Truffles are potato-shaped underground mushrooms that grow in all kinds of different environments ranging from high-rise forests of pine, oak, linden, fir and wild hazelnut to scrubs, under bushes, and in steppes and deserts. They maintain a symbiotic relationship by attaching to the roots of certain herbaceous plants and have a unique aroma with a sharp odor. Some cultures nickname truffles as bingos or buckthorns. There is also the belief that the mushrooms sprout faster under lightning or thunder thus earning them the nickname “daughters of thunder.”

Symbiotic association between truffles and plants

Nature thrives in a harmony that is based upon assistance and solidarity. Truffles have a special place in this harmony. For example, as plant seeds germinate and begin to grow into roots, the hyphae of truffles wrap around the plant roots, just like a glove does around fingers, and help the emergence of a special structure called “mycorrhiza” which facilitates food exchange between truffles and plants. Approximately 90% of plants coexist with different types of mushrooms, and some plants even need truffles to survive. Unable to photosynthesize, truffles need plants for organic nutrients, and plants need truffles, especially for the intake of more water and minerals from barren and arid soil.

It is estimated that the mushroom hyphae can be as long as 1 km in the forest soil is estimated to be more than 1 km. Truffles help to increase the contact surface of the tree roots with the soil hundreds of times while ingesting the water and minerals from remote areas where plant roots cannot reach. In this way, as soon as a drop of rain falls on the soil, it is relayed to the benefit of plants with hyphae that are invisibly thin and kilometers long. If this partnership did not exist between truffles and plants then the giant trees that we see in forests would not be able to grow tall enough and would possibly remain as bushes due to a lack of water and minerals from the soil.

Truffles and wildlife

A similar relationship exists between truffles and animals in the forest. Since they are generally active at night and cannot benefit from sunlight sufficiently, wild animals meet their vitamin D needs especially from truffles, an important food source. Recent studies show that some wild animal species survive solely on truffles. A large number of mice, squirrels, bears, deer, rabbits, hedgehogs, and bird species in the US eat truffles along with some monkeys, kangaroos, and bird species in Australia.

While the toadstools in the open can spread their billions of spores to the environment, the spores of underground mushrooms remain confined in their tissues. It is thanks to animals that can spot and extract the mushrooms that these spores spread from their tissues into the rest of the environment. Wild animals can locate, dig up, and eat underground truffles due to the strong and attractive aroma of the mushrooms. On the other hand, the spores that are expelled from the animals’ digestive systems lead to the production of fresh hyphae to partner with new plants via germination. This allows underground mushrooms to have the opportunity to sustain their generation and expand their natural habitat.

The conservation of animal species that face extinction also depends on the preservation of the variety of truffle species. From this point of view, truffles in the natural habitats are the sustenance of wild animals. Bediuzzaman Said Nursi (d. 1960), a renown Turkish religious scholar, said: “Our share is in vineyards and gardens. God Almighty allocated our sustenance there. These wild fruits are the sustenance for the wild animals. We should not touch their portion.” It is also known that Bediuzzaman discouraged his students who came across plenty of apple and pear trees on the mountains from eating those fruits. This approach also sums up a guiding insight about sustainable forestry and ecosystem.

Nutritional value and medical benefits

Truffles are richer in protein and minerals than other mushrooms. Their nutritional value consists of 53-76% water, 9% protein, 7% carbohydrates, and 8% minerals. Although they have high nutritional value, the most important feature making truffles superior to other mushrooms is their distinctive aromatic compounds. Due to their unique aroma, truffles attract the attention of many gourmets. It is no surprise that truffles have an exceptional place in exclusive cuisines.

Since ancient times, the medical benefits of truffles have been frequently reported. For example, Ibn Sina (Avicenna) is known to have recommended truffles for healing weakness, nausea, pain, and wounds.

Prophet Muhammad, peace be upon him, said, “Truffle is a sustenance like manna. Its sap is also a cure for the eyes.”

The belief in the nutritional value of truffles is also common in the Christian world. Between 827 and 844, Pope Gregory IV had advised the consumption of truffles to gain strength in battles.

Current studies have found that truffles contain several compounds that are essential for human health. A study published in 2016 is an important step for chronicling the fact that the extract obtained from truffle mushrooms proved to be useful in healing eye infections.

Economic value

The number of commercial-value truffles collected from natural habitats constantly decreases worldwide: it has dropped from 2000 tons in 1884 to 100 tons in 1990. Today, it is around 40 tons. The main factors of this decline are the destruction of oak forests, climate change, environmental pollution, global warming, and uncontrolled picking.

Despite the dramatic decrease in the number of truffles collected from natural habitats, they are sold between $250 and $4,000 per kilo depending on the type and quality.

Growing truffles

Under current conditions, truffles have to be grown by special means. People must grow the types of truffles that they wish to consume.

The first idea for the production of truffles came from a French farmer named Joseph Talon. At the beginning of the 19th century, Talon planted fresh seeds in the oak patches where truffles grew naturally. The existing truffle hyphae in the soil infiltrated the roots of new oak saplings and led to an increase in the production of truffles in the natural habitat. In the following years, Talon created new truffle production areas by planting the saplings he had already produced in other patches. Talon’s method is still used today.

In the 1960s, a period when there was a great decrease in the production of truffles in natural habitats, studies were conducted to find new methods. The methods developed by French and Italian scientists in the 1970s led to a massive success in truffle production. Truffle spores were inoculated at the root of oak saplings and plants were grown in greenhouses to develop only the desired truffle mycorrhizal system in tree roots. Having ensured that mycorrhiza had settled in the roots, the first truffle began to be harvested four or five years after planting the oak saplings in open areas. These methods have allowed truffle production in countries such as Australia, the USA, and New Zealand where truffles are not grown naturally.

Commercial truffle types

It is estimated that there are about 10,000 different types of truffles in the world with different sizes, colors, structures, and aromas. These mushrooms, which are now listed in restaurant menus and stocked on the shelves of luxury food suppliers, are only some of the truffles numbered in thousands.

Some of the commercial types are listed below:

Tuber magnatum: Known as the white truffle of Italy, it grows in the Alba region as attached on the roots of oak, hornbeam, pine and poplar trees. It is different from all species by its peculiarly pungent aroma. It is known as the most expensive food in the world because it grows in a very limited area and cannot be grown as a cultivated mushroom.

Tuber melanosporum: Known as the winter black truffle, it grows during winter by attaching to the roots of oak, hazelnut, and pine trees in Italy, France, Spain, and the Balkans. It has a distinctive aroma and has a wider growth area as compared to the white truffle. It is the most cultivated type of truffle in different continents of the world.

