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Connecting the dots in the sky could shed new light on dark matter

image: In a new study, astrophysicists have found a certain gamma-ray glow in the sky, known as unresolved gamma-ray background (yellow), to coincide with cosmic regions that contain a lot of matter (red). The correlation could lead to a better understanding of highly energetic astrophysical objects and dark matter. The gamma-ray map was created with nine years of data from the Fermi spacecraft, and the map showing the density of matter is based on one year of data from the Dark Energy Survey (DES).

Image: 
Daniel Gruen/SLAC/Stanford, Chihway Chang/University of Chicago, Alex Drlica-Wagner/Fermilab

Astrophysicists have come a step closer to understanding the origin of a faint glow of gamma rays covering the night sky. They found that this light is brighter in regions that contain a lot of matter and dimmer where matter is sparser - a correlation that could help them narrow down the properties of exotic astrophysical objects and invisible dark matter.

The glow, known as unresolved gamma-ray background, stems from sources that are so faint and far away that researchers can't identify them individually. Yet, the fact that the locations where these gamma rays originate match up with where mass is found in the distant universe could be a key puzzle piece in identifying those sources.

"The background is the sum of a lot of things 'out there' that produce gamma rays. Having been able to measure for the first time its correlation with gravitational lensing - tiny distortions of images of far galaxies produced by the distribution of matter - helps us disentangle them," said Simone Ammazzalorso from the University of Turin and the National Institute for Nuclear Physics (INFN) in Italy, who co-led the analysis.

The study used one year of data from the Dark Energy Survey (DES), which takes optical images of the sky, and nine years of data from the Fermi Gamma-ray Space Telescope, which observes cosmic gamma rays while it orbits the Earth.

"What's really intriguing is that the correlation we measured doesn't completely match our expectations," said Panofsky fellow Daniel Gruen from the Kavli Institute for Particle Astrophysics and Cosmology (KIPAC) at the Department of Energy's SLAC National Accelerator Laboratory and Stanford University, who led the analysis for the DES collaboration. "This could mean that we either need to adjust our existing models for objects that emit gamma rays, or it could hint at other sources, such as dark matter."

The study was accepted today for publication in Physical Review Letters.

Two sensitive 'eyes' on the sky

Gamma radiation, the most energetic form of light, is produced in a wide range of cosmic phenomena - often extremely violent ones, such as exploding stars, dense neutron stars rotating at high speeds and powerful beams of particles shooting out of active galaxies whose central supermassive black holes gobble up matter.

Another potential source is invisible dark matter, which is believed to make up 85 percent of all matter in the universe. It could produce gamma rays when dark matter particles meet and destroy each other in space.

The Large Area Telescope (LAT) onboard the Fermi spacecraft is a highly sensitive "eye" for gamma radiation, and its data provide a detailed map of gamma-ray sources in the sky.

But when scientists subtract all the sources they already know, their map is far from empty; it still contains a gamma-ray background whose brightness varies from region to region.

"Unfortunately gamma rays don't have a label that would tell us where they came from," Gruen said. "That's why we need additional information to unravel their origin."

That's where DES comes in. With its 570-megapixel Dark Energy Camera, mounted on the Victor M. Blanco 4-meter Telescope at the Cerro Tololo Inter-American Observatory in Chile, it snaps images of hundreds of millions of galaxies. Their exact shapes tell researchers how the gravitational pull of matter bends light in the universe - an effect that shows itself as tiny distortions in galaxy images, known as weak gravitational lensing. Based on these data, the DES researchers create the most detailed maps yet of matter in the cosmos.

In the new study, the scientists superimposed the Fermi and DES maps, which revealed that the two aren't independent. The unresolved gamma-ray background is more intense in regions with more matter and less intense in regions with less matter.

"The result itself is not surprising. We expect that there are more gamma ray producing processes in regions that contain more matter, and we've been predicting this correlation for a while," said Nicolao Fornengo, one of Ammazzalorso's supervisors in Turin. "But now we've succeeded in actually detecting this correlation for the first time, and we can use it to understand what causes the gamma ray background."

Potential hint at dark matter

One of the most likely sources for the gamma-ray glow is very distant blazars - active galaxies with supermassive black holes at their centers. As the black holes swallow surrounding matter, they spew high-speed jets of plasma and gamma rays that, if the jets point at us, are detected by the Fermi spacecraft.

Blazars would be the simplest assumption, but the new data suggest that a simple population of blazars might not be enough to explain the observed correlation between gamma rays and mass distribution, the researchers said.

"In fact, our models for emissions from blazars can fairly well explain the low-energy part of the correlation, but we see deviations for high-energy gamma rays," Gruen said. "This can mean several things: It could indicate that we need to improve our models for blazars or that the gamma rays could come from other sources."

One of these other sources could be dark matter. A leading theory predicts the mysterious stuff is made of weakly interacting massive particles, or WIMPs, which could annihilate each other in a flash of gamma rays when they collide. Gamma rays from certain matter-rich cosmic regions could therefore stem from these particle interactions.

The idea to look for gamma-ray signatures of annihilating WIMPs is not a new one. Over the past years, scientists have searched for them in various locations believed to contain a lot of dark matter, including the center of the Milky Way and the Milky Way's companion galaxies. However, these searches haven't produced identifiable dark matter signals yet. The new results could be used for additional searches that test the WIMP hypothesis.

Planning next steps

Although the probability that the measured correlation is just a random effect is only about one in a thousand, the researchers need more data for a conclusive analysis.

"These results, connecting for the first time our maps of gamma rays and matter, are very interesting and have a lot of potential, but at the moment the connection is still relatively weak, and one has to interpret the data carefully," said KIPAC Director Risa Wechsler, who was not involved in the study.

One of the main limitations of the current analysis is the amount of available lensing data, Gruen said. "With data from 40 million galaxies, DES has already pushed this to a new level, and that's why we were able to do the analysis in the first place. But we need even better measurements," he said.

With its next data release, DES will provide lensing data for 100 million galaxies, and the future Large Synoptic Survey Telescope (LSST) will look at billions of galaxies in a much larger region of the sky.

"Our study demonstrates with actual data that we can use the correlation between the distributions of matter and gamma rays to learn more about what causes the gamma-ray background," Fornengo said. "With more DES data, LSST coming online and other projects like the Euclid space telescope on the horizon, we'll be able to go much deeper in our understanding of the potential sources."

Then, the scientists might be able to tell if some of that gamma-ray glow stems from dark matter's self-destruction.

DES is an international project with over 400 scientists from 25 institutions in 7 countries, who have come together to carry out the survey. Parts of the project were funded by DOE's Office of Science and the National Science Foundation. NASA's Fermi Gamma-ray Space Telescope is an international and multi-agency space observatory. The analysis used Fermi-LAT data that were publicly released by the international LAT collaboration.

Credit: 
DOE/SLAC National Accelerator Laboratory

The advantage of changing sex in fish population recovery

image: California sheephead can transition from female to male when a dominant male dies, and take over the mating territory.

