Medicine & Health

Obesity linked to brain shrinkage and dementia

neurophilosophy — Wed, 16 Jun 2010 14:00:53 +0000

Obesity linked to brain shrinkage and dementia

THE dangers of obesity are very well known. Being overweight is associated with an increased risk of coronary heart disease and stroke, the two leading causes of death in the Western world. Gout is more common in overweight people, with the risk of developing the condition increasing in parallel with body weight. Obese people are twice as likely to develop type 2 diabetes as those who are not overweight, and being overweight is also associated with several types of cancer. The list goes on...

Less well known is the effect of obesity on the brain. In the past few years, however, it has emerged that being overweight in middle age is linked to an increased risk of Alzheimer's Disease and other forms of dementia. Two new studies strengthen this association: the first, just published in the Annals of Neurology, shows that abdominal fat is linked to reduced brain volume in otherwise healthy middle-aged adults. The second, published last month in Proceedings of the National Academy of Sciences, shows that this reduction is associated with a common variant of an obesity-related gene.

Stephanie Debette of Boston University and her colleagues examined the association of various obesity indicators - including body mass index, waist circumference, waist-to-hip ratio and abdominal fat - with brain volume, as measured by structural magnetic resonance imaging. They recruited 733 participants for their study, all of whom were previously enrolled in the Framingham Heart Study, an ambitious longitudinal project started in 1948, whose aim is to identify the common factors contributing to cardiovascular disease by following the disease as it develops over long periods of time in large numbers of people. All of the earlier studies investigating the link between obesity and dementia have involved less than 300 participants, so this is the largest such study of its kind to date.

The researchers found that all of these obesity indicators were inversely associated with total brain volume - that is, the higher any indicator was, the smaller the brain volume - and that the association between abdominal fat and brain volume was the strongest of all. Waist-to-hip ratio was also found to be associated with increased temporal horn volume, independently of other obesity indicators. The temporal horn is a part of the ventricular system; its volume is known to increase with age, and in conditions such as Alzheimer's Disease, depression and schizophrenia. Enlargement of the temporal horn invariably involves a reduction in the volume of temporal lobe structures such as the hippocampus, and thus is closely associated with memory impairments. (Indeed, temporal horn volume could serve as a useful marker for Alzheimer's, in which the temporal lobe is one of the very first brain regions to be affected.)

In the second study, April Ho of the Laboratory of Neuro Imaging at the University of California, Los Angeles and her colleagues analysed data obtained from 206 healthy elderly participants as part of a large five-year research project called the Alzheimer's Disease Neuroimaging Initiative. The data were used to generate 3D maps of the participants' brains, and then to see if brain structure is related to one variant (or allele) of the fat mass and obesity associated (FTO) gene. This risk allele is strongly associated higher body-mass index - carriers have, on average, ~1.2kg higher weight and 1cm greater waist circumference. It is relatively common, being carried by some 46% of Western Europeans.

Ho's group found that the FTO risk allele also has a substantial effect on brain structure. Participants who carried at least one copy of the allele had marked reductions in the volume of various brain structures compared to average volumes in non-carriers and in the general population. Carriers of the allele had, on average, an 8% deficit in the volume of the frontal lobes and a 12% deficit in occipital lobe volume. A reduction in temporal lobe volume was observed in participants with a higher body-mass index, but not in carriers of the risk allele who have a body-mass index within the normal range. Those with higher body-mass index also showed volume deficits in all the other lobes of the brain, as well as in the brain stem and cerebellum (above).

Clearly, body-mass index and the FTO risk allele can affect brain structure independently of another, because significant differences in brain structure were observed in participants carrying the allele. FTO is known to highly expressed in the brain, and particularly in the cerebral cortex, but its function is still unclear, as is the mechanism by which a change in a single base pair in the gene can exert such a significant effect on brain structure. The reduced frontal lobe volume observed in carriers of the risk allele is interesting, as it has previously been associated with impairments of so-called executive functions, as well as in several types of memory, all of which are also impaired in Alzheimer's and other forms of dementia.

How might being overweight or obese lead to a reduction in brain volume? Inflammation could mediate the effects of obesity on the brain. Adipose (fat) tissue is known to produce chemicals called cytokines, which may contribute to neurodegeneration. It contains immune system cells called macrophages and monocytes, too, which are also implicated in Alzheimer's.

Whatever the mechanism, the recent findings have important health implications. Obesity is a major public health concern - there are some 300 million obese, and more than 1 billion overweight, people worldwide. These studies, and others that came before them, suggest that maintaining normal body weight throughout adulthood - and especially middle age - could minimize the risk, or even prevent, the onset of dementia in later life. They also reiterate the emerging view that changing one's lifestyle - and particularly taking regular physical excercise - is probably the most effective way of reducing the risk of dementia in later life.

Debette, S., et. al. (2010). Visceral fat is associated with lower brain volume in healthy middle-aged adults Ann. Neurol. DOI: 10.1002/ana.22062

Ho, A., et. al. (2010). A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly. Proc. Nat. Acad. Sci. 107: 8404-8409. [PDF]

Rosengren, A., et. al. (2005). Body Mass Index, Other Cardiovascular Risk Factors, and Hospitalization for Dementia. Arch. Intern. Med. 165: 321-326 [PDF]

Gorospe E.C. & Dave, J. K. (2007). The risk of dementia with increased body mass index. Age Ageing 36: 23-29. [PDF]

neurophilosophy Wed, 06/16/2010 - 10:00

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Medicine & Health

neuroscience

body-mass index

brain volume

dementia

obesity

neuroscience

so informative, thanks to tell us.

Is the link vitamin D?

Vitamin D deficiency is linked to dementia, schizophrenia and depression and increased obesity is known to reduce serum vitamin D levels.

Those are some very interesting studies!

I'm still trying to think of a mechanism which could explain why waist-to-hip ratio (WHR) is associated with increased temporal horn volume. The thing about WHR is that it's a proxy for visceral fat, which *wasn't* associated with temporal horn volume. I'm wondering if that could be a Type 1 error... because otherwise it's hard to make sense of it.

The associations of BMI and body fat distribution with total brain volume are intriguing. Can inflammation cause the brain to shrink? I ask because in general, obesity (and especially abdominal obesity) is associated with enlarged organs (think fatty liver disease), rather than reduced organs. But it's hard to find an organ that I know less about than the brain, so I'd be interested to hear more on the plausibility of obesity directly leading to smaller brain size.

[there are some 300 million obese, and more than 1 billion overweight, people worldwide..]

These findings sounds scary. Although we all know well how important it is to maintain BMI and body fat at healthy level, there are always people who just simply reluctant to move their feet or change their diet habits.

@Mills: Vitamin D could be involved, but the link between obesity and brain volume is likely to be far more complex than a single small molecule.

@Noel: I don't like comments that are posted purely for promotional purposes - and yours clearly was - so I removed the hyperlink to your bike shop.

@Travis: I know very little about obesity, but what if WHR is not as good a proxy for visceral fat as we think it is? This 2007 paper suggests that skinfold measurements and waist circumference may be better determinants of body fat distribution.

You'll get no argument from me that WHR is a less-than-ideal measure of body fat distribution (although the paper you mention above didn't actually measure visceral fat).

So if we agree that WHR isn't the ideal measure of body fat distribution, how to make sense of the finding that this one weak measure is associated with temporal horn volume, when other far superior measures like visceral fat itself are not? (the study above used a ratio of total central-to-peripheral fat mass, which in general is a much weaker correlate of metabolic health than visceral fat itself)

Travis

On the other hand, maybe early dementia starts with a tendency to eat whatever you damn well want.

Is weight loss surgery (with successful weight loss) linked to a reversal (or stopping) of brain shrinkage and dementia?

It's too bad that I didn't have a baseline brainscan MRI done before the onset of my mental illness so that I could have compared it to my current one. It would have been enlightening to see whether/how much my temporal horn increased in size upon the onset of my mental illness.

Typical case of nonsense correlation. It's getting a bit pathetic the lengths vendors of diets/surgery/pills/sport go to scare people in buying their products.

It's almost like global warming, obesity causes every affliction known to man:

The hypothesis that obesity is detrimental to the health.

It doesnât take much reading to discover this to be completely false but nevertheless time and time again we are brainwashed that we must be slim, be sportive, eat healthy.

So how is it nevertheless possible that weâre brainwashed to believe so, to go so far as to take cholesterol lowering medication, whose dangerous side effects far outweigh the benefits (if any) whereas there only is a correlation between CVD, but no causal relation has ever been proven.
http://petrossa.wordpress.com/2010/04/16/the-disease-fat-does-not-exist/

Working at the coal face I am often asked by my patients, what does this mean to me?
There is a lot of scary information out there, between the cardiac risks, diabetes, osteoarthritis I am already able to demonstrate my patients are suffering I just don't think I will be promoting this information too hard to my patients.

I think the work of doctors is already cut out when it comes to promoting healthy activities so I am working hard to highlight the risks of doing nothing but then working hard to find ways to help reinforce ways to help reverse, well what I hope to reverse, the effects of damage already done.

Bit more carrot a little less stick? Seems to get a little more traction with my patients.

Thanks, Mo, for another fascinating post. Obviously you saw from Twitter that I have a keen interest in the science of obesity. I have a Ph.D. in developmental and molecular biology, and have since also turned science writer.

As a biological scientist who has struggled with my weight for many years, I've come to accept my body as it is, and do what I can to keep myself healthy. Of all the stuff I've learned over the last few years, inflammation does indeed have very serious consequences in obesity. I've also learned, as you mentioned in the last sentence of your post, that physical activity is KEY to maintaining good health in obese people. It literally reverses insulin resistance, and has a remarkably efficient effect on visceral fat, which is by far the most dangerous fat tissue in the body.

