.

After having been fully shredded within this narrow tube, a green liquid (bile), was poured on us as we were approaching its end. This detergent-like liquid was particularly responsible for shredding the fats in my ingredients. I understood, after all of this, that I was passing through a very excellent factory. As I and my fellow meatballs proceeded inside this narrow tube of approximately three meters long, no part of us remained un-shredded, except the cellulose fibers of plants such as parsley and onion which accompanied us. They continued their journey until arriving at a very thick and short tube. I have found out that their sap have been absorbed and their leftovers, after being amassed for some time, have been thrown into a cesspool called a toilet.

In the meantime, we have noticed that the walls of this tube are plicate and protuberant. These walls are apparently the places where our particles penetrate into another realm through two different ways. We understood that, via rather thin capillary channels situated inside these protuberances, we were being transferred into narrower tubes which contained two different (red and white) types of liquids (blood and lymph vessels). Now, there isn’t ‘me’ anymore, instead, there is only an ‘us’ which is composed of very smaller particles. While glucoses, the simplest forms of carbohydrates and aminoacids, the simplest forms of proteins are being transferred into the red liquid, our fat acid siblings are transferred into the white liquid of lymph vessels. Our glucose and aminoacid siblings have been carried by the red liquid to a factory called a liver. They are being returned to the red liquid after having passed through certain processes and being equipped with some useful characteristics here. But, the fats (lymphs) of the white liquid are, for some reason or another, being separately transferred into the red liquid, bypassing this factory. I learned the reason later: if the fat acids came to the liver together with glucoses and aminoacids, they would spoil this factory and kill its workers.

Finally, the red liquid carried us to tiny cell chambers numbering almost 100 trillion. Each of our tiny particles were sent to separate cells. Here, water, carbondioxide and energy were being produced by primarily coupling of our sibling glucose with oxygen. I learned that energy was needed for the functioning of these cells. Our fat siblings were also being utilized (consumed) for producing energy if glucoses were found insufficient for that purpose. Our amino acid siblings were being utilized (consumed) in the production of sound (strong) proteins and glucoses, and of energy in cases of the unavailability of fat sources for use in the cells’ structures. Excessive amounts of fat and glucose were being stored in these tiny cells. That is to say, I, who was a meatball at the beginning, was converted into water, carbondioxide and energy at the end of this painstaking journey. I was promoted (exalted) to the degree of humanness and rewarded a great deal of honor, as some parts of me became constituent of and some other parts of me assumed responsibility in vital cell functions of the human body.

After all these disintegrations and absorptions, some parts of us took their share in the structure of the body, while some others which were used in energy production including me were converted into a choky and dirty gaseous state called carbondioxide. We have been thrown back into the red liquid again since we would perhaps choke the cells we are within should our density increase very much. We have been brought to a marvellous and sponge-like factory named a lung, and composed of millions of vesicles, by being placed onto a molecule called hemoglobin, which is being pushed by a big pump. We have replaced the oxygen of the fresh air arriving to the lung vesicles. Now is the time for bidding farewell the human body. I thanked God, for I regained my freedom as a carbondioxide passing through and escaping from very dark and narrow places.

However, I was placed upon the leaf of a green plant after aimlessly roaming in the air for some time. After being filtered through the little windows (stoma) over the leaf, I was brought inside by the chlorophyll factory marvelously functioning inside these cells. Here, they forced me to unite with the water brought by tubules from the soil. Upon telling them that I cannot afford to do that, they instantly changed my true nature with solar rays and turned met into a chemical energy depot. I was no more a simple carbon atom; thus, I found a place for myself within an energy-emiting glucose molecule. I was in a position suitably convertible to starch, protein or fats in accordance with the true nature and genetic program of the plant I was within. Something incredible happened while I was swinging around on a green clover leaf. The leaf I was in has been eaten by a cow with real pleasure.

A new chapter has now opened inside the cow’s body. I was assigned with certain duties within the muscle proteins of my new host after having passed through a number of chemical processes. And I really enjoyed them. I was feeling myself more as an animal protein than a simple grass. By leaving the grass for a cow’s body, I was promoted (exalted) one more degree on the way to becoming manifestations of the divine attributes of God.

This blessed animal in whom I was assigned has been sacrificed during a Muslim feast of sacrifice, its meat ground into a meat grinder, and I have been served to you once again as a meatball.

Ali Uguz is a teacher of biology. He lives in Turkey.