Tuber aestivum: Known as the summer black truffle, it grows by attaching to the roots of oak, nut, and pine trees in a wide geography spanning from Portugal to Azerbaijan, Morocco to Poland, and Sweden to Afghanistan. It bears lower economic value because it is widely grown and has an easily extracted culture and a lower-density aroma.

Terfezia claveryi: It grows in the spring across steppes and deserts by attaching onto the roots of herbaceous plant species belonging to the genus Helianthemum. It has a unique aroma and has a huge market in the Arab countries. Its culture has started to be extracted in recent years.

Oregon truffle: It grows in winter as attached on the roots of fir trees in Oregon, Washington, and Vancouver. It has white and black types. It has an important market in the U.S despite not being as valuable as the black and white species found in Europe. No results have been obtained from cultural studies yet.

Harvest of truffle

Picking truffles is like picking apples from a tree with the difference that truffles are collected from the root of the tree. It is difficult to understand whether the truffle underground has ripened or not. If the extracted truffle is not ripe enough then its economic value immediately suffers. That is why special dogs are bred to locate truffles. Sensitive to the truffle aroma, these dogs lead their owners by simply pointing out to the places where ripe truffles are found. These dogs are motivated by rewards and are encouraged with better rewards for finding higher quality, larger, and more ripe truffles.

References

• Alhussaini S.M., Saadabi A.M., Hashim K., Al-Ghanayem A.A. (2016). Efficacy of the Desert Truffle Terfezia claveryi to Cure Trachoma Disease with Special Emphasis on Its Antibacterial Bioactivity, Trends in Medical Research, doi: 10.3923/tmr.2016.28.342016, Volume: 11, Issue: 1, pp. 28–34.
• Bukhari, 5708; Muslim, 2049; Abu Dawood, Tibb, 12; Ibn Majah, Tibb, 8.
• Hall I.R., Brown G., Zambonelli A. (2008). Taming the Truffle: The History, Lore, and Science of the Ultimate Mushroom, Timber Press.
• Sahiner Necmeddin, Son Sahitler, Istanbul: Nesil Yayinlari, 2011, Volume 1, pp. 113.
• Trappe M, Claridge AW (2010). “The Hidden Life of Truffles”. Scientific American. April 2010: 78–84.
• Wedén C. (2008). Tryffel. Infotain &Infobooks Sweden AB, Stockholm.

Biggest extinction in Earth’s history caused by global warming—and how it could happen again

Penn JL et al. Temperature-dependent hypoxia explains biogeography and severity of end-Permian marine mass extinction. Science, December 2018.

Some 252 million years ago, long before dinosaurs, the vast majority of species on Earth were wiped out in the “Great Dying,” the worst mass extinction in our planet’s history. Up to 96% of all marine species and 70% of land animals were killed off during this event. Scientists have been trying to find the cause for this catastrophic event, which marked the end of the Permian period. One study suggested that a type of microbe spouted large amounts of methane into the atmosphere. Other studies suggested the event was triggered by a series of volcanic eruptions that released deadly amount of carbon dioxide into the air and led to cataclysmic ocean acidification. A new research study now claims that the Great Dying was primarily as a result of rapidly increasing temperatures. The researchers examined the marine fossil records and simulated the climate conditions to observe the effects of rising temperatures 252 million years ago. Researchers first ran a climate model with Earth’s configuration during the Permian period, when the tropical ocean temperatures at the surface had reached some 10 degrees Celsius (50 degrees Fahrenheit) higher. The model then reproduced dramatic changes in the oceans; oceans lost about 80 percent of their oxygen and about half the oceans’ seafloor became completely oxygen-free. To investigate the effects of these paleoclimate changes on marine species, the researchers then analyzed the varying oxygen and temperature sensitivities of 61 modern marine species including crustaceans, fish, shellfish, corals and sharks. Their calculations predicted that many marine organisms went extinct under these conditions, especially the organisms that lived far from the tropics were most sensitive to oxygen levels and they were nearly completely wiped out. To test this prediction, researchers analyzed late-Permian fossil distributions from the Paleoceanography Database and confirmed that species far from the equator suffered most during the event. The agreement between the simulations and fossils strongly suggests that climate warming and oxygen loss was a primary cause of the extinction. By 2100, warming in the upper ocean is projected to approach 20 percent of warming in the late Permian, and by the year 2300 it will reach between 35 and 50 percent. This study highlights the potential for a mass extinction arising from a similar mechanism under anthropogenic climate change. It is also a clear warning that Earth is on the path to another devastating mass extinction. According to experts, Earth could already be undergoing a sixth mass extinction that would kill off most animal and plant species. The International Union for the Conservation of Nature predicts that 99.9% of critically endangered species and 67% of endangered species will be lost within the next 100 years.

New target for therapeutic brain stimulation to treat depression found

Rao VR et al. Direct Electrical Stimulation of Lateral Orbitofrontal Cortex Acutely Improves Mood in Individuals with Symptoms of Depression. Current Biology, November 2018.

Researchers have finally found an effective target in the brain for electrical stimulation to improve mood in people suffering from depression. Stimulation of a brain region called the lateral orbitofrontal cortex (OFC) reliably produced acute improvement in mood in patients who suffered from depression. In a recent study, researchers studied 25 patients with epilepsy who had electrodes placed in the brain for medical reasons to locate the origin of their seizures. Many of those patients also suffered from depression, which is often comorbid with epilepsy. With the patients’ consent, researchers took advantage of those electrodes to deliver small electrical pulses to areas of the brain thought to be involved in regulating mood. The researchers focused their attention and the electrical stimulation on the OFC, which is a key hub for mood-related circuitry. Moreover, they specifically induced a pattern of activity in brain regions connected to OFC that was similar to patterns seen when patients naturally experienced positive mood states. The researchers applied these stimulation regimes while collecting verbal mood reports and questionnaire scores. Analyses of these reports revealed that unilateral stimulation of the lateral OFC produced acute, dose-dependent mood-state improvement in subjects with moderate-to-severe baseline depression. There is still substantial work remains to be completed before the deep brain stimulation (DBS) treatments could enter routine clinical practice. One major challenge in this study is to see whether stimulation of OFC produces durable improvement in mood over longer periods of time. Biomedical engineers hope to develop a medical device for patients with treatment-resistant mood disorders that can monitor brain activity in OFC and stimulate only when needed to keep that activity within a healthy range. Ultimately, it would be ideal if activity in mood-related brain circuits could be normalized indefinitely without patients needing to do anything.

