Depression Linked to Shortage of a Single Naturally Occurring Chemical


Depression plagues about 300 million people worldwide, and as scientists learn more about the condition they are realizing it’s far more complex than we once thought. This year alone, a new type of depression was identified, and scientists uncovered about 80 genes that might determine why some people are more susceptible than others. Fortunately, these discoveries are also showing us how to better treat depression. A paper released in July took a step in a new direction by identifying a naturally occurring chemical linked to depression that could be a key target for future drugs.

The paper, released in Proceedings of the National Academy of Sciences, focused on acetyl-L-carnitine (ALC), which usually is involved in converting food into energy. Led by Stanford University professor of psychiatry and behavioral sciences, Natalie Rasgon, Ph.D., this study was among the first to show that low levels of ALC are linked to depressive states in humans. Rasgon established this connection by collecting life history details and blood samples from a diverse sample of participants ranging from 20 to 70 years old.

Depression
A future drug that targets ALC might provide a new avenue for depression treatment 

Rasgon compared the blood samples of 45 healthy controls and 71 participants who suffered from either moderate or severe depression and found that those with depression had significiantly lower levels of ALC in their blood. Importantly, she also found that those with the lowest levels of ALC tended to have the most severe symptoms, developed depression later in life, and reported experiencing little relief when they adhered to traditional treatment.

In a previous interview with Inverse, Rasgon speculated that dips in ALC could partially explain patterns of depression that emerge in individuals who had experienced neglect, poverty or other trying circumstances during childhood.

“We’ve known that people who experienced childhood adversity subsequently experience worse overall health, cognitive performance, and are at risk for depression when they reach mid-life,” Rasgon said. “This study mechanistically addresses the link between adversity and depression because of the low ALC levels. This is speculative, but it could decrease the body’s capacity to tolerate stress.”

Rasgon emphasized that while it might be tempting to try to treat low ALC levels with a supplement (ALC supplements are easy to find), she doesn’t think that restoring ALC levels with external sources is the answer. She believes that supplementation could “just derail the potential efficacy of a drug” that may be developed in the future.

“At this point, we want to be very careful in specifying what we’ve achieved: We have found a new biomarker for depression, and it has significant potential for finding a new molecular target for drugs,” Rasgon said.

Instead, it’s best to look at ALC as a target for some future treatment that might provide solace to millions of people in years to come.

Flexible, wearable oral sodium sensor could help improve hypertension control


Summary:
For people who have hypertension and certain other conditions, eating too much salt raises blood pressure and increases the likelihood of heart complications. To help monitor salt intake, researchers have developed a flexible and stretchable wireless sensing system designed to be comfortably worn in the mouth to measure the amount of sodium a person consumes.

For people who have hypertension and certain other conditions, eating too much salt raises blood pressure and increases the likelihood of heart complications. To help monitor salt intake, researchers have developed a flexible and stretchable wireless sensing system designed to be comfortably worn in the mouth to measure the amount of sodium a person consumes.

Based on an ultrathin, breathable elastomeric membrane, the sensor integrates with a miniaturized flexible electronic system that uses Bluetooth technology to wirelessly report the sodium consumption to a smartphone or tablet. The researchers plan to further miniaturize the system — which now resembles a dental retainer — to the size of a tooth.

“We can unobtrusively and wirelessly measure the amount of sodium that people are taking in over time,” explained Woon-Hong Yeo, an assistant professor in the Woodruff School of Mechanical Engineering at the Georgia Institute of Technology. “By monitoring sodium in real-time, the device could one day help people who need to restrict sodium intake learn to change their eating habits and diet.”

Details of the device are reported May 7 in the early edition of the journal Proceedings of the National Academy of Sciences. The device has been tested in three adult study participants who wore the sensor system for up to a week while eating both solid and liquid foods including vegetable juice, chicken soup and potato chips.

