Hsueh MF et al. Analysis of “old” proteins unmasks dynamic gradient of cartilage turnover in human limbs. Science Advances, October 2019.

Humans may not be able to regrow amputated limbs, but a recent study showed that damaged cartilage may regrow through a process similar to that of animals such as salamanders and zebrafish. Scientists collected 18 specimens of joint tissue from the hips, knees, or ankles of patients who underwent surgery. They then placed the tissue in a mass spectrometer and measured the age of the cartilage proteins in the sample. These analyses showed that the age of cartilage largely depended on where it resided in the body. Cartilage in ankles is young, middle-aged in the knee, and old in the hips. This correlation between the age of human cartilage and its location in the body suggests that limb repair occurs in humans in a similar fashion to certain animals in which tissue regeneration takes place at the furthest tips such as the ends of legs or tails. This finding also helps to explain why injuries to people’s knees and, especially, hips take a long time to recover and often develop into arthritis, while ankle injuries heal quicker and less often become severely arthritic. The researchers further identified the molecules that are instrumental in the regulation of this region-specific regeneration process. They are called microRNAs and, not surprisingly, are present at very high levels in animals that are known for limb, fin, or tail repair including salamanders, zebrafish, and lizards. Scientists believe that these regulator microRNAs can be utilized in the regeneration of degenerated cartilage of an arthritic joint to reverse arthritis. Regeneration of part or all of an injured human limb may even be possible by finding components salamanders have and we don’t. Finally, it is also possible that this could be a fundamental mechanism of repair that could be applied to many tissues, not just cartilage, which might open up many new avenues in the regenerative medicine.

The universe might have many Earth-like exoplanets

Doyle AE et al. Oxygen fugacities of extrasolar rocks: Evidence for an Earth-like geochemistry of exoplanets. Science, October 2019.

New astrophysical and geochemical evidence suggests that Earth may not be that unique, and Earth-like planets may be common in the universe. All of the planets in our solar system orbit around the Sun. Planets that orbit around other stars are called exoplanets.  The first exoplanets were discovered in the early 1990s. Since then, thousands of exoplanets have been revealed with over 4,000 confirmed and a further 4,495 potential candidates. There have been major efforts to narrow down the exoplanets that may have properties similar to Earth with conditions suitable for life. This includes being a rocky planet that is not too hot or cold so that liquid water can exist. When searching for exoplanets that are similar to Earth, astronomers typically look for worlds in orbit around a type of star called a red dwarf or an M-dwarf. These types of stars are somewhat similar to our sun and make up about 70% of the stars in our galaxy. However, a new study shows that rocky exoplanets in orbit around a different type of star, a white dwarf, can have interiors that are surprisingly similar to our planet. White dwarf stars are dense remains of normal stars that have exhausted their nuclear fuel. These stars are typically composed of light elements such as hydrogen and helium, but in some cases they attract heavier elements such as magnesium, iron, and oxygen in their atmospheres due to their extreme gravity. These heavy elements are thought to be introduced when a rocky exoplanet crashes into a star, which gives astronomers evidence of what the exoplanets were like before they were destroyed. In this recent study, scientists looked at six white dwarfs located 200 to 665 light-years from Earth and rocks from the planets that once orbited it. Their analyses showed that five out of the six white dwarfs had sucked up fragments whose chemical composition is similar to rocks on Earth, Venus, and Mars. While the conditions suitable for life depend upon many additional factors, this study points towards the idea that many rocky planets are likely very familiar in terms of their general composition and, therefore, structure and behavior. This study also made a substantial leap forward in being able to make inferences for bodies outside of our own solar system and indicates that it is very likely that there are truly Earth analogs out there.

Artificial leaf points to a sustainable path to carbon-neutral fuels

Andrei V et al. Bias-free solar syngas production by integrating a molecular cobalt catalyst with perovskite–BiVO4 tandems. Nature Materials, October 2019.

An artificial leaf from which a “clean” fuel alternative to petrol could be produced has been developed. Synthetic gas can be obtained from the lead by using only sunlight, carbon dioxide, and water.

Synthetic gas, also called syngas, is typically a mixture of carbon monoxide and hydrogen. It is largely produced by exposing fossil fuels such as coal or natural gas to high temperature steam and pressure, and the process releases carbon dioxide. Syngas is broadly used in a wide range of commodities including fuels, plastics, and fertilizers. While the utilization of fossil fuels has enabled large-scale industrial development in human history, the burning of fossil fuels is the largest source of emissions of carbon dioxide, which is one of the greenhouse gases that contributes to global warming. For decades scientists have been trying to discover new ways to produce syngas in order to close the global carbon cycle and to establish a sustainable chemical and fuel industry. In a recent study, researchers got inspired by leaves. These perfect little machines use sunlight to convert carbon dioxide and water into fuel for plants through photosynthesis. An artificial leaf has been designed to have two light absorbers, similar to the molecules in plants that harvest sunlight, and a catalyst made from the naturally abundant element cobalt. When the leaf is immersed in water, one light absorber uses the catalyst to produce oxygen and the other one carries out the chemical reaction that reduces carbon dioxide and water into carbon monoxide and hydrogen, thus forming the syngas mixture. The scientists are now searching for ways to use their technology to produce a sustainable liquid syngas that could serve as an alternative to petrol. Although major efforts to generate renewable energy sources are being made, the development of synthetic petrol is critical as electricity can currently fulfill about 25% of our total global energy demand. There is a huge demand for liquid fuels to power heavy transport, shipping, and aviation sustainably.

