DNA sequencing in a holey new way

By Jason Palmer Science and technology reporter, BBC News

DNA molecules will be held in place by tiny voltages within the nanohole

IBM will announce on Tuesday how it intends to hold DNA molecules in tiny holes in silicon in an effort to decode their genetic secrets letter by letter.

Their microelectronic approach solves one of two long-standing problems in "nanopore" DNA sequencing: how to stop it flying through too quickly.

The aim is to speed up DNA sequencing in a push toward personalised medicine.

IBM's chief executive Sam Palmisano will announce the plans to the Medical Innovation Summit in the US on Tuesday.

While sequencing the genomes of humans and animals has become relatively routine in a laboratory setting, the ability to quickly and cheaply sequence genomes of individuals remains out of reach.

That widely available genetic information will help bring about the era of "personalised medicine" - in which preventative or therapeutic approaches can be tailored to individuals based on their specific genetic makeup.

All-electronic

"There have been a number of attempts to sequence DNA much faster than it was sequenced when the first human genome was announced," said Gustavo Stolovitzky, a computational biologist from IBM.

Individual genetic information will lead to more directed therapies

"All of them use some complicated sample preparation - chopping the DNA, amplifying, reverse transcribing - and some sophisticated and labour-intensive optics," Dr Stolovitzky told BBC News.

"All this makes sequencing faster, but still slower and more expensive than it needs to be before it could be used for personalised medicine."

Instead, Dr Stolovitzky and colleagues are pursuing a method involving silicon peppered with holes just three billionths of a metre across - 20,000 times thinner than a human hair and just wide enough for one strand of DNA to pass through.

Researchers have been looking into using such nanopores for a number of years - mimicking the proteins in cell membranes that perform the same trick - because using a semiconductor offers significant advantages over biochemical and optical techniques.

"DNA nanopore sequencing continues to be one of the great candidates to do fast and cheap DNA sequencing without sample preparation or sophisticated optics, using only electronics to fetch the signal out," Dr Stolovitzky said.

Moreover, the approach could be done in a "massively parallel" way - that is, with hundreds or thousands of DNA strands passing through an array of holes on a single chip.

Trap stack

The idea is conceptually simple but devilishly difficult to carry out. Because DNA naturally carries a net electric charge, simply applying a voltage across the two sides of the chip drives the DNA strands through the holes.

However, the DNA tends to pass through too quickly to decode the identities of the individual nucleotides - letters of the genetic code - as they pass.

More than that, until they can study DNA strands moving at a more carefully controlled pace, researchers cannot develop the techniques to query the precise nucleotide they have trapped in place.

The Blue Gene supercomputer simulated the nanopores' every atom

The IBM team have now hit on the idea of a chip composed of a stack of layers, each of which can hold a precisely-controlled voltage in a thin layer inside the nanopore.

These smaller voltages trap the negatively charged chemical groups called phosphates that separate individual nucleotides.

By cycling this internal voltage, the DNA strand can be made to advance one nucleotide at a time.

The team has used IBM's Blue Gene supercomputer to simulate the process in order to ensure it would work, and the team has built prototypes of the trapping nanopore. Tuesday's announcement marks the beginning of the testing and refinement stages of the process.

What remains is to investigate the means to identify the individual nucleotides trapped inside the nanopores, which is likely to rest on measuring some electrical or electronic property of each as it passes.

Stas Polonsky, another IBM researcher working on the project, remains convinced that with the benefit of a trapping mechanism, this last problem is tractable.

"As a company we have a lot of expertise with electrical measurements," he said.

"We have nanopores plus the whole arsenal of microelectronics - we can integrate all these ultrasensitive circuits right on a chip, which will boost the sensitivity for measurements tremendously."

Source

Why am I the short fat one?

By Dr Alexander van Tulleken Presenter, The Secret Life of Twins

Twin brothers, but not quite identical

My identical twin brother Chris is 2cm taller than me.

Barely noticeable you would think. I can see what it is like to be him by standing on tip-toes just a little and frankly the world does not look much different from up there.

Nonetheless it bothers me: I could have been that tall. I have exactly the same genes as my brother.

