Strikeforce and Dream vet Marius Zaromskis fought Bruno Carvalho in Sweden this weekend, and the ending of the fight will make your jaw drop.
Yep, that's a forward roll into an axe kick. Though Carvalho is dropped by the incredible kick, he does survive to return to his feet, only for Zaromskis to end the bout with sharp elbows and then ground and pound.
Miguel Torres once tried a similar move when in the WEC, but didn't connect. This kick can be put alongside the Anthony Pettis "Showtime Kick," and Anderson Silva and Lyoto Machida's front kicks.
WASHINGTON (Reuters) ? The world economy is on a slippery slope. The euro zone appears to have tipped into a mild recession and the rest of the global economy is struggling to hold onto firm ground.
China is slowing, Japan's exports are tumbling. Eastern European countries are wobbling as credit dries up from a pullback in lending by euro-zone banks.
In the United States, the improving economic picture has clouded somewhat after a mixed batch of economic data and downward revision to third-quarter growth to 2.0 percent doused some of the optimism for a strong fourth quarter. Consumer spending slowed in October and business investment weakened, showing a recovery that remains weak and vulnerable to shocks.
Against this uncertain backdrop, financial markets are volatile as European leaders fail to deliver any credible solutions to the sovereign debt crisis and U.S. lawmakers hit gridlock on slashing the budget deficit, further eroding business and consumer confidence and damaging growth prospects.
The U.S. labor market epitomizes these problems.
Two years into a recovery in which corporate profits are robust, hiring should be rebounding sharply. But U.S. employment numbers due on Friday are expected to show an economy treading water, with 120,000 new hires in November, up from 80,000 the prior month but way below the level needed to improve the outlook.
"The trend has been fairly stable over the last five months, stuck at a level just about strong enough to absorb new entrants into the labor force, but not to reduce the unemployment rate significantly," said Jeoff Hall, economist at IFR Markets, a Thomson Reuters company.
In fact, large U.S, companies are showing new caution.
Boeing Co announced plans last week to shutter a Kansas factory that employs 2,100 as it prepares for U.S. federal budget cuts that will hit defense spending hard. Bank of America began sending lay-off notices last week to technology staff as part of plans to cut 30,000 positions over the next few years, and Wells Fargo & Co also began job cuts.
Whirlpool Corp, the world's largest maker of household appliances, reports softening demand worldwide, including fast-growing emerging Asia and Latin America, and is cutting about 5,000 jobs in North America and Europe.
Srinivas Thiruvadanthai, director of research at the Jerome Levy Forecasting Center, also is concerned that fiscal tightening in the United States -- from the roll-off of 2009 stimulus projects, cutbacks to city and state budgets and possible expiration of the payroll tax cut -- will further weaken the U.S. consumer, who accounts for the bulk of growth.
"Clearly Europe is in bad shape, and the global economic conditions are worsening too. If the U.S. consumer tires, the chances for recession are met," he said.
Since late September, the Levy Center has forecast that Europe's debt crisis will hit the United States through financial markets, its banks, weakened exports, lowered corporate profits and drag the United States into recession in 2012. Thiruvadanthai sees nothing to alter that picture.
EUROPEAN MIRE
European finance ministers meet again on Tuesday to review strengthening the region's bailout fund, seen only a month ago as the centerpiece for halting its debt crisis. But the sharp deterioration in euro-zone debt prices, which sucked in Germany last week in a failed bund auction, has undercut how much the fund can be leveraged, leaving investors highly skeptical that politicians can use it to stem contagion.
Italy issues 8 billion euros in longer term debt on Tuesday. Two-year Italian paper already is priced a 8 percent, one full point above the yield considered affordable by a nation with a stalled economy. Belgium, downgraded from AA-plus to AA by S&P on Friday, raises cash a day earlier, with the cost of insuring its debt having hit a record level.
Goldman Sachs warned on Friday that the public sector funding problems, which are hurting bank profits, are restricting household and corporate credit in Europe. This "could turn the moderate recession we are forecasting into something more akin to the 2008/09 experience."
Ripples from the slowdown are felt as far away as Brazil. Its central bank is expected to lower interest rates on Wednesday for third time since August, by a hefty 50 basis points, to 11 percent.
For the United States, recession remains a minority view, though forecasts are being revised downward for 2012. The Institute of International Finance, for instance, noted near-term resilience in its latest forecast but storm clouds ahead.
"Prospects are much less benign for early 2012, when the combination of a large fiscal contraction and rising spillovers from a recession in the euro area are likely to torpedo the U.S. economy," said Philip Suttle, IIF chief economist.
The ISM manufacturing index for the United States, due on Thursday, may show a slight improvement, to 51.5 in November from 50.8 in October, possibly reflecting inventory rebuilding after a tight third quarter. But grim PMI factory indices that showed worsening contractions in Europe and China last week cast some doubt on U.S. resiliency. Vehicle sales, also due on Thursday, are seen holding around the 13.3 million level, up slightly from the prior month.
From Europe, economic sentiment data due on Tuesday is likely to show further deterioration after financing problems worsened for Italy, Spain and even Germany over the past week. Fears of a sovereign ratings downgrade for France spread as its banking problems festered. Consumer sentiment is forecast to decline to minus 21 from minus 19.9 in October - which usually would portend further economic shrinkage ahead.
As long as European leaders delay in delivering a fiscal union that can rescue the common currency, financial markets will remain in the driving seat and the growth picture shaky.
"The world is struggling along, with downside risks from a bust-up of the euro-zone, or Greece, Italy and Spain leaving. It might be that Europe just runs out of time to fix its problems," said Paul Ashworth, economist at Capital Economics.
We have stuffed ourselves with turkey, and even before the leftovers are gone, it's time for a reality check.?
American men and women, on average, report weighing nearly 20 pounds (9 kilograms) more than they did in 1990, according to the annual Health and Healthcare survey conducted by Gallup in early November.
Men, on average, said they weighed 196 pounds (89 kilograms), while women, said they weighed 160 pounds (73 kilograms), according to a report on Gallup's website.
This puts us further from our ideal weights, which have also gone up: Men reported wanting to weigh 181 pounds (82 kilograms) and women see themselves at 138 pounds (63 kilograms), the survey of 1,012 adults indicated.
Our perceived ideal weight has increased along with our self-reported weight, but not as quickly. As a result, we have gotten further from our ideal weight over the past 20 years. For men, who now say they'd like to weigh 181 pounds, that difference has climbed from 9 to 15 pounds (4 to 7 kilograms). For women, who say their ideal weight is 138 pounds, the gap has risen from 13 to 22 pounds (6 to 10 kilograms).
This year, 39 percent of American adults reported they are very or somewhat overweight.
However, it appears we may be cutting ourselves too much slack. Separate data collected by Gallup and the company Healthways indicate that nearly 62 percent of Americans are overweight or obese based on their body mass index, a ratio of height and weight that gauges a person's level of body fat.
The U.S. Centers for Disease Control and Prevention links being overweight or obese with increasing levels of risk for coronary heart disease, Type 2 diabetes, certain cancers, high blood pressure, stroke and a number of other potentially serious health conditions.
You can follow LiveSciencesenior writer Wynne Parry on Twitter @Wynne_Parry.?Follow LiveScience for the latest in science news and discoveries on Twitter @livescience?and on Facebook.
CHICAGO (AP) ? John Schneider's work is all shouts and hand gestures. Get him on the phone and you'll strain to hear over the barks and cries of his fellow commodities traders in the corn pit at the Chicago Board of Trade.
The board's art deco building has long been an icon, and Schneider compared it at its founding in 1848 to a business like Groupon Inc. today ? operating on the economic frontier and pushing Chicago toward its future. Even as the shouts and gestures gave way to the bits and bytes of modern electronic trading, the Board of Trade and the city's other exchanges had a strong hand in making Chicago the financial center it's become.
But two exchanges, the CME Group Inc., which owns the Board of Trade and the Chicago Mercantile Exchange, and CBOE Holdings Inc., have threatened to leave the state unless they're given significant tax breaks to make staying worth their while. They say a big tax increase enacted this year and what they say are inequalities in the tax code have forced them to pay an outsize share of the state's corporate income taxes.