The miracle of life appears in the form of a baby which develops from a fertilized ovule (zygote) following millions of other events. This series of events, which is almost always the same for every fetus, can be grouped as reproduction, differentiation, and development. The zygote completes its development in the womb; postnatal growth can continue until 20 years of age. Even though every event during the baby’s development seems to take place with chaotic reactions, harmony and order are there for us to discover. One of these astonishing events is the perfectly symmetric growth of the fetus/baby. Most organs in the human body appear in pairs and are symmetric. Babies are born with 300 bones; however, some bones later fuse with other bones, leaving only 208 bones in the adult human. It is still a mystery how long bones such as the humerus, radius, ulna, femur, and tibia are able to grow on both sides of the human body in a symmetrical manner.

Mechanisms that control growth in organs

In vertebrates, both internal developmental programs and the external factors which stimulate or inhibit growth play a role in the ultimate size of an organ. But the relative effects of these two mechanisms can vary significantly in different organs. When pieces of spleen from an embryo that is at a later stage of growth are transplanted to a newly developing embryo, each new piece grows, but not to the size of the original spleen. The total weight of all the transplanted spleen pieces is equal to a normal spleen’s weight. When the spleen reaches a certain weight, growth inhibiting factors are secreted, which stimulate negative feedback mechanisms that limit growth. When a spleen reaches a certain size, the density of the inhibiting factors increases simultaneously, halting growth. Growth in the liver is controlled by extracellular factors (various substances in the blood, hormones, vitamins, minerals, etc.). When a section is cut off of the liver, the section continues growing and developing until it reaches the size of the original liver. The thymus has a growth process that is executed by a cellular genetic program. When sections of a thymus taken from the embryonic period are injected into developing mouse embryos, every section grows until it reaches the ultimate size.

More evidence of cellular growth programs was acquired via an experiment that was carried out with the salamander genus Ambystoma. When the leg bud of the larger species was injected into the smaller species, it would at first grow slowly, but then it would reach the normal size of its own species (the larger species).

Distinguishing growth and symmetry from one another

Both the arms and legs have long bones. A long bone consists of two parts (diaphysis and epiphysis). The diaphysis is the middle (core) part of the long bone. It consists of hard bone tissue, and is like a tube. The hyaline cartilage-covered joint forms the epiphysis of the long bone. In a growing bone, there is a growth plate (epiphysis plaque) made of hyaline cartilage; this is located between the diaphysis and the epiphysis. The epiphysis plaque causes the bone to grow longer; when growth is complete, the epiphysis plaque ossifies (becomes bone). In other words, growth stops. There are some clues that show the existence of positive feedback mechanisms which control the symmetric and balanced development of the arms and legs while the fetus is still growing. The arms and legs grow due to the development and growth of the plaques located at opposite ends of the long bone. The ultimate size of the arms and legs are proportional to the size of the finger bones (phalanx) and the metacarpus. According to current knowledge, growth in our arms and legs is only controlled by internal growth programs and the active growth of the plaques. We do not yet know the mechanism through which how much the bone must grow and symmetrically with the organ (the other arm or leg) on the other side of the body. But even if this is discovered in the future, we will continue to appreciate the perfect and miraculous aspect of this phenomenon.

In addition, in growth-plaque transplant experiments, the development of the transplanted growth plaque is dependent only on the age and size of the donor. Growth plaques cause the bone to grow, but the plaques themselves remain the same size for years. The cartilage cells they produce (chondrocytes) exchange places with the bone cells (osteocytes) in harmony and without destroying the length of the bone. Cells from different areas of the growth plaque act differently. Stem cells are found on the upper section, near the epiphysis. Immediately above them is an area where cells reproduce very quickly. At the bottom of the epiphysis, the cartilage cells grow up to 4 to 10 times larger than their normal size (hypertrophy). Cell reproduction here is mostly due to hypertrophic chondrocytes. The chondrocytes die and break up, then change places with the bone tissue. The dynamic process of these events in the growth plaque repels it from the bone area, and as a result, the bone grows longer.