According to the American Heart Association, Americans on average eat more than 3,400 milligrams of sodium each day, far more than the limit of 1,500 milligrams per day it recommends. The association surveyed a thousand adults and found that “one-third couldn’t estimate how much sodium they ate, and another 54 percent thought they were eating less than 2,000 milligrams of sodium a day.”

The new sodium sensing system could address that challenge by helping users better track how much salt they consume, Yeo said. “Our device could have applications for many different goals involving eating behavior for diet management or therapeutics,” he added.

Key to development of the intraoral sensor was replacement of traditional plastic and metal-based electronics with biocompatible and ultrathin components connected using mesh circuitry. Sodium sensors are available commercially, but Yeo and his collaborators developed a flexible micro-membrane version to be integrated with the miniaturized hybrid circuitry.

“The entire sensing and electronics package was conformally integrated onto a soft material that users can tolerate,” Yeo explained. “The sensor is comfortable to wear, and data from it can be transmitted to a smartphone or tablet. Eventually the information could go a doctor or other medical professional for remote monitoring.”

The flexible design began with computer modeling to optimize the mechanical properties of the device for use in the curved and soft oral cavity. The researchers then used their model to design the actual nanomembrane circuitry and choose components.

The device can monitor sodium intake in real-time, and record daily amounts. Using an app, the system could advise users planning meals how much of their daily salt allocation they had already consumed. The device can communicate with a smartphone up to ten meters away.

Next steps for the sodium sensor are to further miniaturize the device, and test it with users who have the medical conditions to address: hypertension, obesity or diabetes.

The researchers would like to do away with the small battery, which must be recharged daily to keep the sensor in operation. One option would be to power the device inductively, which would replace the battery and complex circuit with a coil that could obtain power from a transmitter outside the mouth.

The project grew out of a long-term goal of producing an artificial taste system that can sense sweetness, bitterness, pH and saltiness. That work began at Virginia Commonwealth University, where Yeo was an assistant professor before joining Georgia Tech.

Journal Reference:

  1. Yongkuk Lee et al. Wireless, Intraoral Hybrid Electronics for Real-Time Quantification of Sodium Intake Toward Hypertension Management. Proceedings of the National Academy of Sciences, 2018 DOI: 10.1073/pnas.1719573115

Weird New Theory Presents Unexpected Reason Huge Mammals Live in the Sea


Fifty million years ago, whales were four-footed, tailed land mammals about the size of wolves. Over the next 12 million years, these terrestrial whales evolved into fully aquatic animals, complete with oceanic adaptations like flippers and flukes. Today, all of the Earth’s largest mammals live in the sea, including blue whales, considered the biggest animal to have ever existed. For a long time, scientists believed these ocean mammals grew to their modern sizes because the ocean provided them with immense space and the ability to float, but a new study presents an entirely different line of reasoning.

According to a study published Monday in the Proceedings of the National Academy of Sciences, mammal growth is actually more constrained in water than on land. Size in the ocean is bound by hard limits, the scientists from Stanford and Louisiana Universities Marine Consortium explain: Mammals that are too small struggle to retain heat in the cold water, and those that are too large must capture enough food to live.

“Many people have viewed going into the water as more freeing for mammals, but what we’re seeing is that it’s actually more constraining,” co-author and Stanford geological sciences professor Jonathan Payne, Ph.D., explained in a statement released Monday. “It’s not that water allows you to be a big mammal, it’s that you have to be a big mammal in water — you don’t have any other options.”

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A marine mammal, the blue whale, is the largest creature in the ocean.

Payne and his team compiled data sets of the body masses for 3,859 living species and 2,999 fossil mammal species, paying attention to when the mammals turned aquatic and when they became their modern size. They determined a pattern: Once the land mammals became aquatic, they evolved very quickly to their new size until they reached a plateau and stalled growth.

The researchers’ reason that being large means being in charge is because larger mammals are better at retaining heat in water that’s lower than their body temperature. Metabolism, however, increases with size more than the animal’s actual ability to gather food, which puts a limit on how big they can get.