How screen time can disrupt sleep

Mure LS et al. Sustained Melanopsin Photoresponse Is Supported by Specific Roles of β-Arrestin 1 and 2 in Deactivation and Regeneration of Photopigment. Cell Reports, 2018

For most of us, the time spent staring at screens on computers, phones and tablets adds up to many hours in a day and can often disrupt sleep. In a recent work, researchers now have pinpointed how certain cells in the eye process ambient light and reset our internal clocks, the daily cycles of physiological processes known as the circadian rhythm. When these cells are exposed to artificial light late into the night, our internal clocks can get confused, resulting in a host of health issues. A protein called melanopsin in these light-sensitive cells helps them process ambient light. Prolonged exposure to light causes melanopsin to regenerate and continuous regeneration of melanopsin triggers signals to the brain that inform it about ambient light conditions. The brain then uses this information to regulate sleep, alertness, and consciousness. In this study, the researchers turned on the production of melanopsin in retinal cells in mice and found that some of these cells are able to sustain light responses, but others lose sensitivity. Further investigations found that proteins called beta arrestin-1 and beta arrestin-2 help keep the melanopsin sensitive when exposed to light. One arrestin does its conventional job of arresting the response, and the other helps the melanopsin protein reload its retinal light-sensing co-factor. When these two steps are done in quick succession, the cell appears to respond continuously to light. This research uncovers the mechanisms behind how cells being exposed to artificial light confuses the internal body clock, and the ability to regulate sleep. It is hoped that this discovery could lead to new targets that could counter the impact of artificial light, for example by finding ways to influence melanopsin to reset the internal clock. This could lead to new treatments for insomnia, jet lag, and migraines.

We live in a magnificent world inhabited by approximately 8,700,000 species. This number includes only general species, not subspecies. Scientists discover around 2,500 new species every year, and the number is soon estimated to reach 10 million.

All living organisms are blessed with unique bodies, systems, and organs, defense and protection mechanisms to survive and protect themselves, and special features to help them forage for food.

When people get ill due to environmental effects or malnutrition they usually consult a doctor. They try to find a cure by using the medicine prescribed by doctors. However, animals living in the wild don’t have this option. When animals living in nature or on the street get ill what can they do if nobody takes them to a vet? How do millions of species get well and find cures for their ailments?

You might think that animals who become sick in the wild must simply live with their symptoms, but this is not the case. In fact, we have given a clue at the introduction: each organism is equipped with features to lead a self-sustaining life. Either their bodily functions perfectly enable them to live in their habitat or their unique metabolisms protect them from harmful external factors. Animals also can use some plants whose health benefits have only recently been discovered by humans.

In recent decades, there has been a growing interest for herbal products such as walnut leaf, cherry stalk tangerine rind, grenadine red, and celery root to find cure for diseases.

Animals perform amazing tasks with mind-blowing adroitness as if each were an expert chemist. Wondrous mechanisms are activated when a need arises to protect animals from harm.

Some plants with healing properties:

Lupine, quassia, bitter wood, hemlock, fishberry, roselle, henbane, giant fennel root, pistachio, resin, pine turpentine, mistletoe, cumin, hibiscus, hibiscus flower, alkanet, flos elaeagni, camphor, cardamom, St John’s wort, French lavender, Flaxseed, linseed oil, henna tree, quillaia, wall germander, cranberry, aspand, daffodil, water lily, common balm and eucalyptus.

Animals have been consuming and finding cures in these plants since the dawn of time. They are also equipped with many surviving capabilities under extremely severe conditions. Here are a few examples:

Antibiotics expert

With a height of up to five meters, the giraffe is the tallest land animal. Scientists who investigated the scent emitted by the giraffe found 11 separate chemical substances in its fur. The chemicals turned out to have antibiotic properties, having an increased efficiency when combined. Only after a series of experiments can these incredibly complex chemicals be extracted in the laboratory. The giraffe has been using these chemicals to prevent fungi and bacteria, repel ticks, and stop the growth of germs. Where did these tall creatures study chemistry to know how to produce antibiotics such as indole?

The stubborn doctor

The bezoar ibex is a type of mountain goat native to Turkey, Iran, Turkmenistan and Pakistan. It has a motley coat of black, brown, grey, reddish-gold, and white. Both the male and female have horns and a goatee. The name means “cure” in Persian, and the locals must have noticed its habit of eating spurge whenever bitten by a snake. Scientists have identified the substance called euphorbone in the spurge plant. Amazingly, an analysis of this substance reveals that certain chemical reactions triggered by euphorbone neutralize the effects of venom. The poisoned creature looks for splurge from among the vegetation, self-medicates, and treats itself free of charge. It sure is no wonder when one realizes that the goat, the snake, and the plant are all created by the same hand.

The master of diving

Divers who ascend too quickly to the surface run the high risk of experiencing the bends, an intense pain that is likely to kill because of the gasses coming out of the bloodstream. But how do billions of creatures that lack oxygen tubes lead their entire lives in the sea without experiencing the bends?

Dolphins and whales, for example, descend to depths humans can’t reach on their own and then rise like it is no big deal. Human lungs cannot endure the pressure under such depths, but the bronchi and air sacs in the lungs of dolphins, however, are placed inside a protective cover of special cartilage. To avoid suffering the bends, dolphins release all the air in their lungs before diving deep. But how then do they breathe? The answer is hidden in their muscles, or rather in the myoglobin protein that is available in much higher amounts than in humans. These proteins have the ability to hold in high amounts of oxygen molecules. The much needed oxygen is provided from this source, enabling dolphins and whales to dive as deep as possible.

Poison for one, food for another

The macaw is an inhabitant of American tropical regions with an average wing span of 80 cm. It is known to be a tough creature that lives as long as 60 years. The macaw feeds on plants that produce a chemical called strychnine (C₂₁H₂₂N₂O₂), a powerful poison intended to ward off enemies. How can a substance that kills some living things nourish others? Immediately after eating the nutritious but poisonous seeds, the macaw flies to the rocky cliffs in a certain area. When they get there, they gnaw at and swallow some clay-based rock pieces. The fact that the bird ingests clay without any apparent reason is quite an interesting behavior. The reason was revealed only after research into the origins of the behavior. It turns out that the rocks that have clay in them include a substance called kaolinite (Al₂O₃.2SiO₂.2H₂O) that can absorb the poison in the seeds. The macaw can digest the normally poisonous seeds thanks to this absorption and live on with its life safely. There is no way the macaw can know about the substances present in the clay, so how does it know to eat the clay that can eliminate toxins?