I attended a weight loss program, from 2004 - 2007, at Columbia University/St. Luke's New York Obesity Research Center. It is run by 3 people: a dietitian, an exercise physiologist, and a cognitive psychologist. At one of our weekly meetings, the exercise physiologist, Rich Weil, showed us a pair of remarkable human abdominal CT scans taken just before and one half hour after moderate cardiovascular exercise - after exercise, the visceral fat was reduced by about 75%. I will never forget this image. Visceral fat is extremely sensitive to exercise. So there are many good reasons for obese people to have hope for a healthy life, even in old age. Waist circumference is an easy, cheap, and very poor substitute for measuring visceral fat. Many health professionals figure that most "people of girth" don't exercise anyway, so they take if for granted that these people have disproportionately high levels of visceral fat. If these people are indeed sedentary, then that's probably true. But it's not true if they exercise regularly. Lifestyle changes, including learning to eat healthier and increasing self-esteem regardless of body size goes a long way to improve health in general.

The reason I'm so passionate about this topic is not only for my own self-interest, but to combat the extreme prejudice that obese people encounter in Western society. The stress from this alone is a huge factor in decreasing the mental and physical health of fat people. Rebecca Puhl of the Rudd Center for Obesity at Yale has done some terrific work on this. Scientists in the field of obesity research are realizing that no matter how much they may have attributed obesity to sloth and gluttony on the part of the individual, there is much more that is as yet unknown. In our obesogenic society, those who are genetically predisposed to obesity will become obese despite their most valiant, repeated efforts at weight loss (and the more "yo-yo dieting cycles, the worse the obesity gets.

This society wrongly believes that anyone can be thin if they try hard enough. Generations of experience tell us otherwise. Rudy Leibel, one of the scientists who first cloned the leptin gene, confirmed this. There is much work to be done. Hopefully we will all move toward a society that is healthier for all of us, with the help of objective scientific inquiry.

Thanks for getting me juiced up for more blogging! I haven't posted anything on my Fat Science blog for over a year. I might just start up again!

This is ridiculous journalism, although I give credit for using the word "association". This does not mean obesity causes temporal lobe or any other brain anomaly. What if the anomaly caused people to eat more trying to self medicate? Way too premature and irresponsible to highlight these so-called studies and allow suggestive headlines to be written!

Pocket Science - geneticist hunts down the cause of his own genetic disorder, and male moths freeze females by mimicking bats

edyong — Thu, 11 Mar 2010 13:53:56 +0000

Pocket Science - geneticist hunts down the cause of his own genetic disorder, and male moths freeze females by mimicking bats

Not Exactly Pocket Science is a set of shorter write-ups on new stories with links to more detailed takes by the world's best journalists and bloggers. It is meant to complement the usual fare of detailed pieces that are typical for this blog.

Geneticist sequences own genome, finds genetic cause of his disease

If you've got an inherited disease and you want to find the genetic faults responsible, it certainly helps if you're a prominent geneticist. James Lupski (right) from the Baylor College of Medicine suffers from an incurable condition called Charcot-Marie-Tooth (CMT) disease, which affects nerve cells and leads to muscle loss and weakness.

Lupski scoured his entire genome for the foundations of his disease. He found 3.4 million placed where his genome differed from the reference sequence by a single DNA letter (SNPs) and around 9,000 of these could actually affect the structure of a protein. Lupski narrowed down this list of candidates to two SNPs that both affect the SH3TC2 gene, which has been previously linked to CMT. One of the mutations came from his father and the other from his mother. Their unison in a single genome was the cause of not just Lipson's disease but that of four of his siblings too.

It's a great example of how powerful new sequencing technologies can pinpoint genetic variations that underlie diseases, which might otherwise have gone unnoticed. The entire project cost $50,000 - not exactly cheap, but far more so than the sequencing efforts of old. The time when such approaches will be affordable and commonplace is coming soon. But in this case, Lupski's job was easier because SH3TC2 had already been linked to CMT. A second paper tells a more difficult story.

Jared Roach and David Gallas sequenced the genomes of two children who have two inherited disorders - Miller syndrome and primary ciliary dyskinesia - and their two unaffected parents. We don't know the genetic causes of Miller syndrome and while the four family genomes narrow down the search to four possible culprits, they don't close the case.

For great takes on these stories and their wider significance, I strongly recommend you to read Daniel Macarthur's post on Genetic Future, Mark Henderson's piece in the Times and Nick Wade's take in the NYT (even if he does flub a well-known concept). Meanwhile, Ivan Oranksy has an interesting insight into the political manoeuvres that go into publicising two papers from separate journals. And check out this previous story I wrote about how genome sequencing was used to reverse the wrong diagnosis of a genetic disorder.

Reference: http://dx.doi.org/10.1056/NEJMoa0908094 and http://dx.doi/org/10.1126/science.1186802

Male moths freeze females by mimicking bats

Flying through the night sky, a moth hears the sound of danger - the ultrasonic squeak of a hunting bat. She freezes to make herself harder to spot, as she always does when she hears these telltale calls. But the source of the squeak is not a bat at all - it's a male moth. He is a trickster. By mimicking the sound of a bat, he fooled the female into keeping still, making her easier to mate with.

The evolutionary arms race between bats and moths has raged for millennia. Many moths have evolved to listen out for the sounds of hunting bats and some jam those calls with their own ultrasonic clicks, produced by organs called tymbals. In the armyworm moth, only the males have these organs and they never click when bats are near. Their tymbals are used for deceptive seductions, rather than defence.

Ryo Nakano found that the male's clicks are identical to those of bats. When the males sung to females, Nakano found that virtually all of them mated successfully. If he muffled them by removing the tymbals, they only got lucky 50% of the time. And if he helped out the muted males by playing either tymbal sounds or bat calls through speakers, their success shot back up to 100%. Nakano says that this is a great example of an animal evolving a signal to exploit the sensory biases of a receiver.

More on bats vs. moths from me

Reference: Biology Letters http://dx.doi.org/10.1098/rsbl.2010.0058

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edyong Thu, 03/11/2010 - 08:53

Genetics has come so far, it's amazing to see what geneticists are doing and will be doing with this new technology.

Mimicking the sound of a clothing store has a similar effect on human females ;)

Smell a lady, shrug off flu - how female odours give male mice an immune boost

edyong — Sun, 07 Mar 2010 11:00:26 +0000

Smell a lady, shrug off flu - how female odours give male mice an immune boost

Sex might be fun but it's not without risks. As your partner exposes themselves to you, they also expose you to whatever bacteria, viruses or parasites they might be carrying. But some animals have a way around that. Ekaterina Litvinova has found that when male mice get a whiff of female odours, their immune systems prepare their airways for attack, increasing their resistance to flu viruses.

Litvinova worked with a group of mice that were exposed to bedding that had previously been soiled by females in the sexually receptive parts of their cycle. She compared them to a second more monastic group that were isolated from female contact.

Male mice use smells to track down females who are ready to mate. They'll follow markings of faeces and urine and when they actually find the female, they'll continue sniffing her nose and genitals. Each of these nasal encounters could be a source of infection. She then pitted both groups against a flu virus. Influenza doesn't affect wild populations of house mice, so the virus in this case is acting as more of an indicator of the animals' defences, rather than a representative of a real threat.

Both groups of mice lost a bit of weight, but at certain doses of virus, those that had been exposed to female aromas kept more of their grams on. They also fared better in the long run - just 20% of them died, compared to 46% of those that had only smelled male odours.

Their lungs revealed the secret behind their resistance. After sniffing the female bedding, the males had conscripted white blood cells to their airways - some of the most potent defences against respiratory infections. This flood of new recruits led to a defensive force almost three times as strong as those marshalled by isolated males. The arrival of white blood cells into the lungs can sometimes cause inflammation, which hampers a mouse's lung capacity. But Litvinova found that the bedding sniffers weren't affected in this way. Their aerobic abilities were normal.

Of course, mouse bedding is a smorgasbord of different chemicals and it isn't exactly free of infectious viruses and bacteria itself. Perhaps when males sniffed the bedding, these resident microbes triggered an immune response that allowed them to resist the later flu attack? Litvinova doesn't rule out this possibility, but she thinks that it's an unlikely explanation. After all, the male mice were all housed in groups. Even those that were isolated from females still got to sniff the bedding of other males, and they weren't significantly protected against the flu.

Instead, she thinks that it's a sensible strategy for mice to get an immune boost if they smell the scent of a sexually receptive female. With mating and close-quarters contact on the cards, it's worth giving yourself better odds of warding away any pesky infections that might transfer alongside those bodily fluids. However, the best test of this hypothesis is one that hasn't been carried out yet - to see if males get different degrees of protection if they smell females at different parts of their sexual cycle.

Reference: Litvinova, E., Goncharova, E., Zaydman, A., Zenkova, M., & Moshkin, M. (2010). Female Scent Signals Enhance the Resistance of Male Mice to Influenza PLoS ONE, 5 (3) DOI: 10.1371/journal.pone.0009473

Photo by Rama

More on immune responses:

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edyong Sun, 03/07/2010 - 06:00

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What happens when mice are housed communally? According to this hypothesis the males would exhibit chronic hyper immune activity. That should be easy to determine. Even with divided housing the bedding would be same, and if it is a chemical, and not microbial, response you should see the same result. If the immune response cycles with the female's receptivity, you have your answer.

A better test would be to isolate the causative agent "mouse bedding is a smorgasbord of different chemicals and it isn't exactly free of infectious viruses and bacteria itself"

The best part of further research would be to see if a similar thing happens in humans! Let's get some ethics approval and DO IT!

Remember, there are three Fs that stress readies us for. Not only fight and flight but also fornicate. Furthermore, the fight can occur at the microscopic level.

I would suggest that as the male mouse goes into "heat" an increase in dopamine levels would occur as they do in other anticipatory conditions. Devoino showed as early as 1984 that dopamine stimulates cytokines associated with the cellular immune system (Th1) while serotonin suppresses them. She could not use current terminology for it had not yet been described and her concepts of the thymus and adrenal may be more Selye than 2010.

The monoamine systems take part in the mechanisms of immunomodulation: the dopaminergic one accelerates and the serotoninergic system inhibits the development of immune response, the final result being determined by their interaction. The immunomodulation is actualized by the dopaminergic system through the thymus and by the serotoninergic one--through the adrenals

The rat would be primed to combat viral and bacterial infections. Of course, if there is excessive allostatic load, the immune system falls apart. Best example, AIDS.

