Monday, June 17, 2013

Iran president-elect carries reform hopes after routing hardliners

By Marcus George

DUBAI (Reuters) - Iran's new president, a moderate cleric known for his conciliatory nuclear talks with world powers, will take office carrying the hopes of reformists seeking less repression of social freedoms and a more pragmatic foreign policy.

Hassan Rohani is someone world powers are likely to welcome as the successor to hardline populist incumbent Mahmoud Ahmadinejad, hoping he might pursue peaceful ways out of an increasingly tense standoff with Iran over its nuclear activity.

To the surprise of many, Rohani polled just over 50 percent of the votes cast in Friday's election, according to the interior ministry, good enough for a landslide first-round victory over conservatives close to Supreme Leader Ayatollah Ali Khamenei.

Rohani's focus on rehabilitating Iran's foreign relations and its sanctions-damaged economy and his call for a "civil rights charter" proved appealing to the significant number of Iranians keen for more political pluralism at home and an end to the Islamic Republic's isolation abroad.

The former nuclear negotiator's bridge-building track record secured the vote of pro-reform Iranians politically muzzled for years, but he could also work well with the wary Khamenei thanks to his impeccable background in Iran's clerical establishment.

Khamenei's grip faltered in 2009 when millions of Iranians took to the streets in protests - stamped out by security forces after months of deadly violence - over alleged fraud in Ahmadinejad's first-round re-election.

Khamenei, who has the last say on over-arching state policies including security and the nuclear program, was widely seen as wanting a loyal hardline "principlist" to win big without dispute this time around.

But U.S.-based Iranian analyst Trita Parsi suggested Rohani's resounding election triumph showed the evolving balance of power in Iran was more complex than many had reckoned.

"Though hardliners remain in control of key aspects of Iran's political system, the centrists and reformists have proven that even when the cards are stacked against them, they can still prevail due to their support among the population," Parsi wrote in an emailed commentary.

Rohani managed to win with a constituency - whose core was believed to be the urban middle class and young - that had been widely disillusioned by years of security crackdowns that stifled virtually any public dissent from Islamist orthodoxy.

Reformists led by former president Mohammad Khatami resurfaced from quiescence to endorse Rohani earlier this month after their own candidate withdrew from a field dominated by conservative Khamenei loyalists.

Rohani picked up further momentum with the endorsement of his mentor, former president Akbar Hashemi Rafsanjani, a veteran rival of Khamenei who was disqualified from running last month.

Rohani has pledged to draw up and implement a "civil rights charter, promote a foreign policy based on "constructive interaction with the world", and has spoken up for the rights of women and ethnic minorities.

CRITICISM OVER CONCILIATORY TALKS

Rohani, 64, headed the Supreme National Security Council under Rafsanjani, a relative pragmatist seen as a master of realpolitik, and under Khatami, who pursued wide-ranging social and political reforms ultimately blocked by hardliners in the dominant elite of clerics and Revolutionary Guards commanders.

He presided over talks with Britain, France and Germany that saw Iran agree in 2003 to suspend uranium enrichment-related activities pending further negotiations on trade and diplomatic concessions to Iran ultimately undone by mutual mistrust.

He resigned after Ahmadinejad took office in August 2005; enrichment activity resumed and expanded. Rohani was accused of being too accommodating in negotiations - a criticism that hardline rivals tried to exploit.

But Rohani deftly counter-attacked. In a May 27 interview on Iranian state television, Rohani sparred with a news anchor, calling him "illiterate" for saying Iran's nuclear program had stopped during his tenure as negotiator.

"This is a lie," he said. Rohani noted that Iran had continued to make advances in nuclear know-how while he headed its security council and he had steered the country away from threats of Israeli or U.S. attack on its nuclear sites.

"We didn't allow Iran to be attacked. Remember the sensitive conditions at the time ... they had gotten Afghanistan, they had occupied Iraq. They imagined tomorrow or the day after tomorrow it would be Iran's turn," referring to the U.S. military.

