news20090829nn1

[naturenews] from [nature.com]

[naturenews]
Published online 28 August 2009 | Nature | doi:10.1038/news.2009.873
News: Q&A
Top scientist's industry move heralds stem-cell shift
Stephen Minger tells Nature why he is leaving academia.
Daniel Cressey

Stephen Minger is one of the leading stem-cell scientists in the United Kingdom, known for his work both as a researcher and as a high-profile public advocate for the field. He gained one of the first UK licences for the derivation of human embryonic stem cells, and generated the first human embryonic stem-cell line in the country.

In September, he will leave his post as director of the Stem Cell Biology Laboratory at King's College London to take up a new role at GE Healthcare, the medical technologies company headquartered near Amersham, UK.

GE Healthcare announced on 30 June that it had struck a deal with biotechnology company Geron, based in Menlo Park, California, to develop drug-screening tests using cells derived from human embryonic stem cells. The project was widely touted as proof that the burgeoning field of stem-cell research was ready for broader applications in industry. Minger, who will lead that effort as head of GE Healthcare's Research and Development for Cell Technologies division, spoke to Nature about the job — and the future of stem-cell technologies.

Why are you making the move to industry?

I decided to move from King's to GE for the simple fact that it was a tremendous opportunity to take our academic, basic science research and really move it to a completely different level — to take stem cells and actually make parts from them, but also at the same time to avail myself of all the technology within GE.

Tell us more about the work you hope to be doing at GE Healthcare?

The basic idea initially is to develop cell lines derived from embryonic stem cells for drug screening and predictive toxicology.

One of the problems with big pharmaceutical companies and their development pipeline is that a number of compounds can go fairly far, even into clinical trials and in some cases even into licensing, where those drugs can begin to show unpredicted toxicological effects in humans. Most of the screening is done using animal cells — for example, rat liver cells — or is done using human tumour-cell lines that don't faithfully represent true primary human cells. In many cases, even if the screens do use human primary cells there are huge problems with the inconsistency of results.

The power of using embryonic-derived cells is consistency, both in terms of quality and genetic background. It allows you to reproducibly use the same population of cells week in, week out.

If you take a drug into the clinic and then it has to be withdrawn either from clinical trials or from licensing, you're looking at losing hundreds of millions if not billions of dollars. So we're really trying to reduce the costs of drug development.

Isn't this work that you could have done in an academic environment?

It's not so much that the work couldn't be done academically. It's about trying to garner the resources to be able to scale the work up, and to work more efficiently, running a very large group of scientists, engineers and cell biologists. It would be very difficult to do within an academic setting. I had no real interest in leaving academia but when you weigh everything up, it became almost impossible to say no.

Do you think your move is part of a growing trend towards commercializing stem cells?

It is clear that the field is maturing. If you look at the number of academic research groups who are pursuing this work, it's ten times what it was five or six years ago.

Whether or not other academic researchers will want to do what I am doing is really an individual decision, but I think it does represent a slight shift away from the research being at a really basic level, and moving towards commercial and clinical applications.

Do any of your colleagues think you're selling out by making this move?
I've yet to hear anyone say, "I think you're selling out". If anything, I feel like I'm taking advantage of an opportunity that will hopefully enhance the field and help develop tools that will support the entire stem-cell community.


[naturenews]
Published online 27 August 2009 | Nature | doi:10.1038/news.2009.864
News
Human mutation rate revealed
Next-generation sequencing provides the most accurate estimate to date.
Elie Dolgin

Every time human DNA is passed from one generation to the next it accumulates 100–200 new mutations, according to a DNA-sequencing analysis of the Y chromosome.

This number — the first direct measurement of the human mutation rate — is equivalent to one mutation in every 30 million base pairs, and matches previous estimates from species comparisons and rare disease screens.

The British-Chinese research team that came up with the estimate sequenced ten million base pairs on the Y chromosome from two men living in rural China who were distant relatives. These men had inherited the same ancestral male-only chromosome from a common relative who was born more than 200 years ago. Over the subsequent 13 generations, this Y chromosome was passed faithfully from father to son, albeit with rare DNA copying mistakes.