Genes that, in the right environment, could have made me a full 185cm tall as opposed to my current 183cm.

Something, somewhere went wrong and I got stunted. Not by much but it is a reminder of what could have been.

And that is the real problem.

It is not the height, not that trousers fit him a little better or that he does not need to reach as far to change a light bulb.

It is that I wonder how many other things I am missing out on.

Ten points of IQ here, some grey hair there. Perhaps I will need glasses at age 35 instead of 40.

Identical twins Chris and Alexander took part in a pain tolerance experiment

Most people do not have any way of knowing whether or not they are getting the most out of their genes but if you have a twin sibling then you have an exact comparison.

So how did these differences arise?

The differences between identical twins - people who should be exactly the same - are becoming increasingly useful to medical researchers interested in everything from mental illness to our ability to do maths.

Long term changes

Most people are used to thinking of our DNA as a fairly fixed code, a bit like a blueprint for a building.

We know that some things can change the code itself - exposure to radiation can cause mutations that lead to an increased risk of cancer for example - but usually the code remains the same.

Finnish twins Miia (left) and Noora (right) are 24-years-old Noora weighs 17kg more than Miia due to their different lifestyles But Miia is also likely to put on weight if she becomes less physically active

However, production of the molecules for which our genes are responsible - things like digestive enzymes and muscle protein - is constantly getting switched on and off.

And it seems that some environmental influences can have much more lasting effects - permanently activating or inactivating certain genes.

It is becoming apparent that this aspect of genetic control - a process dubbed epigenetics - is very important in human health.

In 1944 there was a severe famine in Holland. The children born during this period are more susceptible to diabetes, obesity and heart disease compared to siblings who were older during the famine.

It seems that the period of starvation prompted their bodies to switch certain genes on or off to cope with the lack of food.

These changes may, in subsequent times of plenty, have made them gain weight and get diabetes.

This change in the particular genes we express is controlled chiefly through a process called "methylation" in which chemical groups are attached to the DNA molecule to tell the body whether or not to use the "methylated" genes.

It is one of the ways in which our bodies' attempt to adapt to changing environments.

Twins play a key role in discovering more.

In the summer of 2009 Chris and I joined the twin research study at St Thomas's Hospital where we were investigated in great detail.

They measured our height, weight, bone density, grip strength even ability to hear if a nursery rhyme is in tune.

All these are traits that are to some extent genetic.

Other differences

It turned out that we are different in more ways than height.

For a start I was 15kg heavier than my brother.

What about my missing 20mm of height? It is probably an epigenetic effect caused by some long forgotten environmental difference when we were little

Of the thousands of twins enrolled in the research program only 10 were more different in weight than us.

Professor Tim Spector who leads the research unit was frank: "You're (he meant me) a disgrace."

My excess weight, unlike my brother's excess height, is easily explained.

I have been living in America and eating too much. So far no surprises.

But environmental exposure to a lot of cheap, high-fat food in America may have caused more than temporary weight gain.

It may have permanently altered the way my genes are expressed.

Scientists are only just beginning to understand these processes but it is possible that I may have permanently altered my metabolism to accommodate those extra pounds: the health effects could last a long time.

Key role in disease

Epigenetics seems to play a role in a large number of diseases.

Twins studies show us that some cancers are not caused by DNA mutations but by epigenetic changes, which potentially offers new targets for drugs.

Similarly with heart disease or diabetes we might one day be considering therapies that change our epigenetics.

This is a long way off but twin studies are beginning to shed new light on how our bodies react to the environment.

What about my missing 20mm of height? It is probably an epigenetic effect caused by some long forgotten environmental difference when we were little.

I will never get it back but if it is of use to medical science I can live without it.

The Secret Life of Twins is on BBC One on Wednesday 30 September at 2100 BST.

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Court order served over Twitter

Mr Blaney believes it is the first time a order has been served via Twitter

The High Court has given permission for an injunction to be served via social-networking site Twitter.

The order is to be served against an unknown Twitter user who anonymously posts to the site using the same name as a right-wing political blogger.

