Source: http://news.feedzilla.com/en_us/stories/politics/top-stories/295696781?client_source=feed&format=rss
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Lion kills heron: A video of four lions setting upon a blue heron at a Dutch zoo serves as a reminder of the King of the Jungle's wild instincts.
By Mai Ng?c Ch?u,?Contributor / March 28, 2013
EnlargeA video of four lions preying upon a heron at a Dutch zoo, shot last year and reposted on YouTube Wednesday, reminds us that you can take the lion out of the wild, but you can't take the wild out of the lion.?
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In the video, a blue heron?at the Artis Royal Zoo wandered into a small pool while a group of four lions were basking in the sun, about 25 yards away. ?
As the the bird came into view of a lioness, instinct kicked in.?The lioness darted toward the bird, which desperately attempted to take flight but was pulled from the air with a leaping snatch.?The rest of her pride joined in to finish off the heron. ?
The footage of the killing has drawn thousands of views, because it's not often to see animals prey on one another at zoos. Experts said that, though the kings of the jungle are kept in captivity, cared and fed by humans, their original wildness remains untamed.?
Earlier this month, an African lion broke out of its pen and killed a 24-year-old intern at the Cat Haven sanctuary in California who was cleaning the main enclosure. According to CNN, the?5-year-old, 350-pound?killer was one of the victim's favorites.
Captive lions tend to act on their wild instincts whenever potential prey catches their eyes. A pair of videos titled "lion tries to eat baby" have attracted in total more than 7.6 millions views on YouTube since they were uploaded last April. The clips show an Oregon Zoo lioness snarling and baring her fangs in vain at a happily oblivious toddler protected by reinforced glass.
"Most of the time they seem relaxed and cuddly?so it's easy to forget that they react to meat with the reflexive instincts of a shark." Professor Craig Packer, a leading big cat expert at the University of Minnesota, noted in a recent interview with National Geographic News.?"Ten years ago Roy Horne (of Siegfried ?and Roy) was attacked by a tiger that they had handled for years?these attacks happen when people forget about the shark inside."
Early this month, The Monitor's Gloria Goodale interviewed Zara McDonald, executive director of the Bay Area Felidae?Conservation Fund?regarding the death of the Seattle woman.?
?Cats are predators,? said McDonald.?"I don?t care how tame anyone thinks one might be, they are always a wild animal with the ability to hurt humans.?
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#{example}"); ipb.editor_values.get('templates')['togglesource'] = new Template(""); ipb.editor_values.get('templates')['toolbar'] = new Template(""); ipb.editor_values.get('templates')['button'] = new Template("
Reputation: 0
Posted Yesterday, 09:19 PM
There is no property to set the back color of Datetime Picker, is there another way to set backcolor of it?
Reputation: 200
Posted Yesterday, 09:52 PM
yogesh7136, on 29 March 2013 - 10:19 PM, said:
There is no property to set the back color of Datetime Picker, is there another way to set backcolor of it?
Reputation: 716
Posted Today, 01:36 AM
Yes, weird. It seems that MS in their wisdom haven't filled in these properties (excuse the silly pun! groan).There is code here at SO to achieve this, but it is in C# and needs translation; but it requires creating a custom control that extends DateTimePicker.
const int WM_ERASEBKGND = 0x14; protected override void WndProc(ref System.Windows.Forms.Message m) { if(m.Msg == WM_ERASEBKGND) { Graphics g = Graphics.FromHdc(m.WParam); g.FillRectangle(new SolidBrush(_backColor), ClientRectangle); g.Dispose(); return; } base.WndProc(ref m); }
Reputation: 1297
Posted Today, 05:47 AM
Quote
Starting with Windows Vista and depending on the theme, setting this property might not change the appearance of the calendar. For example, if Windows is set to use the Aero theme, setting this property has no effect. This is because an updated version of the calendar is rendered with an appearance that is derived at run time from the current operating system theme. If you want to use this property and enable the earlier version of the calendar, you can disable visual styles for your application. Disabling visual styles might affect the appearance and behavior of other controls in your application. To disable visual styles in Visual Basic, open the Project Designer and uncheck the Enable XP visual styles check box. To disable visual styles in C#, open Program.cs and comment out Application.EnableVisualStyles();
Doesn't solve your problem but it explains why those properties seem to have no affect. Unless you want everything to have that old ugly Win 98 look and feel
This post has been edited by CharlieMay: Today, 05:55 AM
Reputation: 200
Posted Today, 08:38 AM
andrewsw, on 30 March 2013 - 02:36 AM, said:
There is code here at SO to achieve this, but it is in C# and needs translation; but it requires creating a custom control that extends DateTimePicker.Const WM_ERASEBKGND As Integer = &H14 Protected Overrides Sub WndProc(ByRef m As System.Windows.Forms.Message) If m.Msg = WM_ERASEBKGND Then Dim g As Graphics = Graphics.FromHdc(m.WParam) g.FillRectangle(New SolidBrush(Color.AliceBlue), ClientRectangle) g.Dispose() Return End If MyBase.WndProc(m) End Sub
Page 1 of 1
Source: http://www.dreamincode.net/forums/topic/317172-can-i-set-back-color-of-datetime-picker/
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Engineers at Oregon State University have developed a new interactive system to create networks of small wetlands in Midwest farmlands, which could help the region prevent massive spring floods and also retain water and mitigate droughts in a warming climate.
