Origin of life insight: Peptides can form without amino acids

Molecules of life concept

Peptides, one of the fundamental building blocks of life, can be formed from the primitive precursors of amino acids under conditions similar to those expected on the primordial Earth, finds a new UCL study.

The findings, published in Nature, could be a missing piece of the puzzle of how life first formed.

"Peptides, which are chains of amino acids, are an absolutely essential element of all life on Earth. They form the fabric of proteins, which serve as catalysts for biological processes, but they themselves require enzymes to control their formation from amino acids," explained the study's lead author, Dr Matthew Powner (UCL Chemistry).

"So we've had a classic chicken-and-egg problem -- how were the first enzymes made?"

He and his team have demonstrated that the precursors to amino acids, called aminonitriles, can be easily and selectively turned into peptides in water, taking advantage of their own built-in reactivity with the help of other molecules that were present in primordial environments.

"Many researchers have sought to understand how peptides first formed to help life develop, but almost all of the research has focused on amino acids, so the reactivity of their precursors was overlooked," said Dr Powner.

The precursors, aminonitriles, require harsh conditions, typically strongly acidic or alkaline, to form amino acids. And then amino acids must be recharged with energy to make peptides. The researchers found a way to bypass both of these steps, making peptides directly from energy-rich aminonitriles.

They found that aminonitriles have the innate reactivity to achieve peptide bond formation in water with greater ease than amino acids. The team identified a sequence of simple reactions, combining hydrogen sulfide with aminonitriles and another chemical substrate ferricyanide, to yield peptides.

"Controlled synthesis, in response to environmental or internal stimuli, is an essential element of metabolic regulation, so we think that peptide synthesis could have been part of a natural cycle that took place in the very early evolution of life," said Pierre Canavelli, the first author of the study who completed it while at UCL.

The molecules that served as substrates to help the formation of the amide bonds in the experiments are outgassed during volcanism and are all likely to have been present on the early Earth.

"This is the first time that peptides have been convincingly shown to form without using amino acids in water, using relatively gentle conditions likely to be available on the primitive Earth," said co-author Dr Saidul Islam (UCL Chemistry).

The findings may also be useful to the field of synthetic chemistry, as amide bond formation is essential for many commercially important synthetic materials, bioactive compounds and pharmaceuticals. The method used in this study is chemically unconventional but follows a pathway to ligate (join together) peptides that mimics biological processes, unlike peptide-building pathways more commonly used in chemistry laboratories that run in the opposite direction and require expensive and wasteful reagents.

The research team is furthering their studies by searching for other pathways to peptides using aminonitriles, and investigating the functional properties of the peptides that their experiments have produced, to better understand how they could have helped kick start life 4 billion years ago.

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Insects feel persistent pain after injury, evidence suggests

Fruit fly

Scientists have known insects experience something like pain since 2003, but new research published today from Associate Professor Greg Neely and colleagues at the University of Sydney proves for the first time that insects also experience chronic pain that lasts long after an initial injury has healed.

The study in the peer-reviewed journal Science Advances offers the first genetic evidence of what causes chronic pain in Drosophila (fruit flies) and there is good evidence that similar changes also drive chronic pain in humans. Ongoing research into these mechanisms could lead to the development of treatments that, for the first time, target the cause and not just the symptoms of chronic pain.

"If we can develop drugs or new stem cell therapies that can target and repair the underlying cause, instead of the symptoms, this might help a lot of people," said Associate Professor Neely, whose team of researchers is studying pain at the Charles Perkins Centre with the goal of developing non-opioid solutions for pain management.

Pain and insects

"People don't really think of insects as feeling any kind of pain," said Associate Professor Neely. "But it's already been shown in lots of different invertebrate animals that they can sense and avoid dangerous stimuli that we perceive as painful. In non-humans, we call this sense 'nociception', the sense that detects potentially harmful stimuli like heat, cold, or physical injury, but for simplicity we can refer to what insects experience as 'pain'."

"So we knew that insects could sense 'pain', but what we didn't know is that an injury could lead to long lasting hypersensitivity to normally non-painful stimuli in a similar way to human patients' experiences."

What is chronic pain?

Chronic pain is defined as persistent pain that continues after the original injury has healed. It comes in two forms: inflammatory pain and neuropathic pain.

The study of fruit flies looked at neuropathic 'pain', which occurs after damage to the nervous system and, in humans, is usually described as a burning or shooting pain. Neuropathic pain can occur in human conditions such as sciatica, a pinched nerve, spinal cord injuries, postherpetic neuralgia (shingles), diabetic neuropathy, cancer bone pain, and in accidental injuries.

Testing pain in fruit flies

In the study, Associate Professor Neely and lead author Dr Thang Khuong from the University's Charles Perkins Centre, damaged a nerve in one leg of the fly. The injury was then allowed to fully heal. After the injury healed, they found the fly's other legs had become hypersensitive. "After the animal is hurt once badly, they are hypersensitive and try to protect themselves for the rest of their lives," said Associate Professor Neely. "That's kind of cool and intuitive."

Next, the team genetically dissected exactly how that works.

"The fly is receiving 'pain' messages from its body that then go through sensory neurons to the ventral nerve cord, the fly's version of our spinal cord. In this nerve cord are inhibitory neurons that act like a 'gate' to allow or block pain perception based on the context," Associate Professor Neely said. "After the injury, the injured nerve dumps all its cargo in the nerve cord and kills all the brakes, forever. Then the rest of the animal doesn't have brakes on its 'pain'. The 'pain' threshold changes and now they are hypervigilant."

"Animals need to lose the 'pain' brakes to survive in dangerous situations but when humans lose those brakes it makes our lives miserable. We need to get the brakes back to live a comfortable and non-painful existence."

In humans, chronic pain is presumed to develop through either peripheral sensitisation or central disinhibition, said Associate Professor Neely. "From our unbiased genomic dissection of neuropathic 'pain' in the fly, all our data points to central disinhibition as the critical and underlying cause for chronic neuropathic pain."

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Yield-boosting stay-green gene identified from 118-year-old experiment in corn

A corn gene identified from a 118-year-old experiment at the University of Illinois could boost yields of today's elite hybrids with no added inputs. The gene, identified in a recent Plant Biotechnology Journal study, controls a critical piece of senescence, or seasonal die-back, in corn. When the gene is turned off, field-grown elite hybrids yielded 4.6 bushels more per acre on average than standard plants.

Dating back to 1896, the Illinois experiment was designed to test whether corn grain composition could be changed through artificial selection, a relatively new concept introduced by Charles Darwin just 37 years earlier. Repeated selection of high- and low-protein corn lines had the intended effect within about 10 generations. As selection for the traits continued, however, additional changes were noticeable.

"One of the things that was noted as early as the 1930s was that the low-protein line stays greener longer than the high-protein line. It's really obvious," says Stephen Moose, professor in the Department of Crop Sciences at Illinois and co-author of the study.

