Gene network illuminates stress, mutation and adaptation responses

ScienceDaily (Dec. 6, 2012) ? For much of her professional life, Dr. Susan Rosenberg has studied the puzzling response of bacteria to stress and the mutations that result. In the current issue of the journal Science, she puts together the pieces of that puzzle, describing most of the members of an elaborate gene network that functions in causing mutations during repair of double-stranded breaks in the DNA of stressed cells.

"We now know the 93 genes more than half of which are funneling into three nodes that go down the mutagenesis pathway," said Rosenberg, professor of molecular and human genetics at Baylor College of Medicine and 2009 winner of the National Institutes of Health Director's Pioneer Award.

Groundbreaking work

Rosenberg's groundbreaking work has shown that the rate of mutation can be increased in response to stress such as starvation or environmental challenges such as antibiotics. This changes old ideas about constant and gradual accumulation of mutations over time. Some mutations are detrimental; others can promote survival. In this work, she and her colleagues sought to define the cellular pathways that result in this stress response.

"We screened for every gene in Escherichia coli that is needed to make this happen," said Rosenberg. E. coli is a "model" organism often used in the laboratory to study cells, because its DNA and other components work similarly to those in humans.

They have found that the mutagenic part of the process is not required to repair the broken DNA strands. When they "knock out" or remove the special "error-prone" DNA copying enzyme or polymerase, "the DNA is repaired beautifully and there are no mutations." So, cells do not make mutations because they have to, to repair DNA. Rather, this mechanism appears to regulate production of mutations, making more during stress, when cells are poorly adapted to their environments, and most likely to benefit from mutations.

Painstaking process

"Fewer than 16 proteins that are needed to accomplish stress-inducible mutagenesis were known previously. This is about the number known for any molecular mechanism of DNA biology," said Rosenberg. "Our screen sought the whole list of all proteins the cell uses to make it happen."

The painstaking process, begun by then postdoctoral fellow Dr. Mary-Jane Lombardo, now of Seres Health, Inc., in Cambridge, Mass., was completed by Dr. Amar Al Mamun, an assistant professor in Rosenberg's laboratory at BCM.

Large fractions of the network work "upstream" of the activation of the stress response, showing that these proteins apparently "sense" the stress. In delineating how the network functions, Rosenberg and her colleagues identified specific pathways through which the proteins sense the environment and connected them to the molecular mechanism that promotes the mutations.

Key factors revealed

The findings reveal key factors about the cells, such as that stress-response regulators act as key network hubs, she said. Most of the proteins in the network deal with whether or not the cells feel stress, said Rosenberg.

"The cell devotes a large number of proteins to controlling the process that generates diversity," she said. "And most of them are sensing the environment and coupling mutagenesis to stress."

They have determined the function of about half the network and are working on the rest.

"It's a resounding confirmation of the regulation of mutagenesis by stress responses, which causes mutations specifically when cells are maladapted to their environment when mutations might allow the cell to adapt," said Rosenberg.

Protein networks

It is also a demonstration that one can hope to detangle large protein networks into specific biological functions. Large protein networks are being discovered in many areas of biology, but what roles the proteins play in particular biological processes is often difficult to determine. Rosenberg's study shows that by working backwards from a defined molecular mechanism, they could assign roles to more than half the network proteins. Rosenberg thinks this strategy will be useful for many other protein networks.

Funding for this work came from grants from the National Institutes of Health and National Science Foundation.

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Story Source:

The above story is reprinted from materials provided by Baylor College of Medicine.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.


Journal Reference:

  1. Abu Amar M. Al Mamun, Mary-Jane Lombardo, Chandan Shee, Andreas M. Lisewski, Caleb Gonzalez, Dongxu Lin, Ralf B. Nehring, Claude Saint-Ruf, Janet L. Gibson, Ryan L. Frisch, Olivier Lichtarge, P. J. Hastings, Susan M. Rosenberg. Identity and Function of a Large Gene Network Underlying Mutagenic Repair of DNA Breaks. Science, 7 December 2012: Vol. 338 no. 6112 pp. 1344-1348 DOI: 10.1126/science.1226683

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/top_science/~3/fK3OEfGMG4g/121206142014.htm

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American Horror Story, Season 2

Joseph Fiennes as Monsignor Timothy Howard and Lily Rabe as Sister Eunice in 'American Horror Story: Asylum.'