The planning tool, which is being developed and tested in a crop-dominated watershed near Indianapolis, is designed to identify the small areas best suited to wetland development, optimize their location and size, and restore a significant portion of the region's historic water storage ability by using only a small fraction of its land.
Using this approach, the researchers found they could capture the runoff from 29 percent of a watershed using only 1.5 percent of the entire area.
The findings were published in Ecological Engineering, a professional journal, and a website is now available at http://wrestore.iupui.edu/ that allows users to apply the principles to their own land.
The need for new approaches to assist farmers and agencies to work together and use science-based methods is becoming critical, experts say. Massive floods and summer droughts have become more common and intense in the Midwest because of climate change and decades of land management that drains water rapidly into rivers via tile drains.
"The lands of the Midwest, which is one of the great food producing areas of the world, now bear little resemblance to their historic form, which included millions of acres of small lakes and wetlands that have now been drained," said Meghna Babbar-Sebens, an assistant professor of civil and construction engineering at Oregon State. "Agriculture, deforestation, urbanization and residential development have all played a role.
"We have to find some way to retain and slowly release water, both to use it for crops and to prevent flooding," Babbar-Sebens said. "There's a place for dams and reservoirs but they won't solve everything. With increases in runoff, what was once thought to be a 100-year flood event is now happening more often.
"Historically, wetlands in Indiana and other Midwestern states were great at intercepting large runoff events and slowing down the flows," she said. "But Indiana has lost more than 85 percent of the wetlands it had prior to European settlement."
An equally critical problem is what appears to be increasing frequency of summer drought, she said, which may offer a solid motivation for the region's farmers to become involved. The problem is not just catastrophic downstream flooding in the spring, but also the loss of water and soil moisture in the summer that can be desperately needed in dry years.
The solution to both issues, scientists say, is to "re-naturalize" the hydrology of a large section of the United States. Working toward this goal was a research team from Oregon State University, Indiana University-Purdue University in Indianapolis, the Wetlands Institute in New Jersey, and the U.S. Environmental Protection Agency. They used engineering principles, historic analysis and computer simulations to optimize the effectiveness of any land use changes, so that minimal land use alteration would offer farmers and landowners a maximum of benefits.
In the Midwest, many farmers growing corn, soybeans and other crops have placed "tiles" under their fields to rapidly drain water into streams, which dries the soil and allows for earlier planting. Unfortunately, it also concentrates pollutants, increases flooding and leaves the land drier during the summer. Without adequate rain, complete crop losses can occur.
Experts have also identified alternate ways to help, including the use of winter cover crops and grass waterways that help retain and more slowly release water. And the new computer systems can identify the best places for all of these approaches to be used.
###
Oregon State University: http://www.orst.edu
Thanks to Oregon State University for this article.
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Contact: Mary Beth O'Leary
moleary@cell.com
617-397-2802
Cell Press
Communities that act locally to limit their fish catches will reap the rewards of their action, as will their neighbors. That's the conclusion of a study reported on March 28 in the Cell Press journal Current Biology of the highly sought-after fish known as squaretail coral grouper living in five community-owned reef systems in Papua New Guinea.
"We found that many larvae that were produced by the managed adults return to that same fish population, which means that the same fishers that agree to regulate their catch benefit from their actions," said Glenn Almany of the Australian Research Council Centre of Excellence for Coral Reef Studies at James Cook University. "Although we've been telling fishers for quite some time that they would benefit from protecting some of their adult fishes, we couldn't prove it because it was difficult to track where larvae end up."
Squaretail coral grouper are especially vulnerable to overfishing because they gather in large numbers to reproduce. Fishers know exactly when and where to go fishing. In order to track where young coral grouper produced by those aggregations end up, Almany and his colleagues applied genetic parentage analysis to adults from a single managed spawning aggregation and to juveniles in that tenure area and four others along a 75-kilometer stretch of coastline.
Within the primary area of the study, 17 to 25 percent of juveniles were produced by the focal aggregation, the researchers found. In the four neighboring tenure areas, 6 to 17 percent of juveniles were from the aggregation. The researchers predict from their data that half of all coral grouper young settle within 14 kilometers of the spawning site following their 25-day larval period.
"Over that time, they could certainly travel a lot farther," Almany said. "The fact that many don't was very surprising."
It also means that both local and cooperative management actions can provide fishery benefits to communities over small spatial scales, which should help to inspire local action, the researchers say.
