Boston bombing suspect is walking, mother says

Abdul-Baki Todashev holds a photo he claims is of his dead son Ibragim Todashev, during a news conference in Moscow, Russia, Thursday, May 30, 2013. The father of a Chechen immigrant killed in Florida while being interrogated by the FBI about his ties to a Boston Marathon bombings suspect says agents killed his son ?execution style.? Abdul-Baki Todashev showed journalists 16 photographs on Thursday of his son, Ibragim, in the morgue with what he said were six gunshot wounds to his torso and one to the back of the head. He said the pictures were taken by his son?s friend Khusen Taramov. (AP Photo/Alexander Zemlianichenko)

Abdul-Baki Todashev holds a photo he claims is of his dead son Ibragim Todashev, during a news conference in Moscow, Russia, Thursday, May 30, 2013. The father of a Chechen immigrant killed in Florida while being interrogated by the FBI about his ties to a Boston Marathon bombings suspect says agents killed his son ?execution style.? Abdul-Baki Todashev showed journalists 16 photographs on Thursday of his son, Ibragim, in the morgue with what he said were six gunshot wounds to his torso and one to the back of the head. He said the pictures were taken by his son?s friend Khusen Taramov. (AP Photo/Alexander Zemlianichenko)

Abdul-Baki Todashev holds a photo he claims is of his dead son Ibragim Todashev, during a news conference in Moscow, Russia, Thursday, May 30, 2013. The father of a Chechen immigrant killed in Florida while being interrogated by the FBI about his ties to a Boston Marathon bombings suspect says agents killed his son ?execution style.? Abdul-Baki Todashev showed journalists 16 photographs on Thursday of his son, Ibragim, in the morgue with what he said were six gunshot wounds to his torso and one to the back of the head. He said the pictures were taken by his son?s friend Khusen Taramov. (AP Photo/Alexander Zemlianichenko)

Abdul-Baki Todashev holds a photo he claims is of his dead son Ibragim Todashev during a news conference in Moscow, Russia, Thursday, May 30, 2013. The father of a Chechen immigrant killed in Florida while being interrogated by the FBI about his ties to a Boston Marathon bombings suspect says agents killed his son ?execution style.? Abdul-Baki Todashev showed journalists 16 photographs on Thursday of his son, Ibragim, in the morgue with what he said were six gunshot wounds to his torso and one to the back of the head. He said the pictures were taken by his son?s friend Khusen Taramov. (AP Photo/Alexander Zemlianichenko)

Abdul-Baki Todashev holds a photo he claims is of his dead son Ibragim Todashev, during a news conference in Moscow, Russia, Thursday, May 30, 2013. The father of a Chechen immigrant killed in Florida while being interrogated by the FBI about his ties to a Boston Marathon bombings suspect says agents killed his son ?execution style.? Abdul-Baki Todashev showed journalists 16 photographs on Thursday of his son, Ibragim, in the morgue with what he said were six gunshot wounds to his torso and one to the back of the head. He said the pictures were taken by his son?s friend Khusen Taramov. (AP Photo/Alexander Zemlianichenko)

Zubeidat Tsarnaeva, mother of the two Boston bombing suspects, shows videos on an iPad she says show her sons could not have been involved in last month's Boston Marathon bombings in Makhachkala, regional capital of Dagestan, Russia, Thursday, May 30, 2013. Authorities accuse Tamerlan Tsarnaev, who was slain in a shootout with police, and his younger brother Dzhokhar of organizing the attacks, which killed three. (AP Photo/Musa Sadulayev)

MAKHACHKALA, Russia (AP) ? The remaining suspect in the Boston Marathon bombings has recovered enough to walk and assured his parents in a phone conversation that he and his slain brother were innocent, their mother told The Associated Press on Thursday.

Meanwhile, the father of a Chechen immigrant killed in Florida while being interrogated by the FBI about his ties to the slain brother maintained that the U.S. agents killed his son "execution-style."

Dzhokhar Tsarnaev, 19, walked without a wheelchair to speak to his mother last week for the first and only phone conversation they have had since he has been in custody, Zubeidat Tsarnaeva told the AP.

In a rare glimpse at Dzhokhar Tsarnaev's state of mind, he told her he was getting better and that he had a very good doctor, but was struggling to understand what happened, she said.

"He didn't hold back his emotions either, as if he were screaming to the whole world: What is this? What's happening?," she said.

The April 15 bombings killed three people and wounded more than 260. Elder brother, 26-year-old Tamerlan Tsarnaev, was killed in a shootout with police, and Dzhokhar remains in a prison hospital after being badly wounded.

"I could just feel that he was being driven crazy by the unfairness that happened to us, that they killed our innocent Tamerlan," their mother said, standing by the family's insistence that their children are innocent.

The Tsarnaevs met the AP in their new apartment in a 14-story building in a well-to-do area of Makhachkala, the capital of the restive Caucasus province of Dagestan. The apartment had no furniture apart from a TV, a few rugs, and wallpaper materials lying on the floor.

Anzor Tsarnaev, the suspects' father, said they bought it for Tamerlan, his wife, and their young daughter in the expectation that they would move to Makhachkala later this year. He added that they planned to turn their old home in a dingy district on the outskirts of town into a dentist's office, so that Dzhokhar, a dental hygiene student, could work out of it after completing his studies.

"All I can do is pray to God and hope that one day fairness will win out, our children will be cleared, and we will at least get Dzhokhar back, crippled, but at least alive," Tsarnaev said.

Separately, at a news conference in Moscow, the father of a 27-year-old mixed martial arts fighter who was killed during FBI questioning accused agents of being "bandits" who executed his son.

Abdul-Baki Todashev showed journalists 16 photographs that he said were of his son, Ibragim, in a Florida morgue. He said his son had six gunshot wounds to his torso and one to the back of his head and the pictures were taken by his son's friend, Khusen Taramov.

It was not immediately possible to authenticate the photographs.

The FBI says Todashev was being questioned by an FBI agent and two Massachusetts state troopers about his ties to Tamerlan Tsarnaev, as well as about a 2011 triple slaying in Massachusetts.

Three law enforcement officials said initially that Ibragim Todashev had lunged at the FBI agent with a knife, although two of them later said it was no longer clear what had happened.

The father said his son was "100 percent unarmed."

Taramov confirmed Thursday that he had taken some pictures of Ibragim Todashev's body at an Orlando funeral home and sent them to the father. He said Ibragim Todashev had a decorative sword with a broken handle, but that it was not a weapon.

"The sword wouldn't cut nothing," Tamarov said. "I played with it many times. It wasn't sharp from any angle. It would do the same harm as a piece of wood."

The father said Taramov told him that U.S. agents interrogated him on the street while five officials interrogated Todashev in his Florida house for eight hours on May 22, the night he was shot.