Sustained symmetry despite cell sequence and speed of reproduction

The rapid growth rate in the legs and arms during the embryonic period continues to increase until the child is three years of age. This growth rate slows down until the individual reaches adolescence. During the fastest growth period, which is from adolescence to the early 20s, the growth rate rapidly increases. For example, most people who grow between 30 and 37.5 cm during the first two years of life can grow between another 7.5 and 10 cm every year during adolescence. At the onset of adolescence, rapid growth due to a sudden change in the volume of cells is observed. After adolescence a sudden falling off in the speed of growth can be observed due to the effect of hormones on the growth plaques in the spine and other long bones. The growth plaque now fuses with the neighboring cells and growth stops. However, the fusing of the growth plaque is the result of the cessation of growth, not the cause. After growth stops, the growth plaques begin to disappear. When the reproduction potential of the cartilage cells in the growth plaque has been exhausted, the growth plaque begins to disappear.

Growth plaques in different bones can trigger growth at various rates; these rates can differ as much as seven times. In fact, growth plaques on different ends of a bone can have different growth rates, provided that this rate is consistent with the genetic program. The number of cells on the growth line is 40 times more than in other areas. The number of cells produced here can exceed 10,000 cells per day. For symmetric growth between the arms and legs to be sustained, the number of cells in the growth plaque must be the same or very close. Experiments carried out on rats show that eight cartilage cells leave the growth plaque to exchange places with cells above them every day. It can be said that the growth of the bone is caused by the increase of cells in the growth plaque (which sustains its size). The growth rate caused by the growth plaque can be calculated by multiplying the growth plaque’s cell production rate by the average length of all of its cells. Different growth plaques provide different growth rates. This difference can be caused by the difference in the size of the growth plaques, the difference in cell production rates, and/or the difference in the hypertrophy (growth) rate of every cell. The upper growth plaque in the tibia of mice generates 16,400 cells every day; the average life span of these cells is around 30 hours. Can such harmonious, symmetric, and equivalent growth in the arms and legs-despite the large number and variety of cells-be the work of pure coincidence, mindless nature, or unconscious molecules?

Do hormones play a role?

The main molecular players that organize longitudinal growth in bones during childhood are the growth hormone, the thyroid hormone, and corticoids. The sex hormones (androgens and estrogens) are programmed to influence growth during adolescence. Estrogen is the main determiner of characteristics related to increased height and an increase in bone quality, as well as adolescent-related physiology. These hormones are in charge of coordinating growth throughout the body. It is for this reason for women, after the menopause, the production in estrogen decreases and osteoporosis and brittle bones can occur. According to the current view, cartilage cells have a certain genetic reproduction potential, and when this potential finishes, growth stops. The growth rate during the embryonic period is 20 times higher than that of mid-childhood. The growth rate drops greatly during mid-childhood. If we exclude the noticeable increase during adolescence, the cells responsible for growth have begun to age. The bones on opposite sides of the body stay about the same size, despite all of these changes in growth rates. Circulating hormones and neuroendocrinal factors are believed to play important roles in maintaining symmetric growth. But there is no conclusive evidence to support this belief. Even though one can think of factors such as pressure, tension, and sports as helping control harmonious and symmetric growth of bones, no proof has been attained from controlled experiments. As a person ages, a gradual decrease in growth can be observed. Even if a growth plaque is placed into another organism, be it young or old, the growth rate of the bone does not change. This shows that symmetric growth in long bones is controlled by a program that is operated by internal factors, which is also compatible with the genetic program. When chemical-based medication is given to postpone growth, after the medication has been eliminated, the growth plaques grow faster for a short period to compensate for the lost time. These findings show that timing and the location and circumstances of the cell are critical parameters for reproduction. If the cartilage stem cells in the growth plaque have a certain reproduction potential, then it is clear that cartilage cell reproduction stops when growth comes to an end. If growth inhibiting factors slowly accumulate in the growth plaque, this might cause a deceleration of growth over time. Another possibility is some sort of “meter” in the unconscious and mindless stem cells, which keeps track of the number of cell divisions and thus controls aging. The estrogen in our body has a duty of closing down the growth plaques and speeding up the aging of cells. However, we should not forget that estrogen plays the special role of closing down all of the growth plaques at the same time. Estrogen is one of the visible causes of fertility, growth and development, and resilience. Estrogen also represents femininity and fertility at all levels.

When the signals from unconscious cells in the growth plaques and the quite sophisticated interactions among all the factors that influence growth, all of which require an all-encompassing knowledge to be executed, are taken into account, the impeccable genetic programs of different growth plaques on the two sides of the body that leads to the formation of the arms and legs, as if they have been molded in a factory, is absolutely amazing for anyone who reflects upon it.

References

• Wolpert L. (2010).”Unsolved Mystery: Arms and the Man: The Problem of Symmetric Growth.” PLoS Biology. 2010 Vol. 8(9). pp 1-3
• Extremity Development during the Embryonic Period (www.visembryo.com)