Lawmakers are returning to Springfield on Tuesday to consider special deals to cut the exchanges' tax bills, and the price tag for the financially-strapped state could reach well into the hundreds of millions of dollars. They must decide whether Illinois, where the unemployment rate is just over 10 percent, can afford to give in to exchanges that may no longer need Chicago as much as it needs them, or whether to take their chances that the companies will stay put without new deals.
While some question whether the exchanges would really move, in Schneider's mind, not trying to accommodate them would send a signal that Illinois is no longer the kind of place where the exchanges were born.
"If you can't hold onto a 150-year-old institution, then what's next?" asked Schneider, who works for League Trading. "Would stuff like this stifle companies like Groupon from starting?"
The exchanges are just two of the major Illinois-based businesses that have threatened to walk away from the state this year, demanding tax breaks and other perks. The legislative package also includes breaks for Sears Holding Corp., which has warned of moving its headquarters out of the Chicago suburbs.
The exchanges say it's unfair for the state to tax their trades as if they all happen in Illinois, when the buyers and sellers in electronic trades are often somewhere else. CME Group says it pays close to six percent of all corporate income taxes in the state. It doesn't provide a dollar figure, but the state collected a total of $1.67 billion in 2010; six percent of that would be about $100 million.
The proposed tax package "reflects the global nature of the financial markets and puts the exchanges on more equal footing with other Illinois companies and other U.S. exchanges," CME chief financial officer Jamie Parisi testified at a hearing in Springfield. Neither CME nor CBOE would comment directly for this story.
CME employs about 2,000 people in Chicago while CBOE has about 500 workers in the city.
The companies are pressuring a vulnerable state. Illinois raised its corporate tax rate in January from 4.8 percent to 7 percent to help deal with a massive budget deficit.
That multi-billion dollar means Illinois can't afford to cut any company a break, University of Illinois economist Fred Giertz said, but the tax increase leaves the politicians in a bad position to make a stand.
"I think people who voted for the tax increase also want to not be blamed for having these services and industries leave the state," Giertz said. "You have to stand up at some point (and say no), but it's not easy to do that."
It isn't clear whether the exchanges would really leave. Moving is expensive and disruptive and experts say companies often threaten to pack up for a new location with little intention of doing so, just to force government to come through with deals to keep them in place.
A spokesman for a union that represents thousands of government workers in Illinois said the companies are taking advantage of Illinois, and that lawmakers should find other solutions.
"Rather than holding taxpayers over a barrel and demanding giveaways for themselves, responsible employers that feel they are taxed inordinately should blame the two-thirds of Illinois corporations that pay no state income taxes at all," said Anders Lindall, a spokesman for the American Federation of State, County and Municipal Employees, referring to a figure often cited by some of the biggest backers of the tax breaks, including state Sen. President John Cullerton.
But if any businesses could easily relocate, it might be the exchanges. Their electronic trades could be conducted almost anywhere. There are no assembly lines to move, no raw materials they need to be near. "You can process orders virtually any place," Giertz said.
Indiana reportedly has extended an offer to the CME Group, hoping to lure it away. Officials with the CBOE ? a smaller exchange that says it paid $13.7 million in state taxes in 2010 ? have said they've talked to several states.
Legislators are still working on the tax break package, but last week the governor's office put the cost to the state on one version at $850 million a year, starting three years after passage. The package has grown to include provisions for Sears, low-income taxpayers and others to broaden support for it.
The Board of Trade was founded in 1848, the same year the Illinois and Michigan Canal opened, linking the Chicago River and Lake Michigan with the Mississippi river. The farms to the west flooded the city with crops and livestock destined for the East Coast and beyond, and the exchange smoothed the buying and selling through futures contracts that allow commodity prices to be locked in in advance, avoiding price swings.
Along with that trade, the city quickly grew, from about 30,000 people to roughly 300,000 in two decades. "The Board of Trade became the commodities trading center of the world, basically," said Carl Smith, a professor of American Studies at Northwestern University.
The Mercantile Exchange began in 1898 as a Board of Trade spinoff, the Chicago Butter and Egg Board. Similarly, the Board of Trade opened the Chicago Board Options Exchange, or CBOE, for the trading of stock options in 1973.
The exchanges mean jobs in Chicago, with the area around the Board of Trade full of financial firms and restaurants that cater to the traders. But there's also a symbolic and psychological aspect to the exchanges having called Chicago home for so long.
"CME's position is that, given the choice, it would prefer to stay in Illinois," said John Carpenter, senior vice president of the Chicagoland Chamber of Commerce. "Chicago is a great place to do business for them."
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Associated Press writer Tammy Webber contributed to this report.
A shopper in Los Angeles pepper-sprayed her competition for an Xbox and scuffles broke out elsewhere around the U.S. as bargain-hunters crowded stores in an earlier-than-usual start to the madness known as Black Friday.
For the first time, chains such as Target, Best Buy and Kohl's opened their doors at midnight on the most anticipated shopping day of the year. Toys R Us opened for the second straight year on Thanksgiving itself. And some shoppers arrived with sharp elbows.
Near Muskegon, Mich., a teenage girl was knocked down and stepped on several times after getting caught in the rush to a sale in the electronics department at a Walmart. She suffered minor injuries.
On Thanksgiving night, a Walmart in Los Angeles brought out a crate of discounted Xboxes, and as a crowd waited for the video game players to be unwrapped, a woman fired pepper spray at the other shoppers "in order to get an advantage," police said.
Ten people suffered cuts and bruises in the chaos, and 10 others had minor injuries from the spray, authorities said. The woman got away in the confusion, and it was not immediately clear whether she got an Xbox.
On Friday morning, police said, two women were injured and a man was charged after a fight broke out at an upstate New York Walmart. A man was arrested in a scuffle at a jewelry counter at a Walmart in Kissimmee, Fla.
Wal-Mart Stores, the nation's biggest retailer, has taken steps in recent years to control its Black Friday crowds following the 2008 death of one of its workers in a stampede of shoppers. This year, it staggered its door-buster deals instead of offering them all at once.
Wal-Mart spokesman Greg Rossiter said Black Friday was safe at most of its nearly 4,000 U.S., but there were "a few unfortunate incidents."
The incidents were attributed to two converging Black Friday trends: Crowds are getting bigger as stores open earlier and stay open later. At the same time, cash-strapped shoppers are competing for deals on a small number of gifts that everybody wants ? tablet computers, TVs and game consoles like Xbox, Nintendo 3S and Wii.
That's a shift from years past, when there was a wider range of must-have items.
"The more the people, the more the occurrences," said Marshal Cohen, chief industry analyst with market research firm The NPD Group.
A record number of shoppers are expected this weekend to take advantage of discounts of up to 70 percent. For three days starting on Black Friday, 152 million people are expected to shop, either online or in stores, an increase of about 10 percent from last year, according to the National Retail Federation.
Thanksgiving weekend, particularly Black Friday, is huge for retailers. Over the past six years, Black Friday was the biggest sales day of the year, and it is expected to keep that crown this year, though shoppers seem to be procrastinating more every year, and the fate of the holiday season is increasingly coming down to the last few days before Christmas.
Last year, the Thanksgiving shopping weekend accounted for 12.1 percent of overall holiday sales, according to ShopperTrak, a research firm. Black Friday made up about half of that.
ShopperTrak is expected to release sales data on Saturday on how Black Friday fared, but a better picture will emerge when major retailers report their November sales figures next Thursday.
In addition to opening earlier than usual this year, some stores offered to match their competitors' prices, rolled out layaway programs or offered more door-buster deals than last year.
Emmanuel Merced and his brother showed up at a Best Buy in New York at 3 p.m. on Wednesday so they could be the first in line when it opened at midnight Thursday to grab a Sharp 42-inch TV for $199.99, a PlayStation 3 with games for $199.99 and wireless headphones for $30.
Merced said he likes camping out for Black Friday and figured he saved 50 percent.
"I like the experience of it," said Merced, who plans to spend $3,000 to $4,000 on gifts this season.
To be sure, not every place was full on Black Friday. With so many major stores opening at midnight, many people stayed up late and shopped early. Then there were those who stuck to their normal routine of going to stores that opened later Friday morning. That left a lull in the hours just before and after daybreak.