REVOLUTIONARY CREDENTIALS

No one questions the revolutionary pedigree of the mid-level Shi'ite cleric, who was active in the opposition that overthrew the U.S.-backed shah in 1979. He remains on the security council and on the Expediency Council and the Assembly of Experts, two influential advisory bodies in the multi-tiered power structure.

Rohani boasts military experience through prominent roles in Iran's 1980-88 war with Iraq, including as commander of national air defense, according to his official biography.

He has, however, maintained a centrist outlook shared with former president Rafsanjani, a close ally.

Rohani hinted he would stand aside if Rafsanjani joined the race. But the Guardian Council, the state body that vets all election candidates, barred Rafsanjani, who would have posed the most significant independent threat to Khamenei's supremacy.

Rohani criticized the pre-election increase of police and Islamist militia in the streets, apparently to deter any temptation for new unrest. "Why should there be a security atmosphere everywhere? In the streets, universities, schools, organizations, we must put an end to this security atmosphere."

BROKEN ECONOMY

During Ahmadinejad's two terms in office, friction with the West over the nuclear program has risen with the United States and Europe imposing sanctions on Iran's oil and banks over suspicions Tehran is seeking atomic bombs, something it denies.

The tightening international vice has sent Iran's currency, the rial, into steep decline and exacerbated the impact of what critics say was Ahmadinejad's shambolic economic management.

Rohani has bemoaned the plight of the economy and, suggesting it was caused in part by the increasing ostracism of Iran over its intransigence in the nuclear dispute, pledged the creation of a "government of prudence and hope" if elected.

"Looking at the state of the country and urban and rural problems, the young and the old, the students ... everyone knows what problems and social issues we are facing in everyday life," he said in a recent interview on state television. "Is there a family out there that isn't affected by unemployment?"

(For an Interactive timeline of Mahmoud Ahmadinejad as president of Iran please click on http://link.reuters.com/cas68t ))

Source: http://news.yahoo.com/iran-president-elect-carries-reform-hopes-routing-hardliners-165613338.html

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Navalny aims to run for Moscow mayor

MOSCOW (AP) ? Alexei Navalny, the anti-corruption crusader who has spearheaded opposition to Russian President Vladimir Putin, plans to run for mayor of Moscow.

Navalny, one of the leaders of the anti-Putin demonstrations that rose up in late 2011, submitted documents to register his candidacy on Saturday, Russian news agencies cited the city elections commission as saying.

He was nominated by the liberal opposition RPR-Parnas party on Friday, saying he was entering the Sept. 8 election "to pull our city from the tentacles of Putin."

Moscow Mayor Sergei Sobyanin resigned last week, forcing a snap election in which he likely will be returned.

Sobyanin was appointed by then-President Dmitry Medvedev in 2010. Russia later restored mayoral direct election.

The early election could undermine challengers who may struggle to organize campaigns on short notice.

Source: http://news.yahoo.com/navalny-aims-run-moscow-mayor-131701477.html

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Saturday, June 15, 2013

6 Reasons Why Small Businesses Often Fail With AdWords | Search ...

Managing AdWords campaigns for small businesses offer many challenges besides just optimizing AdWords in the regular sense. Many small businesses have distinct budgetary challenges, their websites are often not optimal and many lack a general understanding of how Google AdWords works.

As an AdWords manager you therefore need to be able to explain more facets than just the basics about AdWords and make yourself understandable to everyone. In White Shark Media we manage small to mid-sized AdWords accounts usually ranging from $1,000 to $10,000 monthly budget.

We evaluate a lot of AdWords campaigns every month and even though there are many different factors, you keep seeing the same mistakes over and over. If most small businesses could avoid these mistakes they would have better chances of reaching success on their own.

I truly believe that you should get your feet wet in a field before you hire external help. The lack of knowledge in the AdWords field is one of the main reasons for many small business owners to say they have been scammed once or more by a so-called AdWords agency.

Here are 6 of the biggest mistakes I see over and over again in small business AdWords accounts.

1) One Campaign with One Ad Group For All Keywords

AdWords campaigns in the mainstream industries can easily be successful with a decent budget. It?s however time-consuming for new advertisers to set up an account properly.