The hectic life style that many of us lead today causes stress which is likely to result in diseases of the heart or nervous system. The fast food culture has become a part of our lives due to our busy work schedules; this sort of a diet obviously causes an excess intake of fat. Office hours spent sitting on a chair without effective physical activity result in the storage of unused energy in the body. Thus, cardiovascular diseases have become one of the most common life-threatening risks for people living in developed countries. In the last five decades, much research has been devoted to investigating and preventing the risk factors that lead to coronary artery diseases.

The mushroom is a food with a rich nutritious content. Some species are known for having characteristics that are helpful in regulating the immunity system, preventing tumor formation, and reducing blood pressure without producing any known side effects. 88–91% of the physical make-up of a mushroom is water, thus fresh mushrooms are rich in proteins which can be more easily digested than many other vegetables. In addition to such proteins that are necessary for general health, mushrooms consist of B-complex vitamins and mineral materials.

Some species of mushrooms act as sources of healing in many ways. Polysaccharide-protein complexes obtained from species like Pleurotus spp., Ganoderma lucidum (Reishi), Grifola frondosa (Maitake), Lentinula edodes (Shiitake) have been found to prevent the spread of tumor cells and AIDS. It has also been discovered after research that mushrooms have antiviral, antibacterial, and antifungal effects; they are useful in the treatment of illnesses like cold, stomach and head aches, and hepatitis B; they can help reduce fatigue and sleeping problems as well as blood cholesterol levels. Mushrooms can also have a positive effect in diseases like arteriosclerosis, kidney failure and high blood pressure, as well as helping in strengthening the immunity system, thus delaying unfavorable conditions of aging.

Research has shown that mushrooms, with their B-complex vitamins, have a positive influence on the nervous system. The mushroom offers a good alternative for anemia, a disease that arises from a deficiency in folic acid and it also helps to regulate the blood sugar level. Mushrooms are often recommended for patients with liver and kidney diseases, as well as being a good source of protein for patients suffering from gout, for it causes the formation of only a small amount of uric acid at the end of the digestion metabolism. Here we provide more specific information about certain species of mushrooms:

Shiitake (lentinula edodes)

This species is cultivated and sold in Japan and China, where it is known as “the elixir of life” or “the secret of long life.” It is traditionally used in wedding meals. This mushroom is effective primarily in the prevention of apoplexy and arteriosclerosis. It is also used in many cancer research programs, due to its antitumor activity. A polysaccharide known as lentinan that is found in this species can suppress sarcoma 180, a solid type tumor, a feature that adds to the value of this mushroom. Patients are advised to consume shiitake mushrooms during chemotherapy.

In Japan, around fifty different types of enzymes have been derived from the shiitake mushroom. These enzymes include pepsin and tripsin, which are used in the treatment of some gastric diseases, as well as asparaginase, which makes up a part of leukemia treatment for children. This species is rich in proteins, vitamins, and minerals. The consumption of 100 grams of fresh mushroom generates only 28 calories, thus making it a good alternative as a food that has limited energy intake. Mushrooms have only a small amount of A and E vitamins, but a large quantity of ergosterol (provitamin D2); this can change to D2 vitamin under sunlight or artificial light. D2 vitamin can adjust the phosphor and calcium balance, thereby contributing to bone and muscle development and preventing rickets. It has been found that the eritadenine compound that is contained in this mushroom reduces blood cholesterol at a rate of 25–45%. This species is known to be useful for all the health problems listed above (regulating blood circulation, apoplexy, arteriosclerosis, kidney failure, and high blood pressure; destroying bacteria, virus, pathogenic fungi).

Pleurotus spp.

This species is rich in proteins, only being surpassed by legumes. Mineral salts, like calcium, phosphor, and iron are contained in this species, in amounts that are proportionally twice as much as those found in beef or fowl. Among mushrooms, pleurotus has the highest levels of B1 vitamin (tiamin) and B2 vitamin (riboflavin).

Hemagglutinin, a substance that causes the agglutination of red blood cells, is contained in pleurotus ostreatus and pleurotus spodoleucus species. Eight of the eighteen amino acids found in pleurotus ostreatus are essential for human life. Extracts obtained from pleurotus spores trigger the formation of interferon, which is the first defense mechanism against viral infections. These spores have been found to help prevent flu and paralyses in laboratory animals.

Some mushroom species have been shown to be effective in strengthening the immune system. Chemotherapy applications used primarily in cancer and some other diseases are known to have many side effects, some of which are severe and can lead to other diseases. The toxic effects of some medications might pave the way for other infections, damaging the kidneys and liver. It is thanks to God, the Healer, that the mushroom is one among millions of other sources of healing that can be found in nature, waiting for us to discover them.

