Thursday, 29 March 2012

Slacker rat, worker rat

Rodent work ethic, like people?s, comes in two types

Web edition : Wednesday, March 28th, 2012

When it comes to intellectual challenges, rats, like people, fall naturally into categories of slackers and workers. And a shot of stimulant sometimes gets slackers to work harder while prompting the workers to ease off, researchers report online March 28 in Neuropsychopharmacology.

Hard work can come in many forms. Animal studies that explore the costs and benefits of such tasks usually involve rodents physically working, such as pushing a lever or scaling a wall for a reward. But those kinds of experiments don?t account for mental effort, says Jay Hosking of the University of British Columbia in Vancouver.

?We were trying to find something that modeled a little more closely what you see in the human experience,? Hosking says. ?In everyday life, it?s the cognitive side where people really have to make those decisions, like whether you work harder throughout the day in hopes of getting a promotion, or coast through and check Facebook every 15 minutes and earn your wages.?

In the study?s rodent analog of a work day, rats poked their nose into one of five holes to indicate the location of a flash of light. By pushing a lever before the trial began, the rats chose either an easy version or a hard one. In the easy task, the light shone for a full second, making its location easy to spot. In the hard version, the light briefly flashed for a fifth of a second, a time so brief that the rats had to really concentrate to choose the right hole. The harder task came with double the sugar-pellet reward.?

When compared to the average behavior, some individuals reliably went for the easy version and collected their small reward. Other animals overwhelmingly chose the intellectually harder route. Not only do these divisions between what the team termed slackers and workers exist, the researchers showed, but the differences persist across many trials.

?This article opens up a new area related to mental effort,? says behavioral neuroscientist John Salamone of the University of Connecticut in Storrs. For instance, scientists can now start to explore the relationship between physical and mental work.

Giving rats the stimulants amphetamine and caffeine produced varied effects depending on individual?s personality, the team found. For slacker rats, amphetamine sharpened the mental work ethic, making the animals more likely to choose the harder task. But for workers, amphetamine caused the animals to choose the easier option more. Meanwhile, caffeine turned worker rats into slackers, but didn?t make the slackers work any harder.?

The researchers can?t yet explain why stimulants would cause workers to choose the easier task. One possibility is that hard workers are already performing optimally, so anything that swings the system out of whack, such as stimulants, could cause a net decrease in productivity.

More generally, the results show that drugs aren?t necessarily one-size-fits-all, Salamone says.


Found in: Body & Brain

Source: http://www.sciencenews.org/view/generic/id/339509/title/Slacker_rat,_worker_rat

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ION Air Pro POV camera: shoot on the piste, upload to the cloud, we go hands-on (video)

Image
You might think the POV / action sports camera world has been a bit of a two horse race recently. That could all change, however, now ION has muscled into the scene with its Air Pro HD sports camera. The firm's dabbled with handy cameras before, but now it's dipping a well armored toe into the helmet-cam market. Needless to say, that means it's rugged, waterproof, and built to eat dirt -- or at least capture the moments when you do.

Your action is scooped-up in full 1080p HD, and there's a 5-megapixel stills option for when you want to frame that killer jump for static posterity. The lens is a 170-degree wide-angle affair, you can change the FOV if you wish, but it's definitely enough to grab all the action. There's also no display on the device itself, but there's a reason for that: operating the Air Pro is a ridiculously straightforward task. With just one click you're recording, even if switched off. The two controls on top are all you need to get the essential jobs done with this device, a button for switching it on and off (and taking stills) and the sliding record switch -- this set-up also means you can physically feel if it's recording, even when you can't see it.

Continue reading ION Air Pro POV camera: shoot on the piste, upload to the cloud, we go hands-on (video)

ION Air Pro POV camera: shoot on the piste, upload to the cloud, we go hands-on (video) originally appeared on Engadget on Wed, 28 Mar 2012 11:33:00 EDT. Please see our terms for use of feeds.

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Wednesday, 28 March 2012

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bj penn

Justin Lin Attached to Live-Action Lone Wolf and Cub

Mike Fleming

EXCLUSIVE: Kamala Films has acquired film rights to the Kazuo Koike-created 1970s Japanese manga Lone Wolf and Cub, attaching David & Janet Peoples to write the script. Fast Five?s Justin Lin had already been attached to direct. Kamala?s Marissa McMahon will produce with 1212 Entertainment?s Elizabeth Grave and Joshua Long, with Roberto Grande exec producing.

The original was set feudal Edo period, and chronicles the story of Ogami Itto, the Shogun?s elite executioner. In an attempt to take his position, the rival Yagyu clan falsely accuses Itto of a crime and murders his wife. Disgraced, Itto is forced to wander Japan with his three-year-old son Daigoro as an assassin for hire, earning the title ?Lone Wolf and Cub.? Ultimately, Itto and Daigoro seek revenge on the Yagyu clan. Koike?s manga, published in the United States by Dark Horse Comics, is considered a seminal work.

The film marks the first collaboration between Kamala Films and 1212 Entertainment. Kamala is currently in development on Jeff Guinn?s Go Down Together: The True, Untold Story of Bonnie and Clyde with Furst Films, and the screen adaptation of the Curtis Sittenfeld novel American Wife with Red Crown. 1212 is producing an adaptation of the Taito video game Space Invaders.

The scribes have storied credits including Blade Runner, Unforgiven and Twelve Monkeys, while Lin is working on Universal?s sixth installment of The Fast and the Furious. ?I?ve long admired the Peoples and their enduring body of work,? Lin said. ?They?re a wonderful match for Lone Wolf and Cub and I?m really looking forward to collaborating with them on this powerful, epic tale.? CAA reps the writers and Lin and the helmer?s also repped by Cinetic and Sloss Eckhouse LawCo.

Get the latest Industry news sent straight to your Wall.

Source: http://www.rottentomatoes.com/m/1924831/news/1924831/

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Sunday, 25 March 2012

NKoreans honor Kim Jong Il as mourning period ends

A North Korean outpost is seen from Observation Post Ouellette in the Demilitarized Zone, the tense military border between the two Koreas, in Panmunjom, South Korea, Sunday, March 25, 2012. U.S. President Barack Obama visited the DMZ earlier in the day. (AP Photo/Susan Walsh)

A North Korean outpost is seen from Observation Post Ouellette in the Demilitarized Zone, the tense military border between the two Koreas, in Panmunjom, South Korea, Sunday, March 25, 2012. U.S. President Barack Obama visited the DMZ earlier in the day. (AP Photo/Susan Walsh)

A view of Ki Jong Dong, North Korea, is seen from Observation Post Ouellette in the Demilitarized Zone, the tense military border between the two Koreas, in Panmunjom, South Korea, Sunday, March 25, 2012. U.S. President Barack Obama visited the DMZ earlier in the day. (AP Photo/Susan Walsh)

(AP) ? North Korea urged its people to rally behind new leader Kim Jong Un as tens of thousands gathered Sunday in a central square to observe the end of a 100-day mourning period following the death of his father, Kim Jong Il.

The commemoration comes as North Korea prepares to launch a satellite into space on a long-range rocket next month ? plans that the United States warns could jeopardize a recent deal that would ship U.S. food aid to the North in exchange for a moratorium on missile and nuclear tests.

To the south, President Barack Obama on Sunday visited the heavily armed border between the Koreas, praising U.S. troops stationed there.

While North Korea isn't on the formal agenda of an international nuclear security summit Monday and Tuesday, Pyongyang's launch plans are expected to dominate discussions by Obama and other world leaders gathering in Seoul.

North Korea said it will fire a rocket carrying an observation satellite around the April 15 celebration of the 100th anniversary of the birth of North Korea founder Kim Il Sung, Kim Jong Un's grandfather.

Washington says North Korea uses such launches as cover for testing missile systems for nuclear weapons that could target Alaska and beyond. The U.N. Security Council condemned North Korea's last long-range rocket launch, in 2009. Pyongyang, which said it was testing satellite technology for peaceful purposes, abandoned six-nation nuclear disarmament talks and, weeks later, carried out a second nuclear test.

On Sunday, state media showed tens of thousands of people gathered in Pyongyang to pay their respects to Kim Jong Il, the longtime leader who died of a heart attack Dec. 17. Top officials made speeches praising the late leader and pledging loyalty to his successor.

"We have to unite, unite and unite again behind dear comrade Kim Jong Un," Premier Choe Yong Rim said from a balcony, where Kim Jong Un and other officials stood.

People's Armed Forces Minister Kim Yong Chun said in a separate speech that his troops would become "guns" and "bombs" to protect Kim Jong Un with their lives.

Top officials and state media have made similar pledges of loyalty to Kim Jong Un, who has assumed a slew of prominent titles such as supreme commander of the 1.2 million-member military since his father's death. Kim Jong Un is expected to further consolidate his power by taking up other top state jobs.

North Korea said Saturday that the country's parliament will hold its annual session on April 13. The session will be closely watched by outsiders for clues to changes in the North's power structure.