Joseph Fiennes as Monsignor Timothy Howard and Lily Rabe as Sister Eunice in 'American Horror Story: Asylum.' Photo by Byron Cohen/FX.

Reading over various recaps around the web this morning, my Christmas cheer has been dampened somewhat by the discovery that, like my chat partner Bryan Reid, most viewers of last night?s episode found Santy Claus?s visit to Briarcliff to be little more than a gruesome distraction. To be fair, I get the general reasoning: AHS is already a seething mass of storylines and half-explained characters, so do we really need to add another, especially one who takes up an entire episode? I guess I just loved Ian McShane?s deranged performance so much that it didn?t bother me.

As Chris Harnick theorized over at HuffPo, the producers may have done this ?solely to show just how creepy McShane could be and to establish that watching people get murdered while wrapped in Christmas lights is upsetting.? Surely that?s justification enough, no? Both he and Brian Juergens of After Elton? kind of say ?no,? so perhaps we?ll just have to agree to disagree.

The American Horror Story holiday card.

The American Horror Story holiday card.

Image courtesy FX.

In other news, one glaring revelation that Bryan R. and I both missed last night was the fact that Lana is almost certainly pregnant by Dr. Thredson because, you know, she ?forced? him to give her ?his intimacy.? (Is that not the sickest euphemism for rape you?ve ever heard?!) Both Harnick and Halle Kiefer of Rolling Stone offered this notion after noticing Lana?s vomiting (even though she hadn?t eaten anything), and Harnick goes a tantalizing step further, prophesying that ?modern-day Bloody Face is growing inside her as we speak.? The previews for next week?s episode seem to indicate that Dylan McDermott (who Murphy has revealed is playing our modern day killer) will be discussing his ?impulses? with a therapist in a nice reversal from last season, so Harnick?s theory may be tested sooner rather than later.

Speaking of theories, I have one that I?d love our readers? help with vetting. Did anyone else notice how tweaked-out Sister Mary Demon got about those rubies? Girl looked like a cat to catnip. I googled around a little, but couldn?t find for sure if demons are supposed to have a weakness for the red gemstones. If any of you out there are of the theological persuasion, satisfy my curiosity. I think that reaction to the ?shit-stained earrings? may have been a clue to the demon?s future downfall. Submit your research papers in the comments!

Source: http://feeds.slate.com/click.phdo?i=9633fc90733639ee161e90234d563ec2

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Democrats: Obama to ask for $50 billion Sandy aid

WASHINGTON (AP) ? President Barack Obama plans to ask Congress for about $50 billion in additional emergency aid for states hit by Superstorm Sandy, Democrats on Capitol Hill said Wednesday.

House Secretary Shaun Donovan told a Senate Appropriations subcommittee that the administration is still working on a request for a supplemental spending bill to provide the aid and expects to send it to Congress this week.

"We do not have a specific number," Donovan said.

The price tag is expected to be anywhere between $45 billion and $55 billion. Two Senate Democratic aides, speaking on condition of anonymity because the request is still being assembled, put the number in the neighborhood of $50 billion.

"The president isn't going to leave New York, New Jersey or the entire region to fight for itself," Donovan, who is coordinating the government's Sandy recovery efforts for Obama, told reporters after the hearing.

Donovan urged Congress to take action in "the next few weeks" on the administration's upcoming request.

On Tuesday, the head of the Federal Emergency Management Agency, Craig Fugate, said the government's disaster relief fund still has $4.8 billion, enough to pay for recovery efforts into early spring. So far the government has spent about $2 billion in the 11 states struck the late October storm, one of the worst ever in the Northeast.

New York, New Jersey and Connecticut are together seeking about $83 billion in aid. Donovan described that figure as more of damage estimate, saying some of might be covered by private insurance and other already-funded government programs.

Given the recent budget talks and the strong pressures against new spending, Congress is not expected to approve large amounts of additional money all at once.

The storm devastated coastal communities from North Carolina to Maine, killing more than 120 people. New York and New Jersey were hit the hardest.

Obama can request up to $5.4 billion more without hitting a spending ceiling. Several Republicans have said that more than that should be matched by spending cuts in other federal programs.

Donovan said people who lost homes or businesses are waiting desperately for help. He said it would be a mistake for Congress to quickly approve the $5.4 billion as a "down payment" and defer until next year providing additional funding.

"A down payment simply means that these families, these communities are going to be waiting for months or longer to get on with their lives," he said.

