The headache of adapting to the cold, literally

Frequency of the adaptive allele in several human populations (from the 1000 Genomes dataset).

A common genetic variant implicated in migraine headaches may have proliferated because it helped early humans adapt to cold weather in northern climates. Felix Key of the Max Planck Institute for Evolutionary Anthropology and colleagues report these findings in a new study published May 3rd, 2018 in PLOS Genetics.

Within the last 50,000 years, some humans left the warm climate of Africa to colonize colder locales in Asia, Europe, and other parts of the world. "This colonization could have been accompanied by genetic adaptations that helped early humans respond to cold temperatures" says Aida Andres, who supervised the study. To find evidence of this adaptation, researchers took a closer look at TRPM8, a gene that codes for the only known receptor that enables a person to detect and respond to cool and cold temperatures. They discovered that a genetic variant upstream from the gene, which may regulate it, became increasingly common in populations living in higher latitudes during the last 25,000 years. Only 5% of people with Nigerian ancestry carry the variant, compared to 88% of people with Finnish ancestry. Currently, the percentage of people in a population that carry the variant increases at higher latitudes and with colder climates. Interestingly, scientists had already identified this variant as being strongly associated with migraine headaches.

Migraine is a debilitating neurological disorder that affects millions worldwide. The percentage of people who suffer from the disorder varies across human populations, but is highest in individuals of European descent, which is also the population with the highest frequency of the cold-adaptive variant. The researchers suspect that adaptation to cold temperatures in early human populations may have contributed, to some extent, to the variation in migraine prevalence that exists among human groups today. Felix Key pointed out that "this study nicely shows how past evolutionary pressures can influence present-day phenotypes."

From Science Daily

Revealing the remarkable nanostructure of human bone

Interweaving mineral and protein form continuous networks to provide the strength essential for functional bones.

Scientists have produced a 3D nanoscale reconstruction of the mineral structure of bone.

Bone performs equally well whether in an accelerating cheetah or in a heavy elephant, thanks to its toughness and strength.

The properties of bone can be attributed to its hierarchical organisation, where small elements form larger structures.

However, the nanoscale organisation and relationship between bone's principle components -- mineral and protein -- have not been fully understood.

Using advanced 3D nanoscale imaging of the mineral in human bone, research teams from the University of York and Imperial College London have shown that the mineral crystals of bone have a hierarchical structure integrated into the larger-scale make-up of the skeleton.

Researchers combined a number of advanced electron microscopy-based techniques, and found that the principal building blocks of mineral at the nanometre scale are curved needle-shaped nanocrystals that form larger twisted platelets that resemble propeller blades.

The blades continuously merge and split throughout the protein phase of bone. The interweaving mineral and protein form continuous networks to provide the strength essential for functional bones.

Lead author, Associate Professor Roland Kröger, from the University of York's Department of Physics, said: "Bone is an intriguing composite of essentially two materials, the flexible protein collagen and the hard mineral called apatite."

"There is a lot of discussion about the way these two stiff and flexible phases uniquely combine to provide toughness and strength to bone.

"The combination of the two materials in a hierarchical manner provides bone with mechanical properties that are superior to those of its individual components alone and we find that there are 12 levels of hierarchy in bone."

Dr Natalie Reznikov, formerly of Imperial College, London and an author on the paper, said: "If we compare this arrangement, for example, to an individual living in a room of a house, this extends to a house in a street, then the street in a neighbourhood, a neighbourhood in a city, a country and on it goes. If you continue to 12 levels you are reaching the size of a galaxy! "

Professor Molly Stevens, from Imperial College, London, added: "This work builds on the shoulders of many beautiful previous studies investigating the fundamental properties and structure of bone and helps to unlock an important missing piece of the puzzle."

Besides the large number of nested structures in bone, a common feature of all of them is a slight curvature, providing twisted geometry. To name a few, the mineral crystals are curved, the protein strands (collagen) are braided, the mineralized collagen fibrils twist, and the entire bones themselves have a twist, such as those seen in the curving shape of a rib for example.

