Posts Tagged ‘science’

Physicist Steven Desch has come up with a novel solution to the problems that now beset the Arctic. He and a team of colleagues from Arizona State University want to replenish the region’s shrinking sea ice – by building 10 million wind-powered pumps over the Arctic ice cap. In winter, these would be used to pump water to the surface of the ice where it would freeze, thickening the cap.

The pumps could add an extra metre of sea ice to the Arctic’s current layer, Desch argues. The current cap rarely exceeds 2-3 metres in thickness and is being eroded constantly as the planet succumbs to climate change.

“Thicker ice would mean longer-lasting ice. In turn, that would mean the danger of all sea ice disappearing from the Arctic in summer would be reduced significantly,” Desch told the Observer.

Desch and his team have put forward the scheme in a paper that has just been published in Earth’s Future, the journal of the American Geophysical Union, and have worked out a price tag for the project: $500bn (£400bn).

It is an astonishing sum. However, it is the kind of outlay that may become necessary if we want to halt the calamity that faces the Arctic, says Desch, who, like many other scientists, has become alarmed at temperature change in the region. They say that it is now warming twice as fast as their climate models predicted only a few years ago and argue that the 2015 Paris agreement to limit global warming will be insufficient to prevent the region’s sea ice disappearing completely in summer, possibly by 2030.

“Our only strategy at present seems to be to tell people to stop burning fossil fuels,” says Desch. “It’s a good idea but it is going to need a lot more than that to stop the Arctic’s sea ice from disappearing.”

The loss of the Arctic’s summer sea ice cover would disrupt life in the region, endanger many of its species, from Arctic cod to polar bears, and destroy a pristine habitat. It would also trigger further warming of the planet by removing ice that reflects solar radiation back into space, disrupt weather patterns across the northern hemisphere and melt permafrost, releasing more carbon gases into the atmosphere.

Hence Desch’s scheme to use wind pumps to bring water that is insulated from the bitter Arctic cold to its icy surface, where it will freeze and thicken the ice cap. Nor is the physicist alone in his Arctic scheming: other projects to halt sea-ice loss include one to artificially whiten the Arctic by scattering light-coloured aerosol particles over it to reflect solar radiation back into space, and another to spray sea water into the atmosphere above the region to create clouds that would also reflect sunlight away from the surface.

All the projects are highly imaginative – and extremely costly. The fact that they are even being considered reveals just how desperately worried researchers have become about the Arctic. “The situation is causing grave concern,” says Professor Julienne Stroeve, of University College London. “It is now much more dire than even our worst case scenarios originally suggested.’

Last November, when sea ice should have begun thickening and spreading over the Arctic as winter set in, the region warmed up. Temperatures should have plummeted to -25C but reached several degrees above freezing instead. “It’s been about 20C warmer than normal over most of the Arctic Ocean. This is unprecedented,” research professor Jennifer Francis of Rutgers University told the Guardian in November. “These temperatures are literally off the charts for where they should be at this time of year. It is pretty shocking. The Arctic has been breaking records all year. It is exciting but also scary.”

Nor have things got better in the intervening months. Figures issued by the US National Snow and Ice Data Center (NSIDC), in Boulder, Colorado, last week revealed that in January the Arctic’s sea ice covered 13.38 million sq km, the lowest January extent in the 38 years since satellites began surveying the region. That figure is 260,000 sq km below the level for January last year, which was the previous lowest extent for that month, and a worrying 1.26 million sq km below the long-term average for January.

In fact, sea ice growth stalled during the second week of January – in the heart of the Arctic winter – while the ice cap actually retreated within the Kara and Barents seas, and within the Sea of Okhotsk. Similarly, the Svalbard archipelago, normally shrouded in ice, has remained relatively free because of the inflow of warm Atlantic water along the western part of the island chain. Although there has been some recovery, sea ice remains well below all previous record lows.

This paucity of sea ice bodes ill for the Arctic’s summer months when cover traditionally drops to its lower annual level, and could plunge to a record minimum this year. Most scientists expect that, at current emission rates, the Arctic will be reliably free of sea ice in summer by 2030.