Todashev's father said that his son moved to the U.S. in 2008 on a study exchange program and met Tsarnaev at a boxing gym in Boston in 2011, about a year before he moved to Orlando. He said the two were "not particularly close friends."

Prior to last month's bombings, Todashev underwent an operation for a sports injury and was on crutches, making it physically impossible for him to have been involved in the bombings, his father said. He added that Todashev had recently received a green card and was planning to return to Chechnya for the summer last Friday, two days after he was killed.

The father said he and his brother were interviewed at the U.S. Embassy in Moscow on Thursday as they sought a visa to take his son's body back to Chechnya.

FBI agents interrogated the younger Todashev twice before the night he was shot, his father said. He said his son told him that he thought Tsarnaev had been set up to take the blame for the bombings.

"I'd only seen and heard things like that in the movies ? they shoot somebody and then a shot in the head to make sure," Todashev said.

"These just aren't FBI agents, they're bandits," he added.

The FBI wouldn't comment on the claims made by Todashev's father.

The Tsarnaevs' parents have held fast to their belief that their sons were framed. Zubeidat Tsarnaeva, dressed all in black and still visibly distressed, showed AP several YouTube videos on an iPad she claimed cleared her sons. They could not be authenticated by the AP.

"I remember when our cat was sick, Tamerlan was sick himself for two days afterward, because he was so worried about her," Tsarnaeva said.

She said Tamerlan told her about Todashev, and that she and her husband had invited him to visit them in Russia, though he never came. Tamerlan later told them that he and Todashev were unlikely to continue training together since they practiced different sports, and he appeared to have lost track of him after Todashev moved to Florida, Tsarnaeva added.

_____

Seddon reported from Moscow. Associated Press writer Denise Lavoie in Boston and Kyle Hightower in Orlando contributed to the story.

_____

Follow Max Seddon on Twitter: http://twitter.com/maxseddon

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/cae69a7523db45408eeb2b3a98c0c9c5/Article_2013-05-30-Russia-Boston%20Bombings/id-cd7212cff45e432fb0781b37d6cb7e38

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Tornadoes touch down in Oklahoma, Arkansas

A wall cloud forms near Interstate 35 and Purcell, Okla. on Thursday, May 30, 2013. At least two tornadoes touched down in Oklahoma and another hit Arkansas on Thursday as a powerful storm system moved through the middle of the country. At least nine injuries were reported. (AP Photo/Alonzo Adams)

A wall cloud forms near Interstate 35 and Purcell, Okla. on Thursday, May 30, 2013. At least two tornadoes touched down in Oklahoma and another hit Arkansas on Thursday as a powerful storm system moved through the middle of the country. At least nine injuries were reported. (AP Photo/Alonzo Adams)

This image provided by KFOR-TV shows storm clouds moving over Guthrie, Okla., on Thursday, May 30, 2013. The Storm Prediction Center in Norman, Okla., warns there?s a moderate risk of severe weather over much of eastern and central Oklahoma on Thursday, the same area where a tornado last week killed 24 people. (AP Photo/KFOR-TV) MANDATORY CREDIT

This image provided by KFOR-TV shows storm clouds moving over Guthrie, Okla., on Thursday, May 30, 2013. The Storm Prediction Center in Norman, Okla., warns there?s a moderate risk of severe weather over much of eastern and central Oklahoma on Thursday, the same area where a tornado last week killed 24 people. (AP Photo/KFOR-TV, Chase Thomason) MANDATORY CREDIT

A wall cloud forms near Interstate 35 and Purcell, Okla. on Thursday, May 30, 2013. At least two tornadoes touched down in Oklahoma and another hit Arkansas on Thursday as a powerful storm system moved through the middle of the country. At least nine injuries were reported. (AP Photo/Alonzo Adams)

OKLAHOMA CITY (AP) ? At least three tornadoes touched down in Oklahoma, including one in Tulsa, and two more hit Arkansas on Thursday as a powerful storm system moved through the middle of the country. At least nine people were injured.

The National Weather Service confirmed at least one tornado touched down Thursday night in the Tulsa suburb of Broken Arrow. However, the tornado did not appear to be a strong twister like the deadly one in suburban Oklahoma City last week.

Meteorologist Pete Snyder with the weather service's Tulsa office said it appeared the roofs of some buildings were damaged, and police told the Tulsa World that they didn't have any reports of buildings being destroyed.

Earlier in the day, tornadoes touched down in Oklahoma and Arkansas, injuring at least nine people.

The National Weather Service reported two tornadoes on the ground near Perkins and Ripley in north central Oklahoma and another west of Oden, Ark.

Thursday's tornadoes all appeared to be much less dangerous than the top-of-the-scale EF5 storm that struck Moore, Okla., on May 20 and killed 24 along its 17-mile path. The U.S. averages more than 1,200 tornadoes a year, but top-of-the-scale storms like the one in Moore ? with winds over 200 mph ? happen only about once per year. The tornado last week was the nation's first EF5 since 2011.

All nine of the injured Thursday were in Arkansas; two of the injuries were attributed to a lightning strike in Rogers. Lightning was also believed to have started a fire that destroyed two floors of a condominium building in northwestern Indiana.

Some trees, homes and power lines were damaged in Arkansas, and the National Weather Service confirmed that tornadoes touched down in Montgomery County and in Clark County. Emergency Management spokesman Tommy Jackson said first responders had trouble reaching a destroyed home where one person was hurt because a number of trees were blocking the road.

In Oklahoma, Perkins Emergency Management Director Travis Majors said there were no injuries or damage there. Ripley, about 10 miles east of Perkins, did not seem to have significant damage. The Payne County emergency management director did not immediately return a phone call seeking comment.

Storms also caused problems in the western Iowa town of Onawa, damaging buildings, breaking windows, tearing awnings and blowing down trees and a stoplight. National Weather Service meteorologist Dave Fobert told the Sioux City Journal that the damage apparently was caused by a thunderstorm, not a tornado.

Some strong winds blew through Moore, in suburban Oklahoma City, on Thursday, but the weather didn't cause significant problems for crews cleaning up from last week's tornado.

Organizers pushed back Thursday's start of the Wakarusa Music Festival north of Ozark, Ark., as threatening weather approached. After a series of storms moved through the area, Franklin County Emergency Manager Fred Mullen said no flooding was reported at the site, located along Arkansas' Pig Trail scenic highway.

In addition to tornadoes, the storms were bringing rain and hail. Flooding was also a concern in parts of Missouri, Iowa and Illinois through Sunday.

This spring's tornado season got a late start, with unusually cool weather keeping funnel clouds at bay until mid-May. The season usually starts in March and then ramps up for the next couple of months.

Of the 60 EF5 tornadoes since 1950, Oklahoma and Alabama have been struck the most, seven times each. More than half of these top-of-the-scale twisters have occurred in just five states: Alabama, Iowa, Kansas, Oklahoma and Texas.

