Century-old drug reverses signs of autism in mice

By Elizabeth Norton

A single dose of a century-old drug has eliminated autism symptoms in adult mice with an experimental form of the disorder. Originally developed to treat African sleeping sickness, the compound, called suramin, quells a heightened stress response in neurons that researchers believe may underlie some traits of autism. The finding raises the hope that some hallmarks of the disorder may not be permanent, but could be correctable even in adulthood.

That hope is bolstered by reports from parents who describe their autistic children as being caught behind a veil. “Sometimes the veil parts, and the children are able to speak and play more normally and use words that didn’t seem to be there before, if only for a short time during a fever or other stress” says Robert Naviaux, a geneticist at the University of California, San Diego, who specializes in metabolic disorders.

Research also shows that the veil can be parted. In 2007, scientists found that 83% of children with autism disorders showed temporary improvement during a high fever. The timing of a fever is crucial, however: A fever in the mother can confer a higher risk for the disorder in the unborn child.

As a specialist in the cell’s life-sustaining metabolic processes, Naviaux was intrigued. Autism is generally thought to result from scrambled signals at synapses, the points of contact between nerve cells. But given the specific effects of something as general as a fever, Naviaux wondered if the problem lay “higher up” in the cell’s metabolism.

To test the idea, he and colleagues focused on a process called the cell danger response, by which the cell protects itself from threats like infection, temperature changes, and toxins. As part of this strategy, Naviaux explains, “the cells behave like countries at war. They harden their borders. They don’t trust their neighbors.” If the cells in question are neurons, he says, disrupted communication could result—perhaps underlying the social difficulties; heightened sensitivity to sights, sounds, and sensations; and intolerance for anything new that often afflict patients with autism.

The key player may be ATP, the chief carrier of energy within a cell, which can also relay messages to other nearby cells. When too much ATP is released for too long, it can induce a hair-trigger cell danger response in neighboring neurons. In 2013, Naviaux spelled out his hypothesis that autism involves a prolonged, heightened cell danger response, disrupting pathways within and between neurons and contributing to the symptoms of the disorder.

The same year, he and his colleagues homed in on the drug suramin as a way to call off the response. The medication has been in use since the early 20th century to kill the organisms that cause African sleeping sickness. In 1988, it was found to block the so-called purinergic receptors, which bind to compounds called purines and pyrimidines—including ATP. These receptors are found on every cell in the body; on neurons, they help orchestrate many of the processes impaired in autism—such as brain development, the production of new synapses, inflammation, and motor coordination.

To determine if suramin could protect these receptors from overstimulation by ATP, Naviaux’s team worked with mice that developed an autism-like disorder after their mothers had been exposed to a simulated viral infection (and heightened cell danger responses) during pregnancy. Like children with autism, the mice born after these pregnancies were less social and did not seek novelty; they avoided unfamiliar mice and passed up the chance to explore new runs of a maze. In the 2013 paper, the researchers reported that these traits vanished after weekly injections of suramin begun when the mice were 6 weeks old (equivalent to 15-year-old humans). Many consequences of altered metabolism—including the structure of synapses, body temperature, the production of key receptors, and energy transport within neurons—were either corrected or improved.

In the new study, published online today in Translational Psychiatry, the researchers found equally compelling results after a single injection of suramin given to 6-month-old mice (equivalent to 30-year-old humans) with the same autism-like condition. Once again, previously reclusive animals approached unknown mice and investigated unfamiliar parts of a maze, suggesting that the animals had overcome the aversion to novelty that’s a hallmark of autism in children. After the single injection, the team lowered the levels of suramin by half each week. Within 5 weeks most, but not all, of the benefits of treatment had been lost. The drug also corrected 17 of 18 metabolic pathways that are disrupted in mice with autism-like symptoms.

Naviaux cautions that mice aren’t people, and therapies that are promising in rodents have a track record of not panning out in humans. He also says that prolonged treatment with suramin is not an option for children, because it can have side effects such as anemia with long-term use. He notes that there are 19 different kinds of purinergic receptors; if suramin does prove to be helpful in humans, newer drugs could be developed that would target only one or a few key receptors. The researchers are beginning a small clinical trial in humans of a single dose of suramin that they hope will be completed by the end of the year.

