LOS ANGELES (AP) ? After a nine-month delay, "G.I. Joe: Retaliation" deployed to the top spot at the box office.
The action film starring Dwayne "The Rock" Johnson, Bruce Willis and Channing Tatum as the gun-toting military toys brought to life marched into the No. 1 position at the weekend box office, earning $41.2 million, according to studio estimates Sunday. "Retaliation" opened Wednesday at midnight, which helped bring its domestic total to $51.7 million.
Paramount postponed the sequel to 2009's "G.I. Joe: Rise of Cobra" last May from its original June opening date to convert the film to 3-D. The last-minute switcheroo came just weeks after "Battleship," another movie based on a Hasbro toy, sank at the box office. At that time, Paramount already began its advertising campaign for "Retaliation."
"It certainly vindicates the decision," said Don Harris, the studio's head of distribution. "Any time you make those sorts of moves, people always assume the worst. The truth is I'd seen this movie a long time ago in 2-D, and the movie worked in 2-D. It's not trying to be 'Schindler's List.' This movie is intended to be enjoyed as a big, action spectacle."
After debuting in the top spot last weekend, the 3-D animated prehistoric comedy "The Croods" from DreamWorks Animation and 20th Century Fox slipped to the No. 2 spot with $26.5 million in its second weekend. The film features the voices of Nicolas Cage, Emma Stone and Catherine Keener as a cave family on the hunt for a new home.
Among the other new films this weekend, "Tyler Perry's Temptation" starring Jurnee Smollett-Bell and Lance Gross opened above expectations at No. 3 with $22.3 million, while the sci-fi adaptation "The Host" featuring Saoirse Ronan, Max Irons, and Jake Abel as characters from the Stephenie Meyer novel landed at No. 6 in its debut weekend with a modest $11 million.
Overall, the weekend box office was on par with last year when "The Hunger Games" continued to dominate in its second weekend of release with $58.5 million. After a slow start, Hollywood's year-to-date revenues are still 12 percent behind last year, heading into next month when summer movie season unofficially kicks off with "Iron Man 3" on May 3.
"It's getting us back on track after many weekends of down trending box office," said Paul Dergarabedian, box office analyst for Hollywood.com. "Last weekend was a turning point with the strength of 'The Croods' and 'Olympus Has Fallen' doing better than expected. We're heading toward the summer movie season on solid footing. It's been a tough year so far."
Estimated ticket sales for Friday through Sunday at U.S. and Canadian theaters, according to Hollywood.com. Where available, latest international numbers are included. Final domestic figures will be released Monday.
1. "G.I. Joe: Retaliation" $41.2 million.
2. "The Croods," $26.5 million.
3. "Tyler Perry's Temptation," $22.3 million.
4. "Olympus Has Fallen," $14 million.
5. "Oz the Great and Powerful," $11.6 million.
6. "The Host," $11 million.
7. "The Call," $4.8 million.
8. "Admission," $3.2 million.
9. "Spring Breakers," $2.7 million.
10. "The Incredible Burt Wonderstone," $1.3 million.
___
Online:
http://www.hollywood.com
___
Universal and Focus are owned by NBC Universal, a unit of Comcast Corp.; Sony, Columbia, Sony Screen Gems and Sony Pictures Classics are units of Sony Corp.; Paramount is owned by Viacom Inc.; Disney, Pixar and Marvel are owned by The Walt Disney Co.; Miramax is owned by Filmyard Holdings LLC; 20th Century Fox and Fox Searchlight are owned by News Corp.; Warner Bros. and New Line are units of Time Warner Inc.; MGM is owned by a group of former creditors including Highland Capital, Anchorage Advisors and Carl Icahn; Lionsgate is owned by Lions Gate Entertainment Corp.; IFC is owned by AMC Networks Inc.; Rogue is owned by Relativity Media LLC.
___
Follow AP Entertainment Writer Derrik J. Lang on Twitter at http://www.twitter.com/derrikjlang.
>>>there is a health scare we're following tonight that involves thousands of people who may have been put at risk simply by going to the dentist. hundreds of them lined up in
tulsa
, oklahoma, today to be tested for hepatitis and hiv, after visiting an
oral surgeon
accused of unsanitary practices. nbc's
charles
hadlock is in
tulsa
tonight with more for us.
charles
?
>> reporter: good evening, lester. today was the first day that patients who may have been exposed to
infectious diseases
at a local dentist's office could come and get tested. 400 people showed up today, but there are thousands more who may have been infected. the line at the
tulsa countyhealth department
stretched out the door today. hundreds of people who have one thing in common, all were patients of dr.
scott harrington
, whose
dental practice
is now at the center of a health scare.
>>i figure i better get tested and be safe. it's the smartest thing to do.
>> reporter: state health officials said
harrington
's clinic may have been the source of hepatitis in at least one patient, and fear there could be more. they've notified 7,000 patients who may have been exposed to hepatitis on hiv.
>>we are here for the long run. we know that it's going to take a couple weeks, to months, to get everyone screened. and so we are here and we'll have this clinic established here until we see the last person.
>> reporter: in a 17-count complaint, the state board of dentistry accuses dr.
harrington
of being a menace to
public health
because of unsanitary practices found in his office. inspectors say
harrington
's clinic had rusty equipment, allowed dental assistants to perform surgery without a license.
harrington
's staff improperly sterilized tools with bleach which caused them to corrode.
harrington
has surrendered his dental license and is cooperating with authorities.
>>i just have been tested for
hepatitis c
.
>> reporter: back at the long line at the clinic, melinda harris waits for the results of her tests.
>>i'm really scared, because i feel like that's my had fiance right there. if anything happens, you know, it's not good news, that he's going to have to be tested.
>> reporter: linda harris and all the others will have to wait at least two more weeks to know the results. lester?