Staying green longer into the season can mean more yield. The plant continues photosynthesizing and putting energy toward developing grain. But, until now, no one knew the specific gene responsible for the stay-green trait in corn.

"The stay-green trait is like a 'fountain of youth' for plants because it prolongs photosynthesis and improves yield," says Anne Sylvester, a program director at the National Science Foundation, which funded this research. "This is a great basic discovery with practical impact."

The discovery of the gene was made possible through a decade-long public-private partnership between Illinois and Corteva Agriscience. Moose and Illinois collaborators initially gave Corteva scientists access to a population derived from the long-term corn protein experiment with differences in the stay-green trait. Corteva scientists mapped the stay-green trait to a particular gene, NAC7, and developed corn plants with low expression for the trait. Like the low-protein parent, these plants stayed green longer. They tested these plants in greenhouses and fields across the country over two field seasons.

Not only did corn grow just fine without NAC7, yield increased by almost 5 bushels per acre compared to conventional hybrids. Notably, the field results came without added nitrogen fertilizer beyond what farmers typically use.

"Collaborating with the University of Illinois gives us the opportunity to apply leading-edge technology to one of the longest running studies in plant genetics," says Jun Zhang, research scientist at Corteva Agriscience and co-author of the study. "The insights we derive from this relationship can result in more bushels without an increase in input costs, potentially increasing both profitability and productivity for farmers."

Moose's team then sequenced the NAC7 gene in the high- and low-protein corn lines and were able to figure out just how the gene facilitates senescence and why it stopped working in the low-protein corn.

"We could see exactly what the mutation was. It seems to have happened sometime in the last 100 years of this experiment, and fortunately has been preserved so that we can benefit from it now," Moose says.

He can't say for sure when the mutation occurred, because in the 1920s crop sciences faculty threw out the original seed from 1896.

"They had no way of knowing then that we could one day identify genes controlling these unique traits. But we have looked in other corn and we don't find this mutation," Moose says.

Future potential for this innovation could include commercialized seed with no or reduced expression of NAC7, giving farmers the option for more yield without additional fertilizer inputs.

Moose emphasizes the advancement couldn't have happened without both partners coming to the table.

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New gene linked to healthy aging in worms

People with the same lifespan do not necessarily have the same quality of life. As we live longer, extending quality of life -- "healthspan" -- is gaining importance. Scientists at the Okinawa Institute of Science and Technology Graduate University (OIST) have discovered a gene linked with healthy ageing in the roundworm C. elegans, shedding light on the genetics of healthspan.

The team has identified a gene called elpc-2 in C. elegans that plays an important role in maintaining healthspan as the worm ages. This gene is conserved in humans -- and worms with defects in this gene showed impaired movement as they aged. Movement at older ages is an indicator of healthspan in both humans and worms.

"As we age, some people keep full locomotor ability while others do not, and we want to understand the genetic reasons," says Dr. Kazuto Kawamura, first author of the study, published in G3: Genes, Genomes, Genetics. "This gene is one among many playing a role in healthy ageing."

"Our new experimental approach also allows us to test hundreds of worms simultaneously, which could be useful for other researchers."

C. "elegance"

C. elegans is a useful model for studying ageing -- it has a short lifespan and can be easily manipulated in the lab. Kawamura inserted random mutations into the genome of these worms. By studying the offspring of the mutated worms, he was able to test which mutations affected healthspan. He measured whether the organisms were able to maintain their ability to move toward a food source as they aged.

Worms were placed at the center of a dish with food at the edge. They naturally head towards food, providing that their movement is not impaired. Any worms that failed to reach the food on the first day were judged to have impaired movement in young age and were removed from the experiment -- Kawamura was only interested in how this ability declined with age.

The remaining mutants were retested as they got older using the same approach, dubbed the "edge assay" because worms migrate to the edge to reach food. In this later testing, several worms showing impaired movement were identified.

These were then sequenced and their DNA was compared with a normal "wild type" worm to pinpoint the mutations and identify the genes responsible.

"Creating hundreds of random mutants is not so difficult," says Kawamura, "but it is difficult to figure out which mutation is responsible for the impact on locomotor ability."

Understanding healthspan

In this way, the researchers identified elpc-2 and its role in healthspan. The gene encodes part of the elongator complex, which has many important functions including orchestrating the correct folding of proteins. Some of these proteins, in turn, may have roles in locomotion.

Mutants with a damaged elpc-2 gene lacked a working elongator complex, which explains why movement was impaired. To confirm this, Kawamura injected these worms with a working copy of the gene, and movement was restored. He also created worms that expressed a fluorescent copy of the elongator complex, illustrating its widespread expression throughout the body.

Interestingly, other genes were identified that had a strong impact on healthspan -- but not lifespan. In other words, the underlying mutations didn't much affect how long a worm lived, but did impact on how they moved. This demonstrates that while healthspan and lifespan overlap, the genetic basis is distinct.

The elongator complex is just one part of the healthspan puzzle. Next, Kawamura intends to explore other genes playing a role in healthy ageing.

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Moon-forming disk discovered around distant planet

Gas and dust around exoplanet concept

Using Earth's most powerful array of radio telescopes, astronomers have made the first observations of a circumplanetary disk of gas and dust like the one that is believed to have birthed the moons of Jupiter.

The find, reported online today in Astrophysical Journal Letters, adds to the intriguing story of planet PDS 70 c, a still-forming gas giant about 370 light years from Earth that was first revealed last month in visible light images.

Using the massive 66-antenna Atacama Large Millimeter/submillimeter Array (ALMA) in Chile, Rice University astronomer Andrea Isella and colleagues collected millimeter wave radio signals that revealed the presence of dust grains throughout the star system where PDS 70 c and its sister planet, PDS 70 b, are still forming.

"Planets form from disks of gas and dust around newly forming stars, and if a planet is large enough, it can form its own disk as it gathers material in its orbit around the star," Isella said. "Jupiter and its moons are a little planetary system within our solar system, for example, and it's believed Jupiter's moons formed from a circumplanetary disk when Jupiter was very young."

But most models of planet formation show that circumplanetary disks disappear within about 10 million years, which means circumplanetary disks haven't existed in our solar system for more than 4 billion years. To look for them elsewhere and gather observational evidence to test theories of planet formation, Isella and colleagues search for very young star systems where they can directly observe disks and the planets still forming inside them. In the new study, Isella and colleagues analyzed observations made by ALMA in 2017.

"There are a handful of candidate planets that have been detected in disks, but this is a very new field, and they are all still debated," Isella said. "(PDS 70 b and PDS 70 c) are among the most robust because there have been independent observations with different instruments and techniques."