By “free” they mean there will be less than 1m sq km of sea ice left in the Arctic, most of it packed into remote bays and channels, while the central Arctic Ocean over the north pole will be completely open. And by “reliably”, scientists mean there will have been five consecutive years with less than 1m sq km of ice by the year 2050. The first single ice-free year will come much earlier than this, however.

And when that happens, the consequences are likely to be severe for the human and animal inhabitants of the region. An ice-free Arctic will be wide open to commercial exploitation, for example. Already, mining, oil and tourism companies have revealed plans to begin operations – schemes that could put severe strain on indigenous communities’ way of life in the region.

Equally worrying is the likely impact on wildlife, says Stroeve. “Juvenile Arctic cod like to hang out under the sea ice. Polar bears hunt on sea ice, and seals give birth on it. We have no idea what will happen when that lot disappears. In addition, there is the problem of increasing numbers of warm spells during which rain falls instead of snow. That rain then freezes on the ground and forms a hard coating that prevents reindeer and caribou from finding food under the snow.”

Nor would the rest of the world be isolated. With less ice to reflect solar radiation back into space, the dark ocean waters of the high latitudes will warm and the Arctic will heat up even further.

“If you warm the Arctic you decrease the temperature difference between the poles and the mid-latitudes, and that affects the polar vortex, the winds that blow between the mid latitudes and the high latitudes,” says Henry Burgess, head of the Arctic office of the UK Natural Environment Research Council.

“Normally this process tends to keep the cold in the high north and milder air in mid-latitudes but there is an increasing risk this will be disrupted as the temperature differential gets weaker. We may get more and more long, cold spells spilling down from the Arctic, longer and slower periods of Atlantic storms and equally warmer periods in the Arctic. What happens up there touches us all. It is hard to believe you can take away several million sq km of ice a few thousand kilometres to the north and not expect there will be an impact on weather patterns here in the UK.”

For her part, Stroeve puts it more bleakly: “We are carrying out a blind experiment on our planet whose outcome is almost impossible to guess.”

This point is backed by Desch. “Sea ice is disappearing from the Arctic – rapidly. The sorts of options we are proposing need to be researched and discussed now. If we are provocative and get people to think about this, that is good.

“The question is: do I think our project would work? Yes. I am confident it would. But we do need to put a realistic cost on these things. We cannot keep on just telling people, ‘Stop driving your car or it’s the end of the world’. We have to give them alternative options, though equally we need to price them.”

THE BIG SHRINK
The Arctic ice cap reaches its maximum extent every March and then, over the next six months, dwindles. The trough is reached around mid-September at the end of the melting season. The ice growth cycle then restarts. However, the extent of regrowth began slackening towards the end of the last century. According to meteorologists, the Arctic’s ice cover at its minimum is now decreasing by 13% every decade – a direct consequence of heating triggered by increased levels of carbon dioxide in the atmosphere.

Climate change deniers claim this loss is matched by gains in sea ice around the Antarctic. It is not. Antarctic ice fluctuations are slight compared with the Arctic’s plummeting coverage and if you combine the changes at both poles, you find more than a million sq km of ice has been lost globally in 30 years.

https://www.theguardian.com/world/2017/feb/12/plan-to-refreeze-arctic-before-ice-goes-for-good-climate-change

Wendy was barely 20 years old when she received a devastating diagnosis: juvenile amyotrophic lateral sclerosis (ALS), an aggressive neurodegenerative disorder that destroys motor neurons in the brain and the spinal cord.

Within half a year, Wendy was completely paralyzed. At 21 years old, she had to be artificially ventilated and fed through a tube placed into her stomach. Even more horrifyingly, as paralysis gradually swept through her body, Wendy realized that she was rapidly being robbed of ways to reach out to the world.

Initially, Wendy was able to communicate to her loved ones by moving her eyes. But as the disease progressed, even voluntary eye twitches were taken from her. In 2015, a mere three years after her diagnosis, Wendy completely lost the ability to communicate—she was utterly, irreversibly trapped inside her own mind.

Complete locked-in syndrome is the stuff of nightmares. Patients in this state remain fully conscious and cognitively sharp, but are unable to move or signal to the outside world that they’re mentally present. The consequences can be dire: when doctors mistake locked-in patients for comatose and decide to pull the plug, there’s nothing the patients can do to intervene.