The study is exciting, says Bruce Cohen, a pediatric neurologist at Akron Children’s Hospital in Ohio. “The authors have come up with a novel idea, tested it thoroughly, and got a very positive response after one dose.” He notes, however, that the mice with a few characteristics of autism don’t necessarily reflect the entire condition in humans. “Autism isn’t a disease. It’s a set of behaviors contributing to hundreds of conditions and resulting from multiple genes and environmental effects. Great work starts with a single study like this one, but there’s more work to be done.”

http://news.sciencemag.org/biology/2014/06/century-old-drug-reverses-signs-autism-mice

New research shows that whales and dolphins can’t taste anything except salt

Tastes are a privilege. The oral sensations not only satisfy foodies, but also on a primal level, protect animals from toxic substances. Yet cetaceans—whales and dolphins—may lack this crucial ability, according to a new study. Mutations in a cetacean ancestor obliterated their basic machinery for four of the five primary tastes, making them the first group of mammals to have lost the majority of this sensory system.

The five primary tastes are sweet, bitter, umami (savory), sour, and salty. These flavors are recognized by taste receptors—proteins that coat neurons embedded in the tongue. For the most part, taste receptor genes present across all vertebrates.

Except, it seems, cetaceans. Researchers uncovered a massive loss of taste receptors in these animals by screening the genomes of 15 species. The investigation spanned the two major lineages of cetaceans: Krill-loving baleen whales—such as bowheads and minkes—were surveyed along with those with teeth, like bottlenose dolphins and sperm whales.

The taste genes weren’t gone per se, but were irreparably damaged by mutations, the team reports online this month in Genome Biology and Evolution. Genes encode proteins, which in turn execute certain functions in cells. Certain errors in the code can derail protein production—at which point the gene becomes a “pseudogene” or a lingering shell of a trait forgotten. Identical pseudogene corpses were discovered across the different cetacean species for sweet, bitter, umami, and sour taste receptors. Salty tastes were the only exception.

“The loss of bitter taste is a complete surprise, because natural toxins typically taste bitter,” says zoologist Huabin Zhao of Wuhan University in China who led the study. All whales likely descend from raccoon-esque raoellids, a group of herbivorous land mammals that transitioned to the sea where they became fish eaters. Plants range in flavors—from sugary apples to tart, poisonous rhubarb leaves—and to survive, primitive animals learned the taste cues that signal whether food is delicious or dangerous. Based on the findings, taste dissipated after this common ancestor became fully aquatic—53 million years ago—but before the group split 36 million years ago into toothed and baleen whales.

“Pseudogenes arise when a trait is no longer needed,” says evolutionary biologist Jianzhi Zhang of the University of Michigan, Ann Arbor, who was not involved in the study. “So it still raises the question as to why whales could afford to lose four of the five primary tastes.” The retention of salty taste receptors suggests that they have other vital roles, such as maintaining sodium levels and blood pressure.

But dulled taste perception might be dangerous if noxious substances spill into the water. Orcas have unwittingly migrated into oil spills, while algal toxins created by fertilizer runoff consistently seep into the fish prey of dolphins living off the Florida coast.

“When you have a sense of taste, it dictates whether you swallow or not,” says Danielle Reed, a geneticist at the Monell Chemical Senses Center in Philadelphia, Pennsylvania. She was not involved with the current work, but co-authored a 2012 paper that found the first genetic inklings that umami and sweet taste receptors were missing in cetaceans, albeit in only one species—bottlenose dolphins.

Flavors are typically released by chewing, but cetaceans tend to swallow their food whole. “The message seems clear. If you don’t chew your food and prefer swallowing food whole, then taste really becomes irrelevant,” Reed says.

http://news.sciencemag.org/biology/2014/05/whales-cant-taste-anything-salt

Thanks to Dr. Rajadhyaksha for bringing this to the attention of the It’s Interesting community.

Brain Injury Turns Man Into Math Genius

In 2002, two men savagely attacked Jason Padgett outside a karaoke bar, leaving him with a severe concussion and post-traumatic stress disorder. But the incident also turned Padgett into a mathematical genius who sees the world through the lens of geometry.