___

Associated Press writers Ken Miller in Oklahoma City, Jeannie Nuss in Little Rock, Ark., and Seth Borenstein in Washington contributed to this report

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/386c25518f464186bf7a2ac026580ce7/Article_2013-05-30-US-Severe-Weather/id-37e04460990340f8b67d30b123deba95

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Iraqi officials: Bomb blasts kill 17 in Baghdad

BAGHDAD (AP) ? Bomb blasts tore through two Baghdad markets Wednesday evening, killing at least 17 people and extending a relentless wave of bloodshed roiling Iraq.

The attacks come as the country is experiencing its most sustained bout of violence since the 2011 U.S. military withdrawal. More than 450 people have been killed since the start of May.

The deadliest bombing struck the northwestern Sunni neighborhood of Ghazaliyah, where a roadside bomb and car bomb exploded near a market, killing 10 people and wounding 25, police said.

Another car bomb exploded in the mixed Sunni-Shiite Jihad neighborhood, killing seven and wounding 18, officials said.

That southwestern neighborhood was one of the earliest flashpoints in Baghdad's descent into sectarian bloodshed in the years following the 2003 U.S. led invasion. It housed mainly Sunni civil servants and security officials under Saddam Hussein's regime, though many Shiites now live there too.

Many of Jihad's Sunni residents earlier this year received threatening leaflets from a Shiite militant group warning them to leave. The group, the Mukhtar Army, is not known to have carried out car bombings in the past.

There was no immediate claim of responsibility. Car bombings in civilian areas are often the work of al-Qaida's Iraq arm, which aims to undermine faith in the Shiite-led government.

Hospital officials confirmed the casualties. All officials spoke on condition of anonymity because they were not authorized to release the information.

Earlier Wednesday, a senior member of an Iraqi Shiite militia that once fought the U.S. military warned that Iraq is heading toward widespread sectarian bloodletting similar to the kind that once pushed the country to the brink of civil war.

The head of the political bureau of the Asaib Ahl al-Haq group, Adnan Faihan, also said the militia is preparing to defend itself, but denied the group's involvement in a spate of attacks targeting Iraq's Sunni Arab minority.

Iraq has been wracked by a wave of the most sustained violence the country has seen since American troops left in late 2011. The bloodshed, which includes coordinated car bombings blamed on Sunni militants as well as a string of attacks on Sunni mosques, is raising fears that Iraq is slipping back toward all-out sectarian fighting like that which nearly tore the country apart at its peak in 2006 and 2007.

"We have major concerns. Because what is going on now is the same that led to what happened in 2006," Faihan told The Associated Press. "We are ready for it and we are ready to protect our people."

Faihan made the comments on the sidelines of a press conference it held in Baghdad under heavy guard by camouflage-clad militia members.

During the event, Faihan distanced the group from recent attacks against Sunnis, saying such allegations were the result of a misleading defamation campaign.

He railed against what he called a Turkish-Qatari agenda to create sectarian strife again and to divide Iraq ? a reference to Sunni countries many Shiites accuse of backing members of Iraq's Sunni community who have been holding months of protests against the Shiite-led government.

Years ago, Asaib Ahl al-Haq ? or the Band of the Righteous ? broke away from radical Shiite cleric Muqtada al-Sadr's political bloc and has been trying to morph into a legitimate political movement.

It said in late 2011 it was moving away from armed struggle after U.S. forces left but it has not handed over its weapons. It and the Hezbollah Brigades were among a group of Shiite militias backed by Iran that carried out lethal attacks against U.S. bases in the summer of 2011.

Faihan on Wednesday also urged the Shiite faithful to defend the Sayida Zeinab shrine in Syria. The holy site outside Damascus has been a rallying point for foreign Shiite militants fighting alongside government troops loyal to President Bashar Assad, whose Alawite sect is an offshoot of Shiite Islam.

"Our stance is ... not to interfere in others' internal affairs. But regarding Sayida Zeinab shrine, we've called on Muslims to go and protect it because any attack on the shrine will lead to bloody events in the region. So protecting this shrine is a must," he said.

Also on Wednesday, Iraqi officials raised the death toll from attacks the previous day that shook Baghdad and towns north of the capital to 28.

Police said the deadliest of Tuesday's attacks struck the southern Dora neighborhood, where back-to-back bombings killed nine people and wounded 10. Bombs in the eastern neighborhood of Sadr City and in the northern Shaab area killed 12 and wounded 33.

Blasts and shootings in Tarmiyah and Mosul killed seven other people.

Medical officials confirmed the casualty figures. All spoke on condition of anonymity because they are not authorized to talk to the media.

___

Associated Press writers Adam Schreck and Sinan Salaheddin contributed.

Source: http://news.yahoo.com/iraqi-officials-bomb-blasts-kill-17-baghdad-182119129.html

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'Menace II Society' Legends O-Dog And Caine Reunite On 'RapFix Live'

'It's definitely going to go in the vaults of classics in all of cinema,' actor Larenz Tate says of 'Menace' 20 years after its release.
By Rob Markman, with reporting by Sway Calloway

Source: http://www.mtv.com/news/articles/1708200/menace-ii-society-larenz-turner-tyrin-turner.jhtml

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Partisan showdown looms over DC circuit nominees (The Arizona Republic)

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Money-laundering scheme hid $6 billion for fraudsters like 'Joe Bogus'

US investigators shut down a vast cyber money-laundering scheme used by clients who sought complete anonymity, calling themselves things like 'Russia Hackers' and saying their address was '123 Fake Main Street.'

By Mark Clayton,?Staff writer / May 29, 2013

Preet Bharara, US attorney for the Southern District of New York, describes a chart showing the global interests of Liberty Reserve, during a news conference in New York on Tuesday. Arthur Budovsky, the founder of Liberty Reserve, was indicted in the United States along with six other people in a $6 billion money-laundering scheme described as 'staggering' in its scope, authorities said.

Richard Drew/AP

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Criminal investigators slammed the digital door on a massive $6 billion cyber money-laundering scheme with 1 million users worldwide, including more than 200,000 users in the US, according to court documents.

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Operating out of Costa Rica, the creators of Liberty Reserve billed their online company as an ?instant, real-time currency for international commerce,? which could be used to ?send and receive payments from anyone, anywhere on the globe,? the documents said. But investigators from the US Secret Service, Internal Revenue Service, Immigrations and Customs Enforcement saw only a scam.

From the start, Liberty Reserve?s creators are alleged to have to crafted a global electronic network intended as a conduit for criminals to launder their ill-gotten gains, according to the federal indictment and other court documents unveiled in New York City Tuesday.

From 2006 to 2013, Liberty Reserve grew exponentially to become one of the world?s most widely used digital currency services, the documents say. But in short order, the company became a ?financial hub of the cybercrime world,? anonymously processing profits from criminal activity that ranged from identity theft and credit card fraud to computer hacking, investment fraud, child pornography, and drug trafficking, the indictment alleges.

