Brain circuitry associated with addictive, depressive behaviors identified

ScienceDaily (Apr. 30, 2012) ? Scientists at the Gladstone Institutes have determined how specific circuitry in the brain controls not only body movement but also motivation and learning, providing new insight into neurodegenerative disorders such as Parkinson's disease -- and psychiatric disorders such as addiction and depression.

Previously, researchers in the laboratory of Gladstone Investigator Anatol Kreitzer, PhD, discovered how an imbalance in the activity of a specific category of brain cells is linked to Parkinson's. Now, in a paper published online April 29 in Nature Neuroscience, Dr. Kreitzer and his team used animal models to demonstrate that this imbalance may also contribute to psychiatric disorders. These findings also help explain the wide range of Parkinson's symptoms -- and mark an important step in finding new treatments for those who suffer from addiction or depression.

"The physical symptoms that affect people with Parkinson's -- including tremors and rigidity of movement -- are caused by an imbalance between two types of medium spiny neurons in the brain," said Dr. Kreitzer, whose lab studies how Parkinson's disease affects brain functions. "In this paper we showed that psychiatric disorders -- specifically addiction and depression -- might be caused by this same neural imbalance."

Normally, two types of medium spiny neurons, or MSNs, coordinate body movements. One type, called direct pathway MSNs (dMSNs), acts like a gas pedal. The other type, known as indirect pathway MSNs (iMSNs), acts as a brake. And while researchers have long known about the link between a chemical in the brain called dopamine and Parkinson's, Gladstone researchers recently clarified that dopamine maintains the balance between these two MSN types.

But abnormal dopamine levels are implicated not only in Parkinson's, but also in addiction and depression. Dr. Kreitzer and his team hypothesized that the same circuitry that controlled movement might also control the process of learning to repeat pleasurable experiences and avoid unpleasant ones -- and that an imbalance in this process could lead to addictive or depressive behaviors.

Dr. Kreitzer and his team genetically modified two sets of mice so that they could control which specific type of MSN was activated. They placed mice one at a time in a box with two triggers -- one that delivered a laser pulse to stimulate the neurons and one that did nothing. They then monitored which trigger each mouse preferred.

"The mice that had only dMSNs activated gravitated toward the laser trigger, pushing it again and again to get the stimulation -- reminiscent of addictive behavior," said Alexxai Kravitz, PhD, Gladstone postdoctoral fellow and a lead author of the paper. "But the mice that had only iMSNs activated did the opposite. Unlike their dMSN counterparts, the iMSN mice avoided the laser stimulation, which suggests that they found it unpleasant." These findings reveal a precise relationship between the two MSN types and how behaviors are learned. They also show how an MSN imbalance can throw normal learning processes out of whack, potentially leading to addictive or depressive behavior.

"People with Parkinson's disease often show signs of depression before the onset of significant movement problems, so it's likely that the neural imbalance in Parkinson's is also responsible for some behavioral changes associated with the disease," said Dr. Kreitzer, who is also an assistant professor of physiology at the University of California, San Francisco, with which Gladstone is affiliated. "Future research could discover how MSNs are activated in those suffering from addiction or depression -- and whether tweaking them could reduce their symptoms and improve their quality of life.

Graduate student Lynne Tye was also a lead author on this paper. Funding came from a variety of sources, including the W.M. Keck Foundation, the Pew Biomedical Scholars Program, the McKnight Foundation and the National Institutes of Health.

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The above story is reprinted from materials provided by Gladstone Institutes.

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


Journal Reference:

  1. Alexxai V Kravitz, Lynne D Tye, Anatol C Kreitzer. Distinct roles for direct and indirect pathway striatal neurons in reinforcement. Nature Neuroscience, 2012; DOI: 10.1038/nn.3100

