Gene silencing spurs fountain of youth in mouse brain

Feb. 7, 2013 ? Cognitive decline in old age is linked to decreasing production of new neurons. Scientists from the German Cancer Research Center have discovered in mice that significantly more neurons are generated in the brains of older animals if a signaling molecule called Dickkopf-1 is turned off. In tests for spatial orientation and memory, mice in advanced adult age whose Dickkopf gene had been silenced reached an equal mental performance as young animals.

The hippocampus -- a structure of the brain whose shape resembles that of a seahorse -- is also called the "gateway" to memory. This is where information is stored and retrieved. Its performance relies on new neurons being continually formed in the hippocampus over the entire lifetime. "However, in old age, production of new neurons dramatically decreases. This is considered to be among the causes of declining memory and learning ability," Prof. Dr. Ana Martin-Villalba, a neuroscientist, explains.

Martin-Villalba, who heads a research department at the German Cancer Research Center (DKFZ), and her team are trying to find the molecular causes for this decrease in new neuron production (neurogenesis). Neural stem cells in the hippocampus are responsible for continuous supply of new neurons. Specific molecules in the immediate environment of these stem cells determine their fate: They may remain dormant, renew themselves, or differentiate into one of two types of specialized brain cells, astrocytes or neurons. One of these factors is the Wnt signaling molecule, which promotes the formation of young neurons. However, its molecular counterpart, called Dickkopf-1, can prevent this.

"We find considerably more Dickkopf-1 protein in the brains of older mice than in those of young animals. We therefore suspected this signaling molecule to be responsible for the fact that hardly any young neurons are generated any more in old age." The scientists tested their assumption in mice whose Dickkopf-1 gene is permanently silenced. Professor Christof Niehrs had developed these animals at DKFZ. The term "Dickkopf" (from German "dick" = thick, "Kopf" = head) also goes back to Niehrs, who had found in 1998 that this signaling molecule regulates head development during embryogenesis.

Martin-Villalba's team discovered that stem cells in the hippocampus of Dickkopf knockout mice renew themselves more often and generate significantly more young neurons. The difference was particularly obvious in two-year old mice: In the knockout mice of this age, the researchers counted 80 percent more young neurons than in control animals of the same age. Moreover, the newly formed cells in the adult Dickkopf-1 mutant mice matured into potent neurons with multiple branches. In contrast, neurons in control animals of the same age were found to be more rudimentary already.

Blocking Dickkopf improves spatial orientation and memory

Several years ago, Ana Martin-Villalba had shown that mice lose their spatial orientation when neurogenesis in the hippocampus is blocked. Now, is it possible that the young neurons in Dickkopf-deficient mice improve the animals' cognitive performance? The DKFZ researchers used standardized tests to study how the mice orient themselves in a maze. While in the control animals, the younger ones (3 months) performed much better in orienting themselves than the older ones (18 months), the Dickkopf-1-deficient mice showed no age-related decline in spatial orientation capabilities. Older Dickkopf-1 mutant mice also outperformed normal animals in tests determining spatial memory.

"Our result proves that Dickkopf-1 promotes age-related decline of specific cognitive abilities," says Ana Martin-Villalba. "Although we had expected silencing of Dickkopf-1 to improve spatial orientation and memory of adult mice, we were surprised and impressed that animals in advanced adult age actually reach the performance levels of young animals."

These results give rise to the question whether the function of Dickkopf-1 may be turned off using drugs. Antibodies blocking the Dickkopf protein are already being tested in clinical trials for treating a completely different condition. "It is fascinating to speculate that such a substance may also slow down age-related cognitive decline. But this is still a dream of the future, since we have only just started first experiments in mice to explore this question."

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The above story is reprinted from materials provided by Helmholtz Association of German Research Centres, via EurekAlert!, a service of AAAS.