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LONDON (AP) ? Richard Griffiths, a versatile British actor who won a Tony Award for "The History Boys" and played the boy wizard's unsympathetic Uncle Vernon Dursley in the "Harry Potter" movies, has died. He was 65.
Agent Simon Beresford announced Friday that Griffiths died a day earlier of complications following heart surgery at University Hospital in Coventry, central England.
He paid tribute to Griffiths as "a remarkable man and one of our greatest and best-loved actors."
Griffiths appeared in dozens of movies and TV shows, but will be most widely remembered as a pair of contrasting uncles ? flamboyant Uncle Monty in 1980s cult classic "Withnail and I" and the hero's grudging Muggle guardian in the "Harry Potter" series.
Griffiths once said he liked playing Uncle Vernon "because that gives me a license to be horrible to kids."
But "Harry Potter" star Daniel Radcliffe paid tribute to the actor, saying "I was proud to say I knew him."
A large man and a huge stage presence, Griffiths was one of Britain's leading theater actors, creating roles including the charismatic teacher Hector at the emotional heart of Alan Bennett's school drama "The History Boys" ? a part he took to Broadway, winning a Tony, and repeated for the film adaptation.
National Theatre artistic director Nicholas Hytner, who directed "The History Boys," called Griffiths' performance in that play "a masterpiece of wit, delicacy, mischief and desolation, often simultaneously."
Griffiths also played poet W.H. Auden in Bennett's "The Habit of Art," a hugely persuasive performance despite the lack of physical resemblance between the two men.
Griffiths was born in northeast England's Thormaby-on-Tees in 1947 to parents who were deaf and mute ? an experience he felt contributed to his exceptional ability to listen and to communicate physically.
He left school at 15 but later studied drama and spent a decade with the Royal Shakespeare Company, making a specialty of comic parts such as the buffoonish knight Falstaff.
On television, he played a crime-solving chef in 1990s' British TV series "Pie in the Sky," and he had parts in movies ranging from "Chariots of Fire" and "Gandhi" to "The Naked Gun 2 ?."
Known for his sense of humor, large store of rambling theatrical anecdotes and occasional bursts of temper, Griffiths was renowned for shaming audience members whose cell phones rang during plays by stopping the performance and ordering the offender to leave.
Griffiths' last major stage role was in a West End production of Neil Simon's comedy "The Sunshine Boys" last year opposite Danny DeVito. The pair had been due to reprise their roles in Los Angeles later this year.
In 2007 he appeared in a London and Broadway production of "Equus" alongside the then 17-year-old Radcliffe.
"Richard was by my side during two of the most important moments of my career," Radcliffe said Friday.
"In August 2000, before official production had even begun on Potter, we filmed a shot outside the Dursleys', which was my first ever shot as Harry. I was nervous and he made me feel at ease.
?"Seven years later, we embarked on 'Equus' together. It was my first time doing a play but, terrified as I was, his encouragement, tutelage and humor made it a joy.
"In fact, any room he walked into was made twice as funny and twice as clever just by his presence."
Griffiths is survived by his wife, Heather Gibson.
By Martyn Herman LONDON, March 28 (Reuters) - Whether by design, necessity, self-interest or because of all three, nurturing youngsters has become fashionable for England's elite with no expense spared in the hunt for the new Wayne Rooney or Steven Gerrard. The length and breadth of the country, scouts from top clubs are hoovering up promising footballers barely old enough to tie their bootlaces in a bid to unearth the 30 million pounds ($45.40 million) treasures of the future. ...
Mar. 28, 2013 ? Scientists have identified a key molecule responsible for triggering the chemical processes in our brain linked to our formation of memories. The findings, published in the journal Frontiers in Neural Circuits, reveal a new target for therapeutic interventions to reverse the devastating effects of memory loss.
The BBSRC-funded research, led by scientists at the University of Bristol, aimed to better understand the mechanisms that enable us to form memories by studying the molecular changes in the hippocampus -- the part of the brain involved in learning.
Previous studies have shown that our ability to learn and form memories is due to an increase in synaptic communication called Long Term Potentiation [LTP]. This communication is initiated through a chemical process triggered by calcium entering brain cells and activating a key enzyme called 'Ca2+ responsive kinase' [CaMKII]. Once this protein is activated by calcium it triggers a switch in its own activity enabling it to remain active even after the calcium has gone. This special ability of CaMKII to maintain its own activity has been termed 'the molecular memory switch'.
Until now, the question still remained as to what triggers this chemical process in our brain that allows us to learn and form long-term memories. The research team, comprising scientists from the University's School of Physiology and Pharmacology, conducted experiments using the common fruit fly [Drosophila] to analyse and identify the molecular mechanisms behind this switch. Using advanced molecular genetic techniques that allowed them to temporarily inhibit the flies' memory the team were able to identify a gene called CASK as the synaptic molecule regulating this 'memory switch'.
Dr James Hodge, the study's lead author, said: "Fruit flies are remarkably compatible for this type of study as they possess similar neuronal function and neural responses to humans. Although small they are very smart, for instance, they can land on the ceiling and detect that the fruit in your fruit bowl has gone off before you can."
"In experiments whereby we tested the flies' learning and memory ability, involving two odours presented to the flies with one associated with a mild shock, we found that around 90 per cent were able to learn the correct choice remembering to avoid the odour associated with the shock. Five lessons of the odour with punishment made the fly remember to avoid that odour for between 24 hours and a week, which is a long time for an insect that only lives a couple of months."
By localising the function of the key molecules CASK and CaMKII to the flies' equivalent brain area to the human hippocampus, the team found that the flies lacking these genes showed disrupted memory formation. In repeat memory tests those lacking these key genes were shown to have no ability to remember at three hours (mid-term memory) and 24 hours (long-term memory) although their initial learning or short-term memory wasn't affected.
Finally, the team introduced a copy of the human CASK gene -- it is 80 per cent identical to the fly CASK gene -- into the genome of a fly that completely lacked its own CASK gene and was therefore not usually able to remember. The researchers found that flies which had a copy of the human CASK gene could remember like a normal wildtype fly.