The antifreeze expert

The arctic beetle survives against the inhospitable cold of the arctic thanks to a type of alcohol produced in its body that works as antifreeze. The glycerol (C₃H₈O₃), also called glycerin, produced by the insect prevents the blood and other fluid molecules from freezing and thus ice crystals from killing the cells and destroying cellular bonds. Furthermore, the shorter the days and the colder the weather, the more resistant the bodily mechanisms of the arctic beetle become. As the temperature drops, the volume of water in their body is reduced and antifreeze substances such as glycerol and sorbitol are produced in greater amounts. Research on this amazing creature has revealed that it can survive in temperatures as low as -87 degrees Celsius due to glycerol. It is beyond reason to expect an insect to know how to produce an organic compound with the complex formula of C₃H₈O₃ and thus protect itself from extreme cold.

The radiation expert

Scientists analyzed a surviving scorpion after an atomic bomb test, yet they couldn’t find a satisfying answer to how this animal survived the radiation shower that exterminated all other living organisms. Note that scorpions which came into existence millions of years ago are basically living fossils. Thanks to the protective system they are blessed with, in the past they have survived more powerful solar explosions and harmful radiation from outer space and the sun, and handed down these features to future generations.

The creature that never feels cold

The tardigrade, or water bear, is one of the most resistant organisms in nature.

The size of a pinhead, these microorganisms have pin-shaped hoses in their mouth.  These microorganisms have a brain, a pair of eyes, and a digestion system, but they do not have a heart or lungs.  600 different subspecies of the animal have been discovered so far. They feed mostly on moss and lichens and can survive in any environment including space.

They have been observed to survive a temperature of 120 ⁰C and a pressure of 1000 atm. In dry environments they contract, causing the water in their tissues to evaporate. During this process, the oxygen consumption of the tardigrade virtually stops. The wind carries the dried tardigrades to other places and when they find a suitable environment (wet moss or humid places) they can come back to life again.

According to Ingemar Jönsson from Kristianstadt University in Sweden who participated in studies on this organism, it is a mystery how these animals survive even when they are subjected to conditions in outer space.

Animals perform amazing tasks with mind-blowing adroitness as if each were an expert chemist. Wondrous mechanisms are activated when a need arises to protect animals from harm. It is wondrous to see how animals can carry out these complex chemical procedures as if they have been instructed at birth.

You need to read “The Very Lonely Firefly,” a story book delighting children of all ages by Eric Carle (1) to get the answer. In the mean time, you can read this article to have better insight into the enchanting world of the firefly. Are they just a pleasure to our eyes, during their short lives in the summer, or do they live on in children’s books?

Fireflies, or lightning bugs, belong to the Lampyridae family. There are thousands of firefly species all over the world and none of them are actually flies. Then what are they? Well, they are beetles, who get the names “firefly” and “lightning bug” because of the flashes of light emanating from their bodies, a process called bioluminescence (2). This “cold light” does not heat up or burn its producer through infrared or ultraviolet frequencies, and is formed by the action of an enzyme called luciferase in the lower abdomen of the firefly. It may be yellow, green, or pale red, with wavelengths from 510 to 670 nanometers. The enzyme luciferase acts on the luciferin, in the presence of magnesium ions, ATP, and oxygen to produce light (3). According to Vieira et al., 2012, in the Journal of Photochemistry and Photobiology, the firefly’s luciferase is the most important and studied bioluminescence system in scientific research(4). The firefly luciferase was cloned and isolated for the purpose of constructing bioassay systems in the late 1980s (5). Since then, due to very interesting characteristics, this system has been used in numerous biomedical, pharmaceutical and bioanalytical applications (4).

In biomedical research, the ability to visualize a biological process is very important because it offers the most direct method to support or disprove any scientific claim (6). Therefore, firefly luciferase is very desirable as a reporter in this area. Typically, the luciferase gene is cloned with a DNA sequence of interest into cells and then the cells are assayed by measuring its bioluminescence. Fusing a protein with luciferase is like putting a reflective vest on a cyclist in the dark to be able to watch him. Because the firefly luciferase lights up, it helps screening for chemical biology and drug discovery applications in academia and the pharmaceutical industry (5). For example, the firefly luciferase gene was used as a reporter to screen tumor-specific promoters in lung cancer (7). Another example showing how beneficial the firefly is for scientific research is a rapid in vivo (Latin for within the living) assessment of drug efficacy against Mycobacterium tuberculosis, which is the causative agent of most cases of tuberculosis, using an improved firefly luciferase (8). In this study, Andreu et al., 2013, used a Mycobacterium tuberculosis strain carrying a red-shifted derivative of the firefly luciferase gene to infect mice, and they monitored disease progression in living animals by bioluminescence imaging before and after treatment with a frontline anti-tuberculosis drug. Furthermore, firefly luciferase was used in a research about anti-malaria drugs, an illness which affects about 5% of the world’s population and brings a death toll of 0.5–2.5 million each year (9).

Firefly luciferase is not only used in biomedical research, but also in molecular plant biology. In the early ’90s, plant scientists were already able to show the bioluminescence of a promoter fragment fused to the firefly luciferase gene and its regulation by phytochrome (a pigment that plants use to detect light) and the circadian clock (a roughly 24 hour cycle in the physiological processes of living beings) (10) in plants. Some examples for the great usage of this system among many others include a firefly luciferase complementation assay that was used to reveal the interacting partners of Open Stomata 1 protein, which is critical for plant drought responses in Brassica oleracea (cabbage) (11) and the characterization of the promoter region of an important gene encoding a copper chaperone for the copper/zinc superoxide dismutase that is involved in oxidative stress protection of the potato plant (12).

Scientists have found many ways to use the firefly light, but what is the function of it for its real owner? Marc Branham, an assistant professor in the department of entomology and nematology at the University of Florida, explains. “Fireflies seem to flash light for a variety of reasons. The larvae produce short glows and are primarily active at night, even though many species are subterranean (underground) or semi-aquatic. Fireflies produce defensive steroids in their bodies that make them unpalatable to predators. Larvae use their glows as warning displays to communicate their distastefulness. As adults, many fireflies have flash patterns distinctive to their species and use them to identify other members of their species as well as to discriminate between members of the opposite sex. Several studies have shown that female fireflies choose mates depending upon specific male flash pattern characteristics. Higher male flash rates, as well as increased flash intensity, have been shown to be more attractive to females in two different firefly species (13).”

