Down’s signs ‘seen in stem cells’

The researchers suggest they may be able to develop treatments for children

Scientists have revealed the earliest developmental changes that lead to Down’s syndrome.

The team from Barts and the Royal London say the changes to embryonic stem cells are caused by the presence of an extra copy of chromosome 21.

The study, in the American Journal of Human Genetics, says the extra chromosome sets off a chain of genetic changes in the developing embryo.

The Down’s Syndrome Association welcomed the “excellent” research.

Down syndrome belongs to a group of conditions called “aneuploidies”, which are defined by an abnormal loss or gain of genetic material, such as fragments of chromosomes or whole chromosomes.

Aneuploidies cause congenital anomalies that are a prime cause of infant death in Europe and the US, and are currently on the increase with advancing maternal age in European countries.

Around one in every 1,000 babies born in the UK will have Down’s syndrome.

There are 60,000 people in the UK with the condition.

Therapeutic potential

The international team of researchers, which also included scientists from the US, Australia, Spain and Switzerland, looked at embryonic stem cells from mice which had been genetically engineered to carry a copy of human chromosome 21.

“It’s not just important for the development of brain cells but for their maintenance throughout life Professor Dean Nizetic

They discovered that the presence of the extra chromosome 21, known as trisomy 21, disturbs a key regulating gene called REST, which then disturbs the cascade of other genes that control normal development at the embryonic stem cell stage.

The scientists also found that one gene (DYRK1A) which is present on chromosome 21, acts as the trigger for this disturbance.

Dean Nizetic, professor of cellular and molecular biology at Barts and the London, said the work could one day lead to molecule-based therapies which could alleviate the effects of Down’s syndrome.

“We hope that further research might lead to clues for the design of new therapeutic approaches tackling developmental delay, mental retardation, ageing and regeneration of brain cells, and Alzheimer’s disease.

He said he believed the genetic effects continue throughout life.

“I suspect that it’s not just important for the development of brain cells but for their maintenance throughout life; how cells age and how they can cope with stress.

“That’s an area that could be approached with regard to therapies.”

‘Extremely positive’

Professor Nizetic suggested future research should be directed into basic molecular mechanisms that could one day develop into treatments to children with Down’s syndrome in the first few years of life when the brains are “plastic” and rapidly developing.

And he said that the same areas of the human genome have been thought to play a part in Alzheimer’s disease – so research could also lead to treatments for that condition.

Carol Boys, chief executive for the Down’s Syndrome Association said: “Any research that helps us to understand more about some of the complex medical conditions that are commonly associated with Down’s syndrome can only be a positive step forward.

“The development of therapeutic treatments for these sometimes complicated health problems that can be associated with the condition will hopefully lead to an improvement in the overall health of people of with Down’s syndrome.”

She added: “We understand that research is slow, but the initial results look extremely positive and we look forward to the continuation of the excellent work of this dedicated research team with interest.”

Palin takes battle to Democrats

Palin takes battle to Democrats

John McCain’s running mate, Sarah Palin, has made a stinging attack on Democratic presidential runner Barack Obama at the US Republican convention.

She gave her first major campaign speech to an enthusiastic crowd at the convention in St Paul, Minnesota.

Defending her small-town roots, she attacked Mr Obama as having talked of change, but done nothing of substance.

Mr McCain made a surprise appearance on stage, with her family, saying: “Don’t you think we made the right choice?”

The Arizona senator has been formally nominated as the party’s presidential candidate in a roll call vote by state delegations. He is expected to accept the nomination on Thursday.

I’ve learned quickly… , that if you’re not a member in good standing of the Washington elite, then some in the media consider a candidate unqualified for that reason alone Sarah Palin

In a speech designed to rally the party base, she spoke of her family, including her elder son, who is about to be deployed to Iraq in the US Army, and her younger son, who has Down’s Syndrome.

The mother-of-five highlighted her background as a small-town “average hockey mom” and stressed that she was not part of the “Washington elite”.

In a salvo directed at media commentators who have questioned her qualifications, she said she was “not going to Washington to seek their good opinion” but to serve the people.

Mrs Palin praised the “determination, resolve and sheer guts” of Mr McCain and said she was honoured to help him.

Mrs Palin also attacked Mr Obama’s “change agenda” and suggested he was more interested in idealism and “high-flown speech-making” than acting for “real Americans”.

“In politics, there are some candidates who use change to promote their careers,” she said.

I liked the parliamentary-style jabs at Obama BBC North America editor Justin Webb

“And then there are those, like John McCain, who use their careers to promote change.”

