Bacterium can reverse autism-like behaviour in mice

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Findings support idea that gut microbiome has a role in disorder.

• Sara Reardon

05 December 2013

Mice displaying symptoms of autism are less social and more anxious than control animals.

BRANDON LAUFENBERG/GETTY

Doses of a human gut microbe helped to reverse behavioural problems in mice with autism-like symptoms, researchers report today in Cell¹. The treatment also reduced gastrointestinal problems in the animals that were similar to those that often accompany autism in humans. 

The work builds on previous research by Paul Patterson, a neurobiologist at the California Institute of Technology (Caltech) in Pasadena. In 2012, he and his team created mice with autism-like symptoms by injecting a chemical that mimics viral infection into pregnant mice; those animals then bore offspring that were less sociable and more anxious than wild-type animals². The autistic mice also had 'leaky guts', in which the walls of the intestine break down and allow substances to leak through. Several studies have found that humans with autism are also more likely to have gastrointestinal disorders, suggesting that the two problems may be linked³.

To investigate what role the gut might play in the animals’ symptoms, Patterson and his Caltech colleagues — microbiologist Sarkis Mazmanian and neuroscientist Elaine Hsiao — took a census of the bacteria living in the guts of the mice. They found that mice with symptoms of autism had lower levels of a bacterium called Bacteroides fragilis that is normally present in the mouse gut. When the researchers fed B. fragilis to these mice, the animals began behaving more normally and their gastrointestinal symptoms improved.

Chemical imbalance

Next, the researchers tried to determine how the bacteria 'talk' to the brain by examining the blood of autistic and wild-type mice for chemicals that indicate how cells are working in the body. They found that the blood of mice with autism symptoms had levels of a chemical called 4-ethylphenylsulphate (4EPS) that were 46 times higher than that of the control group. This substance is structurally similar to a chemical called para-cresol that is elevated in people with autism⁴.

“It’s incredible that putting this one bacteria back can reverse all these widespread changes,” says John Cryan, a pharmacologist at University College Cork in Ireland. Although many anecdotal reports and small studies have suggested that ‘probiotic’ bacteria, such as those found in yoghurt, and antibiotics can help with the symptoms of autism, Cryan says more research needs to be done. Because there are a number of types of autism in humans, it will be important to look at how different symptoms might be affected by different microbes. Another question is whether the microbiomes of the mice — whose symptoms result from maternal infection — differ from those of mice that are genetically predisposed to autism-like symptoms, Cryan adds.When the researchers injected 4EPS into wild-type mice, they started behaving like the untreated autistic mice — obsessively repeating some behaviours and squeaking differently when greeting other mice. Hsiao says that although it is still unclear whether 4EPS is made by B. fragilis, it does seem to be made by gut bacteria.   

“I think there is now sufficient proof of concept where people can start to look at probiotic bacteria to improve brain function in humans,” says gastroenterologist Stephen Collins of McMaster University in Ontario, Canada. The next step, he says, will be to determine more precisely how different bacteria use the immune, metabolic and nervous systems to influence the brain.

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Creativity, Madness and Drugs

San Diego—Would we have Poe’sRaven today if the tormented author had taken lithium to suppress his bipolar illness? Not likely, considering the high frequency of psychiatric illnesses among writers and artists, concluded psychiatrist Kay Jamison of Johns Hopkins Medical School speaking last week at the Society for Neuroscience annual meeting in San Diego. Madness electrifies the creative process, Jamison concluded, but this difficult drug-use dilemma raises an even more provocative question:
Would we have Lucy in the Sky with
Diamonds had the Beatles not taken LSD?

The Beatles as they arrive in New York City in 1964. Credit: Wikimedia Commons: Library of Congress

Lord Tennyson, Virginia Woolf and Vincent Van Gogh are familiar examples of artists and writers who suffered serious mental illnesses, but Jamison explained that psychiatric illness was the cruel engine of their creativity. Tracing their family pedigrees, she showed that many of these artists’ siblings, parents and descendants were institutionalized in mental hospitals, committed suicide, or endured life-long struggles with mania, despair, schizophrenia or other mental disorders. The genetic backbone to mental illness is strong. Ernest Hemingway and his supermodel granddaughter Margaux Hemingway both killed themselves. Separated from one another in environment and experience by a generation, their fates were inevitably tethered by their DNA. In all, seven members of the Hemingway family died at their own hand. This raises the question of why the genes of such devastating brain dysfunctions should persist in the human gene pool.