Image: 
Photo courtesy of Scott Hamilton.

Humans eat a lot of fish, in some areas of the world making up an essential part of our diet. Fishing can sometimes deplete fish populations to the point where the fish have difficulty reproducing and growing their numbers again. Establishing Marine Protected Areas (MPAs) that limit or eliminate fishing within their borders can help fish to replenish their populations. They can then be harvested when they venture outside the MPA, spilling out into surrounding waters where fishers benefit from the recovered abundance.

Some fish species, however, recover their populations at different rates when fishing is eliminated inside MPAs. A new study in the Ecological Society of America's journal Ecological Applications explores how sex-changing fish species can actually recover faster than fixed-sex species. 

Most studies on population recovery within MPAs from overfishing have focused on fixed-sex species, where a female fish stays female its whole life and a male stays male: "I think this is because many MPA studies and many scientists assume that most fish species are single-sex," says Scott Hamilton, Associate Professor at Moss Landing Marine Laboratories and San Jose State University and co-author on the study. But many important fishery species are not fixed-sex, and instead have female fish change to male at some point in their life.

Often, fisheries will only harvest fish over a certain size. Size-selective harvests will end up targeting and catching males because they are usually bigger, which then skews the population towards female. In species that can alter the sex ratio on their own by changing sex, how is their reproduction and long term population recovery affected by male harvesting?

Researchers used computer simulations to investigate how different sex-changing fish populations respond under MPA no-fishing implementation and also under unprotected conditions. They additionally looked at the "when" and "why" different species change sex to see if that has an effect on recovery as well.

Different sex-changing species can follow several rules or signals that prompt them to change sex. For instance, gag grouper change sex at a fixed size or age; once individual female reach a certain size, they transition. The California sheephead, however, follows different rules: large territorial males guard a mating territory of females and limit when those females change sex. In this scenario, only when a large male dies can a female fish transition to male and take over the territory.

In the researchers' simulations involving these different kinds of sex-changing species, it appears the length of time for population recovery heavily depends on the degree to which abundant males are needed for reproduction, or the "mating function."

For species like the gag grouper, a species that mates in large, group spawning events and changes sex only at a certain size or age, male harvesting is problematic. Not enough males are available to fertilize all the eggs produced by the females, and the females are not able to transition and replace the males until they grow big enough to do so. "In this case," Hamilton explains, "our findings indicate that a sex-changing species will likely respond more slowly and unpredictably to MPA implementation than fixed-sex species."

For species like the California sheephead, however, the female-skewed ratio created by harvesting actually works to their favor. When males are taken, a female transitions and takes his place in a territory. Because this species reproduces in a harem-like style in which one male mates with many females each day, these fish are not dependent on having abundant males to regrow their population.

It appears that as long as females readily replace males, and the reproduction rate remains high even with few males, a sex-changing species has an advantage in population recovery over a generic fixed-sex species. Conversely, a species in which many males are needed in their mating function, especially when females do not become male until they grow to a certain size, is at a disadvantage.

The good news is that the researchers expect most sex-changing species are of the first, harem-style type. "Unfortunately," says Hamilton, "the mating functions are unknown for virtually all fishes, so much more empirical research is needed to better understand the shape of the mating function for more species, especially those that are targeted by fishing activities."

Credit: 
Ecological Society of America

Life's clockwork: Scientist shows how molecular engines keep us ticking

image: Escapement mechanisms of clocks as a metaphor for protein function like Maxwell's demons. The Foliot swings back and forth like the pendulum in a clock. The essential features enabling time keeping are labeled. The central function of an escapement is illustrated by the two dark green blades that control the advance of the crown gear in a mechanical clock.

Image: 
Carter, UNC School of Medicine

In the popular book The Demon in the Machine, physicist Paul Davies argues that what's missing in the definition of life is how biological processes create "information," and such information storage is the stuff of life, like a bird's ability to navigate or a human's ability to solve complex problems. The "Demon" Davies refers to is Maxwell's Demon, as proposed by 19th century physicist James Clerk Maxwell as a thought experiment. Maxwell's hypothetical "demon" controls a gate between two chambers of gas and knows when to open the gate only to allow gas molecules moving faster than average to pass through it. This way, a chamber could be heated and create "energy" to be put to work. Such a demon would amount to a workaround of the Second Law of Thermodynamics. And that, as we know, is impossible. We also know, of course, that demons don't exist.

However, living things use many protein devices called enzymes that mimic such a demon each time a muscle contracts or when any chemical reaction needs to be driven uphill and away from thermodynamic equilibrium like the gas molecules chosen by the demon. How these dynamic machines work has long been puzzling. Over the past 75 years, scientists have chipped away at this problem without identifying precise details of how any of these enzyme machines accomplishes the sleight of hand that sustains living things, such as humans who live in a chemical state far from equilibrium.

For the first time, in a paper published in Proteins: Structure, Function, and Bioinformatics by Charlie Carter, PhD, professor in the Department of Biochemistry and Biophysics at the UNC School of Medicine, and supported by the National Institute of General Medical Sciences, describes the details that enable one such machine to work like Maxwell's demon.

The machine in question is an enzyme called tryptophanyl-tRNA synthetase, or TrpRS, which can use the chemical energy stored in the universal fuel molecule - Adenosine triphosphate (ATP) - to ensure that whenever the sequence of any gene specifies tryptophan, the amino acid tryptophan is inserted into the sequence of linked amino acids that compose the translated protein. By assuring that the correct amino acid is selected, TrpRS therefore translates the genetic code for tryptophan when any of the tens of thousands of genes in human cells is translated into the corresponding protein. Translating the code into the amino acid sequence specified by the gene gives the newly created protein sequence the information telling it how to fold up and exert nanoscale control over some aspect of cellular chemistry.

Carter's previous work with TrpRS led to a fundamental revision of how genetic coding began. In this latest paper, Carter investigates how TrpRS mimics Maxwell's demon. The details he describes may represent a solution to the more general problem of how all energy in living things is transformed from fuel to useful work, such as muscles contracting, biosynthetic reactions that build new molecules required by the cell, or information managed by signaling networks driven by hydrolyzing a related fuel --Guanosine triphosphate (GTP)--that keep cellular chemistry under tight regulatory control.

TrpRS has several moving parts that identify tryptophan and attach it specifically to the correct transfer RNA if and only if the relative motions of certain flexible, changing parts of the protein called "domains" are tightly coupled to ATP hydrolysis. These domains are dynamic. How they bend and move is referred to as "domain motion." Carter shows how domain motion in general and ATP hydrolysis both depend on the completion of the other.

Hydrolysis of ATP cannot happen unless the domain motion occurs, but the domain motion itself cannot occur unless ATP is hydrolyzed. Paradoxically, the two conditions, or "gates," occur in coordination. Carter calls this two-way dependence "reciprocally-coupled gating."