Dr Hodge, from the University's School of Physiology and Pharmacology, said: "Research into memory is particularly important as it gives us our sense of identity, and deficits in learning and memory occur in many diseases, injuries and during aging."
"CASK's control of CaMKII 'molecular memory switch' is clearly a critical step in how memories are written into neurons in the brain. These findings not only pave the way for to developing new therapies which reverse the effects of memory loss but also prove the compatibility of Drosophila to model these diseases in the lab and screen for new drugs to treat these diseases. Furthermore, this work provides an important insight into how brains have evolved their huge capacity to acquire and store information."
These findings clearly demonstrate that neuronal function of CASK is conserved between flies and human, validating the use of Drosophila to understand CASK function in both the healthy and diseased brain. Mutations in human CASK gene have been associated with neurological and cognitive defects including severe learning difficulties.
The BBSRC-funded study, entitled 'CASK and CaMKII function in the mushroom body a'/?' neurons during Drosophila memory formation' by Bilal Rashid Malik, John Michael Gillespie, James John Llewellyn Hodge was published on Wednesday 27 March 2013 in the Frontiers in Neural Circuits Journal.
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The above story is reprinted from materials provided by University of Bristol.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
Bilal R. Malik, John Michael Gillespie, James J. L. Hodge. CASK and CaMKII function in the mushroom body ??/?? neurons during Drosophila memory formation. Frontiers in Neural Circuits, 2013; 7 DOI: 10.3389/fncir.2013.00052
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.
By Simon Evans MEXICO CITY, March 27 (Reuters) - United States central defenders Omar Gonzalez and Matt Besler went into Tuesday's game against Mexico at the Azteca Stadium with just two World Cup qualifying starts between them, but looked like they had been alongside each other for years in a spirited 0-0 draw. Gonzalez, making his third start in a qualifier and Besler making his first, held Mexico at bay in front of more than 95,000 fans as the U.S earned just their second point ever at the home of their arch-rivals. ...
A judge on Wednesday approved AMR Corp's plan to merge with US Airways Group , a step toward creating the world's largest airline.
AMR, parent of American Airlines and in bankruptcy since November 2011, must still construct a formal restructuring plan incorporating the merger that meets court and creditor approval before the airline can emerge from bankruptcy.
American Airlines announced the plan to combine with US Airways last month, a deal that also requires regulatory approval.
In a crowded Manhattan courtroom on Wednesday, U.S. Bankruptcy Judge Sean Lane declined to approve, for now, a planned $19.9 million severance package for Tom Horton, AMR's outgoing chief executive.
Lane said he was uncertain as to whether the severance package requires his approval at all, or whether the matter is more appropriate for inclusion in AMR's formal restructuring plan.
That plan, which all debtors in bankruptcy must propose, will lay out how creditors will get paid back, and will require creditor approval.
The fate of the severance payment is unclear. The version of the merger agreement that earned the judge's approval may have to be amended to remove it.
Jack Butler, a lawyer for AMR's creditors' committee, said it was too early to tell how the parties will deal with the severance issue.
"The companies said they were prepared to amend the merger agreement in any respect, and I expect that there will be an amendment," Butler said after the hearing.
AMR filed for bankruptcy citing untenable labor costs after years of futile attempts to negotiate cost savings from its unionized workforce. It had been the last major U.S. carrier to go through bankruptcy, after its competitors underwent the same process in the last decade.
Wednesday's approval was a key moment in AMR's 16-month odyssey through reorganization under Chapter 11 of the bankruptcy code. Stephen Karotkin, a lawyer for AMR, called Wednesday's hearing a "watershed event" that moves AMR a step closer to exiting bankruptcy.
The airline began its bankruptcy process flatly opposed to merging while still in bankruptcy, but eventually relented to pressure from its creditors' committee, represented by Butler and Jay Goffman, both lawyers at Skadden Arps Slate Meagher & Flom.
US Airways Chief Executive Doug Parker wooed AMR aggressively, taking advantage of AMR's labor relations problems to appeal to its unions.
US Airways hammered out a tentative deal with the unions last April, before formal merger talks between the two companies' management teams had gone into full swing.
The creditors' committee eventually convinced AMR to adopt a protocol to evaluate a merger, and played a large role in analyzing the net savings and benefits from a merger.
AMR's current shareholders are expected to receive a 3.5 percent equity stake in the new firm, which would make it one of the few major bankruptcies in which equity holders earn some recovery.
The Skadden legal team advising the creditors' committee also played a central part in negotiating the new management structure, including the details of Horton's severance package.
Parker will serve as CEO of the combined carrier, while Horton, who became AMR's CEO when it filed for bankruptcy, will serve as chairman of the airline through the first annual meeting of shareholders. After that Parker will take on the chairman role.
The merger is expected to close in the third quarter.
The case is In re AMR Corp et al, U.S. Bankruptcy Court, Southern District of New York, No. 11-15463.
Metal-loving researchers analyzed the collective movement of individuals in mosh pits, which could help explain mass movements in other extreme situations. Sophie Bushwick reports.
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A heavy metal concert might be a tough place to think about physics, especially in the mosh pit, where some audience members dance violently. But the mosh pit itself is actually an interesting place to find physics in action. And not just force equals mass times acceleration.
Metal-loving Cornell researchers analyzed videos of mosh pits and mapped the motion of participants. They found that the collisions of moshers was similar to the motion of molecules in an ideal gas. Mosh dancers can also form what is called a circle pit, where they run collectively in a ring, creating a vortex pattern.
The scientists not only modeled mosh and circle pits, they also found how one type of motion transitions into the other. The presented their ongoing work at the American Physical Society's March Meeting. [Matthew Bierbaum et al, Mosh pits and Circle pits: Collective motion at heavy metal concerts]
But why bother to look at mosh pits in the first place? The physicists think their research may also apply to other extreme situations, which could help us understand collective human movement in panics and riots. So I say, rock on.