Creating one campaign with just one ad group and including all your keywords herein is a surefire way to waste a lot of money. AdWords is all about relevance. In most industries and local areas you can find advertisers who have been using AdWords for years.

Their campaigns are frequently set up granularly with properly written and tested ad messages for each keyword theme.

If you just put all your locksmith keywords in the same ad group you?ll end up being less relevant than your competitor who will walk away with all the qualified clicks.

You?ll definitely get clicks ? It?s very rare to see AdWords campaigns set up in such a wrong way as to not get clicks (kudos to Google) ? but the clicks will not be qualified and the users will most likely not convert for you.

90% Relevant Is Not 100% Relevant

I often hear from small businesses that when somebody is searching for a key replacement service they?re actually looking for a locksmith. Setting up an ad mentioning that you?re a locksmith might make sense if you?re thinking in the regular banner ad mindset.

However, in AdWords it?s all about being the most relevant choice on the page. Imagine you?re searching for a key replacement service and you see these two ads:

Fast Key Replacement Services
Get Your New Keys Within 15 Minutes.
Call Today to Schedule.

All Locksmith Services
We Offer Everything In Locksmith Services.
Call Today to Schedule.

Searchers will look at the two ads and compare them. By looking at the second ad they will be 95% sure that you do offer key replacement services. However, with the first ad they are ?100% sure that you offer key replacement services and they even get shown a specific benefit from using that company (15 minute turnaround time).

The more ad groups you choose to use when setting up your AdWords campaigns the better message you can send. This will directly relate to how qualified your visitors are and how good your results will get with AdWords.

2) Limited By Budget

Being limited by budget is one of the most frequent cases of wrongful bid management that I have come across. It?s also one of the easiest things to fix if you?re a small business.

Having campaigns that have the Limited By Budget status means that your budget limit is being reached on a somewhat daily basis before midnight. When your budget limit is reached your ads will stop being shown until midnight which is when your budget is reset.

Often the Limited By Budget status goes hand in hand with high positions and a relatively small budget limit. Some small business owners wrongfully have the idea that being in the top spots is all that counts. Thinking about this is like thinking about normal advertising where you often pay a fixed fee as you need to ensure that you get the most amount of visibility.

In AdWords it?s different. You shouldn?t really care about visibility when you?re a small business. Sure, visibility becomes a metric when your account has matured, but in the beginning it?s all about the conversions and ROI.

You don?t get any conversions out of visibility. The key metric here are clicks. You want to get as many clicks out of your initial budget as possible. With Limited By Budget campaigns you often see that the campaign stops being shown at mid-day and has an avg. position over 4.

By lowering the bidding by ~30-50% you?ll get a lower position and CTR, but you will also pay less per click. Your budget will not be reached too early in the day and you can get more clicks as a whole:

Limited By Budget:

  • 1,000 impressions
  • 2.8 Avg. position
  • 20 clicks
  • $2 per click
  • 2% CTR
  • $20 budget
  • Campaign stops being shown at 2pm

Not limited by budget:

  • 4,000 impressions
  • 5.6 Avg. position
  • 48 clicks
  • $0.41 per click
  • 1.2% CTR
  • $20 budget
  • Campaign is shown all day

You might think this is just a theoretical example, but I?ve seen this change (and even bigger ones) happening at least a hundred times.

3) Only Using Broad Match

By only using Broad Match keywords you?ll end up giving Google more money than you actually have to. Many small businesses don?t know that keywords in AdWords have different types.

The standard match type is Broad Match. Broad Match has an expansion option that lets Google show your ads for anything they find remotely relevant.

A keyword like lawn care services in Broad Match can enable your ads to be shown for the following queries:

  • lawn moving job
  • how to move a lawn
  • cut grass when it rains
  • spring clean up services
  • lawn mover maintenance
  • blade cutters

Keeping to Broad Match Modifier instead of regular Broad Match is a good way to ensure that you?re only paying for the most relevant clicks.