"This tight coupling is like the 'escapement mechanism' in a ticking mechanical clock (see figure)," Carter said. "The two kinds of gates function like the two green plates, each allowing the main "crown" gear to slip one gear at a time, but only in one direction, as the pendulum swings. This is how a clock converts the energy of unwinding the weight around the shaft of the crown gear, driving the pendulum into a time-keeping device."

Scientists are increasingly recognizing escapement mechanisms as fundamental to all cellular processes driven by hydrolysis of fuel molecules like ATP and GTP. Carter's work shows for the first time exactly how domain motions are efficiently coordinated with the consumption of the fuel. Notably, the GTPase superfamily also includes a high proportion of known oncogenes whose mutations make their escapement mechanisms malfunction sufficiently to cause cancer.

"It is likely that most or all of life's motors and signaling devices that use either ATP or GTP will exhibit comparable gating mechanisms," Carter said. "Scientists have known for 75 years that such mechanisms must exist. It is thrilling to uncover such a complete example of how gating mechanisms work together to ensure that we waste so little of the fuel we consume."

Credit: 
University of North Carolina Health Care

When pregnant moms are stressed out, babies' brains suffer

image: This is Catherine Limperopoulos, Ph.D., director of the Center for the Developing Brain at Children's National and the study's corresponding author.

Image: 
Children's National Hospital

WASHINGTON-(Jan. 13, 2020)-Knowing that your unborn fetus has congenital heart disease causes such pronounced maternal stress, anxiety and depression that these women's fetuses end up with impaired development in key brain regions before they are born, according to research published online Jan. 13, 2020, in JAMA Pediatrics.

While additional research is needed, the Children's National Hospital study authors say their unprecedented findings underscore the need for universal screening for psychological distress as a routine part of prenatal care and taking other steps to support stressed-out pregnant women and safeguard their newborns' developing brains.

"We were alarmed by the high percentage of pregnant women with a diagnosis of a major fetal heart problem who tested positive for stress, anxiety and depression," says Catherine Limperopoulos, Ph.D., director of the Center for the Developing Brain at Children's National and the study's corresponding author. "Equally concerning is how prevalent psychological distress is among pregnant women generally. We report for the first time that this challenging prenatal environment impairs regions of the fetal brain that play a major role in learning, memory, coordination, and social and behavioral development, making it all the more important for us to identify these women early during pregnancy to intervene," Limperopoulos adds.

Congenital heart disease (CHD), structural problems with the heart, is the most common birth defect.

Still, it remains unclear how exposure to maternal stress impacts brain development in fetuses with CHD.

The multidisciplinary study team enrolled 48 women whose unborn fetuses had been diagnosed with CHD and 92 healthy women with uncomplicated pregnancies. Using validated screening tools, they found:

65% of pregnant women expecting a baby with CHD tested positive for stress

27% of women with uncomplicated pregnancies tested positive for stress

44% of pregnant women expecting a baby with CHD tested positive for anxiety

26% of women with uncomplicated pregnancies tested positive for anxiety

29% of pregnant women expecting a baby with CHD tested positive for depression and

9% women with uncomplicated pregnancies tested positive for depression

All told, they performed 223 fetal magnetic resonance imaging sessions for these 140 fetuses between 21 and 40 weeks of gestation. They measured brain volume in cubic centimeters for the total brain as well as volumetric measurements for key regions such as the cerebrum, cerebellum, brainstem, and left and right hippocampus.

Maternal stress and anxiety in the second trimester were associated with smaller left hippocampi and smaller cerebellums only in pregnancies affected by fetal CHD. What's more, specific regions -- the hippocampus head and body and the left cerebellar lobe - were more susceptible to stunted growth. The hippocampus is key to memory and learning, while the cerebellum controls motor coordination and plays a role in social and behavioral development.

The hippocampus is a brain structure that is known to be very sensitive to stress. The timing of the CHD diagnosis may have occurred at a particularly vulnerable time for the developing fetal cerebellum, which grows faster than any other brain structure in the second half of gestation, particularly in the third trimester.

"None of these women had been screened for prenatal depression or anxiety. None of them were taking medications. And none of them had received mental health interventions. In the group of women contending with fetal CHD, 81% had attended college and 75% had professional educations, so this does not appear to be an issue of insufficient resources," Limperopoulos adds. "It's critical that we routinely to do these screenings and provide pregnant women with access to interventions to lower their stress levels. Working with our community partners, Children's National is doing just that to help reduce toxic prenatal stress for both the health of the mother and for the future newborns. We hope this becomes standard practice elsewhere."

Adds Yao Wu, Ph.D., a research associate working with Limperopoulos at Children's National and the study's lead author: "Our next goal is exploring effective prenatal cognitive behavioral interventions to reduce psychological distress felt by pregnant women and improve neurodevelopment in babies with CHD."

Credit: 
Children's National Hospital

Study sheds light on link between cannabis, anxiety and stress

image: Sachin Patel, M.D., Ph.D., the paper's corresponding author and director of the Division of General Psychiatry at Vanderbilt University Medical Center.

Image: 
Vanderbilt University Medical Center

A molecule produced by the brain that activates the same receptors as marijuana is protective against stress by reducing anxiety-causing connections between two brain regions, Vanderbilt University Medical Center researchers report.

This finding, published today in Neuron, could help explain why some people use marijuana when they're anxious or under stress. It could also mean that pharmacologic treatments that increase levels of this molecule, known as "2-AG," in the brain could regulate anxiety and depressive symptoms in people with stress-related anxiety disorders, potentially avoiding a reliance on medical marijuana or similar treatments.

When mice are exposed to acute stress, a break in an anxiety-producing connection between the amygdala and the frontal cortex caused by 2-AG temporarily disappears, causing the emergence of anxiety-related behaviors.

"The circuit between the amygdala and the frontal cortex has been shown to be stronger in individuals with certain types of anxiety disorders. As people or animals are exposed to stress and get more anxious, these two brain areas glue together, and their activity grows stronger together," said Sachin Patel, MD, PhD, the paper's corresponding author and director of the Division of General Psychiatry at Vanderbilt University Medical Center.

"We might predict there's a collapse in the endocannabinoid system, which includes 2-AG, in the patients that go on to develop a disorder. But, not everyone develops a psychiatric disorder after trauma exposure, so maybe the people who don't develop a disorder are able to maintain that system in some way. Those are the things we're interested in testing next."

The study also found that signaling between the amygdala and the frontal cortex can be strengthened through genetic manipulations that compromise endogenous cannabinoid signaling in this pathway, causing mice to become anxious even without exposure to stress in some cases. This finding demonstrates that the cannabinoid signaling system that suppresses information flow between these two brain regions is critical for setting the level of anxiety in animals.

