Friday, January 25, 2013

How Democrats Will Win the Budget Debate

148212861 Sen. Patty Murray at a news conference on Capitol Hill on July 12, 2012

Photo by Alex Wong/Getty Images.

Republicans have been complaining for years that Senate Democrats aren?t writing and voting on formal budget plans. Democrats? stated reasoning for this has been that there?s no point in passing a budget resolution that?s dead on arrival in the House of Representatives, especially when budget policy is actually made in high-stakes negotiations between House leaders and the Obama administration.

But their real reason for the budget negligence was more political. Democrats have shied away from voting for budgets that either contain large tax increases or large budget deficits and have been divided among themselves over how best to proceed. The GOP believes that forcing Democrats to go on the record with a budget will be a political bonanza.

A year ago it might have been. But Senate Democrats have a new top budget officer in town?Patty Murray of Washington state?who?s substantially more liberal and also more politically adept than her predecessor. With Kent Conrad, D-North Dakota, now retired and Murray in the chair of the Budget Committee, Democrats are eager to play ?compare the budgets.? They believe they can win the budget politics as soundly as they won the 2012 elections.

Murray was first elected in 1992 as part of a bumper crop of female legislators that earned the year the label ?Year of the Woman.? Her campaign, in particular, was noteworthy for its ironic appropriation of the label ?mom in tennis shoes,? a reference to a dismissive comment directed at her earlier in her career as a citizen lobbyist on environmental issues. Since that time, she hasn?t exactly been a legislative dynamo. There?s no Murray Act or even a major legislative proposal associated with her that?s been stymied. But she has an excellent political record, racking up win after win from the Shoreline, Wash., School Board to the Washington state Senate to four terms in the United States Senate.

Recently, her profile?s been skyrocketing. When she was tapped in 2011 to lead the Democratic Senate Campaign Committee for the 2012 cycle, it was widely viewed as a booby prize, the leadership job nobody wanted. The objective ?map? facing Democratic Senate candidates was terrible. But things kept breaking in Murray?s favor, and Democrats ended up gaining two seats in a cycle when they were initially expected to lose several. Concurrently, Majority Leader Harry Reid tapped Murray to join the supercommittee set up as part of the 2011 deal to lift the debt ceiling. Here she did an impressive job of holding the often-fractious party together. Her charge was to hold the line on the principle that any deal must include meaningful new tax revenue, and when Republicans wouldn?t budge, the Democrats held firm, too.

Party discipline on the supercommittee plus electoral wins in 2012 laid the groundwork for the president?s victory in the fiscal cliff deal?getting Republicans to vote for higher taxes on the richest Americans.

As budget chair, Murray?s job is to keep holding that line. Democrats are willing to cut domestic spending but only in the context of a deal that raises tax revenue and does it in a progressive way. A memo from her office circulated to other Senate Democrats on Thursday says, among other things, ?Revenue Must Be Included in Any Deal,? boldfaced and underlined for emphasis. The focus is on closing or curtailing tax deductions rather than raising rates. It?s politically potent terrain since Republicans from John Boehner to Paul Ryan and beyond have agreed loopholes should be curtailed. The difference is the GOP insists revenue raised from loophole-closing should be spent on reducing tax rates. This sets up what Democrats believe is a winning political argument, with Republicans seeking deep cuts in valuable social programs to pay for what amounts to tax cuts for the rich.

In her introductory statement as chair Friday morning, Murray said she plans ?to bring the voices of the American people into a budget process and conversation that is too often limited to bureaucrats and politicians.?

Her predecessor, Conrad, was for better or worse an incredibly earnest believer in both the budget process and an unusually sincere deficit hawk. In a different era, he?d have been an ideal person to draw up a wonky compromise between moderate senators of both parties. But in our polarized era, those traits tended to leave Conrad undercutting Democratic negotiating stances and still not making a deal. Murray?s more human-centered approach is about laying down a marker and winning a political argument. Meeting House Republicans? goal of balancing the budget within 10 years without higher taxes or defense cuts would require a 17 percent cut in all other spending. Democrats are going to want to counter that with an alternative that?s more balanced but also less austere overall.