"This study can empower coastal communities throughout the Coral Trianglethe area of greatest marine biodiversityto make fishery management decisions that they can be confident will benefit them," Almany said.
The fish will be the better for it, too.
###
?
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.
Contact: Mary Beth O'Leary
moleary@cell.com
617-397-2802
Cell Press
Communities that act locally to limit their fish catches will reap the rewards of their action, as will their neighbors. That's the conclusion of a study reported on March 28 in the Cell Press journal Current Biology of the highly sought-after fish known as squaretail coral grouper living in five community-owned reef systems in Papua New Guinea.
"We found that many larvae that were produced by the managed adults return to that same fish population, which means that the same fishers that agree to regulate their catch benefit from their actions," said Glenn Almany of the Australian Research Council Centre of Excellence for Coral Reef Studies at James Cook University. "Although we've been telling fishers for quite some time that they would benefit from protecting some of their adult fishes, we couldn't prove it because it was difficult to track where larvae end up."
Squaretail coral grouper are especially vulnerable to overfishing because they gather in large numbers to reproduce. Fishers know exactly when and where to go fishing. In order to track where young coral grouper produced by those aggregations end up, Almany and his colleagues applied genetic parentage analysis to adults from a single managed spawning aggregation and to juveniles in that tenure area and four others along a 75-kilometer stretch of coastline.
Within the primary area of the study, 17 to 25 percent of juveniles were produced by the focal aggregation, the researchers found. In the four neighboring tenure areas, 6 to 17 percent of juveniles were from the aggregation. The researchers predict from their data that half of all coral grouper young settle within 14 kilometers of the spawning site following their 25-day larval period.
"Over that time, they could certainly travel a lot farther," Almany said. "The fact that many don't was very surprising."
It also means that both local and cooperative management actions can provide fishery benefits to communities over small spatial scales, which should help to inspire local action, the researchers say.
"This study can empower coastal communities throughout the Coral Trianglethe area of greatest marine biodiversityto make fishery management decisions that they can be confident will benefit them," Almany said.
The fish will be the better for it, too.
###
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Source: http://www.eurekalert.org/pub_releases/2013-03/cp-sfp032513.php
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Mar. 28, 2013 ? Teenagers' struggles to connect with their peers in the early adolescent years while not getting swept along by negative peer influences predict their capacity to form strong friendships and avoid serious problems even ten years later. Those are the conclusions of a new longitudinal study by researchers at the University of Virginia that appears in the journal Child Development.
"Overall, we found that teens face a high-wire act with their peers," explains Joseph P. Allen, Hugh P. Kelly Distinguished Professor at the University of Virginia, who led the study. "They need to establish strong, positive connections with them while at the same time establishing independence in resisting deviant peer influences. Those who don't manage this have significant problems as much as a decade later."
Researchers followed about 150 teens over a 10-year period (starting at age 13 and continuing to 23) to learn about the long-term effects of their peer struggles early in adolescence. They gathered information from multiple sources -- the teens themselves, their parents and peers, and by observing teens' later interactions with romantic partners. The teens comprised a racially, ethnically, and socioeconomically diverse group.
Teens who had trouble connecting well with their peers in early adolescence had difficulty establishing close friendships in young adulthood. Teens who didn't connect well at 13 also had more difficulty managing disagreements in romantic relationships as adults.
Teens who had trouble establishing some autonomy and independence with peers (especially with respect to minor forms of deviance such as shoplifting and vandalism) were found to be at higher risk for problems with alcohol and substance use, and for illegal behavior, almost a decade later.
Conversely, teens who were seen as desirable companions -- those deemed empathetic, able to see things from different perspectives and control their impulses, and having a good sense of humor -- were more likely to have positive relationships in young adulthood.
Teens who were able to establish some autonomy vis a vis peers' influences were more likely to avoid problematic behavior in young adulthood, with teens who showed they were able to think for themselves in the face of negative peer influences using less alcohol as early adults and having fewer problems with alcohol and substance abuse as young adults. But teens who were seen as desirable companions were more likely to have higher levels of alcohol use in early adulthood and future problems associated with alcohol and substance use.
"The findings make it clear that establishing social competence in adolescence and early adulthood is not a straightforward process, but involves negotiating challenging and at times conflicting goals between peer acceptance and autonomy with regard to negative peer influences," Allen notes.
"Teaching teens how to stand up for themselves in ways that preserve and deepen relationships -- to become their own persons while still connecting to others -- is a core task of social development that parents, teachers, and others can all work to promote," adds Allen.
Teens who managed both of these goals simultaneously -- connecting with peers while retaining their autonomy -- were rated by their parents as being most competent overall by age 23. "There is a positive pathway through the peer jungle of early adolescence," says Allen, "but it is a tricky one for many teens to find and traverse."