Now, thanks to a new system developed by an international team of European researchers, Wendy and others like her may finally have a rudimentary link to the outside world. The system, a portable brain-machine interface, translates brain activity into simple yes or no answers to questions with around 70 percent accuracy.

That may not seem like enough, but the system represents the first sliver of hope that we may one day be able to reopen reliable communication channels with these patients.

Four people were tested in the study, with some locked-in for as long as seven years. In just 10 days, the patients were able to reliably use the system to finally tell their loved ones not to worry—they’re generally happy.

The results, though imperfect, came as “enormous relief” to their families, says study leader Dr. Niels Birbaumer at the University of Tübingen. The study was published this week in the journal PLOS Biology.

Breaking Through

Robbed of words and other routes of contact, locked-in patients have always turned to technology for communication.

Perhaps the most famous example is physicist Stephen Hawking, who became partially locked-in due to ALS. Hawking’s workaround is a speech synthesizer that he operates by twitching his cheek muscles. Jean-Dominique Bauby, an editor of the French fashion magazine Elle who became locked-in after a massive stroke, wrote an entire memoir by blinking his left eye to select letters from the alphabet.

Recently, the rapid development of brain-machine interfaces has given paralyzed patients increasing access to the world—not just the physical one, but also the digital universe.

These devices read brain waves directly through electrodes implanted into the patient’s brain, decode the pattern of activity, and correlate it to a command—say, move a computer cursor left or right on a screen. The technology is so reliable that paralyzed patients can even use an off-the-shelf tablet to Google things, using only the power of their minds.

But all of the above workarounds require one critical factor: the patient has to have control of at least one muscle—often, this is a cheek or an eyelid. People like Wendy who are completely locked-in are unable to control similar brain-machine interfaces. This is especially perplexing since these systems don’t require voluntary muscle movements, because they read directly from the mind.

The unexpected failure of brain-machine interfaces for completely locked-in patients has been a major stumbling block for the field. Although speculative, Birbaumer believes that it may be because over time, the brain becomes less efficient at transforming thoughts into actions.

“Anything you want, everything you wish does not occur. So what the brain learns is that intention has no sense anymore,” he says.


First Contact

In the new study, Birbaumer overhauled common brain-machine interface designs to get the brain back on board.

First off was how the system reads brain waves. Generally, this is done through EEG, which measures certain electrical activity patterns of the brain. Unfortunately, the usual solution was a no-go.

“We worked for more than 10 years with neuroelectric activity [EEG] without getting into contact with these completely paralyzed people,” says Birbaumer.

It may be because the electrodes have to be implanted to produce a more accurate readout, explains Birbaumer to Singularity Hub. But surgery comes with additional risks and expenses to the patients. In a somewhat desperate bid, the team turned their focus to a technique called functional near-infrared spectroscopy (fNIRS).

Like fMRI, fNIRS measures brain activity by measuring changes in blood flow through a specific brain region—generally speaking, more blood flow equals more activation. Unlike fMRI, which requires the patient to lie still in a gigantic magnet, fNIRS uses infrared light to measure blood flow. The light source is embedded into a swimming cap-like device that’s tightly worn around the patient’s head.

To train the system, the team started with facts about the world and personal questions that the patients can easily answer. Over the course of 10 days, the patients were repeatedly asked to respond yes or no to questions like “Paris is the capital of Germany” or “Your husband’s name is Joachim.” Throughout the entire training period, the researchers carefully monitored the patients’ alertness and concentration using EEG, to ensure that they were actually participating in the task at hand.

The answers were then used to train an algorithm that matched the responses to their respective brain activation patterns. Eventually, the algorithm was able to tell yes or no based on these patterns alone, at about 70 percent accuracy for a single trial.

“After 10 years [of trying], I felt relieved,” says Birbaumer. If the study can be replicated in more patients, we may finally have a way to restore useful communication with these patients, he added in a press release.

“The authors established communication with complete locked-in patients, which is rare and has not been demonstrated systematically before,” says Dr. Wolfgang Einhäuser-Treyer to Singularity Hub. Einhäuser-Treyer is a professor at Bielefeld University in Germany who had previously worked on measuring pupil response as a means of communication with locked-in patients and was not involved in this current study.

Generally Happy

With more training, the algorithm is expected to improve even further.