North Korea's ruling Workers' Party is also due to hold a separate conference in mid-April.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/cae69a7523db45408eeb2b3a98c0c9c5/Article_2012-03-25-AS-NKorea-Kim-Jong-Il/id-579e98942a7446368030b99cdb4a4e88

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barry larkin

Wade speaks out on shooting death of Florida teen

FILE - This undated family photo shows Trayvon Martin. College students around Florida rallied Monday, March 19, 2012, to demand the arrest of a white neighborhood watch captain who shot the unarmed teen in February, though authorities may be hamstrung by a state law that allows people to defend themselves with deadly force. (AP Photo/Martin Family, File)

FILE - This undated family photo shows Trayvon Martin. College students around Florida rallied Monday, March 19, 2012, to demand the arrest of a white neighborhood watch captain who shot the unarmed teen in February, though authorities may be hamstrung by a state law that allows people to defend themselves with deadly force. (AP Photo/Martin Family, File)

Miami Heat guard Dwyane Wade pauses during the second half of an NBA basketball game against the Chicago Bulls in Chicago, Wednesday, March 14, 2012. (AP Photo/Nam Y. Huh)

(AP) ? Dwyane Wade and LeBron James were only a few miles away from Trayvon Martin on Feb. 26, participating in the NBA All-Star game on the night the unarmed black teenager wearing a hooded sweatshirt was shot to death by a neighborhood crime-watch volunteer.

They never knew the teenager, but on Friday they decided it was time to speak out.

Wade posted a photo of himself from a previous photo shoot wearing a hooded shirt, otherwise known as a hoodie, to his Twitter and Facebook pages on Friday morning.

A couple hours later, James posted another photo ? this one of the Heat team, all wearing hoodies, their heads bowed, their hands stuffed into their pockets. The photo was taken at the team hotel, though it was not clear when it was snapped.

Among the hashtags James linked to the photo: "WeWantJustice." The National Basketball Players Association issued a statement saying it was saddened and horrified by the killing, and accused the police department in Sanford, Fla. ? where Martin was shot ? of "racial bias."

"As a father, this hits home," said Wade, who has 10- and 4-year-old sons.

Martin was killed as he was returning to a gated community, carrying candy and iced tea. A neighborhood crime-watch volunteer, George Zimmerman, said he acted in self-defense. He has not been arrested, though state and federal authorities are still investigating.

Protests have popped up nationwide in recent days, with thousands of people ? many of them wearing hoodies ? calling for action.

"This situation hit home for me because last Christmas, all my oldest son wanted as a gift was hoodies," Wade told The Associated Press on Friday from Auburn Hills, Mich., where the Heat were to play the Detroit Pistons. "So when I heard about this a week ago, I thought of my sons. I'm speaking up because I feel it's necessary that we get past the stereotype of young, black men and especially with our youth."

Wade and James decided Thursday to make their reactions about the Martin situation public, and James felt the best way to do that was the team photo with everyone wearing hoodies.

"Our hearts go out to the family and loved ones of Trayvon Martin for their loss and for everyone involved in this terrible tragedy," the Heat said in a statement Friday afternoon. "We support our players and join them in hoping that their images and our logo can be part of the national dialogue and can help in our nation's healing."

Earlier Friday, Fox News Channel commentator Geraldo Rivera said on "Fox & Friends" the hoodie Martin wore when he was killed was as much responsible for his death as the man who shot him. Rivera later said his comment was "politically incorrect."

Separately, a Florida state lawmaker, Rep. Alan Williams, a Democrat from Tallahassee, urged the Heat stars ? along with New York Knicks forward Amare Stoudemire, a central Florida native ? in an early Friday post on Twitter to wear hoodies during pregame warmups to call attention to the Martin story.

Such a move would not be permitted under the NBA's uniform policy, although Heat players are planning to pay tribute to Martin in some manner when they face the Pistons on Friday night.

"When you see Trayvon, when you see that image, he could be anybody's kid, black or white, Hispanic, Asian, what have you," Williams said in a telephone interview. "Basketball is a sport that kind of transcends race and class and all those things that divide us. For me, as a state representative, we have to go beyond the traditional routes that some people would take."

The NBPA called not only for Zimmerman's "prompt arrest," but a review of the Sanford Police Department.

"Their silence in the face of this injustice is reprehensible and they cannot be trusted to safe guard the citizens of the Sanford community equally," the NBPA said. "The NBPA seeks to ensure that Trayvon Martin's murder not go unpunished and the elimination of the injustices suffered by the innocent."

___

Online:

Wade tweet: http://bit.ly/GJoPGu

James photo: http://campl.us/il4E

___

Follow Tim Reynolds on Twitter at http://www.twitter.com/ByTimReynolds

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/347875155d53465d95cec892aeb06419/Article_2012-03-23-Heat-Neighborhood%20Watch/id-0f52eacaef4740b99bcfc4b8a7618b8d

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five iron frenzy

Scientists reprogram cancer cells with low doses of epigenetic drugs

Friday, March 23, 2012

Experimenting with cells in culture, researchers at the Johns Hopkins Kimmel Cancer Center have breathed possible new life into two drugs once considered too toxic for human cancer treatment. The drugs, azacitidine (AZA) and decitabine (DAC), are epigenetic-targeted drugs and work to correct cancer-causing alterations that modify DNA.

The researchers said the drugs also were found to take aim at a small but dangerous subpopulation of self-renewing cells, sometimes referred to as cancer stem cells, which evade most cancer drugs and cause recurrence and spread.

In a report published in the March 20, 2012, issue of Cancer Cell, the Johns Hopkins team said their study provides evidence that low doses of the drugs tested on cell cultures cause antitumor responses in breast, lung, and colon cancers.

Conventional chemotherapy agents work by indiscriminately poisoning and killing rapidly-dividing cells, including cancer cells, by damaging cellular machinery and DNA. "In contrast, low doses of AZA and DAC may re-activate genes that stop cancer growth without causing immediate cell-killing or DNA damage," says Stephen Baylin, M.D., Ludwig Professor of Oncology and deputy director of the Johns Hopkins Kimmel Cancer Center.

Many cancer experts had abandoned AZA and DAC for the treatment of common cancers, according to the researchers, because they are toxic to normal cells at standard high doses, and there was little research showing how they might work for cancer in general. Baylin and his colleague Cynthia Zahnow, Ph.D., decided to take another look at the drugs after low doses of the drugs showed a benefit in patients with a pre-leukemic disorder called myelodysplastic syndrome (MDS). Johns Hopkins investigators also showed benefit of low doses of the drugs in tests with a small number of advanced lung cancer patients. "This is contrary to the way we usually do things in cancer research," says Baylin, noting that "typically, we start in the laboratory and progress to clinical trials. In this case, we saw results in clinical trials that made us go back to the laboratory to figure out how to move the therapy forward."

For the research, Baylin and Zahnow's team worked with leukemia, breast, and other cancer cell lines and human tumor samples using the lowest possible doses that were effective against the cancers. In all, the investigators studied six leukemia cell lines, seven leukemia patient samples, three breast cancer cell lines, seven breast tumor samples (including four samples of tumors that had spread to the lung), one lung cancer tumor sample, and one colon cancer tumor sample. The team treated cell lines and tumor cells with low-dose AZA and DAC in culture for three days and allowed the drug-treated cells to rest for a week. Treated cells and tumor samples were then transplanted into mice where the researchers observed continued antitumor responses for up to 20 weeks. This extended response was in line with observations in some MDS patients who continued to have anticancer effects long after stopping the drug.

The low-dose therapy reversed cancer cell gene pathways, including those controlling cell cycle, cell repair, cell maturation, cell differentiation, immune cell interaction, and cell death. Effects varied among individual tumor cells, but the scientists generally saw that cancer cells reverted to a more normal state and eventually died. These results were caused, in part, by alteration of the epigenetic, or chemical environment, of DNA. Epigenetic activities turn on certain genes and block others, says Zahnow, assistant professor of oncology and the Evelyn Grolman Glick Scholar at Johns Hopkins.

The research team also tested AZA and DAC's effect on a type of metastatic breast cancer cell thought to drive cancer growth and resist standard therapies. Metastatic cells are difficult to study in standard laboratory tumor models, because they tend to break away from the original tumor and float around in blood and lymph fluids. The Johns Hopkins team re-created the metastatic stem cells' environment, allowing them to grow as floating spheres. "These cells were growing well as spheres in suspension, but when we treated the cells with AZA, both the size and number of spheres were dramatically reduced," says Zahnow.

The precise mechanism of how the drugs work is the focus of ongoing studies by Baylin and his team. "Our findings match evidence from recent clinical trials suggesting that the drugs shrink tumors more slowly over time as they repair altered mechanisms in cells and genes return to normal function and the cells may eventually die," says Baylin.

The results of clinical trials in lung cancer, led by Johns Hopkins' Charles Rudin, M.D., and published late last year in Cancer Discovery, also indicate that the drugs make tumors more responsive to standard anticancer drug treatment. This means, they say, that the drugs could become part of a combined treatment approach rather than a stand-alone therapy and as part of personalized approaches in patients whose cancers fit specific epigenetic and genetic profiles.

Low doses of both drugs are approved by the U.S. Food and Drug Administration for the treatment of MDS and chronic myelomonocytic leukemia (CMML). Clinical trials in breast and lung cancer have begun in patients with advanced disease, and trials in colon cancer are planned.

In addition to Baylin and Zahnow, other investigators participating in this study include Hsing-Chen Tsai, Huili Li, Leander Van Neste, Yi Cai, Carine Robert, Feyruz V. Rassool, James J. Shin, Kirsten M. Harbom, Robert Beaty, Emmanouil Pappou, James Harris, Ray-Whay Chiu Yen, Nita Ahuja, Malcolm V. Brock, Vered Stearns, David Feller-Kopman, Lonny B. Yarmus, Yi-Chun Lin, Alana L. Welm, Jean-Pierre Issa, Il Minn, William Matsui, Yoon-Young Jang, and Saul J. Sharkis.