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Source: http://feeds.sciencedaily.com/~r/sciencedaily/~3/Shaf-2ktyMQ/130328080223.htm
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Please check the URL for proper spelling and capitalization. If you're having trouble locating a destination on Yahoo!, try visiting the Yahoo! homepage or look through a list of Yahoo!'s online services.
Please try Yahoo Help Central if you need more assistance.
Source: http://news.yahoo.com/quotations-day-070627283.html
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NBC's Andrea Mitchell reports on the news conference between Secretary of State John Kerry and Afghan President ?Hamid Karzai.
By Andrea Mitchell and Jamieson Lesko, NBC News
Jason Reed / AP
Secretary of State John Kerry, accompanied by U.S. Ambassador to Afghanistan James Cunningham, left, meets with Afghan President Hamid Karzai at the Presidential Palace in Kabul, Monday.
KABUL -- Afghan President Hamid Karzai, who has infuriated U.S. officials with anti-American rhetoric, on Monday denied suggesting that the U.S. was colluding with the Taliban to convince Afghans that foreign forces were needed in the country beyond 2014.?
In a joint news briefing with Secretary of State John Kerry, Karzai said the media misinterpreted comments he made during a visit by Defense Secretary Chuck Hagel on March 10.
Karzai said the point he was trying to make was that by continuing to bomb and kill innocent Afghans, the Taliban is giving a reason for the U.S. to stay.
It was the media, Karzai said, that misinterpreted that to mean collusion, a word he said he did not use.
?If they want the international forces to leave, the best thing to do is stop hurting Afghans,? Karzai said.
Kerry arrived in Afghanistan?s capital Monday on an unannounced visit that aims to repair fractured ties with President Hamid Karzai.
For his part, Kerry said the United States and Afghan leaders share the same goals ? bringing the Taliban into peace talks.
The meeting came on the same day the U.S. turned over the detention facility at the U.S.-run Bagram military base north of Kabul to Afghan control, which has been a priority for Karzai.?U.S. officials say they've been assured the most dangerous prisoners will not be released.
It is Kerry?s sixth visit to Afghanistan since President Barack Obama took office, but his first as secretary of state.
State Department officials told reporters traveling with Kerry that he is optimistic the U.S. and Afghanistan can overcome recent differences, including the awkward moment earlier this month when Karzai accused the U.S. and the Taliban of colluding to convince Afghans that foreign forces were needed beyond 2014.
The officials said Kerry was not in Kabul to lecture or chide Karzai, adding that he acknowledged the relationship was ?not always going to be easy.?
The secretary of state arrived in Kabul this morning just a day after another unannounced visit to Baghdad. Kerry plans to meet with Afghanistan's president Hamid Karzai to discuss political and security issues. NBC's Andrea Mitchell reports.
Kerry is optimistic the two countries can move in from Karzai?s anti-U.S. rhetoric, which the commander of U.S. forces in Afghanistan warned was putting the lives of Western troops in danger.
Anja Niedringhaus / AP
An Afghan prisoner leaves with his belongings from the Parwan Detention Facility outside Kabul after the U.S. military gave control to Afghan authorities, Monday.
On Sunday, Kerry visited Iraq before leaving for dinner in the Jordanian capital, Amman, with Pakistan's powerful army chief of staff, Ashfaq Kayani.
The secretary of state is not visiting Pakistan during this trip as the country is in the midst of a political transition.
NBC News' Catherin Chomiak and Alastair Jamieson contributed to this report.
Related:
Kerry urges Iraq to stop arms flow to Syria on Baghdad visit
Full Afghanistan coverage from NBC News
This story was originally published on Mon Mar 25, 2013 8:03 AM EDT
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In today's competitive job market, it can be hard to imagine that there are jobs that pay well but don't require years of experience. But many sectors offer high-paying entry-level jobs that are appealing to mid-career changers or recent college graduates (who are likely eager to get out from under a mound of student loan debt).
With the help of PayScale.com, a salary data and software company, AOL Jobs has compiled a list of 10 careers that offer high salaries to entry-level workers -- those who have been on the job for two years or less. Many of them require a college degree, but there are exceptions. (Note: The jobs listed below are a sampling of highly paid entry-level jobs and not a comprehensive, ranked list.)
Check out the list below and tell us what you think. And if you have other suggestions for great-paying entry-level jobs, let us know.
Merchandise Planner (plans, directs and coordinates the activities of buyers, purchasing officers and others involved in buying materials, products and services):
Find a job as a merchandise planner.
Forensic Accountant (examines tax and business records for accuracy and irregularities):
Find a job as a forensic accountant.
Pharmaceutical Sales Representative (provides drug information and product samples to physicians and monitors prescribing patterns of physicians in a designated geographic area):
Find a job as a pharmaceutical sales representative.
Power Plant Operator (controls systems that generate and distribute electric power, which may include shift work):
Find a job as a power plant operator.
Network Security Analyst (plans, installs and monitors security measures that protect computer networks and information):
Find a job as a network security analyst.