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

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

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96% The Kid with a Bike

Cyril: Dad! I'm here.Given that the month of March was packed with an unusual amount of high budget, blockbuster films, I figured I would balance things out with a couple of independent/arthouse features as well. One of these was The Kid with a Bike, a Belgian film from the Dardenne brothers (Jean-Pierre and Luc). This film follows a young boy dealing with being abandoned by his father and attempting to forge new relationships with other potential role models and caretakers. The film is very naturalistic, a key type of style when it comes to the Dardenne's work, as it plays out as more character-driven, as opposed to story-driven and plays around a lot with ambiguity, despite straddling a somewhat familiar path. With that in mind, the film is very good, well-acted, and filled with moments that evoke emotion as well as thoughts based around developing more of an understanding for one's self, rather than letting the film tell you what to think.read the whole review at thecodeiszeek.com

April 2, 2012

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Pancreatic cancer gene discovery

Aggressive pancreatic tumours may be treatable with a new class of drugs, according to Cancer Research UK

Less than one in five people with this form of cancer are still alive a year after being diagnosed.

A study, published in the journal Nature, showed that a gene was being switched off in the cancerous cells.

The reseachers said drugs were already being tested which had the potential to turn the gene back on, to stop the spread of the cancer.

Around 7,800 people in the UK are diagnosed with pancreatic cancer every year and it is the fifth most deadly cancer.

Continue reading the main story

?Start Quote

These results raise the possibility that a class of promising new cancer drugs may be effective at treating some pancreatic cancers?

End Quote Dr Julie Sharp Cancer Research UK On/off

Studies in mice showed that a gene called USP9x, which normally stops a cell from dividing uncontrollably, is switched off in some pancreatic cancer cells.

The gene is not mutated, but other proteins and chemicals become stuck to it and turn the gene off.

Studies then showed that UPS9x was being turned off in human pancreatic cancer.

Prof David Tuveson, from the Cancer Research UK Cambridge Research Institute, said: "We suspected that the fault wasn't in the genetic code at all, but in the chemical tags on the surface of the DNA that switch genes on and off, and by running more lab tests we were able to confirm this.

"Drugs which strip away these tags are already showing promise in lung cancer and this study suggests they could also be effective."

Dr David Adams, from the Wellcome Trust Sanger Institute, said: "This study strengthens our emerging understanding that we must also look into the biology of cells to identify all the genes that play a role in cancer."

They argue that up to 15% of pancreatic cancers could be down the turning this one gene off.

Dr Julie Sharp, Cancer Research UK's senior science information manager, said: "These results raise the possibility that a class of promising new cancer drugs may be effective at treating some pancreatic cancers."

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Analysis: Obama falls short of meteoric expectations abroad

WASHINGTON (Reuters) - It was not just U.S. Democratic voters who were looking forward to "hope and change" when Barack Obama became the 44th U.S. president.

Around the world, many anticipated the United States would behave very differently under the new leader. They wanted to hear less about Americans swaggering and throwing their weight around. Some, perhaps, wanted more talk of U.S.-style freedom and democracy, but not if it meant Washington imposing its will.

Few dispute that Obama's election brought with it a noticeable change in tone. But 3-1/2 years later, there are growing complaints that when it comes to substance, relatively little has changed.

A scandal over the hiring of prostitutes by the U.S. Secret Service in Colombia, killings and Koran burnings in Afghanistan and drone strikes in Pakistan have helped fuel an impression of a United States that globally does what it wants regardless of others.

Even the "Arab Spring," some complain, showcased U.S. hypocrisy: Washington withdrew support from autocratic allies like Egypt's Hosni Mubarak only when it became clear they were on the way out while still supporting authoritarian partners in states such as Bahrain and Saudi Arabia.

The failure to close the Guantanamo Bay military prison in Cuba, where suspected foreign terrorists are held, despite Obama's promises both before and after his election, has added to the disillusionment.

"We were very hopeful at the time Obama was elected," said Abdel Rahman Mansour, an Egyptian political activist whose Facebook postings helped drive the revolution that ousted Mubarak in February last year. "But nothing happened. Obama didn't deliver change but diplomatic rhetoric."

As it struggles with a slow economic recovery, a potentially crippling budget deficit and debt burden, and political gridlock in Washington, some wonder whether the United States itself is in a slow decline.

A poll released last week by Gallup and conducted across 136 countries showed 46 percent of respondents had a positive view of U.S. global leadership. That has fallen gradually from 49 percent in 2009 immediately after Obama's election, the highest since Gallup began polling on the issue in 2005.