As Ader, Cohen and many others have shown, one can not separate emotions from the immune system. IMHO, every psychotropic is an immunomodulator.

Pocket Science - when enslaved bacteria go bad, gut microbes and fat mice, and stretchy beards of iron

edyong — Fri, 05 Mar 2010 08:35:04 +0000

Pocket Science - when enslaved bacteria go bad, gut microbes and fat mice, and stretchy beards of iron

The Not Exactly Pocket Science experiment continues after the vast majority of people who commented liked the pilot post. I'm really enjoying this, for quite unexpected reasons. It's forcing me to flex writing muscles that usually don't get much of a workout. Writing short pieces means being far more economical with language and detail than usual. It means packing in as much information as possible while still keeping things readable. And it means blitz-reading papers and writing quickly without losing any accuracy.

One quick note before the good stuff: last time, a few people suggested that I put each NEPS item in a separate post, but the majority preferred multiple items per post. For now, I'm keeping it that way because otherwise, the longer pieces would be diluted by the smaller ones. We'll see how that works for the foreseeable future.

Rising DAMPs - when enslaved bacteria turn our bodies against themselves

Our immune systems provide excellent defence against marauding hordes of bacteria, viruses and parasites, using sentinel proteins to detect the telltale molecules of intruders. But these defences can be our downfall if they recognise our own bodies as enemies.

All of our cells contain small energy-supplying structures called mitochondria. They're descendents of ancient bacteria that were engulfed and domesticated by our ancestor cells. They've come a long way but they still retain enough of a bacterial flavour to confuse our immune system, should they break free of their cellular homes. An injury, for example, can set them free. If cells shatter, fragments of mitochondria are released into the bloodstream including their own DNA and amino acids that are typical of bacteria. Qin Zhang showed that trauma patients have far higher levels of such molecules in their blood than unharmed people. Our white blood cells have sentinel proteins that latch onto these molecules and their presence (incorrectly) says that a bacterial invasion is underway.

This discovery solves a medical mystery. People who suffer from severe injuries sometimes undergo a dramatic and potentially fatal reaction called "systemic inflammatory response syndrome" or SIRS, where inflammation courses through the whole body and organs start shutting down. This looks a lot like sepsis, an equally dramatic response to an infection. However, crushing injuries and burns can cause SIRS without any accompanying infections. Now we know why - SIRS is caused by the freed fragments of former bacteria setting off a false alarm in the body. The technical term for these enemies within is "damage-associated molecular patterns" or DAMPs.

Reference: Nature DOI:10.1038/nature08780

Different gut bacteria lead to mice to overeat

On Wednesday, I wrote about the hidden legions residing up your bum - bacteria and other microbes, living in their millions and outnumbering your cells by ten to one. These communities wield a big influence over our health, depending on who their members are. Matam Vijay-Kumar found that different species colonise the guts of mice with weakened immune systems, and this shifted membership is linked to metabolic syndrome, a group of obesity-related symptoms that increase the risk of heart disease and type 2 diabetes.

Vijay-Kumar's mice lacked the vital immune gene TLR5, which defends the gut against infections. Their bowels had 116 species of bacteria that were either far more or less common than usual. They also overate, became fat, developed high blood pressure and became resistant to insulin - classic signs of metabolic syndrome. When Vijay-Kumar transplanted the gut menagerie from the mutant mice to normal ones, whose own bacteria had been massacred with antibiotics, the recipients also developed signs of metabolic syndrome. It was clear evidence that the bacteria were causing the symptoms and not the other way round.

Vijay-Kumar thinks that without the influence of TLR5, the mice don't know what to make of their unusual gut residents. They react by releasing chemicals that trigger a mild but persistent inflammation. These same signals encourage the mice to eat more, and they make local cells resistant to the effects of insulin. Other aspects of the metabolic syndrome soon follow. The details still need to be confirmed but for now, studies like this show us how foolish it is to regard obesity as a simple matter of failing willpower. It might all come down to overeating and inactivity, but there are many subtle reasons why an individual might eat too much. The microscopic community within our guts are one of them.

Read an amazing take on this from Carl Zimmer at the Loom and a previous post from me

Reference: Science DOI:10.1126/science.1179721

The stretchy iron-clad beards of mussels

For humans, beards are for catching food, looking like a druid, and getting tenure. But other animals have beards with far more practical purposes - mussels literally have beards of iron that they use as anchors. The beard, or byssus, is a collection of 50-100 sticky threads. Each is no thicker than a human hair but they're so good at fastening the mussels to wave-swept rocks that scientists are using them as the inspiration for glue. So they should. The byssus is a marvel of bioengineering - hard enough to hold the mussel in place, but also stretchy enough so that they can extend without breaking.

The mussel secretes each thread with its foot, first laying down a protein-based core and then covering it in a thick protective layer that's much harder. When Matthew Harrington looked at the strands under a microscope, he saw that the outer layer is a composite structure of tiny granules amid a looser matrix. The granules consist of iron and a protein called mfp-1, heavily linked to one other - this makes the byssus hard. The matrix is a looser collection of the same material, where mfp-is 1 heavily coiled but easy to straighten - this lets the byssus stretch. The granules have a bit of give to them but at higher strains, they hold firm while the matrix continues extending. If cracks start to form, the granules stop them from spreading.

It's unclear how the mussel creates such a complicated pattern, but Harrington suggests that it could be deceptively simple - changing a single amino acid in the mfp-1 protein allows it to cross-link more heavily with iron. That's the difference between the tighter granular bundles, and the looser ones they sit among.

More from Eric Bland at Discovery News and stories of bioengineering from me, including triple-armoured snails, shatter-proof teeth and sharp squid beaks.

Reference: Science DOI:10.1126/science.1181044

Cause of dinosaur extinction ~~revealed~~ confirmed

Sixty-five million years ago, the vast majority of dinosaurs were wiped out. Now, a new paper reveals the true cause of their demise - legions of zombies armed with chaingu... wait... oh. Right. An asteroid. You knew that.

More from Mark Henderson at the Times

Reference: Science DOI:10.1126/science.1177265

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edyong Fri, 03/05/2010 - 03:35

I just wanted to say that I prefer the multiple articles per post for two main reasons:

1) It forces me to look at research I might otherwise avoid since it's already right in front of me to read. Sort of like a newspaper or magazine. I use a feed reader so I'll avoid articles that don't catch my attention.

2) I read from my iPod, so multiple posts in one place is much more convenient. It makes it much more likely for me to read each article.

Further, I'm still loving the pocket science. Great for those of us that are super-busy, want to keep up on interesting finds, but don't have the time to get into a full article.

once again I am glad I have this site bookmarked. Some really fun stuff there! Thank you for spending the time that you do on this blog.

Re: gut bacteria. So does this mean obesity might be contagious after all? :)

I like this pocket science experiment.

I think the longer format is much better. Quality before quanity. Either way, however, you're doing a great job.

I hear you, Steve, and I feel largely the same. If I had infinite time on my hands, I'd give everything the full treatment. The short format does allow me to cover stories that I don't actually have much to say about but I thought were worth a mention. For example, I didn't really have much more to write about the mussel beards than the three paragraphs above. In previous months, I'd have just ignored it.

As I said in the pilot post, if I suspect that the Pocket Science posts are compromising the quality of the longer pieces, I'll cut back or stop them.

Beer makes humans more attractive to malarial mosquitoes

edyong — Thu, 04 Mar 2010 07:00:18 +0000

Beer makes humans more attractive to malarial mosquitoes

We've all heard about "beer goggles", the mythical, invisible eyewear that makes everyone else seem incredibly attractive after a few pints too many. If only beer had the reverse effect, making the drinker seem irresistibly attractive. Well, the good news is that beer does actually do this. The bad news is that the ones who are attracted are malarial mosquitoes.

Anopheles gambiae (the mosquito that transmits malaria) tracks its victims by their smells. By wafting the aromas of humans over thousands of mosquitoes, Thierry Lefevre found that they find the body odour of beer drinkers to be quite tantalising. The smell of tee-total water drinkers just can't compare. The somewhat quirky conclusion from the study, albeit one with public health implications, is that drinking beer could increase the risk of contracting malaria.

Lefevre recruited 43 men from Burkina Faso and sent them individually into one of two sealed, outdoors tents. One tent was kept unoccupied. In the second, the volunteer had to drink either a litre of water (just shy of two pints) or a litre of dolo (a local 3% beer and the country's most popular alcoholic drink). A fan pumped air from the tents, body odour and all, into the two forks of a Y-shaped apparatus. Both branches met in a third arm, which ended in a cup full of mosquitoes. The insects had to decide which branch of the Y to fly down and two pieces of gauze trapped them in their chosen path (and saved the volunteers from an infectious bite).

Lefevre showed that the smell of a beer drinker, 15 minutes after chugging his litre, increased the proportion of mosquitoes inclined to fly into the tubes, and the proportion (65%) who headed down the beer-scented fork. The smell of water-drinkers had no effect, nor did the smell of the occupied tent before its inhabitant started drinking.

What is it about a beer drinker that is so appealing? No one knows. Mosquitoes are drawn to the smell of carbon dioxide, but the beer drinkers weren't exhaling any more of this gas after their drink. Something about the smell of beery body odours attracts mosquitoes. Mosquitoes also fancy body heat, but beer actually lowered the volunteers' temperature by a fraction of a degree. Metabolising beer probably releases a slew of chemicals that mosquitoes are drawn to but the identity of these airborne attractants is a mystery. Nor do we know if the chemicals in question are specific to beer, or common to all alcoholic drinks.

This study is perfect tabloid fodder, but it has a very serious side. To mosquitoes, not all humans are equal. The bloodsuckers are quite picky about whom they suck from, and an important global study revealed that in problem areas, 20% of people receive 80% of all malaria infections. As such, it's quite important to work out what makes one person a delectable feast and another person a bloody turn-off.