?Sophie Bushwick
[The above text is a transcript of this podcast]? ?
BAHIR DAR, Ethiopia (Reuters) - Ethiopia's ruling coalition re-elected Prime Minister Hailemariam Desalegn as chairman on Tuesday, completing a smooth transition after the death last year of his predecessor Meles Zenawi who kept a tight grip on power for 21 years.
Hailemariam, 47, was appointed premier in September, a month after the death of Meles, who was praised for steering economic growth into double figures but drew criticism from his opponents and rights groups for squeezing out dissent.
Meles's death raised questions about whether his Ethiopian People's Revolutionary Democratic Front (EPRDF), a coalition of four ethnic and regional based parties, would hold together or could come under strain as groups jostled for influence.
Opponents say there is infighting behind the scenes, but there was no indication of major rifts in the four-day meeting of the congress in the northern city of Bahir Dar. Some delegates questioned government policies before a 180-member coalition council voted behind closed doors for Hailemariam.
"The transition has gone smoothly - the first peaceful transition in the history of modern Ethiopia," said J. Peter Pham, director of the U.S.-based Michael S. Ansari Africa Centre at the Atlantic Council think tank.
"Whatever his faults, Meles gave Ethiopia a long period of stability and sustained economic growth," he said, adding there was no evidence of tensions that could break up the coalition.
Meles's policies often involved a heavy role for the state and have delivered strong growth. The economy of east Africa's most populous country is expected to expand by 8.5 percent in the 2012/2013 financial year.
"With the principles set forth by our late prime minister, we will carry on with our efforts to develop Ethiopia," Hailemariam told delegates, sporting a baseball cap emblazoned with the coalition's emblems.
MELES' FOOTSTEPS
The post of chairman usually lasts about two or two and a half years, depending on when the congress is called. Hailemariam had been elected to serve out Meles' remaining months as chief of the EPRDF. Tuesday's re-election formalizes his position.
The prime minister's post runs for five years with the next election due in 2015. But the 547-seat parliament has only one seat held by an opposition politician and the EPRDF's opponents say they continue to be pushed to the sidelines of politics.
Four region-based parties make up the EPRDF - the Tigrayan People's Liberation Front (TPLF), the Oromo People's Democratic Movement (OPDM), the Amhara National Democratic Movement (ANDM) and the Southern Ethiopian People's Democratic Movement (SEPDM).
Critics pointed to signs of discontent when it took a month after Meles's death to appoint Hailemariam, who also heads SEPDM. They also said his decision to appoint deputies from the three other parties was a ploy to ease ethnic rivalries.
Ruling party members dismissed those accusations.
"The EPRDF is a solid and cohesive party - cohesive in terms of leadership, cohesive in terms of having very clear political and economic programs," said Abraham Tekeste, state minister at the Ministry of Finance and Economic Development.
Mar. 26, 2013 ? Excess carbon dioxide in Earth's atmosphere created by the widespread burning of fossil fuels is the major driving force of global climate change, and researchers the world over are looking for new ways to generate power that leaves a smaller carbon footprint.
Now, researchers at the University of Georgia have found a way to transform the carbon dioxide trapped in the atmosphere into useful industrial products. Their discovery may soon lead to the creation of biofuels made directly from the carbon dioxide in the air that is responsible for trapping the sun's rays and raising global temperatures.
"Basically, what we have done is create a microorganism that does with carbon dioxide exactly what plants do-absorb it and generate something useful," said Michael Adams, member of UGA's Bioenergy Systems Research Institute, Georgia Power professor of biotechnology and Distinguished Research Professor of biochemistry and molecular biology in the Franklin College of Arts and Sciences.
During the process of photosynthesis, plants use sunlight to transform water and carbon dioxide into sugars that the plants use for energy, much like humans burn calories from food.
These sugars can be fermented into fuels like ethanol, but it has proven extraordinarily difficult to efficiently extract the sugars, which are locked away inside the plant's complex cell walls.
"What this discovery means is that we can remove plants as the middleman," said Adams, who is co-author of the study detailing their results published March 25 in the early online edition of the Proceedings of the National Academy of Sciences. "We can take carbon dioxide directly from the atmosphere and turn it into useful products like fuels and chemicals without having to go through the inefficient process of growing plants and extracting sugars from biomass."
The process is made possible by a unique microorganism called Pyrococcus furiosus, or "rushing fireball," which thrives by feeding on carbohydrates in the super-heated ocean waters near geothermal vents. By manipulating the organism's genetic material, Adams and his colleagues created a kind of P. furiosus that is capable of feeding at much lower temperatures on carbon dioxide.
The research team then used hydrogen gas to create a chemical reaction in the microorganism that incorporates carbon dioxide into 3-hydroxypropionic acid, a common industrial chemical used to make acrylics and many other products.
With other genetic manipulations of this new strain of P. furiosus, Adams and his colleagues could create a version that generates a host of other useful industrial products, including fuel, from carbon dioxide.
When the fuel created through the P. furiosus process is burned, it releases the same amount of carbon dioxide used to create it, effectively making it carbon neutral, and a much cleaner alternative to gasoline, coal and oil.
"This is an important first step that has great promise as an efficient and cost-effective method of producing fuels," Adams said. "In the future we will refine the process and begin testing it on larger scales."
The research was supported by the Department of Energy as part of the Electrofuels Program of the Advanced Research Projects Agency-Energy under Grant DE-AR0000081.
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The above story is reprinted from materials provided by University of Georgia. The original article was written by James Hataway.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
Matthew W. Keller, Gerrit J. Schut, Gina L. Lipscomb, Angeli L. Menon, Ifeyinwa J. Iwuchukwu, Therese T. Leuko, Michael P. Thorgersen, William J. Nixon, Aaron S. Hawkins, Robert M. Kelly, and Michael W. W. Adams. Exploiting microbial hyperthermophilicity to produce an industrial chemical, using hydrogen and carbon dioxide. PNAS, 2013 DOI: 10.1073/pnas.1222607110
Note: If no author is given, the source is cited instead.