Baleen whales, for example, can be so huge because they spend less energy on feeding. Their mouth contains a filter-feeder system, which means that when a baleen whale opens its mouth, it scoops up water, then pushes it out through its bristle-like baleen. While the water is filtered away, the krill captured in the water remains as a meal. This method allows them to grow larger than mammals that use teeth to munch and capture prey, like orcas.

“The sperm whale seems to be the largest you can get without a new adaptation,” lead author and Stanford Ph.D. candidate Will Gearty explained in a statement. “The only way to get as big as a baleen whale is to completely change how you’re eating.”

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Sperm whales are thought to represent an upper size limit for swimming mammals; anything bigger requires additional adaptations.

What sizes comes down to, the researchers contend, are the basic principles of physics and chemistry. Living in water imposes selective pressures on metabolic rates and size — to be a big boy of the sea you need to live a pretty chill existence so that you don’t waste any precious energy not maintaining your largeness.

There’s one exception, though. The only aquatic mammals that didn’t rapidly evolve to be huge once they entered the sea are the much more manageable-sized sea otters. The scientists theorize that’s because these water-loving mammals took to the ocean relatively recently and, per the study’s accompanying statement, “many otter species still live much of their lives on land.”

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Sea otters don’t really follow the marine mammal size pattern.

Flint’s Water Is a Tiny Part of America’s Huge Drinking Problem, Says Study


The Flint, Michigan water crisis in 2014 exposed 98,000 people to dangerous levels of lead, disinfection byproducts, E. coli, and Legionella bacteria, causing long-term repercussions like infertility that are still being felt today. What we might not realize is that the dangerous drinking water in Flint, which still needs to be filtered at home, is not an isolated issue, as researchers report in a new article in the Proceedings of the National Academy of Sciences.

Flint, Michigan water crisis

In the study, released Monday, researchers from Columbia University and the University of California, Irvine report that between four to 28 percent of the population was affected by water quality violations between 1982 and 2015. That means millions of people were exposed to water that could put their health at risk. In total, health-based violations of water quality standards happen in approximately seven to eight percent of community water systems in any given year, the researchers report. In 2015 alone, 21 million Americans drank water from systems that violated health-based quality standards.

It’s very likely, the researchers note, that this level of exposure is connected to the 16.4 million cases of acute gastroenteritis that happen each year in the United States. Acute gastroenteritis is an intestinal infection that comes with diarrhea, nausea, and vomiting and can be caused by contaminated water.

Flint, Michigan drinking water
Contaminated water in Flint, Michigan. 

In the study, the researchers combed through data from 17,900 community water systems collected between 1982 and 2015, looking for violations of the Safe Drinking Water Act. They determined that water health violations happen in 7 to 8 percent of systems every single year and found that repeat violations happen most often in the Southwest, with significant violation “hotspots” in Oklahoma and Texas.

 Overall, they found that water health violations are more prevalent in rural areas than urban areas and are especially bad in low-income rural areas. They’re least likely to happen in regions that rely on privately owned water utilities. Aging infrastructure, impaired source water, and strained community finances contribute to this growing challenge of ensuring American water supplies are safe.
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The National Guard assessing water in West Virginia after the Elk River chemical spill. 

To help America’s water systems improve, we need to rigorously assess how widespread the problem is, the researchers write. Their paper is one of only a few peer-reviewed studies on compliance with the Safe Drinking Water Act, and, the authors write, there’s simply not a “good understanding of quality violations.” While monitoring water systems is federally mandated, most state enforcement agencies actually don’t have a system doing so or a guideline for identifying systems that need extra oversight.

The end result is a country where access to healthy water is determined by wealth and geographic status. “Equity concerns are also gaining recognition as evidence builds regarding lower-income and minority communities receiving poor quality water,” the researchers write.

The goal of the Environmental Protection Agency is to provide at least 91 percent of the American population with reliably safe community water systems. But between 1993 and 2009, the percent of the population that had this access fluctuated between 79 to 94 percent — an inconsistency that means there’s still a ways to go in providing drinking water that’s violation-free.