The order demands the anonymous Twitter user reveal their identity and stop posing as Donal Blaney, who blogs at a site called Blaney's Blarney.

The order says the Twitter user is breaching the copyright of Mr Blaney.

He told BBC News that the content being posted to Twitter in his name was "mildly objectionable".

Mr Blaney turned to Twitter to serve the injunction rather than go through the potentially lengthy process of contacting Twitter headquarters in California and asking it to deal with the matter.

UK law states that an injunction does not have to be served in person and can be delivered by several different means including fax or e-mail.

Danvers Baillieu, a solicitor specialising in technology, said it was possible for anyone to approach the court about any method of serving an injunction if the traditional methods are unavailable.

"The rules already allow for electronic service of some documents, so that they can be sent by e-mail, and it should also be possible to use social networks," he said.

Mr Blaney decided to use Twitter after a recent case in Australia where Facebook was used to serve a court order.

The blogger, who is also a lawyer and owns the firm serving the order, said that he thought that it was the first time Twitter had been used to deliver a court order.

The injunction - known as the Blaney's Blarney Order - is due to be served at 1930 BST and will include a link to the text of the full court order.

Source

Social isolation 'worsens cancer'

Stressed mice grew larger tumours

Social isolation may make cancer more deadly, US research on mice suggests.

Researchers found the social environment can modify the biology of the disease - and lead to significant differences in outcome.

Female mice stressed because they were separated from their mothers developed more and larger mammary gland tumours than more contented animals.

The University of Chicago study appears in the journal Cancer Prevention Research.

It is now widely recognised that stress plays a part in illness, but no-one really knows how much Oliver Childs Cancer Research UK

Previous research has suggested that social support can improve health outcomes for patients with breast cancer, while social isolation has been linked to an increased risk of death from several chronic diseases.

The Chicago team worked with mice genetically predisposed to mammary gland cancer.

They found changes in the activity of genes that play a role in tumour growth in the stressed animals, suggesting that they may have been directly influenced by surging levels of stress hormones.

The researchers said more work was needed to pin down exactly which cell types are affected.

New treatments

But researcher Dr Suzanne Conzen said the study raised hopes of new ways to block cancer growth.

She said: "Given the increased knowledge of the human genome we can begin to objectively identify and dissect the specific alterations that take place in cancer-prone tissues of individuals in at-risk environments and that will help us to better understand and implement cancer prevention strategies."

Dr Caryn Lerman, editor of the journal, said: "This study uses an elegant preclinical model and shows that social isolation alters expression of genes important in mammary gland tumour growth."

Professor Thea Tlsty, of University of California San Francisco, said it had long been known that psychological factors could influence disease, but not how.

She said the study added to growing evidence that chemicals circulating in the blood - such as stress hormones - could influence the development of cancer by turning genes on and off within cells with the potential to turn malignant.

Previous work has also suggested that depression can have a negative effect on cancer prognosis.

Oliver Childs, of the charity Cancer Research UK, warned against drawing any firm conclusions.

He said: "These experiments were carried out in mice, so certainly do not prove that the stress caused by social isolation causes cancer to get worse in humans.

"It is now widely recognised that stress plays a part in illness, but no-one really knows how much and there is no good evidence from controlled studies that stress contributes to cancer progression."

Source

C. diff rise due to 'gene switch'

Most deaths from C. difficile occur in the over 65s

The rise in Clostridium difficile infections in recent years is due to genetic changes rather than dirty hospitals, say UK researchers.

Comparison of an historic strain and a strain from the outbreak at Stoke Mandeville hospital in 2003 found it had evolved to be more virulent.

It can spread more easily and cause more severe symptoms, the team reports in Genome Biology journal.

NHS trusts have a target to cut C. difficile infections by 30% by 2010/11.

The bacteria is present in the gut of as many as 3% of healthy adults and 66% of infants.

It rarely causes problems in healthy people but can lead to illness when the normal balance of bacteria in the gut is disrupted, for example with use of certain antibiotics, and it is the leading cause of hospital-acquired diarrhoea.