Basic nutrients for Agaricus bisporus %

Fat 0.35

Protein 3.43

Carbohydrate 3.78

Ash 0.71

Humidity 91.73

Minerals (ppm)

Zinc 5.46

Copper 1.59

Potassium 2445.50

Iron 8.73

Calcium 39.60

Chromium Iz

Phosphorus 882.30

Vitamins dissolved in water (mg/100g)

B1 (Tiamin) 0.094

B2 (Riboflavin) 0.396

Folic acid 0.078

C (Ascorbic acid) 2.29

Niasin 5.35

At the beginning, I really did not pay much attention to him. He was very small, almost invisible and harmless-looking. However, he started to reproduce all of a sudden. Now, there were billions of his copies on one of my leaves. Everything was happening so quickly. They were taking me over. Something had to be done urgently.

As plants, we cope with such environmental stresses everyday. If the stress factors affecting us are living organisms, such as bacteria, harmful insects, and weeds, we call those as biotic stresses (1). On the other hand, if we are exposed to drought, salinity, heat, cold, and deficiency or excess of a chemical in soil, those are abiotic stresses for us. Both biotic and abiotic stresses impair our growth and even lead to our death sometimes. Therefore, stress response mechanisms are very important for us. Unfortunately in the United States alone, crop losses due to plant pathogens amount to billions of dollars (2). As we are the main food resource for the humans and assigned for so many other important functions on earth by God, our health and productivity is taken very seriously by scientists. So, it is of great interest to them to find out how our defense responses against microbes work. If scientists learn what is going on when a plant is infected by pathogens thoroughly, they can introduce better resistance mechanisms into economically important crop plants via genetic engineering.

Oh “NO,” I am stressed!

Unlike animals, we are firmly attached to the ground so we can not escape from stress factors. However, thanks to God, we have fascinating defense mechanisms against environmental challenges. First of all, I need to know who this infectious agent (pathogen) is so that I can trigger a stress response mechanism against it. The interactions between me and these microbes are controlled by my receptor proteins and Pathogen-associated molecular patterns, or PAMPs, delivered by the pathogen. PAMPs help pathogen growth by suppressing my defenses and manipulating my metabolism (3).When I recognize a PAMP by my receptors, I activate a set of defense mechanisms known as the hypersensitive response (HR) to arrest and terminate pathogen growth before it terminates me (4). Just before or in conjunction with HR, I increase synthesis of several families of pathogenesis-related (PR) proteins in my infected part (5).

Do you want to know what I do after I identify a pathogen? I bet you do, so I am going to tell you about the other components of my signal transduction cascade that is activated upon brutal attack of microbes (Fig. 1). One of the early steps in this signaling cascade is the elevation of cellular calcium (Ca (2+)) levels mediated by my plasma membrane and channels such as cyclic nucleotide gated channels (CNGCs). After the initial Ca(2+) increase, I activate some of my calcium-binding proteins (calmodulin or CaM) and protein kinases, which modify other proteins by chemically adding phosphate groups to them, and ultimately I generate nitric oxide (NO) and reactive oxygen species (ROS) (6). ROS function as signaling molecules that coordinate a wide range of diverse plant processes, such as growth, development, stress adaptation, and cell self-destruction (programmed cell death) (7). However, the real reason I produce ROS under attack is to use them as local toxins to form unfavorable conditions for pathogen growth and reproduction. NO plays a key role in our immunity in synergy with ROS regulating responses that include defense gene expression and programmed cell death (8). As a result, I utilize both ROS and NO to say “NO” to the pathogens. Other important signaling molecules I utilize are salicylic acid and jasmonic acid. These essential plant hormones are chemical messengers that enable me to respond to my environment. Salicylic acid, SA, which is chemically similar to but not identical to the active component of aspirin (acetylsalicylic acid), is involved in the defense against pathogens that feed and reproduce on live host cells and activates signaling processes providing systemic acquired resistance, protecting the plant from further infection after an initial pathogen attack (9) (Fig. 2). On the other hand, jasmonic acid (JA) induces defense against pathogens that kill host cells for nutrition and reproduction (10). Another hormone in the complex cross talk of signaling pathways regulating my defense responses to microbial attack is ethylene, ET (11).