Ibuprofen Associated With Fertility Problems in Men, Study Finds


The next time you’re reaching for a tablet of Advil or Motrin for a quick cure to a headache or back pain or something, you might want to find another pain reliever of choice — especially if you’re a man with a family plan. A new studypublished Monday in the Proceedings of the National Academy of Sciences found ibuprofen can harm testicles and lead to impaired fertility in men.

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The study, led by a group of Danish researchers, is part of a broader investigation of the physiological side-effects of regular use of over-the-counter pain relievers. It’s a direct follow-up of studies on how aspirin, acetaminophen (better known by the brand name Tylenol) and ibuprofen (of which Advil and Motrin are the most well-known brand names) affect pregnant women, finding that each of these medications adversely affected testicles of male babies while inside the womb.

Ibuprofen use is particularly common among athletes who use over-the-counter pain relievers quite frequently. The research team found 31 male volunteers between the ages of 18 and 35, and gave 14 participants daily doses of ibuprofen of about 600 milligrams twice a day — a rate that’s fairly common for professional and amateur athletes alike. That’s the same maximum dosage recommended by drug makers and listed on the label of products like Advil and Motrin. The rest of the volunteers were put on a placebo.

After just 15 days, the researchers observed signs of dysfunction in the testicles for the men taking ibuprofen. The body’s pituitary glads secrete what are called luteinizing hormones that simulate testosterone production by the testicles. Regular ibuprofen use, it turns out, starts to modulate the rates and levels of luteinizing hormone secretion, as well as causing the ratio of testosterone and luteinizing hormones in the blood to decrease.

As a result, the participants started experiencing what’s called compensated hypogonadism, which can lead to decreased fertility, depression, and higher risk of experiencing heart failure or stroke.

The researchers followed up the trial with lab studies of human testicle samples provided by organized donors, verifying that the impact ibuprofen has on testicles and testosterone even outside the body.

There are two big things worth mentioning here. The first is that the sample size for the clinical side of the study is extremely small, so even with the lab experiments, the results as a whole really need to be taken with a grain of salt. The second thing is that with how quickly ibuprofen use affected testicular activity, the research team thinks the effects are pretty easily reversible.

Questions arise, however, whether those same effects are reversible even after long-term use. For athletes or patients with chronic pain, who have used ibuprofen for years, it’s unclear how permanent those hormone changes might be, or to what extent the negative impacts on fertility could be rectified.

Although the study is small, it’s bound to jumpstart greater investigations into how over-the-counter pain relievers affect fertility, given how popular the use of these drugs is. Men using ibuprofen might want to switch to a different drug of choice the next time they feel a headache coming on.

Study Shows How LSD Mimics Infant’s Mind as Ego Dissolves.


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A groundbreaking series of experiments show how LSD (Lysergic acid diethylamide) alters the operation of the brain.  Scientists gave LSD to 20 healthy volunteers in a specialist research center and used cutting-edge brain scanning techniques to understand what happens once the LSD is ingested.

One significant finding of the experiments was that when volunteers took LSD, many parts of their brain contributed to visual processing, not just the visual cortex.  They could essentially see things that weren’t there, experiencing dreamlike hallucinations.

Dr Robin Carhart-Harris, from the Department of Medicine at Imperial College London, who led the research, elaborated on this discovery:

“We observed brain changes under LSD that suggested our volunteers were ‘seeing with their eyes shut’ — albeit they were seeing things from their imagination rather than from the outside world. We saw that many more areas of the brain than normal were contributing to visual processing under LSD — even though the volunteers’ eyes were closed. Furthermore, the size of this effect correlated with volunteers’ ratings of complex, dreamlike visions. “

Dr. Carthart-Harris explained further that under LSD, people’s brain networks behave in a “unified” way, with specialized functions like vision, movement and hearing working without separation.