Software Developer (creates operating systems or applications for computers and other devices):
Find a job as a software developer.
Actuarial Assistant (assists with setting insurance premium rates and performing related data research):
Find a job as an actuarial assistant.
Investment Banking Analyst (provides financial services, investment advice and banking products to wealthy individuals and institutions):
Find a job as an investment banking analyst.
Business Technology Analyst (helps to improve business performance through the use of information technology):
Find a job as an business technology analyst.
Petroleum Engineer (designs and develops methods for extracting oil and gas from deposits below the earth's surface and from older wells using novel methods):
Find a job as a petroleum analyst.
Notes:
*Wages show are for full-time U.S. workers with 0 to 2 years of experience.
**Degrees shown are those typically held by workers for a specific occupation.
Related stories
Looking for a job? Click here to get started.
Source: http://jobs.aol.com/articles/2013/03/25/high-paying-entry-level-jobs/
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DES MOINES, Iowa (AP) ? A single ticket sold in New Jersey matched all six numbers in Saturday night's drawing for the $338.3 million Powerball jackpot, lottery officials said. It was the 13th drawing held in the days since a Virginia man won a $217 million jackpot Feb. 6.
Thirteen other tickets worth $1 million each matched all but the final Powerball number on Saturday night. Those tickets were sold in New Jersey and 10 other states. Lottery officials said there was also one Power Play Match 5 winner in Iowa.
The New Jersey Lottery said Sunday that details about the winning ticket would be released Monday, declining to reveal where it had been purchased and whether anyone had immediately come forward. It was the sixth largest jackpot in history.
The numbers drawn were 17, 29, 31, 52, 53 and Powerball 31. A lump sum payout would be $221 million.
Lottery officials said the 13 tickets worth $1 million apiece ? matching the first five numbers but missing the Powerball ? were sold in Arizona, Florida (2), Illinois, Minnesota, North Carolina, New Jersey, New York, Ohio, Pennsylvania (2), South Carolina and Virginia.
Powerball said on its website that the grand prize jackpot has now been reset to an estimated $40 million or a lump sum cash amount estimated at $25 million for Wednesday's next drawing.
No one had won the Powerball jackpot since early February, when Dave Honeywell in Virginia bought the winning ticket and elected a cash lump sum for his $217 million jackpot.
The largest Powerball jackpot ever came in at $587.5 million in November. The winning numbers were picked on two different tickets ? one by a couple in Missouri and the other by an Arizona man ? and the jackpot was split.
Nebraska still holds the record for the largest Powerball jackpot won on a single ticket ? $365 million. That jackpot was won by eight workers at a Lincoln, Neb., meatpacking plant in February 2006.
Powerball is played in 42 states, Washington, D.C., and the U.S. Virgin Islands. The chance of matching all five numbers and the Powerball number is about 1 in 175 million.
Powerball said on its website that the game is played every Wednesday and Saturday night when five white balls are drawn from a drum of 59 balls and one red ball is picked from a drum with 35 red balls. It added that winners of the Powerball jackpot can elect to be paid out over 29 years at a percentage set by the game's rules ? or in a lump sum cash payment.
Source: http://news.yahoo.com/winning-338m-powerball-jackpot-ticket-sold-nj-074556709.html
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The West Bank will be closed from midnight Sunday until midnight Tuesday, the army said in a statement.
"Persons in need of medical attention, humanitarian aid or exceptional cases will be permitted to pass for care, with the authorization of the Civil Administration," the army added.
Source: http://www.maannews.net/eng/ViewDetails.aspx?ID=578448
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Contact: Anne Doerr
anne_doerr@dfci.harvard.edu
617-632-5665
Dana-Farber Cancer Institute
BOSTONDuring the past 30 years, the number of patients with cancers that originate near the junction of the esophagus and stomach has increased approximately 600 percent in the United States. The first extensive probe of the DNA of these esophageal adenocarcinomas (EACs) has revealed that many share a distinctive mix-up of letters of the genetic code, and found more than 20 mutated genes that had not previously been linked to the disease. The research, led by scientists at Dana-Farber Cancer Institute, the Broad Institute, and other research centers, may offer clues to why EAC rates have risen so sharply. The findings, which are being released as an advanced online publication by Nature Genetics, point to an array of abnormal genes and proteins that may be lynchpins of EAC cell growth and therefore serve as targets for new therapies, according to the study's authors.
"Adenocarcinomas of the esophagus, particularly those that arise at the gastroesophageal junction, were extremely uncommon 40 years ago and now account for approximately 15,000 new cases in the United States each year," said Adam Bass, MD, of Dana-Farber and the Broad Institute, who is co-senior author of the paper with Gad Getz, PhD, of the Broad Institute and Massachusetts General Hospital. "Unfortunately, it's also a disease with a generally poor prognosis: five years after diagnosis, only about 15 percent of patients are still alive. Bass added that despite the increased incidence of EAC, there have been few new approaches to treatment. "The goal of our study was to identify abnormalities within the genome of EAC cells to develop a foundation to better understand these tumors, diagnose them earlier, and develop better treatments," explained Bass.