PDS 70 is a dwarf star about three-quarters the mass of the sun. Both of its planets are 5-10 times larger than Jupiter, and the innermost, PDS 70 b, orbits about 1.8 billion miles from the star, roughly the distance from the sun to Uranus. PDS 70 c is a billion miles further out, in an orbit about the size of Neptune's.

PDS 70 b was first revealed in 2018 in infrared light images from a planet-hunting instrument called SPHERE at the European Southern Observatory's Very Large Telescope (VLT). In June, astronomers used another VLT instrument called MUSE to observe a visible wavelength of light known as H-alpha, which is emitted when hydrogen falls onto a star or planet and becomes ionized.

"H-alpha gives us more confidence that these are planets because it suggests they are still drawing in gas and dust and growing," Isella said.

The millimeter wavelength observations from ALMA provide even more evidence.

"It's complementary to the optical data and provides completely independent confirmation that there is something there," he said.

Isella said direct observation of planets with circumplanetary disks could allow astronomers to test theories of planet formation.

"There's much that we don't understand about how planets form, and we now finally have the instruments to make direct observations and begin answering questions about how our solar system formed and how other planets might form."

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Hubble uncovers black hole that shouldn't exist

Black hole concept

As if black holes weren't mysterious enough, astronomers using NASA's Hubble Space Telescope have found an unexpected thin disk of material furiously whirling around a supermassive black hole at the heart of the magnificent spiral galaxy NGC 3147, located 130 million light-years away.

The conundrum is that the disk shouldn't be there, based on current astronomical theories. However, the unexpected presence of a disk so close to a black hole offers a unique opportunity to test Albert Einstein's theories of relativity. General relativity describes gravity as the curvature of space and special relativity describes the relationship between time and space.

"We've never seen the effects of both general and special relativity in visible light with this much clarity," said Marco Chiaberge of the European Space Agency, and the Space Telescope Science Institute and Johns Hopkins University, both in Baltimore, Maryland, a member of the team that conducted the Hubble study.

"This is an intriguing peek at a disk very close to a black hole, so close that the velocities and the intensity of the gravitational pull are affecting how the photons of light look," added the study's first author, Stefano Bianchi of Università degli Studi Roma Tre, in Rome, Italy. "We cannot understand the data unless we include the theories of relativity."

Black holes in certain types of galaxies like NGC 3147 are malnourished because there is not enough gravitationally captured material to feed them regularly. So, the thin haze of infalling material puffs up like a donut rather than flattening out in a pancake-shaped disk. Therefore, it is very puzzling why there is a thin disk encircling a starving black hole in NGC 3147 that mimics much more powerful disks found in extremely active galaxies with engorged, monster black holes.

"We thought this was the best candidate to confirm that below certain luminosities, the accretion disk doesn't exist anymore," explained Ari Laor of the Technion-Israel Institute of Technology located in Haifa, Israel. "What we saw was something completely unexpected. We found gas in motion producing features we can explain only as being produced by material rotating in a thin disk very close to the black hole."

The astronomers initially selected this galaxy to validate accepted models about lower-luminosity active galaxies -- those with black holes that are on a meager diet of material. Models predict that an accretion disk forms when ample amounts of gas are trapped by a black hole's strong gravitational pull. This infalling matter emits lots of light, producing a brilliant beacon called a quasar, in the case of the most well-fed black holes. Once less material is pulled into the disk, it begins to break down, becomes fainter, and changes structure.

"The type of disk we see is a scaled-down quasar that we did not expect to exist," Bianchi said. "It's the same type of disk we see in objects that are 1,000 or even 100,000 times more luminous. The predictions of current models for gas dynamics in very faint active galaxies clearly failed."

The disk is so deeply embedded in the black hole's intense gravitational field that the light from the gas disk is modified, according to Einstein's theories of relativity, giving astronomers a unique look at the dynamic processes close to a black hole.

Hubble clocked material whirling around the black hole as moving at more than 10% of the speed of light. At those extreme velocities, the gas appears to brighten as it travels toward Earth on one side, and dims as it speeds away from our planet on the other side (an effect called relativistic beaming). Hubble's observations also show that the gas is so entrenched in the gravitational well the light is struggling to climb out, and therefore appears stretched to redder wavelengths. The black hole's mass is around 250 million Suns.

The researchers used Hubble's Space Telescope Imaging Spectrograph (STIS) to observe matter swirling deep inside the disk. A spectrograph is a diagnostic tool that divides light from an object into its many individual wavelengths to determine its speed, temperature, and other characteristics at a very high precision. The astronomers needed STIS's sharp resolution to isolate the faint light from the black-hole region and block out contaminating starlight.

"Without Hubble, we wouldn't have been able to see this because the black-hole region has a low luminosity," Chiaberge said. "The luminosities of the stars in the galaxy outshine anything in the nucleus. So if you observe it from the ground, you're dominated by the brightness of the stars, which drowns the feeble emission from the nucleus."

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Exactly how fast is the universe expanding?

Exactly how fast is the universe expanding?

Scientists are still not completely sure, but a Princeton-led team of astrophysicists has used the neutron star merger detected in 2017 to come up with a more precise value for this figure, known as the Hubble constant. Their work appears in the current issue of the journal Nature Astronomy.

"The Hubble constant is one of the most fundamental pieces of information that describes the state of the universe in the past, present and future," said Kenta Hotokezaka, the Lyman Spitzer, Jr. Postdoctoral Fellow in Princeton's Department of Astrophysical Sciences. "So we'd like to know what its value is."

Currently, the two most successful techniques for estimating the Hubble constant are based on observations of either the cosmic microwave background or stars blowing themselves to pieces in the distant universe.

But those figures disagree: Measurements of exploding stars -- Type Ia supernovae -- suggest that the universe is expanding faster than is predicted by Planck observations of the cosmic microwave background.

"So either one of them is incorrect, or the models of the physics which underpin them are wrong," said Hotokezaka. "We'd like to know what is really happening in the universe, so we need a third, independent check."

He and his colleagues -- Princeton's NASA Sagan Postdoctoral Fellow Kento Masuda, Ore Gottlieb and Ehud Nakar from Tel Aviv University in Israel, Samaya Nissanke from the University of Amsterdam, Gregg Hallinan and Kunal Mooley from the California Institute of Technology, and Adam Deller from Swinburne University of Technology in Australia -- found that independent check by using the merger of two neutron stars.

Neutron star mergers are phenomenally energetic events in which two massive stars whip around each other hundreds of times per second before merging in an extraordinary collision that flings out a burst of gravitational waves and an enormous blast of material. In the case of the neutron star merger that was detected on Aug. 17, 2017, the two stars -- each the size of Manhattan and with almost twice the mass of the sun -- were moving at a significant fraction of the speed of light before they collided.

The gravitational wave burst from a neutron star merger makes a distinctive pattern known as a "standard siren." Based on the shape of the gravitational wave signal, astrophysicists can calculate how strong the gravitational waves should have been. They can then compare that to the measured strength of the signal to work out how far away the merger occurred.

