Brazilian Zika virus strain causes birth defects in experimental models

First direct experimental proof of causal effect, researchers say

Summary:

Researchers have described the first 'direct experimental proof' that the Brazilian strain of Zika virus can actually cause severe birth defects.

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Cross section of a human cerebral organoid shows different structures reminiscent of human embryonic cortical development, such as the proliferative zone in the center, with migrating cells to the surface forming the cortical plate. Cortical progenitor cells are in red, neurons in green and cell nuclei in blue.

Credit: UC San Diego Health

Researchers at University of California San Diego School of Medicine, with colleagues in Brazil and Senegal, have described the first "direct experimental proof" that the Brazilian strain of Zika virus can actually cause severe birth defects. The findings are published in the May 11 online issue of Nature.

The team, headed by Alysson R. Muotri, PhD, associate professor in the UC San Diego School of Medicine departments of Pediatrics and Cellular and Molecular Medicine, and co-corresponding senior author Patricia C.B. Beltrao-Braga, PhD, at the University of Sao Paulo, conducted studies in mouse models, human stem cells and in cerebral organoids -- miniature brains grown in vitro.
"Rising infection rates of Zika virus in places like Brazil, with a corresponding increase in cases of microcephaly, have powerfully suggested an association, but until now hard evidence has been lacking," said Muotri. "Our findings provide direct experimental proof that the Brazilian Zika virus strain causes severe birth defects -- and that the full adverse effect upon health, even beyond microcephaly, is not yet fully understood."
Muotri said the model developed to determine Zika cause-and-effect provides a new tool to assess the effectiveness of potential therapies to counteract the virus during human neurodevelopment.
"Our platform can now be used to understand what is unique about the Brazilian Zika virus and to test drugs to prevent the neurological problems associated with the infection," he said. "Moreover, we now have a robust animal model that will be useful during validation of potential vaccines against the virus."
The Zika virus is not new. It was first described in 1947 in rhesus monkeys in Uganda, but researchers say the twin lineages of Zika -- African and Asian -- did not cause meaningful infections in humans until 2007, when the Asian strain, carried by Aedes aegypti mosquitoes, caused an epidemic on the Pacific island of Yap. Further outbreaks occurred in New Caledonia and French Polynesia from 2013 to 2015.
In 2013, the Asian lineage of Zika reached Brazil and subsequently other countries in South and Central America. In Brazil, the virus has aroused international attention and concern, with infections of pregnant women alarmingly linked to congenital malformations, including microcephaly (an undersized head and brain) in newborns and other severe neurological diseases, such as Guillain-Barre syndrome.
In the Nature paper, authors used mouse models to track Brazilian virus infections to birth defects. "This is the first animal model to document Zika-induced birth defects. It shows that the virus can cross the placenta membrane and infect the fetus," said Muotri. Like humans, newborn mouse pups infected via their mothers with the Brazilian Zika virus strain displayed smaller-than-normal heads and stunted body growth. Tissue and genetic analyses revealed other abnormalities, including eye problems and ongoing cell death.
"The data in mice also suggest that microcephaly is only the tip of the iceberg. The animals have extensive intra-uterine growth arrest, which essentially means poor fetal development in the womb. Media covering the Zika story have focused upon affected babies with small heads because such images are profoundly dramatic, but the true health impact is likely to be more widespread and devastating."
Interestingly, Muotri noted that not all mouse models tested showed a causal effect when infected by the Zika virus. In at least one strain of mice, the Brazilian Zika virus could not cross the placenta of the mother to infect her unborn pups. Muotri said the finding suggests that in mice -- and humans -- some individuals may be more susceptible to infection than others, possibly due to genetic differences or varying robustness of the immune system response.
The researchers also conducted studies using human pluripotent stem cells to generate cortical progenitor cells that ordinarily would differentiate into neurons forming the brain's cerebral cortex or folded outer layer. Infection of these cortical progenitor cells by the Brazilian viral strain resulted in increased progenitor cell death. The effects of the African virus is not as pronounced, indicating that the mutations of the Brazilian strains made the virus more aggressive in human cells.
Finally, researchers exposed human brain organoids -- three-dimensional buds of cells created from pluripotent stem cells that structurally represent specific organs writ small -- to the Zika virus. They noted that infection resulted in reduced areas of growth in the organoids and disrupted cortical layers. Again, the Brazilian virus had a more dramatic impact on cortical malformations in these human organoids.
Muotri said they tested the Brazilian Zika virus in organoids derived from chimpanzees to assess its adaptability compared to the African strain. "The Brazilian virus has a slow replication rate in the chimp organoid compared to the African virus," Muotri said, "which suggests that the Brazilian strain has, somehow, adapted to humans. We are investigating how genetic differences might cause that difference."