At a Target on Chicago's North Side, crowds were light four hours after the store opened at midnight. And door-buster deals, including the typically quick-to-sell-out TVs and game systems, remained piled up in their boxes. Shoppers pushed carts through mostly empty aisles while thumbing through circulars, and employees in Santa hats roamed the store. There was no Christmas music ? or any music ? playing.
Rebecca Carter, a graduate assistant, began Black Friday shopping at 11 p.m. on Thursday and left Target around 4 a.m. carrying a bag full of pillows. Carter said the crowds were noticeably lighter this year as she and a friend picked up a 32-inch TV for $180 and a laptop for $198, along with toys and pajamas.
"It's quiet," she said. "It was shocking."
Melody Snyder of Vancouver, Wash., had braced herself for anarchy when she got to Walmart at 6 a.m. but was pleasantly surprised when she pulled into the parking lot.
"I got here and thought, `Where is everyone?'" said Snyder, who found some Barbies and other toys sold out but was still able to find gifts for her three kids.
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Retail writers Mae Anderson and Anne D'Innocenzio are in New York. Sarah Skidmore in Vancouver, Wash., Christina Rexrode in Cary, N.C., Ashley Heher in Chicago and Tamara Lush in St. Petersburg, Fla., contributed to this report.
Of all the North American directors to emerge in the 1970s, few have been as consistent -- and consistently fascinating -- as Canadian auteur David Cronenberg, the man whose imagination unleashed Videodrome, The Fly, Crash and A History of Violence (to name just a few). While his contemporaries may have courted bigger commercial and critical success, Cronenberg's thematic vision -- whether he's working in genre horror, literary adaptation, or his recent gangster cycle -- has remained singular and endlessly rewarding.
Cronenberg's new film, A Dangerous Method, represents something of an origin piece in his universe, returning to a pivotal moment in the birth of modern psychiatry that predicts the obsession with repressed sexuality, violence and the subconscious so prevalent in his work. Sexual freak du jour Michael Fassbender stars as the young Carl Jung, a doctor whose relationship with his noted mentor, Sigmund Freud (Viggo Mortensen), is complicated via an emotional tryst with a deranged patient -- and aspiring headshrinker -- Sabina Spielrein, performed with acrobatic terror by Keira Knightley. "I sought to make an elegant film that trades on emotional horror," says Cronenberg. Be afraid, period drama. Be very afraid. We met the director in Los Angeles recently, where he shared his thoughts on psychiatry, hysteria, the connections between his movies... and cigars.
I've been immersing myself in some of your films over the last few days, and here you are.
David Cronenberg: Well you seem to be stable still, so it probably hasn't done too much damage.
I grew up watching them, so the damage has been done.
[Laughs] Oh.
You were saying around the time of Spider that you weren't interested in a textbook study of Freud, and this certainly isn't one, either. What was the angle that enticed you on A Dangerous Method?
Well, friends of mine have pointed out that the first film I ever did was a seven minute short called Transfer, and it was about a psychiatrist and a patient. That was the very first film I wrote and made. So I've come to think of [A Dangerous Method] as this invention of a brand new relationship that never existed before; that is, the relationship between an analyst and a patient. We think of it now as being almost as primordial as a family relationship, but actually it's quite odd, you know: you go to someone that you've never met, a stranger, and you tell him your most intimate, embarrassing secrets and he has a sort of clinical distance on it and then you gradually begin to project on to him the emotional connections you have to other people. It's quite odd. And it's quite interesting. And it's become a kind of basic human relationship, but it never existed before -- and in some countries it still doesn't, but in the West, certainly. So I think that's part of the core of it; that is to say that Freud has influenced us in ways that are quite unusual and that we aren't completely aware of. I don't think we're remotely finished with Freud.
When I read [screenwriter Christopher Hampton's] play, it felt like the creation of modern relationships, of modernity. That these two men, these professional men, very highly respected and living in a very relatively repressed and controlled era -- which is also a fascination for me, that era in Central Europe just before the First World War -- would talk about the most intimate things. You see that in the movie. They talk about bodily fluids and orifices and organs and erotic dreams and sexuality in a way that men of that era, especially of that class, would never talk to each other about; it was just inappropriate and not done. Now, you know, we accept this, but at the time it was unheard of -- really quite earthshaking and revolutionary. And then, when Sabina appeared, she did the same thing as a woman, speaking to men, also about her eroticism and her masochism. Because they were their own first subjects, that was the thing that was also intriguing; that's why I have Sabina observing herself in the mirror while she's having this S&M sex, because she would have observed herself. They had no other subjects to begin with. When Freud wrote about the interpretation of dreams it was his dreams that he was using as the subject matter because that's all he had at the time. They were just starting off and inventing this thing, psychoanalysis. All of that was intriguing to me.
They were pioneers, out on the edge and experimenting on themselves -- like many of your other scientist protagonists; Seth Brundle being perhaps the most famous example.
Yeah. I mean, it's obvious that I'm interested in characters whose intellect leads them to places that are perhaps not socially acceptable, or to new places. I've come to think that, for example, psychoanalysis and art do similar things in some ways. I don't really think of art as therapy -- that's not what I mean. What I mean is that the psychoanalyst and the artist, we're presented an official version of reality that the culture kind of generates, but we say, "Okay, that's good for as far as it goes, but what's really going on under the hood?" And we dive underneath, we go underneath and we find the springs and levers; we find the hidden motivations, the dark things that people don't talk about or don't understand, and we look for that and try and bring it out. So I think that, in a way then, these scientists and doctors of mine are sort of circuits for artists or just, you know, for my projection -- of what I think I'm doing.
It's interesting that you bring up Transfer, because the relationship in the film -- like that in A Dangerous Method -- is a patient stalking their psychiatrist.
Basically the only relationship he's had, that means anything to him, is the relationship he has to his psychoanalyst, yeah.
Was there a sense of having come full circle in your career when people reminded you of it?
Well, as I say, until a close friend had pointed it out, I'd forgotten about that. I wasn't even thinking about it. And this is something that comes up a lot, but basically I don't really think about my other movies when I'm making movies; they're completely irrelevant to me -- to this movie. Whatever movie I'm making, the only thing that I bring with me from the other movies is my confidence in the craft, you know -- I know how to make movies; I've done those things -- but I don't think about them thematically, or how they connect thematically; that actually, creatively doesn't give me anything in order to make this movie, you understand what I mean?
Sure.
After the fact you can step back and say, "Wow, that's an interesting parallel." For example, I can say this. I can say Freud, okay: In one way, what Freud did was to insist on the reality of the human body. At a time when the body was covered up and cloaked and people wore stiff rigid collars and women wore corsets, he was talking about orifices and bodily fluids and the sexual abuse of children and incest and stuff, and so that connects him to me and my other movies -- because for me, I've said in the past, the first fact of human existence is the human body. But when I was making the movie, when I was attracted to it, that thought was not anywhere in my mind. So that's me sort of stepping back and being an analyst of my own work -- which comes out when people ask, really. It's not something that I automatically just do for fun. But it also is not something that I bring to the movie, you know; I don't really bring that to the movie, because really, creatively, what would that give me? It doesn't really give me anything. I get excited about this movie for itself, and the research involved into these characters. That's what motivates me and excites me.
It is curious how things do recur in your films. For example, when Sabina is playing with her food in A Dangerous Method, it reminded me so much of Judy Davis kneading the typewriter flesh in Naked Lunch.
Oh yes. But I absolutely never thought of it. I haven't really looked at Naked Lunch since I made it, so I don't even 100 per cent remember it, you know. I don't deny that those things are there, and I don't deny that they're interesting, but as I say, a lot of people think that I go into a movie with a checklist of things that must be there for me to make the movie, and they're all connected to my other movies. But I absolutely don't. It's all intuitive and instinctive.
Sometimes the best part about a getting a hot new gadget isn't actually playing with the device. For inveterate hardware hackers, it's taking the thing apart. The gadget teardown experts at iFixit just received the newly released Nook Tablet, and immediately began to disassemble it. But much like Apple's iPhone 4 and 4S models, the Nook Tablet is held together with an "insidious" set of screws that are resistant to classic screwdriver configurations.
MEKNES, Morocco (Reuters) ? Morocco will not follow other North African states in handing power to Islamists when it votes in an election this week because it has a mature democracy, a leading member of a liberal alliance contesting the vote told Reuters.