But there's a catch -- this only works if they know how the merging stars were oriented with respect to Earth's telescopes. The gravitational wave data can't distinguish between mergers that were nearby and edge-on, distant and face-on, or something in between.

To separate those possibilities, the researchers used a super-high-resolution radio "movie" of the fireball of material that was left behind after the neutron stars merged. To make their movie, they combined data from radio telescopes spread across the world.

"The resolution of the radio images we made was so high, if it was an optical camera, it could see individual hairs on someone's head 3 miles away," said Deller.

"By comparing the miniscule changes in the location and shape of this distant bullet of radio-emitting gas against several models including one developed on supercomputers, we were able to determine the orientation of the merging neutron stars," said Nakar.

Using this, they calculated how far away the merging neutron stars were -- and then, by comparing that with how fast their host galaxy is rushing away from ours, they could measure the Hubble constant.

After the 2017 neutron star merger (GW170817) was registered by nearly every astronomical instrument on the planet, astrophysicists calculated that the Hubble constant value was between 66 and 90 kilometers per second per megaparsec. By using tight constraints on the orientation of the collision, published last year by Mooley and several of the same co-authors, including Hotokezaka, the current group of collaborators were able to pin that estimate down further, to between 65.3 and 75.6 km/s/Mpc.

While that precision is "quite good," said Hotokezaka, it's still not good enough to distinguish between the Planck and Type Ia models. He and his colleagues estimate that to get that level of precision, they would need data from 15 more collisions like GW170817 -- with its helpful abundance of data up and down the entire electromagnetic spectrum -- or 50 to 100 collisions that are detected only with gravitational waves.

"This is the first time that astronomers have been able to measure the Hubble constant by using a joint analysis of a gravitational-wave signals and radio images," said Hotokezaka. "It is remarkable that only a single merger event allows us to measure the Hubble constant with a high precision -- and this approach relies neither on the cosmological model (Planck) nor the cosmic-distance ladder (Type Ia)."

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Cultural drive breeds war in new evolutionary theory

When anthropologists consider the origins of warfare, their evolutionary theories tend to boil it down to the resource-scarcity trifecta of food, territory and mates -- three resources that would justify the loss of life and risk to a warring group of hunter-gatherers.

But researchers from University of Colorado Denver, University of British Columbia and University of Santiago, Chile, created an evolutionary mathematical model to unearth a fourth theory. They found that acculturation -- the adoption and imitation of a victor's culture following defeat -- could promote the evolution of intergroup conflicts. In other words, groups may evolve to fight for fighting's sake, despite the costs.

The study, "Acculturation drives the evolution of intergroup conflict," was published June 21 in the journal PNAS.

"Warriors" and "shepherds" in human evolution

"I've researched the evolution of cooperation and altruism -- paradoxes in the conventional evolutionary theory of survival of the fittest -- by group selection, but in this case, we wanted to understand the evolution of intergroup conflict," said Burton Simon, PhD, associate professor of mathematics at the University of Colorado Denver, who has worked as a sort of "mathematical anthropologist" for the last decade.

The researchers' mathematical model is based on two classes of people: warriors, who specialize in intergroup conflicts and have a low birth rate, and shepherds, who cannot defend themselves but are highly reproductive. The amount of each within a group depended on the probability that an offspring becomes a warrior or shepherd, a cultural trait passed vertically from one generation to the next.

The study determined group dynamics through three types of events: group extinctions (a whole group dies, e.g., as the result of a drought or a bad crop), fissions (when an overly large group splits into two) and group conflicts due to their "belligerence" (assumed to increase a group's probability of trying to conquer another group). When groups fight in the model, the winner imposes its cultural traits on the loser or eliminates the group altogether. The belligerence of a group and the probability that they will impose their culture (acculturation tendency) are two of those traits.

"You need individuals who are shepherds to reproduce and individuals who are warriors to protect the group," said Simon. "But the right numbers of each can change over time in complicated and surprising ways."

Cultural evolution may promote the spread of conflict

How might these cultures thrive or die? Depending on the initial conditions of each group and which parameters (like acculturation and belligerence) were allowed to evolve, researchers found that sometimes groups fought each other into extinction. In other cases, the whole population reached a peaceful equilibrium.

But when researchers allowed all of the parameters to evolve, they found that acculturation coevolved with belligerence and warrior production. In other words, groups became more and more belligerent over time, and they forced their cultures on their victims instead of killing them.

That cultural evolution may promote the spread of conflict, even in cases where it may hurt both the groups and the individuals, is a theory that has received little attention. A mathematical model was one way to see how it could happen, said Simon.

"I realize mathematical anthropology sounds like an oxymoron," said Simon. "Most people who theorize about why there's so much conflict between human groups use economics and political science. But when you look at a hunter-gatherer society with a mathematical model, which forces you to state your assumptions precisely, the results can be enlightening."

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New antibiotics effective without triggering resistance, mouse study shows

Bacterial culture

Not only are they effective against Gram-positive and negative multi-resistant bacteria, they also appear not to trigger resistance when used to treat infection in mice. Such are the promises of the two new antibiotics created by Prof. Brice Felden and his team at the Inserm and Université de Rennes 1 'Bacterial Regulatory RNAs and Medicine' joint laboratory (U1230), in conjunction with a team from the Rennes Institute of Chemical Sciences (ISCR). This French advance could bring both fresh impetus and new possibilities for fighting antibiotic resistance worldwide. Details on this research will be published July 9 in PLOS Biology.

Antibiotics have saved so many lives over the previous century of their use in humans that they are considered to be one of the major breakthroughs of contemporary medicine. Unfortunately, growing resistance is gradually rendering them ineffective, with the threat of catastrophic public health consequences should this trend continue much longer. The few new antibiotics being brought to market essentially consist of so-called me-too drugs -- meaning that they are derived from existing classes of antibiotics.

Researchers from Inserm and Université de Rennes recently identified a new bacterial toxin which they transformed into potent antibiotics active against various bacteria responsible for human infections, whether Gram-positive or negative. "It all started with a fundamental discovery made in 2011," explains Brice Felden, Director of the Bacterial Regulatory RNAs and Medicine laboratory in Rennes. "We realized that a toxin produced by Staphylococcus aureus whose role is to facilitate infection is also capable of killing other bacteria present in our body. What we had identified was a molecule with dual toxic and antibiotic properties. We thought that if we could separate these activities, we would be able to create a new antibiotic non-toxic to the body. A challenge that we accepted!"