Are there other creatures like fireflies producing light? “Besides fireflies, many other organisms, especially marine creatures, use bioluminescence for sexual selection, attracting prey and as a means of camouflage, and it has been estimated that about 90 percent of deep-sea animals are bioluminescent, according to the Scripps Institution of Oceanography,” says Remy Melina, a staff writer for “Life’s Little Mysteries.”(14)

A firefly’s glow is a theme of summer nights, romantic poems, and childhood adventures and books. However, when you enjoy a firework show done by fireflies next time, please look at them more carefully by thinking that they have more than that to offer humanity, including thrilling scientific inventions done with just a single protein from them. Who knows what else they have waiting to be discovered by us? How amazing it is that, like everything else created on earth, a firefly is also a very precious art piece decorated with intricate features, and even though it is very tiny, its service to humanity is, in many ways, enormous.

References

http://www.barnesandnoble.com/sample/read/9780399227745
National Wildlife Federation
http://en.wikipedia.org/wiki/Firefly
Vieira J, Pinto da Silva L, Esteves da Silva JC (2012) Advances in the knowledge of light emission by firefly luciferin and oxyluciferin. J Photochem Photobiol B. 117:33-9.
Thorne N, Inglese J, Auld DS (2010) Illuminating insights into firefly luciferase and other bioluminescent reporters used in chemical biology. Chem Biol. 17(6):646-57>
Brogan J, Li F, Li W, He Z, Huang Q, Li CY (2012) Imaging molecular pathways: reporter genes Radiat Res. 177(4):508-13.
Xu R, Guo LJ, Xin J, Li WM, Gao Y, Zheng YX, Guo YH, Lin YJ, Xie YH, Wu YQ, Xu RA (2013) Luciferase assay to screen tumour-specific promoters in lung cancer.Asian Pac J Cancer Prev. 14(11):6557-62.
Andreu N, Zelmer A, Sampson SL, Ikeh M, Bancroft GJ, Schaible UE, Wiles S, Robertson BD (2013) Rapid in vivo assessment of drug efficacy against Mycobacterium tuberculosis using an improved firefly luciferase. J Antimicrob Chemother. 68(9):2118-27.
Che P, Cui L, Kutsch O, Cui L, Li Q (2012) Validating a firefly luciferase-based high-throughput screening assay for antimalarial drug discovery. Assay Drug Dev Technol. 10(1):61-8.
Millar AJ, Short SR, Chua NH, Kay SA (1992) A novel circadian phenotype based on firefly luciferase expression in transgenic plants. Plant Cell.4(9):1075-87.
Wang M, Yuan F, Hao H, Zhang Y, Zhao H, Guo A, Hu J, Zhou X, Xie CG (2013) BolOST1, an ortholog of Open Stomata 1 with alternative splicing products in Brassica oleracea, positively modulates drought responses in plants. Biochem Biophys Res Commun. 442(3-4):214-20.
Trindade LM, Horvath BM, Bergervoet MJ, Visser RG (2003) Isolation of a gene encoding a copper chaperone for the copper/zinc superoxide dismutase and characterization of its promoter in potato. Plant Physiol. 133(2):618-29.
http://www.scientificamerican.com/article/how-and-why-do-fireflies/
http://www.livescience.com/32677-what-makes-fireflies-light-up.html

The answer was interesting and had deep meanings, but still left questions in my mind. The creatures were told: a new species will be created and arrive soon, and each member of this species will be equivalent and worthy of a whole species.

Those who asked the question were silent, suggesting they were satisfied with the answer. But I wondered how a single member of a species can be worth an entire species – and whether destroying a whole species for a new one can really be just.

Here, it was obvious to me that the new species that would be created is humans, and those condemned were the species who went extinct in ancient times, before humanity appeared on earth. This dream vaguely reminded me something that I read in the “Risale-i Nur Collection” by Bediuzzaman Said Nursi.

Bediuzzaman remarkably states that, “A human being is equivalent to a species of other creatures” (Zuhra – 4th point, Isharat al-I’jaz, and Mathnawi al-Nuriya). This line hadn’t really struck me until I had the dream about older creatures questioning this wisdom.

In this dream, those creatures were dinosaurs. I was not scared; they weren’t threatening with their question. They were fighting for their rights and trying to understand the glorious plan, and beyond.

It seemed to me a lovely coincidence that I had a visit to Washington coming up soon and had a chance to visit the National Museum of Natural History, where you can see well preserved remnants of various dinosaurs.

All of the dinosaurs went extinct long before the first human showed up. Dinos first walked on earth over 200 million years ago and dominated the earth until 66 million years ago. Their dominion on earth ended with the Cretaceous–Paleogene extinction. According to fossil records, there were more than 1000 dinosaur species. Dinosaurs had different habits of eating, as some were herbivorous (plant-eating) and others were carnivorous (meat-eating), including fish-eaters and insectivores, and omnivores (including both animals and plants in their diets). We should be thankful that we never knew many of the carnivores like T-Rex, which measured up to 12m (40ft)! It’s obvious that we could not live on earth if T-Rex were still running around. For our arrival, their departure was necessary.

There is no doubt that the human species is very valuable from various aspects, but what puts each person on the same level with another species?

One of humanity’s great merits is our collective understanding. This collective consciousness can be more fully realized through the glasses of faith in God. With the window of faith, humans not only comprehend His speech, but are better attuned to their fellow living beings – and maybe even non-living creatures. Humans are like one who is that all-inclusive and hears all other things. Hence, we can grasp proofs of the most beautiful names of the Creator from the speeches of all creatures.

The light of such understanding in humans leads to an expansion and improvement in our soul. This makes our value high, our sight universal, and our ability to achieve to perfection limitless. On the other hand, many other species are limited in many aspects by their nature, sights, and capacity of perfection. According to religious texts, though humans and other species are valued differently on earth, the divide grows larger in the hereafter. While every human being is re-created with their names, features, matter, and manner, other species return back to the soil.

When you visit nature museum next time, try to listen what the fossils of extinct species tell you about their complaint. They were created for a purpose; they have finished their job and gone. They have done a fantastic job and flourished, while leaving us many petrol reservoirs. Though countless species have gone extinct, more than 1.6 million other species are still living on earth. Death is not an end; nowadays, they are trying to reach out to us and tell us their secrets. We’re expected to become the best fruit of this universe.

This dream made me think about how the ways that Allah could teach us is not limited to what we do when we are awake. Would you ever think that ancient extinct species would also need the lights of the everlasting speech of the All-Wise and All-Powerful, as explained by why a man could be equivalent and worthy of a species of another creature by Bediuzzaman?