Although, I have not even told you all the details, I bet you have started to think that all these signaling cascades, regulators, hormones, molecular patterns, and receptors are highly complicated. Do not worry; I am not planning to tell you all the molecular mechanism(s) and relevant pathways I execute during biotic stress responses. If I do, then what will the plant scientists who are interested in plant pathogen interactions do for the rest of their lives? Instead I am going to briefly describe to you what strategies I use to prevent the spread of infection that the small microbe started.

Initially, I build physical barriers around the infection by increasing my cuticle, a protective waxy covering, and cell wall thickness, and then I release antimicrobial compounds, such as phenolics and phytoalexins to the sites of invasion (11). However, this effort is usually not enough to stop the microbes. Therefore, most of the time, the cells in the local region surrounding the infection decide to commit suicide to limit the growth of the pathogen through programmed cell death, which is a highly coordinated and sophisticated phenomenon. This resembles to the firefighters’ strategy to put down a forest fire. Firefighters control flames by cutting down trees, clearing brush away from the existing edge of the fire. This way they can form borders to mitigate the forest fire.

While I am fighting the infection, I also try to confer a long-lasting protection against this pathogen. I send mobile signals like salicylic acid to activate defense responses in distal tissues in case a secondary pathogen attack might occur there (12). Salicylic acid also induces numerous genes that encode PR proteins with antimicrobial properties (13).

I have done all those things I have told you here and a lot more that are still undisclosed to humans in a really short time because it was a matter of “to be, or not to be.” After all that stress, I have won the battle against the microbe at least for now. I have gained a life experience and will defend myself better in the future. I am recovering, but unfortunately my leaf, where all that fighting happened, has a big lesion, an abnormal tissue, which was formed when my poor cells died during the attack (Figure3).

As you can tell from my story, plants get stressed out too. However, we are not stressed due to problems at home, school, or work or spending time stuck in traffic. We deal with salinity, heavy metals, temperature, drought, lack of nutrition, herbivores (insects, mammals, etc.), and pathogens. Thanks to God that He gave us astonishingly complicated response mechanisms to resist all sorts of stresses to some extent, especially biotic stress. Otherwise, we might have become extinct. Can you imagine a world without us? You would have no more oxygen in the air, no more food for animals and humans, no more papers or books, no more clothes, no more furniture, no more blooming beautiful gardens, no more roses for your loved ones, and no more trees, which hold the soil in place so that wind and rain don’t cause severe erosion and destruction of homes for so many species. In addition, there will be fewer resources for drugs and dyes. Oh my God, you are the Most Gracious and the Most Merciful. Thank you that You created us, shaped us and gave us smell, taste, color, and resistance to stresses.

Safiye Arslan is a research fellow in the area of biological chemistry and lives in Nevada.

References

1. Holopainen JK, Gershenzon J. 2010. “Multiple stress factors and the emission of plant VOCs.” Trends Plant Sci. 15,176–184.

2. http://www.apsnet.org/online/feature/biotechnology/

3. Wulff BB, Chakrabarti A, Jones DA. 2009. “Recognitional specificity and evolution in the tomato-Cladosporium fulvum pathosystem.” Mol Plant Microbe Interact. 22, 1191–202.

4. Genger RK, Jurkowski GI, McDowell JM, Lu H, Jung HW, Greenberg JT, Bent AF. 2008. “Signaling pathways that regulate the enhanced disease resistance of Arabidopsis ‘defense, no death’ mutants.” Mol Plant Microbe Interact. 21, 1285–96.

5. Klessig DF, Durner J, Noad R, Navarre DA, Wendehenne D, Kumar D, Zhou JM, Shah J, Zhang S, Kachroo P, Trifa Y, Pontier D, Lam E, Silva H. 2000. “Nitric oxide and salicylic acid signaling in plant defense.” Proc Natl Acad Sci USA. 97, 8849–8855.

6. Ma W, Berkowitz GA. 2007. “The grateful dead: calcium and cell death in plant innate immunity.” Cell Microbiol. 9, 2571–85.

7. Gechev TS, Van Breusegem F, Stone JM, Denev I, Laloi C. 2006. “Reactive oxygen species as signals that modulate plant stress responses and programmed cell death.” Bioessays. 28, 1091–101.

8. Asai S, Yoshioka H. 2009. “Nitric oxide as a partner of reactive oxygen species participates in disease resistance to nectrotophic pathogen Botryis cinerea in Nicotiana benthamiana.” Mol Plant Microbe Interact. 22, 619–29.