Padgett, a furniture salesman from Tacoma, Wash., who had very little interest in academics, developed the ability to visualize complex mathematical objects and physics concepts intuitively. The injury, while devastating, seems to have unlocked part of his brain that makes everything in his world appear to have a mathematical structure.

“I see shapes and angles everywhere in real life” — from the geometry of a rainbow, to the fractals in water spiraling down a drain, Padgett told Live Science. “It’s just really beautiful.”

Padgett, who just published a memoir with Maureen Seaberg called “Struck by Genius” (Houghton Mifflin Harcourt, 2014), is one of a rare set of individuals with acquired savant syndrome, in which a normal person develops prodigious abilities after a severe injury or disease. Other people have developed remarkable musical or artistic abilities, but few people have acquired mathematical faculties like Padgett’s.

Now, researchers have figured out which parts of the man’s brain were rejiggered to allow for such savant skills, and the findings suggest such skills may lie dormant in all human brains.

Before the injury, Padgett was a self-described jock and partyer. He hadn’t progressed beyond than pre-algebra in his math studies. “I cheated on everything, and I never cracked a book,” he said.

But all that would change the night of his attack. Padgett recalls being knocked out for a split second and seeing a bright flash of light. Two guys started beating him, kicking him in the head as he tried to fight back. Later that night, doctors diagnosed Padgett with a severe concussion and a bleeding kidney, and sent him home with pain medications, he said.

Soon after the attack, Padgett suffered from PTSD and debilitating social anxiety. But at the same time, he noticed that everything looked different. He describes his vision as “discrete picture frames with a line connecting them, but still at real speed.” If you think of vision as the brain taking pictures all the time and smoothing them into a video, it’s as though Padgett sees the frames without the smoothing. In addition, “everything has a pixilated look,” he said.

With Padgett’s new vision came an astounding mathematical drawing ability. He started sketching circles made of overlapping triangles, which helped him understand the concept of pi, the ratio of a circle’s circumference to its diameter. There’s no such thing as a perfect circle, he said, which he knows because he can always see the edges of a polygon that approximates the circle.

Padgett dislikes the concept of infinity, because he sees every shape as a finite construction of smaller and smaller units that approach what physicists refer to as the Planck length, thought to be the shortest measurable length.

After his injury, Padgett was drawing complex geometric shapes, but he didn’t have the formal training to understand the equations they represented. One day, a physicist spotted him making these drawings in a mall, and urged him to pursue mathematical training. Now Padgett is a sophomore in college and an aspiring number theorist.

Padgett’s remarkable abilities garnered the interest of neuroscientists who wanted to understand how he developed them.

Berit Brogaard, a philosophy professor now at the University of Miami, in Coral Gables, Fla., and her colleagues scanned Padgett’s brain with functional magnetic resonance imaging (fMRI) to understand how he acquired his savant skills and the synesthesia that allows him to perceive mathematical formulas as geometric figures. (Synesthesia is a phenomenon in which one sense bleeds into another.)

“Acquired savant syndrome is very rare,” Brogaard said, adding that only 15 to 25 cases have ever been described in medical studies.

Functional magnetic resonance imaging measures changes in blood flow and oxygen use throughout the brain. During scans of Padgett, the researchers showed the man real and nonsense mathematical formulas meant to conjure images in his mind.

The resulting scans showed significant activity in the left hemisphere of Padgett’s brain, where mathematical skills have been shown to reside. His brain lit up most strongly in the left parietal cortex, an area behind the crown of the head that is known to integrate information from different senses. There was also some activation in parts of his temporal lobe (involved in visual memory, sensory processing and emotion) and frontal lobe (involved in executive function, planning and attention).

But the fMRI only showed what areas were active in Padgett’s brain. In order to show these particular areas were causing the man’s synesthesia, Brogaard’s team used transcranial magnetic stimulation (TMS), which involves zapping the brain with a magnetic pulse that activates or inhibits a specific region. When they zapped the parts of Padgett’s parietal cortex that had shown the greatest activity in the fMRI scans, it made his synesthesia fade or disappear, according to a study published in August 2013 in the journal Neurocase.

Brogaard showed, in another study, that when neurons die, they release brain-signaling chemicals that can increase brain activity in surrounding areas. The increased activity usually fades over time, but sometimes it results in structural changes that can cause brain-activity modifications to persist, Brogaard told Live Science.

