星空健康频道

2013年8月30日星期五

NASA data reveals mega-canyon under Greenland ice sheet

Aug. 29, 2013 — Data from a NASA airborne science mission reveals evidence of a large and previously unknown canyon hidden under a mile of Greenland ice.

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The canyon has the characteristics of a winding river channel and is at least 460 miles (750 kilometers) long, making it longer than the Grand Canyon. In some places, it is as deep as 2,600 feet (800 meters), on scale with segments of the Grand Canyon. This immense feature is thought to predate the ice sheet that has covered Greenland for the last few million years.

"One might assume that the landscape of the Earth has been fully explored and mapped," said Jonathan Bamber, professor of physical geography at the University of Bristol in the United Kingdom, and lead author of the study. "Our research shows there's still a lot left to discover."

Bamber's team published its findings Thursday in the journal Science.

The scientists used thousands of miles of airborne radar data, collected by NASA and researchers from the United Kingdom and Germany over several decades, to piece together the landscape lying beneath the Greenland ice sheet.

A large portion of this data was collected from 2009 through 2012 by NASA's Operation IceBridge, an airborne science campaign that studies polar ice. One of IceBridge's scientific instruments, the Multichannel Coherent Radar Depth Sounder, can see through vast layers of ice to measure its thickness and the shape of bedrock below.

In their analysis of the radar data, the team discovered a continuous bedrock canyon that extends from almost the center of the island and ends beneath the Petermann Glacier fjord in northern Greenland.

At certain frequencies, radio waves can travel through the ice and bounce off the bedrock underneath. The amount of times the radio waves took to bounce back helped researchers determine the depth of the canyon. The longer it took, the deeper the bedrock feature.

"Two things helped lead to this discovery," said Michael Studinger, IceBridge project scientist at NASA's Goddard Space Flight Center in Greenbelt, Md. "It was the enormous amount of data collected by IceBridge and the work of combining it with other datasets into a Greenland-wide compilation of all existing data that makes this feature appear in front of our eyes."

The researchers believe the canyon plays an important role in transporting sub-glacial meltwater from the interior of Greenland to the edge of the ice sheet into the ocean. Evidence suggests that before the presence of the ice sheet, as much as 4 million years ago, water flowed in the canyon from the interior to the coast and was a major river system.

"It is quite remarkable that a channel the size of the Grand Canyon is discovered in the 21st century below the Greenland ice sheet," said Studinger. "It shows how little we still know about the bedrock below large continental ice sheets."

The IceBridge campaign will return to Greenland in March 2014 to continue collecting data on land and sea ice in the Arctic using a suite of instruments that includes ice-penetrating radar.

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NASA's Chandra Observatory catches giant black hole rejecting material

New Chandra images of Sagittarius A* (Sgr A*), which is located about 26,000 light-years from Earth, indicate that less than 1 percent of the gas initially within Sgr A*'s gravitational grasp ever reaches the point of no return, also called the event horizon. Instead, much of the gas is ejected before it gets near the event horizon and has a chance to brighten, leading to feeble X-ray emissions.

These new findings are the result of one of the longest observation campaigns ever performed with Chandra. The spacecraft collected five weeks' worth of data on Sgr A* in 2012. The researchers used this observation period to capture unusually detailed and sensitive X-ray images and energy signatures of super-heated gas swirling around Sgr A*, whose mass is about 4 million times that of the sun.

"We think most large galaxies have a supermassive black hole at their center, but they are too far away for us to study how matter flows near it," said Q. Daniel Wang of the University of Massachusetts in Amherst, who led of a study published Thursday in the journal Science. "Sgr A* is one of very few black holes close enough for us to actually witness this process."

The researchers found that the Chandra data from Sgr A* did not support theoretical models in which the X-rays are emitted from a concentration of smaller stars around the black hole. Instead, the X-ray data show the gas near the black hole likely originates from winds produced by a disk-shaped distribution of young massive stars.

"This new Chandra image is one of the coolest I've ever seen," said co-author Sera Markoff of the University of Amsterdam in the Netherlands. "We're watching Sgr A* capture hot gas ejected by nearby stars, and funnel it in towards its event horizon."