"We don't know how or why this cannabinoid signaling system disappears or disintegrates in response to stress, but it results in the strengthening of the connection between these two regions and heightened anxiety behaviors in mice. Understanding what's causing that compromise, what causes the signaling system to return after a few days, and many other questions about the molecular mechanisms by which this is happening are things we're interested in following up on," said Patel, also the James G. Blakemore Professor of Psychiatry and Behavioral Sciences, Molecular Physiology and Biophysics and Pharmacology.

David Marcus, Neuroscience graduate student and first author on the paper, and Patel are also interested in how the system reacts to more chronic forms of stress and determining whether there are other environmental exposures that compromise or enhance this system to regulate behavior.

Credit: 
Vanderbilt University Medical Center

Nano-objects of desire: Assembling ordered nanostructures in 3D

image: A schematic of the programmable assembly of 3-D ordered nanostructures from material voxels that can carry inorganic or organic nanoparticles with different functions, such as light emitters and absorbers, proteins, and enzymes with chemical activity. Material voxels are fabricated from DNA and nano-objects of different kinds, and their assembly is guided by the voxel design and DNA-programmable interactions.

Image: 
Brookhaven National Laboratory

UPTON, NY--Scientists have developed a platform for assembling nanosized material components, or "nano-objects," of very different types--inorganic or organic--into desired 3-D structures. Though self-assembly (SA) has successfully been used to organize nanomaterials of several kinds, the process has been extremely system-specific, generating different structures based on the intrinsic properties of the materials. As reported in a paper published today in Nature Materials, their new DNA-programmable nanofabrication platform can be applied to organize a variety of 3-D materials in the same prescribed ways at the nanoscale (billionths of a meter), where unique optical, chemical, and other properties emerge.

"One of the major reasons why SA is not a technique of choice for practical applications is that the same SA process cannot be applied across a broad range of materials to create identical 3-D ordered arrays from different nanocomponents," explained corresponding author Oleg Gang, leader of the Soft and Bio Nanomaterials Group at the Center for Functional Nanomaterials (CFN)--a U.S. Department of Energy (DOE) Office of Science User Facility at Brookhaven National Laboratory--and a professor of Chemical Engineering and of Applied Physics and Materials Science at Columbia Engineering. "Here, we decoupled the SA process from material properties by designing rigid polyhedral DNA frames that can encapsulate various inorganic or organic nano-objects, including metals, semiconductors, and even proteins and enzymes."

The scientists engineered synthetic DNA frames in the shape of a cube, octahedron, and tetrahedron. Inside the frames are DNA "arms" that only nano-objects with the complementary DNA sequence can bind to. These material voxels--the integration of the DNA frame and nano-object--are the building blocks from which macroscale 3-D structures can be made. The frames connect to each other regardless of what kind of nano-object is inside (or not) according to the complementary sequences they are encoded with at their vertices. Depending on their shape, frames have a different number of vertices and thus form entirely different structures. Any nano-objects hosted inside the frames take on that specific frame structure.

To demonstrate their assembly approach, the scientists selected metallic (gold) and semiconducting (cadmium selenide) nanoparticles and a bacterial protein (streptavidin) as the inorganic and organic nano-objects to be placed inside the DNA frames. First, they confirmed the integrity of the DNA frames and formation of material voxels by imaging with electron microscopes at the CFN Electron Microscopy Facility and the Van Andel Institute, which has a suite of instruments that operate at cryogenic temperatures for biological samples. They then probed the 3-D lattice structures at the Coherent Hard X-ray Scattering and Complex Materials Scattering beamlines of the National Synchrotron Light Source II (NSLS-II)--another DOE Office of Science User Facility at Brookhaven Lab. Columbia Engineering Bykhovsky Professor of Chemical Engineering Sanat Kumar and his group performed computational modeling revealing that the experimentally observed lattice structures (based on the x-ray scattering patterns) were the most thermodynamically stable ones that the material voxels could form.

"These material voxels allow us to begin to use ideas derived from atoms (and molecules) and the crystals that they form, and port this vast knowledge and database to systems of interest at the nanoscale," explained Kumar.

Gang's students at Columbia then demonstrated how the assembly platform could be used to drive the organization of two different kinds of materials with chemical and optical functions. In one case, they co-assembled two enzymes, creating 3-D arrays with a high packing density. Though the enzymes remained chemically unchanged, they showed about a fourfold increase in enzymatic activity. These "nanoreactors" could be used to manipulate cascade reactions and enable the fabrication of chemically active materials. For the optical material demonstration, they mixed two different colors of quantum dots--tiny nanocrystals that are being used to make television displays with high color saturation and brightness. Images captured with a fluorescence microscope showed that the formed lattice maintained color purity below the diffraction limit (wavelength) of light; this property could allow for significant resolution improvement in various display and optical communication technologies.

"We need to rethink how materials can be formed and how they function," said Gang. "Material redesign may not be necessary; simply packaging existing materials in new ways could enhance their properties. Potentially, our platform could be an enabling technology 'beyond 3-D printing manufacturing' to control materials at much smaller scales and with greater material variety and designed compositions. Using the same approach to form 3-D lattices from desired nano-objects of different material classes, integrating those that would otherwise be considered incompatible, could revolutionize nanomanufacturing."

Credit: 
DOE/Brookhaven National Laboratory

How the solar system got its 'Great Divide,' and why it matters for life on Earth

Scientists, including those from the University of Colorado Boulder, have finally scaled the solar system's equivalent of the Rocky Mountain range.

In a study published today in Nature Astronomy, researchers from the United States and Japan unveil the possible origins of our cosmic neighborhood's "Great Divide." This well-known schism may have separated the solar system just after the sun first formed.

The phenomenon is a bit like how the Rocky Mountains divide North America into east and west. On the one side are "terrestrial" planet, such as Earth and Mars. They are made up of fundamentally different types of materials than the more distant "jovians," such as Jupiter and Saturn.

"The question is: How do you create this compositional dichotomy?" said lead author Ramon Brasser, a researcher at the Earth-Life Science Institute (ELSI) at the Tokyo Institute of Technology in Japan. "How do you ensure that material from the inner and outer solar system didn't mix from very early on in its history?"

Brasser and coauthor Stephen Mojzsis, a professor in CU Boulder's Department of Geological Sciences, think they have the answer, and it may just shed new light on how life originated on Earth.

A sun disk holds vital clues

The duo suggests that the early solar system was partitioned into at least two regions by a ring-like structure that formed a disk around the young sun. This disk might have held major implications for the evolution of planets and asteroids, and even the history of life on Earth.

"The most likely explanation for that compositional difference is that it emerged from an intrinsic structure of this disk of gas and dust," Mojzsis said.

Mojzsis noted that the Great Divide, a term that he and Brasser coined, does not look like much today. It is a relatively empty stretch of space that sits near Jupiter, just beyond what astronomers call the asteroid belt.

But you can still detect its presence throughout the solar system. Move sunward from that line, and most planets and asteroids tend to carry relatively low abundances of organic molecules. Go the other direction toward Jupiter and beyond, however, and a different picture emerges: Almost everything in this distant part of the solar system is made up of materials that are rich in carbon.