She also targeted Mr Obama’s experience as a community organiser and remarks he made earlier this year when he spoke of “bitter” working-class people “clinging to guns or religion”.

“I guess that a small-town mayor is sort of like a ‘community organizer’, except that you have actual responsibilities,” she said.

“I might add that in small towns, we don’t quite know what to make of a candidate who lavishes praise on working people when they are listening, and then talks about how bitterly they cling to their religion and guns when those people aren’t listening.”

Mrs Palin – who supports drilling for oil in Alaska’s Arctic National Wildlife Refuge – said that while drilling “will not solve all of America’s energy problems”, that is “no excuse to do nothing at all”.

Democrats under fire

Former Governors Mitt Romney and Mike Huckabee opened the night by hailing Mr McCain and attacking the Democrats.

Mr Romney, a one-time rival of Mr McCain for the Republican nomination, used his speech to hammer the Democrats over their “liberal” agenda.

“We have a prescription for every American who wants change in Washington – throw out the big government liberals and elect John McCain,” the former Massachusetts governor said.

He also lauded Mr McCain’s national security credentials, saying he was the presidential contender who would defeat “evil” radical Islam.

Mr Huckabee, also a former rival of Mr McCain, joked that he had hoped to be giving the speech on Thursday night – when Mr McCain will accept the party’s nomination to run for president in November’s election.

But, he said, he was delighted to be speaking for his second choice, Mr McCain – “a man with the character and stubborn kind of integrity that we need in a president”.

He defended Mrs Palin against criticism from the media, saying its coverage had been “tackier than a costume change at a Madonna concert”, and attacked the Democrats’ vice-presidential candidate Joe Biden.

You need to face your enemy in order to defeat them. John McCain will face this threat and bring victory to this country Rudy Giuliani

“I am so tired of hearing about her lack of experience. She got more votes running for mayor of Wasilla, Alaska, than Joe Biden got running for president of the United States,” he said, referring to Mr Biden’s performance in the Democratic primaries.

Former New York City Mayor Rudy Giuliani followed Mr Huckabee on stage, calling the 2008 presidential election a “turning point” for the people of the US.

He charged the Democrats with being in denial about the threat from terrorism and said Mr McCain had the foreign policy, national security and leadership experience that counted.

“The choice in this election comes down to substance over style,” he said. “John has been tested. Barack Obama has not. Tough times require strong leadership, and this is no time for on the job training.”

Vetting questions

The Alaska governor’s speech comes amid scrutiny of her record and after two days dominated by the news her daughter Bristol, 17, is pregnant.

Mrs Palin and her family, including Bristol and her boyfriend, greeted Mr McCain at the airport as he arrived in Minnesota on Wednesday.

Ahead of her address, senior McCain campaign adviser Steve Schmidt issued a statement saying that media questions over how thoroughly Mrs Palin was vetted should end.

It has also been revealed that an attorney has been hired to represent Mrs Palin in an Alaska state ethics investigation involving alleged abuse of power.

Mrs Palin told US network CNBC she had “nothing to hide”. Her deposition is expected to be scheduled soon.

There have also been reports that Mrs Palin sought special financial favors for her city and state – something the McCain campaign is against.

She was elected governor of Alaska in 2006 and before that was mayor of the small town of Wasilla, Alaska.

McCain unveils ‘The Barracuda’

There were no late night text messages and perhaps not the same build up that preceded the announcement of Barack Obama’s choice for running mate.

Mrs Palin has been credited with bringing in reforms in her time in office

But because it was kept a secret almost until the end, John McCain’s choice did generate a fair amount of rumor and speculation.

Was he going to pick a traditional candidate, a safe bet – someone like the young governor of Minnesota, Tim Pawlenty, or would the veteran Arizona senator go for the wild card?

The answer came on a private jet that flew in from the Alaskan city of Anchorage on Thursday night and landed outside Dayton, Ohio, apparently carrying on board a woman, two men and two teenagers.

All the journalists who were covering the story started looking up the biography of Sarah Palin, the 44-year-old governor of Alaska.

‘Average hockey mom’

She may be seen by some as a rising star of the Republican Party, but she was relatively unknown on a national level.

As he took to the stage, in front of a packed audience, Mr McCain introduced her as “exactly who I need, exactly who this country needs to help me fight the same old Washington politics of me first and the country second”.

For observers, it showed Mr McCain felt he needed to make a bold move to help change the course of the race to the White House.