9. Beckers GJ, Spoel SH. 2006. “Fine-Tuning Plant Defence Signalling: Salicylate versus Jasmonate.” Plant Biol (Stuttg). 8, 1–10.

10. Spoel SH, Johnson JS, Dong X. 2007. “Regulation of tradeoffs between plant defenses against pathogens with different lifestyles.” Proc Natl Acad Sci USA. 104, 18842–7.

11. Bouchez O, Huard C, Lorrain S, Roby D, Balagué C. 2007. “Ethylene is one of the key elements for cell death and defense response control in the Arabidopsis lesion mimic mutant vad1.” Plant Physiol. 145, 465–77.

12. Ficke A, Gadoury DM, Seem RC, Godfrey D, Dry IB. 2004. “Host Barriers and Responses to Uncinula necator in Developing Grape Berries.” Phytopathology. 94, 438–45.

13. Liu PP, Bhattacharjee S, Klessig DF, Moffett P. 2010. “Systemic acquired resistance is induced by R gene-mediated responses independent of cell death.” Mol Plant Pathol. 11, 155–60.

14. Durrant WE, Dong X. 2004. “Systemic acquired resistance.” Annu Rev Phytopathol. 42, 185–209.

“… there is a stable order in the world as well as a well-established connection, constant norms and fundamental laws. In this sense, the world is analogous to a clock or a well-designed machine. Every single wheel, every single screw, every single nail not only has a role in order of a machine and an impact in its final benefit but also positive consequences for all living beings, especially for humans.” (Signs of Miraculousness, Seven Heavens, p. 186)

There is a strong parallel between the general principles to be observed for a healthy social structure in a society and the necessary conditions that enable cells to make up a healthy tissue. The laws prevalent in the universe present amazing parallels since they derive from the same divine source. In order to have healthy development in societies, it is necessary to have healthy connections, reciprocal understanding, and correct information transfer between people. Similarly, having healthy cells, which can be considered as micro-societies, also depends on the cells’ continual use of complex signal connection networks and their maintenance of connections with their environments. In order to maintain a harmonious and healthy life in the cell, there must be dense information transfer (through chemical molecules) at all levels with neighbor cells. Thanks to the connection networks that start at their membranes, cells can recognize warnings coming to them and produce responses. Through such information networks, a continuous connection is established in living organisms, starting from their lowest level mechanisms (i.e. molecules in cells and organelles) to their highest level mechanisms (i.e. organs, systems, organisms, populations, ecosystems), in order to ensure a healthy and harmonious processes of development, reproduction, differentiation and aging. Organized as a tissue (micro-society), one of the most amazing features of cells is the way they behave in accord with the society they live in, rather than acting as individualistic beings. Cells behave in a way to make micro-societies possible. In cytology (study of cells), this feature is known as “contact inhibition” (i.e. maintenance of healthy and harmonious operation and development that is based on connection), and its damage may lead to cancer. Every cell is sensitively programmed to receive all signals, coming from inside and outside, and to manage the proper responses to them. Here, the question arises whether a lack or disorder of connection is caused by pathological conditions in cells or whether the emergence of pathological conditions is caused by connection problems. It is generally assumed that, molecular changes in the cell occur first (i.e. mutation) and then this mutation leads to abnormalities and connection problems at the levels of tissue, organ, and even organism. Damage to communication or connection and disorders in this system are a very important reason for the appearance of some pathological conditions (such as an abnormal increase of cells, cancer and death). Thus, diagnosis and treatment of many diseases today depends on knowledge of how biological communication and connection are harmoniously established.

Cells are designed to control their behavior through special signal molecules that can themselves function as stimulatory. For instance, using signal molecules, cells can establish colonies or biofilms. Moreover, plant cells, through channels known as plasmodesmata, maintain their connection with neighboring cells and trade certain materials. In the state of illness, the density (among cells) of signal molecules that are transferred in the plasmodesmata changes.