If Democrats can shift the argument off the number-crunching and onto the real consequences of spending cuts, they should have a winning hand. Voters are very concerned about the deficit in the abstract but oppose cuts in virtually all specific programs. Republicans, in other words, are about to get the budget argument they?ve been demanding for years. But faced with an opponent who?s more in line with her party?s base and more focused on winning the debate than cutting a deal, they may find they don?t like the outcome.

Source: http://feeds.slate.com/click.phdo?i=87a45484030814147a0bb5bf0e21cddd

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Wednesday, January 16, 2013

GAC Group Leading Chinese Charge at Detroit Auto Show

The Chinese are running at redline to develop, improve and promote their domestic automotive industry. Brands like FAW, Chang?an Motors and SAIC may be totally obscure to the typical American car buyer, but they may become household names in just a few years. One company that?s pushing hard is the GAC group.

Short for Guangzhou Automobile Group Co., Ltd., the firm is displaying three vehicles at the Detroit Auto Show. Curiously they were all on display in the foyer of COBO Center because in the words of Dr. Xiangdong Huang, Group Vice President of Engineering they ?underestimated the difficulty of booking a booth.? But looking on the bright side he said it?s the ?most noticeable location of the show.? Word of advice, reserve show space in advance.

4?4 HYBRID Trumpchi

As for the vehicles GAC showed off, there was an all-wheel-drive hybrid sedan, an all-electric crossover and an extended range EV. First up: the 4?4 HYBRID Trumpchi sedan. According to the company it?s the first mass-produced hybrid vehicle in China with all-wheel drive. It was independently developed by GAC. It also features an electric rear-axle drive system (ERAD), which means the back wheels are powered by an electric motor. Drivers can switch between two- and four-wheel drive. It even packs in all the hybrid features you?d expect, things like stop/start for the engine, regenerative braking and electric assist.

GALLERY: 4?4 HYBRID Trumpchi

GAC-4x4-Hybrid-01.JPGGAC-4x4-Hybrid-10.JPGGAC-4x4-Hybrid-13.jpgGAC-4x4-Hybrid-11.JPGGAC-4x4-Hybrid-03.JPGGAC-4x4-Hybrid-04.JPGGAC-4x4-Hybrid-02.JPG

BEV Trumpchi GS5

The BEV Trumpchi GS5 is a pure electric SUV. It?s powered by a 35 kilowatt-hour lithium-ion battery pack that should deliver a driving range of 100 miles at a speed of 60 miles an hour. Its electric motor produces up to 200 horsepower, which should be enough to scoot the electric GS5 to 60 miles from a standstill in an altogether respectable 8.5 seconds.

GALLERY: BEV Trumpchi GS5

GAC-BEV-Trumpchi-GS5-04.JPGGAC-BEV-Trumpchi-GS5-09.JPGGAC-BEV-Trumpchi-GS5-03.JPGGAC-BEV-Trumpchi-GS5-07.JPGGAC-BEV-Trumpchi-GS5-02.JPGGAC-BEV-Trumpchi-GS5-11.jpgGAC-BEV-Trumpchi-GS5-10.JPG

NEV E-JET

Arguably the most exciting vehicle GAC on display in Detroit is the NEV E-JET. This concept car is surprisingly stylish, but that?s not its major claim to fame. It?s actually a range-extended EV ? think of it as a Chinese Chevy Volt. It?s built on a brand-new passenger-car platform that offers a pure-electric range of up to 100 kilometers, roughly 62 miles. Top speed is 160 kilometers per hour, about 100 miles an hour. A 13 kilowatt-hour lithium-ion battery pack powers the car?s electric motor. A 1.0-liter gasoline engine serves duty as the range extender. Huang said the production version of the E-JET will launch in about six months and that it will look quite different from the concept on display.

GALLERY: NEV E-JET

GAC-E-JET-08.jpgGAC-E-JET-04.JPGGAC-E-JET-01.JPGGAC-E-JET-05.JPGGAC-E-JET-03.JPGGAC-E-JET-06.JPGGAC-E-JET-07.jpg

GAC Group

The Trumpchi hybrid sedan is already on sale in China, as is the non-hybrid version of the GS5 SUV. AutoGuide was told the other models shown will soon go on sale in the country.

The United States is certainly a potential market for GAC, but obviously they don?t sell vehicles here at the moment, so why are they showing off their products in Motown? Huang said ?because this auto show is so important. Its influence is not just North America,? adding ?we are also going to other important auto shows around the world.?