Beer can't explain all of this variation by any means. After all, Lefevre found that some people were naturally attractive to mosquitoes without drinking anything; beer merely boosted these natural charms. So a pint of lager in the African sunset isn't going to guarantee a raging malarial fever, but it might increase the risk of one.

There are other reasons to think that the beer effect may be more serious than shown in this study. For a start, A.gambiae is a night biter. It's most active after sunset, which probably coincides with the time its prey is most likely to smell of beer. Drinking moderate to heavy amounts of alcohol can also suppress the immune system so regular beer drinkers are not only more likely to encounter malarial mosquitoes but they could be more vulnerable to the parasites they carry. And finally, at least one previous study showed that Aedes mosquitoes, carriers of dengue fever, are drawn to the aroma of beer drinkers, so the public health implications may go beyond just malaria.

Finally, Lefevre even puts forward a completely speculative, but cool, idea - perhaps the fact that mosquitoes wear beer goggles isn't just a coincidence. It's possible that they might have evolved a slight preference for the smell of beer-drinkers, either because their blood is full of nutrients or as he dryly notes, "possibly due to reduced host defensive behaviours"! As Lefevre says, "This hypothesis is appealing but requires further investigations."

Reference: LefÃ¨vre, T., Gouagna, L., DabirÃ©, K., Elguero, E., Fontenille, D., Renaud, F., Costantini, C., & Thomas, F. (2010). Beer Consumption Increases Human Attractiveness to Malaria Mosquitoes PLoS ONE, 5 (3) DOI: 10.1371/journal.pone.0009546

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edyong Thu, 03/04/2010 - 02:00

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Tabloid headline- "to avoid malaria, you should drink beer for breakfast, not dinner".
Or, "Gin and tonic, not beer: a drinkers guide to avoiding malaria"
How do we know the mozzies don't feel the alcohol?
I wish they'd done it with plasmodium carrying mozzies and with plasmodium free mozzies.

I think the reason why they didn't separate out Plasmodium carriers vs. non-carriers is that they wanted to do the study with mosquitoes from populations that hadn't been bred in the lab. So the mozzies in the study were hatched in a lab, but the eggs were laid by pregnant females caught in the wild. Why this is important isn't clear to me, but they make a thing of it in the paper. Anyway, more work to do. It would also be interesting to test other alcoholic beverages

Interesting article. We have terrible mosquito problems around here (Virginia) but I don't know that the beer drinker in the house suffers worse. On the other hand, he smokes so maybe that is a deterrent.

Oh Ed, there's a typo in the first para...The bad news is that the ones who are attracted [at] malarial mosquitoes.

Since you mention that mosquitos are attracted to carbon dioxide, was the beer in question carbonated? Have other carbonated beverages been tested?

Typo fixed - thanks.

@4 - doesn't really matter because the beer didn't increase the concentration of CO2 in the tent air.

I was immediately left wondering why the decision was made to test beer vs water in the first place. Did the authors already suspect a link between beer consumption and 'attractiveness of odour'...? A quick read of the paper answered the question, it seems that a previous study had already made the link between beer consumption and 'odour attractiveness' to laboratory bred Aedes mosquitoes and the authors wished to test the link in malaria mosquitoes from natural populations. I can't find a full copy of the previous study online though (its past my bedtime so I've only looked for a few minutes) so I'm still wondering why that particular link was suspected in the first case. I wonder if it was already part of some common folklore that drunk people are more prone to bites.

In any case, I'm not usually prone to being bitten. I think I might get a case of beer on the weekend and conduct some experiments of my own on my local population of mosquitoes.

This is incredibly interesting. I'm always attacked relentlessly by the mosquitoes here in North Carolina, especially compared to some of my friends.

But this study has some important implications for tailgating during football season!

Shouldn't they have had them drink the beer outside of the tent first, and then enter the tent for the test? How do we know that the odor of the beer itself wasn't still in those tents, mixed in with the odor of the beer drinkers? Does it explain this in the paper?

@Ed: Couldn't belching from the beer tent (esp. if chugged) produce a slight bump in CO2 emissions which the mosquitoes could pick up on?

The title should have been Beer makes humans more attractive. The rest is a detail.

One of my children is a mosquito magnet. It will be interesting to find out more about mosquito preferences. (I will advise her that when she is of age to avoid beer while camping!)

Nathan, did you see the title for Figure 2? ;-)

Jason and Eve - sorry, no time tonight, but the paper's open access and not too difficult a read.

So we have carbon dioxide, nonanal, and now beer that makes us delicious.

Did I read the nonanal findings from Not Exactly Rocket Science? I don't see it in the "more on mosquitoes", but I don't remember where I heard that one...

@Ed: One problem with lab mosquito populations is that they quickly become slow. If you've ever been in a lab that raises houseflies, it's fun swatting the ones that escape, because their reaction time is absolutely terrible. Probably some strong behavioral changes as well, such as rapid selection for willingness to feed on the blood bag membrane.

Anyway, a bunch of things you'd rather not have to account for in your experimental design! So they kept it as close to wild behavior as reasonably possible.

I seem to recall something about the smell of feet being attractive to mosquitoes; if any sort of yeast is involved in that effect, it could follow that beer would cause greater attractiveness. Unfortunately, in that study they were culturing bacteria, although if generalized it could imply that mosquitoes are attracted to feet in other ways also. If so, there might be a whole host of chemical attractants active, and yeast or other fungus could be among of them.

A little contrived, but testable!

I assume the local beer used in the experiment is a live-yeast home-brew, not factory-bottled?
Folklore in Australia claims that drinking home-brewed beer (non-pasteurized live yeast beer) acts as a mosquito repellent, providing you've been consuming the stuff for 6 weeks or so.
But in southern Australia there are no malaria- carrying mosquitoes - yet. Perhaps this needs testing.

Did I read the nonanal findings from Not Exactly Rocket Science?

Probably not - I try to feature only the most anal of discoveries.

ChrisM - Thanks for that.

A.Fleming - The idea that Aussies might drink home-brewed beer for 6 weeks straight does not surprise me in the slightest ;-)

Maybe that explains why mosquitos tend to ignore me, being Australian and a homebrewer... but now I'm confused. Mosquitos are attracted to beer drinkers, or at least Burkinabe males aged between 23 and 40 who drink dolo prepared from the fermented dough of sorghum. But mosquitos are repelled by beer drinkers, or at least according to folklore, Australians who drink homebrew. To be safe, I'll continue to avoid drinking dolo and being Burkinise and stick with homebrew...

@Ed Yes, I've learned to appreciate the wonders of my colon and all it contains thanks to your features.

NSF is where I read that article, in case anyone else is interested: http://www.nsf.gov/discoveries/disc_summ.jsp?cntn_id=116286&org=NSF

Apparently nonanal gives off a fruity odor, as opposed to nutty.

[blockquote]
But in southern Australia there are no malaria- carrying mosquitoes - yet.
[/blockquote]

between Dengue Fever, Ross River Virus, and the tradition of going "fishing" with half a litre of bait and four hundred litres of beer, a local follow up on this is probably going happen any second now...

But in southern Australia there are no malaria- carrying mosquitoes - yet.

Vitamin B1 (Thiamin) deters mesquitoes as most backpackers know. Beer depletes this vitamin in the system. Mystery solved.

The only control is water, rendering the study silly. To say that beer has a specific effect, you need to test it against other foods, taken in similar caloric amounts, at a minimum.

Perhaps a non-specific increase in blood sugar is responsible, for example. It's highly plausible that mosquitoes would be attracted to blood with a higher glucose content. But then almost any snack or meal would have the same effect.

John -

Hard liquor depletes vitamin B1 (except in Australia, where they fortify to prevent Wernicke-Korsikoff syndrome).

Beer, at least high quality all-malt beer, is loaded with thiamine.

The bacterial zoo in your bowel

edyong — Wed, 03 Mar 2010 12:00:19 +0000

The bacterial zoo in your bowel

You are outnumbered by a factor of 10 to one, by forces you cannot see. Your body has around ten trillion cells, but it's also home to a hundred trillion bacteria. For every gene in your genome, there are 100 bacterial ones. Most of these are found the dark, dank environment of your bowel but their incredible diversity is being brought to the surface. Say hello to the gut metagenome.

Together with a team of international scientists, Junjie Qin and Ruiqiang Li from BGI-Shenzen had the unenviable task of studying the bacteria from the faeces of 124 Europeans. They used a formidable and audacious technique called metagenomics, which analyses all the genetic material in a sample, without bothering to culture the individual species first. It's a shoot-first-ask-questions-later method that captures all the data and lets other programmes sort out the mess.

Stool samples from 33 people have already been analysed in this way, but Qin and Li managed to sequence almost 200 times as much DNA. Brace yourself for some big numbers. Their project uncovered just under 3.3 million bacterial genes, more than 150 times as many as reside in the entire human genome. By their estimate, your bowel and mine harbour at least 160 bacterial species each and we share many of our tenants (I say bacteria, but around 1% of the genes came from archaea, a superficially similar group but one that's actually as different from bacteria as bacteria are from us).

The quest to understand gut microbes may seem like an arcane niche of science, but it's actually very important for public health. We rely on these microscopic passengers more than we realise. They harvest energy from our food, provide us with nutrients that would otherwise be denied to us, prevent the growth of harmful bacteria, and more. In many ways, they're like a forgotten organ. They can also go rogue, changing their community in ways that are linked to obesity or bowel diseases. Indeed, Qin and Li showed that the gut microbiome of a health person looks very different to that of someone with a bowel condition like Crohn's disease or ulcerative colitis.

All in all, over 1,000 species make their living in the human bowel but a common cadre of 57 are shared by the vast majority of us. Even for this common set, each individual species could be thousands of times more common in your gut compared to mine. With such variation, it's no wonder that earlier smaller studies concluded that people have very different gut lodgers.

Of the 3.3 million genes, most are fairly rare. Some 2.3 million of them are found in less than a fifth of the people in the study. There is, however, a set that is shared across all bowels. Some of these core genes as "housekeepers", essential for the survival of any bacterium, but others are specific requirements for life in the bowel.