The missing brown dwarfs

Summary:

When re-analyzing cataloged and updated observational data of brown dwarfs in the solar neighborhood, astronomers have found that a significant number of nearby brown dwarfs should still be out there, awaiting their discovery. The study challenges the previously established picture of brown dwarfs in the solar neighborhood.

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Possible manifestations of brown dwarfs (artist's impression). As brown dwarfs are nearly invisible in the optical light and only emit radiation in the IR regime, they exhibit different colors in that range.

Credit: AIP/J. Fohlmeister

When re-analysing catalogued and updated observational data of brown dwarfs in the solar neighbourhood, astronomers from Potsdam have found that a significant number of nearby brown dwarfs should still be out there, awaiting their discovery. The corresponding study by Gabriel Bihain and Ralf-Dieter Scholz from the Leibniz Institute for Astrophysics Potsdam (AIP) challenges the previously established picture of brown dwarfs in the solar neighbourhood.

Brown dwarfs are objects that are too large to be called planets, yet too small to be stars. Having a mass of only less than seven per cent of the mass of the Sun, they are unable to create sufficient pressure and heat in their interiors to ignite hydrogen-to-helium fusion, a fundamental physical mechanism by which stars generate radiation. In this sense brown dwarf are "failed stars." It is therefore important to know how many brown dwarfs really exist in different regions of the sky in order to achieve a better understanding of star formation and of the motion of stars in the Milky Way.
Gabriel Bihain and Ralf-Dieter Scholz have taken a careful look at the distribution of nearby known brown dwarfs from a point of view that was not looked at before. To their surprise they discovered a significant asymmetry in the spatial configuration, strongly deviating from the known distribution of stars.
"I projected the nearby brown dwarfs onto the galactic plane and suddenly realized: half of the sky is practically empty! We absolutely didn't expect this, as we have been looking at an environment that should be homogeneous.," Gabriel Bihain explained. Seen from Earth, the empty region overlaps with a large part of the northern sky.
The scientists concluded that there should be many more brown dwarfs in the solar neighbourhood that are yet to be discovered and that will fill the observed gap. If they are right, this would mean that star formation fails significantly more often than previously thought, producing one brown dwarf for every four stars. In any case, it appears, the established picture of the solar neighbourhood and of its brown dwarf population will have to be rethought.
"It is quite possible that not only brown dwarfs are still hiding in the observational data, but also other objects with even smaller, planetary-like masses. So it is definitely worth it to take another deep look at both existing and future data.," Ralf-Dieter Scholz concluded.

Supernova iron found on the moon

Confirmation of supernova explosion in the neighborhood of our solar system

Summary:

Approximately two million years ago a star exploded in a supernova close to our solar system: Its traces can still be found today in the form of an iron isotope found on the ocean floor. Now scientists have found increased concentrations of this supernova-iron in lunar samples as well. They believe both discoveries to originate from the same stellar explosion.

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Since the moon generally provides a better cosmic record than Earth, the scientists were also able to specify for the first time an upper limit for the flow of 60Fe that must have reached the moon.

Credit: © SkyLine / Fotolia

A dying star ends its life in a cataclysmic explosion, shooting the majority of the star's material, primarily new chemical elements created during the explosion, out into space.