The research was funded by a SPORE grant for lung cancer from the National Institutes of Health, the Hodson Trust Foundation, Entertainment Industry Foundation, Lee Jeans, Samuel Waxman Cancer Research Foundation, Department of Defense Breast Cancer Research Program, Huntsman Cancer Foundation, and the Cindy Rosencrans Fund for Triple Negative Breast Cancer Research. All of the studies have been accelerated by funding from the Stand Up to Cancer (SU2C) project in partnership with the American Association of Cancer Research (AACR).

###

Johns Hopkins Medical Institutions: http://www.hopkinsmedicine.org

Thanks to Johns Hopkins Medical Institutions for this article.

This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.

This press release has been viewed 20 time(s).

Source: http://www.labspaces.net/118683/Scientists_reprogram_cancer_cells_with_low_doses_of_epigenetic_drugs

ground hog

'Antimagnet' Cloak Hides Objects From Magnetic Fields

Since metal detectors use electromagnetic waves (call those non-static magnetic fields if you want), instead of magnetic fields, that cloak wouldn't be a problem at all. Well, ok, it would cloak its interior, like any piece of conductor would. It would also trigger the alarm itself, like any piece of conductor.

But now, why are people so concerned about airport security anyway? The invention has no relation to it.

Source: http://rss.slashdot.org/~r/Slashdot/slashdotScience/~3/YN5O_QnvyNM/antimagnet-cloak-hides-objects-from-magnetic-fields

blake griffin

Psychology of Pleasure, Addiction & Over-Stimulation? - PsycheTruth

Psychology of Pleasure, Addiction & Over-Stimulation?

Psychology of Pleasure, Addiction & Over-Stimulation?
Psychetruth

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cliff harris

Accounting Tips: Outsource Payroll Solutions - Business - EzineMark

For most people new to business, it can be tempting to do payroll yourself to try and save money.

However, it is not necessarily so. Managing and processing payroll involves time and expertise.

Managing small business payroll involves than writing checks and handing them out to employees on time. It also requires complying with numerous ATO requirements such as keeping accurate records, calculating and correctly paying payroll taxes and meeting superannuation requirements. Salary packaging can also introduce more complex tasks that are important to get correct so as not to alienate staff.

Insisting on doing your payroll in house not only predispose you to potentially costly implications of making mistakes with payroll taxes and super, it also takes your attention away from the more pressing concerns of running a business.

Outsourcing payroll management is becoming more popular among many small business owners as well as bigger businesses.

Outsourcing payroll is a smart decision for business owners as it can simplify the process as the outsourced payroll provider will now be responsible for managing the entire process cost-effectively, correctly and efficiently.

However, as it is you the employer who is ultimately responsible for the payment of payroll liabilities to the ATO and correctly paying your staff,? it is very important to choose the most reliable and trusted outsourced payroll provider that is right for your business.

Here are some tips:

-Identify and Determine Your Business Needs.

Make an assessment of your payroll needs.

-Assess and Evaluate the Features and Benefits. Shop around. Do comparisons. Learn all the features.? Avoid picking a provider based on price alone. Instead make sure that they can provide all the services your business needs.

-Do Research. Don?t hesitate to ask around from your fellow business owners, chamber of commerce or trade association members if they use an outsourced payroll provider. Ask them about the services they receive and if their provider have met their needs. Find out also their frustrations about the service and the provider itself.

-Do A Cost Comparison. Find out if the payroll company charges a setup fee, do they charge on a per payslip basis, do they charge for additions or deletions of employees and other additional costs. Then make a comparison.

-Make sure to Choose an Outsourced Payroll Provider that Guarantees Confidentiality and Information Security. Providers are known to have a range of payroll submission methods - such as by phone, fax, and email and over the internet. So, you should know what they are going to use. As payroll data is sensitive, make sure that you are comfortable with what they are using. Make sure that you choose a provider that protects your employees? data.

-Ask if the Outsourced Payroll Provider Assumes Tax Filing Responsibilities. Make that you?ve chosen a provider that prepares quarterly and annual employee tax filing and assume liability for accurate and timely submission.

-Makes sure that the Payroll Products and Services are User-Friendly.? Aside from making sure the program is easy to use, you should also find out what type of support is available - such as a help desk and professionals who can assist with program troubleshooting.

Outsourcing your payroll, though very beneficial for your business, should also be done carefully, armed with the correct and most-up-to-date information with regards to the provider?s services, security, customer support and software functionality.

Source: http://business.ezinemark.com/accounting-tips-outsource-payroll-solutions-7d34f373dfd0.html

budweiser shootout

Thursday, 22 March 2012

Lebanese suspect in Thailand denies terror link

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[ [ [['French police stepped up the search',17]], ', '0' ], [ [['Seeking to elevate his candidacy back to a general', 8]], '28660934', '0' ], [ [['The tragic story of Trayvon Martin', 4]], '28647343', '0' ], [ [['Karzai will get a chance soon to express', 8]], '28630306', '0' ], [ [['powerful storms stretching', 8]], '28493546', '0' ], [ [['basic norm that death is private', 6]], '28413590', '0' ], [ [['songwriter also saw a surge in sales for her debut album', 6]], '28413590', '1', 'Watch music videos from Whitney Houston ', 'on Yahoo! Music', 'http://music.yahoo.com' ], [ [['keyword', 99999999999999999999999]], 'videoID', '1', 'overwrite-pre-description', 'overwrite-link-string', 'overwrite-link-url' ] ]

Source: http://news.yahoo.com/lebanese-suspect-thailand-denies-terror-070450090.html

ron paul

Woman's 'Obsession' leads to 35 carrot tattoos

By Ree Hines

Some of us really enjoy a fresh, crunchy carrot, but few of us can boast a carrot penchant that could rival that of one veg-loving woman. Zizi Howell, the subject of an upcoming episode of TLC's "My Crazy Obsession" can't get enough of carrots -- and her interest goes far beyond the dinner table.

Howell's goal is to have more carrots than anyone else in the world, and if the following sneak peek is anything to go by, she's off to a good start.

Currently Howell's collection features over 1000 items, which include pillows, candles, soaps and a $4000 carrot dresser that holds her mother's ashes. And that's not all. She even collects carrots on her body.

"I have 35 carrots tattooed on my body," Howell revealed. "I've got a 24-carrot armband. I've got four tattooed on my other arm, six on my back, (and) a big carrot on my stomach."

Now that's devotion to a vegetable.

Learn more about Howell's carrot-filled life when "My Crazy Obsession" airs Wednesday night at 10:30 p.m. ET on TLC.

Do you think Howell's carrot obsession is healthy, or has she surrounded herself with too much of a good thing? Share your thoughts on our Facebook page.

?

Also in The Clicker:

Source: http://theclicker.today.msnbc.msn.com/_news/2012/03/21/10793496-woman-covers-her-body-in-carrot-tattoos-on-my-crazy-obsession

scott hall

Wednesday, 21 March 2012

Obama welcomes Irish PM to White House

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Source: http://news.yahoo.com/obama-welcomes-irish-pm-white-house-152504543.html

packers stock sale

Food52: 7 One-Pot Dinners

This savory, rich stew may be named after one secret ingredient, but it's because of a complex mix of components that it succeeds so well. Tomatoes and tomato paste give it a sunny sweetness, diced veggies lend texture, and red wine and vinegar brighten everything up. Anchovies, the "secret ingredient," are briny and buttery, giving the sauce a smooth, complex finish. We recommend using beef with generous marbling for the best results. - Amanda & Merrill

Get the recipe Photo: Sarah Shatz

Source: http://www.huffingtonpost.com/food-52/one-pot-dinners_b_1298198.html

etta james at last

Tuesday, 20 March 2012

Illinois Primary: Suburban Slog (The Note)

By MICHAEL FALCONE ( @michaelpfalcone ) and AMY WALTER ( @amyewalter )

CHICAGO - Turn on the television in Illinois and you know there is an election coming up. But travel around the Chicago suburbs and you don't see or feel any sign of it.

As we learned in our conversations with activists in the suburbs yesterday, this low energy could be problematic for Romney - who needs to run up the score in the collar counties surrounding Chicago.

More than 60 percent of the vote is expected to come from the 'burbs, while a much smaller portion of the vote comes from rural downstate. Suburban voters are typically less ideological and focused more on pocket book issues than social issues, something that should prove?right up Romney's alley.

Romney supporter state Rep. David Harris, who represents the Cook County suburb of Mt. Prospect, worries that Romney still hasn't been able to connect with skeptical conservative Republicans. http://abcn.ws/GA7luv

"I think Mitt Romney is just as conservative as Ronald Reagan - when Reagan said something, you kind of felt it's coming from his soul. You just know that's the way the guy feels," said Harris, whose office displays photos of his days as a Reagan campaign aide. "And while I believe that Mitt Romney is just as conservative and feels those same things, it just doesn't come across or get conveyed the same way."

Lake County Sheriff Mark Curran is one of those enthusiastic Santorum supporters who should worry the Romney camp. At a local tavern in leafy Long Grove, Curran, a former Democrat, denounced Romney as out of touch or, as he put it, "off in la-la-land."