This dichotomy "was really a surprise when it was first found," Mojzsis said.

Many scientists assumed that Jupiter was the agent responsible for that surprise. The thinking went that the planet is so massive that it may have acted as a gravitational barrier, preventing pebbles and dust from the outer solar system from spiraling toward the sun.

But Mojzsis and Brasser were not convinced. The scientists used a series of computer simulations to explore Jupiter's role in the evolving solar system. They found that while Jupiter is big, it was probably never big enough early in its formation to entirely block the flow of rocky material from moving sunward.

"We banged our head against the wall," Brasser said. "If Jupiter wasn't the agent responsible for creating and maintaining that compositional dichotomy, what else could be?"

A solution in plain sight

For years, scientists operating an observatory in Chile called the Atacama Large Millimeter/submillimeter Array (ALMA) had noticed something unusual around distant stars: Young stellar systems were often surrounded by disks of gas and dust that, in infrared light, looked a bit like a tiger's eye.

If a similar ring existed in our own solar system billions of years ago, Brasser and Mojzsis reasoned, it could theoretically be responsible for the Great Divide.

That's because such a ring would create alternating bands of high- and low-pressure gas and dust. Those bands, in turn, might pull the solar system's earliest building blocks into several distinct sinks--one that would have given rise to Jupiter and Saturn, and another Earth and Mars.

In the mountains, "the Great Divide causes water to drain one way or another," Mojzsis said. "It's similar to how this pressure bump would have divided material" in the solar system.

But, he added, there's a caveat: That barrier in space likely was not perfect. Some outer solar system material may still have climbed across the divide. And those fugitives could have been important for the evolution of our own world.

"Those materials that might go to the Earth would be those volatile, carbon-rich materials," Mojzsis said. "And that gives you water. It gives you organics."

The rest is Earth history.

Credit: 
University of Colorado at Boulder

Rising temperatures may cause over 2,000 fatal injuries per year in the US, predict researchers

A 2 degrees Celsius rise in temperatures could result in around 2,100 additional deaths from injuries every year in the United States.

This is the finding of research from Imperial College London, Columbia University and Harvard University, published in the journal Nature Medicine.

In the study, funded by the US Environmental Protection Agency and the Wellcome Trust, the researchers calculated the number of additional fatal injuries that would occur in the US if temperatures rose by 1.5 and 2 degrees Celsius. The results revealed an additional 1,600 and 2,100 fatal injuries every year in these two scenarios.

Most of these deaths would be among young men, between the ages of 15-34 years. The three states with potentially the highest number of deaths would be California, Texas, and Florida.

The researchers studied the number of deaths from injuries a year in every state and county in the mainland United States (excluding Hawaii and Alaska) between the years of 1980 to 2017. These injuries were classed as unintentional, which include those from transport, falls and drowning, and intentional, which include assault and suicide.

The team then tracked unusual, or anomalous, temperature changes in every month in every county in mainland United States over this 38-year period. By comparing unusual temperatures with injury records, the team estimated the rise in deaths from injuries associated with a rising global temperatures triggered by climate change.

Most of the additional deaths seen during times of unusual temperature rises were among young men, and caused by transport accidents, suicides, drownings and violence explained Professor Majid Ezzati, senior author from J-IDEA, the Abdul Latif Jameel Institute for Disease and Emergency Analytics at Imperial College London. "These predictions suggest we should expect to see more deaths from transport accidents, suicides, drownings and violence as temperatures rise. These new results show how much climate change can affect young people. We need to respond to this threat with better preparedness in terms of emergency services, social support and health warnings."

In the research, the team used data from the National Center for Health Statistics to calculate the number of deaths from injuries between 1980 and 2017. This revealed 4.1 million boys and men and 1.8 million girls and women died from an injury during this 38-year period. Transport, falls, drownings, assault and suicide accounted for the majority of these deaths.

Using a statistical model, the researchers then calculated the number of additional deaths from injuries caused by unusual temperatures in different months of the year. The biggest effects of warm temperature were on risk of dying from drowning and transport accidents, which the researchers say is due to increased swimming, more driving and increased alcohol consumption in warm temperatures.

The researchers then used this model to predict number of additional deaths for an increase in average temperatures of 1.5 and 2 degrees Celsius. The research group chose these temperature rises, as the Paris Climate Agreement pledged to ensure global temperatures do not exceed 1.5 or 2 degrees Celsius.

The results suggest more than 1,200 of the 1,600 excess deaths associated with a 1.5 degrees Celsius rise would be in males. However, among older men and women, warmer winter months were associated with a reduction in deaths from falls.

There were also rises in risk of dying from suicide and assault in warmer temperatures, though not as large as those seen for drowning and transport.

The researchers say the reasons for these increases are not still fully understood. One possible explanation could be people spend more time outdoors in hot weather with more chance of confrontation. People also tend to be more agitated in hot weather, and perhaps drink more alcohol - which could all lead to increased number of assaults. In terms of suicides, previous research has suggested high temperatures are associated with higher levels of mental distress, especially in young people.

Dr Robbie Parks, lead author from Columbia University's Earth Institute, said: "Our work highlights how deaths from injuries including assaults, suicides, transport and drowning deaths currently rise with warm temperature, and could also worsen by rising temperatures resulting from climate change, unless countered by social and health system infrastructure that mitigate these impacts."

Credit: 
Imperial College London

Boost to lung immunity following infection

The strength of the immune system in response to respiratory infections is constantly changing, depending on the history of previous, unrelated infections, according to new research from the Crick.

There are two types of immunity to infections. Adaptive immunity provides immune "memory", allowing a fast and strong immunological response when the same disease is encountered more than once. In contrast, innate immunity provides a broad and less specific first line of defence against all pathogens, and is vital to controlling infections the body has not experienced previously.

The study, published in Nature Immunology, found that after recovery from a respiratory infection, particular cells in the innate immune system in the lung are more effective, offering extra protection against new infections in the following weeks. Specifically, they found that mice given the flu virus were significantly less likely to catch a completely different, bacterial, infection a month later.

This heightened immunity is the result of how, during the initial infection, a particular type of immune cell travels from the bone marrow to the lungs and turns into a lung macrophage, a type of white blood cell. Once in the lungs, these cells produce cytokines, hormone-like molecules which cause inflammation and help fight pathogens.

As these special macrophages remain in a more reactive state in the lungs after the infection is resolved, they offer an extra layer of protection from future infections over the following weeks. However, over time the ability of these macrophages to produce high levels of cytokines disappears. This means that, after a couple of months, protection against infection decreases and eventually returns to the same level as in animals which had not previously been infected. The researchers believe this mechanism could also be true for humans.