The deep clean programme was never going to work against this organism in the long term Professor Brendan Wren

In the past five years, a new group of highly virulent C. difficile strains has emerged - PCR-ribotype 027 - which cause more severe diarrhoea and a higher rate of deaths.

Analysis of the full genome of the "hypervirulent" strains and an older strain showed the bacteria has acquired genes which enable it to survive better in the environment, spread more easily and make patients more severely ill.

In all, five different genetic regions appear to have accumulated in the bacteria in past couple of decades, the team reported in Genome Biology.

Fighting back

The number of cases of C. difficile has risen dramatically since the 1990s, although latest figures show cases are now consistently falling.

Stoke Mandeville Hospital saw two major outbreaks of C. difficile between 2003 and 2006 that caused 35 deaths.

Study leader Professor Brendan Wren, from the London School of Hygiene and Tropical Medicine, said the study would help scientists understand how C. difficile became so aggressive.

"These strains came from nowhere and the sudden rise in C. difficile was due to their spread.

"The bugs are fighting back and the one clear thing that comes out of this study is it is not down to cleaning but that the strain has evolved with new chunks of DNA.

"The deep clean programme was never going to work against this organism in the long term."

Hygiene measures are still needed to keep the infection under control, he added.

A spokeswoman for the Health Protection Agency said it closely monitored the evolution of C. difficile strains.

"All strains of C. difficile require intervention and control - the intervention involved when dealing with the 027 strain is no different than how any other strain is treated.

"All C. difficile requires treatment and vigilant infection control procedures in order to reduce rates of infection."

Source

California mulls legalising marijuana

Emilio San Pedro BBC News

The Bulldog Cafe is allowed to sell marijuana for medicinal purposes

In 1996, voters in California approved a referendum that made it legal for the first time in decades in the US for people to consume cannabis for medicinal purposes.

More than a dozen states have followed suit since and several others - the most recent of which is Massachusetts - have approved laws decriminalising the possession of small amounts of the drug.

Now, there are moves afoot in California to go further to fully legalise marijuana.

Evidence of the impact that the approval of medicinal marijuana has had on some areas of California is clear in Oakland.

Across the bay from San Francisco, it has come to be known as Oaksterdam, in a nod to the symbolic global capital of marijuana deregulation, Amsterdam.

The relaxed approach to marijuana use in this part of Oakland has led to the opening of several marijuana dispensaries.

They are establishments in this once deprived area of town which sell a broad array of cannabis related products, from food products such as brownies and cereal bars laced with cannabis to traditional marijuana for smoking.

Oaksterdam University

"This is where it all started," says Richard Lee, a leading advocate for the legalisation of cannabis, pointing to a building where the first ever dispensary was opened in 1996.

His sense of excitement is palpable as he shows me around Oaksterdam, which beyond dispensaries is also home to a facility where state residents can go through the process of getting the ID needed for their right to use cannabis for medical purposes.

Richard Lee runs Oaksterdam University which opened in 2007

The area is also home to the Oaksterdam University, which Mr Lee runs.

He shows me around the student union of the university, which he describes as a trade school for all of those interested in finding a place in the thriving cannabis trade that medicinal marijuana has spawned.

Mr Lee tells me that making cannabis use legal makes economic sense but would also help in the fight against the Mexican drugs cartels.

"According to some estimates, the Mexican cartels get about 60-70% of their money - their profit - from cannabis," he tells me.

"So if we cut that out of the equation then theoretically 60-70% of the violence they perpetrate would be cut out, because they'd have less money for the guns and weapons and ammunition to kill people and to spend on bribing officials and all the rest," Mr Lee says.

Trailblazing

That perspective, along with the fact that the California state authorities estimate that marijuana could bring in nearly $1.5bn a year in much needed tax revenue if it were legalised, has led to an increased support among the state's voters for the full legalisation of the drug.

And, politicians like Tom Ammiano, who represents one of the most liberal districts of San Francisco in the California state assembly, have been paying close attention.

Mr Ammiano came into politics as a trailblazing gay rights activist in the 1970s and has long advocated greater tolerance for cannabis use.