Fractals are common in Nature: you can see self-similar patterns in lightning bolts, coast lines, tree branches, clouds and snowflakes. This means that the structure of bone follows a fundamental order principle in Nature.

Read more at Science Daily

Cracking open the formation of fossil concretions

Gigantic concretions formed in mudstone on New Zealand's Moeraki coast; about 50 million years old. The present research shows that even concretions of this size formed very rapidly, within several decades.

All over the world, spectacular fossils have frequently been found preserved inside solid, roughly spherical rocks called "concretions." From geologists to casual observers, many have wondered why these hardened masses of carbonate formed around dead organisms, with round shapes and sharp boundaries with the surrounding material, typically in marine mud and mudstone.

Several important questions regarding concretions have long puzzled scientists. What conditions cause them to form? How long do they take to grow? Why do they stop growing? Why are they so distinct from the surrounding rock or sediments?

Now, researchers led by Nagoya University have developed a method to analyze concretions using L-shaped "cross-plot diagrams" of diffusion and growth rate, reported in a new study published in Scientific Reports. With this method, they analyzed dozens of concretions from three sites across Japan and compared them with concretions from England and New Zealand.

The results of this new study dramatically impact understanding of the rate at which concretions form. "Until now, the formation of spherical carbonate concretions was thought to take hundreds of thousands to millions of years," co-author Koshi Yamamoto says. "However, our results show that concretions grow at a very fast rate over several months to several years." This rapid sealing mechanism could explain why some concretions contain well-preserved fossils of soft tissues that are rarely fossilized under other conditions.

Study first author Hidekazu Yoshida explains, "The concretions maintained their characteristics, with well-preserved fossils at their centers or textures indicative of the original presence of organic matter. Simple mass balance calculations also demonstrate that the carbon fixed in the carbonate concretions came predominantly from the organs of organisms inside the concretions."

All of the studied concretions were composed of calcite, with relatively consistent compositions throughout, distinct from the surrounding muddy matrix. Fine-grained, generally clay-rich sediments were found to be important to limit diffusion and permeability, and to slow the migration of solutes. Thus, bicarbonate concentrations would rise high enough at a reaction front to cause rapid precipitation of calcium carbonate, with sharp boundaries from the surrounding mud.

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First-in-world robot-assisted spinal surgery

Noah Pernikoff is back to his life in New York City after becoming the first patient in the world to undergo a complex three-part, robotic-assisted surgery. The robotic arms made it possible for the multidisciplinary team at Penn to successfully remove a rare tumor from Noah's neck, where the skull meets the spine. The ground breaking surgery was completed by a multi-surgeon team, led by Dr. Neil Malhotra, at the Hospital of the University of Pennsylvania in August 2017 over a span of two days and more than 20 hours.

Chordoma is a rare type of cancer that occurs in the bones of the skull base and spine. A chordoma tumor usually grows slowly and is often asymptomatic for years. In the case of 27-year-old Noah Pernikoff, a 2016 car accident revealed his surprising diagnosis.

Among his injuries from the accident, Noah -- who was working in New York City for a commercial contracting firm -- tore his rotator cuff and had several herniated discs. More important, however, was his post-accident nagging neck pain, which lead to an x-ray that revealed a concerning lesion in his neck, on his cervical spine. The lesion was clearly unrelated to the accident, and far more concerning than the minor injuries he had endured. After making a recovery from the accident, Pernikoff's father, a physician, encouraged his son to see a neurosurgeon for evaluation of the injury. The neurosurgeon Pernikoff saw ultimately recommended a biopsy of the spot, which resulted in a diagnosis of chordoma.

"I'm lucky because they caught mine early. For a lot of people, if it's not found and treated early, it's lethal," Pernikoff said. "The doctor said if I hadn't discovered it through the car accident it probably would have kept growing until it came to a point on my spinal cord where it caused paralysis or death. I feel very lucky in that regard." Unfortunately, the neurosurgeon explained to Pernikoff, while surgery is known to be the best option for chordoma, Pernikoff's would be too difficult to resect and he would have to try the second option, radiation with proton therapy.