A moderate Islamist party says it believes it can win the November 25 parliamentary election, buoyed by the resurgence of Islamists in the wake of the "Arab Spring" uprisings in Tunisia, Egypt and Libya.
The Islamists' main challenger is the newly-formed Coalition for Democracy which is centered around secularist parties with ties to the court of Morocco's ruler King Mohammed.
"Morocco is different. It is not Tunisia, nor is it Libya or Egypt," Salaheddine Mezouar, Morocco's Finance and Economy Minister who is also one of the leaders of the coalition, said in an interview.
"Here in Morocco we have a plurality. Morocco has never known one-party rule. Moroccan political parties have practiced democracy and are well-educated, which makes an outcome of that kind (an Islamist victory) improbable," he said.
"To my knowledge, the Islamists in Morocco are very far from winning first place, but at the end of the day it is the ballot boxes which will decide."
The election is a test of the king's commitment to respond to the uprisings around the region by moving his kingdom closer to democracy and ceding some of his powers to elected officials.
The vote will almost certainly remove the present government, which many Moroccans associate with corruption and nepotism. Whoever takes over will nevertheless be no less loyal to the monarch.
At issue is whether the election will hand power to the Coalition for Democracy, whose leaders are younger and less tainted by governing than many of those currently in power, or to the opposition Islamist Justice and Development Party (PJD).
Islamist party officials have accused their opponents of trying to keep them out of power by bribing voters, a phenomenon that has blighted previous elections.
Mezouar, whose National Rally of Independents is one of eight parties making up the liberal coalition, said it was time for a break with the murky electoral practices of the past.
"We want a new Morocco with competent elected officials," he said. "These practices have always existed in all Morocco's political parties, but it is not encouraged by the parties. These are individual practices, by certain elected officials."
"We have been firm in the coalition: anyone found carrying out these practices will be expelled."
ELECTION TURNOUT
The biggest challenge facing the palace in the election is the risk that voters, disillusioned with a contest that many do not believe will bring real change to their lives, will stay at home on polling day, analysts say.
A protest movement, inspired by the "Arab Spring" uprisings, is urging people to boycott the election, saying it is not truly democratic.
"We do not have any problems with those who call for a boycott," said Mezouar in the city of Meknes, about 150 km east of the capital, where he was on the campaign trail.
"But the problem that arises if you propose a boycott is, what's the alternative? Should we leave the country without constitutional institutions? ... We are betting on a big turnout in this election."
If the Coalition for Democracy wins enough seats to form the next government, it will have to re-balance public finances.
The outgoing government, in an effort to prevent "Arab Spring" unrest spreading to Morocco, spent heavily on increasing public wages and subsidizing staple goods.
That leaves little for major infrastructure projects that are planned to create jobs and stimulate growth.
Mezouar said if his alliance wins it will promote partnerships with the private sector to get big projects off the ground and raise tax revenue to curb the budget deficit.
He said the coalition would tackle the hugely inefficient subsidy system by taking half of the cash devoted to it and using that money instead for targeted assistance for the poorest people. Some state assets could also be sold.
"Our program does not rule out privatization. We say that to subsidize investment funds, it is possible to sell a part of the state's shares in certain enterprises," said Mezouar.
(Writing by Christian Lowe; Editing by Peter Graff)
British actor Steve Coogan arrives to testify at the Leveson inquiry at the Royal Courts of Justice in central London, Tuesday, Nov. 22, 2011. The Leveson inquiry is Britain's media ethics probe that was set up in the wake of the scandal over phone hacking at Rupert Murdoch's News of the World, which was shut in July. (AP Photo/Lefteris Pitarakis)
British actor Steve Coogan arrives to testify at the Leveson inquiry at the Royal Courts of Justice in central London, Tuesday, Nov. 22, 2011. The Leveson inquiry is Britain's media ethics probe that was set up in the wake of the scandal over phone hacking at Rupert Murdoch's News of the World, which was shut in July. (AP Photo/Lefteris Pitarakis)
British actor Steve Coogan arrives to testify at the Leveson inquiry at the Royal Courts of Justice in central London, Tuesday, Nov. 22, 2011. The Leveson inquiry is Britain's media ethics probe that was set up in the wake of the scandal over phone hacking at Rupert Murdoch's News of the World, which was shut in July. (AP Photo/Lefteris Pitarakis)
Garry Flitcroft, former English Premier League soccer player , arrives to testify at the Leveson inquiry at the Royal Courts of Justice in central London, Tuesday, Nov. 22, 2011. The Leveson inquiry is Britain's media ethics probe that was set up in the wake of the scandal over phone hacking at Rupert Murdoch's News of the World, which was shut in July . (AP Photo/Lefteris Pitarakis)
LONDON (AP) ? Elle Macpherson fired her business adviser for leaking secrets when journalists were actually getting juicy details about the supermodel by hacking into her phone, the former aide told a British inquiry into media ethics Tuesday.
In testimony which illuminated the human costs of the illegal practice, Mary-Ellen Field described how she lost both her job for Macpherson and one at an advisory firm because of the unfounded suspicions ? a double-blow that was all the more serious because she was in poor health.
"It had a very serious effect," she told the inquiry. "I had become ill and was falling down all the time." She didn't identify her illness.
Field said her relationship with Macpherson was once close, but it fell apart after the model's intimate secrets began appearing in the press in 2005. Macpherson became convinced that Field, a fellow Australian, was an alcoholic and ordered her to go to an American rehabilitation clinic.
Field said she was shocked by the allegations she was a drunk who'd been blabbing about her employer, but went along with Macpherson's recommendation because she needed her job.
"I have a severely disabled child who can never look after himself, so walking away from a high-paying position is not a good idea," Field said.
The rehab was grueling ? she described it as being "like one of those CIA renditions, except they don't put you in chains" ? but it didn't help the situation.
Even though staff at the clinic said Field was not an alcoholic, Macpherson fired her anyway, and Field lost her job at her firm shortly afterward. She told the inquiry there was no doubt the sacking was the result of what happened with Macpherson.
Although it has since emerged that the media leaks were the result of phone hacking by the News of the World tabloid, not any indiscretions, Field said she has not heard from Macpherson in years. Macpherson's office did not respond to emails sent by The Associated Press seeking comment.
Field was one of several victims of press intrusion testifying Tuesday at Britain's Royal Courts of Justice. The inquiry, headed by Lord Justice Brian Leveson, was set up by Prime Minister David Cameron after the scandal over phone hacking and other underhanded tactics used at the News of the World, which was closed in July amid allegations of widespread criminality. The inquiry plans to issue a report next year and could recommend major changes to the way the media in Britain are regulated.
Soccer player Garry Flitcroft told of his family's harassment by the media after the failure of a judicial bid to block news of his affair, saying that at one point journalists used a helicopter to track his movements.
Flitcroft said journalists "wanted to make a statement to me: 'Never take on the press again.'"
Margaret Watson, whose daughter Diane was stabbed to death at her Scottish school two decades ago, gave emotional evidence about the way in which her child's memory was smeared in the press. She demanded that English libel laws be extended to cover those who have passed away.
"Just because a person's died, their reputation shouldn't die with them," she said.
British comedian Steve Coogan also testified, claiming that Andy Coulson ? who later went on to become British Prime Minister David Cameron's top media aide ? had eavesdropped on a phone conversation he was having with a woman in a bid to trick him into making indiscretions.
The parents of murdered British schoolgirl Milly Dowler and film star Hugh Grant were the first victims to testify to the panel on Monday, with Grant being particularly scathing about the Mail on Sunday tabloid, which he suggested had hacked his phone.
The Daily Mail called Grant's allegations "mendacious smears driven by his hatred of the media," but that response in turn sparked outrage, with lawyers at the inquiry saying it smacked of an attempt to intimidate witnesses.
David Sherborne, who represents victims of media intrusion at the inquiry, said his clients feared "the sort of intimidatory tactics that we've seen in the press this morning."
Lawyer Jonathan Caplan defended The Mail, saying the paper's comments were "a response to the fact that (Grant) was commenting freely that there was not a substratum of evidence" to support his allegation.
Leveson had limited sympathy for the Mail's argument, noting that while the paper had defended itself, it had also accused Grant of lying under oath.