GAC has numerous joint ventures with other companies. They?re shacked up with Fiat and Chrysler, Toyota, Honda, Mitsubishi and Hino, building numerous vehicles for these companies. On a component-level they have too many partners to list. Talk about getting around.

Last year GAC produced about 720,000 vehicles. From a volume perspective they were the sixth largest automaker in China.

When asked about a timetable for selling vehicles in the United States Huang said he couldn?t answer the question because ?this is not my direct business.? The figure of two years was thrown out during the interview but he said that would be a very optimistic timetable. One thing?s for certain, the Chinese are coming, the only question is when.

Discuss this story at ChinaCarForums.com

Source: http://www.autoguide.com/auto-news/2013/01/gac-group-leading-chinese-charge-at-detroit-auto-show.html

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Monday, January 14, 2013

Victims of Costa shipwreck mark anniversary

Relatives of the 32 victims of the Costa Concordia shipwreck, aboard a ferry approach the ship off the Tuscan Island Isola del Giglio, Italy, Sunday, Jan. 13, 2013. Survivors of the Costa Concordia shipwreck and relatives of the 32 people who died marked the first anniversary of the grounding Sunday. The first event of Sunday's daylong commemoration was the return to the sea of part of the massive rock that tore into the hull of the 112,000-ton ocean liner on Jan. 13, 2012 and remained embedded as the vessel capsized along with its 4,200 passengers and crew. (AP Photo/Gregorio Borgia)

Relatives of the 32 victims of the Costa Concordia shipwreck, aboard a ferry approach the ship off the Tuscan Island Isola del Giglio, Italy, Sunday, Jan. 13, 2013. Survivors of the Costa Concordia shipwreck and relatives of the 32 people who died marked the first anniversary of the grounding Sunday. The first event of Sunday's daylong commemoration was the return to the sea of part of the massive rock that tore into the hull of the 112,000-ton ocean liner on Jan. 13, 2012 and remained embedded as the vessel capsized along with its 4,200 passengers and crew. (AP Photo/Gregorio Borgia)

Italian Coast Guard Capt. Gregorio De Falco salutes as he arrives on the Tuscan Island Isola del Giglio, Italy, Sunday, Jan. 13, 2013. De Falco was heard ordering the captain, who had abandoned the ship with his first officers, back on board to oversee the evacuation. But Capt. Francesco Schettino resisted the order, saying it was too dark and the ship was tipping dangerously. Survivors of the Costa Concordia shipwreck and relatives of the 32 people who died marked the first anniversary of the grounding Sunday. (AP Photo/Gregorio Borgia)

Workers observe a minute silence as they stand on the Costa Concordia cruise ship leaning on its side off the Tuscan Island Isola del Giglio, Italy, Sunday, Jan. 13, 2013. Survivors of the Costa Concordia shipwreck and relatives of the 32 people who died marked the first anniversary of the grounding Sunday. The first event of Sunday's daylong commemoration was the return to the sea of part of the massive rock that tore into the hull of the 112,000-ton ocean liner on Jan. 13, 2012 and remained embedded as the vessel capsized along with its 4,200 passengers and crew. (AP Photo/Gregorio Borgia)

Workers place part of the "Le Scole" rock which was hit by the Costa Concordia cruise ship off the Tuscan Island Isola del Giglio, Italy, Sunday, Jan. 13, 2013. Survivors of the Costa Concordia shipwreck and relatives of the 32 people who died marked the first anniversary of the grounding Sunday. The first event of Sunday's daylong commemoration was the return to the sea of part of the massive rock that tore into the hull of the 112,000-ton ocean liner on Jan. 13, 2012 and remained embedded as the vessel capsized along with its 4,200 passengers and crew. (AP Photo/Antonello Nusca)

Relatives of the 32 victims of the Costa Concordia shipwreck, aboard a ferry approach the ship off the Tuscan Island Isola del Giglio, Italy, Sunday, Jan. 13, 2013. Survivors of the Costa Concordia shipwreck and relatives of the 32 people who died marked the first anniversary of the grounding Sunday. The first event of Sunday's daylong commemoration was the return to the sea of part of the massive rock that tore into the hull of the 112,000-ton ocean liner on Jan. 13, 2012 and remained embedded as the vessel capsized along with its 4,200 passengers and crew. (AP Photo/Gregorio Borgia)

(AP) ? Survivors of the Costa Concordia shipwreck and relatives of the 32 people who died marked the first anniversary of the grounding Sunday with the unveiling of memorials to the victims, a tearful Mass in their honor and a minute of silence to recall the exact moment that the cruise ship rammed into a reef off Tuscany.