4) Too Many Changes All The Time

Even though many small businesses set up their AdWords campaigns and forget about optimizing them, then there is the opposite category as well. If you keep making changes in your AdWords campaigns you?ll never get the necessary consistency to achieve statistical significance.

Advertisers having a new promotion every week or making changes on a daily basis is one of the most frequent mistakes I keep seeing. But don?t take this as a suggestion not to optimize your AdWords account at all. Optimizing your account is an important aspect of getting a successful AdWords account, but making changes every day clashes with the fact that you should optimize your AdWords account based on statistics.

Optimizing solely based on the statistics for the day is bad practice that in most cases will make your AdWords account perform worse and worse.

5) Wrongful Implementation of Conversion Tracking

Mistaking the implementation instructions for AdWords Conversion Tracking with the instructions for Google Analytics can lead you to not get any real information out of your AdWords campaigns.

Implementing the Conversion Tracking code on each page will give you nearly 100% conversion rate. It is quite easy to spot that this is wrong.

The problem gets bigger when you implement the code on the actual contact form page or another individual page on the website and you mistake the conversions for real statistics. I?ve disappointed many AdWords advertisers who have come to me, rather proudly, saying that they are pretty successful with AdWords, until they hear me say that they shouldn?t ?really be using their conversion statistics too much.

6) The Ads Aren?t Written For The AdWords Format

Writing for the AdWords format is a challenge to say the least. Even I get challenged at times when I think of the perfect ad message that subsequently can?t seem to fit into the AdWords format. On top of that, I?m also required to fit in a Call-To-Action which makes it even harder.

Dimmers net SEJ

The mistake with the dimmers.net ad is: Missing a period after Selection causes the ad to be hard to read. Adding a period would also increase the ad exposure by putting the first description line in the headline.

PTC-CH SEJ

The mistake with the teamwavelength.com ad isThe headline and description lines are written like a full sentence. AdWords ads aren?t suited for full sentences. Small messages with a conscious choice of words work best.

Work Smarter With AdWords When You Know The Basics

Even though many AdWords experts differ in their strategies many others agree on the approaches that are most effective for smaller accounts. Working with AdWords is somewhat simple for the advertisers who take the time to understand how the search engine works and how AdWords plays a role in the online ecosystem.

Getting your feet wet and understanding the basics of AdWords will give you a better chance of finding success with AdWords either by managing your campaigns in-house or through a Third Party AdWords Agency.

Andrew Lolk is the author of the 189-page free AdWords ebook The Proven AdWords Strategy. He's worked in AdWords since 2009 and have co-founded White Shark Media; A Paid Search agency specialized in delivering results for small to mid-sized businesses in the US.

Source: http://www.searchenginejournal.com/6-reasons-why-small-businesses-often-fail-with-adwords/64012/

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It's officially OK to say "Merry Christmas" in public schools in Texas

Districts can also put up decorations like Nativity scenes, Christmas trees, and menorahs on school property as long as they follow the rules.

Gov. Rick Perry signed House Bill 308 which allows public school students and staff to use traditional holiday greetings and display religious symbols on school property. He was joined by bill author Rep. Dwayne Bohac R-Houston, Bahac's son Reagan, Sen. Robert Nichols, as well as several Santas, Rabbi Zev Johnson, and cheerleaders from Kountze High School.

Photo by Marjorie Kamys Cotera

Gov. Rick Perry signed House Bill 308 which allows public school students and staff to use traditional holiday greetings and display religious symbols on school property. He was joined by bill author Rep. Dwayne Bohac R-Houston, Bahac's son Reagan, Sen. Robert Nichols, as well as several Santas, Rabbi Zev Johnson, and cheerleaders from Kountze High School.

This holiday season, teachers and students will officially have permission to wish each other "Merry Christmas" ? or the traditional greeting of their choice ? in Texas public schools.

Flanked by high school cheerleaders who recently fought a legal battle to carry banners with Bible verses on them at athletic events, Gov. Rick Perry ceremonially signed legislation Thursday clarifying that school districts can acknowledge traditional winter celebrations.