"I think Romney travels in circles of only the uber-rich and as a result he has a hard time connecting with large blocks of America - certainly the middle class, which is very much overlooked right now," Curran said. "Santorum is being outspent?10-1, he is being destroyed in misleading ads, but he's still there. Why? Because when people meet him, they see he's the real deal, his authenticity."

There's little doubt that Romney has done an effective job trashing Santorum - Republican sources tracking ad buys show he's outspent the former Pennsylvania senator in the state by a 7 to 1 margin and in the Chicago metro area by a 20-1 margin. But, he has yet to prove that he's made an effective case for himself.

The only way to prove that: a big margin of victory.

ABC News' Matthew Jaffe contributed reporting from Illinois.

?

CLOSING ARGUMENTS IN THE LAND OF LINCOLN:

SANTORUM: Ahead of the primary in Illinois today, Rick Santorum pounded Mitt Romney throughout the day Monday arguing that he "abandoned freedom" as governor of Massachusetts, ABC's Arlette Saenz notes. But as he attempted to paint his campaign as one based on freedom, Santorum flubbed a comment about unemployment rates by saying "I don't care what the unemployment rate is."? When he made the comment, Santorum intended to stress that his campaign isn't focused on one main issue but looking at the broader goal of preserving freedom.? Santorum later attempted to clarify his statement to reporters by saying "of course" he was concerned about unemployment rates but that his "candidacy doesn't hinge" on them.? By the end of the day, Santorum said he sometimes wishes he could have a "do-over" but thinks it's important for voters to see an unscripted candidate like himself, "mistakes and all."

ROMNEY: Mitt Romney delivered an economic speech yesterday that slammed the president's handling of the economy, accusing him of allowing regulators to "multiple like rabbits" that have, in turn, stifled Americans' economic freedom, ABC's Emily Friedman reports. "Our status and our standing in the world are in peril because the source of our economic strength is threatened," Romney said, delivering a speech at the University of Chicago. "Over the last several decades, and particularly over the last three years, Washington has consistently encroached upon our freedom. "The Obama administration's assault on our economic freedom is the principal reason why the recovery has been so tepid, and why it couldn't meet their projections, let alone our expectations," he said. "If we don't change course now, this assault on freedom could damage our economy and the well-being of American families for decades to come." http://abcn.ws/yD4tDu

?

SHOTS FIRED: ROMNEY AND GAS PRICES. Ahead of today's Illinois primary, the Democratic super PAC, American Bridge, has released a slick new web video exposing what the groups sees as Mitt Romney's inconsistency on the issue of gas prices - a new hot topic in the presidential race. The clip highlights differences between what Romney wrote in his 2010 book, "No Apology," and what he's been saying on the campaign trail this year. WATCH: http://bit.ly/xy8jik

?

PRIMARY PRIMER. ABC's Elizabeth Hartfield identifies five important things to know going into today's primary.

1.) There's a hefty delegate prize: 69 delegates are at stake in Illinois. Only 54 of them will be allocated tonight, leaving an additional 15 delegates to be awarded at the state's convention in June.

2.) The popular vote won't affect the delegates awarded, which?might cause a problem for Rick Santorum: Illinois's primary is a bit complex as far as awarding delegates is concerned. The state holds a presidential preference vote, which determines the overall winner of the state. But the vote has no bearing on the allocation of the 54 delegates being doled out today. Instead, voters will directly elect delegates from a list of names on the ballot in their own congressional districts. This is a?disadvantage for Santorum. He failed to qualify for the ballot in four out of Illinois' 18 congressional districts, making him ineligible for a total of 10 delegates. So it will be difficult for him to win the majority of delegates today, regardless of who wins that statewide vote.

3.) Big money has been spent in the state: Romney and his allies have spent a lot of money on ad buys leading up to the March 20 primary - more than $3.5 million.? By comparison, Santorum has not spent nearly as much - only about $500,000.

4.) Any registered voter can participate: There are?8,282,924 registered voters in Illinois, all of whom could, technically, participate in the primary, provided they registered by March 13, and verbally confirm at their polling place that they are indeed a Republican.

5.) Lots of votes have already been cast: Voters in Illinois looking to cast ballots before today had a myriad of options from which to choose, and tabulations from the state elections board show they took advantage of the smorgasbord.

THE STAKES. ABC's Rick Klein writes that Santorum needs an upset today. He needs it to come in a big state, and fast, for him to change the dynamics of the race sufficiently for him to actually win.Why Illinois? For starters, it's next on a calendar that isn't particularly friendly to Santorum these next few weeks. After Louisiana votes this weekend, Maryland, Wisconsin, and the District of Columbia (where Santorum isn't even on the ballot) are up next, and will be tough for Santorum to break through in. Plus, voting in Illinois takes place as Santorum has something to prove. His decision to burn two gaffe-filled campaign days in Puerto Rico, where he secured just 8 percent of the vote and zero delegates yesterday, may stand as one of the biggest miscalculations of the election. http://abcn.ws/A1rSry

?

THE BUZZ

SANTORUM CAMPAIGN FLOATS NEW DELEGATE MATH SHOWING A TIGHTER RACE. Rick Santorum's number crunchers are under no illusions that they are facing a tooth-and-nail fight with Mitt Romney over delegates, but their calculations show a significantly narrower gap between the two contenders than most estimates. The Santorum campaign offered ABC News a sneak peek at their in-house delegate tally, which still shows the former Pennsylvania senator trailing Romney but in a much better position to catch him. "There is the Romney way of going about the counting and then there is the real way of going about the counting," John Yob, Santorum's delegate strategist, said in an interview on Monday. http://abcn.ws/FSAHmJ

Here's how the Santorum campaign sees the standings in the race for delegates:

Romney: 435

Santorum: 311

Gingrich: 158

Paul: 91

The Santorum campaign's version of the count puts them 124 delegates shy of Romney. By comparison, the ABC News delegate estimate shows Santorum 268 delegates behind Romney. Here is the ABC News delegate estimate, which tracks closely with tallied kept by other news organizations, including the Associated Press:

Romney: 521

Santorum: 253

Gingrich: 136

Paul: 50

Uncommitted: 2

KAREN SANTORUM: WOMEN HAVE 'NOTHING TO FEAR' FROM HER HUSBAND. Former senator and GOP candidate Rick Santorum often jokes that American voters prefer hearing more from his wife and less from him. ABC's Alexa Keyes notes that Karen Santorum heeded her husband's call last night for "less Rick, more Karen" on a solo interview with CNN's Piers Morgan. The 51-year-old mother of seven was interviewed on "Piers Morgan Tonight" before Sen. Scott Brown, R-Mass., who?recently took a jab at Santorum's contraception beliefs?(and the couple's large brood) when he joked that Santorum's Secret Service detail is the first time he has "used protection." "Sometimes you have to just laugh and other times you just shut it out and ignore it," Karen Santorum told Morgan. "But I thought that was funny." The neo-natal nurse and former law student also insisted her husband would not make changes to contraception laws if he becomes president. "Women have nothing to fear when it comes to contraceptives," she said, adding that her husband would "absolutely not" bring his personal religious beliefs "to play" as president. http://abcn.ws/GzWpOd

ROMNEY RED ALERT. ABC's Jake Tapper spots a flashing red light for Mitt Romney. In the latest Quinnipiac University poll of Virginia not only does President Obama win head to head against Romney 50 percent to 42 percent in a hypothetical match up, but Obama leads among women 52 percent to 39 percent. Obama's favorables are 51 percent (favorable) 44 percent (unfavorable). Romney's are negative: 36 percent (favorable) 43 percent (unfavorable). It's more grist for the Obama argument that Romney is doing himself real damage in this primary.

SUPREME COURT TO HEAR HEALTH CARE CHALLENGE: WHAT TO EXPECT. Next week when the U.S. Supreme Court considers the constitutionality of the president's health care reform law and whether the government can require Americans to buy health insurance through a so-called "individual mandate" there will be six hours of arguments featuring six different lawyers over three days, ABC's Ariane de Vogue notes. That's a marathon by Supreme Court standards. Most cases are heard over a single day and rarely for longer than an hour. For starters, the court will allow audio recording of the proceedings. This is rare, but not unprecedented, and is usually reserved for big cases. The first time the court permitted audio recording was during Bush v. Gore in 2000. But don't expect a live feed of the case. And handheld devices aren't allowed in the court either, so there won't be any Tweeting of the arguments as they're happening. Audio and court transcripts will be turned around after arguments same day. Supporters and opponents of the law have extensive plans for reaction outside of court. Here's a brief look at the schedule and the issues: http://abcn.ws/GAnq4Z

WHO'S TWEETING?

@mckaycoppins : The secret of Mitt's success - blue states, Mormon bastions, and U.S. territories that can't vote in November? http://shar.es/p54TU

@BuzzFeedBen : The secret of Obama's success was red states, territories, African-American strongholds? nature of the process, to a degree at least.

@RyanLizza : Love that Gingrich is reading Ballots & Bandwagons, a 1964 book about 5 historic brokered conventions b/w 1900 & 1956.

@googlepolitics : Watch the 1st in a series of GOP presidential candidate hangouts on Google+ w/? @MittRomney?at 2:45 PM ET? http://goo.gl/QCvUu #AskMitt

@brianstelter : NYT "will be moving the pay gate at? http://NYTimes.com?to 10 free articles a month from 20, beginning in April," publisher tells staff.

?