The researchers cultured cells taken from the two men, and using next-generation sequencing technologies found 23 candidate mutations. Then they validated twelve of these mutations using traditional sequencing techniques. Eight of these mutations, however, had arisen in their cell-culturing process, which left just four genuine, heritable mutations. Extrapolating that result to the whole genome gives a mutation rate of around one in 30 million base pairs.

"It was very reassuring that our application of the new sequencing technologies seems to give a reliable result and that the number we've been using for the mutation rate is pretty much the right one," says Chris Tyler-Smith of the Wellcome Trust Sanger Institute in Hinxton, UK, who led the study, published today in Current Biology¹.

Tyler-Smith says that direct measurement of the mutation rate can be used to infer events in our evolutionary past, such as when humans first migrated out of Africa, more accurately than previous methods. But before that's possible, researchers will need a more precise estimate, notes Laurent Duret, an evolutionary biologist at the University of Lyon in France. "The confidence interval for the mutation rate is still quite wide," he says. Sequencing more pairs of Y chromosomes from distant male cousins in other families should provide a more robust measurement and reveal how mutation rates vary between individuals, Duret adds.

Most of the Y chromosome doesn't mix with any other chromosomes, which makes estimating its mutation rate easier. But the mutation rate might be somewhat different on other chromosomes, points out Adam Eyre-Walker, an evolutionary biologist at the University of Sussex in Brighton, UK. Other projects that involve sequencing parents and their offspring, such as the 1000 Genomes Project, should start to illuminate how DNA changes across the rest of the genome.

"I'm sure this is just the first of many papers that will be doing the same sort of thing," says Tyler-Smith.

References
1. Xue, Y. et al. Curr. Biol. 19, 1-5 (2009). | Article | PubMed | ChemPort |

news20090829nn2

[naturenews] from [nature.com]

[naturenews]
Published online 28 August 2009 | Nature | doi:10.1038/news.2009.870
News
Human-chimp interbreeding challenged
Mutation rates may be explained by differences in female promiscuity.
Elie Dolgin

A genetic analysis has called into question the controversial claim that early humans and chimpanzees interbred before splitting into separate species.

"Many evolutionary biologists were pretty sceptical" about the interbreeding scenario, says evolutionary geneticist Soojin Yi of the Georgia Institute of Technology in Atlanta. She argues that her explanation — which stems from promiscuity differences among primate species — is "simpler and hence more likely".

In 2006, David Reich and his colleagues at the Broad Institute in Cambridge, Massachusetts, compared the genomes of humans, chimps and three other primate species, and found that the separation of ancient humans from our closest cousins was more complex than a clean break. The time from the beginning to the completion of human-chimp divergence ranged over more than four million years across different parts of the genome, and the X chromosome seemed youngest of all, they reported in Nature¹. The authors argued that there were in fact two splits — an initial divide, followed by interbreeding, and then final separation in which only a young X chromosome was retained.

Many researchers took issue with this interpretation, arguing that large ancestral population sizes could explain the wide range in genetic divergence times, so there was no need to invoke a complex speciation process. But these critiques still could not account for the youth of the X chromosome.

Now Yi, together with Daven Presgraves of the University of Rochester in New York, have reanalysed the data and suggest that species differences in the levels of female promiscuity can account for the chromosomal inconsistency. The original hypothesis is "way more of a headache for evolutionary biologists", says Yi. The data "can also be explained very well by well-established ideas in molecular evolution".

Relationships matter

Males competing for mates produce different amounts of sperm depending on the mating habits of the species. Chimps are highly promiscuous, humans less so and gorillas not much at all. As such, male chimps face the stiffest competition, so they have the highest sperm counts and the largest testes of the three species. That means that they also undergo more rounds of sperm cell division and make more DNA copying mistakes, leading to higher mutation rates in males than in females. Reich and others had assumed that all primates had the same mutation bias, but Yi and Presgraves argue that mating relationships should be taken into account.

Because females have two X chromosomes and males have only one, the X spends more of its evolutionary history in females, whereas non-sex chromosomes split their time evenly between each gender. Thus, a male-biased mutation rate will lead to proportionally fewer genetic changes on the X and will seem to be younger when using a molecular clock, even if all the chromosomes diverged at around the same time, the researchers argue. Complex speciation is therefore unlikely to be the cause, they report in an invited opinion article in the October issue of Trends in Ecology & Evolution².