One of the most moving tributes came first, with the daybreak return to the sea of part of the massive rock that tore a 70-meter (230-foot) gash into the hull of the ocean liner on Jan. 13, 2012, when the captain took it off course in a stunt. The boulder remained embedded in the mangled steel as the 112,000-ton vessel capsized off Giglio island along with its 4,200 passengers and crew.

As fog horns and sirens wailed, a crane on a tug lowered the boulder back onto the reef off Giglio where it belonged, returning it to the seabed affixed with a memorial plaque. Relatives of the dead threw flowers into the sea and embraced as they watched the ceremony from a special ferry that bobbed in the waves under a gray sky.

They wept during the Mass and tearfully ran their fingers over the names of the 32 dead that were engraved on a bronze plaque unveiled at the end of Giglio's jetty, near where the Concordia still lays on its side. But others seemed to have also found comfort in coming to Giglio, where residents opened their homes and hearts to the survivors that frigid night.

"Having the possibility to see everything, we can accept it a bit more, but there is still a long way to overcome this loss, especially for my mother who suffered a lot for her son," said Madeleine Costilla Mendoza, whose brother Tomas Alberto Costilla Mendoza of Peru was a steward on the ship.

Later Sunday, a minute of silence was scheduled for 9:45 p.m., the exact moment when the Concordia slammed into the reef after Capt. Francesco Schettino took it off its pre-programmed course and brought it closer to Giglio as a favor to friends from the island.

Schettino is accused of manslaughter, causing a shipwreck and leaving the ship before all passengers were evacuated. He hasn't been charged but is living under court-ordered restrictions pending a decision on whether to indict him. Schettino maintains he saved lives by bringing the ship closer to shore rather than letting it sink in the open sea, and claims the reef he hit wasn't on his nautical charts.

In an interview broadcast Sunday with RAI state television, Schettino again defended his actions and blamed others on the bridge for failing to inform him of the situation in time, and then of botching his orders once he tried to steer clear of the reef.

He said he wanted to "share in the pain of all the victims and the families of the victims."

At Schettino's home in Meta di Sorrento, on the Gulf of Naples, no one answered the doorbell Sunday and the window shutters were closed.

Taking part in the anniversary commemoration was Capt. Gregorio De Falco of the Italian coast guard, who became something of a hero to survivors after his recorded conversations with Schettino during the evacuation were made public. In them, De Falco excoriated Schettino for having abandoned the ship before all passengers were off and ordered him to return, shouting the now-infamous order "Go on board (expletive)!"

De Falco said he wanted to go to Giglio to "embrace the victims, and the relatives of the victims." De Falco said he has shied from media attention since the disaster out of respect for the victims.

"I'm not a hero," he told reporters in Giglio on Sunday. "I just did my job."

The 32 people who died included 12 Germans, seven Italians, six French nationals, two Americans ? Barbara and Gerald Heil of White Bear Lake, Minnesota ? two Peruvian crew members, one Hungarian, one Spaniard and an Indian.

Indian waiter Russel Rebello was one of the two victims whose bodies were never recovered. His brother, Kevin Rebello spent weeks on Giglio in the aftermath of the disaster awaiting word of the fate of his brother and said he couldn't sleep ahead of Sunday's anniversary.

"I have been constantly thinking it is going to be again the same agony, even tonight, because it is going to be the same exact moment when all this happened," he told The Associated Press on Sunday. "So my heart is beating a bit faster I guess."

Elio Vincenzi, the husband of Maria Grazia Trecarichi of Italy, whose body also was never recovered, wept as he presented a ceramic statue of the Madonna to Giglio's mayor as a gesture of thanks during a ceremony honoring the coast guard, firemen and other rescue crews.