To plunge over the event horizon, material captured by a black hole must lose heat and momentum. The ejection of matter allows this to occur.

"Most of the gas must be thrown out so that a small amount can reach the black hole," said Feng Yuan of Shanghai Astronomical Observatory in China, the study's co-author. "Contrary to what some people think, black holes do not actually devour everything that's pulled towards them. Sgr A* is apparently finding much of its food hard to swallow."

The gas available to Sgr A* is very diffuse and super-hot, so it is hard for the black hole to capture and swallow it. The gluttonous black holes that power quasars and produce huge amounts of radiation have gas reservoirs much cooler and denser than that of Sgr A*.

The event horizon of Sgr A* casts a shadow against the glowing matter surrounding the black hole. This research could aid efforts using radio telescopes to observe and understand the shadow. It also will be useful for understanding the effect orbiting stars and gas clouds may have on matter flowing toward and away from the black hole.

NASA's Marshall Space Flight Center in Huntsville, Ala., manages the Chandra program for NASA's Science Mission Directorate in Washington. The Smithsonian Astrophysical Observatory controls Chandra's science and flight operations from Cambridge, Mass.

For Chandra images, multimedia and related materials, visit: http://www.nasa.gov/chandra

For an additional interactive image, podcast, and video on the finding, visit: http://chandra.si.edu

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'Trojan' asteroids in far reaches of solar system more common than previously thought

Trojans are asteroids that share the orbit of a planet, occupying stable positions known as Lagrangian points. Astronomers considered their presence at Uranus unlikely because the gravitational pull of larger neighbouring planets would destabilize and expel any Uranian Trojans over the age of the Solar System.

To determine how the 60 kilometre-wide ball of rock and ice ended up sharing an orbit with Uranus the astronomers created a simulation of the Solar System and its co-orbital objects, including Trojans.

"Surprisingly, our model predicts that at any given time three per cent of scattered objects between Jupiter and Neptune should be co-orbitals of Uranus or Neptune," says Mike Alexandersen, lead author of the study to be published tomorrow in the journal Science. This percentage had never before been computed, and is much higher than previous estimates.

Several temporary Trojans and co-orbitals have been discovered in the Solar System during the past decade. QF99 is one of those temporary objects, only recently (within the last few hundred thousand years) ensnared by Uranus and set to escape the planet's gravitational pull in about a million years.

"This tells us something about the current evolution of the Solar System," says Alexandersen. "By studying the process by which Trojans become temporarily captured, one can better understand how objects migrate into the planetary region of the Solar System."

UBC astronomers Brett Gladman, Sarah Greenstreet and colleagues at the National Research Council of Canada and Observatoire de Besancon in France were part of the research team.

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Poor concentration: Poverty reduces brainpower needed for navigating other areas of life

Aug. 29, 2013 — Poverty and all its related concerns require so much mental energy that the poor have less remaining brainpower to devote to other areas of life, according to research based at Princeton University. As a result, people of limited means are more likely to make mistakes and bad decisions that may be amplified by -- and perpetuate -- their financial woes.

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Published in the journal Science, the study presents a unique perspective regarding the causes of persistent poverty. The researchers suggest that being poor may keep a person from concentrating on the very avenues that would lead them out of poverty. A person's cognitive function is diminished by the constant and all-consuming effort of coping with the immediate effects of having little money, such as scrounging to pay bills and cut costs. Thusly, a person is left with fewer "mental resources" to focus on complicated, indirectly related matters such as education, job training and even managing their time.

In a series of experiments, the researchers found that pressing financial concerns had an immediate impact on the ability of low-income individuals to perform on common cognitive and logic tests. On average, a person preoccupied with money problems exhibited a drop in cognitive function similar to a 13-point dip in IQ, or the loss of an entire night's sleep.

But when their concerns were benign, low-income individuals performed competently, at a similar level to people who were well off, said corresponding author Jiaying Zhao, who conducted the study as a doctoral student in the lab of co-author Eldar Shafir, Princeton's William Stewart Tod Professor of Psychology and Public Affairs. Zhao and Shafir worked with Anandi Mani, an associate professor of economics at the University of Warwick in Britain, and Sendhil Mullainathan, a Harvard University economics professor.