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

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Journal Reference:

1. D?sir?e?R.M. Seib, Nina?S. Corsini, Kristina Ellwanger, Christian Plaas, Alvaro Mateos, Claudia Pitzer, Christof Niehrs, Tansu Celikel, Ana Martin-Villalba. Loss of Dickkopf-1 Restores Neurogenesis in Old Age and Counteracts Cognitive Decline. Cell Stem Cell, 2013; 12 (2): 204 DOI: 10.1016/j.stem.2012.11.010

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.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/~3/PDoks_6owgE/130207150911.htm

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John Leguizamo pilot picked up by ABC

NEW YORK (TheWrap.com) - ABC has picked up a pilot for an untitled John Leguizamo half-hour comedy, the network announced.

Co-created by and starring Leguizamo, it is executive produced by David Hoberman, Todd Lieberman and Jeff Golenberg. It comes from ABC Studios and Mandeville.

The pilot is based on the Broadway and film actor's life as a husband and father who feels like a fish out of water on Manhattan's Upper West Side. He balances a privileged wife, friends from back home in the Bronx, and a mother and grandfather "who try to keep him grounded in his Latin roots," according to ABC. He also worries that his kids are becoming spoiled.

The "Ice Age" actor has starred in a series of one-man shows that aired on HBO, including "Mambo Mouth," "Spic-O-Rama," "Freak," and "Sexaholix."

Source: http://news.yahoo.com/john-leguizamo-pilot-picked-abc-204340168.html

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Video: Memo reveals legal case for drone strikes on Americans

>>> developing news within the past hour, the white house reacting to a secret 16-page justice department memo exclusively obtained by nbc news. in it, obama administration lawyers argue the government can kill americans believed to be top taliban leaders posing, quote, an imminent threat of attack against the united states .

>> we have acknowledged the united states that sometimes we use remotely piloted aircraft to conduct targeted strikes against specific al qaeda terrorists to prevent attacks on the united states and to save american lives. we conduct those strikes because they're necessary to mitigate ongoing actual threats, to stop plots, prevent future attacks and save american lives. the strikes are legal, ethical an wise.

>> but as expected, the memo coming under fire from civil rights activists because of how broadly imminent threat is defined. quote, the condition that an operational leader present an imminent threat of violent attack against the united states does not require the united states to have clear evidence that a specific attack on u.s. persons and interests will take place in the immediate future. now, the memo also has new details on legal case behind more drone strikes against al qaeda suspects. such as a strike happened in yemen in september 2011 killing alleged al qaeda operatives, both american citizens not indicted or charged with crimes. all of this could come to a head on thursday for john brennan . eight democratic and three republican senators have written to president obama asking for the legal opinions authorizing the killing of americans . joining me now, national investigative correspondent michael isacoff. i saw your report and the reaction to the report. is it really surprising at this point?

>> well, i think it's not that surprising, mainly because the administration has been so resistant to releasing any of the memos that explain its legal reasoning behind these drone strikes and in particular the drone strikes targeting american citizens. members of congress have asked to see copies. "the new york times" went to court and sued under the freedom of information act to obtain copies. and the administration has completely shut those requests down saying these memos are classified. if they exist and they're not going to discuss or release anything. so that has sort of built pressure up for the administration to show its cards. these are very consequential policies. we are here talking about american citizens who have constitutional rights to life and liberty which can't be deprived without due process of law under the constitution so if they're going to be targeted, with drone strikes, who's making those decisions and what are the criteria that are being used?

>> all right. michael , thank you very much. joining me to talk about the questions posed by michael , jameel jeff ford and director of aclu national security project. thank you for joining us.

>> thank you for the invitation.

>> i would like to play attorney general holder just said today in response to the white paper . let's play it, please.

>> one of the things i want to make sure everybody understands is our primary concern is to keep the american people safe. but to do so in a way that's consistent with our laws and consistent with our values. we are -- we have as a basis for action that we take a congressional statute that allows us to operate against al qaeda and associated entitentities, not only in pakistan or not only in afghanistan but other parts of the world. we say that we only take these kinds of actions when there's an imminent threat , when capture is not feasible and when we are confident that we're doing so in a way that's consistent with federal and international law .

>> does that answer or satisfy your concerns?