In conjunction with the team of ISCR chemist Michèle Baudy Floc'h, a new family of so-called peptidomimetics was synthesized. As their name suggests, these peptides are inspired by the existing natural bacterial peptides but have been shortened and modified. Out of the twenty molecules created, two proved effective against resistant Staphylococcus aureus and Pseudomonas aeruginosa in mouse models of severe sepsis or skin infection. In addition, no toxicity to the other cells and organs, whether in animals or human cells was observed. These new compounds are well tolerated at their active doses -- and even beyond -- and are devoid of the renal toxicity issues often encountered with this type of compound. "We tested them at doses 10 to 50 times higher than the effective dose without seeing toxicity" specifies Felden, adding that "the participation and imagination of the team and our chemist colleagues was needed to devise the most active molecules possible."

Little resistance observed under experimental conditions

Important to note was that the bacteria that the researchers had left in contact for several days in the animals with these antibiotics showed no signs of resistance. In order to go further, the researchers created conditions favorable to the development of resistance in vitro and in vivo -- with nothing happening. However, caution is still required here given the short experimental time periods (up to 15 days).

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Coral reefs shifting away from equator

Coral reef

Coral reefs are retreating from equatorial waters and establishing new reefs in more temperate regions, according to new research in the journal Marine Ecology Progress Series. The researchers found that the number of young corals on tropical reefs has declined by 85 percent -- and doubled on subtropical reefs -- during the last four decades.

"Climate change seems to be redistributing coral reefs, the same way it is shifting many other marine species," said Nichole Price, a senior research scientist at Bigelow Laboratory for Ocean Sciences and lead author of the paper. "The clarity in this trend is stunning, but we don't yet know whether the new reefs can support the incredible diversity of tropical systems."

As climate change warms the ocean, subtropical environments are becoming more favorable for corals than the equatorial waters where they traditionally thrived. This is allowing drifting coral larvae to settle and grow in new regions. These subtropical reefs could provide refuge for other species challenged by climate change and new opportunities to protect these fledgling ecosystems.

The researchers believe that only certain types of coral are able to reach these new locations, based on how far the microscopic larvae can swim and drift on currents before they run out of their limited fat stores. The exact composition of most new reefs is currently unknown, due to the expense of collecting genetic and species diversity data.

"We are seeing ecosystems transition to new blends of species that have never coexisted, and it's not yet clear how long it takes for these systems to reach equilibrium," said Satoshi Mitarai, an associate professor at Okinawa Institute of Science and Technology Graduate University and an author of the study. "The lines are really starting to blur about what a native species is, and when ecosystems are functioning or falling apart."

New coral reefs grow when larvae settle on suitable seafloor away from the reef where they originated. The research team examined latitudes up to 35 degrees north and south of the equator, and found that the shift of coral reefs is perfectly mirrored on either side. The paper assesses where and when "refugee corals" could settle in the future -- potentially bringing new resources and opportunities such as fishing and tourism.

The researchers, an international group from 17 institutions in 6 countries, compiled a global database of studies dating back to 1974, when record-keeping began. They hope that other scientists will add to the database, making it increasingly comprehensive and useful to other research questions.

"The results of this paper highlight the importance of truly long-term studies documenting change in coral reef communities," said Peter Edmunds, a professor at the University of California Northridge and author of the paper. "The trends we identified in this analysis are exceptionally difficult to detect, yet of the greatest importance in understanding how reefs will change in the coming decades. As the coral reef crisis deepens, the international community will need to intensify efforts to combine and synthesize results as we have been able to accomplish with this study."

Coral reefs are intricately interconnected systems, and it is the interplay between species that enables their healthy functioning. It is unclear which other species, such as coralline algae that facilitate the survival of vulnerable coral larvae, are also expanding into new areas ¬- or how successful young corals can be without them. Price wants to investigate the relationships and diversity of species in new reefs to understand the dynamics of these evolving ecosystems.

"So many questions remain about which species are and are not making it to these new locations, and we don't yet know the fate of these young corals over longer time frames," Price said. "The changes we are seeing in coral reef ecosystems are mind-boggling, and we need to work hard to document how these systems work and learn what we can do to save them before it's too late."

Some of the research that informed this study was conducted at the National Science Foundation's Moorea Coral Reef Long-Term Ecological Research site near French Polynesia, one of 28 such long-term research sites across the country and around the globe.

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A clearer picture of global ice sheet mass

Fluctuations in the masses of the world's largest ice sheets carry important consequences for future sea level rise, but understanding the complicated interplay of atmospheric conditions, snowfall input and melting processes has never been easy to measure due to the sheer size and remoteness inherent to glacial landscapes.

Much has changed for the better in the past decade, according to a new review paper co-authored by researchers at the University of Colorado Boulder, NASA, Utrecht University and Delft University of Technology and recently published in the Review of Geophysics.

The study outlines improvements in satellite imaging and remote sensing equipment that have allowed scientists to measure ice mass in greater detail than ever before.

"We've come a long way in the last 10 years from an observational perspective," said Jan Lenaerts, lead author of the research and an assistant professor in CU Boulder's Department of Atmospheric and Oceanic Sciences (ATOC). "Knowing what happens to ice sheets in terms of mass in, mass out allows us to better connect climate variations to ice mass and how much the mass has changed over time."

Ice sheets primarily gain mass from precipitation and lose it due to solid ice discharge and runoff of melt water. Precipitation and runoff, along with other surface processes, collectively determine the surface mass balance. The Antarctic Ice Sheet, the world's largest, is cold year-round with only marginal summer melting. A small increase or decrease in yearly snowfall, then, can make a considerable difference in surface mass because the addition or subtraction is compounded over a massive area.

"Snowfall is dominant over Antarctica and will stay that way for the next few decades," Lenaerts said. "And we've seen that as the atmosphere warms due to climate change, that leads to more snowfall, which somewhat mitigates the loss of ice sheet mass there. Greenland, by contrast, experiences abundant summer melt, which controls much of its present and future ice loss."

In years past, climate models would have been unable to render the subtleties of snowfall in such a remote area. Now, thanks to automated weather stations, airborne sensors and Earth-orbit satellites such as NASA's Gravity Recovery and Climate experiment (GRACE) mission, these models have been improved considerably. They produce realistic ice sheet surface mass balance, allow for greater spatial precision and account for regional variation as well as wind-driven snow redistribution -- a degree of detail that would have been unheard of as recently as the early 2000s.

"If you don't have the input variable right, you start off on the wrong foot," Lenaerts said. "We've focused on snowfall because it heavily influences the ice sheet's fate. Airborne observations and satellites have been instrumental in giving a better view of all these processes."

Ground-based radar systems and ice core samples provide a useful historical archive, allowing scientists to go back in time and observe changes in the ice sheet over long periods of time. But while current technologies allow for greater spatial monitoring, they lack the ability to measure snow density, which is a crucial variable to translate these measurements into mass changes.

The biggest opportunity may lie in cosmic ray counters, which measure surface mass balance directly by measuring neutrons produced by cosmic ray collisions in Earth's atmosphere, which linger in water and can be read by a sensor. Over long periods of time, an array of these devices could theoretically provide even greater detail still.