EAC is thought to be associated with chronic gastroesophageal reflux, which sends stomach acid gurgling into the esophagus. This produces a condition known as Barrett's esophagus, in which cells at the lower end of the esophagus change to resemble cells in the intestine. Patients with Barrett's esophagus often go on to develop EAC.
Researchers don't know why EAC rates are increasing, but they speculate that it may be due to a rise in obesity, particularly in men: A heavier abdomen puts increased pressure on the stomach, causing acid to back up into the esophagus.
In the new study, researchers "sequenced" specific sections of DNA in cells from 149 EAC tissue samples, reading the individual letters of the genetic code within those areas. They focused on the one percent of the genome that holds the codes for making cell proteins. They also sequenced the entire genome all the DNA within the cell nucleus of cells from 15 of these EAC samples. Prior to this study, the largest sequencing study of EAC involved only a dozen tumor samples.
"We discovered a pattern of DNA changes that had not been seen before in any other cancer type," Getz remarked. The pattern involved a subtle swap in one of the four "nucleobases" that form the rungs of the DNA double helix, often designated by the letters C, T, G, and A. The investigators found that in many places where an A nucleobase was followed by another A nucleobase, the second "A" was replaced by a "C," a process known as transversion.
"We found this type of transversion throughout the genomes of the EAC cells we analyzed," Bass stated. "Overall, about one-third of all the mutations we discovered within these cells involved this type of transversion. In some tumor samples, these transversions accounted for nearly half of all mutations," Getz added.
Although A-to-C changes are not commonly observed in cancer, there is some evidence that oxidative damage can produce these changes. (Oxidative damage occurs when cells cannot neutralize the potentially harmful products of oxygen's reactions with other molecules.) "Gastric reflux can produce this type of damage, suggesting that reflux may underlie this pattern of mutations," Bass commented.
In addition to the mutational "signature" of AA becoming AC, the research team identified 26 genes that were frequently mutated in the tumor samples.
Five of these were "classic cancer genes" that had previously been implicated in EAC, Bass said, and the others were involved in a variety of cell processes.
Among the genes not previously linked to EAC were ELMO1 and DOCK2, mutations that can switch on a gene called RAC1, which can cause cancer cells to invade surrounding tissue. "The discovery of mutated ELMO1 and DOCK2 in many of these tumors may indicate that this invasive process is particularly active in EAC, promoting metastasis," Bass related. "We know that EAC tumors tend to spread at an earlier stage than many other cancers, which may help explain why survival rates for EAC patients tend to be low."
The RAC1 pathway the network of genes that control RAC1 activity is being pursued for pharmaceutical development. The discovery of ELMO1 and DOCK2 mutations in EAC samples may spur testing of new agents targeting this pathway in EAC, said Bass.
"Identifying the mutated genes within these tumors will help us understand the underlying biology of the disease," said Bass. "It also presents us with a slate of known genetic abnormalities that can someday be used to diagnose the disease at an early stage, classify tumors by the particular mutations within EAC cells, and ultimately develop treatment geared to precisely those mutations."
###
The lead authors of the study are Austin Dulak, PhD, and Petar Stojanov of Dana-Farber and the Broad Institute. Co-authors are: Shouyong Peng, PhD, Cameron Fox and Yu Imamura, MD, PhD, of Dana-Farber; Michael Lawrence, PhD, Chip Stewart, Erica Shefler, Aaron McKenna, Scott Carter, PhD, Kristian Cibulskis, Andrey Sivachenko, Gordon Saksena, Douglas Voet, Alex Ramos, PhD, Daniel Auclair, PhD, Kristin Thompson, PhD, Carrie Sougnez, Robert Onofrio, Stacey Gabriel, PhD, and Candace Guiducci, of the Broad Institute; Steven Schumacher, of Dana-Farber and the Broad; Rameen Beroukhim, MD, PhD, of Dana-Farber, the Broad Institute, and Brigham and Women's Hospital; Shuji Ogino, MD, PhD, of Dana-Farber, Brigham and Women's, and the Harvard School of Public Health; Todd Golub, MD, of Dana-Farber, the Broad Institute, and the Howard Hughes Medical Institute; Santhoshi Bandla, PhD, Tony Godfrey, PhD, and Zhongren Zhou, PhD, of the University of Rochester; Lin Lin, MD, PhD, Jules Lin, MD, Rishindra Reddy, MD, David Beer, PhD, and Andrew Chang, MD, of the University of Michigan; James Luketich, MD, Rodney Landrenau, MD, and Arjun Pennathur, MD, of the University of Pittsburgh Medical Center; and Eric Lander, DPhil, of the Broad Institute, and MIT.