Not everyone who used Liberty Reserve to transmit a type of digital currency instantly and anonymously around the world was a criminal. But most were,???????? federal investigators said. Court documents describe an Internet-based operation of ?staggering? scope that served as a vital tool for cyber thieves and criminals to first convert ill-gotten cash to an anonymous digital currency ? then, later, convert it back into cash and transmit it to banks worldwide.

Anonymity was the real currency, however. With no real names necessary, and no proof of identification required, anonymous accounts could be opened and cash deposited at Liberty Reserve-affiliated ?exchangers? worldwide.

It was common, for instance, for Liberty Reserve users to establish accounts under false names, including such obvious criminal names as ?Russia Hackers? and ?Hacker Account,? the court documents said. During the investigation, one agent opened and executed transactions under the name of ?Joe Bogus? with the address ?123 Fake Main Street? in ?Completely Made Up City, New York.?

Once an account was set up, the user could transfer a digital currency called ?LR? to other account holders. In these transactions, the user could receive LR transfers, including any ?merchants? that accepted LR as payment. Along the way, Liberty Reserve charged a percent fee for every transfer.

For a ?privacy fee? of 75 cents per transaction, a user could hide their Liberty Reserve account number when transferring funds, making the transfer completely untraceable, the indictment said.

Cyber bank thieves who recently stole $45 million by hacking into two Middle Eastern banks, and then raising the limits on prepaid debit cards, used Liberty Reserve to distribute their proceeds, the court documents allege.

?The only liberty that Liberty Reserve gave many of its users was the freedom to commit crimes ? the coin of its realm was anonymity, and it became a popular hub for fraudsters, hackers, and traffickers,? Manhattan US Attorney Preet Bharara said, in a statement. ?As crime goes increasingly global, the long arm of the law has to get even longer, and in this case, it encircled the earth.?

Seven principals of Liberty Reserve are charged with money laundering and operating an unlicensed money transmitting business that processed 55 million transactions worth $6 billion, virtually all illegal. Five arrests were announced along with the seizure of online domains linked to Liberty Reserve, digital storefronts or ?exchangers? that were vital conduits for bringing cash into the global network.

Among the five arrested were Arthur Budovsky, the principal founder of Liberty Reserve, who was arrested in Spain. Vladimir Kats, the company?s co-founder, was arrested in the Brooklyn borough of New York.

In all, 45 bank accounts were frozen and forfeiture sought for 35 exchanger websites, including the exchangers? domain names, because the websites were used ?to facilitate the Liberty Reserve money laundering,? the indictment said.

Treasury Undersecretary for Terrorism and Financial Intelligence David Cohen told reporters that the government was not trying to crack down on new digital currencies. "I want to make clear that today's action does not mean that we are trying to eliminate virtual currencies and their providers," he said.

But the message to future digital currency criminals was equally clear. Anyone visiting the company website on Wednesday would have seen an unambiguous message: "This domain name has been seized by the United States Global Illicit Financial Team."

Source: http://rss.csmonitor.com/~r/feeds/csm/~3/vz5vAvKR-Xk/Money-laundering-scheme-hid-6-billion-for-fraudsters-like-Joe-Bogus

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iNFORMATiON FARM: Soylent | Replace Food With Fuel

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?We're all mad here. I'm mad. You're mad.? said the Cat. ?How do you know I'm mad?? said Alice. ?You must be?, said the Cat, ?or you wouldn't have come here.?

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House Judiciary: Did Eric Holder lie under oath? (cbsnews)

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Crown Estate, Canada's Oxford Properties sign $483 million London JV

LONDON (Reuters) - Britain's Crown Estate has signed a 320 million pound joint venture with Canada's Oxford Properties to redevelop London's upmarket St James's Market district, the two companies said on Tuesday.

The Crown Estate, which manages the Queen's property portfolio, said the deal creates a 50-50 partnership in which each will own 150 year leasehold interests in two blocks located between London's Regent Street and Haymarket district.

Oxford Properties is owned by Ontario Municipal Employees Retirement System, one of Canada's largest pension funds.

The scheme is part of the Crown Estate's ten year plan to redevelop the St James's Market area, and will provide 210,000 square feet of prime office and 50,000 square feet of retail and restaurant space once completed, the two companies said.

The Crown Estate is by law not allowed to take on debt and previously signed a joint venture with Norway's $660 billion oil fund to finance the redevelopment of shopping belt Regent Street. It owns 4 million square feet of retail, office and residential space in the St James's district.

(Reporting by Brenda Goh; Editing by Neil Maidment)

Source: http://news.yahoo.com/crown-estate-canadas-oxford-properties-sign-483-million-091039808.html

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Medium Term Treasury Bond ETF Investing 101 - May 28, 2013 ...

As far as ETFs are concerned, 2013 has been pretty much a year for the short term segment so far. Besides the huge surge in interest for Japan ETFs, short term bond ETFs were among the hottest picks for investors (read DXJ vs. DBJP: Which is the Better Hedged Japan ETF?).

The space saw great inflows in their asset bases with funds like Vanguard Short Term Bond ETF (BSV), iShares Barclays 1-3 Year Credit Bond ETF (CSJ) and iShares Barclays Short Treasury Bond ETF (SHV) topping the creation list in the short term bond ETF space (see Are Short Term Bond ETFs the New Safe Haven?).

Nevertheless, the recent surge in the asset inflow of medium term U.S Treasury bond ETFs point towards the fact that the safety of U.S treasuries has not entirely been discarded by investors, even amidst the overall optimism in the equity markets.

Investment case for the Intermediate Term Treasury Bond ETFs

These ETFs predominantly target the intermediate part of the treasury yield curve and carry moderate levels of interest rate risk. In fact, these can be considered to be the sweet spots across the yield curve which do not limit the income opportunity as opposed to short term bond funds. At the same time, the medium term bonds limit the interest rate risks as opposed to longer dated Treasury bond ETFs.

In fact, considering the present circumstances, the intermediate term Treasury bond ETFs may have the most lucrative investment opportunity compared to the long and short dated counterparts.

The short term interest rates are almost nearing zero percentin yields resulting in negative real returns. At the same time, concerns are rising over a possible interest rate increase for the longer dated Treasury bonds, which would cause big losses in these products (see Time to Buy Floating Rate ETFs?).

If one takes the above scenarios together, investors primarily need two things from their bond ETFs? adecent payout ofincome coupled with relative insulation from rising interest rates. And nothing fits the bill like the intermediate term Treasury bond ETFs.

ETF Choices to Target Intermediate Treasury Bonds

Probably two of the most popular and widely traded funds from the medium term bond ETF space are the iShares Barclays 3-7 Year Treasury Bond ETF (IEI) and the iShares Barclays 7-10 Year Treasury Bond ETF (IEF). The former has an asset base of around $3.8 billion while the latter has managed to amass $4.7 billion in total assets.