Another lesson is that as we live in an oil dependent-century, we are counting on reservoirs that formed millions years ago by the remnants of ancient living beings; but just as we depend on them, ancient extinct species are also counting on us and expecting us to contemplate our purpose for being here, and to show that we’re worthy of being the most glorious fruit in the universe. As the All-wise make things with infinite wisdom, he sends oil to people of this century to help in technology and he also sends further mercy in the form of knowledgeable scholars to answer our questions.

I am sure that there are a lot of people who’ve found themselves in a similar situation to the man above. Unfortunately, most of us are usually not aware of the things happening in this universe. One of the things we tend to overlook is the cleanliness of nature. This is a topic which needs to be considered carefully, but I will just touch on some important aspects of this issue.

First, let’s look at the oceans. The oceans cover three-fourths of the Earth’s surface. There is a bigger world under the ocean than above it. This huge mass hosts jelly fish and tuna, dolphins and octopus, crabs and plankton, sea stars and sea plants. Currently, there are 120,000 species living in the ocean. This is just the number of the species, and doesn’t account for how many variations there are within each species. When we consider the number of living organisms, there are millions of them. Every single day, lots of these organisms die. If there are millions of organisms and thousands of them die each day, then why cannot we see them on the surface of the ocean? Even if these dead organisms are very small, such as plankton, which has a size range from 0.2 m to 20mm, when millions of their dead bodies cluster on the surface, we should be able to see them. The answer lies in a perfect arrangement. For example, the job of cleaning the dead bodies of plankton (also the live bodies!) is performed by fish, sharks, and whales. A large percentage of the daily diet of these animals depends on plankton. Since these animals perform their job well, it is impossible to see any dirt that would have been caused by the dead plankton.

It might seem easy to get rid of the dead bodies of plankton, because they are small organisms. But what about big animals such as whales? What happens to dead whales? Let’s consider the cleaning of dead whales. When a whale dies, its dead body sinks to the bottom of the ocean. This is called a “whale fall” by scientists. There are a lot of species whose diet depends on dead whales. In 1988, a group of researchers at the University of Hawaii found that there are at least 12,490 single organisms which supply their daily diet from a whale fall in the deep North Pacific Ocean. After bigger organisms, such as fish, finish their job, which includes eating the flesh of the dead whale, the other cleaners come to the scene to perform their roles. At this part of the fall, bacteria play a key role in cleaning the bones left from the whale fall. This is not as easy as it might seem. Actually, it takes several years to really clean the dead body from the bottom of the ocean. This is not just a cleaning process at all. While the whale fall is being cleaned from the bottom of the ocean, the ecosystem is supported by the energy from the dead whale.

This cleaning process is not only seen in the oceans, but also on the land. Even though it is more apparent than undersea, we are not totally aware of the cleaning process on land. Decomposition is the chain of events by which a dead organism breaks down to its smaller parts. We must stop here and ask this question: “What would happen if these dead organisms stayed on the land forever?”

So let’s look at what happens to a dead animal on land.

When an organism dies, the process of decomposition starts shortly after its death. There are some stages in the decomposition of an animal. Shortly after the death of the organism, the enzymes in the cytoplasm of the cells start to break down the tissues. This process is called autolysis. It is one of the stages of decomposition in which bacteria plays a role. Bacteria start to break down the tissues. This is called putrefaction. Bacteria are not the only players who have roles in this process. Besides them, some fungi, insects, and even some carnivores are also involved. Live animals, water, air, and temperature (higher temperatures increase the decomposition rate) also help this process. During this time, fungi and bacteria, by using compounds from the dead organisms, convert carbon to carbon dioxide and organic nitrogen to ammonium (NH4+), and so they contribute to both the Carbon and Nitrogen Cycle. After this process is done, many organisms living in the ecosystem have benefitted. At the end of this cycle, soil is enriched with new nutrients which will help the new plants to grow up and the Carbon and Nitrogen cycles are enhanced.

By looking at the processes above, as well as other cycles (e.g. the Carbon cycle), it can be said that the Earth has its own recycling system. While modern societies have only recently understood the importance of recycling, Earth has been using this system thanks to the arrangements given to it.

The things shown here are just some examples of the extraordinary systems existing on the Earth. These systems have always been like this, since the very beginning of the universe. These perfects systems in nature perform their tasks without any human help. The only thing for us to do is to appreciate this harmony, understand its value, and keep it going for the next generations.

Termites are 1-2 cm in size, but they live in mud towers that can grow to five meters tall. The scale, between termite and tower, is comparable to that between a human and a skyscraper. When their life style, which seems chaotic from the outside, is investigated, one finds that termites maintain social lives within perfect urban communities. These wondrous mini cities feature air conditioning and ventilation systems, in addition to a queen chamber, and rooms for incubation and juveniles.

An instinctual sense of solidarity that has been ingrained among living organisms also plays an important role among termites. They display an amazing form of cooperation in matters like foraging and defense. As termites live in colonies, they follow a particular arrangement of duties. The queen is in charge of new generations; workers meet the nest’s needs, and soldiers are responsible for its defense. When necessary, workers also participate in defensive tasks. One of the termite’s defense mechanisms, which amazed scientists, was recently discovered in June 2012.

Jan Sobotnik, with the Academy of Sciences of the Czech Republic, and Thomas Bourguignon, of Université Libre de Bruxelles at French Guiana, discovered an unseen feature of the termite species Neocapritermes taracua. The workers of this species are, in a sense, enlisted to military duty when they “retire” due to old age and an inability to forage due to weakened mouths. They serve the defense of the nest as something of a chemical weapon specialist. When the colony is under attack, these veterans blow up a droplet-size balloon filled with a type of chemical generated in between segments of their neck and dorsal region.

When worker termites get older, blue crystal chambers, which resemble backpacks, grow on their two shoulder blades on their back. These crystals are a kind of protein called hemocyanin that contains copper, and they join together with saliva when under threat. This fusion causes a chemical reaction. The end product is a sticky liquid, like a gel, that is compressed to expand and then burst. This can fatally injure a predator. The poisonous substance that is dispersed causes rotting upon contact. The chemical formula of this blue crystal substance, along with its reactions, are still unknown.

Researchers from Oregon University (USA) reported that the mouth of an ant is worn down by age. When this occurs, these senior individuals, which used to cut leaves, now take on different jobs, like carrying the leaves. Leaf cutter ants, which are also known as the ranchers of the animal kingdom for their ability to cultivate fungi in their nests, can cut and carry leaves whose weight can be up to 50 times their body weight.