Hemingway in 1939. Credit: Wikimedia Commons/Lloyd Arnold

Statistics show that among all categories of creative artists, writers suffer by far the highest incidence of bipolar disorder, outstripping all other artistic professions. Why? Jamison concludes that the manic phase of bipolar disorder infuses the writer with furious energy and limitless stamina. The author foregoes sleep, is driven to take daring risks, expands their imagination and embraces grandiose thinking.

The crash of depression ending the manic phase immerses the writer in the depths of human suffering. This infuses poets and writers with the most monumental and profound dimensions of human experiences, moving them to contemplate the meaning of life, confront the certainty of death, and struggle against the agony of despair to survive adversity.

Once upon a midnight dreary, while I pondered weak and weary,
[from The Raven]

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Optimizing carbon nanotube arrays for use in hot spots

Optimizing carbon nanotube arrays for use in hot spots

Sooty skies

Technology Quarterly Monitor

Aviation: A novel coating made of nanotubes offers a faster and more convenient alternative to chemicals for de-icing planes

DE-ICING an aeroplane is tedious. Just ask any passenger stuck in one while ground staff spray it with gallons of antifreeze. It is also important. Layers of ice can interfere with a wing’s aerodynamics, increasing drag and reducing lift, with potentially catastrophic consequences—hence the chemicals’ garish colours, meant to ensure that no nook or cranny is missed. De-icing can take as long as 40 minutes, and costs around $2,000 a pop.And sometimes, as Dawid Janas of Cambridge University found on a flight from his native Poland, it needs to be performed several times, because in harsh conditions the antifreeze itself can freeze if left to chill for long enough—as when awaiting the go-ahead for take-off. Now, though, Mr Janas, a materials scientist and aviation buff, thinks he has found a way to make life easier for passengers and airlines. It involves covering aircraft wings with a form of soot.

Not any old soot, mind you. Mr Janas creates his by pumping methane into a furnace heated to around 1,200°C. There, in the presence of an iron catalyst, the gas coalesces into a sticky substance akin to candyfloss, called an aerogel. When an iron poker is inserted into the furnace, the aerogel sticks to it. As the rod is retracted, it pulls out a thin filament, which is spun to create a film. Ten minutes later you get a sooty equivalent of an A4 piece of paper.

The film, about 10 microns thick, is composed of a mesh of carbon nanotubes, themselves just a few billionths of a metre across. Individual nanotubes are, famously, better conductors of electricity than even copper. In Mr Janas’s aerogel, however, they are no longer than 1mm each, with air in between them. That means the film, far from being a good conductor, exhibits high electrical resistance. Passing a current through it causes a near instantaneous rise in temperature.

Indeed, when Mr Janas compared his material with nichrome, the heating element of choice for applications from kettles to aeroplane wings (where it is used mainly for in-flight de-icing), he found that it heats up twice as fast using half as much energy as the metal alloy. It is also one ten-thousandth of the weight. The amount of film needed to cover the wings of a jumbo jet weighs just 80 grams.

Finally, whereas an A4 sheet of nichrome costs around $12,000, its carbon-film equivalent could be had for a hundredth of the price; probably less when the process is commercialised, as Mr Janas hopes it will be. Once installed, the heaters would be so cheap to run that they could be left on continuously at low power, to stop ice forming in the first place. And they last. A piece tested by Mr Janas retained its properties after being folded and unfolded 100,000 times.