"The real issue is whether it's appropriate to go from the defensive to the offensive in that way," Leveson said. He added later: "I would be unhappy if it was felt that the best form of defense was always attack."
In this Nov. 14, 2011 image released by ABC, TV Personality Rob Kardashian, right, and his partner Cheryl Burke perform on the celebrity dance competition series "Dancing with the Stars," in Los Angeles. (AP Photo/ABC, Adam Taylor)
In this Nov. 14, 2011 image released by ABC, TV Personality Rob Kardashian, right, and his partner Cheryl Burke perform on the celebrity dance competition series "Dancing with the Stars," in Los Angeles. (AP Photo/ABC, Adam Taylor)
FILE - In this Nov. 14, 2011 file image released by ABC, war veteran J.R. Martinez, left, and his partner Karina Smirnoff perform on the celebrity dance competition series "Dancing with the Stars," in Los Angeles. Two routines stand between the three ?Dancing With the Stars? finalists and the show's disco-ball trophy. Reality star Rob Kardashian, TV personality Ricki Lake and actor and Army veteran J.R. Martinez will each perform two numbers on Monday's final dance-off. A new champion will be named Tuesday. (AP Photo/ABC, Adam Taylor)
FILE - In this Nov. 14, 2011 file image released by ABC, Ricki Lake, left, and her partner Derek Hough perform on the celebrity dance competition series "Dancing with the Stars," in Los Angeles. Two routines stand between the three ?Dancing With the Stars? finalists and the show's disco-ball trophy. Reality star Rob Kardashian, TV personality Ricki Lake and actor and Army veteran J.R. Martinez will each perform two numbers on Monday's final dance-off. A new champion will be named Tuesday. (AP Photo/ABC, Adam Taylor)
LOS ANGELES (AP) ? No one has the mirrorball in the bag.
The glittery "Dancing With the Stars" trophy will be awarded during Tuesday's season finale, and any one of the three finalists ? Rob Kardashian, Ricki Lake and J.R. Martinez ? could easily waltz away with it.
Kardashian, 24, comes into the final episode in first place. The reality star has shown steady development throughout the season, and he and professional partner Cheryl Burke dazzled on the penultimate dance-off with an elegant waltz and a rip-roaring, swing-inspired freestyle routine that judges rewarded with a perfect score.
"I couldn't have asked for a better ending of the season," Kardashian said Monday. "We got our first perfect score. We're in first place. We did it with the most crucial dance, which is the freestyle. It's just surreal and I still can't even believe it."
Lake and Martinez, who have each topped the judges' leaderboard throughout the 10-week competition, are tied for second place.
Lake said she's pleased with what she's accomplished on the show, regardless of the final outcome. She earned high scores all season, dropped more than 25 pounds and performed some impressive dance moves.
"I've come way further than I ever thought or anyone else thought, so, I don't expect to win," the 43-year-old TV personality said. "I'm just happy to be among these two other guys. J.R. and Rob really have proven themselves. They're amazing people and I'm just happy to be one of them."
Lake's professional partner, Derek Hough, said they've had "a winning season."
"I feel like we can walk away (Tuesday), win or lose, and say, 'Yeah, we won,'" he said.
Martinez and partner Karina Smirnoff are happy about the tricky stunts they pulled off in their freestyle routine ? which earned a perfect score ? but they'll be even happier if they win the trophy Tuesday.
"I think we have a great shot at it," said Martinez, 28, an actor and Iraq war veteran. "It would be an amazing thing. It'd be her first mirrorball trophy, which she deserves, and it would be my first, of course. We both want to win it for each other."
Smirnoff, who has been on the hit ABC show for 10 seasons, said taking the title would be like "a perfect ending to a perfect story."
"With everything we went through... it's like this mirrorball would justify everything," she said. "No matter what happens, I feel like it has been such a fulfilling experience overall. But the mirrorball trophy would make it that much better. It's the truth."
The three couples will perform their favorite dance of the season for another score from the judges before the third-place finalists are eliminated. The remaining two pairs will compete in one final routine for the season 13 title.
Viewer votes count for half of each contestant's overall score, but the last chance to cast votes was Monday.
The two-hour season finale is also set to feature music by Lady Antebellum and is expected to include appearances by this season's former contestants: TV personalities Nancy Grace and Carson Kressley, reality star Kristin Cavallari, actors David Arquette and Elisabetta Canalis, singer Chynna Phillips, activist Chaz Bono, basketball player Metta World Peace and soccer star Hope Solo.
___
ABC is owned by The Walt Disney Co.
___
Online:
http://abc.go.com/shows/dancing-with-the-stars
___
AP Entertainment Writer Sandy Cohen can be reached at www.twitter.com/APSandy .
JCI online early table of contents: Nov. 21, 2011Public release date: 21-Nov-2011 [ | E-mail | Share ]
Contact: Karen Honey press_releases@the-jci.org 734-546-5242 Journal of Clinical Investigation
EDITOR'S PICK: Boosting the aged immune response to flu virus
As people age, their immune system becomes less robust. This makes them more susceptible to serious and frequently life-threatening infections with viruses that affect the respiratory tract such as influenza A virus (IAV). Stanley Perlman and colleagues, at the University of Iowa, Iowa City, have now identified a new immune system defect in aged mice that makes them more susceptible than young mice to developing severe clinical disease upon infection with respiratory viruses such as IAV. Importantly, they were able to reverse the defect by inhibiting the immune molecule PGD2. Perlman and colleagues therefore suggest that inhibition of PGD2 could provide a way to improve clinical outcomes in older patients with severe respiratory viral infections and perhaps more importantly enhance the efficacy of flu vaccines in the elderly.
In an accompanying commentary, Thomas Braciale and Taeg Kim, at the University of Virginia, Charlottesville, discuss in more detail the clinical significance of the work of Perlman and colleagues.
TITLE: Age-related increases in PGD2 expression impair respiratory DC migration, resulting in diminished T cell responses upon respiratory virus infection in mice
AUTHOR CONTACT:
Stanley Perlman
University of Iowa, Iowa City, Iowa, USA.
Phone: 319-335-8549; Fax: 319-335-9006; E-mail: Stanley-perlman@uiowa.edu.
View this article at: http://www.jci.org/articles/view/59777?key=58c21b72794ae3c4465b
ACCOMPANYING COMMENTARY
TITLE: Slowing down with age: lung DCs do it too
AUTHOR CONTACT:
Thomas J. Braciale
University of Virginia, Charlottesville, Virginia, USA.
Phone: 434-924-1219; Fax: 434-924-1221; E-mail: tjb2r@virginia.edu.
View this article at: http://www.jci.org/articles/view/61367?key=d308c58ebf42286ad3a5
EDITOR'S PICK: BRAF addiction of thyroid cancers makes them therapeutically vulnerable
Papillary carcinoma is the most common form of thyroid cancer. Approximately one quarter of these carcinomas have mutations in the BRAF gene. The prevalence of such mutations is even greater in high-grade carcinomas, particularly those that are refractory to standard treatment, which is radioactive iodine (RAI). A team of researchers led by James Fagin, at Memorial Sloan-Kettering Cancer Center, New York, has now identified a way to potentially exploit the expression of BRAF by such cancers for therapeutic purposes.
Despite the prevalence of BRAF mutations in papillary carcinoma it has remained unclear how dependent thyroid cancers are on BRAF expression. Fagin and colleagues first showed that thyroid tumors in mice expressing one of the most commonly detected BRAF mutations in human papillary thyroid carcinomas were exquisitely dependent on BRAF for viability. Of therapeutic significance, treating thyroid tumorbearing mice with drugs that inhibited the BRAF signaling pathway rendered the tumor cells susceptible to a therapeutic dose of RAI. Fagin and colleagues therefore suggest that their data provide rationale for clinical trials testing whether such drugs can restore the efficacy of RAI therapy in patients with papillary thyroid carcinomas expressing BRAF mutations.
TITLE: Small-molecule MAPK inhibitors restore radioiodine incorporation in mouse thyroid cancers with conditional BRAF activation
AUTHOR CONTACT:
James A. Fagin
Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Phone: 646-888-2136; Fax: 646-422-0890; E-mail: faginj@mskcc.org.