PRIMARY STATE SPEED READ

by ABC's Chris Good

-Romney Avoids Mentioning Santorum. Campaigning in Illinois ahead of today's primary, Mitt Romney has repeatedly avoided mentioning his opponent, instead framing his stump speeches around the general election against President Obama. The Rock Island Argus reports that on Monday, Romney failed to mention Santorum's name during a 10-minute speech in Springfield and "hardly talked about" the state's primary. http://bit.ly/GCbrEv

-Santorum vs. Wall Street. Since early in the 2012 race, Rick Santorum has pitched his electability against President Obama, highlighting his rust-belt background as a former Pennsylvania senator. On Monday, he put it differently in attacking his rival during a speech in Rockford, Ill.: "I'm not a Wall Street financier like [Romney] was ? Do you think this country wants to elect a Wall Street financier?" http://trib.in/FQaRBp

-Santorum Visits Reagan's Hometown. Santorum used his last bit of time before Tuesday's primary to visit Dixon, Ill., where Ronald Reagan attended high school. "I need you to rise up and speak loudly from the place of freedom here in Dixon, Illinois," the Chicago Sun-Times quotes Santorum as saying. "Let the voice of Reagan be heard across this land." http://bit.ly/GzN6Lx

-Romney Picks Up an Endorsement in Louisiana. Having enjoyed establishment-GOP backing in multiple primary states so far, Mitt Romney picked up the endorsement of Louisiana Lt. Gov. Jay Dardenne (R) on Monday, ahead of Saturday's primary. "Conservatives looking to win in November and replace President Obama's failed policies with a pro-growth agenda should look no further than Mitt Romney," Dardenne said. Gov. Bobby Jindal supported Rick Perry's presidential bid.

?

POLITICAL RADAR:

- Mitt Romney starts primary day with a visit to Google Headquarters in Chicago, IL. This evening, Romney will watch the returns at the Renaissance Hotel in Schaumberg, IL.

- Rick Santorum spends the day back home in Virginia before heading to Gettysburg, Pennsylvania for his election night party at the Gettysburg Hotel.

- Newt Gingrich is on the trail in Louisiana ahead of their Saturday Primary. Gingrich will make stops in Shreveport, Ruston, and Monroe.

- Ron Paul is out west in California attending a luncheon at the Los Angeles Marriott Burbank Airport and making an appearance on The Tonight Show with Jay Leno.

-ABC's Josh Haskell (@HaskellBuzz)

?Check out The Note's Futures Calendar:? http://abcn.ws/ZI9gV

* Get? The Note delivered ?to your inbox every day.

* For breaking political news and analysis check out The Note blog:? http://blogs.abcnews.com/thenote/ and ABCNews.com/Politics:? http://abcnews.com/politics

Also Read

Source: http://news.yahoo.com/illinois-primary-suburban-slog-note-131941340--abc-news.html

project runway all stars

Sri Lanka ethnic groups divided over UN resolution

Buddhist monks walk during the street march ahead of a prayer session, denouncing the proposed U.N. Human Rights Council resolution on alleged rights abuses during the country's civil war, in Colombo, Sri Lanka, Monday, March 19, 2012. Hundreds of Buddhist, Hindu, Muslim and Christian clergy representing the main religions of Sri Lanka too part in a ceremony to pray for the defeat of a United States-backed resolution urging the country to investigate allegations of war crimes in the final stages of the country's civil war. The resolution is expected to be put to voting at the United Nations Human Rights Council sessions in Geneva this week. (AP Photo/Gemunu Amarasinghe)

Buddhist monks walk during the street march ahead of a prayer session, denouncing the proposed U.N. Human Rights Council resolution on alleged rights abuses during the country's civil war, in Colombo, Sri Lanka, Monday, March 19, 2012. Hundreds of Buddhist, Hindu, Muslim and Christian clergy representing the main religions of Sri Lanka too part in a ceremony to pray for the defeat of a United States-backed resolution urging the country to investigate allegations of war crimes in the final stages of the country's civil war. The resolution is expected to be put to voting at the United Nations Human Rights Council sessions in Geneva this week. (AP Photo/Gemunu Amarasinghe)

Young Buddhist monks walk during a street march ahead of a prayer session, denouncing the proposed U.N. Human Rights Council resolution on alleged rights abuses during the country's civil war, in Colombo, Sri Lanka, Monday, March 19, 2012. Hundreds of Buddhist, Hindu, Muslim and Christian clergy representing the main religions of Sri Lanka took part in a ceremony to pray for the defeat of a United States-backed resolution urging the country to investigate allegations of war crimes in the final stages of the country's civil war. The resolution is expected to be put to voting at the United Nations Human Rights Council sessions in Geneva this week. (AP Photo/ Gemunu Amarasinghe)

(AP) ? The Sri Lankan government's campaign to stave off any U.N. call to investigate its wartime conduct is hampering efforts to heal long-simmering ethnic tensions, according to Tamil politicians, rights activists and clergy members.

Nearly three years after the end of a decades-long civil war that pitted the majority Sinhalese government against minority Tamil Tiger rebels seeking an ethnic homeland, the U.N. rights council is expected to vote this week on a resolution urging Sri Lanka to investigate allegations of human rights abuses and seek reconciliation.

The war ended in 2009 with a bloody offensive into Tiger-controlled northern areas by the government of President Mahinda Rajapaksa, a military push that critics say saw thousands of civilians killed as the Tigers were crushed.

But talk of a U.N. resolution calling for a probe and moves toward reconciliation has infuriated Rajapaksa's governments as well as his supporters, who see it as outside interference in Sri Lanka's internal affairs.

In Geneva, where the rights council is based, Sri Lankan diplomats have been quietly urging members of the 47-nation body to defeat the U.S.-backed resolution.

At home, the reaction has been constant and noisy. Pro-government politicians, voters and Buddhist monks have turned out for daily protests denouncing the resolution, carrying larger-than-life cutout posters of the president. The government's official website has accused local rights activists who support the resolution of aiming to "betray Sri Lanka in Geneva."

The Catholic church, which has both Tamil and Sinhalese members and which has largely been seen as neutral in the ethnic dispute, has also gotten involved.

The proposed resolution is an "undue meddling in the sovereignty and integrity of Sri Lanka," said a statement from the office of Cardinal Malcolm Ranjith.

The Tigers, a cult-like group known for suicide-bombers and child soldiers, fought for 25 years to create an independent state for Tamils. Despite the bloody end to the war, the government victory was still seen by many as an opportunity for Sri Lanka to rebuild its ethnic relations, which long before the war had been battered by decades of anti-Tamil discrimination by successive Sinhalese-controlled governments.

Many activists suggested quickly resettling people displaced by the war and negotiating Tamil demands for power sharing. Instead, the government is accused of further alienating Tamils by promoting Sinhalese settlements in predominantly Tamil areas, and disregarding all requests to share power.

Now, with the government fighting the proposed U.N. resolution, Tamils say they are being further pushed aside.

Calling the Sri Lankan government "one of the parties of the abuses" at the war's end, a Tamil Catholic bishop and 30 other priests from the country's Tamil north said in a letter to the U.N. rights group that the resolution "could best address concerns of truth-seeking, accountability and reparations for victims in a way that victims, survivors and their families will have confidence. It is only by addressing these that we believe we can move towards genuine reconciliation."

Such talk is widely heard in Sri Lanka's Tamil community.

"Tamils have struggled through peaceful means and through arms, and nothing has succeeded. There is no way there can be another armed insurrection, so the only solution seems to be something that comes through U.N. intervention," said S. Ravichandran, 37, a Tamil taxi driver in Colombo, the capital.

The Tamil National Alliance, the main Tamil political party, calls the resolution a "first and necessary step towards ensuring peace, justice and reconciliation in Sri Lanka."

"The council must ensure that the Sri Lankan government immediately takes steps to offer a political solution to the Tamil people to resolve the long-festering and deep-seated national problem," party leader Rajavarothayam Sampanthan said in a statement.

The government insists, though, that its own investigations were sufficient.

In 2010, the government created a Lessons Learnt and Reconciliation Commission, which gathered evidence on the conflict from both sides. It released its report last December.

While it disputed an earlier U.N. report ? which said Sri Lankan troops deliberately targeted civilians ? it did recommend that the government give more power to Tamils in areas where they are in the majority. Those recommendations have been ignored by the government.

Now, analysts say the government fears the fallout of another investigation.

Jehan Perera of National Peace Council, a Sri Lankan organization that promotes peace and good governance, said the government is resisting the proposed resolution because it fears "that this could be the thin edge of the wedge that finally ends in war crimes trials of the government leadership."

The proposal's passage appeared to be one step closer Monday when Indian Prime Minister Manmohan Singh told Parliament that New Delhi was "inclined to vote in favor of the resolution." India wants "a future for the Tamil community in Sri Lanka that is marked by equality, dignity, justice and self-respect," said Singh, who has been under unrelenting pressure from key Tamil political allies to back the resolution.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/cae69a7523db45408eeb2b3a98c0c9c5/Article_2012-03-20-AS-Sri-Lanka-Reconciliation/id-a75b56b67d7747a8a28da1789f5d4a75

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JCI early table of contents for March 19, 2012

JCI early table of contents for March 19, 2012 [ Back to EurekAlert! ] Public release date: 19-Mar-2012
[ | E-mail | Share Share ]

Contact: Sarah Jackson
press_releases@the-jci.org
Journal of Clinical Investigation

EDITOR'S PICK

A clearer understanding of glaucoma | Back to top

Glaucoma is one of the leading causes of vision loss and blindness worldwide. In glaucoma patients, the optic nerve, which relays information from the eye to the brain, is damaged, though the molecular cause of nerve damage is unclear. Dr. Simon John, from Tufts University in Boston, and colleagues specifically wanted to understand the earliest events that lead to optic nerve damage in glaucoma. Using a mouse model of the disease, the researchers showed that inflammatory immune cells called monocytes cross blood vessels and invade the optic nerve. Remarkably, mice treated with a single X-ray treatment in eyes prior to the onset of glaucoma were protected from developing the disease later in life. Through an unknown mechanism, the X-ray treatment prevented neuroinflammation and allowed mice to avoid glaucoma development, even in the presence of other risk factors. Continuing research by the John team will examine why the X-ray treatment effectively blocked glaucoma in the mouse model system and if this strategy might someday be adapted to prevent glaucoma in humans.