Both these iShares ETFs charge investors 15 basis points in fees and expenses and have high average daily volumes. However, IEF tracks the performance of Treasury bonds which are further away in terms of residual maturity compared to IEI.

This fact is highlighted by the average maturity of the two ETFs, with IEI having a weighted average maturity of 4.62 years compared to IEF?s 8.36 years.

Also, IEF lies higher in the hierarchy of risk return tradeoff as its average duration of 7.53 years is one of the highest in the intermediate term Treasury Bond ETF space. In comparison, IEI has an average duration of 4.41 years suggesting it has a much lower level of duration risk (see Time to Buy The Hedged European ETF?).

Launched in May of 2007, the SPDR Barclays Intermediate Term Treasury ETF (ITE) is another choice from the intermediate term Treasury bond ETF space. It has a fairly large window of maturity from which it can pick treasury bonds for its portfolio. It targets Treasuries having a residual maturity between 1 and 10 years.

It has an asset base of $169.69 million and trades in fairly large quantities. Not surprisingly, it sports a paltry dividend yield of 1.53%.

It holds around 194 securities in its portfolio and has an average maturity of 3.88 years. The ETF also has moderate levels of interest rate risk as measured by its average duration of 3.68 years.

The Vanguard Intermediate Term Government Bond ETF (VGIT) is another option available to the investors to gain exposure in the medium term treasury bond ETF space. Still investors should note that it does not have a large asset base and more shares are traded in most of the fund?s counterparts.

Nevertheless, it targets bonds having a residual maturity between 5 to 10 years; however, most of the bonds in its portfolio are comprised of the shorter end of this maturity spectrum.

This fact is highlighted by the fact that it has a weighted average of 5.4 years to maturity and a moderate level of interest rate sensitivity as measured by an average duration of 5.1 years (read ECB Rate Cut: How Did It Impact Euro ETFs?).

VGIT has an asset base of approximately $186.13 million and charges investors 12 basis points in fees and expenses.

For investors who are willing to welcome some extra risk in their portfolio the ProShares Ultra 7-10 Year Treasury Bond ETF (UST) might come in handy. The ETF has been an extremely popular choice among investors lately as the fund has seen abnormally high inflows in its asset base lately.

The ETF is a 2X leveraged version of IEF and tracks twice the daily performance of the Barclays Capital U.S. 7-10 Year Treasury Index. Since it involves leverage and daily rebalancing, the ETF charges a hefty premium in the form of expense ratio which stands at 95 basis points.

However, investors should note that the ETF might not prove to be a good candidate for a buy and hold strategy since the rebalancing is done on a daily basis. Therefore, the actual results may vary from the targeted 200% of the Index returns if held for more than one day.

However, with the backdrop of falling interest rates and an ultra loose interest rate policy by the Federal Reserve, the leveraged ETF, UST, has completely crushed its non leveraged counterparts in terms of cumulative performance.

The following chart depicts the performance of all the non leveraged ETFs discussed in the article from the medium term ETF space. The time horizon in consideration is 3 years.

Bottom Line

As we can see, all of the funds have performed in a relatively tight range over the past few years. The biggest winner has easily been IEF though, as this product has crushed its competitors.

A large part of this outperformance is due to IEF?s position on the yield curve when compared to other treasury bond ETFs in the medium segment of the curve. And in a scenario of falling interest rates, the returns for this are bound to be higher for these higher duration securities rather than those that have comparatively shorter durations (see Cambria Launches Shareholder Yield ETF (SYLD)).

Nevertheless, it is important to consider that all Treasury ETFs have had an extremely impressive run thus far, therefore the possibility of a top in these ETFs cannot be ruled out.

This is especially true considering a possible QE exit by the Fed and interest rates creeping upwards, especially for the longer dated bonds. Investors should therefore exercise caution before investing in these products, especially higher duration ones.

Until that time though, products in the middle portion of the curve, such as those highlighted above, could present themselves as solid options for investors seeking to make a low risk investment that still has a bit of yield in today?s market environment.

Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free report >>

Source: http://www.zacks.com/stock/news/100215/medium-term-treasury-bond-etf-investing-101

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Syrian troops gain ground, TV reporter killed

In this photo released on Sunday, May 26, 2013, by the Syrian official news agency SANA, Syrian forces loyal to Syrian President Bashar Assad take their position during a clashes against Syrian rebels, in Aleppo, Syria. Syria's Information Ministry says rebels have killed a TV correspondent who was covering clashes near the border with Lebanon. (AP Photo/SANA)

In this photo released on Sunday, May 26, 2013, by the Syrian official news agency SANA, Syrian forces loyal to Syrian President Bashar Assad take their position during a clashes against Syrian rebels, in Aleppo, Syria. Syria's Information Ministry says rebels have killed a TV correspondent who was covering clashes near the border with Lebanon. (AP Photo/SANA)

In this photo released on Sunday May 26, 2013, by the Syrian official news agency SANA, Syrian forces loyal to Syrian President Bashar Assad run to take their position during clashes against Syrian rebels, in Aleppo, Syria. Syria's Information Ministry says rebels have killed a TV correspondent who was covering clashes near the border with Lebanon. (AP Photo/SANA)

In this photo released on Sunday, May 26, 2013, by the Syrian official news agency SANA, Syrian forces loyal to Syrian President Bashar Assad take their position during clashes against Syrian rebels, in Aleppo, Syria. Syria's Information Ministry says rebels have killed a TV correspondent who was covering clashes near the border with Lebanon. (AP Photo/SANA)

In this image taken from video obtained from the Shaam News Network, which has been authenticated based on its contents and other AP reporting, Syrians participate in the funeral prayer for Youssef Ghazi al-Sarmani who was killed in fighting between rebel and government forces, May 27. Logo in red reads, "Talbiseh". (AP Photo/Shaam News Network via AP video)

DAMASCUS, Syria (AP) ? Syrian troops gained ground Monday in a nine-day offensive against a key rebel-held town, and a Syrian TV correspondent covering the fighting there was killed by gunfire, state media and a pro-opposition group reported.

The fighting raged as European Union foreign ministers met in Brussels to try to bridge divisions over easing an arms embargo, a step that would allow weapons shipments to rebels fighting Syrian President Bashar Assad.

In Paris, U.S. Secretary of State John Kerry and Russian Foreign Minister Sergey Lavrov exchanged updates on their efforts to launch Syrian peace talks at an international conference in Geneva next month.

The Assad regime has said it is willing to attend the talks in principle, while Syria's fractured political opposition is still holding internal discussions about it.

There is little evidence that either side is ready to halt the violence that has killed more than 70,000 people since March 2011.

In Syria, heavy fighting was reported Monday in the western town of Qusair, the target of a regime offensive that began May 19, and around the nearby Dabaa military base.