View this article at: http://www.jci.org/articles/view/46382?key=428ffb7aa30c6c74a9ef
EDITOR'S PICK: Expanding treatment options for Cushing disease
Cushing disease is a hormone disorder that causes a diverse array of symptoms, including fat accumulation, high blood pressure, osteoporosis, muscle wasting, and ultimately death. It is caused by a tumor in the anterior pituitary gland that results in the secretion of excess amounts of adrenocorticotropic hormone (ACTH). Treatment options are essentially limited to surgical resection. However, tumors commonly recur, meaning that new treatment options are needed. A team of researchers, led by Shlomo Melmed, at Cedars-Sinai Medical Center, Los Angeles, has now identified a potential new therapeutic target the protein EGFR, which is the target of a drug used to treat some patients with nonsmall cell lung cancer (gefitinib). As discussed by Melmed and colleagues in their paper, as well as Frederic Wondisford, at Johns Hopkins University School of Medicine, Baltimore, in an accompanying commentary, the data generated in human, canine, and mouse models provide strong support to investigate the clinical effects of gefitinib in patients with Cushing disease.
TITLE: EGFR as a therapeutic target for human, canine, and mouse ACTH-secreting pituitary adenomas
AUTHOR CONTACT:
Shlomo Melmed
Cedars-Sinai Medical Center, Los Angeles, California, USA.
Phone: 310-423-4691; Fax: 310-423-0119; E-mail: Melmed@csmc.edu.
View this article at: http://www.jci.org/articles/view/60417?key=ea692326753d599db723
ACCOMPANYING COMMENTARY
TITLE: A new medical therapy for Cushing disease?
AUTHOR CONTACT:
Fredric E. Wondisford
Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Phone: 410-502-5761; Fax 410-502-5779; E-mail: fwondisford@jhmi.edu.
View this article at: http://www.jci.org/articles/view/61127?key=70bc5a72e9b76e5ee825
OTOLOGY: The proteins TMC1 and 2 key to sensing sound and gravity
Central to our ability to hear and to sense gravity is a cellular process known as mechanotransduction. Essential for this process is the opening of special channels in the surface membrane of inner ear hair cells. The molecular identity of these channels has eluded researchers despite intensive investigations over the years. But now, a team of researchers led by Andrew Griffith, at the National Institutes of Health, Rockville; and Jeffrey R. Holt, at Children's Hospital Boston, Boston has determined that in mice, the channel proteins TMC1 and TMC2 are necessary for inner ear hair cell mechanotransduction. These data are consistent with the fact that mutations in the TMC1 gene cause hearing loss in both humans and mice and provide new insight into the molecular mechanisms underlying the condition.
In an accompanying commentary, Xi Lin, at Emory University School of Medicine, Atlanta, discusses the importance of the findings of Griffith, Holt, and colleagues, and highlights the future utility of the mice they generated during their studies.
AUTHOR CONTACT:
Andrew J. Griffith
National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland, USA.
Phone: 301-402-2829; Fax: 301-402-7580; E-mail: griffita@nidcd.nih.gov.
Jeffrey R. Holt
Children's Hospital Boston, Boston, Massachusetts, USA.
Phone: 617-919-3574; Fax: 617-919-2771; E-mail: jeffrey.holt@childrens.harvard.edu.
MEDIA CONTACT
Robin Latham
National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland, USA.
Phone: 301-496-7243; E-mail: lathamr@nidcd.nih.gov.
View this article at: http://www.jci.org/articles/view/60405?key=4e596583c59e4453ef6c
ACCOMPANYING COMMENTARY
TITLE: Perception of sound and gravity by TMC1 and TMC2
AUTHOR CONTACT:
Xi Lin
Emory University School of Medicine, Atlanta, Georgia, USA.
Phone: 404-727-3723; Fax: 404-727-6356; E-mail address: xlin2@emory.edu.
View this article at: http://www.jci.org/articles/view/61167?key=2aa1292c2d54f036ffe6
CARDIOVASCULAR DISEASE: Visualizing the effectiveness of candidate anti-atherosclerotic approaches
Atherosclerosis is a disease of the major arterial blood vessels. It is one of the major causes of heart attack and stroke. An early event in the development of atherosclerosis is modification of the molecule LDL by oxidation. A team of researchers led by Yury Miller, at the University of California San Diego, La Jolla, has developed an approach to visualize the accumulation of oxidized LDL in zebrafish fed a diet high in cholesterol. Using their approach they were able to visualize the effects of treatment with an antioxidant it reversed the accumulation of oxidized LDL, as did switching the zebrafish to a diet low in cholesterol. Miller and colleagues therefore suggest that they have developed an efficient method of testing the potential effectiveness of dietary and/or other therapeutic antioxidant strategies under development as anti-atherosclerotic agents in humans.
TITLE: In vivo visualization and attenuation of oxidized lipid accumulation in hypercholesterolemic zebrafish
AUTHOR CONTACT:
Yury I. Miller
University of California, San Diego, La Jolla, California, USA.
Phone: 858-822-5771; Fax: 858-534-2005; E-mail: yumiller@ucsd.edu.
View this article at: http://www.jci.org/articles/view/57755?key=7f775f5c0cc68a36cd06
NEUROLOGICAL DISEASE: Linking distinct genetic disorders together
Inclusion body myopathy with Paget disease of the bone and frontotemporal dementia (IBMPFD) is a multisystem degenerative disorder characterized by progressive muscle weakness that is often accompanied by bone weakening and/or frontotemporal dementia. A team of researchers led by Yi-Ping Hsueh, at Academia Sinica, Taiwan; and Ming-Jen Lee, at National Taiwan University Hospital, Taiwan has now identified a potential link between the mechanisms underlying the dementia seen in patients with IBMPFD and those causing the cognitive deficits observed in patients with neurofibromatosis type 1.
IBMPFD is an inherited disease caused by mutations in the VCP gene. Neurofibromatosis type 1 is caused by mutations in the NF1 gene. Hsueh, Lee, and colleagues found that the proteins templated by the VCP and NF1 genes (VCP and NF1) interact to control the formation of nerve cell structures critical for nerve cell communication (dendritic spines). IBMPFD- and neurofibromatosis type 1associated mutations that disrupted the VCP/NF1 interaction resulted in reduced dendritic spine density. Hsueh, Lee, and colleagues therefore suggest that the dementia seen in individuals with IBMPFD might be a result of defects in VCP regulated dendritic spine formation.
In an accompanying commentary, Conrad Weihl, at Washington University School of Medicine, Saint Louis, highlights the importance of the work of Hsueh, Lee, and colleagues to understanding the complex genetic interactions that can lead to different patients experiencing different symptoms even if they have the same underlying VCP or NF1 mutation.
TITLE: Valosin-containing protein and neurofibromin interact to regulate dendritic spine density
AUTHOR CONTACT:
Yi-Ping Hsueh
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
Phone: 886-2-27899311; Fax: 886-2-27826085; E-mail: yph@gate.sinica.edu.tw.
Ming-Jen Lee,
National Taiwan University Hospital, Taipei, Taiwan.
Phone: 886-2-23123456 ext. 65342; Fax: 886-2-23418395; E-mail: mjlee@ntu.edu.tw.
View this article at: http://www.jci.org/articles/view/45677?key=c4a822afbb932fcc0c27
ACCOMPANYING COMMENTARY
TITLE: Another VCP interactor: NF is enough
AUTHOR CONTACT:
Conrad C. Weihl
Washington University School of Medicine, Saint Louis, Missouri, USA.
Phone: 314-362-6981; Fax 314-362-4391; E-mail: weihlc@neuro.wustl.edu.
View this article at: http://www.jci.org/articles/view/61126?key=997b610235a30f5a867d
IMMUNOLOGY: Identification of new genetic defects underlying Herpes simplex encephalitis
Herpes simplex encephalitis (HSE) is a rare but severe condition caused primarily by infection of the brain and spinal cord with herpes simplex virus-1 (HSV-1), the same virus that causes cold sores. Even with treatment, the condition is often fatal, and survivors, affected children in particular, usually suffer long-term brain damage. In some children, genetic mutations that affect the immune system underlie their susceptibility to HSE. A team of researchers led by Vanessa Sancho-Shimizu, at Necker Hospital, France; and Jean-Laurent Casanova, at The Rockefeller University, New York has now identified two new mutations, this time in the gene TRIF, as the reason for two unrelated children being susceptible to HSE. Further analysis defined the molecular mechanism by which these mutations, both of which resulted in TRIF deficiency, impaired the immune system and made the children susceptible to the condition.