For now, researchers can average out mistakes by repeatedly asking a patient the same question multiple times. And even at an “acceptable” 70 percent accuracy rate, the system has already allowed locked-in patients to speak their minds—and somewhat endearingly, just like in real life, the answer may be rather unexpected.

One of the patients, a 61-year-old man, was asked whether his daughter should marry her boyfriend. The father said no a striking nine out of ten times—but the daughter went ahead anyway, much to her father’s consternation, which he was able to express with the help of his new brain-machine interface.

Perhaps the most heart-warming result from the study is that the patients were generally happy and content with their lives.

We were originally surprised, says Birbaumer. But on further thought, it made sense. These four patients had accepted ventilation to support their lives despite their condition.

“In a sense, they had already chosen to live,” says Birbaumer. “If we could make this technique widely clinically available, it could have a huge impact on the day-to-day lives of people with completely locked-in syndrome.”

For his next steps, the team hopes to extend the system beyond simple yes or no binary questions. Instead, they want to give patients access to the entire alphabet, thus allowing them to spell out words using their brain waves—something that’s already been done in partially locked-in patients but never before been possible for those completely locked-in.

“To me, this is a very impressive and important study,” says Einhäuser-Treyer. The downsides are mostly economical.

“The equipment is rather expensive and not easy to use. So the challenge for the field will be to develop this technology into an affordable ‘product’ that caretakers [sic], families or physicians can simply use without trained staff or extensive training,” he says. “In the interest of the patients and their families, we can hope that someone takes this challenge.”

https://singularityhub.com/2017/02/12/families-finally-hear-from-completely-paralyzed-patients-via-new-mind-reading-device/?utm_source=Singularity+Hub+Newsletter&utm_campaign=978304f198-Hub_Daily_Newsletter&utm_medium=email&utm_term=0_f0cf60cdae-978304f198-58158129


No ink required to print on this paper — yet look how readable the type is. (Photo: University of California, Riverside/YouTube)

by BRYAN NELSON

As much as 40 percent of our landfills consist of paper and cardboard, and a major source of that material comes from office supplies. Just think of all the paper that gets used and discarded on a daily basis through the printer in your office alone. Even if that paper gets recycled, it still presents a different sort of problem due to pollution associated with the ink removal process.

Then there’s the concern about deforestation. In the United States, about one-third of all harvested trees are used for paper and cardboard production.

Paper and printing is a problem, to be sure. But now, thanks to a breakthrough from a team of scientists at Shandong University in China, the University of California, Riverside, and Lawrence Berkeley National Laboratory, it might be a problem with a solution.

The researchers have invented a new type of rewritable paper that can be printed with light — no ink required. The paper feels like normal paper to the touch, but it’s coated in color-changing nanoparticles that react to UV light. The technology works simply enough: a UV light printer zaps the paper everywhere except where the text is meant to be. The text then boldly stands out against the clear, light-zapped background.

“The greatest significance of our work is the development of a new class of solid-state photoreversible color-switching system to produce an ink-free light-printable rewritable paper that has the same feel and appearance as conventional paper, but can be printed and erased repeatedly without the need for additional ink,” explained Yadong Yin, chemistry professor at the University of California, Riverside. “Our work is believed to have enormous economic and environmental merits to modern society.”

The researchers published a paper on their work in the journal Nano Letters.

The nanoparticles return to their original background state if left untreated for five days, so the text will disappear naturally. (It certainly beats a paper shredder.) But if you wanted to erase and rewrite onto the same paper sooner than that, it will also revert back if heated for only about 10 minutes at 250 degrees Fahrenheit. It’s kind of like a hardcopy version of Snapchat, assuming you’ve got the proper equipment on hand to erase a message after it’s been read.

“We believe the rewritable paper has many practical applications involving temporary information recording and reading, such as newspapers, magazines, posters, notepads, writing easels, product life indicators, oxygen sensors, and rewritable labels for various applications,” said Yin.

Aside from producing little waste, the technology is also inexpensive. The coating materials are so cheap that they add almost nothing to the cost of a sheet of paper. Meanwhile, the printing technology ought to be cheaper than traditional inkjet printers simply because no ink is required. (Imagine never having to change out your ink cartridge again!)

And of course, because the paper can be re-used more than 80 times before the effect is dulled, the technology saves on the cost of paper as well.