Chordoma is extremely rare; it affects only one in 1 million people each year. Pernikoff's specific type of chordoma, located on his C2 vertebrae, is even rarer, making treatment a challenge. Pernikoff's neurosurgeon immediately referred him to Penn, where a multidisciplinary team reviewed his case, and his options, and began crafting a treatment plan -- not through radiation, but a complex surgery that had never been performed before.

Neil Malhotra, MD, an assistant professor of Neurosurgery and Orthopaedic Surgery and the vice chair of operations in the department of Neurosurgery, gathered a multidisciplinary team of physicians to treat Pernikoff's chordoma. Malhotra planned to remove the tumor through a rare and complex spinal surgery approach. Bert W. O'Malley Jr., MD, a professor and chairman of the department of Otorhinolaryngology: Head and Neck Surgery, planned to aid Malhotra's approach and improve Pernikoff's recovery by using a trans-oral robotic (TORS) approach for the second part of the surgery. TORS is the world's first group of minimally invasive robotic surgery techniques, invented at Penn, to remove benign and malignant tumors of the mouth and throat.

"This would be a first ever use of a robot in this manner -- a rare approach to an already rare and complex case," Malhotra said. "Our team needed to reconstruct the removed area of Pernikoff's spine using bone and rods, and that was only the beginning."

The stakes were high. Because of the placement of the tumor, Malhotra said removal could compromise the structural integrity of Pernikoff's spine, causing permanent paralysis. There was also a risk of complications such as bone and tissue breakdown, loss of sense of smell, fine motor skill issues, and complete paralysis. And, he said, "if we couldn't remove the entire tumor, it would likely grow back, perhaps more aggressive than before."

The surgery was performed in three parts. First, the neurosurgeons went through the back of Pernikoff's neck and cut the spine around the tumor to prepare for the second stage, removing the tumor through his mouth. The key to this stage would be to make ultrasonic bone cuts -- removing a piece of bone -- around the tumor without touching it, and without injuring the spinal cord that lay between the neurosurgeon and the tumor/spinal column. With stage one success, O'Malley and a team of three head and neck surgeons used the surgical robot to clear a path so Malhotra could remove the tumor, and part of the spinal column, in its entirety through the mouth. Finally, the team reconstructed Pernikoff's spinal column, which was now missing an important bone in his neck, using some of Pernikoffs' own bone from his hip and rods to finalize stabilization of the newly built portion of his spine.

Read more at Science Daily

Gray hair linked to immune system activity and viral infection

Researchers at UAB and NIH report that loss of hair pigmentation, or gray hair, is associated with innate immune activation in mouse.

A new study on mice offers insights into why some people's hair may turn gray in response to a serious illness or chronic stress. Publishing May 3 in the open access journal PLOS Biology, researchers at the National Institutes of Health and the University of Alabama, Birmingham have discovered a connection between the genes that contribute to hair color and the genes that notify our bodies of a pathogenic infection.

When a body is under attack from a virus or bacteria, the innate immune system kicks into gear. All cells have the ability to detect foreign invaders and they respond by producing signaling molecules called interferons. Interferons signal to other cells to take action by turning on the expression of genes that inhibit viral replication, activate immune effector cells, and increase host defenses.

The connection between hair pigmentation and innate immune regulation was initially a bit surprising. Melissa Harris, primary author and assistant professor within the Department of Biology at UAB explains, "Genomic tools allow us to assess how all of the genes within our genome change their expression under different conditions, and sometimes they change in ways that we don't anticipate. We are interested in genes that affect how our stem cells are maintained over time. We like to study gray hair because it's an easy read-out of melanocyte stem cell dysfunction." Melanocyte stem cells are essential to hair color as they produce the melanocytes that are responsible for making and depositing pigment into the hair shaft.

In this case, an unexpected link was found between gray hair, the transcription factor MITF, and innate immunity. MITF is best known for its role in regulating the many functions within melanocytes. But the researchers found that MITF also serves to keep the melanocytes' interferon response in check. If MITF's control of the interferon response is lost in melanocyte stem cells, hair-graying results. Furthermore, if innate immune signaling is artificially activated in mice that are predisposed for getting gray hair, increased numbers of gray hairs are also produced.