TITLE: Herpes simplex encephalitis in children with autosomal recessive and dominant TRIF deficiency
Jean-Laurent Casanova
The Rockefeller University, New York, New York, USA.
Phone: 212-327-7331; Fax: 212-327-7330; E-mail: casanova@rockefeller.edu.
View this article at: http://www.jci.org/articles/view/59259?key=e3042b370c4f05f59b12
HEPATOLOGY: The source of the liver cell uncovered
The liver has the remarkable ability to rapidly regenerate after tissue injury or partial resection. Many researchers are seeking to harness this ability to treat individuals with a wide range of liver diseases. However, in order to do this it is vital to know from what cell new liver cells (hepatocytes) arise in the adult. A team of researchers led by Holger Willenbring, at the University of California, San Francisco, has now generated a hepatocyte fate-tracing model that enabled them to demonstrate definitively in mice that hepatocytes themselves, and not specialized progenitor cells, are the source of new hepatocytes in the healthy liver and the predominant source of new liver cells in the acutely injured liver. As noted by Willenbring and colleagues, harnessing these cells for therapy will require knowing the signals that trigger their activation.
In an accompanying commentary, Klaus Kaetsner and Joshua Friedman, at the University of Pennsylvania, Philadelphia, discuss how the work of Willenbring and colleagues helps settle recent controversy regarding the origins of hepatocytes in adults.
TITLE: Fate tracing of mature hepatocytes in mouse liver homeostasis and regeneration
AUTHOR CONTACT:
Holger Willenbring
University of California at San Francisco, San Francisco, California, USA.
Phone: 415-476-2417; Fax: 415-514-2346; E-mail: willenbringh@stemcell.ucsf.edu.
View this article at: http://www.jci.org/articles/view/59261?key=969533400d3303d8af4c
ACCOMPANYING COMMENTARY
TITLE: On the origin of the liver
AUTHOR CONTACT:
Klaus Kaestner
University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Phone: 215-898-8759; Fax: 215-573-5892; E-mail: kaestner@mail.med.upenn.edu.
View this article at: http://www.jci.org/articles/view/59652?key=36cbd0c4abf88df63e89
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JCI online early table of contents: Nov. 21, 2011Public release date: 21-Nov-2011 [ | E-mail | Share ]
Contact: Karen Honey press_releases@the-jci.org 734-546-5242 Journal of Clinical Investigation
EDITOR'S PICK: Boosting the aged immune response to flu virus
As people age, their immune system becomes less robust. This makes them more susceptible to serious and frequently life-threatening infections with viruses that affect the respiratory tract such as influenza A virus (IAV). Stanley Perlman and colleagues, at the University of Iowa, Iowa City, have now identified a new immune system defect in aged mice that makes them more susceptible than young mice to developing severe clinical disease upon infection with respiratory viruses such as IAV. Importantly, they were able to reverse the defect by inhibiting the immune molecule PGD2. Perlman and colleagues therefore suggest that inhibition of PGD2 could provide a way to improve clinical outcomes in older patients with severe respiratory viral infections and perhaps more importantly enhance the efficacy of flu vaccines in the elderly.
In an accompanying commentary, Thomas Braciale and Taeg Kim, at the University of Virginia, Charlottesville, discuss in more detail the clinical significance of the work of Perlman and colleagues.
TITLE: Age-related increases in PGD2 expression impair respiratory DC migration, resulting in diminished T cell responses upon respiratory virus infection in mice
AUTHOR CONTACT:
Stanley Perlman
University of Iowa, Iowa City, Iowa, USA.
Phone: 319-335-8549; Fax: 319-335-9006; E-mail: Stanley-perlman@uiowa.edu.
View this article at: http://www.jci.org/articles/view/59777?key=58c21b72794ae3c4465b
ACCOMPANYING COMMENTARY
TITLE: Slowing down with age: lung DCs do it too
AUTHOR CONTACT:
Thomas J. Braciale
University of Virginia, Charlottesville, Virginia, USA.
Phone: 434-924-1219; Fax: 434-924-1221; E-mail: tjb2r@virginia.edu.
View this article at: http://www.jci.org/articles/view/61367?key=d308c58ebf42286ad3a5
EDITOR'S PICK: BRAF addiction of thyroid cancers makes them therapeutically vulnerable
Papillary carcinoma is the most common form of thyroid cancer. Approximately one quarter of these carcinomas have mutations in the BRAF gene. The prevalence of such mutations is even greater in high-grade carcinomas, particularly those that are refractory to standard treatment, which is radioactive iodine (RAI). A team of researchers led by James Fagin, at Memorial Sloan-Kettering Cancer Center, New York, has now identified a way to potentially exploit the expression of BRAF by such cancers for therapeutic purposes.
Despite the prevalence of BRAF mutations in papillary carcinoma it has remained unclear how dependent thyroid cancers are on BRAF expression. Fagin and colleagues first showed that thyroid tumors in mice expressing one of the most commonly detected BRAF mutations in human papillary thyroid carcinomas were exquisitely dependent on BRAF for viability. Of therapeutic significance, treating thyroid tumorbearing mice with drugs that inhibited the BRAF signaling pathway rendered the tumor cells susceptible to a therapeutic dose of RAI. Fagin and colleagues therefore suggest that their data provide rationale for clinical trials testing whether such drugs can restore the efficacy of RAI therapy in patients with papillary thyroid carcinomas expressing BRAF mutations.
TITLE: Small-molecule MAPK inhibitors restore radioiodine incorporation in mouse thyroid cancers with conditional BRAF activation
AUTHOR CONTACT:
James A. Fagin
Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Phone: 646-888-2136; Fax: 646-422-0890; E-mail: faginj@mskcc.org.
View this article at: http://www.jci.org/articles/view/46382?key=428ffb7aa30c6c74a9ef
EDITOR'S PICK: Expanding treatment options for Cushing disease
Cushing disease is a hormone disorder that causes a diverse array of symptoms, including fat accumulation, high blood pressure, osteoporosis, muscle wasting, and ultimately death. It is caused by a tumor in the anterior pituitary gland that results in the secretion of excess amounts of adrenocorticotropic hormone (ACTH). Treatment options are essentially limited to surgical resection. However, tumors commonly recur, meaning that new treatment options are needed. A team of researchers, led by Shlomo Melmed, at Cedars-Sinai Medical Center, Los Angeles, has now identified a potential new therapeutic target the protein EGFR, which is the target of a drug used to treat some patients with nonsmall cell lung cancer (gefitinib). As discussed by Melmed and colleagues in their paper, as well as Frederic Wondisford, at Johns Hopkins University School of Medicine, Baltimore, in an accompanying commentary, the data generated in human, canine, and mouse models provide strong support to investigate the clinical effects of gefitinib in patients with Cushing disease.
TITLE: EGFR as a therapeutic target for human, canine, and mouse ACTH-secreting pituitary adenomas
AUTHOR CONTACT:
Shlomo Melmed
Cedars-Sinai Medical Center, Los Angeles, California, USA.
Phone: 310-423-4691; Fax: 310-423-0119; E-mail: Melmed@csmc.edu.
View this article at: http://www.jci.org/articles/view/60417?key=ea692326753d599db723
ACCOMPANYING COMMENTARY
TITLE: A new medical therapy for Cushing disease?
AUTHOR CONTACT:
Fredric E. Wondisford
Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Phone: 410-502-5761; Fax 410-502-5779; E-mail: fwondisford@jhmi.edu.
View this article at: http://www.jci.org/articles/view/61127?key=70bc5a72e9b76e5ee825
OTOLOGY: The proteins TMC1 and 2 key to sensing sound and gravity
Central to our ability to hear and to sense gravity is a cellular process known as mechanotransduction. Essential for this process is the opening of special channels in the surface membrane of inner ear hair cells. The molecular identity of these channels has eluded researchers despite intensive investigations over the years. But now, a team of researchers led by Andrew Griffith, at the National Institutes of Health, Rockville; and Jeffrey R. Holt, at Children's Hospital Boston, Boston has determined that in mice, the channel proteins TMC1 and TMC2 are necessary for inner ear hair cell mechanotransduction. These data are consistent with the fact that mutations in the TMC1 gene cause hearing loss in both humans and mice and provide new insight into the molecular mechanisms underlying the condition.