“Our immediate next step is to construct a laser printer to work with this rewritable paper to enable fast printing,” said Yin. “We will also look into effective methods for realizing full-color printing.”

http://www.mnn.com/green-tech/research-innovations/stories/scientists-invent-paper-can-be-printed-light-instead-ink

By Drake Baer

Everybody knows that humpback whales make excellent professional wrestlers: With zero hesitation, these gentle giants will leap out of the sea, corkscrew their bodies, and then slam back into the water with 66,000 pounds of fury.

It turns out that these cetaceans aren’t just doing this to show off: According to a recent paper in Marine Mammal Science, the breaching serves as an acoustic telegram, communicating with far-off pods. It’s like how European or African peoples would send sonic signals from village to village via drum, or how wolves howl at the moon. Make a big enough splash, and the percussion speaks for itself.

As noted in the marine-life publication Hakai magazine, University of Queensland marine biologist Ailbhe S. Kavanagh and colleagues observed 76 humpback groups off the coast of Australia for 200 hours between 2010 and 2011. They found that breaching is way more common when pods are at least 2.5 miles apart, with fin- or fluke-slapping deployed when fellow whales are nearby.

The breaching probably carries better than whales’ signature songs: “They’re potentially using [these behaviors] when background noise levels are higher,” Kavanagh tells Hakai, “as the acoustic signal possibly travels better than a vocal signal would.” Given that whale songs have regional accents, you have to wonder if their aerial gymnastics have a certain patois, too.

http://nymag.com/scienceofus/2017/02/why-whales-jump-into-the-air.html

Thanks to Pete Cuomo for bringing this to the It’s Interesting community.

By Jason Bittel

Do baboons fart? What about salamanders? Millipedes?

These questions sound like the sort Bart Simpson might have asked to derail science class. But real-life scientists are now taking to Twitter to provide answers. So far, they’ve created a hashtag — #DoesItFart — and a Google Spreadsheet that details the flatulence habits of more than 60 animals.

So, which animals cut the proverbial cheese? Tons, it turns out. Bats do, according to David Bennett, a PhD candidate at Queen Mary University of London. And the bigger they are, the harder they honk.

Rats, zebras and bearded dragons are also among Those Creatures That Fart. Birds, on the other hand, do not seem to have a biological need for passing gas, but they could let one rip, theoretically. Marine invertebrates such as oysters, mussels and crabs? Alas, they are whoopee-impaired.

The science of farts is not just about potty humor, by the way. Cattle gas, for example, is a significant contributor to atmospheric methane that contributes to climate change. And fauna flatulence is also a hot topic among certain crowds — ones scientists want to engage.

“Does it fart?” is one of most frequent questions zoologists receive from kids, said Dani Rabaiotti of the Zoological Society of London. In fact, the whole #DoesItFart adventure started when her teenage brother asked if snakes ever experience flatulence. Rabaiotti knew from her own work that the wild dogs of Africa definitely fart, as do the extremely gassy seals that reside on the Atlantic island of South Georgia. But she wasn’t sure about snakes, so she consulted snake expert David Steen.

The short answer is yes, says Steen, a wildlife ecologist at Auburn University. “Snakes sometimes discharge feces and musk as a defensive strategy, and this is often accompanied by what I would consider classic fart noises,” he said.

Steen said this is far from the first time he’s fielded this question, as it seems to be a favorite of the preteen crowd.

“I don’t know if animal flatulence questions can serve as a significant gateway to a greater appreciation of biodiversity, but it is always fun to see what captures people’s attention,” he said. “It is at least an opportunity to engage with a larger audience and bring new folks into the conversation.”

And if engagement is the goal — or at least a byproduct — does it really matter what the topic is? “Just because it’s flatulence doesn’t mean it’s inherently silly,” said Adriana Lowe, a researcher of biological anthropology at the University of Kent in the United Kingdom. “The diets and digestive systems of animals are an important and fascinating field of study, and gas is just a part of that.”