One or more such supernovae appear to have occurred close to our solar system approximately two million years ago. Evidence of the fact has been found on Earth in the form of increased concentrations of the iron isotope 60Fe detected in Pacific ocean deep-sea crusts and in ocean-floor sediment samples.
This evidence is highly compelling: The radioactive 60Fe isotope is created almost exclusively in supernova explosions. And with a half-life of 2.62 million years, relatively short compared to the age of our solar system, any radioactive 60Fe originating from the time of the solar system's birth should have long ago decayed into stable elements and thus should no longer be found on Earth.
Lunar samples from the Apollo missions
This supernova hypothesis was first put forth in 1999 by researchers at the Technical University of Munich (TUM) who had found initial evidence in a deep-sea crust. Now their claim has received further substantiation: Physicists at the TUM and their colleagues from the USA have succeeded in demonstrating an unusually high concentration of 60Fe in lunar ground samples as well.
The samples were gathered between 1969 and 1972 during Apollo lunar missions 12, 15 and 16, which brought the lunar material back to earth.
It's also conceivable that 60Fe can occur on the moon as the result of bombardment with cosmic particles, since these particles do not break up when colliding with air molecules, as is the case with Earth's atmosphere. Instead they directly impact the lunar surface and can thus result in transmutation of elements. "But this can only account for a very small portion of the 60Fe found," explains Dr. Gunther Korschinek, physicist at TUM and scientist of the Cluster of Excellence Structure and Origin of the Universe.
Deposits of newly produced stellar matter
"We therefore assume that the 60Fe found in both terrestrial and lunar samples has the same source: These deposits are newly created stellar matter, produced in one or more supernovae," says Dr. Korschinek.
Since the moon generally provides a better cosmic record than Earth, the scientists were also able to specify for the first time an upper limit for the flow of 60Fe that must have reached the moon. Among other things this also makes it possible for the researchers to infer the distance to the supernova event: "The measured 60Fe-flow corresponds to a supernova at a distance of about 300 light years," says Korschinek. "This value is in good agreement with a recently theoretical estimation published in nature."
The lunar samples were investigated using the high-sensitivity accelerator mass spectrometer of the Maier-Leibnitz Laboratory near Munich.

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This 5-fingered robot hand learns to get a grip on its own.

Summary:

Computer science experts and engineering researchers have built a robot hand that can not only perform dexterous manipulation -- one of the most difficult problems in robotics to solve -- but also learn from its own experience.

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This five-fingered robot hand developed by University of Washington computer science and engineering researchers can learn how to perform dexterous manipulation -- like spinning a tube full of coffee beans -- on its own, rather than having humans program its actions.

Credit: University of Washington

Robots today can perform space missions, solve a Rubik's cube, sort hospital medication and even make pancakes. But most can't manage the simple act of grasping a pencil and spinning it around to get a solid grip.