In an accompanying commentary, Xi Lin, at Emory University School of Medicine, Atlanta, discusses the importance of the findings of Griffith, Holt, and colleagues, and highlights the future utility of the mice they generated during their studies.
AUTHOR CONTACT:
Andrew J. Griffith
National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland, USA.
Phone: 301-402-2829; Fax: 301-402-7580; E-mail: griffita@nidcd.nih.gov.
Jeffrey R. Holt
Children's Hospital Boston, Boston, Massachusetts, USA.
Phone: 617-919-3574; Fax: 617-919-2771; E-mail: jeffrey.holt@childrens.harvard.edu.
MEDIA CONTACT
Robin Latham
National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland, USA.
Phone: 301-496-7243; E-mail: lathamr@nidcd.nih.gov.
View this article at: http://www.jci.org/articles/view/60405?key=4e596583c59e4453ef6c
ACCOMPANYING COMMENTARY
TITLE: Perception of sound and gravity by TMC1 and TMC2
AUTHOR CONTACT:
Xi Lin
Emory University School of Medicine, Atlanta, Georgia, USA.
Phone: 404-727-3723; Fax: 404-727-6356; E-mail address: xlin2@emory.edu.
View this article at: http://www.jci.org/articles/view/61167?key=2aa1292c2d54f036ffe6
CARDIOVASCULAR DISEASE: Visualizing the effectiveness of candidate anti-atherosclerotic approaches
Atherosclerosis is a disease of the major arterial blood vessels. It is one of the major causes of heart attack and stroke. An early event in the development of atherosclerosis is modification of the molecule LDL by oxidation. A team of researchers led by Yury Miller, at the University of California San Diego, La Jolla, has developed an approach to visualize the accumulation of oxidized LDL in zebrafish fed a diet high in cholesterol. Using their approach they were able to visualize the effects of treatment with an antioxidant it reversed the accumulation of oxidized LDL, as did switching the zebrafish to a diet low in cholesterol. Miller and colleagues therefore suggest that they have developed an efficient method of testing the potential effectiveness of dietary and/or other therapeutic antioxidant strategies under development as anti-atherosclerotic agents in humans.
TITLE: In vivo visualization and attenuation of oxidized lipid accumulation in hypercholesterolemic zebrafish
AUTHOR CONTACT:
Yury I. Miller
University of California, San Diego, La Jolla, California, USA.
Phone: 858-822-5771; Fax: 858-534-2005; E-mail: yumiller@ucsd.edu.
View this article at: http://www.jci.org/articles/view/57755?key=7f775f5c0cc68a36cd06
NEUROLOGICAL DISEASE: Linking distinct genetic disorders together
Inclusion body myopathy with Paget disease of the bone and frontotemporal dementia (IBMPFD) is a multisystem degenerative disorder characterized by progressive muscle weakness that is often accompanied by bone weakening and/or frontotemporal dementia. A team of researchers led by Yi-Ping Hsueh, at Academia Sinica, Taiwan; and Ming-Jen Lee, at National Taiwan University Hospital, Taiwan has now identified a potential link between the mechanisms underlying the dementia seen in patients with IBMPFD and those causing the cognitive deficits observed in patients with neurofibromatosis type 1.
IBMPFD is an inherited disease caused by mutations in the VCP gene. Neurofibromatosis type 1 is caused by mutations in the NF1 gene. Hsueh, Lee, and colleagues found that the proteins templated by the VCP and NF1 genes (VCP and NF1) interact to control the formation of nerve cell structures critical for nerve cell communication (dendritic spines). IBMPFD- and neurofibromatosis type 1associated mutations that disrupted the VCP/NF1 interaction resulted in reduced dendritic spine density. Hsueh, Lee, and colleagues therefore suggest that the dementia seen in individuals with IBMPFD might be a result of defects in VCP regulated dendritic spine formation.
In an accompanying commentary, Conrad Weihl, at Washington University School of Medicine, Saint Louis, highlights the importance of the work of Hsueh, Lee, and colleagues to understanding the complex genetic interactions that can lead to different patients experiencing different symptoms even if they have the same underlying VCP or NF1 mutation.
TITLE: Valosin-containing protein and neurofibromin interact to regulate dendritic spine density
AUTHOR CONTACT:
Yi-Ping Hsueh
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
Phone: 886-2-27899311; Fax: 886-2-27826085; E-mail: yph@gate.sinica.edu.tw.
Ming-Jen Lee,
National Taiwan University Hospital, Taipei, Taiwan.
Phone: 886-2-23123456 ext. 65342; Fax: 886-2-23418395; E-mail: mjlee@ntu.edu.tw.
View this article at: http://www.jci.org/articles/view/45677?key=c4a822afbb932fcc0c27
ACCOMPANYING COMMENTARY
TITLE: Another VCP interactor: NF is enough
AUTHOR CONTACT:
Conrad C. Weihl
Washington University School of Medicine, Saint Louis, Missouri, USA.
Phone: 314-362-6981; Fax 314-362-4391; E-mail: weihlc@neuro.wustl.edu.
View this article at: http://www.jci.org/articles/view/61126?key=997b610235a30f5a867d
IMMUNOLOGY: Identification of new genetic defects underlying Herpes simplex encephalitis
Herpes simplex encephalitis (HSE) is a rare but severe condition caused primarily by infection of the brain and spinal cord with herpes simplex virus-1 (HSV-1), the same virus that causes cold sores. Even with treatment, the condition is often fatal, and survivors, affected children in particular, usually suffer long-term brain damage. In some children, genetic mutations that affect the immune system underlie their susceptibility to HSE. A team of researchers led by Vanessa Sancho-Shimizu, at Necker Hospital, France; and Jean-Laurent Casanova, at The Rockefeller University, New York has now identified two new mutations, this time in the gene TRIF, as the reason for two unrelated children being susceptible to HSE. Further analysis defined the molecular mechanism by which these mutations, both of which resulted in TRIF deficiency, impaired the immune system and made the children susceptible to the condition.
TITLE: Herpes simplex encephalitis in children with autosomal recessive and dominant TRIF deficiency
Jean-Laurent Casanova
The Rockefeller University, New York, New York, USA.
Phone: 212-327-7331; Fax: 212-327-7330; E-mail: casanova@rockefeller.edu.
View this article at: http://www.jci.org/articles/view/59259?key=e3042b370c4f05f59b12
HEPATOLOGY: The source of the liver cell uncovered
The liver has the remarkable ability to rapidly regenerate after tissue injury or partial resection. Many researchers are seeking to harness this ability to treat individuals with a wide range of liver diseases. However, in order to do this it is vital to know from what cell new liver cells (hepatocytes) arise in the adult. A team of researchers led by Holger Willenbring, at the University of California, San Francisco, has now generated a hepatocyte fate-tracing model that enabled them to demonstrate definitively in mice that hepatocytes themselves, and not specialized progenitor cells, are the source of new hepatocytes in the healthy liver and the predominant source of new liver cells in the acutely injured liver. As noted by Willenbring and colleagues, harnessing these cells for therapy will require knowing the signals that trigger their activation.
In an accompanying commentary, Klaus Kaetsner and Joshua Friedman, at the University of Pennsylvania, Philadelphia, discuss how the work of Willenbring and colleagues helps settle recent controversy regarding the origins of hepatocytes in adults.
TITLE: Fate tracing of mature hepatocytes in mouse liver homeostasis and regeneration
AUTHOR CONTACT:
Holger Willenbring
University of California at San Francisco, San Francisco, California, USA.
Phone: 415-476-2417; Fax: 415-514-2346; E-mail: willenbringh@stemcell.ucsf.edu.
View this article at: http://www.jci.org/articles/view/59261?key=969533400d3303d8af4c
ACCOMPANYING COMMENTARY
TITLE: On the origin of the liver
AUTHOR CONTACT:
Klaus Kaestner
University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Phone: 215-898-8759; Fax: 215-573-5892; E-mail: kaestner@mail.med.upenn.edu.
View this article at: http://www.jci.org/articles/view/59652?key=36cbd0c4abf88df63e89
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Public release date: 21-Nov-2011
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