It remains well above the 34 percent recorded in 2008, the last year of the George W. Bush administration.

Obama is also seen as much more popular internationally than his presumptive Republican challenger in November's election, former Massachusetts Governor Mitt Romney, who has indicated he would take a hard line with countries such as Russia and China.

The enthusiasm verging on euphoria that initially greeted Obama, however, seems to be gone for good.

Karl Lemberg, one of thousands who thronged a Berlin park in July 2008 for a pre-election address by Obama, says he believed at the time he was seeing a seismic shift in relations between the United States and the rest of the world.

Four years later, now married to an American woman and studying in Washington, he says he has trimmed his expectations, particularly after learning how Congress limits the freedom of any president. "I have a much more realistic view of the U.S. now," he said.

Some now say the world's embrace of Obama had less to do with the candidate himself - and even less to do with his policies - and more to do with what he was seen to represent as the first black U.S. president.

"To me, what the Obama presidency has done ... is to show that with good ... institutional structures... anybody can rise up to any level they would want to achieve," said James Shikwati, founder and director of the Nairobi-based Inter Regional Economic Network think tank.

Certainly, the United States - with its enduring if occasionally troubled democracy, wealth, image and power - exerts a powerful draw. A separate Gallup poll shows it the most popular desired destination for potential global migrants.

Most polls show greater trust in U.S. leadership than that of other powers, such as China. Indeed, Beijing's rise is seen prompting many other countries in Asia to tighten relations with Washington.

ALWAYS A "ROLLER COASTER"

For Obama "it was always going to be a roller coaster," says P.J. Crowley, State Department spokesman between 2009 and 2011 and now a university lecturer, pointing to the shift in expectations after the eight years under Bush.

Global sentiment towards the United States has always ebbed and flowed. President Ronald Reagan was far from universally loved in Europe at the time of his Cold War standoff with the Soviet Union, while presidents Lyndon Johnson and Richard Nixon were heavily criticized during the Vietnam War.

But recent months have certainly seen the kind of image-damaging news flow Washington could do without.

This month's Americas Summit in Colombia was marred by the embarrassing disclosure that U.S. Secret Service agents had been caught bringing prostitutes into their hotel. The United States also found itself isolated over its tough Cuba policy.

Of greater damage to Washington's image was a string of incidents in Afghanistan, where it is struggling to create security and promote development.

"What happened in Colombia was a distraction from the summit itself, but that was it," said Douglas Ollivant, a former director for Iraq for the National Security Council who is now at the New America Foundation think tank. "In Afghanistan, though, there is something of a drum beat of events. And there it really matters."

In March, a U.S. Army sergeant was accused of killing 17 Afghan civilians. He was arrested and flown back to the United States for trial. Before that a video circulated showing U.S. troops apparently urinating on dead Taliban fighters.

In February, there were protests and reprisals after it emerged U.S. forces had burned several copies of the Koran.

Jon B. Wolfsthal, a former NSC director for nuclear issues and special adviser to Vice President Joe Biden, said it was vital for the government to build up international capital to help it better weather such storms.

Wolfstahl, now deputy head of the University of Monterey's Center for Nonproliferation Studies, said there was a big difference between recent scandals and some of the more unpopular actions of the Bush administration, like the use of controversial interrogation techniques such as waterboarding. Under Obama the acts were by misguided individuals and they were not official policy, he said.

In Obama's first year in office, he said, the president and his aides pursued a deliberate policy of trying to build international capital with big speeches in Prague and Cairo so they could trade off it in later years.

"There are times when it has been very useful," says Wolfsthal, pointing to negotiations to get countries to surrender atomic material or cooperate on sanctions against nuclear smuggling. "You have national leaders that were willing to do things they didn't want to do because they got to meet with or be photographed with the president."

Administration insiders said they always knew Obama's sky-high global popularity would not be sustainable. Romney might accuse Obama of too often apologizing for the United States, but the president's defenders said he had no problem making internationally unpopular decisions when necessary.

"I don't think the Obama administration is particularly any more worried about what people in the rest of the world think," says former NSC member Ollivant, who served both Bush and Obama.