"The holidays are coming early this year," for students of all faiths "who want to freely express the simplest of appropriate greetings during holy days," said Perry, who was also joined by an off-duty Santa Claus and an orthodox rabbi.

Under the new law, as long as displays include more than one religious symbol ? or at least one secular symbol ? and don't encourage adherence to a particular religious belief, districts can put up decorations like Nativity scenes, Christmas trees, and menorahs on school property. Public school staff and students can also offer each other seasonal greetings like Merry Christmas and Happy Hanukkah.

House Bill 308 was intended to help protect school districts from lawsuits, said state Rep. Dwayne Bohac, the Spring Branch Republican who carried the legislation, adding that it would "restore some sanity" to "political correctness run amuck." He said he hoped the bill, which passed overwhelmingly in both the House and Senate, would become a model for other states.

Texas public schools have seen several high-profile lawsuits attempting to define students' rights to religious expression, including the landmark 2000 U.S. Supreme Court decision Santa Fe ISD v. Doe. In that case, the court outlawed student-led prayer over the loudspeakers at football games, saying it amounted to government endorsement of religion, a violation of the First Amendment?s establishment clause. More recently, a state district court judge ruled in favor of cheerleaders who sued their East Texas high school after they were told to stop displaying Bible verses at school events. The school district is appealing the ruling.

Though the cheerleaders' situation remained an example of the oppression facing those who want to express their faith publicly, Perry said, the new law would not directly apply to their case.

"It's a shame that a bill like this one I'm signing today is even required. But I'm proud that we are standing up for religious freedom in the state," he said. "Religious freedom does not mean freedom from religion."

Source: http://www.pegasusnews.com/news/2013/jun/13/officially-ok-say-merry-christmas-public-texas/

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Play the Slate News Quiz

The nice thing about taking a news quiz online nowadays is that the American government knows your score even before you do! Please don't miss any of the easy ones this week, or you may raise a few eyebrows at Fort Meade.

Question 1 of 12

On Tuesday, a suicide bomber killed 14 people in the second recent attack on Marjeh Square, a busy commercial district in what city?

Question 2 of 12

The initial Guardian reports on NSA whistle-blower Edward Snowden emphasized that, surprisingly, he had never done what?

Snowden has a GED in lieu of a high school diploma.

Question 3 of 12

The state of New Hampshire took what official action toward Zebulon Gardner, Cipio Hubbard, Kittindge Tuckerman, and 11 other men last week?

The slaves had petitioned the state for freedom back in 1779, but the request was lost for two centuries. Governor Maggie Hassan granted it posthumously last Friday.

Question 4 of 12

Who described herself as a "pantsuit aficionado" this week?

The list of credentials in Clinton's bio ends with a coy "TBD," teasing a possible 2016 presidential run.

Question 5 of 12

In the face of the protests in Turkey, Prime Minister Tayyip Erdogan steamed last week that "the thing that is called" what "is the biggest trouble for society right now"?

Twitter and Facebook continue to be the opposition's most successful path around Turkey's government-controlled media.

Question 6 of 12

Last week, Texas actress Shannon Richardson, who has appeared on TV's The Walking Dead and The Vampire Diaries, confessed to what crime?

According to investigators, Richardson's plan was to frame her husband for the letters she sent to President Obama, Mayor Michael Bloomberg, and a gun control group.

Question 7 of 12

PRISM, the name of the National Security Agency's secret surveillance tool, has long been a U.S. intelligence acronym standing for what?

Question 8 of 12

In a memo leaked this week from a private meeting, a leader was quoted as saying that "the 'gay lobby' is mentioned, and it is true, it is there. ... We need to see what we can do." Where is this so-called "gay lobby"?

Pope Francis seemed to confirm rumors of a group of influential gay prelates in an audience with a Latin American Catholic organization.

Question 9 of 12

An Austin, Texas-based candy company told the Los Angeles Times last week that it has finally perfected a lollipop that tastes like what?

The (vegan) treats don't actually contain any breast milk, but several lactating moms made ongoing donations until the Lollyphile labs could "candify" the taste accurately.