"Flu is a serious disease, especially for vulnerable groups, and we're not suggesting that a flu infection is desirable. Rather, this research provides valuable insights into how a viral infection that is cleared quickly can continue to affect immunity for weeks afterwards, through long-term changes in innate immune cells. This could partially explain why our response to diseases can vary - what you could fight off with no symptoms one week, could have nasty effects a couple of weeks later," says Helena Aegerter, lead author and PhD student in the Immunoregulation Laboratory at the Crick.

The researchers plan to look further into how a history of infection affects the immune system, including in conditions such as asthma or chronic obstructive pulmonary disease, where the heightened inflammatory response explained in this research could worsen symptoms.

"Our immune system is a mosaic of protective mechanisms and the level of protection is not constant. This means it's important people take long-term precautions against infection where appropriate, such as winter flu vaccinations," says Andreas Wack, author and group leader in the Immunoregulation Laboratory.

Credit: 
The Francis Crick Institute

TESS dates an ancient collision with our galaxy

A single bright star in the constellation of Indus, visible from the southern hemisphere, has revealed new insights on an ancient collision that our galaxy the Milky Way underwent with another smaller galaxy called Gaia-Enceladus early in its history.

An international team of scientists led by the University of Birmingham adopted the novel approach of applying the forensic characterisation of a single ancient, bright star called ν Indi as a probe of the history of the Milky Way. Stars carry "fossilized records" of their histories and hence the environments in which they formed. The team used data from satellites and ground-based telescopes to unlock this information from ν Indi. Their results are published in the journal Nature Astronomy.

The star was aged using its natural oscillations (asteroseismology), detected in data collected by NASA's recently launched Transiting Exoplanet Survey Satellite (TESS). Launched in 2018, TESS is surveying stars across most of the sky to search for planets orbiting the stars and to study the stars themselves. When combined with data from the European Space Agency (ESA) Gaia Mission, the detective story revealed that this ancient star was born early in the life of the Milky Way, but the Gaia-Enceladus collision altered its motion through our Galaxy.

Bill Chaplin, Professor of Astrophysics at the University of Birmingham and lead author of the study said: "Since the motion of ν Indi was affected by the Gaia-Enceladus collision, the collision must have happened once the star had formed. That is how we have been able to use the asteroseismically-determined age to place new limits on when the Gaia-Enceladus event occurred."

Co-author Dr Ted Mackereth, also from Birmingham, said: "Because we see so many stars from Gaia-Enceladus, we think it must have had a large impact on the evolution of our Galaxy. Understanding that is now a very hot topic in astronomy, and this study is an important step in understanding when this collision occurred."

Bill Chaplin added: "This study demonstrates the potential of asteroseismology with TESS, and what is possible when one has a variety of cutting-edge data available on a single, bright star"

The research clearly shows the strong potential of the TESS programme to draw together rich new insights about the stars that are our closest neighbours in the Milky Way. The research was funded by the Science and Technology Facilities Council and the European Research Council through the Asterochronometry project.

Credit: 
University of Birmingham

Global diets are converging, with benefits and problems

Research carried out by the University of Kent has shown that diets are changing in complex ways worldwide. International food supply patterns are supporting healthier diets in parts of the world, but causing underweight and obesity elsewhere. They are also having important effects on environmental sustainability, with potentially worrying consequences.

Dr James Bentham, Lecturer in Statistics at Kent's School of Mathematics, Statistics and Actuarial Science, led the research alongside Professor Majid Ezzati from the School of Public Health at Imperial College London and other UK and international colleagues. The researchers carried out the study analysing food supply data for 171 countries from the 1960's to 2010's.

The team discovered that South Korea, China and Taiwan have experienced the largest changes in food supply over the past five decades, with animal source foods such as meat and eggs, sugar, vegetables, seafood and oilcrops all becoming a much larger proportion of diet. In contrast, in many Western countries the supply of animal source foods and sugar has declined, particularly in high-income English-speaking countries such as the UK, US, Canada and Australia. The researchers also found that many countries around the world have seen an increase in vegetable-based diets. The sub-Saharan Africa region showed the least change, with a lack of diverse food supply, and this could be an explanation for the region's malnutrition.

The declines in diets based on animal source foods and sugar and corresponding increases in vegetable availability indicate a possible trend towards more balanced and healthier foods in some parts of the world. However, in South Korea, China and Taiwan in particular, the increase in animal source and sugar availability has occurred at the same time as a dramatic rise in obesity, and also suggests that changes in diet may be having a substantial negative effect on the environment.

Dr Bentham said: 'There are clear shifts in global food supply, and these trends may be responsible for strong improvements in nutrition in some parts of the world. However, obesity remains a long-term concern, and we hope that our research will open doors to analysis of the health impacts of global diet patterns. Equally, we must also consider carefully the environmental impacts of these trends.'

Professor Ezzati added: 'Advances in science and technology, together with growing incomes, have allowed many nations to have access to a diversity of foods. We must harness these advances and set in place policies that provide healthier foods for people everywhere, especially those who can currently least afford them.'

Credit: 
University of Kent

College students use more marijuana in states where it's legal, but they binge drink less

image: Marijuana use among college students has been trending upward for years, but in states that have legalized recreational marijuana, use has jumped even higher. A study published today in Addiction shows that in states where marijuana was legalized by 2018, both occasional and frequent use among college students has continued to rise beyond the first year of legalization, suggesting an ongoing trend rather than a brief period of experimentation.

Image: 
OSU

CORVALLIS, Ore. - Marijuana use among college students has been trending upward for years, but in states that have legalized recreational marijuana, use has jumped even higher.

An Oregon State University study published today in Addiction shows that in states where marijuana was legalized by 2018, both occasional and frequent use among college students has continued to rise beyond the first year of legalization, suggesting an ongoing trend rather than a brief period of experimentation.

Overall, students in states with legal marijuana were 18% more likely to have used marijuana in the past 30 days than students in states that had not legalized the drug. They were also 17% more likely to have engaged in frequent use, defined as using marijuana on at least 20 of the past 30 days.

The differences between states with and without legalization escalated over time: Six years after legalization in early-adopting states, students were 46% more likely to have used marijuana than their peers in non-legalized states.

Between 2012 and 2018, overall usage rates increased from 14% to 17% in non-legalized states, but shot up from 21% to 34% in the earliest states to legalize the drug. Similar trends appeared in states that legalized marijuana more recently.

Conducted by Harold Bae from OSU's College of Public Health and Human Sciences and David Kerr from OSU's College of Liberal Arts, this is the first study of college students to look broadly at multiple states that have legalized recreational marijuana and to go beyond the first year following legalization.

It includes data from seven states and 135 colleges where marijuana was legalized by 2018 and from 41 states and 454 colleges where recreational use was not legal.

That scope allowed Bae and Kerr to examine trends in the earliest adopting states as well as more recent adopters - though, the data for the study is stripped of state- and college-identifying information, so does not speak specifically to any one state or institution.

The data comes from the National College Health Assessment survey from 2008 to 2018, which asks about a wide range of health behaviors including drug and alcohol use and is administered anonymously to encourage students to respond more honestly. More than 850,000 students participated.