"This new discovery suggests that genes that control pigment in hair and skin also work to control the innate immune system," said William Pavan, study co-author and chief of the Genetic Disease Research Branch at NIH's National Human Genome Research Institute (NHGRI). "These results may enhance our understanding of hair graying. More importantly, discovering this connection will help us understand pigmentation diseases with innate immune system involvement like vitiligo." Vitiligo, which causes discolored skin patches, affects between 0.5 percent to 1 percent of all humans.

Read more at Science Daily

Researchers defy biology: Mice remain slim on burger diet

Mouse eating cheese.

We are our own worst enemy when it comes to developing obesity. The body is naturally geared to assimilate energy from the food we eat and store it as fat until it is needed. This is the result of millions of years of evolution under the pressure of low food availability.

But today, where many of us have constant access to high calorie foods, our body's impressive ability to convert food into fat has, ironically, become problematic. Consequently, the number of overweight people worldwide is skyrocketing, leading to large health consequences for both the individual and society.

However, as part of a new study, researchers at the University of Copenhagen have now managed to inhibit the body's ability to store fat. They genetically delete the enzyme NAMPT in fat tissue of mice, and this renders the animals completely resistant to becoming overweight or obese, even on a very fatty diet.

'We gave the mice a diet that more or less corresponds to continuously eating burgers and pizza. Still, it was impossible for them to expand their fat tissue. Our ultimate goal is that by understanding these fundamental underpinnings of how we become obese, we can apply our finding to the development of novel treatment strategies for metabolic disease,' says Karen Nørgaard Nielsen, first author on the publication and a Ph.D. student at the Novo Nordisk Foundation Center for Basic Metabolic Research.

High-Fat Food, Same Weight

The findings are in line with results obtained from humans. Several studies have shown that the presence of large amounts of the enzyme NAMPT in blood and in stomach fat tissue is significantly connected with being overweight or obese. However, this study provides the first evidence that NAMPT is absolutely required to become overweight or obese and that lack of NAMPT in fat tissue fully protects against obesity.

In the University of Copenhagen study, the researchers compared how normal mice and mice lacking NAMPT in fat tissue gained weight when given either high-fat food or a healthier, lower-fat diet. When on the healthy diet, there was no difference in body weight or the amount of fat between the normal mice and the mice lacking NAMPT.

However, when the mice were given high-fat food, the control mice became very obese, yet the mice lacking NAMPT gained no more weight from high-fat food than when they were on the healthier diet. In addition, the mice lacking NAMPT maintained better control of blood glucose than normal mice when eating high-fat food.

Contradicts the General View

The result challenges the general view of NAMPT, which is largely seen as an enzyme that should be boosted for therapeutic purposes.

'NAMPT appears to increase the metabolic functionality of almost every tissue in the body in which it has been studied. For example, there are indications that the liver and skeletal muscle may benefit from increased NAMPT activity. We similarly find that NAMPT is critical for fat tissue function. Unfortunately, that function is efficiently storing fat. NAMPT in fat tissue was likely once an extraordinary benefit to our ancestors but in today's society full of high-fat, calorically-dense foods, it may now pose a liability', says Associate Professor Zachary Gerhart-Hines from the Novo Nordisk Foundation Center for Basic Metabolic Research and corresponding author on the study.

He does not necessarily believe that generally decreasing NAMPT is a viable treatment strategy in humans. There would be too great a risk for potentially harmful consequences in other tissues of the body.

Read more at Science Daily

What the gorilla microbiome tells us about evolution and human health

A study of the microbiomes of wild gorillas and chimpanzees offers insights into the evolution of the human microbiome and might even have implications for human health. The research project was led by scientists at the Center for Infection and Immunity (CII) at Columbia University's Mailman School of Public Health. Findings appear in the journal Nature Communications.

The researchers used genetic sequencing to analyze fecal samples collected by the Wildlife Conservation Society (WCS) from wild African great apes living the Sangha region of the Republic of Congo over the course of three years. Their goal was to understand the mix of gut microbes living in gorillas and chimpanzees and compare them to those already documented in other non-human primates and human populations. They found that gorilla and chimpanzee microbiomes fluctuate with seasonal rainfall patterns and diet, switching markedly during the summer dry period when succulent fruits abound in their environment and make up a larger proportion of their diet, as opposed to their usual, more fiber-rich diet of leaves and bark.