The Britain-based Syrian Observatory for Human Rights, a pro-opposition group, said regime troops and allied fighters from the Lebanese militia Hezbollah captured the nearby town of Hamidiyeh, tightening their siege of Qusair. Observatory director Rami Abdul-Rahman said troops were trying to capture the village of Haret al-Turkumen in order to put Qusair under "complete siege."

Syrian state TV said troops captured more parts of the northern and central rebel-held neighborhoods of Qusair. The town had been under rebel control almost from the start of the uprising against Assad in 2011.

Al-Mayadeen TV, which has several reporters embedded with Syrian troops, aired video from the town showing widespread destruction. At least three bodies could be seen on one of the streets.

In an incident apparently related to the fighting, a rocket struck the Lebanese town of Hermel, just across the border from Qusair. A 17-year-old girl was killed and a woman was wounded by the rocket, said a Lebanese security official, speaking on condition of anonymity in line with regulations.

The Observatory said that Hezbollah has lost 79 fighters in Syria in 10 days of fighting, all of them but four of them in the Qusair area.

The battle for Qusair has exposed Hezbollah's growing role in the Syrian conflict. The Shiite militant group, which has been fighting alongside Assad's troops, initially tried to play down its involvement, but could no longer do so after dozens of its fighters were killed in the area and buried in large funerals in Lebanon.

On Saturday, Hezbollah leader Hassan Nasrallah firmly linked his militant group's fate to the survival of the Syrian regime, raising the stakes not just in Syria, but also in Hezbollah's relations with rival groups in Lebanon.

Qusair's value lies in its location along a land corridor linking two of Assad's strongholds, the capital of Damascus and towns on the Mediterranean coast, the heartland of his minority Alawite sect, an offshoot of Shiite Islam. For the rebels, holding Qusair means protecting a supply line to Lebanon, just 10 kilometers (six miles) away.

The Syrian reporter killed Monday, Yara Abbas, had been covering the fighting near Qusair.

Abbas, who worked for state-owned Al-Ikhbariyah TV, was attacked by rebels who ambushed the car carrying her and her crew near the Dabaa base close to Qusair, the Syrian Information Ministry said in a statement carried by state TV. A cameraman and his assistant were wounded, the report said.

Dozens of journalists have been killed, wounded or kidnapped since Syria's crisis began.

Amnesty International said this month that Syria's government and some rebels are deliberately targeting journalists.

In the central city of Homs, a car bomb exploded near a gas station, killing at least four people and wounding dozens, the Observatory said. Syria's state-run news agency SANA put the number of dead at six.

The EU debate on easing the arms embargo showed deep divisions among member states. Britain was the most outspoken proponent of relaxing the arms embargo but faced strong opposition from EU members like Austria who feel that pouring more weapons into the war zone will only make the Syria conflict deadlier.

French Foreign Minister Laurent Fabius said Monday there were more indications than ever that gas warfare has become part of the Syrian civil war. France said it has been looking into such reports since early this month.

"(There are) are stronger and better substantiated indications of the local use of chemical arms. We have to check this and are doing this with our partners," Fabius said.

He did not specify which side was accused of using them.

___

Mroue reported from Beirut.

.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/cae69a7523db45408eeb2b3a98c0c9c5/Article_2013-05-27-Syria/id-8279e06371c243e1bf6250dad51c9576

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Sky's Apps Have Been Hacked And Are Off Google Play

The British Sky Broadcasting Group has removed their Android apps (Sky News, Sky Go, Sky+ and Sky Wi-Fi) from Google Play because of concerns that the Syrian Electronic Army has hacked the apps. Sky is advising users to delete the apps while they respond to the problem.

Read more...

Source: http://feeds.gawker.com/~r/gizmodo/full/~3/dKpVgL85I7E/skys-apps-have-been-hacked-and-are-off-google-play-509924532

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Samsung ATIV Book 7 review: a high-end Ultrabook arriving just before Haswell

If you've been waiting for Samsung to refresh last year's Series 9 Ultrabook, don't hold your breath; apart from a recent upgrade to 1080p resolution, it's basically stayed the same. That doesn't mean Samsung is taking a break from ultraportables, though: the company recently started shipping the Series 7 Ultra (now called the ATIV Book 7), which debuted at CES. Regardless of the name, the idea was always for it to be part of Samsung's performance line, ranking right below the flagship Series 9 family. To that end, it ships for $1,060 with all the specs you'd expect to find in a mid- to high-end Ultrabook: a Core i5 processor, 4GB of RAM, a 128GB SSD, a 13.3-inch, 1080p display and a stronger set of speakers than on the Series 9. Obviously, the fact that it's launching with Ivy Bridge is one knock against it, but how does it stack up otherwise? Might it be a good deal if it ever gets a CPU refresh?

Gallery: Samsung ATIV Book 7 review

Filed under: Laptops, Samsung

Comments

Source: http://www.engadget.com/2013/05/26/samsung-ativ-book-7-review/?utm_medium=feed&utm_source=Feed_Classic&utm_campaign=Engadget

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Rats have a double view of the world

May 27, 2013 ? Scientists from the Max Planck Institute for Biological Cybernetics in T?bingen, using miniaturised high-speed cameras and high-speed behavioural tracking, discovered that rats move their eyes in opposite directions in both the horizontal and the vertical plane when running around. Each eye moves in a different direction, depending on the change in the animal's head position. An analysis of both eyes' field of view found that the eye movements exclude the possibility that rats fuse the visual information into a single image like humans do. Instead, the eyes move in such a way that enables the space above them to be permanently in view -- presumably an adaptation to help them deal with the major threat from predatory birds that rodents face in their natural environment.

Like many mammals, rats have their eyes on the sides of their heads. This gives them a very wide visual field, useful for detection of predators. However, three-dimensional vision requires overlap of the visual fields of the two eyes. Thus, the visual system of these animals needs to meet two conflicting demands at the same time; on the one hand maximum surveillance and on the other hand detailed binocular vision.

The research team from the Max Planck Institute for Biological Cybernetics have now, for the first time, observed and characterised the eye movements of freely moving rats. They fitted minuscule cameras weighing only about one gram to the animals' heads, which could record the lightning-fast eye movements with great precision. The scientists also used another new method to measure the position and direction of the head, enabling them to reconstruct the rats' exact line of view at any given time.

The Max Planck scientists' findings came as a complete surprise. Although rats process visual information from their eyes through very similar brain pathways to other mammals, their eyes evidently move in a totally different way. "Humans move their eyes in a very stereotypical way for both counteracting head movements and searching around. Both our eyes move together and always follow the same object. In rats, on the other hand, the eyes generally move in opposite directions," explains Jason Kerr from the Max Planck Institute for Biological Cybernetics.