The Concordia remains on its side, grounded off Giglio's port. Officials now say it may take until September to prepare the ship to be rolled upright and towed from the rocks to a port to be dismantled ? an operation on a scale that has never before been attempted. The cost has swelled to ?400 million ($530 million).

While Sunday's commemoration was focused on the relatives of those who died, Giglio's residents were also being remembered for having opened their doors to the survivors who came ashore that night, cold, wet and traumatized after a chaotic evacuation.

Italian President Giorgio Napolitano sent a message of thanks to the island, praising its people for their "high sense of civic duty and humanity."

"It was something that was too big for us," said Giglio resident Silvana Anichini. "We are just not used to things like this, and then it turned out to be one of the biggest shipwrecks in the world."

Many survivors have stayed in touch with their Giglio hosts, connected in ways they never expected. Claudia Urru, who stayed home in Sardinia on the anniversary, says she speaks monthly with the Giglio family that took in her family and two other families that night. The hosts gave the survivors warm clothes and food.

For Christmas, her Giglio family sent a package of local sweets, and they have discussed having a reunion in Sardinia.

"This is the only thing good that has come of it," Urru said by phone last week.

___

Winfield reported from Rome.

___

Follow Nicole Winfield at www.twitter.com/nwinfield

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/3d281c11a96b4ad082fe88aa0db04305/Article_2013-01-13-EU-Italy-Ship-Aground/id-5dfb80a30fb445bd99a109be93ae85c7

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Friday, January 4, 2013

Fighting rages around Syrian military air base

A Syrian rebel plays football in the Saif al-Dawlah neighborhood of Aleppo, Syria, Wednesday, Jan. 2, 2013. The United Nations estimated Wednesday that more than 60,000 people have been killed in Syria's 21-month-old uprising against authoritarian rule, a toll one-third higher than what anti-regime activists had counted. The U.N. human rights chief called the toll "truly shocking." (AP Photo/Andoni Lubacki)

A Syrian rebel plays football in the Saif al-Dawlah neighborhood of Aleppo, Syria, Wednesday, Jan. 2, 2013. The United Nations estimated Wednesday that more than 60,000 people have been killed in Syria's 21-month-old uprising against authoritarian rule, a toll one-third higher than what anti-regime activists had counted. The U.N. human rights chief called the toll "truly shocking." (AP Photo/Andoni Lubacki)

In this image taken from video obtained from the Shaam News Network, which has been authenticated based on its contents and other AP reporting, A Free Syrian Army fighter stands on a vehicle as he holds his weapon in Taftanaz village, Idlib province, northern Syria, on Wednesday, Jan. 2, 2013. Rebels attacked a sprawling air base on Wednesday as the opposition expanded its offensive on military airports in an attempt to sideline a major weapon in the hands of President Bashar Assad?s forces. The Observatory said the rebel assault on the Taftanaz base was preceded by heavy shelling of the area, and the fighters appeared to be trying to storm the facility. (AP Photo/Shaam News Network via AP video)

Syrian rebels gather around a fire as they plan patrols in the Saif al-Dawlah neighborhood of Aleppo, Syria, Wednesday, Jan. 2, 2013. The United Nations estimated Wednesday that more than 60,000 people have been killed in Syria's 21-month-old uprising against authoritarian rule, a toll one-third higher than what anti-regime activists had counted. The U.N. human rights chief called the toll "truly shocking." (AP Photo/Andoni Lubaki)

In this image taken from video obtained from the Shaam News Network, which has been authenticated based on its contents and other AP reporting, smoke rises from buildings due to heavy shelling in Damascus countryside, Syria, on Wednesday, Jan. 2, 2013. (AP Photo/Shaam News Network via AP video)

BEIRUT (AP) ? Syrian troops and rebels fought intense battles Thursday around a strategic air base in the country's north and a suburb of the capital that government forces have been trying to capture since last month, activists and state media said.

The fighting is part of the escalating violence in a Syrian civil war that the United Nations estimates has killed more than 60,000 people since the revolt against President Bashar Assad began in March 2011.

The Britain-based Syrian Observatory for Human Rights said rebels stormed parts of the Taftanaz air base in the northwestern province of Idlib before withdrawing. The state-run SANA news agency said government forces protecting the base "repelled the terrorists' attempt to attack the airport" and inflicted heavy losses. The Syrian regime routinely refers to rebel forces as "terrorists."