Disclaimer: Views expressed in this article do not necessarily reflect those of ScienceDaily or its staff.
New insights into how genes turn on and offPublic release date: 27-Mar-2013 [ | E-mail | Share ]
Contact: Phyllis Brown phyllis.brown@ucdmc.ucdavis.edu 916-734-9023 University of California - Davis Health System
Findings could enhance our understanding of human development, cancer therapies and autism
(SACRAMENTO, Calif.) Researchers at UC Davis and the University of British Columbia have shed new light on methylation, a critical process that helps control how genes are expressed. Working with placentas, the team discovered that 37 percent of the placental genome has regions of lower methylation, called partially methylated domains (PMDs), in which gene expression is turned off. This differs from most human tissues, in which 70 percent of the genome is highly methylated.
While PMDs have been identified in cell lines, this is the first time they have been found in regular human tissue. In addition to enhancing our understanding of epigenetics, this work could influence cancer research and help illuminate how environmental toxins affect fetal development. The paper was published online this week in the Proceedings of the National Academy of Sciences (PNAS).
Since it was unraveled more than ten years ago, the human genome has been the focus of both popular interest and intense scientific focus. But the genome doesn't act alone; there are many factors that influence whether genes are turned on or off. One of these is an epigenetic process called methylation, in which a group of carbon and hydrogen atoms (a methyl group) attaches to DNA, adjusting how genes are expressed.
"I like to think of epigenetics as a layer on top of your genetic code," said senior author Janine LaSalle, professor of medical microbiology and immunology. "It's not the DNA sequence but it layers on top of that and methylation is the first layer. Those layers provide a lot of information to the cells on where and when to turn on the genes."
How and when genes are activated (or inactivated) can have a profound impact on human development, cancer and the biological legacy of environmental toxins. Prior to this research, PMDs had only been found in cultured cell lines, which led some scientists to wonder if they existed outside the test tube. This study confirms they exist in placental tissue, a critically important window into fetal development.
"The placenta is the interface between mother and fetus," said LaSalle, who is a researcher affiliated with the UC Davis MIND Institute. "It's a time capsule from when a lot of important methylation events occurred."
In addition, placental tissue was interesting to study because it has a number of invasive characteristics often associated with cancer. In fact, a number of cancers, such as breast and colon, have widespread PMDs. LaSalle notes that anti-cancer epigenetic therapies that adjust methylation could be refined based on this improved understanding of PMDs.
This work could also enhance our ability to detect genetic defects. Methylation, and other epigenetic data, provides information that cannot be found in the genome alone. For example, the vast majority of cells in the body contain identical genetic code. However, the added information provided by methylation allows scientists to determine where specific DNA came from.
"Methylation patterns are like fingerprints, showing which tissue that DNA is derived from," LaSalle said. "You can't get that information from just the DNA sequence. As a result, methylation studies could be a very rich source for biomarkers."
In the study, PMDs encompassed 37 percent of the placental genome, including 3,815 genes, around 17 percent of all genes. When found in low-methylation regions, these genes were less likely to be transcribed into proteins. Researchers also found that PMDs also contain more highly methylated CpG islands (genomic areas with large numbers of cytosine-guanine pairs), which are often associated with gene transcriptional silencing of promoters.
Because the placental PMDs contained many genes associated with neuronal development, and specifically autism, LaSalle notes that future research could investigate how epigenetics impacts autism genes at birth.
"We are looking for biomarkers that predict neurodevelopmental outcomes," LaSalle said. "Now we have a series of snap shots from a critical period where we think environmental factors are playing a role in the developing brain."
###
The study's other authors include: Diane I. Schroeder, John Blair, Paul Lott, Hung On Ken Yu, Danna Hong, Florence Crary, Paul Ashwood, Cheryl Walker, Ian Korf and Wendy P. Robinson.
At the UC Davis MIND Institute, world-renowned scientists engage in collaborative, interdisciplinary research to find the causes of and develop treatments and cures for autism, attention-deficit/hyperactivity disorder (ADHD), fragile X syndrome, 22q11.2 deletion syndrome, Down syndrome and other neurodevelopmental disorders. For more information, visit http://mindinstitute.ucdavis.edu.
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New insights into how genes turn on and offPublic release date: 27-Mar-2013 [ | E-mail | Share ]
Contact: Phyllis Brown phyllis.brown@ucdmc.ucdavis.edu 916-734-9023 University of California - Davis Health System
Findings could enhance our understanding of human development, cancer therapies and autism
(SACRAMENTO, Calif.) Researchers at UC Davis and the University of British Columbia have shed new light on methylation, a critical process that helps control how genes are expressed. Working with placentas, the team discovered that 37 percent of the placental genome has regions of lower methylation, called partially methylated domains (PMDs), in which gene expression is turned off. This differs from most human tissues, in which 70 percent of the genome is highly methylated.
While PMDs have been identified in cell lines, this is the first time they have been found in regular human tissue. In addition to enhancing our understanding of epigenetics, this work could influence cancer research and help illuminate how environmental toxins affect fetal development. The paper was published online this week in the Proceedings of the National Academy of Sciences (PNAS).
Since it was unraveled more than ten years ago, the human genome has been the focus of both popular interest and intense scientific focus. But the genome doesn't act alone; there are many factors that influence whether genes are turned on or off. One of these is an epigenetic process called methylation, in which a group of carbon and hydrogen atoms (a methyl group) attaches to DNA, adjusting how genes are expressed.
"I like to think of epigenetics as a layer on top of your genetic code," said senior author Janine LaSalle, professor of medical microbiology and immunology. "It's not the DNA sequence but it layers on top of that and methylation is the first layer. Those layers provide a lot of information to the cells on where and when to turn on the genes."