Lowe studies chimpanzees in Uganda’s Budongo forest, animals whose gas appears to vary with their diet. “Fruit is tootier than leaves, and figs seem to be the worst offenders,” she said. On occasion, these bodily functions have even aided in her research. “Several times I have been with one or two chimps and not been aware others are nearby until the farts start,” says Lowe. “Some of them have that very long, air-being-released-from-a-balloon quality, which is handy because it gives you a bit longer to pinpoint where it’s coming from.”

https://www.washingtonpost.com/news/animalia/wp/2017/01/11/scientists-are-building-an-animal-fart-database/?utm_term=.f1296e0091da

by Philip Perry

Researchers at the Salk Institute in La Jolla, California have discovered a way to turn back the hands of time. Juan Carlos Izpisua Belmonte led this study, published in the journal Cell. Here, elderly mice underwent a new sort of gene therapy for six weeks. Afterward, their injuries healed, their heart health improved, and even their spines were straighter. The mice also lived longer, 30% longer.

Today, we target individual age-related diseases when they spring up. But this study could help us develop a therapy to attack aging itself, and perhaps even target it before it begins taking shape. But such a therapy is at least ten years away, according to Izpisua Belmonte.

Many biologists now believe that the body, specifically the telomeres—the structures at the end of chromosomes, after a certain time simply wear out. Once degradation overtakes us, it’s the beginning of the end. This study strengthens another theory. Over the course of a cell’s life, epigenetic changes occur. This is the activation or depression of certain genes in order to allow the organism to respond better to its environment. Methylation tags are added to activate genes. These changes build up over time, slowing us down, and making us vulnerable to disease.


Chromosomes with telomeres in red.

Though we may add life to years, don’t consider immortality an option, at least not in the near-term. “There are probably still limits that we will face in terms of complete reversal of aging,” Izpisua Belmonte said. “Our focus is not only extension of lifespan but most importantly health-span.” That means adding more healthy years to life, a noble prospect indeed.

The technique employs induced pluripotent stem cells (iPS). These are similar to those which are present in developing embryos. They are important as they can turn into any type of cell in the body. The technique was first used to turn back time on human skin cells, successfully.

By switching around four essential genes, all active inside the womb, scientists were able to turn skin cells into iPS cells. These four genes are known as Yamanaka factors. Scientists have been aware of their potential in anti-aging medicine for some time. In the next leg, researchers used genetically engineered mice who could have their Yamanaka factors manipulated easily, once they were exposed to a certain agent, present in their drinking water.

Since Yamanaka factors reset genes to where they were before regulators came and changed them, researchers believe this strengthens the notion that aging is an accumulation of epigenetic changes. What’s really exciting is that this procedure alters the epigenome itself, rather than having the change the genes of each individual cell.


The mechanics of epigenetics.

In another leg of the experiment, mice with progeria underwent this therapy. Progeria is a disease that causes accelerated aging. Those who have seen children who look like seniors know the condition. It leads to organ damage and early death. But after six months of treatment, the mice looked younger. They had better muscle tone and younger looking skin, and even lived around 30% longer than those who did not undergo the treatment.

Luckily for the mice, time was turned back the appropriate amount. If turned back too far, stem cells can proliferate in an uncontrolled fashion, which could lead to tumor formation. This is why researchers have been reticent to activate the Yamanaka factors directly. However, these scientists figured out that by intermittently stimulating the factors, they could reverse the aging process, without causing cancer. The next decade will concentrate on perfecting this technique.

Since the threat of cancer is great, terminally ill patients would be the first to take part in a human trial, most likely those with progeria. Unfortunately, the method used in this study could not directly be applied to a fully functioning human. But researchers believe a drug could do the job, and they are actively developing one.

“This study shows that aging is a very dynamic and plastic process, and therefore will be more amenable to therapeutic interventions than what we previously thought,” Izpisua Belmonte said. Of course, mouse systems and human one’s are far different. This only gives us an indication of whether or not it might work. And even if it does, scientists will have to figure out how far to turn back the clock. But as Izpisua Belmonte said, “With careful modulation, aging might be reversed.”


St. Jude Children’s Research Hospital scientists have linked disruption of a brain circuit associated with schizophrenia to an age-related decline in levels of a single microRNA in one brain region

St. Jude Children’s Research Hospital scientists have identified a small RNA (microRNA) that may be essential to restoring normal function in a brain circuit associated with the “voices” and other hallucinations of schizophrenia. The microRNA provides a possible focus for antipsychotic drug development. The findings appear today in the journal Nature Medicine.