Hormones, reproduction factors and neurotransmitters are charged with ensuring transportation and communication at different levels. Cell and tissue elasticity and their adaptability are increased by this diversity in signal operations. Different ways are used to transmit signals into the cell depending upon the characteristics of the signals. For example, hydrophobic (water-avoiding) molecules like steroid hormone pass directly through the cell membrane and connect to their receptors in the cell. The receptors that are responsible for decoding genes stimulate the decoding of related genes. If a problem (mutation) occurs in the molecules that are responsible for transportation and communication, the transportation and communication breaks down and the cancer process is triggered. The existence of continuously reproducing cells in inappropriate times and places is an important symptom of cancer initiation. For example, in colon and rectum cancer, if a mutation occurs on the Ras protein, which is one of the signal proteins that takes the “Reproduce!” message from the cell membrane the cutting off of the GTP molecule, which is responsible for turning the signal molecule on and off, is blocked, and since the molecule stays permanently active a signal like “Reproduce!” is permanently sent inside the cell. Thus, the benefits of the medicines that are used in cancer treatment and that show their effects by hindering signals on the cell membrane level are observed in the non-existence of this mutation on Ras proteins. If the mutation happens the medicines mentioned above cannot be effective. Today, the presence of the mutation can be determined by a biopsy taken from the patient, thus, it has become possible to choose the type of therapy that will be most helpful to that person.

Communication inside the cell can be carried out through ion channels (such as sodium, potassium, and calcium). These channels in membrane behave selectively for every different ion. For example, while voltage-gated channels open and close according to electric charge ligand, (key)-gated (receptor) channels let ions transfer when ligands are tied up. Sodium and potassium ions and the molecular channels that these two passes are responsible for organizing the changes that effect the communication of nerves in the membrane potential. The calcium channel, on the other hand, plays an important role in muscle contraction, and biological incidents like the formation and deformation of bone.

In recent years, the proteins (matrix) that fill the vacancies among cells have been shown to be the main actor in the general control of communication between cells and in the integration of signals coming from their surroundings by hundreds of proofs. It has been pointed out that CCN proteins, which are one of the adaptors, as well as proteins with multiple modules that are responsible for the connection between cell membranes and matrix proteins have a regulatory role at different levels in the control of signal transfers in ion channels, cell differentiation, adherence of cells to each other, cell collapse, programmed cell-death, cartilage formation and the synthesis of new veins. The multi-dimensional and dynamic communication and connections mentioned above related to cells also apply to people. When individuals develop a healthy connection between their inner world and other people, a healthy society emerges. Every individual is granted these potential connection points, which make the existence of an individual possible. The development of a healthy person depends upon activating these connections, organizing them dynamically and keeping them active.

If we place human beings at the center of creation, the first connection that the individuals should make between their Creator and their ego (nafs) is called worship. The ego is both a help and a hindrance to the construction of this connection. The second connection, which is between individuals and their friends, is ensured by good morals, good conduct, and personal virtue. The construction of a healthy social life depends on how many people have good morals, good conduct and virtuous character in a society. If virtue is not accompanied by knowledge, it is highly unlikely that knowledge will raise an individual to a standard of human perfection.

The third essential, the individual’s healthy connection with their surroundings is established through the “ecological dimension of ego,” which is sensitive to the external world. It is very difficult for people whose dimension of ego, which is sensitive to ecological problems and the environment, has not developed to keep the environment clean and take precautions against pollution. The fourth connection that individuals should establish is the connection with their internal world (heart-consciousness, transcendental ego, real self). “O Man! Know yourself first!” and, “The one that knows himself knows his God,” are expressions pointing out the importance of this connection.

For individuals, groups, and societies to have a healthy life as well as to maintain their health at all levels depends on activating these four connections, in other words, establishing coordination and harmony among them and then maintaining this state. When one ignores one of the connections or some of them, or when the coordination between these connections is defective, troubles and illnesses at various levels emerge. Hence, the links that a healthy individual establishes may include those in civil society organizations, and through these further networked and reciprocal communications. Like our cells, which maintain their connection with their environment and neighboring cells via the “contact inhibition” mechanism so that we feel healthy, for people to become healthy at personal and societal level, individuals should actively join civil society organizations and service-centered communities that can enable activation of these four connections and ensure harmony and coordination among them. The Islamic scholar, Bediüzzaman Said Nursi paid special attention to connection in the letters he wrote to his students (the Kastamonu letters) and highlighted it as a point of progress that should be reached:

Since, in today’s world, saving people’s belief for the sake of God is a very important mission that is above everything; since quantity is not very significant compared to quality; since transient and changing political worlds are trivial compared to everlasting, constant, stable services in the name of God-they should not be even compared; they can never be objectives; therefore, we should be satisfied with valuable positions that are granted in the circle of Risale-i Nur. Instead of having extremely well-thoughts about other people or seeing them at high positions superfluously, we need to have extreme loyalty and steadfastness, and utmost connection and sincerity. We should have progress on these points.

Hamza Aydin has a PhD in bio-medicine. He is a freelance writer from Izmir, Turkey.