Question 10 of 12

Which of these major world rivers reached a record-high level of 29 feet Monday, threatening to flood at least one national capital?

Tens of thousands have fled their homes in Central Europe due to the flooding, but Budapest's dams held, saving the city.

Question 11 of 12

What three people has China sent to spend the next two weeks at Tiangong, or "Heavenly Palace"?

Tiangong-1 is China's experimental space station module in low Earth orbit. The manned Shenzhou 10 spacecraft will stay docked at Tiangong until late June.

Question 12 of 12

Speaking to the Knesset last week on prison smuggling, Israel's education minister erupted into a two-minute-27-second giggling fit over what word?

Shai Piron, a rabbi, finally gave up on the speech and had Israel's welfare minister complete it for him.

You got 8 out of 12 answers correct in 20 minutes 30 seconds.

Source: http://www.slate.com/articles/news_and_politics/the_slate_quiz/2013/06/the_slate_quiz_with_quizmaster_ken_jennings_play_the_news_quiz_for_the_week_1.html

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Sunday, June 9, 2013

South Africa: Mandela taken to hospital

FILE - In this Wednesday, July 18, 2012 file photo, former South African President Nelson Mandela celebrates his 94th birthday with family in Qunu, South Africa. Mandela was taken to a hospital Saturday to be treated for a recurrence of a lung infection and is in "serious but stable" condition, the president's office said. (AP Photo/Schalk van Zuydam-file)

FILE - In this Wednesday, July 18, 2012 file photo, former South African President Nelson Mandela celebrates his 94th birthday with family in Qunu, South Africa. Mandela was taken to a hospital Saturday to be treated for a recurrence of a lung infection and is in "serious but stable" condition, the president's office said. (AP Photo/Schalk van Zuydam-file)

Press gather outisde the hospital in Pretoria, South Africa where it is believed that former president Nelson Mandela was hospitalized with a recuring lunch infection early Saturday, June 8, 2013. A presidential statement said that Mandela was in a serious but stable condition. (AP Photo)

Press gather outisde the hospital, unseen, in Pretoria, South Africa where it is believed that former president Nelson Mandela was hospitalized with a recuring lunch infection early Saturday, June 8, 2013. A presidential statement said that Mandela was in a serious but stable condition. (AP Photo)

(AP) ? Former South African President Nelson Mandela is in "serious but stable" condition after being taken to a hospital to be treated for a lung infection, the government said Saturday, prompting an outpouring of concern from admirers of a man who helped to end white racist rule.

Mandela's wife, humanitarian activist Graca Machel, canceled an appearance at an international forum on hunger and nutrition in London on Saturday, citing "personal reasons," said Colleen Harris, a spokeswoman for the meeting.

Mandela, who is 94 years old, was treated in a hospital several times in recent months, with the last discharge coming on April 6 after doctors drained fluid from his lung area after diagnosing him with pneumonia. He has been particularly vulnerable to respiratory problems since contracting tuberculosis during his 27-year imprisonment under apartheid.

"During the past few days, former President Nelson Mandela has had a recurrence of lung infection," said a statement from the office of President Jacob Zuma. "This morning at about 1.30a.m., his condition deteriorated and he was transferred to a Pretoria hospital."

It said Mandela was receiving expert medical care and "doctors are doing everything possible to make him better and comfortable."

Zuma wished Mandela a quick recovery on behalf of the government and the nation and requested that the media and the public respect the privacy of the former leader and his family, the statement said.

"We need to hold our thoughts and keep him in our minds," said Mac Maharaj, the president's spokesman. "He is a fighter, he has recovered many times from very serious conditions and he will be with us. Let's pray for him and help him to get better."

The African National Congress, the ruling party that has dominated politics in South Africa since the end of apartheid, said it hoped Mandela, known affectionately by his clan name Madiba, would get better soon.

"We will keep President Mandela and his family in our thoughts and prayers at this time and call upon South Africans and the peoples of the globe to do the same for our beloved statesman and icon, Madiba," the party said in a statement.