Looking at specific demographics, researchers found that the effect was stronger among older students ages 21-26 than minors ages 18-20; older students were 23% more likely to report having used marijuana than their peers in non-legalized states. The effect was also stronger among female students and among students living in off-campus housing, possibly because universities adhere to federal drug laws that still classify marijuana as an illegal substance.

"It's easy to look at the findings and think, 'Yeah, of course rates would increase,'" Kerr said. "But we need to quantify the effects these policy changes are having."

Furthermore, he said, researchers are not finding increases in adolescents' marijuana use following legalization. "So it is surprising and important that these young adults are sensitive to this law. And it's not explained by legal age, because minors changed too."

A recent companion study published in Addictive Behaviors in November by OSU doctoral candidate Zoe Alley along with Kerr and Bae examined the relationship between recreational marijuana legalization and college students' use of other substances.

Using the same dataset, they found that after legalization, students ages 21 and older showed a greater drop in binge drinking than their peers in states where marijuana was not legal. Binge drinking was defined as having five or more drinks in a single sitting within the previous two weeks.

Researchers have not yet tested any hypotheses as to why binge drinking fell, but they have some ideas.

An outside study previously found that illegal marijuana use decreases sharply when people hit 21 - where there is a sharp increase in alcohol use.

"When you're under 21, all substances are equally illegal," Alley said. "In most states, once you reach 21, a barrier that was in the way of using alcohol is gone, while it's intact for marijuana use. But when marijuana is legal, this dynamic is changed."

Binge drinking has been on the decline among college students in recent years, but dropped more in states that legalized marijuana than in states that did not.

"So in these two studies we saw changes after legalization that really differed by substance," Kerr said. "For marijuana we saw state-specific increases that went beyond the nationwide increases, whereas binge drinking was the opposite: a greater decrease in the context of nationwide decreases."

The magnitude of effect was much larger with marijuana than with any of the other substances, Bae added. "So the changes following recreational marijuana legalization were quite specific to cannabis use."

Future research is needed to see how those trends hold up over time, as additional states legalize marijuana and existing states continue to tweak their current policies, the researchers said.

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Oregon State University

Stars need a partner to spin universe's brightest explosions

image: This is an artist's impression of gamma-ray burst with orbiting binary star.

Image: 
University of Warwick/Mark Garlick

When it comes to the biggest and brightest explosions seen in the Universe, University of Warwick astronomers have found that it takes two stars to make a gamma-ray burst.

New research solves the mystery of how stars spin fast enough to create conditions to launch a jet of highly energetic material into space, and has found that tidal effects like those between the Moon and the Earth are the answer.

The discovery, reported in Monthly Notices of the Royal Astronomical Society, has been made using simulated models of thousands of binary star systems, that is, solar systems that have two stars orbiting one another.

More than half of all stars are located in binary star systems and this new research has shown that they need to be in binary star systems in order for the massive explosions to be created.

A long gamma-ray burst (GRB), the type examined in this study, occurs when a massive star about ten times the size of our sun goes supernova, collapses into a neutron star or black hole and fires a relativistic jet of material into space. Instead of the star collapsing radially inwards, it flattens down into a disc to conserve angular momentum. As the material falls inwards, that angular momentum launches it in the form of a jet along the polar axis.

But in order to form that jet of material, the star has to be spinning fast enough to launch material along the axis. This presents a problem because stars usually lose any spin they acquire very quickly. By modelling the behaviour of these massive stars as they collapse, the researchers have been able to constrain the factors that cause a jet to be formed.

They found that the effects of tides from a close neighbour - the same effect that has the Moon and the Earth locked together in their spin - could be responsible for spinning these stars at the rate needed to create a gamma-ray burst.

Gamma-ray bursts are the most luminous events in the Universe and are observable from Earth when their jet of material is pointed directly at us. This means that we only see around 10-20% of the GRBs in our skies.

Lead author Ashley Chrimes, a PhD student in the University of Warwick Department of Physics, said: "We're predicting what kind of stars or systems produce gamma-ray bursts, which are the biggest explosions in the Universe. Until now it's been unclear what kind of stars or binary systems you need to produce that result.

"The question has been how a star starts spinning, or maintains its spin over time. We found that the effect of a star's tides on its partner is stopping them from slowing down and, in some cases, it is spinning them up. They are stealing rotational energy from their companion, a consequence of which is that they then drift further away.

"What we have determined is that the majority of stars are spinning fast precisely because they're in a binary system."

The study uses a collection of binary stellar evolution models created by researchers from the University of Warwick and Dr J J Eldridge from the University of Auckland. Using a technique called binary population synthesis, the scientists are able to simulate this mechanism in a population of thousands of star systems and so identify the rare examples where an explosion of this type can occur.

Dr Elizabeth Stanway, from the University of Warwick Department of Physics, said: "Scientists haven't modelled in detail for binary evolution in the past because it's a very complex calculation to do. This work has considered a physical mechanism within those models that we haven't examined before, that suggests that binaries can produce enough GRBs using this method to explain the number that we are observing.

"There has also been a big dilemma over the metallicity of stars that produce gamma-ray bursts. As astronomers, we measure the composition of stars and the dominant pathway for gamma-ray bursts requires very few iron atoms or other heavy elements in the stellar atmosphere. There's been a puzzle over why we see a variety of compositions in the stars producing gamma-ray bursts, and this model offers an explanation."

Ashley added: "This model allows us to predict what these systems should look like observationally in terms of their temperature and luminosity, and what the properties of the companion are likely to be. We are now interested in applying this analysis to explore different astrophysical transients, such as fast radio bursts, and can potentially model rarer events such as black holes spiralling into stars."

Credit: 
University of Warwick

High temperatures due to global warming will be dramatic even for tardigrades

image: A research group from Department of Biology, University of Copenhagen has just shown that tardigrades are very vulnerable to long-term high temperature exposures. Animals, which in their desiccated state are best known for their extraordinary tolerance to extreme environments.

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Ricardo Neves

Global warming, a major aspect of climate change, is already causing a wide range of negative impacts on many habitats of our planet. It is thus of the utmost importance to understand how rising temperatures may affect animal health and welfare. A research group from Department of Biology, University of Copenhagen has just shown that tardigrades are very vulnerable to long-term high temperature exposures. Animals, which in their desiccated state are best known for their extraordinary tolerance to extreme environments.

In a study published recently in Scientific Reports (an open access journal published by Nature Publishing Group), Ricardo Neves and Nadja Møbjerg and colleagues at Department of Biology, University of Copenhagen present results on the tolerance to high temperatures of a tardigrade species.

Tardigrades, commonly known as water bears or moss piglets, are microscopic invertebrates distributed worldwide in marine, freshwater and terrestrial microhabitats.