He said: ”Our results suggest that this effect underlies the profound altered state of consciousness that people often describe during an LSD experience. It is also related to what people sometimes call ‘ego-dissolution’, which means the normal sense of self is broken down and replaced by a sense of reconnection with themselves, others and the natural world. This experience is sometimes framed in a religious or spiritual way — and seems to be associated with improvements in well-being after the drug’s effects have subsided.”

lsd study

FIG. 1: Whole-brain cerebral blood flow maps for the placebo and LSD conditions, plus the difference map (cluster-corrected, P < 0.05; n = 15).

Interestingly, Dr. Carthart-Harris also said that the brain in the LSD state resembles the free and unconstrained brain of infancy, with its inherent hyper-emotionality and imaginative nature.  He added that “our brains become more constrained and compartmentalized as we develop from infancy into adulthood, and we may become more focused and rigid in our thinking as we mature.”

It’s noteworthy that the study was crowdfunded, raising almost $80,000 from individual donations. You can see their crowdfunding pitch which explains some of their approaches here:

Additional research from the same team showed for the first time that listening to music while on LSD trigged more information to be received from the parahippocampus, which is involved in mental imagery and personal memory.  The combination of music and LSD triggered complex visions in the subjects, such as evoking scenes from their lives.

The researchers hope that their findings will eventually lead to new therapies involving LSD, in particular directed at conditions with entrenched negative thought patterns such as depression or addiction.  The intention is to disrupt negative patterns by employing psychedelics.

“Scientists have waited 50 years for this moment — the revealing of how LSD alters our brain biology. For the first time we can really see what’s happening in the brain during the psychedelic state, and can better understand why LSD had such a profound impact on self-awareness in users and on music and art. This could have great implications for psychiatry, and helping patients overcome conditions such as depression,” said Professor David Nutt, the senior researcher on the study and Edmond J Safra Chair in Neuropsychopharmacology at Imperial College London.

Source:Proceedings of the National Academy of Sciences (PNAS).

A Quasicrystal’s Shocking Origin


By blasting a stack of minerals with a four-meter-long gun, scientists have found a new clue about the backstory of a very strange rock.

Electron backscatter diffraction pattern of a newly created quasicrystal displaying pentagonal symmetry.

Electron backscatter diffraction pattern of a newly created quasicrystal displaying pentagonal symmetry.

The story of what must surely be the most interesting rock in the world has taken yet another turn.

First, a recap: The rock, found some years ago in the basement of an Italian museum, turned out to be the only known natural “quasicrystal” — a dazzling, enigmatic form of matter in which atoms tessellate space in a pattern that never quite repeats. Additional tests revealed that the rock is the most ancient kind of meteorite, forged at the birth of the solar system. But it contains such chemically antithetical ingredients that no one could conceive of how, 4.5 billion years ago, they all got corralled into the same rock.

In search of more clues about the space rock’s formation, the Princeton physicist Paul Steinhardt, the Italian geologist Luca Bindi and collaborators managed to track down its unwitting discoverer, who had plucked it from a streambed in remote northeastern Russia in 1979 while panning for platinum. As I reported two years ago, Steinhardt and company then left their ivory towers and ventured out in rickety snowcats across the tundra, not only managing to find the stream their specimen came from, but even collecting additional grains of the ancient meteorite.

The spoils of the expedition generated new questions. Some of the newfound meteorite grains displayed signs of extreme shock, which is completely uncharacteristic of meteorites that formed at the birth of the solar system, typically through the gradual accretion of material. Perhaps the meteorite first formed that way, then later became embedded in an asteroid that experienced an epic collision. The question is: Were the patches of quasicrystal there from the start, or did the shock from the asteroid collision trigger their formation?

 

A rock specimen found in the collection of an Italian museum eight years ago that contains granules of icosahedrite, a natural quasicrystal.