Earlier this year, he took that approach one step further and introduced a bill in the California state assembly, which, if approved, would grant cannabis the same legal status in the state as alcohol and tobacco.

We like to say prohibition is chaos and regulation is control Tom Ammiano California State Assemblyman

That would put California ahead of even Amsterdam, where marijuana use is tolerated but not altogether legal.

Sitting with him in his office in the state government building in San Francisco, with its sweeping views of the city, it becomes very clear that his proposal is far from a flight of fancy.

He tells me he has been finding that more and more of his colleagues in the state assembly are coming around to seeing why moving towards legalisation makes perfect sense.

'Lighten up'

"People across the board, whether they're conservative or liberal, have come to realise that the so-called war on drugs has failed and failed miserably," Mr Ammiano says.

"In fact, it's costing us money instead of saving us money. This new approach would be a way for the policing efforts to be focused on the big bad guys, the cartels, with their violence and murder, and lighten up on the more minor offenses. We like to say prohibition is chaos and regulation is control," he adds.

"On the streets a drug dealer does not ask a kid for his ID before selling him cannabis," he concludes with an acerbic, humorous tone that serves as proof that he has, beyond politics, also had some success in his other career as a stand-up comedian.

But, despite his optimistic tone, Mr Ammiano says that he knows that those who oppose his proposal, including key figures in the medical and law enforcement community, are armed with statistics pointing to the damaging long-term effect of the drug and have the stamina and resources to wage a major fight to ensure that the bill never gets signed into law.

One of those opponents of the proposal is Ronald Brooks, the president of the National Narcotic Officers' Associations' Coalition, which represents more than 70,000 narcotics enforcement officers in the US.

We meet in the town of Redwood City, south of San Francisco, and as I get in his car, we drive past what appears to be a nondescript office building.

'Seriously flawed'

However, he tells me that, in the 1980s, it was a bank - the place where his partner on the police force was killed in front of him by a ruthless marijuana dealer, who was carrying out a bank robbery to fund his drug business.

He says experiences like that have strengthened his resolve that America can't allow itself to take on a more lenient approach to marijuana.

"This argument of freeing up law enforcement so that we can take on the cartels is seriously flawed," he tells me.

Ronald Brooks is firmly against the proposed change in the law

"This is really a hoax being perpetrated on the voters of California to authorise their political agenda - that is to legalise marijuana as one step to legalise drugs in America because they simply don't think that the government ought to control drugs," he adds.

"The people who are going to lose if this gets approved are the taxpayers because we're going to have increased costs associated with this, both healthcare and law enforcement costs, and the people who have to drive on the state's highways who are going to be in danger from being hit by someone intoxicated from using cannabis. This is simply a reckless public policy," he concludes.

Back across the San Francisco Bay in Oakland, specifically Oaksterdam, the patrons of the Bulldog Cafe are enjoying their legally sanctioned right to consume marijuana for medicinal purposes.

Emerging industry

Gary has travelled from Texas for the weekend to attend a seminar on the cannabis trade at the Oaksterdam University across the street.

He is in his 50s, but says he is hoping to take the information he has picked up in his course on the cannabis business and make a life-transforming move in the coming months to California.

"My girlfriend and I are interested in moving to California from Texas to become a part of this here. We're not quite sure where we fit in but we want to get into the business itself. We feel it's an emerging industry, and this is where I feel compelled to come," he tells me as the smell of cannabis wafts through the room.

Like Gary, there are hundreds of others participating in the courses at the Oaksterdam University on any given week.

Beyond that, there are more than 200,000 people in the state registered as consumers of marijuana for medicinal purposes.

As for Mr Ammiano's proposal to legalise marijuana in the state, that is still making its way through the California state assembly and it is difficult to say whether it will succeed or not.

What is clear, however, is that whatever the outcome of the legalisation proposal, the medical marijuana law and the multi-million dollar industry it has spawned appear to be here to stay in California.