Already a number of industries, though not yet aircraft-makers, have expressed an interest in the material. But if aviation does take to the stuff, the upshot will be more soot in the air—but of an entirely welcome variety.

found by Rhea

Nanotechnology provides a way to detect potentially dangerous blood clots, without the need for tiny submarines

Technology Quarterly

ONE of the dreams of nanotechnologists—those who try to engineer machines mere billionths of a metre across—is to build medical devices that can circulate in the bloodstream. This aspiration often prompts ridicule, frequently accompanied by a still from “Fantastic Voyage”, a film made in the 1960s about a team of doctors in a submarine that had been miniaturised with them inside it, so they could destroy a blood clot which threatened to kill a scientist who had been working behind the iron curtain.

Well, titter ye not. For although Sangeeta Bhatia’s nanoscale devices are not really submarines, are certainly not crewed by Raquel Welch and do not actually destroy blood clots, they do go around the bloodstream finding such clots—and report back what they have found, so that destruction can take place if necessary.

• 
  

Dr Bhatia is a bioengineer and physician at the Massachusetts Institute of Technology. She was impressed by the extraordinary sensitivity of modern urine testing, which can detect conditions ranging from diabetes and pregnancy to breast and brain cancer. But she noticed that one thing it cannot detect is clots attached to the walls of blood vessels. Nor is there an effective blood test for such clots.

That matters, because if a clot breaks free from its site of formation and lodges somewhere critical, it can kill. A clot in the coronary artery induces a heart attack. In a pulmonary artery, a clot causes a pulmonary embolism; in an artery in the brain, it causes a stroke. Dr Bhatia thought she might be able to design something that detects and reports the presence of clots and, as she recently outlined in the journalACS Nano, she has succeeded.

What Dr Bhatia’s clot-detector is actually detecting are not the clots themselves, but an enzyme called thrombin, which induces clotting and is thus an indicator of the presence of clots. Her “submarines” are tiny particles of iron oxide (though not so tiny that they pass through the kidney’s filters into the urine, and are lost). They are coated with small fragments of protein, called peptides, specially chosen because they react with thrombin. That, however, is not enough—because there is no way to tell from the outside whether such a reaction has taken place. To manage this Dr Bhatia attached reporter chemicals to the free ends of the peptides. When a peptide binds to a thrombin molecule the reporter is released. And the reporter, unlike the iron-oxide particle, is small enough to pass into the urine, where it can be detected by a simple test.

When tried out in mice, this idea worked perfectly. The urine of animals with clots in their lungs turned orange when tested, as it was supposed to do. That of clot-free animals remained unchanged. As for the iron oxide particles, these slowly dissolve in the bloodstream in a way that should cause no damage.

No trials have yet been carried out on people. But if such tests work and the procedure proves safe, then it might be used to give early warning, in those thought at risk of developing internal clots, that such clots have indeed developed. They can then be attacked with clot-busting drugs before they can break away and do serious harm.

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Found by Rhea Advani

Australians Cryogenically Freeze Coral Sperm From The Great Barrier Reef

The Great Barrier Reef around Cape Flattery, Australia, 2003 

Photo by Ed Lu, made available through the International Space Station Program

Well, that's one way to go about it. Over the past few weeks, Australian scientists have collected billions of sperm from spawning coral in the Great Barrier Reef, Australian news station ABC News reports. The sperm are to be cryogenically frozen, in case scientists want to rebuild parts of the reef in the future.

Since 1985, the Great Barrier Reef has lost more than half of its coral, one study found last year. The losses stem primarily from tropical cyclones, coral bleaching and predation by a certain species of starfish. Storms and coral bleaching will worsen with climate change.

If Australian scientists decide one day to thaw their collected sperm, they would use it to seed the ocean, where hopefully it will combine with fresh eggs released by existing coral. The frozen sperm could add genetic diversity back into coral populations that have fallen too low to be diverse. The reseeding could help the reef better weather further change, Taronga Zoo researcher Rebecca Spindler told ABC News. Spindler will be in charge of the Great Barrier Reef sperm bank, which will be the largest cryogenically frozen population in the world.

Several zoos in the U.S. maintain conservation-minded sperm banks, including the National Zoo (many species), the Cincinnati Zoo & Botanical Garden (rhinos) and the Memphis Zoo (amphibians). Researchers in Hawaii pioneered the techniques needed to freeze coral sperm and embryos, and there's a bank at the University of Hawaii. One of the technique's creators, marine biologist Mary Hagedorn, will help with the Australian effort.