Overall, Lenaerts said, the field of ice sheet observation has come of age in recent years, but still stands to benefit from additional resources.

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Want to boost creativity? Try playing Minecraft

The next time you need to get the creative juices flowing, playing some types of video games may help.

Video games that foster creative freedom can increase creativity under certain conditions, according to new research from Iowa State University. The experimental study compared the effect of playing Minecraft, with or without instruction, to watching a TV show or playing a race car video game. Those given the freedom to play Minecraft without instruction were most creative.

"It's not just that Minecraft can help induce creativity. There seems to be something about choosing to do it that also matters," said Douglas Gentile, a professor of psychology.

If you are not familiar with the game, Gentile says Minecraft is like a virtual Lego world. The game, which has sold more than 100 million copies, allows players to explore unique worlds and create anything they can imagine. Study participants randomly assigned to play Minecraft were split into two groups. The one receiving instruction was told to play as creatively as possible.

After 40 minutes of play or watching TV, the 352 participants completed several creativity tasks. To measure creative production, they were asked to draw a creature from a world much different than Earth. More human-like creatures scored low for creativity and those less human-like scored high. Surprisingly, those instructed to be creative while playing Minecraft were the least creative.

Gentile says there's no clear explanation for this finding. In the paper published by Creativity Research Journal, he, Jorge Blanco-Herrera, lead author and former master's student in psychology; and Jeffrey Rokkum, former Ph.D. student in psychology, outlined possible reasons why the instructed Minecraft group scored lower. Blanco-Herrera says the instructions may have changed subjects' motivation for play.

"Being told to be creative may have actually limited their options while playing, resulting in a less creative experience," Blanco-Herrera said. "It's also possible they used all their 'creative juices' while playing and had nothing left when it came time to complete the test."

Games teach creativity similar to aggression

Video games can have both harmful and beneficial effects. Gentile's previous research has shown the amount, content and context of video games influence what players learn through repeated experiences. While much of Gentile's research has focused on aggression or prosocial behavior, he says the same appears to be true for creativity.

Most video games encourage players to practice some level of creativity. For example, players may create a character and story for role-playing games or be rewarded for creative strategies in competitive games. The researchers say even first-person shooter games can potentially inspire creativity as players think about strategy and look for advantages in combat.

"The research is starting to tell a more interesting, nuanced picture. Our results are similar to other gaming research in that you get better at what you practice, but how you practice might matter just as much," Gentile said.

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Good home learning in early years boosts your secondary school achievements

The positive effects of a rich home learning environment during a child's early years continue into adolescence and help improve test scores later in life, according to a new study published in School Effectiveness and School Improvement.

This research shows pre-schoolers whose parents regularly read and talked about books with them scored better on math tests at age 12. The study, lead by Dr Simone Lehrl of the University of Bamberg, is one of the first to provide detail on the importance of early years home learning on children's development up to early adolescence.

Researchers studied 229 German children from age three until secondary school and participants' literacy and numeracy skills were tested annually in their three years of preschool (ages 3-5), and again when they were 12 or 13 years old.

They found that children gained from home stimulation in their preschool years in literacy, language and arithmetic skills which, in turn, led to higher outcomes in reading and mathematical skills in secondary school, regardless of the home learning environment then.

Dr Lehrl said: "Our results underline the great importance of exposing children to books for development not just in literacy but numeracy too: early language skills not only improve a child's reading but also boost mathematical ability.

"Encouraging caregivers to engage with their children in direct literacy activities, shared book reading and advanced verbal interactions during reading, and to include language and mathematical content during these activities, should promote children's reading and mathematical abilities in secondary school. Such experiences lay a strong foundation for later school success."

Formal literacy activities not only boosted language skills and reading comprehension but also improved numerical skills. Book exposure and the quality of verbal interactions regarding mathematical content during shared book reading (for example, talking about numbers and counting) when children were of preschool age were also associated with better math outcomes at age 12. The effect also worked the other way with the quality of parent-child interaction regarding mathematics also improving children's language skills.

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Supercomputer shows 'Chameleon Theory' could change how we think about gravity

Andromeda Galaxy

Supercomputer simulations of galaxies have shown that Einstein's theory of General Relativity might not be the only way to explain how gravity works or how galaxies form.

Physicists at Durham University, UK, simulated the cosmos using an alternative model for gravity -- f(R)-gravity, a so called Chameleon Theory.

The resulting images produced by the simulation show that galaxies like our Milky Way could still form in the universe even with different laws of gravity.

The findings show the viability of Chameleon Theory -- so called because it changes behaviour according to the environment -- as an alternative to General Relativity in explaining the formation of structures in the universe.

The research could also help further understanding of dark energy -- the mysterious substance that is accelerating the expansion rate of the universe.

The findings are published in Nature Astronomy.

General Relativity was developed by Albert Einstein in the early 1900s to explain the gravitational effect of large objects in space, for example to explain the orbit of Mercury in the solar system.

It is the foundation of modern cosmology but also plays a role in everyday life, for example in calculating GPS positions in smartphones.

Scientists already know from theoretical calculations that Chameleon Theory can reproduce the success of General Relativity in the solar system.

The Durham team has now shown that this theory allows realistic galaxies like our Milky Way to form and can be distinguished from General Relativity on very large cosmological scales.

Research co-lead author Dr Christian Arnold, in Durham University's Institute for Computational Cosmology, said: "Chameleon Theory allows for the laws of gravity to be modified so we can test the effect of changes in gravity on galaxy formation.

"Through our simulations we have shown for the first time that even if you change gravity, it would not prevent disc galaxies with spiral arms from forming.

"Our research definitely does not mean that General Relativity is wrong, but it does show that it does not have to be the only way to explain gravity's role in the evolution of the universe."

The researchers looked at the interaction between gravity in Chameleon Theory and supermassive black holes that sit at the centre of galaxies.

Black holes play a key role in galaxy formation because the heat and material they eject when swallowing surrounding matter can burn away the gas needed to form stars, effectively stopping star formation.

The amount of heat spewed out by black holes is altered by changing gravity, affecting how galaxies form.

However, the new simulations showed that even accounting for the change in gravity caused by applying Chameleon Theory, galaxies were still be able to form.

General Relativity also has consequences for understanding the accelerating expansion of the universe.

Scientists believe this expansion is being driven by dark energy and the Durham researchers say their findings could be a small step towards explaining the properties of this substance.

Research co-lead author Professor Baojiu Li, of Durham University's Institute for Computational Cosmology, said: "In General Relativity, scientists account for the accelerated expansion of the universe by introducing a mysterious form of matter called dark energy -- the simplest form of which may be a cosmological constant, whose density is a constant in space and time.