"This elegant and simple explanation will be the last piece of the puzzle," says Hideki Innan, a population geneticist at the Graduate University for Advanced Studies in Kanagawa, Japan.

The X factor

But Reich is not convinced. Yi and Presgraves' model "is an exciting hypothesis, but it simply can't explain the data", he says. Their model predicts that chimps should continue to accumulate more mutations on the autosomes compared to the X chromosome even after the species split. But even when Reich reanalysed 30 times more sequence data than his team considered in the original paper, he could not find any difference between the human and chimp lineages.

What's more, only the double-split scenario could explain why genes shared by humans and gorillas, but not chimps, are found everywhere on the non-sex chromosomes but are largely absent on the X. Complex speciation "remains a far-out hypothesis", admits Reich. "But no one has come up with an alternative explanation for the data that holds water."

Presgraves counters that when he included orang-utan data in the analysis, he found that humans and chimps had similarly strong male-biased mutation rates, so he wouldn't expect differences between the two species. What matters, he says, is that both species are more biased than gorilla, which makes the divergence seem younger than when compared to the older primates. In addition, he says, humans share genes with gorillas — albeit at lower levels — which is consistent with his expectations.

Nicholas Barton, an evolutionary geneticist at the Institute of Science and Technology Austria in Klosterneuburg, says that the new theory has the advantage that it is testable. Researchers can survey more species to confirm whether male-biased mutation rates vary with sperm competition. Reich's idea, however, cannot be disproved.

Indeed, in 2003, Hans Ellegren, an evolutionary biologist at Uppsala University in Sweden, calculated the mutation bias in 31 bird species, and found that those with higher rates of extrapair paternity also had higher male mutation rates³.

Yi concedes that she can't definitively invalidate Reich's model. "Proof is very hard to come by in evolution biology, unfortunately," she says.

References
1. Patterson, N. , Richter, D. J. , Gnerre, S. , Lander, E. S. & Reiche, D. Nature 441, 1103-1108 (2006).
2. Presgraves, D. C. & Yi, S. V. Trends Ecol. Evol. advance online publication doi:10.1016/j.tree.2009.04.007 (2009).
3. Bartosch-Härlid, A. , Berlin, S. , Smith, N. G. , Møller, A. P. & Ellegren, H. Evolution 57, 2398-2406 (2003).

news20090829bn

[One-Minute World News] from [BBC NEWS]

[Asia-Pacific]
Page last updated at 08:44 GMT, Saturday, 29 August 2009 09:44 UK
N Korea frees S Korea fishermen
North Korea has freed four South Korean fishermen and their boat, the South Korean Coast Guard has said.

Two Coast Guard vessels had retrieved the fishermen and their boat, a Coast Guard spokesman told the media.

North Korea seized the fishermen and their boat last month when they strayed into their waters after their satellite navigation system malfunctioned.

On Friday, the two sides agreed to resume family reunions called off by North Korea two years ago.

"We have taken over the Yonan," a Coast Guard official said, referring to the name of the boat.

In recent weeks, South Korean activists have held protests, demanding the return of the fishermen as well as an end to nuclear and missile tests.

The release of the boat, which was captured on 30 July, is perceived by analysts as a conciliatory move by the North Korean government and the latest sign of tensions easing between the two Koreas.

Relations between North Korea and the rest of the world were extremely strained earlier in the year.

The North was heavily criticised in May for conducting its second nuclear test and a series of ballistic missile launches, after which the UN Security Council agreed to tighten sanctions.


[Asia-Pacific]
Page last updated at 11:11 GMT, Saturday, 29 August 2009 12:11 UK
Voters wooed on eve of Japan poll
Candidates across Japan have made their last pitches to voters ahead of Sunday's election, which is expected to herald a rare change of power.

Most polls suggest the ruling LDP will lose to the opposition Democratic Party of Japan (DPJ), amid disaffection about the recession and high unemployment.

The Liberal Democratic Party has ruled for more than 50 years, with just one single break of less than one year.

DPJ leader Yukio Hatoyama said that this election could change history.

"At last, it is the election tomorrow, one that we will be able to tell the next generation changed Japanese history," Mr Hatoyama told crowds in Sakai in the west of Japan.