The latter group include genes for sticky proteins that allow the bacteria to latch onto the cells of their hosts, essential when your home is constantly washed by tsunamis of digested food. Others are all about sugars - they harvest, break down and ferment these complex molecules from their nutritious surroundings, including several sugars from fruits and vegetables that we don't absorb very well. Yet others produce vitamins and fatty acids that we'd otherwise lack and some may even help to convert unusual chemicals, like the food supplement benzoate (E211), into useful substances like the vitamin biotin. The majority, however, are still a mystery, and that's just the essential genes. There are millions more with functions still to be unpicked.

So far, the data reads like a litany of massive numbers and impressive stats. But the true value of Qin and LI's work is as a source of data for future discoveries yet to come. Jonathan Eisen from University of California, Davis says, "Much of the science in here is not that novel but the scope of this project alone is awesome. This is most valuable as a reference data set for future work." He adds that we still need to decipher the genomes of many other gut microbes, to give us reference sequences that can be compared against the sprawling mass of data thrown up by Qin and Li's study. For the moment, the best way to do that is to take the species that can already be identifed, and sequence close relatives that can be cultured in the lab. In the not-too-distant future, it should also be possible to seqeunce the genome of a single cell.

Once this work is done, we can start to answer some of the more intriguing questions. How, for example, does the gut metagenome interact with our own squadron of genes? How does it change when people put on or lose weight, when we get gut infections or when we develop bowel cancer? How are these passengers influenced by our diet or other aspects of our environment? And so far, the team have only examined European faeces. Who knows what revelations lurk within the poo of other nations?

Reference: Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K., Manichanh, C., Nielsen, T., Pons, N., Levenez, F., Yamada, T., Mende, D., Li, J., Xu, J., Li, S., Li, D., Cao, J., Wang, B., Liang, H., Zheng, H., Xie, Y., Tap, J., Lepage, P., Bertalan, M., Batto, J., Hansen, T., Le Paslier, D., Linneberg, A., Nielsen, H., Pelletier, E., Renault, P., Sicheritz-Ponten, T., Turner, K., Zhu, H., Yu, C., Li, S., Jian, M., Zhou, Y., Li, Y., Zhang, X., Li, S., Qin, N., Yang, H., Wang, J., Brunak, S., DorÃ©, J., Guarner, F., Kristiansen, K., Pedersen, O., Parkhill, J., Weissenbach, J., Antolin, M., Artiguenave, F., Blottiere, H., Borruel, N., Bruls, T., Casellas, F., Chervaux, C., Cultrone, A., Delorme, C., Denariaz, G., Dervyn, R., Forte, M., Friss, C., van de Guchte, M., Guedon, E., Haimet, F., Jamet, A., Juste, C., Kaci, G., Kleerebezem, M., Knol, J., Kristensen, M., Layec, S., Le Roux, K., Leclerc, M., Maguin, E., Melo Minardi, R., Oozeer, R., Rescigno, M., Sanchez, N., Tims, S., Torrejon, T., Varela, E., de Vos, W., Winogradsky, Y., Zoetendal, E., Bork, P., Ehrlich, S., & Wang, J. (2010). A human gut microbial gene catalogue established by metagenomic sequencing Nature, 464 (7285), 59-65 DOI: 10.1038/nature08821

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edyong Wed, 03/03/2010 - 07:00

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And I thought I had a shit post-doc...

What a great article! well done - I'm sending this to all my friends who wonder why I love microbiology...

How about the difference between meat eaters and vegetarians?

If people are interested in the dataset they can also download it via BioTorrents:
http://www.biotorrents.net/details.php?id=48

Microbiology is so not my area, but I couldn't help but notice a quasi-link between this post, your later one on the research connecting specific mouse-gut bacteria with obesity, and this guest post over at Aetiology: http://scienceblogs.com/aetiology/2010/02/c-sections_allergies_and_prob… about vaginal versus C-section birth processes and correlated outcomes of gut microflora colonization in newborns. So, I wonder... if the mouse research holds true for humans too and if a mother has this "bad" bacteria (listed in the other post) that is linked to obesity, and gives birth vaginally, then does that put the infant at increased risk for obesity straight from birth?

Ooh interesting call. Inheritance of gut bacteria is not the only route that mice could inherit a higher risk of obesity from their parents - check this out.

Interesting, I think I remember this one now; and I did not mean to imply that might be the "only" route, was just musing about the synergy of these concepts. Funny, but this describes my significant other: "..the ever-present gene also blocks signals in the animals' brains that tell them that they're full." <>

"The latter group include genes for sticky proteins that allow the bacteria to latch onto the cells of their hosts"

Absolutely intriguing! My wife has celiac disease which manifests when one of the proteins that make up gluten, gliadin a long chain of amino acids, is not completely broken down by digestive enzymes, and for unknown reasons, when this longer chain attaches to an enzyme in the small intestine called tissue-transglutaminase, the body interprets this union as toxic and the immune system attacks it. Maybe this will bring a new avenue to research of the disease?
How would you go about discovering if one or several bacteria were related to digestion of the protein gliadin? Determine if is similar in different people, and different or unique in celiac patients?
And the laymanâs question, can you introduce bacteria of this nature to an individual?

How would you go about discovering if one or several bacteria were related to digestion of the protein gliadin?>/blockquote>

Never heard of that protein, but it should be as easy as: Make an agar plate with gliadin, put bacteria on it, see if the gliadin is broken down.

And the laymanâs question, can you introduce bacteria of this nature to an individual?

In a word, yes. But it's a bit more complicated than that. Adding bacteria (like the yoghurts advertising "good bacteria") is a big enough area of research becuase there's money in it. For functinoal foods, enough of the bacterial culture has to survive the food processing and the passage through your digestive system. You can avoid that problem if you're willing to go up instead of down, but that isn't as in demand, understandably.

The problem there's no real getting around is making the bacteria establish themselves in sufficient numbers.

There's trillions of bacteria in your gut, and they're all competeing with each other. The bacteria has to be able to survive, and in suffcient numbers to have the desired effect. If the bacteria can survive in your gut, I would speculate that it's very likely already present. If it can't, there's no hope for adding it as it is, so a similar bacteria (or at least one which can do what you want) which can survive must be found, and if necessary/possible optimised for survival (genetic manipulation through genetic engineering or through selective breeding).

Take everything I've said with a pinch of salt though, because I'm only basing this on my undergrad and the odd talk from scientists in this area.

Thanks for Post 9 Marc

I really appreciate the input. This potential avenue to understand celiac disease may have been pursued already? But in the sampling of the research papers I have read on this subject matter I have not come across this link in the research.
I will inquire with a celiac research center at the University of Columbia to see if they are aware of approaching it from this direction.

Thanks,
Matt

Another interesting line of research would be the effect on this gutsy ecosystem of antibiotics, both (a) over the time they are being prescribed, and (b) over the long haul.

Can a sniff of oxytocin improve the social skills of autistic people?

edyong — Mon, 15 Feb 2010 14:00:55 +0000

Can a sniff of oxytocin improve the social skills of autistic people?

The social interactions that come naturally to most people are difficult for people with autism and Asperger syndrome. Simple matters like making eye contact, reading expressions and working out what someone else is thinking can be big challenges, even for "high-functioning" and intelligent individuals. Now, a preliminary study of 13 people suggests that some of these social difficulties could be temporarily relieved by inhaling a hormone called oxytocin.

The participants, who either had Asperger or high-functioning autism, experienced stronger feelings of trust, showed stronger social interactions in a simulated game, and paid more attention to socially important cues like someone else's eyes. These results will need to be confirmed in larger studies in real-world situations, but for the moment, they're promising.

Oxytocin is involved a myriad of emotions and social behaviours including trust, social interactions, sexual arousal, the bond between mother and child (see SciCurious's epic oxytocin series for more). It has been linked to autism before. Autistic children have lower levels of the hormone coursing through their blood and what little there is appears to be made in an abnormal way. Some researchers are testing oxytocin as a treatment for some symptoms of autism, including repetitive behaviours, but the new results are some of the most interesting yet.

The experiment

Elissar Andari gave oxytocin in the form of a nose spray to 13 autistic people and 13 typical ones of similar ages and genders. Each volunteer came into the lab twice and was given either oxytocin or a saline spray and neither they nor the scientists knew which was which until the experiment was over.

The recruits played an online game where they passed a ball to three other 'players', who were actually controlled by the computer. The aim of the game was the catch the virtual ball as many times as possible, so it's worth identifying and playing with cooperative characters. Most people do this easily, returning the ball most often to players who pass it to them. Autistic people, however, will pass the ball equally to all the players, regardless of their behaviour.

But a whiff of oxytocin changed all of that. The autistic players became more likely to engage with "good" players who passed the ball to them and shun "bad" players who ignored them (see left side of image below). And they became more and more entrenched in these preferences as the games progressed and the behaviour of the good and bad players became more evident (see right side of image below). They didn't quite match the behaviour of the neurotypical volunteers, but they weren't significantly different either.

After the game was over, a questionnaire confirmed that the autistics strongly preferred the good player and trusted them more if they played under the influence of oxytocin. This suggests that oxytocin helped the autistic players to intuit and interpret social cues that they would normally gloss over.

In another test, Andari tracked the eye movements of her volunteers as they looked at pictures of faces on a computer. As you'd expect, typical people look at the faces themselves but autistics clearly find this uncomfortable. They spend half of their time looking elsewhere and when they do look at the faces, they their dart their eyes around with anxious haste and specifically avoid staring at the eyes. Again, a whiff of oxytocin narrowed the gap between typical and autistic behaviour. The autistics spent more time looking at the face and the eyes in particular, and they explored the images with more deliberate and relaxed eye movements.

Reactions - caution and optimism

A lack of eye contact is one of autism's core problems and oxytocin's ability to overturn it is certainly promising. But looking at eyes in a laboratory test doesn't necessarily translate into real-world behaviour. Between this and a very small sample, it's unsurprising that other scientists are wary of the results. Everyone I spoke said that the study needed to be repeated with more people in realistic settings.