The work was supported in part by grants from the U.S. National Human Genome Research Institute (U54 HG003067), the National Cancer Institute (K08 CA134931), the DeGregorio Family Foundation, the Karin Grunebaum Cancer Research Foundation, Target Cancer, and Connecticut Conquers Cancer.
About Dana-Farber Cancer Institute
Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute. It provides adult care with Brigham and Women's Hospital as Dana-Farber/Brigham and Women's Cancer Center, and it provides pediatric care with Boston Children's Hospital as Dana-Farber/Children's Hospital Cancer Center. Dana-Farber is the top-ranked cancer center in New England, according to U.S. News & World Report, and one of the largest recipients among independent hospitals of National Cancer Institute and National Institutes of Health grant funding. Follow Dana-Farber on Twitter or Facebook.
About the Broad Institute of MIT and Harvard
The Eli and Edythe L. Broad Institute of MIT and Harvard was founded in 2003 to empower this generation of creative scientists to transform medicine with new genome-based knowledge. The Broad Institute seeks to describe all the molecular components of life and their connections; discover the molecular basis of major human diseases; develop effective new approaches to diagnostics and therapeutics; and disseminate discoveries, tools, methods and data openly to the entire scientific community.
Founded by MIT, Harvard and its affiliated hospitals, and the visionary Los Angeles philanthropists Eli and Edythe L. Broad, the Broad Institute includes faculty, professional staff and students from throughout the MIT and Harvard biomedical research communities and beyond, with collaborations spanning over a hundred private and public institutions in more than 40 countries worldwide. For further information about the Broad Institute, go to http://www.broadinstitute.org.
Contact:
Anne Doerr
Anne_doerr@dfci.harvard.edu
Rob Levy
Robert_Levy@dfci.harvard.edu
(617) 632-4090
?
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.
Contact: Anne Doerr
anne_doerr@dfci.harvard.edu
617-632-5665
Dana-Farber Cancer Institute
BOSTONDuring the past 30 years, the number of patients with cancers that originate near the junction of the esophagus and stomach has increased approximately 600 percent in the United States. The first extensive probe of the DNA of these esophageal adenocarcinomas (EACs) has revealed that many share a distinctive mix-up of letters of the genetic code, and found more than 20 mutated genes that had not previously been linked to the disease. The research, led by scientists at Dana-Farber Cancer Institute, the Broad Institute, and other research centers, may offer clues to why EAC rates have risen so sharply. The findings, which are being released as an advanced online publication by Nature Genetics, point to an array of abnormal genes and proteins that may be lynchpins of EAC cell growth and therefore serve as targets for new therapies, according to the study's authors.
"Adenocarcinomas of the esophagus, particularly those that arise at the gastroesophageal junction, were extremely uncommon 40 years ago and now account for approximately 15,000 new cases in the United States each year," said Adam Bass, MD, of Dana-Farber and the Broad Institute, who is co-senior author of the paper with Gad Getz, PhD, of the Broad Institute and Massachusetts General Hospital. "Unfortunately, it's also a disease with a generally poor prognosis: five years after diagnosis, only about 15 percent of patients are still alive. Bass added that despite the increased incidence of EAC, there have been few new approaches to treatment. "The goal of our study was to identify abnormalities within the genome of EAC cells to develop a foundation to better understand these tumors, diagnose them earlier, and develop better treatments," explained Bass.
EAC is thought to be associated with chronic gastroesophageal reflux, which sends stomach acid gurgling into the esophagus. This produces a condition known as Barrett's esophagus, in which cells at the lower end of the esophagus change to resemble cells in the intestine. Patients with Barrett's esophagus often go on to develop EAC.
Researchers don't know why EAC rates are increasing, but they speculate that it may be due to a rise in obesity, particularly in men: A heavier abdomen puts increased pressure on the stomach, causing acid to back up into the esophagus.
In the new study, researchers "sequenced" specific sections of DNA in cells from 149 EAC tissue samples, reading the individual letters of the genetic code within those areas. They focused on the one percent of the genome that holds the codes for making cell proteins. They also sequenced the entire genome all the DNA within the cell nucleus of cells from 15 of these EAC samples. Prior to this study, the largest sequencing study of EAC involved only a dozen tumor samples.
"We discovered a pattern of DNA changes that had not been seen before in any other cancer type," Getz remarked. The pattern involved a subtle swap in one of the four "nucleobases" that form the rungs of the DNA double helix, often designated by the letters C, T, G, and A. The investigators found that in many places where an A nucleobase was followed by another A nucleobase, the second "A" was replaced by a "C," a process known as transversion.
"We found this type of transversion throughout the genomes of the EAC cells we analyzed," Bass stated. "Overall, about one-third of all the mutations we discovered within these cells involved this type of transversion. In some tumor samples, these transversions accounted for nearly half of all mutations," Getz added.