In a series of behavioural experiments, the neurobiologists also discovered that the eye movements largely depend on the position of the animal's head. "When the head points downward, the eyes move back, away from the tip of the nose. When the rat lifts its head, the eyes look forward: cross-eyed, so to speak. If the animal puts its head on one side, the eye on the lower side moves up and the other eye moves down." says Jason Kerr.

In humans, the direction in which the eyes look must be precisely aligned, otherwise an object cannot be fixated. A deviation measuring less than a single degree of the field of view is enough to cause double vision. In rats, the opposing eye movements between left and right eye mean that the line of vision varies by as much as 40 degrees in the horizontal plane and up to 60 degrees in the vertical plane. The consequence of these unusual eye movements is that irrespective of vigorous head movements in all planes, the eyes movements always move in such a way to ensure that the area above the animal is always in view simultaneously by both eyes -something that does not occur in any other region of the rat's visual field.

These unusual eye movements that rats possess appear to be the visual system's way of adapting to the animals' living conditions, given that they are preyed upon by numerous species of birds. Although the observed eye movements prevent the fusion of the two visual fields, the scientists postulate that permanent visibility in the direction of potential airborne attackers dramatically increases the animals' chances of survival.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/~3/-VslgCEbl9k/130527100530.htm

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Stanford researchers identify genetic suspects in sporadic Lou Gehrig's disease

Public release date: 26-May-2013
[ | E-mail | Share ]

Contact: Krista Conger
kristac@stanford.edu
650-725-5371
Stanford University Medical Center

STANFORD, Calif. - Researchers at the Stanford University School of Medicine have identified mutations in several new genes that might be associated with the development of spontaneously occurring cases of the neurodegenerative disease known as amyotrophic lateral sclerosis, or ALS. Also known as Lou Gehrig's disease, the progressive, fatal condition, in which the motor neurons that control movement and breathing gradually cease to function, has no cure.

Although researchers know of some mutations associated with inherited forms of ALS, the majority of patients have no family history of the disease, and there are few clues as to its cause. The Stanford researchers compared the DNA sequences of 47 patients who have the spontaneous form of the disease, known as sporadic ALS, with those of their unaffected parents. The goal was to identify new mutations that were present in the patient but not in either parent that may have contributed to disease development.

Several suspects are mutations in genes that encode chromatin regulators - cellular proteins that govern how DNA is packed into the nucleus of a cell and how it is accessed when genes are expressed. Protein members of one these chromatin-regulatory complexes have recently been shown to play roles in normal development and some forms of cancer.

"The more we know about the genetic causes of the disorder, the greater insight we will have as to possible therapeutic targets," said Aaron Gitler, PhD, associate professor of genetics. "Until now, researchers have primarily relied upon large families with many cases of inherited ALS and attempted to pinpoint genetic regions that seem to occur only in patients. But more than 90 percent of ALS cases are sporadic, and many of the genes involved in these cases are unknown."

Gitler is the senior author of the study, which will be published online May 26 in Nature Neuroscience. Postdoctoral scholar Alessandra Chesi, PhD, is the lead author. Gitler and Chesi collaborated with members of the laboratory of Gerald Crabtree, MD, professor of developmental biology and of pathology. Crabtree, a Howard Hughes Medical Institute investigator, is also a co-author of the study.

Chesi and Gitler combined deductive reasoning with recent advances in sequencing technology to conduct the work, which relied on the availability of genetic samples from not only ALS patients, but also the patients' unaffected parents. Such trios can be difficult to obtain for diseases like sporadic ALS that strike well into adulthood when a patient's parents may no longer be alive. Gitler and Chesi collaborated with researchers from Emory University and Johns Hopkins University to collect these samples.

The researchers compared the sequences of a portion of the genome called the exome, which directly contributes to the amino acid sequences of all the proteins in a cell. (Many genes contain intervening, non-protein-coding regions of DNA called introns that are removed prior to protein production.) Mutations found only in the patient's exome, but not in that of his or her parents', were viewed as potential disease-associated candidates - particularly if they affected the composition or structure of the resulting protein made from that gene.

Focusing on just the exome, which is about 1 percent of the total amount of DNA in each human cell, vastly reduced the total amount of DNA that needed to be sequenced and allowed the researchers to achieve relatively high coverage (or repeated sequencing to ensure accuracy) of each sample.

"We wanted to find novel changes in the patients," Chesi said. "These represent a class of mutations called de novo mutations that likely occurred during the production of the parents' reproductive cells." As a result, these mutations would be carried in all the cells of patients, but not in their parents or siblings.

Using the exome sequencing technique, the researchers identified 25 de novo mutations in the ALS patients. Of these, five are known to be in genes involved in the regulation of the tightly packed form of DNA called chromatin - a proportion that is much higher than would have been expected by chance, according to Chesi.

Furthermore, one of the five chromatin regulatory proteins, SS18L1, is a member of a neuron-specific complex called nBAF, which has long been studied in Crabtree's laboratory. This complex is strongly expressed in the brain and spinal cord, and affects the ability of the neurons to form branching structures called dendrites that are essential to nerve signaling.

"We found that, in one sporadic ALS case, the last nine amino acids of this protein are missing," Gitler said. "I knew that Gerald Crabtree's lab had been investigating SS18L1, so I asked him about it. In fact, they had already identified these amino acids as being very important to the function of the protein."

When the researchers expressed the mutant SS18L1 in motor neurons isolated from mouse embryos, they found the neurons were unable to extend and grow new dendrites as robustly as normal neurons in response to stimuli. They also showed that SS18L1 appears to physically interact with another protein known to be involved in cases of familial, or inherited, ALS.

Although the results are intriguing, the researchers caution that more work is necessary to conclusively prove whether and how mutations in SS18L1 contribute to sporadic cases of ALS. But now they have an idea of where to look in other patients, without requiring the existence of patient and parent trios. They are planning to sequence SS18L1 and other candidates in an additional few thousand sporadic ALS cases.

"This is the first systematic analysis of ALS triads for the presence of de novo mutations," Chesi said. "Now we have a list of candidate genes we can pursue. We haven't proven that these mutations cause ALS, but we've shown, at least in the context of SS18L1, that the mutation carried by some patients is damaging to the protein and affects the ability of mouse motor neurons to form dendrites."

###

Other Stanford co-authors include graduate student Brett Staahl and postdoctoral scholars Ana Jovicic, PhD, Julien Couthouis, PhD, Alya Raphael, PhD, and Laura Elias, PhD.

The research was funded by a National Institutes of Health Director's New Innovator Award (1DP2OD004417), the National Institutes of Health (1R01NS065317 and 5U01NS062713), the Department of Defense ALS Research Program, the Pew Charitable Trusts, the Rita Allen Foundation, the Packard Center for ALS Research at Johns Hopkins, the National Health and Medical Research Council of Australia and the Motor Neurone Disease Research Institute of Australia.

Information about Stanford's Department of Genetics, which also supported the work, is available at http://genetics.stanford.edu.