How and when genes are activated (or inactivated) can have a profound impact on human development, cancer and the biological legacy of environmental toxins. Prior to this research, PMDs had only been found in cultured cell lines, which led some scientists to wonder if they existed outside the test tube. This study confirms they exist in placental tissue, a critically important window into fetal development.
"The placenta is the interface between mother and fetus," said LaSalle, who is a researcher affiliated with the UC Davis MIND Institute. "It's a time capsule from when a lot of important methylation events occurred."
In addition, placental tissue was interesting to study because it has a number of invasive characteristics often associated with cancer. In fact, a number of cancers, such as breast and colon, have widespread PMDs. LaSalle notes that anti-cancer epigenetic therapies that adjust methylation could be refined based on this improved understanding of PMDs.
This work could also enhance our ability to detect genetic defects. Methylation, and other epigenetic data, provides information that cannot be found in the genome alone. For example, the vast majority of cells in the body contain identical genetic code. However, the added information provided by methylation allows scientists to determine where specific DNA came from.
"Methylation patterns are like fingerprints, showing which tissue that DNA is derived from," LaSalle said. "You can't get that information from just the DNA sequence. As a result, methylation studies could be a very rich source for biomarkers."
In the study, PMDs encompassed 37 percent of the placental genome, including 3,815 genes, around 17 percent of all genes. When found in low-methylation regions, these genes were less likely to be transcribed into proteins. Researchers also found that PMDs also contain more highly methylated CpG islands (genomic areas with large numbers of cytosine-guanine pairs), which are often associated with gene transcriptional silencing of promoters.
Because the placental PMDs contained many genes associated with neuronal development, and specifically autism, LaSalle notes that future research could investigate how epigenetics impacts autism genes at birth.
"We are looking for biomarkers that predict neurodevelopmental outcomes," LaSalle said. "Now we have a series of snap shots from a critical period where we think environmental factors are playing a role in the developing brain."
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The study's other authors include: Diane I. Schroeder, John Blair, Paul Lott, Hung On Ken Yu, Danna Hong, Florence Crary, Paul Ashwood, Cheryl Walker, Ian Korf and Wendy P. Robinson.
At the UC Davis MIND Institute, world-renowned scientists engage in collaborative, interdisciplinary research to find the causes of and develop treatments and cures for autism, attention-deficit/hyperactivity disorder (ADHD), fragile X syndrome, 22q11.2 deletion syndrome, Down syndrome and other neurodevelopmental disorders. For more information, visit http://mindinstitute.ucdavis.edu.
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Excerpts from the arguments before the Supreme Court on Tuesday about California's Proposition 8 ban on same-sex marriage, from a transcript released by the Supreme Court:
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On whether the case should be before them (Chief Justice John Roberts and Justice Anthony Kennedy):
ROBERTS: But a state can't authorize anyone to proceed in federal court, because that would leave the definition under Article III of the federal Constitution as to who can bring ? who has standing to bring claims up to each state. And I don't think we've ever allowed anything like that.
KENNEDY: The problem ? the problem with the case is that you're really asking, particularly because of the sociological evidence you cite, for us to go into uncharted waters, and you can play with that metaphor, there's a wonderful destination, it is a cliff. Whatever that was. ... But you're ? you're doing so in a ? in a case where the opinion is very narrow. Basically that once the state goes halfway, it has to go all the way or 70 percent of the way, and you're doing so in a case where there's a substantial question on ? on standing. I just wonder if ? if the case was properly granted.
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On the question of children of same-sex parents (Kennedy and Charles Cooper, the lawyer for the defenders of Proposition 8):
KENNEDY: I think there's ? there's substantial ? that there's substance to the point that sociological information is new. We have five years of information to weigh against 2,000 years of history or more. On the other hand, there is an immediate legal injury or legal ? what could be a legal injury, and that's the voice of these children. There are some 40,000 children in California, according to the red brief, that live with same-sex parents, and they want their parents to have full recognition and full status. The voice of those children is important in this case, don't you think?
COOPER (in response): I certainly would not dispute the importance of that consideration. That consideration especially in the political process, where this issue is being debated and will continue to be debated, certainly, in California. It's being debated elsewhere. But on that ? on that specific question, Your Honor, there simply is no data.
___
On the issue of same-sex marriage (Justice Samuel Alito):
ALITO: The one thing that the parties in this case seem to agree on is that marriage is very important. It's thought to be a fundamental building block of society and its preservation essential for the preservation of society. Traditional marriage has been around for thousands of years. Same-sex marriage is very new. I think it was first adopted in The Netherlands in 2000. So there isn't a lot of data about its effect. And it may turn out to be a -- a good thing; it may turn out not to be a good thing, as the supporters of Proposition 8 apparently believe.
___
On the question of redefining marriage (Justice Antonin Scalia):
SCALIA: Mr. Cooper, let me ? let me give you one ? one concrete thing. I don't know why you don't mention some concrete things. If you redefine marriage to include same-sex couples, you must ? you must permit adoption by same-sex couples, and there's ? there's considerable disagreement among -- among sociologists as to what the consequences of raising a child in a -- in a single-sex family, whether that is harmful to the child or not. Some states do not ? do not permit adoption by same-sex couples for that reason.
___
On the rights of same-sex couples (Theodore Olson, the lawyer for two same-sex couples):
OLSON: This is a measure that walls off the institution of marriage, which is not society's right. It's an individual right that this Court again and again and again has said the right to get married, the right to have the relationship of marriage is a personal right. It's a part of the right of privacy, association, liberty, and the pursuit of happiness.