These seasonal shifts in the microbiomes of gorillas and chimpanzees are similar to seasonal microbiome changes observed in the human Hadza hunter-gatherers from Tanzania, who also rely heavily on the seasonal availability of foods in their environment. Seasonal shifts in the microbiomes of human industrialized cultures, such as the United States, are likely less prevalent owing to reduced reliance on seasonally available foods and globalization of the food supply, as evident in any grocery store.

"While our human genomes share a great deal of similarity with those of our closest living relatives, our second genome (the microbiome) has some important distinctions, including reduced diversity and the absence of bacteria and archaea that appear to be important for fiber fermentation," says first author Allison L. Hicks, MS, a researcher at CII. "Understanding how these lost microbes influence health and disease will be an important area for future studies."

"We observed dramatic changes in the gorilla and chimpanzee microbiomes depending on seasons and what they are eating," says senior author Brent L. Williams, PhD, assistant professor of Epidemiology at CII. "Bacteria that help gorillas break down fibrous plants are replaced once a year by another group of bacteria that feed on the mucous layer in their gut during the months they are eating fruits.

"The fact that our microbiomes are so different from our nearest living evolutionary relatives says something about how much we've changed our diets, consuming more protein and animal fat at the expense of fiber," says Williams. "Many humans may be living in a constant state of fiber deficiency. Such a state may be promoting the growth of bacteria that degrade our protective mucous layer, which may have implications for intestinal inflammation, even colon cancer."

All great apes are endangered or critically endangered. Down to fewer than 500,000, their numbers have been reduced through deforestation-which destroys their habitat-and through hunting, including for meat. Even infectious disease is a major factor-as many as one-quarter of the world's gorilla population has died because of Ebola.

"We are losing biodiversity on a global scale," cautions co-author Sarah Olson, PhD, associate director of wildlife health at WCS. "In fact, our own human microbiome is not immune to this phenomenon. There is an ever growing need for conservation efforts to preserve environments that are vital to the health of animal populations."

Read more at Science Daily

Flares in the universe can now be studied on Earth

Solar flares are caused by magnetic reconnection in space and can interfere with our communications satellites, affecting power grids, air traffic and telephony. Now, researchers at Chalmers University of Technology, Sweden, have found a new way to imitate and study these spectacular space plasma phenomena in a laboratory environment.

Solar flares, cosmic radiation, and the northern lights are well known phenomena. But exactly how their enormous energy arises is not as well understood.

Now, physicists at Chalmers University of Technology, Sweden, have discovered a new way to study these spectacular space plasma phenomena in a laboratory environment. The results have been published in the journal Nature Communications.

"Scientists have been trying to bring these space phenomena down to earth for a decade. With our new method we can enter a new era, and investigate what was previously impossible to study. It will tell us more about how these events occur," says Longqing Yi, researcher at the Department of Physics at Chalmers.

The research concerns so-called 'magnetic reconnection' -- the process which gives rise to these phenomena. Magnetic reconnection causes sudden conversion of energy stored in the magnetic field into heat and kinetic energy. This happens when two plasmas with anti-parallel magnetic fields are pushed together, and the magnetic field lines converge and reconnect. This interaction leads to violently accelerated plasma particles that can sometimes be seen with the naked eye -- for example, during the northern lights.

Magnetic reconnection in space can also influence us on earth. The creation of solar flares can interfere with communications satellites, and thus affect power grids, air traffic and telephony.

In order to imitate and study these spectacular space plasma phenomena in the laboratory, you need a high-power laser, to create magnetic fields around a million times stronger than those found on the surface of the sun. In the new scientific article, Longqing Yi, along with Professor Tünde Fülöp from the Department of Physics, proposed an experiment in which magnetic reconnection can be studied in a new, more precise way. Through the use of grazing incidence of ultra-short laser pulses, the effect can be achieved without overheating the plasma. The process can thus be studied very cleanly, without the laser directly affecting the internal energy of the plasma.