TITLE:

Radiation treatment inhibits monocyte entry into the optic nerve head and prevents neuronal damage in a mouse model of glaucoma

AUTHOR CONTACT:

Simon W.M. John

Howard Hughes Medical Institute, The Jackson Laboratory, 600 Main St., Bar Harbor, Maine 04609, USA. Phone: 207-288-6496; Fax: 207-288-6078; E-mail: simon.john@jax.org.

View this article at: http://www.jci.org/articles/view/61135?key=82201f32dfe421d1d337

CARDIOVASCULAR DISEASE

At the heart of it all: myosin regulatory protein key for cardiac muscle function | Back to top

A groundbreaking study by Ju Chen and colleagues at the University of California at San Diego sheds new light on the regulation of cardiac muscle contraction. The dynamic interaction of the proteins actin and myosin, which are key components of muscle fibers, is responsible for contractions. The binding of calcium to actin-bound regulatory proteins has long been regarded as the primary regulatory mechanism for muscle contraction. However, some data suggests that myosin regulatory proteins, such as ventricular myosin light chain-2 (MLC2v), might also contribute to the regulation of muscle contractions through unknown mechanisms.

The Chen team specifically examined the role of MLC2v phosphorylation on cardiac muscle. They show in cardiac tissue that MLC2v phosphorylation controls dynamic myosin and actin interactions. The team also extrapolates the molecular actions of MLC2v phosphorylation using computation models, which suggest that cross bridge attachment dynamics are controlled by MLC2v phosphorylation. Their model of MLC2v regulation of cardiac muscle contraction is supported by defects in the rate of twitch relaxation that they observed in a mouse model system in which MLC2v cannot be phosphorylated. Their study provides new appreciation for the role of myosin regulatory proteins in muscle contraction, and has important clinical implications for understanding heart disease.

TITLE:

Mouse and computational models link Mlc2v dephosphorylation to altered myosin kinetics in early cardiac disease

AUTHOR CONTACT:

Farah Sheikh

The University of California San Diego, La Jolla, CA, USA

Phone: 858-246-0754; E-mail: fasheikh@ucsd.edu

View this article at: http://www.jci.org/articles/view/61134?key=2d474e8f8bbd89c3c3e2

CARDIOVASCULAR DISEASE

A big role for microRNA in protecting heart tissue | Back to top

During a heart attack, a block in blood flow damages cardiac tissue. Though counterintuitive, significant tissue damage also occurs in response to the restoration of blood flow, known as ischemia/reperfusion injury, which activates stress pathways in the heart. This second wave of cardiac damage is caused by a many factors, including a disruption in the balance of calcium, which is a key regulator of heart contractions and cellular signaling. Dr. Eric Olson and his colleagues at the University of Texas Southwestern Medical Center in Dallas recently explored one of the causes of calcium overload during ischemia/reperfusion injury using a mouse model system. They suspected that regulatory RNA molecules known as microRNAs (miRNAs) may play a role in tissue damage in response to the restoration of blood flow to the heart. The team showed that miRNA-214, which is upregulated during the block in blood flow to the heart, helped protect tissue from ischemis/reperfusion injury. They found that mice that lack miRNA-214 lost heart contractility and showed an increase in fibrosis due to aberrant regulation of a key regulator of calcium influx. Their work has identified a new pathway that is important in regulating calcium homeostasis and protecting heart function.

TITLE:

microRNA-214 protects the heart from ischemic injury by controlling Ca2+ overload and cell death in mice

AUTHOR CONTACT:

Eric Olson

UT Southwestern Medical Center, Dallas, TX, USA

Phone: 214-648-1187; Fax: 214-648-1196; E-mail: Eric.Olson@utsouthwestern.edu

View this article at: http://www.jci.org/articles/view/59327?key=a681696f8fc27eb4f99a

CARDIOVASCULAR BIOLOGY

Endothelial Hypoxia Inducible Factor-2alpha (HIF-2?) regulates murine pathological angiogenesis and revascularization processes | Back to top

Understanding what triggers new blood vessels to grow has clinical implications for disorders characterized by restricted blood flow, such as macular degeneration and peripheral arterial disease, and for the growth of solid tumors, which require new blood flow to maintain aggressive growth. The development of new blood vessels, termed angiogenesis, is triggered in part by low oxygen levels. A transcription factor called Hypoxia Inducible Factor can respond to low oxygen and induce the expression of multiple genes required for angiogenesis.

A research group at the University of Pennsylvania in Philadelphia delved into the detailed mechanism of how the protein hypoxia inducible factor 2? (HIF-2 ?) contributes to new blood vessel formation. Led by M. Celeste Simon, the team specifically disrupted the Hif-2? gene from mouse endothelial cells, which make up the walls of blood vessels, and observed an increase in blood vessel formation. However, the blood vessels that formed in the mouse model system had reduced blood flow and poor tissue oxygenation due to ineffective vessel remodeling. Their study distinguishes the role of Hif-2? from a related gene, Hif-1?, and suggest that these genes work synergistically to promote proper blood vessel formation.

TITLE:

Endothelial Hypoxia Inducible Factor-2alpha (HIF-2?) regulates murine pathological angiogenesis and revascularization processes

AUTHOR CONTACT:

M. Celeste Simon

University of Pennsylvania/HHMI, Philadelphia, PA, USA

Phone: 215-746-5532; Fax: 215-746-5511; E-mail: celeste2@mail.med.upenn.edu

View this article at: http://www.jci.org/articles/view/57322?key=ffe5c51b522aa2341952

VIROLOGY

Understanding how herpes simplex virus invades the central nervous system | Back to top

Herpes Simplex virus (HSV) 1 and 2 are the cause of cold sores and genital herpes, respectively, in humans. Even in the absence of outbreaks, remaining reservoirs of virus linger in the body. Both viruses can infect neurons and occasionally cause diseases such as encephalitis and meningitis, especially in people with compromised immune system. Sren Paludan and colleagues at Aarhus University in Denmark investigated what triggers increased susceptibility to HSV2 in the central nervous system using a mouse model system. The found that toll-like receptor 3 (TLR3) is critical for maintaining immunoprotective responses in the central nervous system and that mice lacking Tlr3 showed increased susceptibility to central nervous system complications following HSV-2 infection. Importantly, their work clarifies when and where TLR3 activity is necessary, and they demonstrate that TLR-3 elicits an interferon response in astrocytes following viral entry in the central nervous system. Their work clarifies the mechanisms whereby central nervous system diseases arise in HSV-infected individuals.

TITLE:

TLR3 deficiency renders astrocytes permissive to herpes simplex virus infection and facilitates establishment of CNS infection in mice

AUTHOR CONTACT:

Sren Paludan

University of Aarhus, Aarhus C, UNK, DNK

Phone: 45-8942-1767; Fax: 45-8619-6128; E-mail: srp@microbiology.au.dk

View this article at: http://www.jci.org/articles/view/60893?key=b1c8e06ace14d57b6549

IMMUNOLOGY

Immune response gone awry: treating autoimmune disorders with rituximab | Back to top

Rituximab is an antibody therapy that targets immune cells called B cells for destruction. The FDA has approved rituximab for treatment of specific disorders characterized by too many B cells, such as B cell lymphoma, or autoimmune disorders, such as rheumatoid arthritis. However, it has been unclear why some autoimmune patients show good long-term clinical response to rituximab while others do not.

In a clinical study of patients with anti-myelin-associated glycoprotein (MAG) neuropathy, an autoimmune disorder characterized by an immune system attack towards a protein expressed in the myelin sheath of peripheral nerves, Dr. Jan Lunemann and colleagues at the University of Zurich in Switzerland sought to discover why some patients respond well to rituximab. The team looked at memory B cell expansion before and after rituximab therapy in patients, and found that a good response was associated with depletion of non-circulating B cells and reconfiguration of B cell memory. The team suggests that non-responders may benefit from additional rituximab rounds of therapy to further reduce self-reactive B cells. Their findings support continued exploration of rituximab therapy for other autoimmune disorders where B cell depletion could alleviate symptoms.

TITLE:

Rituximab induces sustained reduction of pathogenic B cells in patients with peripheral nervous system autoimmunity

AUTHOR CONTACT:

Jan Lunemann

University of Zurich, Zurich, UNK, CHE

Phone: 41-44-635-3710; Fax: ; E-mail: jan.luenemann@uzh.ch

View this article at: http://www.jci.org/articles/view/58743?key=ff7ccbe1d4fa25c37448

METABOLIC DISEASE

Uncovering the links between diabetes and atherosclerosis | Back to top

Diabetic patients are at increased risk for cardiovascular disease and a hardening of blood vessel walls called atherosclerosis. One factor that drives atherosclerosis development in diabetes is abnormal blood cholesterol levels. Researchers suspect that a breakdown of LDL in early Type 2 diabetes by the low density lipoprotein receptor (LDLR) in liver leads to a compensatory increase in levels of very low density lipoprotein (VLDL).