SARAH PALIN Elected Alaska’s youngest and first woman governor in 2006 Grew up in Wasilla, near Anchorage, and was voted Miss Wasilla in 1984 Studied journalism and political science at University of Idaho Is mother of five, including a son with Down’s syndrome Her husband Todd is an oil production operator Likes hunting and fishing

The two presidential hopefuls have been running head to head, with Mr Obama gaining eight percentage points in the polls in recent days.

The choice of Sarah Palin is a high risk bet that could bring high rewards, but there are no guarantees.

Mrs Palin, a mother of five, is the first woman to be on a Republican presidential ticket.

Married for 20 years to Todd Palin, her high school sweetheart, she was nicknamed “Sarah Barracuda” during her college years for her aggressive basketball playing style – the name has stuck.

On stage, dressed in a conservative black power suit, her hair raised in a high ponytail, she described herself as “an average hockey mom from Alaska”.

She drew applause when talking about her anti-corruption drive, her standing up to big oil companies and even the “good old boys club”, which drew a smile from Mr McCain.

She eats moose meat and is an inveterate hunter, a lifelong member of the National Rifle Association (NRA).

One of her sons is heading to Iraq in September. The other, born in April, is diagnosed with Down’s syndrome.

‘Exciting choice’

In many ways, her story is all American and her values will appeal to the conservative base and to blue-collar voters.

With 80% approval ratings back home, she seemed to also get the approval of the crowd she was addressing, drawing very enthusiastic cheers, as she spoke in a relaxed, accessible way.

It turns out the women of America aren’t finished yet, and we can shatter that glass ceiling once and for all Sarah Palin

Mrs Palin also ticks several required boxes – she is fiscally conservative, in favor of drilling for oil and very staunchly anti-abortion.

Most of all she is a reformer and a fresh face for the Republican ticket.

President George W Bush said she was “an exciting choice” and Mrs Palin certainly adds energy and sizzle to the McCain campaign.

She also clearly reached out to disaffected Hillary Clinton supporters, who are disappointed their candidate did not make it on to the Democratic ticket, not even as vice-president.

“I can’t begin this great effort without honoring the achievement of Geraldine Ferraro in 1984 and of course, Hillary Clinton, who showed determination in her presidential campaign,” Mrs Palin said.

“It was rightly noted in Denver this week that Hillary left 18 million cracks in the highest, hardest glass ceiling in America. But it turns out the women of America aren’t finished yet, and we can shatter that glass ceiling once and for all.”

The Democrats for McCain group sent out an e-mail saying its supporters, especially the women, were “ecstatic” about the choice of Mrs Palin.

But other Democrats said they felt insulted that Mr McCain thought he could woo women by just putting any woman on his ticket, with one sentence making the rounds: “Palin, you are no Hillary Clinton”.

Experience questioned

It all made for an exciting day in Dayton, a city of just over 150,000 that has been hard hit by job losses in the past few years.

But the whole of the US is probably now scouring the internet for more information about Governor Palin and trying to assess her credentials.

What is it exactly that a VP does every day? Sarah Palin

Many will be wondering whether she is ready to be vice-president and even lead the US, should something happen to Mr McCain if he is elected president.

As commander of the Alaska National Guard, she visited troops in Kuwait last year, but has a very thin foreign policy background.

Similarly, while she does have executive experience, the Obama campaign wryly pointed out she had been the mayor of a town with just 9,000 people.

As governor of Alaska during the past two years she has gained more experience, but even some Alaskans calling into talk shows on US network television said they doubted whether that had prepared her for the challenge of national politics.

She did herself no favors in a recent interview.

“As for that VP talk all the time, I can’t answer until someone answers me. What is it exactly that a VP does every day?” she said just a month ago on CNBC when asked about her chances of being on the ticket.

“I’m used to being very productive and working real hard in an administration. We want to make sure that this VP slot would be fruitful type of position especially for Alaskans and for the kind of things we are trying to accomplish here for the rest of the US.”

Investigation

By choosing her, Mr McCain may have undercut his best attack against Senator Obama – if he uses the inexperience card now it will be turned against him and his running mate.

While conservatives, such as radio host Rush Limbaugh and former Bush adviser Karl Rove, hailed the Palin surprise, there were also dismayed reactions from some Republicans, who felt the choice underscored Mr McCain’s weaknesses and was too risky.

Polls in the coming days, and Mrs Palin’s performance at the Republican National Convention, will help assess the impact of Mr McCain’s decision.

In the meantime, Mr McCain and his new partner have something else to worry about – Mrs Palin is facing an investigation in Alaska for alleged abuse of power involving her former brother-in-law. Her deposition is expected to be scheduled soon.

She says she has “nothing to hide” and is “cool” about the investigation.