Ricardo Neves, Nadja Møbjerg and colleagues investigated the tolerance to high temperatures of Ramazzottius varieornatus, a tardigrade frequently found in transient freshwater habitats.

- "The specimens used in this study were obtained from roof gutters of a house located in Nivå, Denmark. We evaluated the effect of exposures to high temperature in active and desiccated tardigrades, and we also investigated the effect of a brief acclimation period on active animals", explains postdoc Ricardo Neves.

Rather surprisingly the researchers estimated that for non-acclimated active tardigrades the median lethal temperature is 37.1°C, though a short acclimation periods leads to a small but significant increase of the median lethal temperature to 37.6°C. Interestingly, this temperature is not far from the currently measured maximum temperature in Denmark, i.e. 36.4°C. As for the desiccated specimens, the authors observed that the estimated 50% mortality temperature is 82.7°C following 1 hour exposures, though a significant decrease to 63.1°C following 24 hour exposures was registered.

The research group used logistic models to estimate the median lethal temperature (at which 50% mortality is achieved) both for active and desiccated tardigrades.

Approximately 1300 tardigrade species have been described so far. The body of these minute animals is barrel-shaped (or dorsoventrally compressed) and divided into a head and a trunk with four pairs of legs. Their body length varies between 50 micrometers and 1.2 millimeters. Apart from their impressive ability to tolerate extreme environments, tardigrades are also very interesting because of their close evolutionary relationship with arthropods (e.g., insects, crustaceans, spiders).

As aquatic animals, tardigrades need to be surrounded in a film of water to be in their active state (i.e., feeding and reproducing). However, these critters are able to endure periods of desiccation (anhydrobiosis) by entering cryptobiosis, i.e., a reversible ametabolic state common especially among limno-terrestrial species. Succinctly, tardigrades enter the so-called "tun" state by contracting their anterior-posterior body axis, retracting their legs and rearranging the internal organs. This provides them with the capacity to tolerate severe environmental conditions including oxygen depletion (anoxybiosis), high toxicant concentrations (chemobiosis), high solute concentration (osmobiosis) and extremely low temperatures (cryobiosis).

The extraordinary tolerance of tardigrades to extreme environments includes also high temperature endurance. Some tardigrade species were reported to tolerate temperatures as high as 151°C. However, the exposure time was only of 30 minutes. Other studies on thermotolerance of desiccated (anhydrobiotic) tardigrades revealed that exposures higher than 80°C for 1 hour resulted in high mortality, with almost all specimens dying at temperatures above 103°C. It remained, yet, unknown how anhydrobiotic tardigrades handle exposures to high temperatures for long periods, i.e., exceeding 1 hour.

- "From this study, we can conclude that active tardigrades are vulnerable to high temperatures, though it seems that these critters would be able to acclimatize to increasing temperatures in their natural habitat. Desiccated tardigrades are much more resilient and can endure temperatures much higher than those endured by active tardigrades. However, exposure-time is clearly a limiting factor that constrains their tolerance to high temperatures.", says Ricardo Neves.

Indeed, although tardigrades are able to tolerate a diverse set of severe environmental conditions, their endurance to high temperatures is noticeably limited and this might actually be the Achilles heel of these otherwise super-resistant animals.

Credit: 
University of Copenhagen - Faculty of Science

First robust cell culture model for the hepatitis E virus

Even though hepatitis E causes over three million infections and about 70,000 deaths each year, the virus has been little studied as yet. This may be about to change, because a research team from Bochum and Hanover has developed a robust and improved cell model of the pathogen. It produces about 100 times more infectious virus particles than previous models. "As a result, we are finally able to study the virus in depth," says Professor Eike Steinmann, Head of the Department for Molecular & Medical Virology at Ruhr-Universität Bochum (RUB). The researchers published their results in the journal PNAS from 2 January 2020.

Mutation leads to increased proliferation

The lack of a robust cell culture model is one of the reasons why the hepatitis E virus (HEV) has been little investigated to date. "The number of infectious virus particles produced in previous models was simply too small to generate reproducible results," explains Dr. Daniel Todt, author from Bochum.

In previous studies, the research team analysed virus populations resulting from genetic mutations of the virus in patients and identified a specific genetic change that leads to a significantly higher proliferation of the pathogen. The scientists inserted this mutation into the previously used cell lines and were thus able to increase the production of new virus particles by a factor of five to ten.

In their current article, they optimised the cell culture conditions by adding special culture media and using different liver cell lines. These measures resulted in approximately 100 times more infectious virus particles than previously published.

Extensive tests show that the model works

In order to verify whether the new cell culture model can be used to study the virus, the researchers carried out several experiments. For example, they tested whether enveloped and naked viruses are produced in the same way. "Both variants of the virus occur in HEV patients," explains study author Martina Friesland from the Experimental Virology at Twincore Centre for Experimental and Clinical Infection Research in Hanover. "However, they are responsible for different routes of infection. While the enveloped virus is transmitted by blood-blood contact, such as transfusions, the naked virus is excreted via the stool and causes infection for example through contaminated drinking water." Both variants can now be studied with the new cell culture model.

In a previous study, the authors had shown that the mutation leads to increased proliferation in all hepatitis E viruses, and that this is also the case in various liver cell lines used in the research. In the current study, they optimised the model once again. "To this end, we have used insights gained in the clinic to improve a preclinical in-vitro model," elaborates Daniel Todt. The effect of increased proliferation is also evident in healthy human liver cells, as well as in the animal model. Here, virus particles could be detected in the blood and faeces of rodents for more than a month. "In previous models, detection was only ever possible in faeces, because the number of virus particles produced was too low," points out Daniel Todt. "Now, we can produce infectious viruses in almost unlimited quantities for research purposes and do not have to resort to virus isolates from patients."

Full grasp of details

Since this was the first time that they were able to infect cells isolated from healthy liver tissue reproducibly with cell culture-derived HEV, the researchers performed deep sequencing: they analysed the entire genetic information of the virus at different points in time of infection, both under and without the influence of drugs. Moreover, they studied the altered expression of different proteins of affected liver cells in response to the infection, both under the influence of drugs and without the influence of drugs. "We wanted to know how the cell reacts to the infection," says Daniel Todt. "Our aim was to gain a full understanding of the details," points out Eike Steinmann. "This is the only way to identify genes that are particularly important for the course of the infection and take them under consideration as possible targets for therapeutic approaches in future." The researchers are making the data set and the optimised protocol available to the public, in order to enable the entire scientific community to conduct follow-up research using the model and the previous findings.

Hepatitis E

The hepatitis E virus (HEV) is the main cause of acute viral hepatitis. After the first documented epidemic outbreak in 1955-1956, more than 50 years passed before researchers took up in-depth research into the disease. In patients with an intact immune system, acute infections usually heal on their own. However, HEV can become chronic in patients with reduced or suppressed immune systems, such as organ transplant recipients or HIV-infected patients. HEV is also particularly dangerous for pregnant women.

Credit: 
Ruhr-University Bochum