The challenge of understanding the link between insulin and liver LDLR levels was addressed by Ding Ai and colleagues at the University of Texas Southwestern Medical Center in Dallas. Using several different mouse models, they showed that insulin receptor signaling via mTORC1 blocks LDLR breakdown by PCSK9. Thus LDLR is stabilized and more LDL is broken down, leading to disturbed cholesterol levels. Their results also help explain why rapamycin, a drug that inhibits mTORC1 and is used to suppress the immune system during transplantation, causes an increase in cholesterol levels.

TITLE:

Regulation of hepatic LDL receptors by mTORC1 and PCSK9

AUTHOR CONTACT:

Ding Ai

Columbia University Medical Center, new york, NY, USA

Phone: 212-305-5789; Fax: ; E-mail: da2424@columbia.edu

View this article at: http://www.jci.org/articles/view/61919?key=3d4f1e4a9bd3d7f71c60

NEUROBIOLOGY

A painful lesson: understanding what causes hypersensitivity to pain | Back to top

An increased sensitivity to pain, called hyperalgesia, can be debilitating for suffering patients. Hyperalgesia can be a complication of several disorders including stroke, fibromyalgia, diabetes, and neuropathic disorders. Inflammation, tissue damage, and nervous system disorders can all contribute to development of hyperalgesia, but the underlying molecular mechanisms are still unknown. Researchers at the Ernest Gallo Clinic in Emerville, CA set out to better understand the molecular cause of hyperalgesia. Led by Robert Messing, the team searched for the molecular target of PKC?, an enzyme that regulates hyperalgesia through a poorly understood mechanism. The research team identified a sodium channel that is targeted by PKC? in sensory neurons called nociceptors. Further, they showed depleting these specific sodium channels from nociceptors in a mouse model system blocked the development of hyperalgesia. These results provide new evidence for the molecular causes of hyperalgesia and suggest that targeting this pathway may be an effective strategy for designing new therapeutics to treat hyperalgesia.

TITLE:

PKC epsilon phosphorylation of NaV1.8 increases sodium channel function and produces mechanical hyperalgesia in mice

AUTHOR CONTACT:

Robert Messing

Univ. of Calif. San Francisco, Emeryville, CA, USA

Phone: 510-985-3950; Fax: 510-985-3101; E-mail: romes@gallo.ucsf.edu

View this article at: http://www.jci.org/articles/view/61934?key=df6009bb3364cd6c8a9b

ONCOLOGY

Learning from mistakes: why a promising therapy for follicular lymphoma failed | Back to top

Follicular lymphoma is a cancer characterized by abnormal proliferation of immune cells called B cells. One therapeutic strategy, Interleukin (IL) -12 therapy, was predicted to increase the clearing of malignant B cells by activating natural killer (NK) cells and T cells, components of the immune system. Unfortunately, this strategy had very limited efficacy in a previously conducted clinical trial of follicular lymphoma patients. Dr. Stephen Ansell and colleagues at the Mayo Clinic in Rochester, MN wanted to understand why IL-12 therapy had failed. They found that activation of the IL-12 pathway exhausted T cell populations through a previously unknown mechanism, rather than stimulating clearance of tumor cells. When the therapy was designed, it was hoped that IL-12 would promote T cell responsiveness through the production of interferon gamma (IFN-?), which stimulates immune system activity. The research team found that instead T cell exhaustion is induced in patients by IL-12-induced expression of TIM-3, a family member of T-cell immunoglobulin and mucin domain proteins, that negatively regulates immune response. Thus, their study explains why IL-12 therapy was ineffective in treating follicular lymphoma patients and highlights the importance of TIM-3 downstream of the IL-12 pathway.

TITLE:

IL-12 upregulates TIM-3 expression and induces T cell exhaustion in patients with follicular B cell non-Hodgkin lymphoma

AUTHOR CONTACT:

Stephen Ansell

Mayo Clinic, Rochester, , USA

Phone: 507-284-3805; Fax: ; E-mail: ansell.stephen@mayo.edu

View this article at: http://www.jci.org/articles/view/59806?key=508276a4858aa2a078bc

###



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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.


JCI early table of contents for March 19, 2012 [ Back to EurekAlert! ] Public release date: 19-Mar-2012
[ | E-mail | Share Share ]

Contact: Sarah Jackson
press_releases@the-jci.org
Journal of Clinical Investigation

EDITOR'S PICK

A clearer understanding of glaucoma | Back to top

Glaucoma is one of the leading causes of vision loss and blindness worldwide. In glaucoma patients, the optic nerve, which relays information from the eye to the brain, is damaged, though the molecular cause of nerve damage is unclear. Dr. Simon John, from Tufts University in Boston, and colleagues specifically wanted to understand the earliest events that lead to optic nerve damage in glaucoma. Using a mouse model of the disease, the researchers showed that inflammatory immune cells called monocytes cross blood vessels and invade the optic nerve. Remarkably, mice treated with a single X-ray treatment in eyes prior to the onset of glaucoma were protected from developing the disease later in life. Through an unknown mechanism, the X-ray treatment prevented neuroinflammation and allowed mice to avoid glaucoma development, even in the presence of other risk factors. Continuing research by the John team will examine why the X-ray treatment effectively blocked glaucoma in the mouse model system and if this strategy might someday be adapted to prevent glaucoma in humans.

TITLE:

Radiation treatment inhibits monocyte entry into the optic nerve head and prevents neuronal damage in a mouse model of glaucoma

AUTHOR CONTACT:

Simon W.M. John

Howard Hughes Medical Institute, The Jackson Laboratory, 600 Main St., Bar Harbor, Maine 04609, USA. Phone: 207-288-6496; Fax: 207-288-6078; E-mail: simon.john@jax.org.

View this article at: http://www.jci.org/articles/view/61135?key=82201f32dfe421d1d337

CARDIOVASCULAR DISEASE

At the heart of it all: myosin regulatory protein key for cardiac muscle function | Back to top

A groundbreaking study by Ju Chen and colleagues at the University of California at San Diego sheds new light on the regulation of cardiac muscle contraction. The dynamic interaction of the proteins actin and myosin, which are key components of muscle fibers, is responsible for contractions. The binding of calcium to actin-bound regulatory proteins has long been regarded as the primary regulatory mechanism for muscle contraction. However, some data suggests that myosin regulatory proteins, such as ventricular myosin light chain-2 (MLC2v), might also contribute to the regulation of muscle contractions through unknown mechanisms.

The Chen team specifically examined the role of MLC2v phosphorylation on cardiac muscle. They show in cardiac tissue that MLC2v phosphorylation controls dynamic myosin and actin interactions. The team also extrapolates the molecular actions of MLC2v phosphorylation using computation models, which suggest that cross bridge attachment dynamics are controlled by MLC2v phosphorylation. Their model of MLC2v regulation of cardiac muscle contraction is supported by defects in the rate of twitch relaxation that they observed in a mouse model system in which MLC2v cannot be phosphorylated. Their study provides new appreciation for the role of myosin regulatory proteins in muscle contraction, and has important clinical implications for understanding heart disease.

TITLE:

Mouse and computational models link Mlc2v dephosphorylation to altered myosin kinetics in early cardiac disease

AUTHOR CONTACT:

Farah Sheikh

The University of California San Diego, La Jolla, CA, USA

Phone: 858-246-0754; E-mail: fasheikh@ucsd.edu

View this article at: http://www.jci.org/articles/view/61134?key=2d474e8f8bbd89c3c3e2

CARDIOVASCULAR DISEASE

A big role for microRNA in protecting heart tissue | Back to top

During a heart attack, a block in blood flow damages cardiac tissue. Though counterintuitive, significant tissue damage also occurs in response to the restoration of blood flow, known as ischemia/reperfusion injury, which activates stress pathways in the heart. This second wave of cardiac damage is caused by a many factors, including a disruption in the balance of calcium, which is a key regulator of heart contractions and cellular signaling. Dr. Eric Olson and his colleagues at the University of Texas Southwestern Medical Center in Dallas recently explored one of the causes of calcium overload during ischemia/reperfusion injury using a mouse model system. They suspected that regulatory RNA molecules known as microRNAs (miRNAs) may play a role in tissue damage in response to the restoration of blood flow to the heart. The team showed that miRNA-214, which is upregulated during the block in blood flow to the heart, helped protect tissue from ischemis/reperfusion injury. They found that mice that lack miRNA-214 lost heart contractility and showed an increase in fibrosis due to aberrant regulation of a key regulator of calcium influx. Their work has identified a new pathway that is important in regulating calcium homeostasis and protecting heart function.