"WE LOVE YOU OBAMA"

Still, in some parts of the world the president remains much more popular than many local politicians.

When he visited the Indonesian island of Bali for the Association of Southeast Asian Nations summit in November, adoring crowds lined the route cheering "We love you Obama." An Indonesian provincial governor passing along the same route hours later was met with jeers and complaints over flooding and poor roads. Obama lived in the capital Jakarta for three years with his mother and Indonesian stepfather between 1969 and 1971.

But in Pakistan, where U.S. Navy SEALs killed Osama bin Laden a year ago and where drones stalk militants in the lawless tribal areas, Obama's leadership has proved divisive.

"Things seem to have gotten worse under Obama," said Shayan Jafri, 21, a law student in Islamabad. "America has been violating our sovereignty ... how can they expect us to respect them when they don't respect us."

Some Pakistanis do express sympathy with the policy challenge for the United States. "As long as we are not willing to solve our own problems, what options do the Americans have?" said fellow Islamabad resident Ali Qureshi, 28.

It is a similar picture across the border in Afghanistan. While some Afghans credit the United States - and even Obama in particular - with some development and security gains, there are widespread complaints that go beyond the scandals, particularly over failure to build up the economy and infrastructure.

MOVING BEYOND AMERICA?

In the Middle East, there seems little doubt the Obama presidency scaled back perceptions widespread under Bush that the United States was at war with the Muslim world.

Obama's supporters say that has helped him build regional and international coalitions to help contain Iran, particularly when it comes to tightening sanctions designed to rein in Tehran's nuclear program.

The Obama administration's unwillingness to intervene militarily to prevent the Syrian government from firing on its own people as it seeks to put down an uprising has upset some. But another U.S.-led intervention in the Muslim world would have carried heavy risks.

Given the growing strength of nations such as China, India and Brazil - not to mention the power of popular unrest showed by the "Arab Spring" - the idea that U.S. policy might be key to another region's destiny is itself being questioned.

Under Bush, many, particularly the Middle East, saw the United States as a "rogue state" that endangered others. Under Obama, some believe that while it may sometimes be a stabilizing force, it could also be becoming quietly less important.

"I have simply moved on from looking at America," said Sultan Sooud Al Qassemi, a blogger and political commentator based in the United Arab Emirates. "It's not America that is going to bring change to the Middle East or anywhere else. We have to look to ourselves, produce the change ourselves."

The State Department and White House declined comment on this story.

(Additional reporting by Reuters bureaus in Nairobi, Cairo, Jakarta, Islamabad, Kabul and Beijing; Editing by Martin Howell and David Storey)

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Success in Pay Per Click Advertising - How to Earn a Living Online

There are many business models to maximize your profits online and allow you to earn huge of money on the internet. In this article, you will discover and learn 5 affiliate business models in pay per click search engine marketing to earn huge affiliate commission and grow your home based affiliate business.

1. PPC ? Merchant Site.Basically, this approach is the easiest affiliate marketing strategy to earn commission online. You can start earning affiliate commission in PPC online advertising by: (1) joining the affiliate programs and getting the affiliate links (2) signing up the PPC search engine account and (3) creating PPC online advertising campaigns with those affiliate links. It is used to drive directly visitors from pay per click (PPC) search engine, like Google Adwords, Overture and MSNAdCenter, to merchants? website. The approach is suitable for testing the new affiliate products in your affiliate marketing business only. With the niche keywords, this technique is a great way for testing whether those new products can be sold in the markets. You can not maximize profits online and earn huge commission with this approach.

The purpose of this approach is to test driving traffic to the merchant sites. It will be perfectly fit for new products entering into the markets. You can easily setup your PPC advertising campaigns for testing those new products. Obviously, you can use this technique only for testing those products to evaluate whether it can be sold or not.

2. PPC ? Review Page ? Merchant Site.The next affiliate business model is to provide quality contents along with the product reviews in the review web page. You should consider creating your own review page. This is one of the most popular affiliate marketing business models for affiliate marketing entrepreneurs. Also, it is an effective way to convenience the visitors with the contents, before they make any purchases. You can drive visitors from PPC search engine to your review page directly. Within the review page, you can give high quality content and unbiased products reviews. Also, you can embed the affiliate links into the review page in order to drive forward your visitors to merchants? website.