ROBERTS (in response): I'm not sure, counsel, that it makes -- I'm not sure that it's right to view this as excluding a particular group. When the institution of marriage developed historically, people didn't get around and say let's have this institution, but let's keep out homosexuals. The institution developed to serve purposes that, by their nature, didn't include homosexual couples. It is -- yes, you can say that it serves some of the other interests where it makes sense to include them, but not all the interests. And it seems to me, your friend argues on the other side, if you have an institution that pursues additional interests, you don't have to include everybody just because some other aspects of it can be applied to them.
___
On the Constitution and same-sex couples (Olson and Scalia):
SCALIA: The California Supreme Court decides what the law is. That's what we decide, right? We don't prescribe law for the future. We decide what the law is. I'm curious, when -- when did -- when did it become unconstitutional to exclude homosexual couples from marriage? 1791? 1868, when the Fourteenth Amendment was adopted? Sometimes -- some time after Baker, where we said it didn't even raise a substantial Federal question? When -- when -- when did the law become this?
OLSON: May I answer this in the form of a rhetorical question? When did it become unconstitutional to prohibit interracial marriages? When did it become unconstitutional to assign children to separate schools.
SCALIA: It's an easy question, I think, for that one. At -- at the time that the Equal Protection Clause was adopted. That's absolutely true. But don't give me a question to my question. (laughter) ... When do you think it became unconstitutional? Has it always been unconstitutional?
OLSON: When the California Supreme Court faced the decision, which it had never faced before, is -- does excluding gay and lesbian citizens, who are a class based upon their status as homosexuals -- is it -- is it constitutional.
___
On sexual orientation (Justice Sonia Sotomayor and Cooper):
SOTOMAYOR: Outside of the marriage context, can you think of any other rational basis, reason, for a state using sexual orientation as a factor in denying homosexuals benefits or imposing burdens on them? Is there any other rational decision-making that the government could make? Denying them a job, not granting them benefits of some sort, any other decision?
COOPER (in response): I cannot. I do not have any -- anything to offer you in that regard. ... We are saying the interest in marriage and the -- and the state's interest and society's interest in what we have framed as responsible procreation is -- is vital, but at bottom, with respect to those interests, our submission is that same-sex couples and opposite-sex couples are simply not similarly situated.
___
On procreation and age (Justice Elena Kagan and Cooper, and later Scalia):
KAGAN: If you are over the age of 55, you don't help us serve the government's interest in regulating procreation through marriage. So why is that different?
COOPER: Even with respect to couples over the age of 55, it is very rare that both couples -- both parties to the couple are infertile, and the traditional -- (laughter)
KAGAN: No, really, because if the couple -- I can just assure you, if both the woman and the man are over the age of 55, there are not a lot of children coming out of that marriage. (laughter)
COOPER: Society's interest in responsible procreation isn't just with respect to the procreative capacities of the couple itself. The marital norm, which imposes the obligations of fidelity and monogamy, Your Honor, advances the interests in responsible procreation by making it more likely that neither party, including the fertile party to that --
KAGAN: Actually, I'm not even --
SCALIA: I suppose we could have a questionnaire at the marriage desk when people come in to get the marriage -- you know, Are you fertile or are you not fertile? (laughter.) I suspect this court would hold that to be an unconstitutional invasion of privacy, don't you think?
KAGAN: Well, I just asked about age. I didn't ask about anything else. That's not -- we ask about people's age all the time.
COOPER: Your Honor, and even asking about age, you would have to ask if both parties are infertile. Again --
SCALIA: Strom Thurmond was -- was not the chairman of the Senate committee when Justice Kagan was confirmed. (laughter)
Mar 26 (Reuters) - Leading money winners on the 2013 PGATour on Monday (U.S. unless stated): 1. Tiger Woods $3,787,600 2. Brandt Snedeker $2,859,920 3. Matt Kuchar $2,154,500 4. Steve Stricker $1,820,000 5. Phil Mickelson $1,650,260 6. Hunter Mahan $1,553,965 7. John Merrick $1,343,514 8. Dustin Johnson $1,330,507 9. Russell Henley $1,313,280 10. Kevin Streelman $1,310,343 11. Keegan Bradley $1,274,593 12. Charles Howell III $1,256,373 13. Michael Thompson $1,254,669 14. Brian Gay $1,171,721 15. Justin Rose $1,155,550 16. Jason Day $1,115,565 17. Chris Kirk $1,097,053 18. ...
Penn research: Quitting marshmallow test can be a rational decisionPublic release date: 26-Mar-2013 [ | E-mail | Share ]
Contact: Evan Lerner elerner@upenn.edu 215-573-6604 University of Pennsylvania
A psychological experiment known as "the marshmallow test" has captured the public's imagination as a marker of self control and even as a predictor of future success. This test shows how well children can delay gratification, a trait that has been shown to be as important to scholastic performance as traditional IQ.
New research from University of Pennsylvania psychologists suggests, however, that changing one's mind about delaying gratification can be a rational decision in situations when the timing of the payoff is uncertain.
The research was conducted by assistant professor Joseph Kable and postdoctoral researcher Joseph McGuire, both of the Department of Psychology in Penn's School of Arts and Sciences.
The study was published in the journal Psychological Review.
In the classic marshmallow test, researchers give children a choice between one marshmallow and two. After the children enthusiastically choose two, the experimenter says that they need to leave for "a few minutes" or "a little while." The children are also told that, if they can hold off eating the one marshmallow until the researcher returns, they can have the two marshmallows they prefer. With the children left alone in the room, hidden cameras track how long they resist temptation. Most try to wait but end up caving within a few minutes.
"The kids' responses seem illogical if you decided to wait in the first place, why wouldn't you wait the whole way through?" Kable said.
This behavior was an intriguing puzzle for Kable; he studies how people make value-based decisions, especially when they require comparing the value of something in the present with something else in the future. But, in conducting his own variants of the marshmallow test, he found that a key fact had been glossed over in both popular and academic discussions: the children don't know how long they will have to wait.
"I didn't even know that there was uncertainty in the marshmallow test until we started trying to do that type of experiment ourselves on adults and weren't getting any interesting behavior," Kable said. "That the kids don't know how long it's going to be until the researcher returns changes the entire decision problem!"