>> no. i think that this is a memo that sets out a very broad authority. there are some limit that is are stated in the memo. for example, the administration says that they will carry out these strikes only against people who pose imminent threat but imminence is so broadly defined. and true of the other limitations. the limitations aren't really limitations at all. the other, you know, other issue with the limitations is that the administration says that they're not enforceable by any court so at the end of the day it is executive branch officials making the decision about whether any particular person presents a threat and nobody is looking over their shoulder.

>> i want to read senator diane dpin stei feinstein, her statement this morning says in part as president obama said at time of his death, alaki was the operations leader of aqap. he directed the failed attempt to blow up an airplane on christmas day 2009 and responsible for attempts to blow up cargo planes in 2010 . recruiting others to kill americans until the time of his death in yemen. essentially people read in to that this is a statement that the bad guys were planning something. so this is what needs to happen. you hear a lot of people say, how can you defend these people who were plotting against americans .

>> right. so let's just assume that everything that that statement says about al alawaki is true? this is going to be true of others killed by drone strikes. they have not been under him. one was khan that grew up here in new york. another was a 16-year-old kid. nobody has ever alleged he did anything wrong. you have to make sure that you have checks and balances in place because some of the people that the government target may not be the worse guys in the world and make sure that the next administration has checks on it and the administration after that. even if you trust this administration with the power.

>> especially urgent with the number of drone strikes since 2002 . 4,700 killed in the use of drones. we did the segment with the "time" magazine writer. the cover was a drone nation and talking about the use internationally there.

>> not only actual battlefields but afghanistan. there's no geographic limit set out in the memo that was released yesterday that mike isikoff got hold of. you're not talking about battlefield. you're talking about far removed from actual battlefields and you need to make sure that there are limits in place and for the executive branch to say just trust us is not enough.

>> what do you need to hear from nominee cia nominee john brennan then on the hearing thursday?

>> i think wuone thing the administration should do is release the legal memos before that hearing because this briefing paper is a summary of the legal memos, not the legal memos themselves. that should inform the debate about john brennan 's nomination and then asked about the drone program, about his role in it, what he thinks of the checks and balances in place.

>> thank you very much for joining us. i hope we can talk with you the day of the hearing, as well. thank you.

>> thank you.

Source: http://video.msnbc.msn.com/newsnation/50708414/

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Lower drinking ages lead to more binge drinking, study of U.S. states finds

Feb. 6, 2013 ? People who grew up in U.S. states where it was legal to drink alcohol before age 21 are more likely to be binge drinkers later in life, according to a study by researchers at Washington University School of Medicine in St. Louis.

The findings are available online in Alcoholism: Clinical & Experimental Research.

The researchers tracked the long-term drinking behavior of more than 39,000 people who began consuming alcohol in the 1970s, when some states had legal drinking ages as low as 18.

"It wasn't just that lower minimum drinking ages had a negative impact on people when they were young," explains first author Andrew D. Plunk, PhD, a post-doctoral research fellow in psychiatry. "Even decades later, the ability to legally purchase alcohol before age 21 was associated with more frequent binge drinking."

The study shows that people who lived in states with lower minimum drinking ages weren't more likely to consume more alcohol overall or to drink more frequently than those from states where the drinking age was 21, but when they did drink, they were more likely to drink heavily.

The effect was most pronounced among men who did not attend college. And the researchers say the findings should be a warning to those who advocate lowering the minimum drinking age.

"Binge drinking on college campuses is a very serious problem," Plunk says. "But it's also important not to completely forget about young people who aren't on college campuses. In our study, they had the greatest risk of suffering the long-term consequences linked to lower drinking ages."

Plunk and his colleagues found that even decades later, men who grew up in states with a legal drinking age lower than 21 were 19 percent more likely to binge drink more than once per month. Among those who didn't go to college, the odds of binging more than once a month increased by 31 percent.

Through surveys conducted in the early 1990s and again in the early 2000s, the researchers tracked the average daily alcohol intake, overall drinking frequency and the frequency of binge episodes -- defined as five or more drinks during a single period of drinking for a man or four-plus drinks for a woman. They also looked at how often a person drank but did not binge, which is thought to be a less harmful drinking pattern.