Although A-to-C changes are not commonly observed in cancer, there is some evidence that oxidative damage can produce these changes. (Oxidative damage occurs when cells cannot neutralize the potentially harmful products of oxygen's reactions with other molecules.) "Gastric reflux can produce this type of damage, suggesting that reflux may underlie this pattern of mutations," Bass commented.
In addition to the mutational "signature" of AA becoming AC, the research team identified 26 genes that were frequently mutated in the tumor samples.
Five of these were "classic cancer genes" that had previously been implicated in EAC, Bass said, and the others were involved in a variety of cell processes.
Among the genes not previously linked to EAC were ELMO1 and DOCK2, mutations that can switch on a gene called RAC1, which can cause cancer cells to invade surrounding tissue. "The discovery of mutated ELMO1 and DOCK2 in many of these tumors may indicate that this invasive process is particularly active in EAC, promoting metastasis," Bass related. "We know that EAC tumors tend to spread at an earlier stage than many other cancers, which may help explain why survival rates for EAC patients tend to be low."
The RAC1 pathway the network of genes that control RAC1 activity is being pursued for pharmaceutical development. The discovery of ELMO1 and DOCK2 mutations in EAC samples may spur testing of new agents targeting this pathway in EAC, said Bass.
"Identifying the mutated genes within these tumors will help us understand the underlying biology of the disease," said Bass. "It also presents us with a slate of known genetic abnormalities that can someday be used to diagnose the disease at an early stage, classify tumors by the particular mutations within EAC cells, and ultimately develop treatment geared to precisely those mutations."
###
The lead authors of the study are Austin Dulak, PhD, and Petar Stojanov of Dana-Farber and the Broad Institute. Co-authors are: Shouyong Peng, PhD, Cameron Fox and Yu Imamura, MD, PhD, of Dana-Farber; Michael Lawrence, PhD, Chip Stewart, Erica Shefler, Aaron McKenna, Scott Carter, PhD, Kristian Cibulskis, Andrey Sivachenko, Gordon Saksena, Douglas Voet, Alex Ramos, PhD, Daniel Auclair, PhD, Kristin Thompson, PhD, Carrie Sougnez, Robert Onofrio, Stacey Gabriel, PhD, and Candace Guiducci, of the Broad Institute; Steven Schumacher, of Dana-Farber and the Broad; Rameen Beroukhim, MD, PhD, of Dana-Farber, the Broad Institute, and Brigham and Women's Hospital; Shuji Ogino, MD, PhD, of Dana-Farber, Brigham and Women's, and the Harvard School of Public Health; Todd Golub, MD, of Dana-Farber, the Broad Institute, and the Howard Hughes Medical Institute; Santhoshi Bandla, PhD, Tony Godfrey, PhD, and Zhongren Zhou, PhD, of the University of Rochester; Lin Lin, MD, PhD, Jules Lin, MD, Rishindra Reddy, MD, David Beer, PhD, and Andrew Chang, MD, of the University of Michigan; James Luketich, MD, Rodney Landrenau, MD, and Arjun Pennathur, MD, of the University of Pittsburgh Medical Center; and Eric Lander, DPhil, of the Broad Institute, and MIT.
The work was supported in part by grants from the U.S. National Human Genome Research Institute (U54 HG003067), the National Cancer Institute (K08 CA134931), the DeGregorio Family Foundation, the Karin Grunebaum Cancer Research Foundation, Target Cancer, and Connecticut Conquers Cancer.
About Dana-Farber Cancer Institute
Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute. It provides adult care with Brigham and Women's Hospital as Dana-Farber/Brigham and Women's Cancer Center, and it provides pediatric care with Boston Children's Hospital as Dana-Farber/Children's Hospital Cancer Center. Dana-Farber is the top-ranked cancer center in New England, according to U.S. News & World Report, and one of the largest recipients among independent hospitals of National Cancer Institute and National Institutes of Health grant funding. Follow Dana-Farber on Twitter or Facebook.
About the Broad Institute of MIT and Harvard
The Eli and Edythe L. Broad Institute of MIT and Harvard was founded in 2003 to empower this generation of creative scientists to transform medicine with new genome-based knowledge. The Broad Institute seeks to describe all the molecular components of life and their connections; discover the molecular basis of major human diseases; develop effective new approaches to diagnostics and therapeutics; and disseminate discoveries, tools, methods and data openly to the entire scientific community.
Founded by MIT, Harvard and its affiliated hospitals, and the visionary Los Angeles philanthropists Eli and Edythe L. Broad, the Broad Institute includes faculty, professional staff and students from throughout the MIT and Harvard biomedical research communities and beyond, with collaborations spanning over a hundred private and public institutions in more than 40 countries worldwide. For further information about the Broad Institute, go to http://www.broadinstitute.org.
Contact:
Anne Doerr
Anne_doerr@dfci.harvard.edu
Rob Levy
Robert_Levy@dfci.harvard.edu
(617) 632-4090
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Source: http://www.eurekalert.org/pub_releases/2013-03/dci-sfm032113.php
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