On April 29, state television broadcast footage of a visit by Zuma and other ANC leaders to Mandela at his Johannesburg home. Zuma said at the time that Mandela was in good shape, but the footage - the first public images of Mandela in nearly a year - showed him silent and unresponsive, even when Zuma tried to hold his hand.

"Nelson Mandela is a father to South Africa and South Africans; every time he is admitted to hospital we feel saddened along with the rest of our country," the Democratic Alliance, the main political opposition party, said in a statement.

South Africans expressed hope that Mandela would recover from his latest setback.

"He is going to survive," said Willie Mokoena, a gardener in Johannesburg. "He's a strong man."

Another city resident, Martha Mawela, said she thought the former president would recover because: "Everybody loves Mandela."

Mandela was robust during his decades as a public figure, endowed with charisma, a powerful memory and an extraordinary talent for articulating the aspirations of his people and winning over many of those who opposed him.

In recent years, however, he has become more frail and last made a public appearance at the 2010 World Cup soccer tournament, where he didn't deliver an address and was bundled against the cold.

In another recent hospitalization, Mandela was treated for a lung infection and had a procedure to remove gallstones in December. In March, he spent a night in a hospital for what authorities said was a scheduled medical test.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/cae69a7523db45408eeb2b3a98c0c9c5/Article_2013-06-08-South%20Africa-Mandela/id-e4aa3a7e11c44d76b13a0c42298cc13c

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Friday, June 7, 2013

The swing of architect genes

June 6, 2013 ? A few days. This is the short period of time during which our body's construction plan is put in place, during its embryonic life. The appearance of limbs and vertebrae is orchestrated by a family of 'architect' genes called Hox, each providing precise instructions at a given time. Denis Duboule, a geneticist at the Faculty of Science of the University of Geneva (UNIGE) and at the Swiss Federal Institute of Technology in Lausanne (EPFL), demonstrated that these genes were aligned within our chromosomes according to the order of structures that will emerge: first the components of the shoulder, then the arm, and finally the fingers.

The cluster of Hoxd genes coordinates the operations of limb formation, in particular. These genes are transcribed in two successive waves, allowing the development of the arm, then the hand. "We had already discovered that the genes responsible for the hand were controlled by enhancers, specific DNA sequences located in an adjacent area, at one end of the Hoxd cluster. This regulatory domain takes on a different three-dimensional configuration, according to the degree of activity of the enhancers," says Professor Duboule.

Two distinct regulatory domains

In order to understand the molecular processes that preside over arm formation, as well as the transition to wrist and hand formation, the researchers used sophisticated techniques of genetic engineering, molecular biology, and murine embryo cell lines. "Curiously, certain Hoxd genes are involved in the origin of both the arm and the hand, while it is their absence of expression that enables wrist formation," notes Guillaume Andrey, former doctoral student at the Frontiers in Genetics National Research Center and first author of the article.

The biologists demonstrated the existence of a second regulatory domain.

However, there is an intermediary cellular territory that escapes the two regulatory controls and in which the switch is not activated: this zone will generate the wrist.

However, it is responsible for arm development and is located at the other end of the Hoxd gene cluster. They decrypted the complex dialogue established between these genes and the two adjacent domains: "Certain Hoxd genes associate with only one of the two domains, whereas others interact with both, but in different cells and at separate times," explains Guillaume Andrey.

The wrist emerges from a no man's land

During the growth of the limb bud, certain Hoxd genes will shift toward the opposite regulatory domain to establish new contacts. This swing from one domain to the other is the equivalent of a genetic switch, signaling the transition between the creation of the arm and the hand. However, there is an intermediary cellular territory that escapes the two regulatory controls and in which the switch is not activated: this zone will generate the wrist. Thus, the articulation of activities between domains A and B enables the appearance of a morphological articulation between our arms and our hands. "The three-dimensional organization of these two regulatory domains, which gives them physical and functional independence, plays an essential role in stimulating the Hoxd genes. These experiments allowed us to demonstrate that there is an additional, topological level of information to modulate gene expression. This is a first!"' says Guillaume Andrey.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/top_environment/~3/Dyme0lxyav0/130606154704.htm

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