"These pressures create a salient concern in the mind and draw mental resources to the problem itself. That means we are unable to focus on other things in life that need our attention," said Zhao, who is now an assistant professor of psychology at the University of British Columbia.

"Previous views of poverty have blamed poverty on personal failings, or an environment that is not conducive to success," she said. "We're arguing that the lack of financial resources itself can lead to impaired cognitive function. The very condition of not having enough can actually be a cause of poverty."

The mental tax that poverty can put on the brain is distinct from stress, Shafir explained. Stress is a person's response to various outside pressures that -- according to studies of arousal and performance -- can actually enhance a person's functioning, he said. In the Science study, Shafir and his colleagues instead describe an immediate rather than chronic preoccupation with limited resources that can be a detriment to unrelated yet still important tasks.

"Stress itself doesn't predict that people can't perform well -- they may do better up to a point," Shafir said. "A person in poverty might be at the high part of the performance curve when it comes to a specific task and, in fact, we show that they do well on the problem at hand. But they don't have leftover bandwidth to devote to other tasks. The poor are often highly effective at focusing on and dealing with pressing problems. It's the other tasks where they perform poorly."

The fallout of neglecting other areas of life may loom larger for a person just scraping by, Shafir said. Late fees tacked on to a forgotten rent payment, a job lost because of poor time-management -- these make a tight money situation worse. And as people get poorer, they tend to make difficult and often costly decisions that further perpetuate their hardship, Shafir said. He and Mullainathan were co-authors on a 2012 Science paper that reported a higher likelihood of poor people to engage in behaviors that reinforce the conditions of poverty, such as excessive borrowing.

"They can make the same mistakes, but the outcomes of errors are more dear," Shafir said. "So, if you live in poverty, you're more error prone and errors cost you more dearly -- it's hard to find a way out."

The first set of experiments took place in a New Jersey mall between 2010 and 2011 with roughly 400 subjects chosen at random. Their median annual income was around $70,000 and the lowest income was around $20,000. The researchers created scenarios wherein subjects had to ponder how they would solve financial problems, for example, whether they would handle a sudden car repair by paying in full, borrowing money or putting the repairs off. Participants were assigned either an "easy" or "hard" scenario in which the cost was low or high -- such as $150 or $1,500 for the car repair. While participants pondered these scenarios, they performed common fluid-intelligence and cognition tests.

Subjects were divided into a "poor" group and a "rich" group based on their income. The study showed that when the scenarios were easy -- the financial problems not too severe -- the poor and rich performed equally well on the cognitive tests. But when they thought about the hard scenarios, people at the lower end of the income scale performed significantly worse on both cognitive tests, while the rich participants were unfazed.

To better gauge the influence of poverty in natural contexts, between 2010 and 2011 the researchers also tested 464 sugarcane farmers in India who rely on the annual harvest for at least 60 percent of their income. Because sugarcane harvests occur once a year, these are farmers who find themselves rich after harvest and poor before it. Each farmer was given the same tests before and after the harvest, and performed better on both tests post-harvest compared to pre-harvest.

The cognitive effect of poverty the researchers found relates to the more general influence of "scarcity" on cognition, which is the larger focus of Shafir's research group. Scarcity in this case relates to any deficit -- be it in money, time, social ties or even calories -- that people experience in trying to meet their needs. Scarcity consumes "mental bandwidth" that would otherwise go to other concerns in life, Zhao said.

"These findings fit in with our story of how scarcity captures attention. It consumes your mental bandwidth," Zhao said. "Just asking a poor person to think about hypothetical financial problems reduces mental bandwidth. This is an acute, immediate impact, and has implications for scarcity of resources of any kind."

"We documented similar effects among people who are not otherwise poor, but on whom we imposed scarce resources," Shafir added. "It's not about being a poor person -- it's about living in poverty."

Many types of scarcity are temporary and often discretionary, said Shafir, who is co-author with Mullainathan of the book, "Scarcity: Why Having Too Little Means So Much," to be published in September. For instance, a person pressed for time can reschedule appointments, cancel something or even decide to take on less.