The proposed experiment would therefore allow us to seek answers to some of the most fundamental questions in astrophysics.

"We hope that this can inspire many research groups to use our results. This is a great opportunity to look for knowledge that could be useful in a number of areas. For example, we need to better understand solar flares, which can interfere with important communication systems. We also need to be able to control the instabilities caused by magnetic reconnection in fusion devices," says Tünde Fülöp.

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Frequent sauna bathing reduces risk of stroke

Frequent sauna bathing reduces the risk of stroke.

Frequent sauna bathing is associated with a reduced risk of stroke, according to a new international study. In a 15-year follow-up study, people taking a sauna 4-7 times a week were 61% less likely to suffer a stroke than those taking a sauna once a week. This is the first prospective large-scale study on this topic, and the findings were reported in Neurology.

Stroke is one of the leading causes of disability worldwide, placing a heavy human and economic burden on societies. The reduced risk associated with sauna bathing was found by a team of scientists from the Universities of Eastern Finland, Bristol, Leicester, Atlanta, Cambridge and Innsbruck.

The findings are based on the population-based Kuopio Ischaemic Heart Disease Risk Factor (KIHD) study and involved 1,628 men and women aged 53 to 74 years living in the eastern part of Finland. Based on their frequency of taking traditional Finnish sauna baths (relative humidity 10-20%), the study participants were divided into three groups: those taking a sauna once a week, those taking a sauna 2-3 times a week, and those taking a sauna 4-7 times a week.

The more frequently saunas were taken, the lower was the risk of stroke. Compared to people taking one sauna session per week, the risk was decreased by 14% among those with 2-3 sessions and 61% among those with 4-7 sessions. The association persisted even when taking into account conventional stroke risk factors, such as age, sex, diabetes, body mass index, blood lipids, alcohol consumption, physical activity and socio-economic status. The strength of association was similar in men and women.

Previous results from the KIHD study at the University of Eastern Finland have shown that frequent sauna bathing also significantly reduces the risk of cardiovascular and all-cause mortality. According to the researchers, mechanisms driving the association of sauna bathing with reduced stroke may include a reduction in blood pressure, stimulation of immune system, a positive impact on the autonomic nervous system, and an improved cardiovascular function. In a recent experimental study, the same group of scientists also showed that sauna bathing has acute effects on the stiffness of the arterial wall, hence influencing blood pressure and cardiac function parameters.

From Science Daily

Engraved Crimean stone artifact may demonstrate Neanderthal symbolism

The engraved flint flake from Kiik-Koba layer IV.

A flint flake from the Middle Paleolithic of Crimea was likely engraved symbolically by a skilled Neanderthal hand, according to a study published May 2, 2018 in the open-access journal PLOS ONE by Ana Majkic from the University of Bordeaux, France and colleagues. The authors developed a detailed framework for interpreting engravings on stone artifacts.

Engraved stone artifacts are important clues to the history of human culture and cognition. Incisions on the cortex (soft outer layer) of flint or chert flakes are known from Middle and Lower Paleolithic sites across Europe and the Middle East. However, it can be difficult to determine the action that created an incision: was it an accidental scrape or purposeful engraving? To address this issue, Majkic and colleagues created an interpretive framework that allows researchers to classify the structure and patterns of engraved cortexes and cross-check these attributes with a list of possible causal actions.

They tested this methodology with an engraved flake from the cave site of Kiik-Koba in Crimea. The many stone artifacts at the site are associated with Neanderthal remains and date to around 35,000 years ago. Following microscopic examination of the grooved lines on the flint cortex, the researchers concluded that the incisions represent deliberate engravings that would have required fine motor skills and attention to detail. These engravings appear to have been made with symbolic or communicative intent.

If this interpretation is correct, this engraved flake would join a growing list of signs that Neanderthals engaged in symbolic activities, along with evidence of intentional burial, personal ornaments, and other decorated objects. This has implications for the question of when and how many times this sort of cultural expression has evolved among hominin populations. The researchers hope to hone their framework further for use with artifacts of varying ages and cultural contexts.

From Science Daily