The leaves that are transported to the nest comprise the main ingredient required for the growth of fungi in a suitable environment regulated for the right temperature and humidity. This fungi is ultimately used to feed the colony. This is a fine example of senior members of a community staying active in a new role. And this is not just unique to termites: research shows that members of animal societies adapt to changes in their lives, and continue serving their colonies even if they lose some dexterity.

Our universe seems to be set up this way. As mentioned in the above examples, there is a change of occupation instead of just retirement. Just as there is no termite that stops working, there is no bird that says “I do not want to fly anymore because I am old,” or no tree that says, “I will retire and stop giving fruit because of my old age.” Organisms adapt to new conditions and find new ways to provide for our planet.

Our aging planet will continue rotating and the sun will keep smiling on us with its heat and light until the end of such organism’s lifetimes.

When it comes to humans, continuing with occupation and business as much as they can should be the desired effort. Especially for charity work, no one should mention retirement or leave of a duty, and receding to one’s quarters. Let us renew our intentions now, and review our senior living plans.

In the northern hemisphere, where annual average rainfall is around 100 kg per square meter in cold and dry regions, boreal forests, with needle-leaf trees, dominate. The southern hemisphere is dominated by savanna; bushes and meadows occupy millions of hectares.. In these regions, natural fires can be the most important factor of ecosystem changes. When looking at the results of these fires, it sometimes seems they were preprogrammed as to when, where, and how they spread.

Examples of fire dependent ecosystems

The cone of the Jack Pine species (Pinus banksiana), which is widely distributed throughout North American forests, requires absolute forest fire in order to release its seeds. The cone of this species can remain on the trees without releasing seeds for years because of climate and the resin layer covering it. Seeds preserved in the cones wait for the next fire; the cone’s scales open with the heat generated during such a fire. The seeds then start their journey towards a piece of soil that they can grow into. Here the role of fire is very important, not only for the dispersal of seeds but also in preparation of germination. The high humidity and low temperatures in the forests of these regions delays the decomposition of fallen leaves. This layer of dead material over the mineral soil is another hindrance for seeds to meet the soil. When scales of the cones open with the help of forest fire, this thick layer of dead leaves is also removed, having burned down to create fertile new soil.

Another example of fire benefiting plants is the chaparral vegetation of the North American forest. This type of plant cover is composed of short, perennial wooden plants and annual non-woody plants. During the hot, dry weather of summer, this vegetative cover becomes particularly vulnerable to fire. A dark black cover composed of unburned parts, frames, and ashes of the plants is left behind. This sight, which is saddening at first, actually hides various beauties in it, and these beauties only emerge after a series of events.

Golden eardrops (Dicentra chrysantha), which is a member of the perennial Chaparral family, is deeply affected by fire. The seed of this plant requires a fire event in the germination season and should be exposed to smoke for at least 10 minutes.

The positive effects of forest fires can also be seen in the healthy survival of an ecosystem. Due to its thick bark, the widely distributed Ponderosa pine (Pinus ponderosa), of North America, is minimally affected by the low, medium level cover fires that happen every five to twenty years. The weak and unhealthy individuals in this dense forest get burned as a result of natural forest fires, leaving healthy, thick barked trees. This way, possible epidemics of harmful forest organisms, via these unhealthy trees, is prevented. In the meantime, due to periodic fires, dead cover, or fallen and dead trees are removed, thus preventing bigger fires.

In the eastern Mediterranean, brutia pine, yellow pine, black pine, aleppo pine, and stone pine can are widely distributed. Among these, brutia pine is spread across a wide area, especially in most fire sensitive regions. It is created with a thicker bark around the trunk compared to other pines. This species can be minimally impacted from low and medium level cover fires. On the other hand, seeds in the cones of brutia pine are thrown far away by the heat of the fire, reaching fertile germinating grounds, thus helping to spread the forest.

References

• Fuller, M. 1991. Forest Fires: An Introduction to Wildland Fire Behavior, Management, Firefighting, and Prevention, SD421.F84, Wiley & Sons, Inc., NY, pp. 238.
• Keeley, J. E. 2007. “Chaparral and Fire,” Fremontia, Volume 35:4, pp. 16-21.
• Bond, W. J., Wilgen, B.W. 1996. Fire and Plants, SE18HN, UK, Chapman & Hall, UK, pp. 259.

These findings might help researchers to design more effective drugs for various human infections by focusing on the minimization of the inflammation. Moreover, bats are capable of sustained long flights, as some bat species can fly more than 1,000 km in a single night. With such intense physical activity, cells often produce high levels of toxic (free radicals) that would usually damage DNA sequence.

This study also found that bats are equipped with a highly functional set of genes that mediates DNA repair in response to DNA damage, thus bats are protected from toxic cellular waste with this advanced mechanism. Aging, cancer and infectious diseases are the three major issues medicine is facing today and biological abilities granted to bats seem to provide important clues for us to discover new ways to combat these big health problems

Hierarchy of hematopoietic stem cells

The blood system, also known as hematopoietic system, has enormous regenerative capacity to maintain functional mature blood cells that arise from highly proliferative but short-lived progenitor cells. Those progenitors in turn are generated from very rare blood stem cells called hematopoietic stem cells (HSCs). HSCs are one of the most studied stem cells in our body which has greatly shaped our thinking on the features of adult stem cells. These stem cells are kept at the bone marrow in close proximity to bone cells and other supporting cells forming the specialized home known as niche. In several aspects, a niche resembles a cellular stronghold that a queen lives in a safe and protected environment.

The interaction of stem cells with the niche is crucial as this prevents exhaustion of stem cells from uncontrolled cellular divisions and proliferation. While active progenitors account for the generation of mature blood cells, hematopoietic stem cells function as a reserved cell population. Interestingly, we observe the importance of the balance between those two cell populations in the aging process. Although the number of HSCs increases in aged animals, there is a decline in self-renewal of HSCs.

Other protective mechanisms include the low proliferation rates of HSCs in a relatively quiescent state, residing in a low oxygen environment [3], a relatively low degree of metabolism and preferential use of glycolysis as energy source, and additional protection mechanism against oxidative stress.

Low in oxygen but a good place to be!