"When you're poor you can't say, 'I've had enough, I'm not going to be poor anymore.' Or, 'Forget it, I just won't give my kids dinner, or pay rent this month.' Poverty imposes a much stronger load that's not optional and in very many cases is long lasting," Shafir said. "It's not a choice you're making -- you're just reduced to few options. This is not something you see with many other types of scarcity."

The researchers suggest that services for the poor should accommodate the dominance that poverty has on a person's time and thinking. Such steps would include simpler aid forms and more guidance in receiving assistance, or training and educational programs structured to be more forgiving of unexpected absences, so that a person who has stumbled can more easily try again.

"You want to design a context that is more scarcity proof," said Shafir, noting that better-off people have access to regular support in their daily lives, be it a computer reminder, a personal assistant, a housecleaner or a babysitter.

"There's very little you can do with time to get more money, but a lot you can do with money to get more time," Shafir said. "The poor, who our research suggests are bound to make more mistakes and pay more dearly for errors, inhabit contexts often not designed to help."

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Single gene change increases mouse lifespan by 20 percent

A detailed study of these mice revealed that gene-influenced lifespan extension did not affect every tissue and organ the same way. For example, the mice retained better memory and balance as they aged, but their bones deteriorated more quickly than normal.

This study appears in the Aug. 29 edition of Cell Reports.

"While the high extension in lifespan is noteworthy, this study reinforces an important facet of aging; it is not uniform," said lead researcher Toren Finkel, M.D., Ph.D., at NIH's National Heart, Lung, and Blood Institute (NHLBI). "Rather, similar to circadian rhythms, an animal might have several organ-specific aging clocks that generally work together to govern the aging of the whole organism."

Finkel, who heads the NHLBI's Laboratory of Molecular Biology in the Division of Intramural Research, noted that these results may help guide therapies for aging-related diseases that target specific organs, like Alzheimer's. However, further studies in these mice as well as human cells are needed to identify exactly how aging in these different tissues is connected at the molecular level.

The researchers engineered mice that produce about 25 percent of the normal amount of the mTOR protein, or about the minimum needed for survival. The engineered mTOR mice were a bit smaller than average, but they otherwise appeared normal.

The median lifespan for the mTOR mice was 28.0 months for males and 31.5 months for females, compared to 22.9 months and 26.5 months for normal males and females, respectively. The mTOR mice also had a longer maximal lifespan; seven of the eight longest-lived mice in this study were mTOR mice. This lifespan increase is one of the largest observed in mice so far.

While the genetically modified mTOR mice aged better overall, they showed only selective improvement in specific organs. They generally outperformed normal mice of equivalent age in maze and balance tests, indicating better retention of memory and coordination. Older mTOR mice also retained more muscle strength and posture. However, mTOR mice had a greater loss in bone volume as they aged, and they were more susceptible to infections at old age, suggesting a loss of immune function.

In addition to the NHLBI, this study was carried out by intramural researchers at the NIH's National Cancer Institute; National Institute of Diabetes and Digestive and Kidney Diseases; and National Institute on Aging.

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Reproducing nature's chemistry: Researchers alter molecular properties in a new way

Aug. 29, 2013 — In their search for molecules with certain characteristics, chemists have produced millions of new, increasingly complex synthetic materials by altering molecules' chemical structures.

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Taking cues from nature, Northwestern University researchers have recently tested a new method for achieving the molecular properties they seek: by changing the geometry of the surface to which molecules are bound.

"For years chemists have been making molecules to solve problems -- each one more synthetically complicated than the last -- but we still haven't come close to achieving what nature can do with much simpler chemistry,'" said Bartosz A. Grzybowski, Kenneth Burgess Professor of Chemical and Biological Engineering and Chemistry at Northwestern's McCormick School of Engineering and Applied Science. "Nature's most complex component of life, the protein, is made from only 21 simple amino acids. This research explores the idea that it's not the molecule you have that's important, it is how it interacts with its environment."

Using this idea, the researchers developed a technique in which a single type of molecule is placed on nanoparticles with two different regions of curvature. Although the molecules are atomically identical, they demonstrate unique chemical properties depending on what region of curvature they are bound to.