However, many people are optimistic. Larry Young from Emory University described Andari's work as as "promising" and "one of the better papers" in this area. However, he adds, "I would caution the public in their interpretation that this is definitely not a cure. They did these tests in a very controlled laboratory setting and they need more sophisticated studies of real social situations. Does oxytocin help people to read body language? Will they really look at the eyes more?"

Uta Frith from University College London agrees. "Against my initial scepticism... I found the paper very persuasive," she says. But she echoes Young's concerns and she wants to know exactly how the oxytocin effect works so that proper treatments could be designed. "Nevertheless," she says, "this form of pharmacological intervention would be a first in the treatment of the key social impairments of autistic disorder. This could be revolutionary."

Frith also wants to see if oxytocin could work on all autistics or just high-functioning ones. Even in Andari's study, some of the recruits responded strongly to oxytocin but others were totally unaffected. Other scientists have tried to categorise autistic people based on their style of social interactions, and it may be that oxytocin only 'works' for some of these groups.

For example, Andari noted that most of those who showed improvements in the ball-throwing game would be classified as "active-but-odd" - they normally approach other people but do so awkwardly. In contrast, most of the people who didn't show improvements fell into the "aloof" category - they avoid any close contact and actively reject social advances.

George Anderson from the Yale Child Study Centre is more skeptical about the future potential of oxytocin. He notes that the hormone doesn't easily reach the brain it doesn't last for long in the blood. It has a half-life of just a few minutes. Even if future studies replicate Andari's results, it's not clear if oxytocin could ever be used in practice.

Young agrees and says, "I don't think that this particular treatment will become widely used." He sees these experiments as a starting point for developing drugs that mimic the effect of natural oxytocin but with longer half-lives. "We could try to target the oxytocin pathway with other drugs that do penetrate the brain and that have longer half-lives. But I personally think that this kind of treatment may be more beneficial when it's combined with behavioural therapy sessions, with their defined settings."

Advice for parents

For now, many people, especially parents of autistic children, may be tempted to try out oxytocin. But Frith warns, "In previous cases, such as treatment with chelation, hormones or large doses of vitamins, initially positive results which led to immediate applications, had either no effects or rather harmful ones." Young agrees, saying that the risks are still unknown. "I would definitely not recommend that people try to do this on their own," he adds. "It shouldn't be done without the assistance of a physician and I don't think physicians should be doing this until we have more data."

Anderson, despite his skepticism, takes a more pragmatic stance. "It's not recommended but it may be hard for some parents not to try," he acknowledges. "If anyone does go ahead at this point, they could try to blind their efforts by using saline in a similar bottle. One parent could administer the oxytocin or saline and the other parent [who doesn't know which was used] could rate the [child's] behaviour over the next hour. For a number of reasons, this wouldn't constitute a true double-blind study, but it might reduce false-positive responses."

Reference: Andari, E., Duhamel, J., Zalla, T., Herbrecht, E., Leboyer, M., & Sirigu, A. (2010). Promoting social behavior with oxytocin in high-functioning autism spectrum disorders Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0910249107

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edyong Mon, 02/15/2010 - 09:00

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Genes from Chagas parasite can transfer to humans and be passed on to children

edyong — Sun, 14 Feb 2010 10:00:35 +0000

Genes from Chagas parasite can transfer to humans and be passed on to children

Millions of people in Latin America have been invade by a parasite - a trypanosome called Trypanosome cruzi. They are passed on through the bite of the blood-sucking assassin bug and they cause Chagas disease, a potentially fatal illness that affects the heart and digestive system. The infections are long-lasting; it can take decades for symptoms to show and a third of infected people eventually die from the disease. But T.cruzi does much more than invade our flesh and blood; it also infiltrates our genomes.

T.cruzi is unusual in that a massive proportion of its DNA, around 15-30%, lies outside of its main genome. These accessory sequences are stored in the form of thousands of interlinked DNA rings. In the parasite, these sequences are found in the mitochrondria - small structures that provide it with energy - but they have found a way to spread much further.

According to new research from Mariana Hecht and a team of Brazilian scientists, T.cruzi has the ability to inveigle its DNA rings into the genomes of those it infects. Once inside, the parasite genes can hop around, hitchhiking from one chromosome to another and leaving genetic chaos in their wake. They can even be passed on from one generation to the next. Hitching a ride aboard sperm and eggs, they can add themselves to the genomes of children, who've never been in direct contact with trypanosomes.

Hecht's discovery suggests that T.cruzi is an unexpected source of genetic diversity in our species. It's certainly not the only parasite to do this. Viruses have been infiltrating our genes since time immemorial and a massive part of our genome has a viral origin. These events, where viruses joined our family tree, provided raw material for natural selection. Some viral genes wreaked havoc by disrupting important genes, while others were eventually domesticated to act as helpful, even necessary, parts of our genome.

But T.cruzi is a different story. Despite its microscopic, single-celled nature, it's a vastly complex creature compared to a simple virus. And it continues to breach our DNA today. Now that we're getting technically better at detecting such "horizontal gene transfers", we may find that many other parasites are also smuggling their genes into ours. In Hecht's words, the "human population may be a patchwork of all the organisms to which it has ever been exposed."

Hecht's discovery began with a simple observation - some rabbits and human patients would still die from chronic Chagas disease even after antibiotics had exterminated the last of the trypanosomes in their bodies. The hearts of these individuals were under attack from their own immune system - a common Chagas symptom. Hecht suggested that genetic fragments left behind by the parasites could be sustaining these chronic attacks, so she set out to find them.

Hecht analysed the genes of 87 people from five Brazilian families, whose oldest members all suffered from Chagas disease. These family heads, along with some of their descendants, still had antibodies that targeted T.cruzi, meaning that they still had active infections. Twenty-five of these people had trypanosome DNA in their genomes.

The trypanosome mostly inserts its DNA into parts of the human genome that are already mobile. They're especially fond of jumping into small sequences called LINEs that can copy and paste themselves into new parts of the genome. LINEs make up around a fifth of our genome so they're plentiful targets for the trypanosomes. During an infection, Hecht envisages the parasite flooding the nucleus of host cells with thousands of DNA rings that form hundreds of junctions with LINE sequences.

The parasite can also infect the "germ-line cells" that produce sperm and eggs, giving it a chance to transfer its genes into not just the current host, but all the host's children too. Indeed, among the three families that Hecht worked with, 29 sons and daughters had trypanosome DNA in their genes, despite never having been infected by the parasite themselves. Trypanosome genes can become unplanned heirlooms, passed down the generations and jumping into new places every time.

And the close association between these genetic parasites allows the trypanosome sequences to hop into new sites from their initial staging grounds. This invading DNA can have dire consequences depending on where it's inserted. In many cases, Hecht found that they fused disparate parts of different chromosomes, and one in eight insertions knocked out important genes, involved in everything from cell communication to the immune system to our sense of smell.

Hecht thinks that in some cases, the fusions of human and parasite genes could produce actual proteins. They may not do anything, but their presence could draw the attention of the immune system, leading to many of the autoimmune symptoms of Chagas disease. For now, this is just speculation. To truly understand how these jumping genes contribute to Chagas, we'll need to sequence the complete genomes of many patients and compare symptoms with sequences.

T.cruzi has the potential to be an important driver of genetic diversity. It infects millions of people from Latin America, about a million of whom are migrating to other continents. It also affects over 1,250 species of wild mammals.

This might just be the tip of the iceberg. Other complex parasites set up shop in the human body for long, persistent infections, including other species of trypanosome. We don't know whether these body-snatchers also donate their DNA to us but finding out should occupy Hecht and other scientists for years to come. What other genetic duets await discovery?

Reference: Hecht, M., Nitz, N., Araujo, P., Sousa, A., Rosa, A., Gomes, D., Leonardecz, E., & Teixeira, A. (2010). Inheritance of DNA Transferred from American Trypanosomes to Human Hosts PLoS ONE, 5 (2) DOI: 10.1371/journal.pone.0009181

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edyong Sun, 02/14/2010 - 05:00

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Very interesting, as usual. Is the gene transfer an accidental by-product of infestation, or is it part of a life cycle? It's hard to imagine how T.cruzi would evolve this capability unless it's purely accidental, or unless there's some way for the genes that hop into humans to hop back into T.cruzi and direct it to keep doing what it's doing. Or maybe the genes don't hop back, but they alter human biology somehow in a way that benefits the parasite.

I like how you used the word "inveigle"!

Ed, what a lovely discussion of an absolutely fascinating article.

In my work on DNA topoisomerase II, I came to use the kinetoplast DNA networks of another trypanosome, Crithidia fasciculata as a substrate for the unlinking of the networks via the double-strand DNA cleavage, strand passage, and religation activity of the enzyme. When run by agarose gel electrophoresis, the network remain in the wells while the decatenated "minicircles" run into the gel in proportion to topoisomerase II activity.

The authors note that topoisomerase II could be involved in the recombination event at LINE sequences, but they do not mention whether it may be due to the enzyme in the trypanosome of the cellular host. Human topoisomerase II inhibiting drugs are used primarily for cancer chemotherapy (etoposide, doxorubicin and, most recently, pixantrone) but we commonly use as antibiotics bacterial topoisomerase II (DNA gyrase) poisons such as the fluoro-4-quinolone antibiotics because they are more selective for bacteria vs. human topo II.

Therefore, I'll be interested to learn of follow up studies to this paper on the mechanism of recombination. Should the event be catalyzed by the trypanosomal topoisomerase II, there may be a therapeutic opportunity to selectively inhibit this activity responsible for the long-term sequelae of Chagas disease.

Fascinating. Thank you.

Interesting in the extreme. Thanks, Ed.

I'm wondering... There is a longstanding controversy about what disease afflicted Charles Darwin. Peter Medawar argued it was Chagas. (There was also a recent article in the Christmas edition of BMJ that suggested it was cyclical vomiting syndrome or something). Could it be possible to test the Chagas hypothesis by looking at the DNA of his descendants?