Source

Q&A: Why Michael Moore Hates Capitalism

By Bill Saporito Saturday, Sep. 26, 2009

Michael Moore, director/writer/producer/star of the documentary Capitalism: A Love Story

Chris Pizzello / AP

Since his debut in 1979's Roger and Me, documentary filmmaker/agitator Michael Moore has aimed his blunderbuss of a lens against large American corporations and the institutions that he believes have flat-out screwed the working class. In his latest film, Capitalism, Moore ridicules the business philosophy that has blown up the economy, resulted in 6 million job losses and required more than a $1 trillion in bailout money to keep the banks afloat — while millions of people have lost their homes to foreclosure. He's a man who has made perpetual outrage an art form in every sense of the word. He had some choice words for TIME's business editor, Bill Saporito.

What brought you back to a film about the economy?
I've been thinking about this for about the entire 20 years I've been making movies. Most of the subject matter all comes back to the simple theme of an economic system that is unfair and unjust, in which a few people with a lot of money are making decisions that cause a lot misery and heartache for millions of people.

So it wasn't a specific incident?
The Republicans and the Right Wing gave permission for all of us to use words we haven't used before: capitalism and socialism. So let's have a discourse. They called Obama a socialist because he told Joe the plumber he wanted to spread the wealth around. Then we had the crash and a month later Bush is talking about the glories of capitalism. I don't' remember in my lifetime where the President starts off a speech says, "And now class, today's topic is capitalism." They started using these words, so now it's on the table. Let's talk about it.

Bank of America wants to give back the TARP money it borrowed. In one very funny sequence in Capitalism, you back up an armored truck to various banks and demand the return of our money. Maybe you were just a tad early?
And the AIG money? I don't think we're going to see any of that. You cannot steal money, and then invest the money and then give it back. You can't, let's say you are the president of the Kiwanis. You can't take the organization's money, go make a profitable investment and then slip it back. It's a felony. It's as if you beat up your spouse and then take your spouse to the hospital and then say: 'How about that: I took her all the way down to the hospital. That's the kind of guy I am.'

You've called the TARP program part of a financial coup d'etat. But if we get our money back, with interest, and the banking system reverts to doing what it should do, haven't the citizens won?
If you give me $700 billion per year, hey I have some good ideas. I can make some money with that, for me and for you. I'm going to have my best quarter if you gave me that money. I wonder how many people in the inner cities would love a little bailout money to get out the hole they are in and have one of their best years ever. This wasn't a gift; it was a theft. They stole the people's money by gambling with it. They took the pension funds of working people and gambled away their money, and went back to the same working people and asked for $700 billion more of their money.

Capitalism documents, very powerfully, sheriffs departments evicting families after their homes have been sold in foreclosure. Clearly, lots of people got put into bad mortgages by sleazeball operators. But didn't ordinary homeowners get greedy too?
That's a completely a diversionary tactic— how greedy can you get that you'd want a roof over you head? The FBI has said that 80% of mortgage fraud has been instituted by banks, not the people, not the home buyer; that's an FBI's statistic. The No. 1 cause of bankruptcies is medical bills. The mass media has done a pretty good job of placing blame on lower income people. For two hours this week I'm going to give the other side and here's the other side: don't blame the victim.

Real wages have not increased in a decade. You would think that labor unions would have been able to take advantage of the situation and recruit more members? Why haven't they?
This is the crux of the problem: because the Republicans and the right wing have been successful in almost eliminating unions, everyone else has suffered as a result. Because unions fought for good pay and benefits, so many other people who weren't union members benefited. By decimating the working class the corporations may have increased profits short term. But what they found is that [by forcing down wages] they couldn't sell their products to their employees three years down the road. The wealthy have never liked to pay for the labor that enriches them. Ever since slavery was eliminated, they have been trying to keep it as close to slavery as they can without violating the slave laws. When you have a United or a Continental pilot having to walk dogs as a side job [to supplement their salaries], you have admitted on the spot that capitalism doesn't work. What will historians and anthropologists call it? They are not going to call us employees or associates. They are going to call us wage slaves.