A paper describing the research, "Geometric Curvature Controls the Chemical Patchiness and Self-Assembly of Nanoparticles," was published August 18 in Nature Nanotechnology.

The researchers began by affixing molecules of a carboxylic acid at various points on several gold nanoparticles, some as small as five nanometers in diameter. Each nanoparticle possessed a different geometry. On nanoparticles exhibiting a greater curvature, the molecules were naturally spaced father apart; on nanoparticles with more gradual curvature, they were closer together.

The differences in curvature influences the distance between the molecules, making it possible for the researchers to induce so-called "patchiness" on cylindrical- and dumbbell-shaped nanoparticles. Essentially, the molecules can "feel" each other through repulsive electrostatic interactions and, as the carboxylic acids are depronated, the difficulty in adding more charges onto the nanoparticles is controlled by how crowded the molecules are. These "patchy" nanoparticles can interact and self-assemble directionally, mimicking chemical molecular bonds -- and, the researchers found, altering when the charge of these attached molecules changes.

"Changing molecular properties by altering environments instead of molecular structure could free scientists to accomplish more with a smaller library of already existing molecules, and could offer alternatives to chemical processes that often require toxic chemicals," said David Walker, a graduate student in McCormick's Department of Chemical and Biological Engineering and the paper's first author.

The curvature phenomenon is specific to the nano-scale, where most of the chemistry in biological systems is performed, and begins to fail for nanoparticles above 10 nanometers in diameter, the researchers said. "Larger particles have curvatures that are just too subtle for the molecules to feel the effect -- similar to how humans might perceive the Earth to be flat, even though we now know better," Walker said.

The researchers are currently working to extend the work to other classes of molecules that could be beneficial for catalysis and energy purposes.

Other authors of the paper are Igal Szeifer, Christina Enroth-Cugell Professor of Biomedical Engineering and professor of chemistry, chemical and biological engineering, and professor of medicine; graduate student Emily Leitsch; and postdoctoral researcher Rikkert Nap, all of Northwestern.

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'Safe' levels of environmental pollution may have long-term health consequences

Aug. 29, 2013 — If you're eating better and exercising regularly, but still aren't seeing improvements in your health, there might be a reason: pollution. According to a new research report published in the September issue of The FASEB Journal, what you are eating and doing may not be the problem, but what's in what you are eating could be the culprit.

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"This study adds evidences for rethinking the way of addressing risk assessment especially when considering that the human population is widely exposed to low levels of thousands of chemicals, and that the health impact of realistic mixtures of pollutants will have to be tested as well," said Brigitte Le Magueresse-Battistoni, a researcher involved in the work from the French National Institute of Health and Medical Research (INSERM). "Indeed, one pollutant could have a different effect when in mixture with other pollutants. Thus, our study may have strong implications in terms of recommendations for food security. Our data also bring new light to the understanding of the impact of environmental food contaminants in the development of metabolic diseases."

To make this discovery, scientists used two groups of obese mice. Both were fed a high-fat, high-sucrose enriched diet, with one group receiving a cocktail of pollutants added to its diet at a very low dosage. These pollutants were given to the mice throughout -- from pre-conception to adulthood. Although the researchers did not observe toxicity or excess of weight gain in the group having received the cocktail of pollutants, they did see a deterioration of glucose tolerance in females, suggesting a defect in insulin signaling. Study results suggest that the mixture of pollutants reduced estrogen activity in the liver through enhancing an enzyme in charge of estrogen elimination. In contrast to females, glucose tolerance was not impacted in males exposed to the cocktail of pollutants. However, males did show some changes in liver related to cholesterol synthesis and transport. This study fuels the concept that pollutants may contribute to the current prevalence of chronic diseases including metabolic diseases and diabetes.

"This report that confirms something we've known for a long time: pollution is bad for us," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "But, what's equally important, it shows that evaluating food contaminants and pollutants on an individual basis may be too simplistic. We can see that when "safe" levels of contaminants and pollutants act together, they have significant impact on public health."

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Power Lapis hikes MCU clock accuracy for motor control

2013/08/29

LapisMotorControl 403 Lapis Semiconductor has raised the accuracy of on-chip oscillators in its 8bit microcontrollers for motor control.