Well that gets my vote for Comment of the Year.

Fascinating! I haven't had the time to read the whole paper yet but I'm wondering if the study showed whether the transferred sequences are from T.cruzi itself or from parasitic transposon-like elements that previously parasitized the T.cruzi genome? Does it mention which genes were transferred?

IANAS (I am not a scientist), but as I understand it if a parasite somehow inveigles itself into a host's germ line, as you mention sometimes happens here, it eventually reaches a less hostile relationship with the host. The host's survival becomes a positive factor for the parasite instead of a matter of indifference to it, because host reproduction helps carry on the parasite's line too. Charles Darwin just needed to wait a further 100,000 years or so. (No mockery intended of the immortal Charles).

Suddenly, a thousand B-movies become plausible; being bitten by a bloodsucker really can alter your genes.

I imagine it still might be possible to get some of Darwin's DNA directly. (?)

Getting Darwin's DNA directly? I don't know. I suppose it might be, but it all depends on what's preserved of him and how well. (Is there hair?). I doubt we could exhume his body...

Truly fascinating stuff and also quite logical. The intracellular amastigote cycle of the parasite makes it likely to occur DNA swapping if the cell reacts to the infection or if the cell dies from the infection. It probably works both ways but it might be a little harder to identify human genes in the right T. cruzi unless you do a populational study. Hm, that's actually more interesting than my old line of research on Chagas disease.

Evolution without genes - prions can evolve and adapt too

edyong — Thu, 31 Dec 2009 13:00:19 +0000

Evolution without genes - prions can evolve and adapt too

If you search for decent definitions of evolution, the chances are that you'll see genes mentioned somewhere. The American Heritage Dictionary talks about natural selection acting on "genetic variation", Wikipedia discusses "change in the genetic material of a population... through successive generations", and TalkOrigins talks about changes that are inherited "via the genetic material". But, as the Year of Darwin draws to a close, a new study suggests that all of these definitions are too narrow.

Jiali Li from the Scripps Institute in Florida has found that prions - the infectious proteins behind mad cow disease, CJD and kuru - are capable of Darwinian evolution, all without a single strand of DNA or its sister molecule RNA.

Prions are rogue version of a protein called PrP. Like all proteins, they are made up of chains of amino acids that fold into a complex three-dimensional structure. Prions are versions of PrP that have folded incorrectly and this misfolded form, called PrP^Sc, is social, evangelical and murderous. It converts normal prion proteins into a likeness of its abnormal self, and it rapidly gathers together in large clumps that damage and kill surrounding tissues.

Li has found that variation can creep into populations of initially identical prions. Their amino acid sequence stays the same but their already abnormal structures become increasingly twisted. These "mutant" forms have varying degrees of success in different environments. Some do well in brain tissue; others thrive in other types of cell. In each case, natural selection culls the least successful ones. The survivors pass on their structure to the "next generation", by altering the folds of normal prion proteins.

This process follows the principles of Darwinian evolution, the same principles that shape the genetic material of viruses, bacteria and other living things. In DNA, mutations manifest as changes in the bases that line the famous double helix. In prions, mutations are essentially different styles of molecular origami. In both cases, they are selectively inherited and they can lead to adaptations such as drug resistance. In prions, it happens in the absence of any genetic material.

If prions can evolve, and if they can show the same sort of adaptive resistance as bacteria or fungi, does this mean that they are alive? Charles Weissman, who heads up Li's lab, doesn't think so on the grounds that prions are completely dependent on their hosts for reproduction. They need normal proteins that are encoded within the genome of their host to make more copies of themselves.. He says, "The remarkable finding that prions can mutate and adapt to their environment imbues them with a further attribute of living things, without however elevating them to the status of being 'alive'."

There are many distinct strains of prion. Each is a version of PrP^Sc folded in a subtly different way, and new strains can arise out of the blue. Working out their exact structure has been difficult and they're usually characterised by the symptoms and disease they cause, and how long it takes for these to become apparent.

Li found that prions taken from brain tissue are different to those grown in cells cultured in a laboratory. The brain-adapted prions are capable of infected nerve tissue and they're resistant to a drug called swainsonine (swa) that completely blocks the growth of other strains. The cell-adapted prions lack both these abilities but they're better at growing in cell cultures.

When Li transferred brain prions into cell cultures, she found that they gradually adapted to their new environment. By the 12^th 'generation', they were indistinguishable from cell-adapted prions. They had lost their ability to infect nerve tissue in favour of the ability to grow faster in cultured cells. When Li returned these prions back to brain tissue, the brain-adapted forms once again rose to dominance.

Li also found that prions are capable to evolving resistance to drugs. She treated the cell-prions with swa. At first, the drug blitzed the prion population, slashing the proportion of infected cells by five times from 35% to 7%. But the rogue proteins staged a resurgence, bouncing back to infect around 25% of the cells. After just two rounds of growth, prions from cells that were exposed to swa completely resisted the drug. If the drug was removed, they faded into the background once more as the non-resistant forms took over again.

Further experiments showed that the resistant strains were already there in the population. But their slower growth rates mean that they're typically in the minority, accounting for just 1 in 200 prions. When swa blasted the population, these resistant few rose to dominance. Li says that prion populations consist of a multitude of strains and substrains, all of which are different ways of folding the same sequence of amino acids. Evolutionary pressures from the environment determine which of these strains is in power.

But mutants can arise out of the blue too. Even if a population consists entirely of the same strain (which you can set up through cloning), resistant or sensitive mutants develop spontaneously in a very short span of time. Prions, it seems, are very quick to adapt.

The fact that prions can evolve drug resistance so quickly is important news for scientists trying to find new treatments for prion diseases, such as Creutzfeld-Jacob Disease (CJD) and bovine spongiform encephalitis (BSE). Rather than trying to target the abnormal proteins themselves, it might be better to reduce the levels of the production of the normal PrP in the first place. The former tactic could be easily thwarted by the rise of resistant strains, while the latter tactic denies natural selection of raw materials to work with.

Reference: Li et al. 2009. Darwinian Evolution of Prions in Cell Culture. Science DOI: 10.1126/science.1183218

More on prions:

edyong Thu, 12/31/2009 - 08:00

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Very interesting. But I think it's another reason to review the definition of life. If prions are capable of transmitting some quite complex information (breeding), and this information is subject to random errors (mutation) which are then selected by environmental pressure (evolution), then they are similar to viruses. And there are other parasites (like chlamydia) who depend on their host completely, yet we call them living organisms...

Fascinating and somehow scary. I wonder what other things in this world are like prions, not alive, but adaptable.

Quick question: What do you mean by "Darwinian evolution"? Should we say âNewtonian gravityâ or âEinsteinian(?) relativityâ as well?

Evolution by itself merely means "change over time". Darwinian evolution specifically indicates change via mutation and natural selection. Although, I agree that it's unnecessary in contexts like this to specify. It's not like, say, anyone's suggesting Lamarkian evolution.

Cool is all I can say.

Reducing levels of a brain protein doesn't seem like a good idea. Has anyone ever tried to raise a mouse or something with the appropriate genes knocked out?

Also, doesn't evolution predict that there won't be a clear line between life and non-life; that wherever we try to draw a line, eventually something will be found that exists in the gray area?

For a good discussion of evolution and why it does not necessarily require either RNA or DNA, see Dennett's Darwin's Dangerous Idea.<\i>

Really, what you need is a stable substrate of some sort (be it 1s and 0s or biological goo); high fidelity replication (but not 100% accuracy!); and a selection function that roots out some of the resultant offspring.

Dennett's characterization has the advantage of working equally well for genetic algorithms in computer science and for biological systems, including prions.

wait.

prion populations consist of a multitude of strains and substrains, all of which are different ways of folding the same sequence of amino acids.

That much I'll buy. How, though, do the different strains "breed" (nearly) true? How is it that one folded protein causes another to misfold in exactly the same way, while another protein (identical amino acid sequence) that's folded differently induces this precise different fold instead?

Do they know that it's not just each prion inducing a variety of slightly different folds, which are then culled (by what?) to give the differential tissue results?

There's an important chunk of mechanism missing here, and it's not anything like evolution by natural selection if there is nothing like inheritance.

Duh. What's so fascinating in this study?

We've known for ages that if you have an imperfect replicator and selective pressure, then you'll get evolution. In fact, we routinely use genetic (sic!) algorithms in software to exploit this fact.

Also, the word 'genetic' itself is NOT related in any way to genes and/or (R|D)NA. Look it up in the dictionary.

Thus the Wikipedian definition: "change in the genetic material of a population... through successive generations" is absolutely correct. In case of prions, the genetic material is the prion itself.

BSE does not mean Bovine Spongiform ENCEPHALITIS it means
Bovine Spongiform Encephalopathy.

Encephalitis means inflammation of the brain, encephalopathy is a broader term relating to any number of possible causations affesting the structure of the brain.

Encephalitis could be termed as coming under the general heading of encephalopathy but the term Bovine Spongiform Encephalitis is misleading.

Also, the word 'genetic' itself is NOT related in any way to genes and/or (R|D)NA. Look it up in the dictionary.

No, YOU look it up in "the" dictionary, please, and then link to the particular dictionary definition that you think supports this assertion.

Prions are not "genetic material." They are not inherited in any meaningful sense.

What is apparently/putatively/allegedly passed on is a folding pattern. So far what I understand is that there is variation in folding patterns and that different patterns tend to accumulate in diffeent tissues.

What is missing (afaict; please set me straight if I am woti)are 1) evidence that each variant folding pattern induces an identical folding pattern in other (sequence-identical) proteins (occasional "mutation" notwithstanding). The null hypothesis here would be that initial variation in induced folding patterns is uncorrelated to the folding patterns of the inducing prions.
2) information about the putative "selection pressures" that favor the persistence of different folding patterns in different tissues.