Scientists have long debated how quasicrystals form. Their existence flies in the face of traditional crystallography. Whereas crystals consist of atomic motifs such as squares or hexagons whose exact repetitions fill space (a rule that allows only four types of rotational symmetry), quasicrystals consist of motifs of pentagons, decagons and any other shapes that tile space only in non-repeating arrangements, a freedom that allows the overall structure to have an infinite number of possible rotational symmetries. Hundreds of synthetic quasicrystals have been fabricated since the first was accidentally forged in a lab in 1982, yet it isn’t clear how or why atoms enter into such complicated configurations — only that they do so when certain elements are combined in the right ratios.

That’s what makes the latest plot twist so interesting.

Paul Asimow of the California Institute of Technology, collaborating with Steinhardt, Bindi and others, set out to re-create the shock experienced by the ancient meteorite. They loaded the minerals found in the rock into a chamber, and then, using a four-meter-long propellant gun, fired a projectile into the stack of ingredients.

In the mishmash of materials produced by the impact, the scientists found islands of a new kind of quasicrystal that had never been created in a lab. (The pentagonal symmetry of one of these microscopic regions can be seen in the electron backscatter diffraction image at the top.)

The findings, reported in the current issue of Proceedings of the National Academy of Sciences, indicate that the quasicrystals in the Russian meteorite did indeed form during a shock event. But the scientists were extremely surprised by how readily shock induced quasicrystals to form. Their experiment was nothing like the tightly controlled, low-pressure conditions under which quasicrystals are manufactured in the lab.

“What this suggests is that, at these high pressures, the formation of quasicrystals is so energetically favored that it forms even though this was not intended,” Steinhardt said. “What this tells us about quasicrystals is that they are not as delicate as many supposed — even under shock conditions and in air and without specially prepared starting materials, they can form. Also, since we produce what is a new quasicrystal by this approach, it suggests that other novel quasicrystals might be formed by similar experiments.”

We still don’t know why shock is such a great quasicrystal catalyst, or how certain elements came together inside the Russian meteorite in the first place. But these scientists are on it.

MODERN GENETICS CONFIRM ANCIENT RELATIONSHIP BETWEEN FINS AND HANDS


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Paleontologists have documented the evolutionary adaptations necessary for ancient lobe-finned fish to transform pectoral fins used underwater into strong, bony structures, such as those of Tiktaalik roseae. This enabled these emerging tetrapods, animals with limbs, to crawl in shallow water or on land. But evolutionary biologists have wondered why the modern structure called the autopod — comprising wrists and fingers or ankles and toes — has no obvious morphological counterpart in the fins of living fishes.

In the Dec. 22, 2014, issue of the Proceedings of the National Academy of Sciences, researchers argue previous efforts to connect fin and fingers fell short because they focused on the wrong fish. Instead, they found the rudimentary genetic machinery for mammalian autopod assembly in a non-model fish, the spotted gar, whose genome was recently sequenced.

“Fossils show that the wrist and digits clearly have an aquatic origin,” said Neil Shubin, PhD, the Robert R. Bensley Professor of organismal biology and anatomy at the University of Chicago and a leader of the team that discoveredTiktaalik in 2004. “But fins and limbs have different purposes. They have evolved in different directions since they diverged. We wanted to explore, and better understand, their connections by adding genetic and molecular data to what we already know from the fossil record.”

Initial attempts to confirm the link based on shape comparisons of fin and limb bones were unsuccessful. The autopod differs from most fins. The wrist is composed of a series of small nodular bones, followed by longer thin bones that make up the digits. The bones of living fish fins look much different, with a set of longer bones ending in small circular bones called radials.

The primary genes that shape the bones, known as the HoxD and HoxAclusters, also differ. The researchers first tested the ability of genetic “switches” that control HoxDand HoxA genes from teleosts — bony, ray-finned fish — to shape the limbs of developing transgenic mice. The fish control switches, however, did not trigger any activity in the autopod.

Teleost fish — a vast group that includes almost all of the world’s important sport and commercial fish — are widely studied. But the researchers began to realize they were not the ideal comparison for studies of how ancient genes were regulated. When they searched for wrist and digit-building genetic switches, they found “a lack of sequence conservation” in teleost species.