The two chips offered are optimised to be built into single-phase fan motors, and it illustrates the need for accuracy with an example where multiple fans (one per MPU) run side-by-side in a server.

“If rotational variations exist between fans, wind noise due to the differences in frequencies will produce a buzzing sound. Fan rotation control via high-accuracy oscillator enables quiet operation,” said the firm.

In this case, it is offering 8.192MHz ±1% operation at (25°C), spreading to +/-2% from -10 to 85°C, and to +/-2.5% (-40 to 85°C). The data sheet describes these as ‘typical maximums and minimums’.

For Hall sensors, it has a hysteresis comparator with reference voltage and differential input switching, and for timing there are six 8bit timers, two of which can be added to make a 16bit timer.

Alongside this to control the motor is a 16.384MHz 16bit PWM with dead time.

This resolution, combined with oscillator accuracy said the firm, allows soft switching which reduces interference: “If the change in current during on/off switching in the motor coil current control is too large, irritating electromagnetic noise can result.”

The core is Lapis’ own risc ‘U8′, with 4kbyte if flash in the ML610Q101, and 6kB in the ML610Q102 variant. Both have 256bytes of RAM.

“The U8 enables efficient command execution of one instruction per clock with parallel processing of future commands by a three layer pipeline,” said Lapis. “Built-in on-chip debug function enables on-board software debugging and rewriting.”

For analogue measurement, there is a six channel 10bit ADC.

Operation is over 30kHz to 8.4MHz, -40 to 85°C, and 2.7 to 5.5V, with SSOP16 and WQFN16 package options, the smallest being 2x2mm.

The internal logic supply regulator does not need an external capacitor, and noise testing is to the +/-30kV level in IEC61000-4-2.

“Carefully designed circuit and layout have enabled high noise immunity, making it possible to clear the ±30kV level, which exceeds the measurement limit of Class 4 [+/-15kV], the highest class defined by the IEC61000-4-2 standard established by the IEC. This makes the LSIs suitable for use in industrial equipment with stringent noise requirements.”

Support includes a ML610Q102 reference board and software development environment. Applications are expected in home appliances, industrial equipment, single-phase fan motors, LED lights, and battery charge controllers.

Samples are available now, with mass SSOP16 production scheduled for September, and the WQFN16 version in October.

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2013年8月29日星期四

Echolocation for humans: Playing it by ear

As blind people can testify, we humans can hear more than one might think. The blind learn to navigate using as guides the echoes of sounds they themselves make. This enables them to sense the locations of walls and corners, for instance: by tapping the ground with a stick or making clicking sounds with the tongue, and analyzing the echoes reflected from nearby surfaces, a blind person can map the relative positions of objects in the vicinity. LMU biologists led by Professor Lutz Wiegrebe of the Department of Neurobiology (Faculty of Biology) have now shown that sighted people can also learn to echolocate objects in space, as they report in the biology journal Proceedings of the Royal Society B.

Wiegrebe and his team have developed a method for training people in the art of echolocation. With the help of a headset consisting of a microphone and a pair of earphones, experimental subjects can generate patterns of echoes that simulate acoustic reflections in a virtual space: the participants emit vocal clicks, which are picked up by the microphone and passed to a processor that calculates the echoes of a virtual space within milliseconds. The resulting echoes are then played back through the earphones. The trick is that the transformation applied to the input depends on the subject's position in virtual space. So the subject can learn to associate the artificial "echoes" with the distribution of sound-reflecting surfaces in the simulated space.

A dormant skill

"After several weeks of training, the participants in the experiment were able to locate the sources of echoes pretty well. This shows that anyone can learn to analyze the echoes of acoustic signals to obtain information about the space around him. Sighted people have this ability too; they simply don't need to use it in everyday situations," says Lutz Wiegrebe. "Instead, the auditory system actively suppresses the perception of echoes, allowing us to focus on the primary acoustic signal, independently of how the space alters the signals on its way to the ears." This makes it easier to distinguish between different sound sources, allowing us to concentrate on what someone is saying to us, for example. The new study shows, however, that it is possible to functionally invert this suppression of echoes, and learn to use the information they contain for echolocation instead.