The Observatory said rebels resumed their assault early Thursday in an attempt to capture the base, which has resisted several opposition efforts to take the facility in recent months.

The rebels have been pursuing a strategy of attacking airports and military airfields, targeting five air bases in Idlib and the nearby province of Aleppo, trying to chip away at the government's air power, which poses the biggest obstacle to advances by opposition fighters.

With its troops struggling to make headway ? let alone gain ground ? against the rebels in the field, the government has increasingly relied on its warplanes and helicopters to target opposition forces.

The Observatory and the Local Coordination Committees, another activist group, reported clashes, air raids and shelling in several suburbs of the capital Damascus, including Daraya, which the regime has been trying to capture from hundreds of opposition fighters for weeks.

The pro-government al-Watan daily said Thursday that the army destroyed rebel strongholds in Daraya and inflicted heavy losses, adding that the area would be declared safe later in the day.

Daraya lies in a key location, and a government takeover there would provide a boost to the regime's defense of Damascus.

The suburb is just a few kilometers (miles) from the strategic military air base of Mazzeh in a western neighborhood of the capital. It borders the Kfar Sousseh neighborhood that is home to the government headquarters, the General Security intelligence agency head office and the Interior Ministry, which was the target of a recent suicide bombing that wounded the interior minister.

Al-Watan said thousands of rebel fighters from the extremists Jabhat al-Nusra group have holed up in Daraya in preparation to storm Damascus. Jabhat al-Nusra, which has been branded a terrorist organization by the U.S. and which Washington claims is affiliated with al-Qaida, has been among the most effective fighting forces on the rebel side.

One of the airstrikes hit a building in the Damascus suburb of Douma. Amateur videos showed the top floor of the building heavily damaged as wounded were rushed away in cars and pickup trucks. Many of the wounded were covered with dust.

People rushed to rescue the wounded in a street that was covered with debris and mangled metal. The Observatory and the LCC said eight people were killed Thursday in Douma and nearby areas. Damascus.

The videos appeared genuine and corresponded with other AP reporting on the events.

In another air raid, the Observatory said dozens of people were killed or wounded in the town of Hayan in Aleppo province.

The Observatory reported that rebels attacked a power station in the central province of Hama. Syrian TV said troops protecting the station repelled the attackers.

The Observatory and the Local Coordination Committees reported fighting and shelling in different areas of the southern province of Daraa, which borders Jordan. Daraa was the region where the anti-Assad uprising began in March 2011.

In Jordan, the U.N. refugee agency said Thursday that there has been a steady increase of Syrians fleeing into Jordan over the past two weeks.

UNHCR reporting officer Danita Topcagic said in the past three days, an average of 1,200-1,300 crossed the border, mainly due to fighting and skyrocketing prices of basic commodities.

Topcagic said refugees told UNHCR that the Free Syrian Army was also encouraging them to flee due to increased fighting in the area. Also, markets and shops are often shuttered making it difficult for people to find food, electricity and water supplies are intermittent and hospitals in many places have shut.

She said that in mid-December a daily average of 757 Syrians had crossed Jordan's northern frontier, while in November the average number daily was around 600.

Syria's civil war has turned more than half a million Syrians into refugees. Most have sought safe haven in Jordan, Lebanon and Turkey.

___

Associated Press writer Dale Gavlak contributed from Amman, Jordan.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/3d281c11a96b4ad082fe88aa0db04305/Article_2013-01-03-ML-Syria/id-bacc0f0e7cde43798a447c6e32819270

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Thursday, January 3, 2013

Study hints that stem cells prepare for maturity much earlier than anticipated

Wednesday, January 2, 2013

Unlike less versatile muscle or nerve cells, embryonic stem cells are by definition equipped to assume any cellular role. Scientists call this flexibility "pluripotency," meaning that as an organism develops, stem cells must be ready at a moment's notice to activate highly diverse gene expression programs used to turn them into blood, brain, or kidney cells.

Scientists from the lab of Stowers Investigator Ali Shilatifard, Ph.D., report in the December 27, 2012 online issue of Cell that one way cells stay so plastic is by stationing a protein called Ell3 at stretches of DNA known as "enhancers" required to activate a neighboring gene. Their findings suggest that Ell3 parked at the enhancer of a developmentally regulated gene, even one that is silent, primes it for future expression. This finding is significant as many of these same genes are abnormally switched on in cancer.