The Stanford University School of Medicine consistently ranks among the nation's top medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://mednews.stanford.edu. The medical school is part of Stanford Medicine, which includes Stanford Hospital & Clinics and Lucile Packard Children's Hospital. For information about all three, please visit http://stanfordmedicine.org/about/news.html.

Print media contacts:

Krista Conger

Ruthann Richter
650-725-8047
(richter1@stanford.edu)

Broadcast media contact:

M.A. Malone
650-723-6912
(mamalone@stanford.edu)

---

[ | E-mail | Share ]

?

AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

Public release date: 26-May-2013
[ | E-mail | Share ]

Contact: Krista Conger
kristac@stanford.edu
650-725-5371
Stanford University Medical Center

STANFORD, Calif. - Researchers at the Stanford University School of Medicine have identified mutations in several new genes that might be associated with the development of spontaneously occurring cases of the neurodegenerative disease known as amyotrophic lateral sclerosis, or ALS. Also known as Lou Gehrig's disease, the progressive, fatal condition, in which the motor neurons that control movement and breathing gradually cease to function, has no cure.

Although researchers know of some mutations associated with inherited forms of ALS, the majority of patients have no family history of the disease, and there are few clues as to its cause. The Stanford researchers compared the DNA sequences of 47 patients who have the spontaneous form of the disease, known as sporadic ALS, with those of their unaffected parents. The goal was to identify new mutations that were present in the patient but not in either parent that may have contributed to disease development.

Several suspects are mutations in genes that encode chromatin regulators - cellular proteins that govern how DNA is packed into the nucleus of a cell and how it is accessed when genes are expressed. Protein members of one these chromatin-regulatory complexes have recently been shown to play roles in normal development and some forms of cancer.

"The more we know about the genetic causes of the disorder, the greater insight we will have as to possible therapeutic targets," said Aaron Gitler, PhD, associate professor of genetics. "Until now, researchers have primarily relied upon large families with many cases of inherited ALS and attempted to pinpoint genetic regions that seem to occur only in patients. But more than 90 percent of ALS cases are sporadic, and many of the genes involved in these cases are unknown."

Gitler is the senior author of the study, which will be published online May 26 in Nature Neuroscience. Postdoctoral scholar Alessandra Chesi, PhD, is the lead author. Gitler and Chesi collaborated with members of the laboratory of Gerald Crabtree, MD, professor of developmental biology and of pathology. Crabtree, a Howard Hughes Medical Institute investigator, is also a co-author of the study.

Chesi and Gitler combined deductive reasoning with recent advances in sequencing technology to conduct the work, which relied on the availability of genetic samples from not only ALS patients, but also the patients' unaffected parents. Such trios can be difficult to obtain for diseases like sporadic ALS that strike well into adulthood when a patient's parents may no longer be alive. Gitler and Chesi collaborated with researchers from Emory University and Johns Hopkins University to collect these samples.

The researchers compared the sequences of a portion of the genome called the exome, which directly contributes to the amino acid sequences of all the proteins in a cell. (Many genes contain intervening, non-protein-coding regions of DNA called introns that are removed prior to protein production.) Mutations found only in the patient's exome, but not in that of his or her parents', were viewed as potential disease-associated candidates - particularly if they affected the composition or structure of the resulting protein made from that gene.

Focusing on just the exome, which is about 1 percent of the total amount of DNA in each human cell, vastly reduced the total amount of DNA that needed to be sequenced and allowed the researchers to achieve relatively high coverage (or repeated sequencing to ensure accuracy) of each sample.

"We wanted to find novel changes in the patients," Chesi said. "These represent a class of mutations called de novo mutations that likely occurred during the production of the parents' reproductive cells." As a result, these mutations would be carried in all the cells of patients, but not in their parents or siblings.

Using the exome sequencing technique, the researchers identified 25 de novo mutations in the ALS patients. Of these, five are known to be in genes involved in the regulation of the tightly packed form of DNA called chromatin - a proportion that is much higher than would have been expected by chance, according to Chesi.

Furthermore, one of the five chromatin regulatory proteins, SS18L1, is a member of a neuron-specific complex called nBAF, which has long been studied in Crabtree's laboratory. This complex is strongly expressed in the brain and spinal cord, and affects the ability of the neurons to form branching structures called dendrites that are essential to nerve signaling.

"We found that, in one sporadic ALS case, the last nine amino acids of this protein are missing," Gitler said. "I knew that Gerald Crabtree's lab had been investigating SS18L1, so I asked him about it. In fact, they had already identified these amino acids as being very important to the function of the protein."

When the researchers expressed the mutant SS18L1 in motor neurons isolated from mouse embryos, they found the neurons were unable to extend and grow new dendrites as robustly as normal neurons in response to stimuli. They also showed that SS18L1 appears to physically interact with another protein known to be involved in cases of familial, or inherited, ALS.

Although the results are intriguing, the researchers caution that more work is necessary to conclusively prove whether and how mutations in SS18L1 contribute to sporadic cases of ALS. But now they have an idea of where to look in other patients, without requiring the existence of patient and parent trios. They are planning to sequence SS18L1 and other candidates in an additional few thousand sporadic ALS cases.

"This is the first systematic analysis of ALS triads for the presence of de novo mutations," Chesi said. "Now we have a list of candidate genes we can pursue. We haven't proven that these mutations cause ALS, but we've shown, at least in the context of SS18L1, that the mutation carried by some patients is damaging to the protein and affects the ability of mouse motor neurons to form dendrites."

###

Other Stanford co-authors include graduate student Brett Staahl and postdoctoral scholars Ana Jovicic, PhD, Julien Couthouis, PhD, Alya Raphael, PhD, and Laura Elias, PhD.

The research was funded by a National Institutes of Health Director's New Innovator Award (1DP2OD004417), the National Institutes of Health (1R01NS065317 and 5U01NS062713), the Department of Defense ALS Research Program, the Pew Charitable Trusts, the Rita Allen Foundation, the Packard Center for ALS Research at Johns Hopkins, the National Health and Medical Research Council of Australia and the Motor Neurone Disease Research Institute of Australia.

Information about Stanford's Department of Genetics, which also supported the work, is available at http://genetics.stanford.edu.

The Stanford University School of Medicine consistently ranks among the nation's top medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://mednews.stanford.edu. The medical school is part of Stanford Medicine, which includes Stanford Hospital & Clinics and Lucile Packard Children's Hospital. For information about all three, please visit http://stanfordmedicine.org/about/news.html.

Print media contacts:

Krista Conger

Ruthann Richter
650-725-8047
(richter1@stanford.edu)

Broadcast media contact:

M.A. Malone
650-723-6912
(mamalone@stanford.edu)

---

[ | E-mail | Share ]

?

AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

Source: http://www.eurekalert.org/pub_releases/2013-05/sumc-sr052413.php

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