The work was done in a mouse model of a human disorder that is one of the genetic causes of schizophrenia. Building on previous St. Jude research, the results offer important new details about the molecular mechanism that disrupts the flow of information along a neural circuit connecting two brain regions involved in processing auditory information. The findings also provide clues about why psychotic symptoms of schizophrenia are often delayed until late adolescence or early adulthood.

“In 2014, we identified the specific circuit in the brain that is targeted by antipsychotic drugs. However, the existing antipsychotics also cause devastating side effects,” said corresponding author Stanislav Zakharenko, M.D., Ph.D., a member of the St. Jude Department of Developmental Neurobiology. “In this study, we identified the microRNA that is a key player in disruption of that circuit and showed that depletion of the microRNA was necessary and sufficient to inhibit normal functioning of the circuit in the mouse models.

“We also found evidence suggesting that the microRNA, named miR-338-3p, could be targeted for development of a new class of antipsychotic drugs with fewer side effects.”

There are more than 2,000 microRNAs whose function is to silence expression of particular genes and regulate the supply of the corresponding proteins. Working in a mouse model of 22q11 deletion syndrome, researchers identified miR-338-3p as the microRNA that regulates production of the protein D2 dopamine receptor (Drd2), which is the prime target of antipsychotics.

Individuals with the deletion syndrome are at risk for behavior problems as children. Between 23 and 43 percent develop schizophrenia, a severe chronic disorder that affects thinking, memory and behavior. Researchers at St. Jude are studying schizophrenia and other brain disorders to improve understanding of how normal brains develop, which provides insights into the origins of diseases like cancer.

The scientists reported that Drd2 increased in the brain’s auditory thalamus when levels of the microRNA declined. Previous research from Zakharenko’s laboratory linked elevated levels of Drd2 in the auditory thalamus to brain-circuit disruptions in the mutant mice. Investigators also reported that the protein was elevated in the same brain region of individuals with schizophrenia, but not healthy adults.

Individuals with the deletion syndrome are missing part of chromosome 22, which leaves them with one rather than the normal two copies of more than 25 genes. The missing genes included Dgcr8, which facilitates production of microRNAs.

Working in mice, researchers have now linked the 22q11 deletion syndrome and deletion of a single Dgcr8 gene to age-related declines in miR-338-3p in the auditory thalamus. The decline was associated with an increase in Drd2 and reduced signaling in the circuit that links the thalamus and auditory cortex, a brain region implicated in auditory hallucination. Levels of miR-338-3p were lower in the thalamus of individuals with schizophrenia compared to individuals of the same age and sex without the diagnosis.

The miR-338-3p depletion did not disrupt other brain circuits in the mutant mice, and the findings offer a possible explanation. Researchers found that miR-338-3p levels were higher in the thalamus than in other brain regions. In addition, miR-338-3p was one of the most abundant microRNAs present in the thalamus.

Replenishing levels of the microRNA in the auditory thalamus of mutant mice reduced Drd2 protein and restored the circuit to normal functioning. That suggests that the microRNA could be the basis for a new class of antipsychotic drugs that act in a more targeted manner with fewer side effects. Antipsychotic drugs, which target Drd2, also restored circuit function.

The findings provide insight into the age-related delay in the onset of schizophrenia symptoms. Researchers noted that microRNA levels declined with age in all mice, but that mutant mice began with lower levels of miR-338-3p. “A minimum level of the microRNA may be necessary to prevent excessive production of the Drd2 that disrupts the circuit,” Zakharenko said. “While miR-338-3p levels decline as normal mice age, levels may remain above the threshold necessary to prevent overexpression of the protein. In contrast, the deletion syndrome may leave mice at risk for dropping below that threshold.”

The study’s first authors are Sungkun Chun, Fei Du and Joby Westmoreland, all formerly of St. Jude. The other authors are Seung Baek Han, Yong-Dong Wang, Donnie Eddins, Ildar Bayazitov, Prakash Devaraju, Jing Yu, Marcia Mellado Lagarde and Kara Anderson, all of St. Jude.

https://www.stjude.org/media-resources/news-releases/2016-medicine-science-news/small-rna-identified-that-offers-clues-for-quieting-the-voices-of-schizophrenia.html