Donovan said requiring spending cuts in other federal programs to cover the cost of additional disaster aid makes no sense. "We believe strongly that the country has to come together even in difficult times and stand behind places that have been devastated," he said.

Officials in the affected state expect the fight for more recovery money will last for months and probably require a series of spending bills. They also fear it will fade as a priority next year.

Sens. Chuck Schumer, D-N.Y., Kirsten Gillibrand, D-N.Y., Frank Lautenberg, D-N.J., and Robert Menendez, D-N.J., voiced disappointment in a joint statement.

"While $50 billion is a significant amount of money, it unfortunately does not meet all of New York and New Jersey's substantial needs," they said. "While we know there will be additional supplementals, the administration needs to come as close as possible to meeting our states' needs in the first request."

Source: http://news.yahoo.com/democrats-obama-ask-50-billion-sandy-aid-194150907.html

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Facebook Talks App Traction: 350 Apps Have 1M Monthly Actives On Site; Facebook Now Integrated In 200K Mobile Applications

facebook-gamesFacebook today announced new numbers related to Facebook app usage on its site, as well as its integration into mobile platforms like iPhone and Android. The company said that there are now over 350 apps on Facebook.com that see more than 1 million monthly active users each. The company also said that there are nearly 200,000 iPhone and Android applications which are integrated with Facebook, including 9 of the top 10 grossing iPhone applications.

Source: http://feedproxy.google.com/~r/Techcrunch/~3/Gg_sT4vG3x4/

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That Will Do The Trick (talking-points-memo)

Ex-Goldman director to stay free on bail: court

NEW YORK (Reuters) - Former Goldman Sachs Group Inc board member Rajat Gupta can remain free on bail while he appeals his insider-trading conviction, an appeals court ruled on Tuesday.

Gupta had been scheduled to surrender January 8 to start a two-year prison sentence. But after hearing arguments from Gupta's lawyer and prosecutors, a two-judge panel of the 2nd U.S. Circuit Court of Appeals in New York granted Gupta's request to stay out of prison.

Gupta, 64, was convicted in June of leaking Goldman boardroom secrets to Raj Rajaratnam, the Galleon Group hedge-fund manager at the center of a U.S. government crackdown on insider trading over the past four years. Gupta, also a former head of management consultancy McKinsey & Co, has been free on $10 million bail.

The former Goldman director attended the hearing with his family. After the hearing, he hugged his lawyer, Seth Waxman, and patted him on the back.

Waxman declined to comment on the appeals court's ruling. A spokeswoman for Manhattan U.S. Attorney Preet Bharara declined to comment.

The U.S. Justice Department had argued that Gupta should not be able to delay going to prison while he awaits the outcome of his appeal, which is expected to be heard by the 2nd Circuit as early as April.

At Tuesday's hearing, Waxman argued that Gupta's appeal would raise substantial questions that likely would result in his conviction being reversed.

The government hadn't proved its case, which relied on "classically inadmissible" or "entirely circumstantial" evidence, Waxman said. "It totally failed in that regard."

Waxman said the trial judge, Jed Rakoff, erred in admitting an October 24, 2008 wiretapped conversation between Rajaratnam and David Lau, a Singapore-based portfolio manager at Galleon.

On the call, Rajaratnam told Lau that he "heard yesterday from somebody who's on the board of Goldman Sachs, that they are gonna lose $2 per share." But Waxman said there was no evidence Lau traded on the tip, and the call had been focused on the general discussions of the global financial crisis.

Reed Brodsky, the prosecutor who argued before the 2nd Circuit, countered that the wiretaps show that Rajaratnam had provided information to Lau so he could also benefit from it.

"The government's evidence showed this was in furtherance of the conspiracy," he said.

The 2nd Circuit had earlier denied Rajaratnam's similar bid to remain free on bail pending his appeal, which was argued October 25. The fund manager is serving an 11-year prison sentence.

Gupta is facing a related civil proceeding brought by the U.S. Securities and Exchange Commission. In a court filing late Tuesday, his lawyers argued that he should not pay any civil penalty in connection with the SEC's claims. The SEC has asked the court to impose the maximum allowable penalty of $15.3 million.

The case is USA v. Rajat Gupta, 2nd U.S. Circuit Court of Appeals, No 12-4448.