The DPJ wants to shift the focus of government from supporting corporations to helping consumers and workers - challenging the status quo that has existed since the end of World War II.

'Experienced'

But Taro Aso, the prime minister and leader of the LDP, questioned if the opposition, with little experience of power, could really run the country.

"I beg you to give power to the LDP so we can complete the recovery," he told a rally in Tokyo.

In Oyama, north of Tokyo, he added: "Can you trust these people? It's a problem if you feel uneasy whether they can really run this country."

Many voters are likely to use the election to voice their frustration with the government's handling of the economy during the global recession.

Figures released on Friday showed that the jobless rate was at a record high of 5.7% last month. In July, 3,590,000 Japanese were out of work, over a million more than a year ago.

While its economy grew by 0.9% between April and June, the latest unemployment figures cast doubt on the strength of the recovery.

Eager for change?

Turnout is expected to be high, with roughly 10% of the country's eligible voters expected to cast early ballots.

Some voters simply want to ring the changes after almost a half century of LDP rule.

"The government now is just not effective. I am not sure if the Democratic Party is good or bad, for now I just want change," Kotaro Kobayashi, a 75-year-old in Tokyo, told the Reuters news agency.

In fact, one analyst argued, few voters are paying close attention to the rival parties' policies.

"The election is more about emotions than policies," said Takashi Mikuriya, a professor of political science at Tokyo University.

"Most voters are making the decision not about policies but about whether they are fed up with the ruling party."


[Asia-Pacific]
Page last updated at 01:43 GMT, Saturday, 29 August 2009 02:43 UK
Suu Kyi visitor tells of 'sorrow'
The man who swam to the lakeside home of Burmese opposition leader Aung San Suu Kyi has spoken of his sorrow that his action led to her arrest and trial.
John Yettaw told the BBC that he had a dream that Ms Suu Kyi was going to be murdered, and swam to her home wearing home-made flippers to warn her.

Mr Yettaw was sentenced to seven years in prison but is now back home after US Senator Jim Webb intervened.

Ms Suu Kyi was sentenced to 18 months' further house arrest.

Mr Yettaw, a devout Mormon from Falcon, Missouri, told the BBC's Newshour programme that he had had many strong visions or dreams which he called "impressions" or "camcorder moments".

In one he says he foresaw an official plot to murder Ms Suu Kyi and this prompted him to swim twice to her home to warn her of the danger.

On the first occasion he says he left some Mormon scriptures for her but did not enter her home.

As he left he was challenged by an armed guard. He says he shook hands with the guard who then walked away and he took a taxi away from the scene.

Another dream

But he again swam to her house in May after another dream.

"I had been researching Myanmar (Burma) and researching about the internally displaced families and about the numbers of people who had been murdered and then about the numbers of people through the Cyclone (Nargis) and then about Aung San Suu Kyi's release date and I went to sleep that night and I had a dream that when she was released she was going to be murdered and I saw a plot," he said.

He said that he believed the inevitable publicity surrounding his trips would make it impossible for the Burmese military authorities to carry out their alleged plan to assassinate her.

"When I was in the water the first time... I had seen myself returning to the house and being in her house two days. When I had the dream of the assassination I thought: OK, I'll go back and I will share with her this message.

"I shared with many people that I had this overwhelming feeling that I was going to be imprisoned and become a political prisoner. The theme was that the eyes of the world would be on Aung San Suu Kyi and that this would spare her life, that the junta (Burma's military government) would not dare try to assassinate her."

Mr Yettaw, 53, said that when he arrived at Ms Suu Kyi's home for the second time she was "shocked" to see him.

"When I got in to talk to Aung San Suu Kyi I said there's a plot to assassinate you," he said. "She said: 'If I die I die.' I said no way, Burma needs you."

Both Mr Yettaw and Ms Suu Kyi were arrested and the pro-democracy leader was charged with breaking the terms of her house arrest by sheltering Mr Yettaw.

Mr Yettaw, who suffered ill health during his detention, spoke of his sorrow that his actions had led to Ms Su Kyi's arrest.

"I was sorrowful that she was arrested," he said. "I had impressions that I would be on trial and that Aung San Suu Kyi would either testify for or against me but not that she would be placed on trial because I think that if I had seen that I wouldn't have done it."