But aren't you really a model capitalist? You raise money. You hire people. You create a product and sell it to the public, bearing the risk and gaining the rewards that goes along with it.
Capitalism would have never let me be a filmmaker, living in Flint, Michigan with a high school education. I was going to have to make that happen myself. My last movie, I gave it away for free on the Internet: Slacker Uprising. If I were a capitalist I would not give my employees health insurance with no deductible, which I do, including dental, and paid pregnancy leave. That's not called capitalism, that's called being a Christian and someone who believes in democracy, so that everyone should get a fair slice of the pie.

What do you want people to feel when they walk out of the theater?
I want what all filmmakers want: I want people to walk out and say to each other: 'Wow, that was great way to spend two hours. That was exhilarating. I haven't seen anything like that in a while.'

Source

Thought Bonds Were Safe? Think Again

By Justin Fox Monday, Oct. 05, 2009

Illustration by Harry Campbell for Time

Investors have spent the past year or so relearning an important lesson: stocks are risky. From May of last year to March of this one, stocks in the U.S., as measured by the S&P 500 index, lost more than half their value. Many overseas stock markets did even worse.

After being burned, we humans tend to avoid what singed us and seek something soothing. High-quality bonds — in particular, the "risk free" ones issued by the U.S. government — were the most soothing investments of all during the financial crisis. While stocks were losing more than half their value, 10-year Treasuries returned more than 10% during that May-to-March period. And so — big surprise — investors have poured $240 billion into bond mutual funds so far this year, according to the Investment Company Institute. Stock funds — despite a big rebound in stock prices since March — have taken in less than $15 billion. (See 10 things to buy during the recession.)

Makes sense, right? Stocks, risky. Bonds, safe. Or at least safer. But risk in financial markets has an irritating habit of following investors around. The big rush into bonds — especially high-quality, low-risk bonds such as Treasuries and government-guaranteed mortgage securities — may have created a situation in which most of today's bond investors are bound to lose money. Not 50% losses, as in the stock market, but losses nonetheless. Which for many newcomers to bonds will be a big shock.

"They lost money on their house, they lost money on stocks," says Tom Atteberry, co-manager of the FPA New Income mutual fund. "They put money in bonds because they think it's safe. Then interest rates are going to rise on them, and they're going to lose money on bonds too."

The first time I heard Atteberry say this, I thought my ears needed cleaning. You see, FPA New Income is a bond fund — a very successful one. The mutual-fund raters at Morningstar named Atteberry and his co-manager and boss, Robert Rodriguez, 2008's fixed-income managers of the year. Yet Atteberry sees only trouble ahead. "I've got a bull market in bonds that's unsustainable," he contends. "It might last another six months. It might last another year. Is it going to last another three to five years? I don't think so."

Before we get into the details, it's worth going over the difference between stocks and bonds. When you buy stock, you get part ownership of a company. If it does well, you share in the gains. If it flounders, you lose money. Bonds, on the other hand, represent a promise from a company or government or other borrower to pay you back, with interest. When you buy a bond, you're making a loan. Sometimes bond issuers (a.k.a. borrowers) renege on their promises. The financial crisis originated with a rash of defaults on subprime mortgages that had been packaged into bonds. But the bond risks that vex Atteberry have little to do with that default risk — Uncle Sam will make the payments. The worry is over rising interest rates. (See pictures of retailers which have gone out of business.)

Right now the interest rate on a 10-year Treasury bond is about 3.5%. That could go lower — in fact, it did go lower at the height of the panic last fall, to just above 2%. But the likeliest future path for Treasury yields, Atteberry figures — on the basis of history and the fact that rates have been kept low this year by Federal Reserve purchases, investor demand and other factors — is up. If you own a 10-year Treasury bond yielding 3.5%, interest rates rising to 4% or 5% or higher mean your bond (with its rate stuck at 3.5%) falls in value. That's the logic of bonds: when interest rates rise, bond prices fall. Since 1981, when the 10-year Treasury rate topped 15% amid fears of runaway inflation, the interest-rate trend has been downward, bringing on a long bull market in bonds. One of these days, the trend will shift.

Atteberry is hoping to navigate the minefield ahead by holding only bonds that come due soon, which are less sensitive to changes in interest rates (but also have a lower yield than longer-dated bonds). He may ask FPA New Income's board for permission to increase the fund's limit on foreign bond holdings from its current 10%. And he has positive things to say about the inflation-indexed bonds that Treasury has issued since 1997, although he doesn't think they're a particularly good deal now.