TITLE:

microRNA-214 protects the heart from ischemic injury by controlling Ca2+ overload and cell death in mice

AUTHOR CONTACT:

Eric Olson

UT Southwestern Medical Center, Dallas, TX, USA

Phone: 214-648-1187; Fax: 214-648-1196; E-mail: Eric.Olson@utsouthwestern.edu

View this article at: http://www.jci.org/articles/view/59327?key=a681696f8fc27eb4f99a

CARDIOVASCULAR BIOLOGY

Endothelial Hypoxia Inducible Factor-2alpha (HIF-2?) regulates murine pathological angiogenesis and revascularization processes | Back to top

Understanding what triggers new blood vessels to grow has clinical implications for disorders characterized by restricted blood flow, such as macular degeneration and peripheral arterial disease, and for the growth of solid tumors, which require new blood flow to maintain aggressive growth. The development of new blood vessels, termed angiogenesis, is triggered in part by low oxygen levels. A transcription factor called Hypoxia Inducible Factor can respond to low oxygen and induce the expression of multiple genes required for angiogenesis.

A research group at the University of Pennsylvania in Philadelphia delved into the detailed mechanism of how the protein hypoxia inducible factor 2? (HIF-2 ?) contributes to new blood vessel formation. Led by M. Celeste Simon, the team specifically disrupted the Hif-2? gene from mouse endothelial cells, which make up the walls of blood vessels, and observed an increase in blood vessel formation. However, the blood vessels that formed in the mouse model system had reduced blood flow and poor tissue oxygenation due to ineffective vessel remodeling. Their study distinguishes the role of Hif-2? from a related gene, Hif-1?, and suggest that these genes work synergistically to promote proper blood vessel formation.

TITLE:

Endothelial Hypoxia Inducible Factor-2alpha (HIF-2?) regulates murine pathological angiogenesis and revascularization processes

AUTHOR CONTACT:

M. Celeste Simon

University of Pennsylvania/HHMI, Philadelphia, PA, USA

Phone: 215-746-5532; Fax: 215-746-5511; E-mail: celeste2@mail.med.upenn.edu

View this article at: http://www.jci.org/articles/view/57322?key=ffe5c51b522aa2341952

VIROLOGY

Understanding how herpes simplex virus invades the central nervous system | Back to top

Herpes Simplex virus (HSV) 1 and 2 are the cause of cold sores and genital herpes, respectively, in humans. Even in the absence of outbreaks, remaining reservoirs of virus linger in the body. Both viruses can infect neurons and occasionally cause diseases such as encephalitis and meningitis, especially in people with compromised immune system. Sren Paludan and colleagues at Aarhus University in Denmark investigated what triggers increased susceptibility to HSV2 in the central nervous system using a mouse model system. The found that toll-like receptor 3 (TLR3) is critical for maintaining immunoprotective responses in the central nervous system and that mice lacking Tlr3 showed increased susceptibility to central nervous system complications following HSV-2 infection. Importantly, their work clarifies when and where TLR3 activity is necessary, and they demonstrate that TLR-3 elicits an interferon response in astrocytes following viral entry in the central nervous system. Their work clarifies the mechanisms whereby central nervous system diseases arise in HSV-infected individuals.

TITLE:

TLR3 deficiency renders astrocytes permissive to herpes simplex virus infection and facilitates establishment of CNS infection in mice

AUTHOR CONTACT:

Sren Paludan

University of Aarhus, Aarhus C, UNK, DNK

Phone: 45-8942-1767; Fax: 45-8619-6128; E-mail: srp@microbiology.au.dk

View this article at: http://www.jci.org/articles/view/60893?key=b1c8e06ace14d57b6549

IMMUNOLOGY

Immune response gone awry: treating autoimmune disorders with rituximab | Back to top

Rituximab is an antibody therapy that targets immune cells called B cells for destruction. The FDA has approved rituximab for treatment of specific disorders characterized by too many B cells, such as B cell lymphoma, or autoimmune disorders, such as rheumatoid arthritis. However, it has been unclear why some autoimmune patients show good long-term clinical response to rituximab while others do not.

In a clinical study of patients with anti-myelin-associated glycoprotein (MAG) neuropathy, an autoimmune disorder characterized by an immune system attack towards a protein expressed in the myelin sheath of peripheral nerves, Dr. Jan Lunemann and colleagues at the University of Zurich in Switzerland sought to discover why some patients respond well to rituximab. The team looked at memory B cell expansion before and after rituximab therapy in patients, and found that a good response was associated with depletion of non-circulating B cells and reconfiguration of B cell memory. The team suggests that non-responders may benefit from additional rituximab rounds of therapy to further reduce self-reactive B cells. Their findings support continued exploration of rituximab therapy for other autoimmune disorders where B cell depletion could alleviate symptoms.

TITLE:

Rituximab induces sustained reduction of pathogenic B cells in patients with peripheral nervous system autoimmunity

AUTHOR CONTACT:

Jan Lunemann

University of Zurich, Zurich, UNK, CHE

Phone: 41-44-635-3710; Fax: ; E-mail: jan.luenemann@uzh.ch

View this article at: http://www.jci.org/articles/view/58743?key=ff7ccbe1d4fa25c37448

METABOLIC DISEASE

Uncovering the links between diabetes and atherosclerosis | Back to top

Diabetic patients are at increased risk for cardiovascular disease and a hardening of blood vessel walls called atherosclerosis. One factor that drives atherosclerosis development in diabetes is abnormal blood cholesterol levels. Researchers suspect that a breakdown of LDL in early Type 2 diabetes by the low density lipoprotein receptor (LDLR) in liver leads to a compensatory increase in levels of very low density lipoprotein (VLDL).

The challenge of understanding the link between insulin and liver LDLR levels was addressed by Ding Ai and colleagues at the University of Texas Southwestern Medical Center in Dallas. Using several different mouse models, they showed that insulin receptor signaling via mTORC1 blocks LDLR breakdown by PCSK9. Thus LDLR is stabilized and more LDL is broken down, leading to disturbed cholesterol levels. Their results also help explain why rapamycin, a drug that inhibits mTORC1 and is used to suppress the immune system during transplantation, causes an increase in cholesterol levels.

TITLE:

Regulation of hepatic LDL receptors by mTORC1 and PCSK9

AUTHOR CONTACT:

Ding Ai

Columbia University Medical Center, new york, NY, USA

Phone: 212-305-5789; Fax: ; E-mail: da2424@columbia.edu

View this article at: http://www.jci.org/articles/view/61919?key=3d4f1e4a9bd3d7f71c60

NEUROBIOLOGY

A painful lesson: understanding what causes hypersensitivity to pain | Back to top

An increased sensitivity to pain, called hyperalgesia, can be debilitating for suffering patients. Hyperalgesia can be a complication of several disorders including stroke, fibromyalgia, diabetes, and neuropathic disorders. Inflammation, tissue damage, and nervous system disorders can all contribute to development of hyperalgesia, but the underlying molecular mechanisms are still unknown. Researchers at the Ernest Gallo Clinic in Emerville, CA set out to better understand the molecular cause of hyperalgesia. Led by Robert Messing, the team searched for the molecular target of PKC?, an enzyme that regulates hyperalgesia through a poorly understood mechanism. The research team identified a sodium channel that is targeted by PKC? in sensory neurons called nociceptors. Further, they showed depleting these specific sodium channels from nociceptors in a mouse model system blocked the development of hyperalgesia. These results provide new evidence for the molecular causes of hyperalgesia and suggest that targeting this pathway may be an effective strategy for designing new therapeutics to treat hyperalgesia.

TITLE:

PKC epsilon phosphorylation of NaV1.8 increases sodium channel function and produces mechanical hyperalgesia in mice

AUTHOR CONTACT:

Robert Messing

Univ. of Calif. San Francisco, Emeryville, CA, USA

Phone: 510-985-3950; Fax: 510-985-3101; E-mail: romes@gallo.ucsf.edu

View this article at: http://www.jci.org/articles/view/61934?key=df6009bb3364cd6c8a9b

ONCOLOGY

Learning from mistakes: why a promising therapy for follicular lymphoma failed | Back to top

Follicular lymphoma is a cancer characterized by abnormal proliferation of immune cells called B cells. One therapeutic strategy, Interleukin (IL) -12 therapy, was predicted to increase the clearing of malignant B cells by activating natural killer (NK) cells and T cells, components of the immune system. Unfortunately, this strategy had very limited efficacy in a previously conducted clinical trial of follicular lymphoma patients. Dr. Stephen Ansell and colleagues at the Mayo Clinic in Rochester, MN wanted to understand why IL-12 therapy had failed. They found that activation of the IL-12 pathway exhausted T cell populations through a previously unknown mechanism, rather than stimulating clearance of tumor cells. When the therapy was designed, it was hoped that IL-12 would promote T cell responsiveness through the production of interferon gamma (IFN-?), which stimulates immune system activity. The research team found that instead T cell exhaustion is induced in patients by IL-12-induced expression of TIM-3, a family member of T-cell immunoglobulin and mucin domain proteins, that negatively regulates immune response. Thus, their study explains why IL-12 therapy was ineffective in treating follicular lymphoma patients and highlights the importance of TIM-3 downstream of the IL-12 pathway.

TITLE:

IL-12 upregulates TIM-3 expression and induces T cell exhaustion in patients with follicular B cell non-Hodgkin lymphoma

AUTHOR CONTACT:

Stephen Ansell

Mayo Clinic, Rochester, , USA

Phone: 507-284-3805; Fax: ; E-mail: ansell.stephen@mayo.edu

View this article at: http://www.jci.org/articles/view/59806?key=508276a4858aa2a078bc

###



[ Back to EurekAlert! ] [ | E-mail | Share Share ]

?


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


Source: http://www.eurekalert.org/pub_releases/2012-03/joci-jet031412.php

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