The purpose of this approach is to drive quality content to your visitors before they will make any purchases. It can be used perfectly when you have profitable several affiliate products at the same time. Otherwise, it can be used if you ensure that those affiliate products are profitable.

3. PPC ? Review Page ? Tell a Friend ? Merchant Site.This approach is applied the concept of viral marketing strategy in order to spread your review page or website to other people. The viral marketing strategy is one of the quickest approaches to increase your reputation, creditability and reliability. It is all about the ?Word of Mouth? strategy. The ?Tell a Friend? script is a great example of viral marketing strategy and it can be used perfectly for this business model. With this script, your review page will be sent out to other people quickly, like a virus. After sending to the other people, it will redirect your visitors to the merchants? website for selling further.

The purpose of this approach is to spread out your review page, where the content is, to other people quickly and massively as much as possible. With the ?Tell a Friend? script, your web page will be sent massively out as soon as possible too.

4. PPC ? Squeeze Page ? Review Page ? Merchant Site.Another great affiliate marketing business model is to combine both of email promotion internet marketing, review page approach and back-end selling process. You can drive visitors from PPC search engine to a squeeze page, which is a web page used for capturing visitors? personal information. When you capture completely the personal information in the squeeze page, it will redirect your visitors to the review page where you can give them the product recommendation. Finally, it will lead your visitors to the merchants? website for purchasing purpose from the review page.

There is doubt that the combination of email promotion internet marketing and product review approach is used for utilizing the power of back-end selling process. You can sell other affiliate products to those visitors or even your existing buyers in the future. You can follow-up them about the products or services. This will create the impressive to your customers or potential buyers.

5. PPC ? Squeeze Page ? Tell a Friend ? Review Page ? Merchant Site.The last affiliate marketing business model is the best approach for affiliate entrepreneurs to earn huge affiliate commission and maximize the power of several affiliate marketing strategies in this article. Obviously, you can insert the viral marketing strategies, particularly the ?Tell a Friend? script, in order to spread out to the world. You can redirect from your squeeze page to the web page with the ?Tell a Friend? script, before forwarding to the review page, where the content is, and merchant site respectively.

The purpose of this business model is used for affiliate marketing entrepreneurs who want to increase massively profits online through the affiliate products. With the power of emails, viral marketing strategy and product review approach, you will maximize return on investment and profits in PPC online advertising for your home based affiliate business.

Final thoughts, the inside secret of affiliate millionaires to your success in those business models is to drive high quality traffic through hot niche keywords with low competitors from PPC engines. Without the appropriate techniques in PPC online advertising, you can not maximize your profits online with those above business models in the affiliate marketing business.


Siripong R. or zMillionDollars is a recognized authority on the subject of building super-profitable pay per click campaigns. His website, http://www.iPayByClick.com, provides a wealth of informative articles and resources on everything you?ll ever need to know about pay per click advertising. Free special reports at: http://www.iPayByClick.com/free-report.>Discount Wall Art swim team record boards travel plumbing and heating West Chester PA

1 dead, 100 hurt as storm blows away bar's tent

By NBC News and msnbc.com staff

ST. LOUIS, Mo. -- A storm blasting through the city blew away a tent outside a downtown bar, leaving one man dead Saturday afternoon, NBC station KSDK reported.

Twenty?others -- three?in critical condition -- were taken to?a hospital after the incident at Kilroy?s Sports Bar on South Seventh Street, a couple of blocks south of Busch Stadium, KSDK reported. A total of 100 people received medical treatment, KSDK said. Photos?showed the tent impaled on a nearby railroad trestle.


KSDK via NBC News

A beer garden tent at Kilroy's Sports Bar near Busch Stadium in St. Louis is shown impaled on a train trestle Saturday after winds blew it away, killing one man and injuring about 100 other people.

It was not clear whether the man who died was struck during the incident or went into cardiac arrest because of shock, officials said.