"We now know that some enhancer misregulation is involved in the pathogenesis of solid and hematological malignances," says Shilatifard. "But a problem in the field has been how to identify inactive or poised enhancer elements. Our discovery that Ell3 interacts with enhancers in ES cells gives us a hand-hold to identify and to study them."

In 2000, Shilatifard identified Ell3 as the third member of the Ell (for "Eleven-nineteen lysine-rich leukemia gene") family of elongation factors, proteins that increase the rate at which genes are expressed. "At the time, we didn't think much of Ell3 because it was highly expressed in testes," says Shilatifard, noting that then people thought that sperm were merely vessels used to carry paternal DNA to an egg and that associated factors would have little relevance to the regulation of future gene expression in the resulting embryo.

But a few years back, a curious Open University graduate student working in the Shilatifard lab, Chengqi Lin, started exploring a potential function for the neglected gene by initiating a global search for regions occupied by Ell3 in the genome of mouse embryonic stem cells. His search in collaboration with a bioinformatician in the Shilatifard lab, Alexander S. Garruss, revealed that Ell3 sits on more than 5,000 enhancers, including many that regulate genes governing stem cell maturation into spinal cord, kidney, and blood cells.

"What was interesting was that Ell3 marked enhancers that are active and inactive, as well as enhancers that are known as "poised," says Lin, referring to a transition state from inactive to active. "That indicated that Ell3's major function might be to prime activation of genes that are just about to be expressed during development."

The fact that silent genes can be "primed" for expression was no surprise: researchers knew that the enzymatic machine that copies DNA into the RNA blueprint for proteins?a protein called Pol II?often pauses at the start of a gene, presumably revving its engine in preparation to jump across the genetic start gate in response to a developmental signal. However, Shilatifard and colleagues showed several years ago that paused Pol II is not a prerequisite for rapid transcriptional induction.

The surprise came when researchers used a molecular trick to deplete mouse ES cells of Ell3 and then did a "genomic" survey. They found that paused Pol II vanished from the start sites of many genes in Ell3-deficient cells. This means that not only does Ell3 preferentially mark stem enhancers, but also that its presence there is necessary to keep an idling Pol II ready for action.

Most of the current study defines how, when the developmental time is right, enhancer-bound Ell3 cooperates with components of a big-boss elongation factor called the Super Elongation Complex to release Pol II from the start gate, allowing the expression of genes required for stem cell differentiation. Critical among those findings is their observation that mouse stem cells depleted of Ell3 failed to activate genes expressed in mature cell types.

These results alone are cause for any lab to start chilling the champagne, yet a surprising coda to the study, leaves readers with yet another revelation. Collaborating with Fengli Guo, Ph.D., head of the Stowers electron microscopy core, the team prepared highly magnified images of mouse sperm and observed that both Ell3 and Pol II were present, in sperm nuclei.

In mammals, gene expression regulated by Pol II, a process known as transcription, does not begin until the formation of a single-celled zygote, that is, well after the union of sperm and egg germ cells. "It is very significant that Ell3 and other factors that regulate transcription are found in sperm," says Lin, the study's first author. Lin is cautious in interpreting this finding, "but it would be very exciting to further investigate whether transcription factors found in sperm could contribute to the decondensation of sperm chromatin or even further gene activation after fertilization by serving as epigenetic markers."

Shilatifard is also cautious as questions remain to be explored, among them whether Ell3 and Pol II actually contact DNA inside sperm or whether similar processes occur in unfertilized eggs and function in this process. Nonetheless, he feels this finding has fundamental implications, not only for development, but also for where he's going next.

"This work has opened up a whole new area of research in my lab," says Shilatifard, who has in the last decade focused on aberrant gene expression associated with leukemia. "If we find that transcription factors bind to specific regions of chromatin in germ cells, I may focus on germ cells in the next few decades. This would open a huge door enabling us to determine the role of these factors in early development."

###

Stowers Institute for Medical Research: http://www.stowers-institute.org

Thanks to Stowers Institute for Medical Research for this article.

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Source: http://www.labspaces.net/126097/Study_hints_that_stem_cells_prepare_for_maturity_much_earlier_than_anticipated

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