Intricate tasks that require dexterous in-hand manipulation -- rolling, pivoting, bending, sensing friction and other things humans do effortlessly with our hands -- have proved notoriously difficult for robots.
Now, a University of Washington team of computer science and engineering researchers has built a robot hand that can not only perform dexterous manipulation but also learn from its own experience without needing humans to direct it. Their latest results are detailed in a paper to be presented May 17 at the IEEE International Conference on Robotics and Automation.
"Hand manipulation is one of the hardest problems that roboticists have to solve," said lead author Vikash Kumar, a UW doctoral student in computer science and engineering. "A lot of robots today have pretty capable arms but the hand is as simple as a suction cup or maybe a claw or a gripper."
By contrast, the UW research team spent years custom building one of the most highly capable five-fingered robot hands in the world. Then they developed an accurate simulation model that enables a computer to analyze movements in real time. In their latest demonstration, they apply the model to the hardware and real-world tasks like rotating an elongated object.
With each attempt, the robot hand gets progressively more adept at spinning the tube, thanks to machine learning algorithms that help it model both the basic physics involved and plan which actions it should take to achieve the desired result.
This autonomous learning approach developed by the UW Movement Control Laboratory contrasts with robotics demonstrations that require people to program each individual movement of the robot's hand in order to complete a single task.
"Usually people look at a motion and try to determine what exactly needs to happen --the pinky needs to move that way, so we'll put some rules in and try it and if something doesn't work, oh the middle finger moved too much and the pen tilted, so we'll try another rule," said senior author and lab director Emo Todorov, UW associate professor of computer science and engineering and of applied mathematics.
"It's almost like making an animated film -- it looks real but there was an army of animators tweaking it," Todorov said. "What we are using is a universal approach that enables the robot to learn from its own movements and requires no tweaking from us."
Building a dexterous, five-fingered robot hand poses challenges, both in design and control. The first involved building a mechanical hand with enough speed, strength responsiveness and flexibility to mimic basic behaviors of a human hand.
The UW's dexterous robot hand -- which the team built at a cost of roughly $300,000 -- uses a Shadow Hand skeleton actuated with a custom pneumatic system and can move faster than a human hand. It is too expensive for routine commercial or industrial use, but it allows the researchers to push core technologies and test innovative control strategies.
"There are a lot of chaotic things going on and collisions happening when you touch an object with different fingers, which is difficult for control algorithms to deal with," said co-author Sergey Levine, UW assistant professor of computer science and engineering who worked on the project as a postdoctoral fellow at University of California, Berkeley. "The approach we took was quite different from a traditional controls approach."
The team first developed algorithms that allowed a computer to model highly complex five-fingered behaviors and plan movements to achieve different outcomes -- like typing on a keyboard or dropping and catching a stick -- in simulation.
Most recently, the research team has transferred the models to work on the actual five-fingered hand hardware, which never proves to be exactly the same as a simulated scenario. As the robot hand performs different tasks, the system collects data from various sensors and motion capture cameras and employs machine learning algorithms to continually refine and develop more realistic models.
"It's like sitting through a lesson, going home and doing your homework to understand things better and then coming back to school a little more intelligent the next day," said Kumar.
So far, the team has demonstrated local learning with the hardware system -- which means the hand can continue to improve at a discrete task that involves manipulating the same object in roughly the same way. Next steps include beginning to demonstrate global learning -- which means the hand could figure out how to manipulate an unfamiliar object or a new scenario it hasn't encountered before.

Introducing the disposable laser

Ultra-low-cost, easy to fabricate 'lasing capsules' made with an inkjet printer.

Summary:

Since lasers were invented more than 50 years ago, they have transformed a diverse swath of technology -- from CD players to surgical instruments. Now researchers have invented a way to print lasers that's so cheap, easy and efficient they believe the core of the laser could be disposed of after each use.

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Inkjet printed "lasing capsules" serve as the core of an organic laser. Figure (a) shows a schematic of the laser setup, while figure (b) shows actual lasing capsules, which would cost only a few cents to produce. OC stands for "Output Coupler" and FP stands for Febry-Perot etalon.

Credit: Sanaur, et al/JAP

Since lasers were invented more than 50 years ago, they have transformed a diverse swath of technology -- from CD players to surgical instruments.