This confusion may stem from the explanations provided for children's decisions in the marshmallow test. Some of the researchers who have employed the marshmallow test and its variants have hypothesized that participants' decision to eat the marshmallow could be attributed to a strong impulse overriding the original decision to wait, or that the ability to wait was drawing on a reserve of self control that is depleted over time. Since these hypotheses make the same predictions even when there is no uncertainty, the uncertainty was often downplayed.
Kable and McGuire's analysis of data from earlier marshmallow-test studies showed problems for these hypotheses, however. If reversing the decision to wait was a function of the wearing down of self control, the time at which children eat the first marshmallow should be clustered in the middle or towards the end of the waiting period. Instead, children who gave up waiting tended to do so within the first few minutes.
After this analysis, Kable and McGuire did their own survey-based research to see how people estimate the lengths of waiting times in different situations.
The researchers asked participants to imagine themselves in a variety of scenarios, such as watching a movie, practicing the piano or trying to lose weight. Participants were told the amount of time they had been at the activity and were asked to respond how long they thought it would be until they reached their goal or the end.
The results showed a marked difference between the scenario with a relatively well-defined length and those that were more ambiguous.
"Our intuition is that when we are waiting for something, the longer we wait the closer and closer we get to that thing, which is what we see when we ask people about familiar things, like how long a movie will last," Kable says. "But what we've found is that, if you don't know anything about when the outcome will occur, the longer you wait the more you think you're getting farther and farther away from that outcome."
While the marshmallow test remains a good predictor of who is better or worse at delaying gratification, Kable's research suggests the mechanism behind that ability needs to be reinterpreted. It may also suggest some tools and techniques people can use to improve self control, or at least become aware of situations where delaying gratification will be particularly challenging.
"This is exciting to us because it suggests a way to get people to persist to the end," Kable said. "Your previous experience and your expectations can change your behavior, so you need to give them experiences that provide them with the right kinds of expectations."
###
The research was supported by the National Institutes of Health.
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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.
Penn research: Quitting marshmallow test can be a rational decisionPublic release date: 26-Mar-2013 [ | E-mail | Share ]
Contact: Evan Lerner elerner@upenn.edu 215-573-6604 University of Pennsylvania
A psychological experiment known as "the marshmallow test" has captured the public's imagination as a marker of self control and even as a predictor of future success. This test shows how well children can delay gratification, a trait that has been shown to be as important to scholastic performance as traditional IQ.
New research from University of Pennsylvania psychologists suggests, however, that changing one's mind about delaying gratification can be a rational decision in situations when the timing of the payoff is uncertain.
The research was conducted by assistant professor Joseph Kable and postdoctoral researcher Joseph McGuire, both of the Department of Psychology in Penn's School of Arts and Sciences.
The study was published in the journal Psychological Review.
In the classic marshmallow test, researchers give children a choice between one marshmallow and two. After the children enthusiastically choose two, the experimenter says that they need to leave for "a few minutes" or "a little while." The children are also told that, if they can hold off eating the one marshmallow until the researcher returns, they can have the two marshmallows they prefer. With the children left alone in the room, hidden cameras track how long they resist temptation. Most try to wait but end up caving within a few minutes.
"The kids' responses seem illogical if you decided to wait in the first place, why wouldn't you wait the whole way through?" Kable said.
This behavior was an intriguing puzzle for Kable; he studies how people make value-based decisions, especially when they require comparing the value of something in the present with something else in the future. But, in conducting his own variants of the marshmallow test, he found that a key fact had been glossed over in both popular and academic discussions: the children don't know how long they will have to wait.
"I didn't even know that there was uncertainty in the marshmallow test until we started trying to do that type of experiment ourselves on adults and weren't getting any interesting behavior," Kable said. "That the kids don't know how long it's going to be until the researcher returns changes the entire decision problem!"
This confusion may stem from the explanations provided for children's decisions in the marshmallow test. Some of the researchers who have employed the marshmallow test and its variants have hypothesized that participants' decision to eat the marshmallow could be attributed to a strong impulse overriding the original decision to wait, or that the ability to wait was drawing on a reserve of self control that is depleted over time. Since these hypotheses make the same predictions even when there is no uncertainty, the uncertainty was often downplayed.
Kable and McGuire's analysis of data from earlier marshmallow-test studies showed problems for these hypotheses, however. If reversing the decision to wait was a function of the wearing down of self control, the time at which children eat the first marshmallow should be clustered in the middle or towards the end of the waiting period. Instead, children who gave up waiting tended to do so within the first few minutes.
After this analysis, Kable and McGuire did their own survey-based research to see how people estimate the lengths of waiting times in different situations.
The researchers asked participants to imagine themselves in a variety of scenarios, such as watching a movie, practicing the piano or trying to lose weight. Participants were told the amount of time they had been at the activity and were asked to respond how long they thought it would be until they reached their goal or the end.
The results showed a marked difference between the scenario with a relatively well-defined length and those that were more ambiguous.
"Our intuition is that when we are waiting for something, the longer we wait the closer and closer we get to that thing, which is what we see when we ask people about familiar things, like how long a movie will last," Kable says. "But what we've found is that, if you don't know anything about when the outcome will occur, the longer you wait the more you think you're getting farther and farther away from that outcome."
While the marshmallow test remains a good predictor of who is better or worse at delaying gratification, Kable's research suggests the mechanism behind that ability needs to be reinterpreted. It may also suggest some tools and techniques people can use to improve self control, or at least become aware of situations where delaying gratification will be particularly challenging.
"This is exciting to us because it suggests a way to get people to persist to the end," Kable said. "Your previous experience and your expectations can change your behavior, so you need to give them experiences that provide them with the right kinds of expectations."
###
The research was supported by the National Institutes of Health.
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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.
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Public release date: 27-Mar-2013
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