Stem cells as the cell bank of the body are protected against internal and external insults by a number of mechanisms. Stem cell niche not only provides an environment that they can survive but also poses the lesser degree of internal and external insults. Those possible stresses on cells include, but not limited to, UV exposure, radiation, toxic chemicals, and free oxygen species that cause various damages in the cell including mutations in DNA (Fig. 3). Cells respond to those external and internal issues by various ways such as senescence (loss of stem cell activity), cell death or DNA repair. For example, blood stem cells mainly house in the bone marrow next to osteoblastic lining (blood-forming cells) and endothelial cells where they form the hypoxic (low oxygen tension) endosteal region. This hypoxic niche of HSCs provides lower levels of oxygen so that there are lower levels of free oxygen radicals that mainly arise from electrons leaking from mitochondria during oxidative phosphorylation. In addition, it has been shown that HSC express higher levels of hypoxia inducible factor-1α, a master regulator at low oxygen tension with hundreds of downstream targets regulating various aspects of metabolism including defense against oxidative stress and survival at low oxygen environment. It has also been shown that hypoxia increases self-renewal abilities of HSCs, thus keeps them healthy and functional for longer periods.

Protection from detrimental effects of reactive oxygen species (ROS)

Excess amounts of reactive oxygen species are detrimental to cells. ROS are found to cause hematopoietic stem cell defects as shown in mouse lacking FoxO and Atm genes. In those mutant mice, the hematopoietic defects could be rescued by the use of an antioxidant N-acetyl-cysteine. Anti-oxidants are one of the scavengers that diminish unwanted effects of reactive oxygen species. A number of fruits and vegetables such as beans, blueberry, strawberry, and apple are known with their high content of anti-oxidants. It is amazing to observe anti-oxidants being placed into our sustenance just as much as in some special genes (such as SOD2 and Hypoxia Inducible factor-2α) that provide additional protection for cells. Amazingly, stem cells show high levels of ROS scavenger genes.

Low metabolism provide protection for stem cells

Recent studies demonstrate that hematopoietic stem cells have lower rates metabolism as measured by lower oxygen consumption, lower ATP content and higher lactate production (an end product of cytoplasmic glycolysis) [4]. This means that stem cells produce and consume lesser energy (ATP) compared to more differentiated cells and the by-products of the energy production are kept lower. As higher energy demand brings higher rates of internal insults like production of ROS which is associated with aging and cellular damages, HSCs are granted with another protective mechanism by preferential use of glycolysis (anaerobic) instead of oxidative phosphorylation (aerobic).

Hematopoietic stem cells are quiescent

Another defense mechanism is the quiescence of stem cells which is associated with slow cell-cycle progression. Quiescence of stem cells means that they are kept at a resting, inactive state thus sustaining a self-renewing HSC compartment for life. Because when cell divides, they have to undergo thousands of chemical reactions including making a copy of the three billion letter long DNA, which puts cells at risk to get mutations. Thus, they don’t undergo division unless there is a stimulus. In addition, it has been found that HSCs divide only once every 145 days on average.

There are a number of studies indicating that there are signals in the niche that keeps HSCs in a quiescent state. Tie2/Ang-1 signaling, for instance, has been demonstrated to contribute to the maintenance of HSCs by inducing quiescence. While Ang-1 is expressed in the mesenchymal/stromal cells of niche, its receptor Tie2 is expressed at HSCs. In addition, it has been shown that Ang-1 can inhibit HSC division in culture and promote quiescence of HSCs in the bone marrow [5].

It is also reported that the cell adhesion molecules that allow physical interaction between stem cells and their niche components may participate in regulation of stem cell quiescence through a process called contact dependent inhibition of proliferation. For instance, it has been found that cell adhesion molecules such as N-cadherin, β1-integrin, and osteopontin might be involved in the regulation of cell cycle status of HSCs [6].

One advantage of quiescence of HSC comes from the lower susceptibility of slowly proliferating cells to radiation than other cells due to the expression of cell cycle inhibitors like p21 and anti-apoptotic (controlled cell death) machinery like ATM in HSCs. In addition, studies in p21 (a cell cycle inhibitor gene) knockout mice suggest that maintaining cell cycle quiescence is directly linked to self-renewal of HSCs [7].

Toxics are exported from hematopoietic stem cells

There are other issues concerning external insults against toxics and unwanted chemicals. An HSC population described as side population has been equipped with a number of transporters such as ATP Binding Cassette (ABC) transporters, P-glycoprotein (P-gp/ABCB1) and Breast Cancer Resistance Protein (BCRP/ABCG2) on their membrane providing high efflux ability [8]. They play an important role in the excretion of drugs and endogenous compounds. Those transporters work actively when there is an entrance or excess of such chemicals thus keeping damage minimal.

HSCs are placed in such an environment that even minimum damages by internal and external insults are prevented by different defense mechanisms including residing HSCs in the hypoxic niche, expression of ROS scavenger genes, preferential use of glycolytic metabolism, quiescence nature of HSCs, and removal of toxins by ABC transporters. It is very wise to home such an important cell in a place where it can prosper with a carefully balanced rate of cell division and metabolism. Hypoxic niche seems key to the protection of hematopoietic stem cells by supporting self-renewal and preservation of hematopoietic functions both at the same time. The presence of these protective systems that are graciously placed in our cells with perfect measurements provides an elusive mechanism to ensure healthy life-long reservoir of HSCs.

Ali Fethi Toprak is a PhD candidate at Southwestern Medical Center, Texas University.

Selected References

1. Kobayashi, C.I. and T. Suda, Regulation of reactive oxygen species in stem cells and cancer stem cells. J Cell Physiol, 2012. 227(2): p. 421-30.

2. Li, L. and H. Clevers, Coexistence of quiescent and active adult stem cells in mammals. Science, 2010. 327(5965): p. 542-5.

3. Eliasson, P. and J.I. Jonsson, The hematopoietic stem cell niche: low in oxygen but a nice place to be. J Cell Physiol. 222(1): p. 17-22.

4. Simsek, T., et al., The Distinct Metabolic Profile of Hematopoietic Stem Cells Reflects Their Location in a Hypoxic Niche. Cell Stem Cell, 2010. 7(3): p. 380-390.

5. Arai, F., et al., Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell, 2004. 118(2): p. 149-61.

6. Yamashita, Y.M., D.L. Jones, and M.T. Fuller, Orientation of asymmetric stem cell division by the APC tumor suppressor and centrosome. Science, 2003. 301(5639): p. 1547-50.

7. Cheng, T., et al., Hematopoietic stem cell quiescence maintained by p21cip1/waf1. Science, 2000. 287(5459): p. 1804-8.

8. Huls, M., F.G. Russel, and R. Masereeuw, The role of ATP binding cassette transporters in tissue defense and organ regeneration. J Pharmacol Exp Ther, 2009. 328(1): p. 3-9.

9. Antioxidant Riches Found in Unexpected Foods. Retrieved from http://www.webmd.com/food-recipes/news/20040617/antioxidants-found-unexpected-foods, January 31, 2012.