They traced the problem to a radical change in the genetics of teleost fish. More than 300 million years ago, after the fish-like creatures that would become tetrapods split off from other bony fish, a common ancestor of the teleost lineage went through a whole-genome duplication (WGD) — a phenomenon that has occurred multiple times in evolution.

By doubling the entire genetic repertoire of teleost fish, this WGD provided them with enormous diversification potential. This may have helped teleosts to adapt, over time, to a variety of environments worldwide. In the process, “the genetic switches that control autopod-building genes were able to drift and shuffle, allowing them to change some of their function, as well as making them harder to identify in comparisons to other animals, such as mice,” said Andrew Gehrke, a graduate student in the Shubin lab and lead author of the study.

Not all bony fishes went through the whole genome duplication, however. The spotted gar, a primitive freshwater fish native to North America, split off from teleost fishes before the WGD.

When the research team compared Hox gene switches from the spotted gar with tetrapods, they found “an unprecedented and previously undescribed level of deep conservation of the vertebrate autopod regulatory apparatus.” This suggests, they note, a high degree of similarity between “distal radials of bony fish and the autopod of tetrapods.”

They tested this by inserting gar gene switches related to fin development into developing mice. This evoked patterns of activity that were “nearly indistinguishable,” the authors note, from those driven by the mouse genome.

“Overall,” the researchers conclude, “our results provide regulatory support for an ancient origin of the ‘late’ phase of Hox expression that is responsible for building the autopod.”

SUGAR MOLECULE LINKS RED MEAT CONSUMPTION AND ELEVATED CANCER RISK IN MICE


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While people who eat a lot of red meat are known to be at higher risk for certain cancers, other carnivores are not, prompting researchers at the University of California, San Diego School of Medicine to investigate the possible tumor-forming role of a sugar called Neu5Gc, which is naturally found in most mammals but not in humans.

In a study published in the Dec. 29 online early edition of the Proceedings of the National Academy of Sciences, the scientists found that feeding Neu5Gc to mice engineered to be deficient in the sugar (like humans) significantly promoted spontaneous cancers. The study did not involve exposure to carcinogens or artificially inducing cancers, further implicating Neu5Gc as a key link between red meat consumption and cancer.

“Until now, all of our evidence linking Neu5Gc to cancer was circumstantial or indirectly predicted from somewhat artificial experimental setups,” said principal investigator Ajit Varki, MD, Distinguished Professor of Medicine and Cellular and Molecular Medicine and member of the UC San Diego Moores Cancer Center. “This is the first time we have directly shown that mimicking the exact situation in humans — feeding non-human Neu5Gc and inducing anti-Neu5Gc antibodies — increases spontaneous cancers in mice.”

Varki’s team first conducted a systematic survey of common foods. They found that red meats (beef, pork and lamb) are rich in Neu5Gc, affirming that foods of mammalian origin such as these are the primary sources of Neu5Gc in the humandiet. The molecule was found to be bio-available, too, meaning it can be distributed to tissues throughout the body via the bloodstream.

The researchers had previously discovered that animal Neu5Gc can be absorbed into human tissues. In this study, they hypothesized that eating red meat could lead to inflammation if the body’s immune system is constantly generating antibodies against consumed animal Neu5Gc, a foreign molecule. Chronic inflammation is known to promote tumor formation.

To test this hypothesis, the team engineered mice to mimic humans in that they lacked their own Neu5Gc and produced antibodies against it. When these mice were fed Neu5Gc, they developed systemic inflammation. Spontaneous tumor formation increased fivefold and Neu5Gc accumulated in the tumors.

“The final proof in humans will be much harder to come by,” Varki said. “But on amore general note, this work may also help explain potential connections of red meat consumption to other diseases exacerbated by chronic inflammation, such as atherosclerosis and type 2 diabetes.

“Of course, moderate amounts of red meat can be a source of good nutrition for young people. We hope that our work will eventually lead the way to practical solutions for this catch-22.”