Now researchers from France and Hungary have invented a way to print lasers that's so cheap, easy and efficient they believe the core of the laser could be disposed of after each use. The team reports its findings in the Journal of Applied Physics, from AIP Publishing.
"The low-cost and easiness of laser chip fabrication are the most significant aspects of our results," said Sébastien Sanaur, an associate professor in the Center of Microelectronics in Provence at the Ecole Nationale Supérieure des Mines de Saint-Étienne in France.
Sanaur and his colleagues made organic lasers, which amplify light with carbon-containing materials. Organic lasers are not as common as inorganic lasers, like those found in laser pointers, DVD players, and optical mice, but they offer benefits such as high-yield photonic conversion, easy fabrication, low-cost and a wide range of wavelengths.
One obstacle that has held back organic lasers is the fact that they degrade relatively quickly -- but that hurdle might be less daunting if the lasers are so cheap they could be tossed when they fail.
Sanaur's research team produced their ultra-low-cost organic laser using a familiar technology: an inkjet printer.
Inkjet printing is a relatively inexpensive manufacturing process that works by squirting small jets of fluid onto an underlying material. The inkjet printer at your office is only one form of the technology -- scientists have also adapted it to print electronic circuits, pharmaceutical drugs and even biological cells.
"By piezoelectric inkjet printing, you print 'where you want, when you want,' without wasting raw materials," Sanaur said. The technique doesn't require masks, can be done at room temperature and can print onto flexible materials.
The researchers tested a variety of possible inks, before settling on a commercial ink variety called EMD6415, which they mixed with dyes. The ink was printed in small square shapes onto a quartz slide.
The dyed ink acted as the core of the laser, called a gain medium. A gain medium amplifies light and produces the characteristically narrow, single-color laser beam.
A laser also requires mirrors to reflect light back and forth through the gain medium and an energy source, called a pump, to keep the light amplification going.
The disposable part of the new laser is the printed gain medium, which the researchers call the "lasing capsule." They estimate it could be produced for only a few cents. Like the replaceable blades in a razor, the lasing capsule could be easily swapped out when it deteriorates.
The research team used two different types of dyes to produce laser emission ranging from yellow to deep red. Other dyes could cover the blue and green part of the spectrum, they predict.
With further development, the inexpensive inkjet-printed laser could send data over short plastic fibers and serve as a tool for analysing chemical or biological samples.

Second strongest shock wave found in merging galaxy clusters

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Astronomers have discovered the second-strongest merger shock in clusters of galaxies ever observed.

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The RGB (Red Green Blue image) of the cluster. Red color shows optical radiation, Green shows Radio and Blue color shows X-rays emission.

Credit: Chandra X-Ray Observatory

The discovery by a physics doctoral student at The University of Alabama in Huntsville (UAH) of the second-strongest merger shock in clusters of galaxies ever observed has generated excitement that is opening doors to further scientific exploration.

Sarthak Dasadia, who is advised by assistant physics professor Dr. Ming Sun, discovered the very strong shock in the merging galaxy cluster Abell 655 using observations from the Chandra X-ray Observatory.
The shock to the north of this cluster is second in strength only to the Bullet Cluster shock.
The shock is traveling with an astonishing speed of 2,700 kilometers per second, about three times the local speed of sound in the cluster. By comparison, NASA's Juno spacecraft in 2013 became the fastest human-made object when it was slingshot around Earth toward Jupiter at a relatively pedestrian 40 kilometers a second.
"Studying mergers of galaxy clusters has proven to be crucial to our understanding of how such large scale objects form and evolve," says Dasadia. Shocks provide unique opportunities to study high-energy phenomena in the intra-cluster medium -- the hot plasma between galaxies.
"This could open a door, where people can do a number of different studies based on what I have found," Dasadia says. Already, scientists are targeting shocks in galaxy clusters to study dark matter, the magnetic field in the intracluster space, particle acceleration and energy transfer in the intracluster medium.
In only 10 days, Dasadia's research was accepted for publication by The Astrophysical Journal Letters. Dasadia recently received one year of research support from the Alabama EPSCoR Graduate Research Scholars Program (ALEPSCoR). He also gave an oral presentation on his research in August at the International Astronomical Union (IAU) General Assembly in Honolulu, Hawaii.
The universe is populated with galaxy clusters that are relaxed and unrelaxed, Dasadia says. The relaxed ones are mellow -- they've been around a lot longer, have seen lots of past mergers and really aren't dynamically active. It's the unrelaxed clusters like Abell 665 that are good candidates to study merger features such as shocks and turbulence.
"These galaxy clusters are not boundary objects," he says. "They do not have a very well-defined boundary around them."
When the undefined boundaries of massive clusters of galaxies 3 million light-years across are drawn together in a slow-motion collision, their cold cores and surrounding hot gases are disrupted into shock waves and gas fronts of various temperatures.
"When two cold cores collide, they may create a shock of heated gas," Dasadia says. "Such mergers are actually among the most energetic events in the universe, other than the Big Bang itself."
If talking about fronts and shock waves and temperature differentials sounds lot like the weather on Earth, Dasadia says that's because there is not much difference as far as the physics involved.
"Technically, we observe the same features in space that we do on Earth," he says. "This area has been studied extensively before at small scales, but few had done the work to discover what I found here at such big scales."
He was able to measure the velocity of the collision and the dynamics of what is happening in it -- or rather, what was happening in it. It took 3.2 billion years for the light in the observations to reach Earth, so the events all happened that far back in time. Dynamic observations included the energy in the collision, the gas movement, and measurements of the discrepancy between the visible and dark matter involved.
"It amazes me how long it takes for this information to even reach the Earth," Dasadia says. "Then I am also amazed by our technology, by how much we have advanced in developing the telescopes and equipment it takes to be able to observe and study these interactions."