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27-Hydroxycholesterol Links Hypercholesterolemia and Breast Cancer Pathophysiology

Science

Hypercholesterolemia is a risk factor for estrogen receptor (ER)–positive breast cancers and is associated with a decreased response of tumors to endocrine therapies. Here, we show that 27-hydroxycholesterol (27HC), a primary metabolite of cholesterol and an ER and liver X receptor (LXR) ligand, increases ER-dependent growth and LXR-dependent metastasis in mouse models of breast cancer. The effects of cholesterol on tumor pathology required its conversion to 27HC by the cytochrome P450 oxidase CYP27A1 and were attenuated by treatment with CYP27A1 inhibitors. In human breast cancer specimens, CYP27A1 expression levels correlated with tumor grade. In high-grade tumors, both tumor cells and tumor-associated macrophages exhibited high expression levels of the enzyme. Thus, lowering circulating cholesterol levels or interfering with its conversion to 27HC may be a useful strategy to prevent and/or treat breast cancer.

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Parental olfactory experience influences behavior and neural structure in subsequent generations

NATURE NEUROSCIENCE 

Fearful memories haunt mouse descendants

Genetic imprint from traumatic experiences carries through at least two generations.

Mouse pups — and even the offspring's offspring — can inherit a fearful association of a certain smell with pain, even if they have not experienced the pain themselves, and without the need for genetic mutations.

ACTION PRESS/REX FEATURES

Certain fears can be inherited through the generations, a provocative study of mice reports¹. The authors suggest that a similar phenomenon could influence anxiety and addiction in humans. But some researchers are sceptical of the findings because a biological mechanism that explains the phenomenon has not been identified.

According to convention, the genetic sequences contained in DNA are the only way to transmit biological information across generations. Random DNA mutations, when beneficial, enable organisms to adapt to changing conditions, but this process typically occurs slowly over many generations.

Yet some studies have hinted that environmental factors can influence biology more rapidly through 'epigenetic' modifications, which alter the expression of genes, but not their actual nucleotide sequence. For instance, children who were conceived during a harsh wartime famine in the Netherlands in the 1940s are at increased risk of diabetes, heart disease and other conditions — possibly because of epigenetic alterations to genes involved in these diseases². Yet although epigenetic modifications are known to be important for processes such as development and the inactivation of one copy of the X-chromsome in females, their role in the inheritance of behaviour is still controversial.

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Autism Diagnosis Rise

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Fresh dispute about MMR 'fraud'

 Andrew Wakefield's discredited theory linking vaccination and autism stirred public fears.It is one of the most serious allegations that could be made about a doctor: manipulating patients' histories to make money.

Wakefield was the lead author of a 1998 paper in The Lancet (A. J. Wakefield et al. Lancet 351, 637–641; 1998) reporting on the case histories of 12 children who had received the MMR vaccine and developed symptoms of autism or inflammatory bowel disease.

The paper inflamed public fears about vaccines, but it was retracted in 2010 after the UK General Medical Council (GMC) concluded that Wakefield had a charge of serious professional misconduct to answer, in part because it found that his team did not have proper ethical approval for tests performed on the children. Later in the year, the GMC found him guilty of the misconduct charge and revoked his licence to practice as a doctor. By then, more than 12 large-scale epidemiological studies had failed to find evidence of the hypothesized link (J. S. Gerber and P. A. Offit Clin. Infect. Dis. 48,456–461; 2009) and the MMR vaccine is today regarded as safe.

But was the paper merely mistaken, or a deliberate fraud? Articles by medical journalist Brian Deer published in the BMJ in 2010 and 2011 accused Wakefield of reporting histories for the children that were not consistent with their records and their parents' recollections, at a time when Wakefield was also being paid by lawyers intending to sue MMR manufacturers. Deer's articles themselves did not allege fraud, but on their basis a BMJ editorial in January 2011 called the paper fraudulent.

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xkcd Nearby Habitable Planets