Scientists don’t know whether the changes in Padgett’s brain are permanent, but if he had structural changes, it’s more likely his abilities are here to stay, Brogaard said.

So do abilities like Padgett’s lie dormant in everyone, waiting to be uncovered? Or was there something unique about Padgett’s brain to begin with?

Most likely, there is something dormant in everyone that Padgett tapped into, Brogaard said. “It would be quite a coincidence if he were to have that particular special brain and then have an injury,” she said. “And he’s not the only [acquired savant].”

In addition to head injuries, mental disease has also been known to reveal latent abilities. And Brogaard and others have done studies that suggest zapping the brains of normal people using TMS can temporarily bring out unusual mathematical and artistic skills.

Yet Padgett wouldn’t change his new abilities if he could. “It’s so good, I can’t even describe it,” he said.

It’s always possible that having savant skills may come with trade-offs. In Padgett’s case, he developed fairly severe post-traumatic stress disorder and obsessive-compulsive disorder, and he still finds it difficult to appear in public.

http://news.discovery.com/human/life/brain-injury-turns-man-into-math-genius-1405061.htm

End The War On Drugs, Say Nobel Prize-Winning Economists

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The decades-long global war on drugs has failed and it’s time to shift the focus from mass incarceration to public health and human rights, according to a new report endorsed by five Nobel Prize-winning economists.

The report, titled “Ending the Drug Wars” and put together by the London School of Economics’ IDEAS center, looks at the high costs and unintended consequences of drug prohibitions on public health and safety, national security and law enforcement.

“The pursuit of a militarized and enforcement-led global ‘war on drugs’ strategy has produced enormous negative outcomes and collateral damage,” says the 82-page report. “These include mass incarceration in the US, highly repressive policies in Asia, vast corruption and political destabilization in Afghanistan and West Africa, immense violence in Latin America, an HIV epidemic in Russia, an acute global shortage of pain medication and the propagation of systematic human rights abuses around the world.”

The report urges the world’s governments to reframe their drug policies around treatment and harm reduction rather than prosecution and prison.

It is also aimed at the United Nations General Assembly, which is preparing to convene a special session on drug policy in 2016. The hope is to push the U.N. to encourage countries to develop their own policies, because the report declares the current one-size-fits-all approach has not proved to be effective.

“The UN must recognize its role is to assist states as they pursue best-practice policies based on scientific evidence, not undermine or counteract them,” said Danny Quah, a professor of economics at LSE and a contributor to the report. “If this alignment occurs, a new and effective international regime can emerge that effectively tackles the global drug problem.”

In addition to contributions from Quah and a dozen other foreign and drug policy experts, the report has been endorsed by five past winners of the Nobel Prize in Economics: Kenneth Arrow (1972), Sir Christopher Pissarides (2010), Thomas Schelling (2005), Vernon Smith (2002) and Oliver Williamson (2009). Also signing on to the report’s foreword are a number of current and former international leaders, including George Shultz, secretary of state under President Ronald Reagan; Nick Clegg, British deputy prime minister; and Javier Solana, the former EU high representative for common foreign and security policy.

Guatemalan President Otto Perez Molina, who has announced that his government may present a plan to legalize production of marijuana and opium poppies by the end of 2014, has also publicly backed the report. Molina plans to discuss the report at the U.N.

A recent Pew survey suggests that Americans may be ready to refocus the U.S. end of the drug war, with 67 percent favoring policies that would provide drug treatment.

“The drug war’s failure has been recognized by public health professionals, security experts, human rights authorities and now some of the world’s most respected economists,” said John Collins, the International Drug Policy Project coordinator at LSE IDEAS. “Leaders need to recognize that toeing the line on current drug control strategies comes with extraordinary human and financial costs to their citizens and economies.”

http://www.huffingtonpost.com/2014/05/06/end-drug-war_n_5275078.html?utm_hp_ref=politics

Thanks to Dr. Lutter for bringing this to the attention of the It’s Interesting community.

Our universe may reside within a vast black hole.

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By Michael Finkel
for National Geographic

Published February 18, 2014

Let’s rewind the clock. Before humans existed, before Earth formed, before the sun ignited, before galaxies arose, before light could even shine, there was the Big Bang. This happened 13.8 billion years ago.