(Editing by Martha Graybow, Andrew Hay, Tim Dobbyn and Michael Urquhart)

Source: http://news.yahoo.com/ex-goldman-director-gupta-stay-free-bail-court-002906552--sector.html

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Dykstra sentenced in bankruptcy fraud case

By GREG RISLING

Associated Press

Associated Press Sports

updated 5:32 p.m. ET Dec. 3, 2012

LOS ANGELES (AP) - Former All-Star outfielder Lenny Dykstra has been sentenced in Los Angeles to six and a half months in prison for hiding and selling sports memorabilia and other items that were supposed to be part of his bankruptcy filing.

U.S. District Judge Dean Pregerson also ordered Dykstra to pay $200,000 in restitution and perform 500 hours of community service. He pleaded guilty to bankruptcy fraud and money laundering charges and prosecutors were asking for a 2 1/2-year prison sentence.

Monday's sentencing is part of a downward spiral for Dykstra, who has had a host of legal problems over the past year.

Dykstra is currently serving a three-year prison sentence after pleading no contest to grand theft auto and providing a false financial statement. He also was sentenced this year to nine months in jail after pleading no contest to charges he exposed himself to women he met through Craigslist.

? 2012 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.


advertisement

Source: http://nbcsports.msnbc.com/id/50063092/ns/sports-baseball/

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Food for Thought? - Scotland Food and Drink

Daniel Millard (10), Oran McKenna (10), Richard Lochhead MSP, Kylah Munro (10) and Freya Main (10), P6 pupils at Hopeman Primary School

Around 2,000 pupils from more than 120 schools across Scotland will soon be up to their elbows in enzymes, iodising ice cream and building jelly towers thanks to the launch of an exciting new science pack.

Date:

Tue, 04 Dec 2012

Source:

Liddell Thomson

Science on the Menu is an interactive food science kit jammed with goodies providing primary school science clubs and their teachers with all they need for exciting hands-on experiments using food and drink.?

Launched by Young Engineers & Science Clubs Scotland, a Scotland-wide programme run by the Scottish Council for Development and Industry, Science on the Menu was unveiled yesterday at Hopeman Primary School in Moray by local MSP Richard Lochhead, Cabinet Secretary for Rural Affairs and the Environment ? whose department supported SCDI with funding the science investigation kits.?

Speaking at the launch Richard Lochhead MSP said: ?Using Science to educate young people about Scotland?s food and drink is vital for Scotland?s Economy. We need even more young people with the skills, knowledge and enthusiasm for science. The food and drink manufacturing sector employs around 50,000 people in Scotland so we are hopeful that the Science on the Menu packs will feed the curiosity and imagination of the next generation of food technologists and entrepreneurs.??

Melanie Riddell of the Young Engineers & Science Clubs Scotland said; ?The packs include a wide range of teaching aides such as chemicals and colourings that make problem solving fun, helping children to learn about food and drink and hopefully making science subjects more engaging.??

She added: ?It?s also good to use products from Scotland?s larder as a great way to fuel the imagination of children to the many Science, Technology, Engineering and Maths (STEM) careers open to them in the food and drink sector?.?

The Young Engineers and Science Club has a network of over 650 clubs throughout Scotland, from Orkney to Dumfries with a membership of more than 12,000 school children. The Clubs are supported by the Scottish Government and as well as many private sector sponsors.?

Source: http://www.scotlandfoodanddrink.org/news/article-info/4103/food-for-thought%E2%80%A6science-on-the-menu-for-scottish-schools.aspx

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Notre Dame vs. Alabama: Star power, power football

NEW YORK (AP) ? On one side, a blossoming dynasty from the college football capital of the Deep South. On the other, the sport's most famous team, trying to reclaim its place among the elite.

Notre Dame and Alabama bring star power and power football to the BCS championship.

The matchup became official Sunday night when the final standings were released and, to no one's surprise, the Fighting Irish were first and the Crimson Tide was second.

The one bit of drama on college football's selection Sunday was whether Northern Illinois could be this year's BCS buster. The Huskies got in, getting a spot in the Orange Bowl against Florida State, taking a bid away from Oklahoma and sparking heated debate about a system that never fails to tick off fans in some way.

As for the main event in the penultimate Bowl Championship Series, there was little controversy: No. 1 Notre Dame against No. 2 Alabama in Miami on Jan. 7.

The Irish clinched their spot a week ago in Los Angeles by completing a perfect season against rival Southern California.