St. Louis Fire Chief Dennis Jenkerson told KSDK that a few hundred people were celebrating in the tent after the Cardinals' 7-3 victory over the Milwaukee Brewers when the storm hit.

"We've got severe injuries to quite a few people," Jenkerson said, noting live wires were left on the ground after the tarp tied to galvanized pipes blew away. "We don't like this type of building.?It gives us nightmares, and as you can see, it caused one."

The pipes "beat up" many of the people in the tent, Jenkerson said.

The tent was set up as a beer garden next to Kilroy's, the St. Louis Post-Dispatch reported.

Eddie Roth, director of?the St. Louis Department of Public Safety, said the tent had passed inspection and it didn't appear there would be any violation, although an investigation would continue, The Associated Press reported.

"I thought a train fell off the track," Art Randall, Kilroy's?owner, told the Post-Dispatch. "We all ducked for cover. Everything was going sideways. I had metal chairs ripping across the beer garden."

"People were pushing and shoving,"?said Christy Eilermann, 42, of St. Louis, the Post-Dispatch reported.?"The wind just picked up and they started dragging people inside."

Storms packing hail up to baseball-size hail slammed eastern Missouri and western Illinois on Saturday.

Weather spotters in O?Fallen, Baden and Lebanon, Ill., reported baseball-size hail, 2.75 inches, smashing car windshields and home windows at 4:22 CDT.

The National Weather Service issued tornado warnings for parts of Daviess, Knox and Martin counties in southwest Indiana and severe thunderstorm warnings for east-central Missouri and south-central Illinois.

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India?s Looming Energy Crisis

Indian laborers work at a coal warehouse in Ahmadabad, India, Tuesday, Oct. 19, 2010. According to news reports, Coal India Ltd?s $3.5 billion initial public share offer, the largest in India?s history, was oversubscribed by 1.57 times hours before closure of the second day of the issue on Tuesday. The government is divesting 10 per cent of its stake in CIL ? the world?s largest coal producer coal reserve holder in the world, contributing 82 per cent of total coal production in India.(AP Photo/Ajit Solanki)

India?s impending energy crisis is an urgent and growing concern as fuel inefficiency are greatly bearing down on homes and industries in most parts of the country. The country is struggling to provide round-the-clock power as around 50 power plants have just a few days of coal stock to fuel the power stations in the country. With the shortage of electricity reaching 21,000 megawatts, the energy crisis is expected to worsen this summer.

The situation which has been deteriorating with every passing year, is running out of options as Coal India Limited has faced a shortage of 142 million tonnes. The country cannot get enough fuel, primarily due to political corruption, lack of proper transportation facilities, poor management, incompetent policies and environmental concerns.

Coal India which controls 80 percent of the production of coal in India has been hit by government policies, which requires it to sell coal at 70 percent discount to market prices. India sits on one of the largest reserves of coal in the world, but CIL has been criticized for failing to invest in new mines and technologies. India cannot produce enough coal to meet the growing energy demands. Coal production is growing at an average of 5 percent every year, but demand is escalating between 10 to 15 percent per year.

A few of electricity producers have been importing coal from Indonesia but even that is not a very viable option as Indonesia has doubled the coal prices.

Lack of availability of coal is not just a daunting energy crisis that is unable to provide power to one third of India?s total population, but it is also slowing the country?s economic growth. GDP is expected to climb 7 percent this year from a 10 percent that was enjoyed in 2010.

Moreover, India has not exploited clear energy sources like solar or wind power to meet the growing need of energy. For a fast developing nation like India that is expected to attract foreign investments, power woes could have been easily addressed by the politicians. But political battles and corruption scandals have kept them distracted from the grave energy crisis faced by India today.

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How the iPad Is Changing Education

There's also some early evidence that an iPad could provide a more engaging learning experience and might even improve student performance. It's purely anecdotal, but students at Riverside Unified School District have said that using an iPad makes learning and doing homework more enjoyable. Their teachers confirmed that students seem more eager to participate thanks to the iPad. Anybody who's ever spent a long stretch of uninterrupted time reading or watching video on their iPad can see why this might be the case.

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