But what about before that? Many physicists say there is no before that. Time began ticking, they insist, at the instant of the Big Bang, and pondering anything earlier isn’t in the realm of science. We’ll never understand what pre-Big Bang reality was like, or what it was formed of, or why it exploded to create our universe. Such notions are beyond human understanding.

But a few unconventional scientists disagree. These physicists theorize that, a moment before the Big Bang, all the mass and energy of the nascent universe was compacted into an incredibly dense—yet finite—speck. Let’s call it the seed of a new universe.

This seed is thought to have been almost unimaginably tiny, possibly trillions of times smaller than any particle humans have been able to observe. And yet it’s a particle that can spark the production of every other particle, not to mention every galaxy, solar system, planet, and person.

If you really want to call something the God particle, this seed seems an ideal fit.

So how is such a seed created? One idea, bandied about for several years—notably by Nikodem Poplawski of the University of New Haven—is that the seed of our universe was forged in the ultimate kiln, likely the most extreme environment in all of nature: inside a black hole.

It’s important to know, before we go further, that over the last couple of decades, many theoretical physicists have come to believe that our universe is not the only one. Instead, we may be part of the multiverse, an immense array of separate universes, each its own shining orb in the true night sky.

How, or even if, one universe is linked to another is a source of much debate, all of it highly speculative and, as of now, completely unprovable. But one compelling idea is that the seed of a universe is similar to the seed of a plant: It’s a chunk of essential material, tightly compressed, hidden inside a protective shell.

This precisely describes what is created inside a black hole. Black holes are the corpses of giant stars. When such a star runs out of fuel, its core collapses inward. Gravity pulls everything into an increasingly fierce grip. Temperatures reach 100 billion degrees. Atoms are smashed. Electrons are shredded. Those pieces are further crumpled.

The star, by this point, has turned into a black hole, which means that its gravitational pull is so severe that not even a beam of light can escape. The boundary between the interior and exterior of a black hole is called the event horizon. Enormous black holes, some of them millions of times more massive than the sun, have been discovered at the center of nearly every galaxy, including our own Milky Way.

If you use Einstein’s theories to determine what occurs at the bottom of a black hole, you’ll calculate a spot that is infinitely dense and infinitely small: a hypothetical concept called a singularity. But infinities aren’t typically found in nature. The disconnect lies with Einstein’s theories, which provide wonderful calculations for most of the cosmos, but tend to break down in the face of enormous forces, such as those inside a black hole—or present at the birth of our universe.

Physicists like Dr. Poplawski say that the matter inside a black hole does reach a point where it can be crushed no further. This “seed” might be incredibly tiny, with the weight of a billion suns, but unlike a singularity, it is real.

The compacting process halts, according to Dr. Poplawski, because black holes spin. They spin extremely rapidly, possibly close to the speed of light. And this spin endows the compacted seed with a huge amount of torsion. It’s not just small and heavy; it’s also twisted and compressed, like one of those jokey spring-loaded snakes in a can.

Which can suddenly unspring, with a bang. Make that a Big Bang—or what Dr. Poplawski prefers to call “the big bounce.”

It’s possible, in other words, that a black hole is a conduit—a “one-way door,” says Dr. Poplawski—between two universes. This means that if you tumble into the black hole at the center of the Milky Way, it’s conceivable that you (or at least the shredded particles that were once you) will end up in another universe. This other universe isn’t inside ours, adds Dr. Poplawski; the hole is merely the link, like a shared root that connects two aspen trees.

And what about all of us, here in our own universe? We might be the product of another, older universe. Call it our mother universe. The seed this mother universe forged inside a black hole may have had its big bounce 13.8 billion years ago, and even though our universe has been rapidly expanding ever since, we could still be hidden behind a black hole’s event horizon.

http://news.nationalgeographic.com/news/2014/02/140218-black-hole-blast-explains-big-bang/

Ted Talk by Lawrence Lessig on why Washington is corrupt: ‘Lesterland’

Lawrence Lessig is the Roy L. Furman Professor of Law and Leadership at Harvard Law School and director of the Edmond J. Safra Foundation Center for Ethics. Lessig spoke at the TED2013 conference in February.