Alabama earned its spot Saturday, beating Georgia 32-28 in a thrilling Southeastern Conference title game.

The program that coach Paul Bryant turned into an SEC behemoth in the 1960s and 70s, winning five national championships and sharing another during his tenure, is again dominating college football with a modern-day version of the Bear leading the way in Tuscaloosa, Ala.

Coach Nick Saban and the Crimson Tide are on the verge of one of the great runs in history. Alabama would become the first team to repeat as champs since the BCS was implemented in 1998, and it would be the 11th time a team has won consecutive AP titles since the poll started in 1936. Alabama is already one of seven programs to repeat. The Tide has done it twice. Notre Dame is another.

Alabama also won the 2009 BCS championship under Saban. The last team to win three major national titles in four seasons was Nebraska, which went back-to-back in 1994 and '95 and finished No. 1 in the final coaches' poll in 1997.

In a world full of spread-the-field, hurry-up offenses, Alabama is a bastion of traditional football.

The Tide put its no-frills muscle on display Saturday, mashing Georgia with 350 yards rushing, most impressively when Alabama trailed 21-10 in the second half and you might have expected the Tide to open up its passing game.

Eddie Lacy, listed at a conservative 220 pounds, went for 181 against the Bulldogs to up his season total to 1,182 with 17 touchdowns. T.J. Yeldon, at 216 pounds, provides more speed with his punch. The freshman has run for 1,000 yards and scored 12 touchdowns.

But this is no 3 yards and a cloud of dust. Both backs average over 6 yards per carry, behind an offensive line anchored by All-American center Barrett Jones. And quarterback AJ McCarron has thrown for 26 touchdowns with only three interceptions.

The Tide has been more potent offensively this season than last to make up for a defense that has slipped, but only a bit. Alabama leads the nation in total defense (246 yards per game) and is second in points allowed (10.7 per game). Linebackers Adrian Hubbard, Nico Johnson, CJ Mosley and Trey Depriest average 242 pounds.

When Brian Kelly was hired at Notre Dame three years ago, he looked at Alabama and the SEC, which has won six straight BCS titles, and decided the Irish needed to play like that.

Kelly built his reputation and winning teams at previous stops on fast-paced spread offenses. In South Bend, Ind., he has put the fight back in the Irish, who have won eight AP national titles ? only Alabama has as many ? but none since 1988.

Notre Dame has allowed the fewest touchdowns in the country (10) and is sixth overall in total defense (286 yards per game). The face of the Irish isn't a strong-armed quarterback or speedy ball carrier. It's middle linebacker Manti Te'o, a 255-pound offense wrecker with a nose for the ball. The senior has seven interceptions and is a likely Heisman finalist.

Te'o, along with 300-pound linemen Stephon Tuitt and Louis Nix, have formed a red-zone wall for the Irish. Late goal-line stands highlighted victories against Stanford and USC.

While nurturing redshirt freshman Everett Golson, Kelly has leaned on Notre Dame's running game, which averages 202 yards. Alabama averages 224 on the ground.

If Notre Dame, making its first appearance in a BCS championship, is going to break the SEC's strangle hold on the crystal ball trophy, the Irish will try to beat 'Bama at its own game.

And Kelly will try to uphold a Notre Dame tradition, by winning a national title in his third season as coach. Frank Leahy, Ara Parseghian, Dan Devine and Lou Holtz all won it all in Year 3 playing in the shadows of the Golden Dome.

Notre Dame will try to become the first team since BYU in 1984 to start the season unranked and win a national title.

Expect plenty of fans to be watching. With the popularity of both programs, the second-to-last BCS title game is expected to be the highest rated ever.

In two years, college football switches to a four-team playoff to determine its champion. No doubt fans of Florida (11-1), Oregon (11-1), Stanford (11-2) and Kansas State (11-1) wish they could push the start date up on that, but for the most part there isn't much griping about this championship matchup.

Notre Dame is the only undefeated team that is eligible ? thanks to Ohio State's NCAA sanctions ? and Alabama is the champion of the league that has produced the last half-dozen national champs.

Roll Tide or return to glory? To be determined in South Florida.

___

AP Sports Writer Tim Reynolds contributed to this report.

___

Follow Ralph D. Russo at www.Twitter.com/ralphdrussoap

Source: http://news.yahoo.com/notre-dame-vs-alabama-star-power-power-football-215332107--spt.html

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