Cosmic dust reveals Earth's ancient atmosphere

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Using the oldest fossil micrometeorites -- space dust -- ever found, new research has made a surprising discovery about the chemistry of Earth's atmosphere 2.7 billion years ago.

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This is one of 60 micrometeorites extracted from 2.7 billion year old limestone, from the Pilbara region in Western Australia. These micrometeorites consist of iron oxide minerals that formed when dust particles of meteoritic iron metal were oxidised as they entered Earth's atmosphere, indicating that the ancient upper atmosphere was surprisingly oxygen-rich.

Credit: Andrew Tomkins

Using the oldest fossil micrometeorites -- space dust -- ever found, Monash University-led research has made a surprising discovery about the chemistry of Earth's atmosphere 2.7 billion years ago.

The findings of a new study published today in the journal Nature -- led by Dr Andrew Tomkins and a team from the School of Earth, Atmosphere and Environment at Monash, along with scientists from the Australian Synchrotron and Imperial College, London -- challenge the accepted view that Earth's ancient atmosphere was oxygen-poor. The findings indicate instead that the ancient Earth's upper atmosphere contained about the same amount of oxygen as today, and that a methane haze layer separated this oxygen-rich upper layer from the oxygen-starved lower atmosphere.
Dr Tomkins explained how the team extracted micrometeorites from samples of ancient limestone collected in the Pilbara region in Western Australia and examined them at the Monash Centre for Electron Microscopy (MCEM) and the Australian Synchrotron.
"Using cutting-edge microscopes we found that most of the micrometeorites had once been particles of metallic iron -- common in meteorites -- that had been turned into iron oxide minerals in the upper atmosphere, indicating higher concentrations of oxygen than expected," Dr Tomkins said.
"This was an exciting result because it is the first time anyone has found a way to sample the chemistry of the ancient Earth's upper atmosphere," Dr Tomkins said.
Imperial College researcher Dr Matthew Genge -- an expert in modern cosmic dust -- performed calculations that showed oxygen concentrations in the upper atmosphere would need to be close to modern day levels to explain the observations.
"This was a surprise because it has been firmly established that the Earth's lower atmosphere was very poor in oxygen 2.7 billion years ago; how the upper atmosphere could contain so much oxygen before the appearance of photosynthetic organisms was a real puzzle," Dr Genge said.
Dr Tomkins explained that the new results suggest the Earth at this time may have had a layered atmosphere with little vertical mixing, and higher levels of oxygen in the upper atmosphere produced by the breakdown of CO 2 by ultraviolet light.
"A possible explanation for this layered atmosphere might have involved a methane haze layer at middle levels of the atmosphere. The methane in such a layer would absorb UV light, releasing heat and creating a warm zone in the atmosphere that would inhibit vertical mixing," Dr Tomkins said.
"It is incredible to think that by studying fossilised particles of space dust the width of a human hair, we can gain new insights into the chemical makeup of Earth's upper atmosphere, billions of years ago." Dr Tomkins said.
Dr Tomkins outlined next steps in the research.
"The next stage of our research will be to extract micrometeorites from a series of rocks covering over a billion years of Earth's history in order to learn more about changes in atmospheric chemistry and structure across geological time. We will focus particularly on the great oxidation event, which happened 2.4 billion years ago when there was a sudden jump in oxygen concentration in the lower atmosphere."