In the absence of visual information, we and most other mammals find navigation difficult. So it is not surprising that evolution has endowed many mammalian species with the ability to "read" reflected sound waves. Bats and toothed whales, which orient themselves in space primarily by means of acoustic signals, are the best known.

Wiegrebe and his colleagues are now exploring how the coordination of self-motion and echolocation facilitates sonar-guided orientation and navigation in humans.

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'Mini human brains' created: Scientists grow human brain tissue in 3-D culture system

Aug. 29, 2013 — Complex human brain tissue has been successfully developed in a three-dimensional culture system established in an Austrian laboratory. The method described in the current issue of Nature allows pluripotent stem cells to develop into cerebral organoids -- or "mini brains" -- that consist of several discrete brain regions.

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Instead of using so-called patterning growth factors to achieve this, scientists at the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences (OeAW) fine-tuned growth conditions and provided a conducive environment. As a result, intrinsic cues from the stem cells guided the development towards different interdependent brain tissues. Using the "mini brains," the scientists were also able to model the development of a human neuronal disorder and identify its origin -- opening up routes to long hoped-for model systems of the human brain.

The development of the human brain remains one of the greatest mysteries in biology. Derived from a simple tissue, it develops into the most complex natural structure known to man. Studies of the human brain's development and associated human disorders are extremely difficult, as no scientist has thus far successfully established a three-dimensional culture model of the developing brain as a whole. Now, a research group lead by Dr. Jürgen Knoblich at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA) has just changed that.

Brain Size Matters

Starting with established human embryonic stem cell lines and induced pluripotent stem (iPS) cells, the group identified growth conditions that aided the differentiation of the stem cells into several brain tissues. While using media for neuronal induction and differentiation, the group was able to avoid the use of patterning growth factor conditions, which are usually applied in order to generate specific cell identities from stem cells. Dr. Knoblich explains the new method: "We modified an established approach to generate so-called neuroectoderm, a cell layer from which the nervous system derives. Fragments of this tissue were then maintained in a 3D-culture and embedded in droplets of a specific gel that provided a scaffold for complex tissue growth. In order to enhance nutrient absorption, we later transferred the gel droplets to a spinning bioreactor. Within three to four weeks defined brain regions were formed."

After only 15 -- 20 days, so-called "cerebral organoids" formed which consisted of continuous tissue (neuroepithelia) surrounding a fluid-filled cavity that was reminiscent of a cerebral ventricle. After 20 -- 30 days, defined brain regions, including a cerebral cortex, retina, meninges as well as choroid plexus, developed. After two months, the mini brains reached a maximum size, but they could survive indefinitely (currently up to 10 months) in the spinning bioreactor. Further growth, however, was not achieved, most likely due to the lack of a circulation system and hence a lack of nutrients and oxygen at the core of the mini brains.

Microcephaly in Mini Brains

The new method also offers great potential for establishing model systems for human brain disorders. Such models are urgently needed, as the commonly used animal models are of considerably lower complexity, and often do not adequately recapitulate the human disease.

Knoblich's group has now demonstrated that the mini brains offer great potential as a human model system by analysing the onset of microcephaly, a human genetic disorder in which brain size is significantly reduced. By generating iPS cells from skin tissue of a microcephaly patient, the scientists were able to grow mini brains affected by this disorder. As expected, the patient derived organoids grew to a lesser size.

Further analysis led to a surprising finding: while the neuroepithilial tissue was smaller than in mini brains unaffected by the disorder, increased neuronal outgrowth could be observed. This lead to the hypothesis that, during brain development of patients with microcephaly, the neural differentiation happens prematurely at the expense of stem and progenitor cells which would otherwise contribute to a more pronounced growth in brain size. Further experiments also revealed that a change in the direction in which the stem cells divide might be causal for the disorder.

"In addition to the potential for new insights into the development of human brain disorders, mini brains will also be of great interest to the pharmaceutical and chemical industry," explains Dr. Madeline A. Lancaster, team member and first author of the publication. "They allow for the testing of therapies against brain defects and other neuronal disorders. Furthermore, they will enable the analysis of the effects that specific chemicals have on brain development."

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