Even with information about issue 2, though, the point remains that environmental sorting alone does not cause evolution by natural selection, nor true adaptation. This is why evolutionary biologists are careful to distinguish between phenotypic selection--the sorting of variant phenotypes by differential reproduction in a particular environment--and the evolutionary response to selection, which is a resultant change in population/genepool-level allele frequencies (= evolution). Without heritability (e.g. if all variation is of purely environmental cause), even strong selection does not necessarily cause any evolution in response.

In short, the analogy to evolution by natural selection relies entirely on the analogy to inheritance, which I am still not buying.

Sven, the issue you bring up was discussed over at ERV, and someone drug up a few papers on true-breeding traits in prions. Not all their "interesting" traits are heritable, of course--in fact, the drug-resistance trait discussed in ERV's post turned out to not to be--but apparently many traits are.

The Li et al. paper treats the existence of individual true-breeding strains as well-established:

Prions occur in the form of distinct strains, originally characterized by the incubation time and the neuropathology they elicit in a particular host (2). Many different strains can be propagated indefinitely in hosts homozygous for the PrP gene (Prnp); the protein-only hypothesis assumes each strain is associated with a different conformer of PrPSc (3â5), implying that there are as many stable conformations of PrP as there are stable prion strains that can be propagated in a particular mouse strain, perhaps fifteen or more (6).

The concept of âconformation templatingâ at the protein level was first supported by cell-free conversion experiments (7) and extended by the development of protein misfolding cyclic amplification (PMCA), which mimics PrPSc autocatalytic replication in vitro (8).

The important bit is "in a particular mouse strain." These are highly inbred and virtually 100% homozygous strains of mice, so if distinct true-breeding strains of prions can be bred within mice from the same lineage, the differences in prion strain are probably due to heritable properties in the prions themselves, rather than differences in the mouse hosts.

I think this is a very important demonstration of the way biomolecules probably function which is that they adopt a finite number of conformers with a further degree of conformational plasticity in key functional domains e.g. catalytic sites etc

I favour the induced-fit model for bimolecular interactions which underlie the specificity of biological systems. In this case it would be expected that the are a finite number of strains for a particular PrP gene and thus a limited level of infectivity. it should be possible to demonstrate this with existing technology, although I do not know enough about these molecules!

"No, YOU look it up in "the" dictionary, please, and then link to the particular dictionary definition that you think supports this assertion."

Sorry for 'the', English is not my native language and articles is my weak spot. Here's the definition, anyway: "Genome is the entirety of an organism's hereditary information".

It's that simple. There's no mention of DNA or RNA or folding pattern of a peptide chain. In fact, you can make artificial organism whose genome will be encoded in a bit of silicon.

"Prions are not "genetic material." They are not inherited in any meaningful sense.
What is apparently/putatively/allegedly passed on is a folding pattern. So far what I understand is that there is variation in folding patterns and that different patterns tend to accumulate in diffeent tissues. "

Prions ARE a genetic material. It is 'inherited', prions pass their folding patterns to their 'offspings'.

Prions are a bit special in that their 'phenotype' is also their 'genotype'. But it's not that different from viriods, for example.

Treating tinnitus with an individually tailored piece of music

edyong — Tue, 29 Dec 2009 08:30:48 +0000

Treating tinnitus with an individually tailored piece of music

Many of us have just spent the Christmas season with a persistent and irritating ringing noise in our ears. But now that the relatives have gone home for the year, it's worth remembering that a large proportion of the population suffers from a more persistent ringing sensation - tinnitus. It happens in the absence of noise, it's one of the most common symptoms of hearing disorders, and it's loud enough to affect the quality of life of around 1-3% of the population.

There have been many suggested treatments but none of them have become firmly established and most simply try to help people manage or cope with their symptom. Now, Hidehiko Okamoto from Westfalian Wilhelms University has developed a simple, cheap and enjoyable way of reducing the severity of the ringing sound. The treatment has showed some promise in early trials and even better, it is personally tailored to individual patients.

The method is simple. Find out the main frequency of the ringing sound that the patient hears - this becomes the target. Ask the patient to select their favourite piece of music and digitally cut out the frequencies one octave on either side of this target. Get the patient to listen to this "notched" piece of music every day. Lather, rinse and repeat for a year.

Okamoto tried this technique in a small double-blind trial of 23 people, eight of whom were randomly selected to receive the right treatment. Another eight listened to a piece of music that had a random set of frequencies cut out of it, while seven were just monitored. The treatment seemed to work. After a year, the treatment group felt that their ringing sensation was around 30% quieter, while the other two groups showed no improvements.

This is obviously a very preliminary study with only a small number of people. Nonetheless, it's encouraging because finding workable treatments for tinnitus has been difficult because until recently, we didn't really understand what causes it. The key point is that it's not a problem with the ears, but with the brain - specifically, the auditory cortex which processes the sounds we hear.

The neurons of the auditory cortex are arranged in a sort of frequency map, with cells that respond to low frequencies at one end and those that respond to high frequencies at the other. Distortions or damage to parts of this map result in tinnitus. This could be due to an injury directed at specific groups of neurons. It could even be due to the gradual hearing loss that accompanies old age.

As the connections between the auditory cortex and other parts of the brain start to wane, some neurons within the cortex stop working properly. But rather than slide into inactivity, they become rewired so that they respond to the same frequencies as their neighbours. Certain parts of the frequency map essentially fuse with one another. Indeed, scientists have found that the activity of the auditory cortex neurons corresponding to the tinnitus frequency is greater than normal, and the more active they are, the more intrusive the ringing is. It's a case of the brain's own flexibility becoming its undoing.

Okamoto's treatment was inspired by earlier work, which showed that you could reduce the activity of neurons in the auditory map by playing people music with the frequency in question removed. It's possible that listening to this music silences the overactive neurons corresponding to the notched frequency. Alternatively, these neurons could be actively suppressed by their buzzing neighbours.

Either way, Okamoto found that the notched music reduced the activity of the affected neurons within the auditory cortex of his patients. These physical measurements matched the patients' descriptions of their own experiences, and the two measures were strongly related.

Okamaoto thinks that getting patients to pick their own favourite music was an important part of the technique. The music we like can grab our attention and triggers the release of dopamine, a chemical involved in feelings of reward and pleasure. It's also important for rewiring parts of the cortex, when our brain needs to be flexible.

Reference: Okamoto et al. 2009. Listening to tailor-made notched music reduces tinnitus loudness and tinnitus-related auditory cortex activity. PNAS doi: 10.1073/pnas.0911268107

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edyong Tue, 12/29/2009 - 03:30

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That's interesting. I wonder if the brain goes wonky when hearing is impaired. I noticed some tinnitus when I've had outer ear infections.

I'm one of the 1-3% who suffer from tinnitus enough to affect my quality of life. It's really really unfun. But as it happens, I've actually been using a treatment very like this for years. I have a very high frequency noise, and when I get an attack, I play music with lots of (relatively) low frequency stuff. Or even any music at all.
My friend has five different noises; I wonder how this treatment would work with her?

Also, it's not entirely accurate that tinnitus occurs in the absence of external noise. It is certainly less irritating, and less noticable when there is external noise. However, depending on the type and volume of external noise, I can usually hear my tinnitus anyway. If I actively listen for the noise, I can usually pick up on it.
It is actively exacerbated by certain kinds of noise as well. I especially avoid external noise of frequencies near what I hear in my head, as that often encourages or triggers an attack. I have more than one cowered in corners with hands over my ears humming frantically as the neighbour mowed the lawn.
I can also not bear to be in a house with a tv on standby. It makes a noise that I can hear through three walls and it's completely unbearable.

I've got some damage in the left ear which gives me a little bit of tinnitus. It's not bad and I can pretty much ignore it now.

At some point I need to do something about it though. Either a CI or the new laser treatment to fix the screwed up conduction mechanism in that ear would be good.

I wonder if wearing a hearing aid type device that would filter out the surrounding octaves for a prescribed time each day would help-- so that the targeted frequencies would be eliminated from whatever sound was going on. Except singing in the shower!

This is really interesting. I have pretty constant but low-volume tinnitus (it's only really noticible if it's quiet, but I can hear it most of the time) that has a range of frequencies (all of them quite high). If this proves to be a viable treatment, I hope it is as inexpensive as it seems like it ought to be. A whole cd of frequency-deleted tracks would be even better, just from a listener's point of view--you could choose a new one daily, so there'd be perhaps 2 weeks' worth of songs rather than just 1 (listening to a song 26 times a year instead of 365 sounds excellent).

I would love to try this technique. Do you have any suggestions for how to digitally remove frequencies from a piece of music?

Dorene

Really nice advance I want to try, i think all of us want it. Do anybody knows how to try the treatment? How to find the exact frecuency of the tinnitus? and how to remove the frecuency from the song? I have tried with some software but i feel i am wasting time, somebody can help?

Iâm a practicing psychologist who happens to suffer from tinnitus. Iâve spent a lot of time dealing with my own tinnitus, and helping other people deal with theirs. I am guardedly optimistic at the prospect of a treatment that can reduce the ringing. If this really does reduce it, then that would be terrific. At the same, I think that a large part of tinnitus-related impairment is related to the anxiety and anger that result from attempts to AVOID the ringing in our ears. Personally, I have found that applying cognitive-behavioral principles and practicing mindfulness meditation have been incredibly helpful to me. I still hear the noise all the time, but I am much less frequently annoyed or anxious about it than I used to be. So, until this technology is widely available, it might be helpful for folks to try CBT and mindfulness approaches.

You have broaden my knowledge regarding tinnitus. It explained
well and elaborate the causes and effect. Hope to
read more about these symptom. thanks

IntÃ©ressent, en effet attention tout de mÃªme pour les gens sensibles aux bruits, aux hyperacousies, a la qualitÃ© du son Ã©coutÃ© et aux autres personnes qui mettent encore le son trop fort, j'en avait dÃ©jÃ entendu parler sur le site http://www.traitementacouphene.com quand je m'Ã©tais inscrit, je trouve que sa se rapproche fort de la TRT.

En tout cas merci pour cette article, et bonne continuation pour le blog.

Cordialement. Nicolas.