"However, alternatives to a cosmological constant which explain the accelerated expansion by modifying the law of gravity, like f(R) gravity, are also widely considered given how little is known about dark energy."

The Durham researchers expect their findings can be tested through observations using the Square Kilometre Array (SKA) telescope, based in Australia and South Africa, which is due to begin observations in 2020.

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Massive stars grow same way as light stars, just bigger

Astronomers obtained the first detailed face-on view of a gaseous disk feeding the growth of a massive baby star. They found that it shares many common features with lighter baby stars. This implies that the process of star formation is the same, regardless of the final mass of the resulting star. This finding paves the way for a more complete understanding of star formation.

A protostar, a baby star still in the process of forming, is fed by a surrounding disk of gas falling towards the center. The details of the process, such as why stars form with a wide range of masses, are still unclear. Low mass stars are being formed in the vicinity of the Solar System, allowing astronomers to see the process up-close. On the other hand, massive protostars are rare, and even the nearest are located quite far away from us.

Kazuhito Motogi, an assistant professor at Yamaguchi University, Japan, and his team used the Atacama Large Millimeter/submillimeter Array (ALMA) to observe a massive protostar called G353.273+0.641 (hereafter G353). Located 5500 light-years away in the constellation Scorpius, G353 has a mass 10 times larger than the Sun, and is still growing. It is a unique target among massive protostars because we can see its gaseous disk from straight above. ALMA has revealed detailed views of several other massive infant stars, however, most of them are in edge-on configurations, making it difficult to see the inner regions of the disks.

ALMA observations captured a rotating disk around G353 with a radius eight times larger than the orbit of Neptune. This sounds huge, but it is one of the smallest disks yet found around a massive protostar. ALMA also found that the disk is surrounded by an envelope of gas three times larger than the disk.

"We measured the gas infall rate from the outer envelope to the inner disk," says Motogi. "This helps us to estimate the age of the baby star. Surprisingly it is only 3000 years old, the youngest among known massive protostars. We are witnessing the earliest phase of the growth of a giant star."

Interestingly, the disk is not uniform; the south-eastern side of the disk is brighter than other parts. This is the first time astronomers have seen an asymmetric disk around a massive protostar. The team also found that the disk is highly unstable and going to fragment. The uneven disk might be caused by this instability. These features are often seen around smaller protostars, suggesting that the essential physical processes are the same in low-mass and high-mass star formation.

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Producing graphene from carbon dioxide

The general public knows the chemical compound of carbon dioxide as a greenhouse gas in the atmosphere and because of its global-warming effect. However, carbon dioxide can also be a useful raw material for chemical reactions. A working group at Karlsruhe Institute of Technology (KIT) has now reported on this unusual application in the ChemSusChem journal. They are using carbon dioxide as a raw material to produce graphene, a technological material which is currently the subject of intense study.

The combustion of fossil fuels such as coal and oil produces energy for electricity, heat and mobility, but it also leads to an increase of the amount of carbon dioxide in the atmosphere and therefore to global warming. Cutting this causal chain is what motivates scientists to search for alternative energy sources but also for alternative uses of carbon dioxide. One possibility could be to see carbon dioxide as an inexpensive raw material for the synthesis of valuable materials, feeding it back into the reusability cycle -- maybe even in a profitable way.

An example can be found in nature. During photosynthesis in the leaves of plants, the combination of light, water and carbon dioxide creates biomass, closing the natural material cycle. In this process, it is the job of the metal-based enzyme RuBisCo to absorb the carbon dioxide from the air and make it usable for the further chemical reactions in the plant. Inspired by this metal enzyme-based natural conversion, researchers at KIT are now presenting a process in which the greenhouse gas carbon dioxide together with hydrogen gas is converted directly into graphene at temperatures of up to 1000 degrees Celsius with the help of specially prepared, catalytically active metal surfaces.

Graphene is the two-dimensional form of the chemical element carbon, which has interesting electrical properties and is therefore an option for new future electronic components. Its discovery and workability in 2004 led to worldwide, intensive research and earned the discoverers, Andre Geim and Konstanin Novoselov, the Nobel Prize for Physics in 2010. The two removed the graphene manually from a block of graphite using tape.

Several working groups at KIT have collaborated to present a method in the ChemSusChem journal for separating graphene from carbon dioxide and hydrogen by means of a metal catalyst. "If the metal surface exhibits the correct ratio of copper and palladium, the conversion of carbon dioxide to graphene will take place directly in a simple one-step process," explains the head of the study, Professor Mario Ruben, from the Molekulare Materialien working group at the Institute of Nanotechnology (INT) and the Institute for Inorganic Chemistry (AOC) at KIT. In further experiments the researchers were even able to produce graphene several layers thick, which could be interesting for possible applications in batteries, electronic components or filter materials. The working group's next research goal is to form functioning electronic components from the graphene thus obtained. Carbon materials such as graphene and magnetic molecules could be the building blocks for future quantum computers, which enable ultra-fast and energy-efficient calculations but are not based on the binary logic of today's computers.

From Science Daily

Quitting alcohol may improve mental well-being, health-related quality of life

Quitting alcohol may improve health-related quality of life for women, especially their mental well-being, according to a study from Hong Kong published in CMAJ (Canadian Medical Association Journal).

"More evidence suggests caution in recommending moderate drinking as part of a healthy diet," says Dr. Michael Ni, School of Public Health and The State Key Laboratory of Brain and Cognitive Science, University of Hong Kong (HKU).

The study carried out by Dr. Xiaoxin Yao, Dr. Michael Ni, Dr. Herbert Pang and colleagues at HKU included 10 386 people from the FAMILY Cohort in Hong Kong who were nondrinkers or moderate drinkers (14 drinks or less per week for men and 7 drinks or less per week for women) between 2009 and 2013. The researchers compared their findings with data from the National Epidemiologic Survey on Alcohol and Related Conditions, a representative survey of 31 079 people conducted by the National Institute on Alcohol Abuse and Alcoholism in the United States.

The mean age of participants in the FAMILY Cohort was 49 years and 56% were women. About 64% of men were nondrinkers (abstainers and former drinkers) and almost 88% of women were nondrinkers. Men and women who were lifetime abstainers had the highest level of mental well-being at the start of the study (baseline). For women who were moderate drinkers and quit drinking, quitting was linked to a favourable change in mental well-being in both Chinese and American study populations. These results were apparent after adjusting for sociodemographic characteristics, body mass index, smoking status, and other factors.

"Global alcohol consumption is expected to continue to increase unless effective strategies are employed," says Dr. Ni. "Our findings suggest caution in recommendations that moderate drinking could improve health-related quality of life. Instead, quitting drinking may be associated with a more favourable change in mental well-being, approaching the level of lifetime abstainers."