Most bondholders, though, will find it hard to avoid losses. And what will retail investors do once bonds have burned them too? Atteberry thinks many will just put their money in the bank. The trade-off there is a measly return: the highest savings-account rate in the land is currently just 1.83%, according to Bankrate.com and most banks pay far less. Less than inflation. But hey, at least the money's safe.

Source

Gut worms protect against allergy

Hookworms have infected humans for thousands of years

Parasitic gut worms, such as hookworm, might aid the development of new treatments for asthma and other allergies, a study in Vietnam suggests.

Infection with hookworm and other parasitic worms is endemic in Vietnam, but rates of asthma and other allergies are low.

British and Vietnamese scientists gave local children treatment to clear their body of worms.

They found this led to an increase in dust mite allergy among the children.

The next step is to understand exactly how and when gut parasites programme the human immune system Dr Carsten Flohr University of Nottingham

Thanks to improved hygiene, practices parasitic worms have been mostly eradicated among human populations living in developed countries.

However, experts believe that over millions of years of co-evolution worms have found methods to dampen down host immune responses to prolong their own survival inside humans.

This relationship seems to have become so intertwined that without gut worms or other parasites, our immune system can become unbalanced, which, in turn, could contribute to the development of asthma and other allergies.

The latest study was conducted in a rural area of central Vietnam where two in every three children have hookworm and other gut parasite infections, and where allergies are extremely rare.

More than 1,500 schoolchildren aged six to 17 took part.

Regular tablets

Some of the children were given repeated tablet treatments to clear their body of gut worms.

The treatment did not produce any conclusive effect on rates of asthma or eczema.

However, those children who received the tablets did have a significantly increased risk of developing allergies to the house-dust mite.

Up to 80% of people with asthma also have allergies to house-dust mites and other environmental allergens.

The researchers said this strongly suggests that gut worms have the potential to tone down human immune responses.

Researcher Dr Carsten Flohr, of the University of Nottingham, said: "The next step is to understand exactly how and when gut parasites programme the human immune system in a way that protects against allergies, and for such studies, follow-up from birth will be essential."

The hope is that the work could aid the development of new treatments which work in the same way as gut parasites, by dampening down or rebalancing the immune system so that the body does not respond to allergens and trigger asthma attacks.

Dr Elaine Vickers, Research Relations Manager at the charity Asthma UK, which funded the research, said: "The prospects of further studies in this area are very exciting as we could see groundbreaking treatments for asthma and other allergies developed as a result."

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My own allergies were cured after I went on a trip to the middle east 5 years ago in 2004.

I was on flonase, clairiton, and zyrtec. Breathing wasn't really my issue, as was using my nose. My nose seemed to always be stuffy. I also had a serious allergy to dust. Since then though, after the trip, I haven't been on any of those medications and I'm perfectly fine.

Just goes to show how important germs, parasites, and bacteria are for a healthy immune system.

Twitter confirms major cash boost

There are an estimated 45 million users of Twitter

Social networking website Twitter has confirmed that it has closed a "significant round of funding".

Co-founder Evan Williams said in a blog post that the site had secured money from five investment firms.

However, he did not confirm earlier reports that suggested the firm had managed to secure $100 million (£62m), which would value the firm at $1bn.

The site, which allows users to write and share 140-character messages, has more than 45 million users worldwide.

The site had previously raised $35m in February in a deal that valued the business then at $255m.

"It was important to us that we find investment partners who share our vision for building a company of enduring value," wrote Mr Williams.

"Twitter's journey has just begun."

Industry watchers have pointed out that the firm still has no way of making money.

However, earlier this month the site revised its terms and conditions to allow advertising on its service.

"We leave the door open for advertising. We'd like to keep our options open," wrote co-founder Biz Stone in a blog.

The new funding has come from new investors Insight Venture Partners and T Rowe Price, as well as existing backers Institutional Venture Partners, Spark Capital and Benchmark Capital.

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