From Science Daily

How the brain remembers where you're heading to

The brain appears to implement a GPS system for spatial navigation; however, it is not yet fully understood how it works. In the journal Science Advances, researchers from Freiburg, Bochum and Beijing now suggest that rhythmic fluctuations in brain activity, so-called theta oscillations, may play a role in this process. These brainwaves might help remember the locations to which a person is navigating. This is the result of the researchers' study conducted with epilepsy patients who had electrodes implanted in the brain for the purpose of surgical planning. With the aid of these electrodes, the researchers recorded neuronal activity during a navigation task in a virtual reality setting.

A team headed by Dr. Lukas Kunz, Universitätsklinikum Freiburg, and Professor Nikolai Axmacher, Head of the Department of Neuropsychology at Ruhr-Universität Bochum, published their findings on 3 July 2019.

Experiments in virtual reality

Previous studies had demonstrated that brain oscillations show a characteristic pattern during navigation. Theta oscillations, during which brain activity changes at a frequency of approximately four hertz, appear to play a crucial role in this process. But it had not been fully understood how, exactly, they support spatial navigation.

In the experiments, the epilepsy patients learned to associate individual objects with specific locations in a virtual environment. For each of the acquired object-location associations, the researchers identified a characteristic brain activity pattern.

Subsequently, the participants had to remember which object was associated with which location. While they navigated to that location in the virtual environment, the brain reactivated the location-specific activity patterns. The reactivation of brain activity for different object-location pairs occurred at different points of time during the theta cycles. "Accordingly, theta oscillations may coordinate the reactivation of different memories and, moreover, may help distinguish between competing memories," says Lukas Kunz.

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Obese people outnumber smokers two to one

New figures from Cancer Research UK show that people who are obese now outnumber people who smoke two to one in the UK, and excess weight causes more cases of certain cancers than smoking, as the charity urges Government action to tackle obesity.

Almost a third of UK adults are obese and, while smoking is still the nation's biggest preventable cause of cancer and carries a much higher risk of the disease than obesity, Cancer Research UK's analysis revealed that being overweight or obese trumps smoking as the leading cause of four different types of cancer.

Excess weight causes around 1,900 more cases of bowel cancer than smoking in the UK each year. The same worrying pattern is true of cancer in the kidneys (1,400 more cases caused by excess weight than by smoking each year in the UK), ovaries (460) and liver (180).

Cancer Research UK launched a nationwide campaign this week to increase awareness of the link between obesity and cancer. Extra body fat sends out signals that can tell cells to divide more often and can cause damage that builds up over time and raises the risk of cancer.

The campaign compares smoking and obesity to show how policy change can help people form healthier habits, not to compare tobacco with food.

Michelle Mitchell, Cancer Research UK's chief executive, said: "As smoking rates fall and obesity rates rise, we can clearly see the impact on a national health crisis when the Government puts policies in place -- and when it puts its head in the sand.

"Our children could be a smoke-free generation, but we've hit a devastating record high for childhood obesity, and now we need urgent Government intervention to end the epidemic. They still have a chance to save lives.

"Scientists have so far identified that obesity causes 13 types of cancer but the mechanisms aren't fully understood. So further research is needed to find out more about the ways extra body fat can lead to cancer."

The charity wants the Government to act on its ambition to halve childhood obesity rates by 2030 and introduce a 9pm watershed for junk food adverts on TV and online, alongside other measures such as restricting promotional offers on unhealthy food and drinks.

Professor Linda Bauld, Cancer Research UK's prevention expert, commented: "There isn't a silver bullet to reduce obesity, but the huge fall in smoking over the years -- partly thanks to advertising and environmental bans -- shows that Government-led change works. It was needed to tackle sky-high smoking rates, and now the same is true for obesity.

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The neuroscience of autism: New clues for how condition begins

Abstract brain concept.

UNC School of Medicine scientists unveiled how a particular gene helps organize the scaffolding of brain cells called radial progenitors necessary for the orderly formation of the brain. Previous studies have shown that this gene is mutated in some people with autism.

The discovery, published in Neuron, illuminates the molecular details of a key process in brain development and adds to the scientific understanding of the biological basis of autism spectrum disorder (ASD), a condition linked to brain development and estimated to affect about one in 59 children born in the United States.

"This finding suggests that ASD can be caused by disruptions occurring very early on, when the cerebral cortex is just beginning to construct itself," said study senior author Eva S. Anton, PhD, professor of cell biology and physiology at the UNC School of Medicine and member of the UNC Neuroscience Center and the UNC Autism Research Center.

The cerebral cortex -- which in humans is responsible for higher brain functions including perception, speech, long-term memory, and consciousness -- is relatively large and dominant compared to other brain structures.

How the cortex constructs itself in the developing brain of a human or other mammal is far from fully understood. But scientists know that early in cortical development, precursor cells called radial glial cells (RGCs) appear at the bottom of the developing cortex in a regularly spaced or tiled pattern. Each RGC sprouts a single stalk-like structure, called a basal process that extends to the top of the cortex. Collectively these RGCs and their basal processes form a scaffold, much like the scaffolds of a construction site.

RGCs divide to form young cortical neurons, and these baby neurons climb the scaffold to find their proper places in the developing brain. The cortex, thanks to this scaffolding system, normally develops a highly regular structure with six distinct layers of neurons required for the normal formation of functional neural cortical circuits.

Anton and colleagues discovered that a gene encoding for a protein called Memo1 is needed to organize the tiled radial glial cell scaffold. Mutations in the Memo1 gene also have been found in some people with autism and are suspected of causing the condition. To explore Memo1's role in brain development and autism, Anton's team first engineered mice in which the Memo1 gene is deleted early in brain development in RGCs.

They found the resulting RGC scaffold is disrupted. Each RGC's stalk-like basal process formed too many branches and no longer forms a guiding scaffold, resulting in neuronal misplacement and disorganized layers. The scientists traced this ill effect, in part, to unstable microtubules, which normally help reinforce the scaffold structure and serve as railways for the internal traffic of key molecules necessary for RGC function.

Intriguingly, studies of the brains of children with autism found patches of similar neuronal disorganization. The scientists then analyzed MEMO1 gene mutations reported recently in individuals with autism behaviors and intellectual disabilities. They discovered the human MEMO1 genetic mutation resulted in a shortened form of the Memo1 protein and this can disrupt RGC development

Further supporting the autism connection, Anton and his colleagues discovered the mice lacking Memo1 in their RGCs behaved abnormally, showing a lack of explorative activity similar to those seen in some people with autism.

The findings overall suggest that Memo1-associated autism may be wired into the brain very early in development than are other forms of autism with origins in disrupted neuronal differentiation and connectivity.

"For disorders of brain development such as ASD, it is important to understand the origins of the problem even if we are still far away from being able to correct developmental disruptions occurring in utero," Anton said. "We need this foundational knowledge if we are to truly get to the root causes of these conditions and eventually develop better diagnostic or therapeutic strategies."

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