"There's a difference between tracking average daily consumption of alcohol and measuring drinking patterns," explains senior author Richard A. Grucza, PhD, an associate professor of psychiatry. "Merely tracking average daily consumption can hide harmful drinking patterns. Averaging one drink per day doesn't sound like much, but if that same person has all their drinks for the week in one sitting, well that's a potential problem."

Due to concerns about binge drinking on college campuses, some policymakers think that lowering the drinking age may encourage college students to moderate their alcohol use.

"The 'take away message' is that we need to consider all of the potential consequences of changing the drinking age," Plunk explains. "We shouldn't be too narrow in our focus when we think about how young people are affected by these laws. This study shows there's a large population that benefitted from a higher legal drinking age. Laws apply to everyone, but if they are based only on the impact on one group like college students, we may end up forgetting about how those laws affect other people."

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The above story is reprinted from materials provided by Washington University School of Medicine. The original article was written by Jim Dryden.

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

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Journal Reference:

1. Andrew D. Plunk, Patricia Cavazaos-Rehg, Laura J. Bierut, Richard A. Grucza. The Persistent Effects of Minimum Legal Drinking Age Laws on Drinking Patterns Later in Life. Alcoholism: Clinical and Experimental Research, 2013; DOI: 10.1111/j.1530-0277.2012.01945.x

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.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/living_well/~3/9jAwr5BfeIs/130206162327.htm

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Bulgaria: IDs, location of 2 terror suspects known

SOFIA, Bulgaria (AP) ? The two living suspects behind a bus attack that killed five Israeli tourists in Bulgaria last year have been identified and both are now living in Lebanon, a top Bulgarian security official said Wednesday.

The bomb that exploded July 18 as the Israeli tourists were boarding a bus at the airport in Burgas also killed a Bulgarian bus driver and the suspected bomber. Three men are suspected in the attack, including the dead bomber.

On Tuesday, an official Bulgarian report said investigators had "well-grounded reasons to suggest" that two of the suspects belonged to the militant wing of the Islamist group Hezbollah. The report said they had been living in Lebanon for years, one with a Canadian passport and the other with an Australian one.

Stanimir Florov, head of Bulgaria's anti-terror unit, said Wednesday that the names of the suspects were known, they were now based in the same country and "we have asked Lebanese authorities to assist in our investigation." He did not elaborate.

The identity of the bomber remains unknown even though his DNA samples have been shared with intelligence agencies in other nations, he said, adding that no DNA match has been found in their databases.

Florov said the bomb was likely supposed to explode while the bus was in motion "but the terrorists obviously made a mistake."

Europol Director Rob Wainwright confirmed that comment, telling The Associated Press that investigators believe the bomber never intended to die. A Europol expert who analyzed a fragment of a circuit board from the bomb determined that it was detonated remotely, he said.

If the explosives had blown up while the bus was full, there would have been many more victims and much of the evidence would have been destroyed, Florov said.

"In that case, the investigation would have started from ground zero," he said.

Canadian Immigration Minister Jason Kenney told the National Post that one of the suspects was born in Lebanon, came to Canada at age eight, became a Canadian citizen and then left at age 12. He said he assumed the man was a dual Lebanese-Canadian citizen.

"I understand he may have been back to Canada a few times since then, but he has not has been a habitual resident in Canada since the age of 12," Kenney said.

___

AP bureau chief Rob Gillies in Toronto contributed to this story.

Source: http://news.yahoo.com/bulgaria-ids-location-2-terror-suspects-known-175509437.html

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Danish critic of Islam says gunman shot at him

COPENHAGEN, Denmark (AP) ? A gunman tried to shoot a Danish writer and prominent critic of Islam on Tuesday, but missed and fled after a scuffle with his intended victim, police and the writer said.

Lars Hedegaard, who heads a group that claims press freedom is under threat from Islam, told The Associated Press he was shaken but not physically injured in the attack at his Copenhagen home.

Police said they were searching for the suspect, whom they described as a "foreign" man aged 20-25.

Hedegaard, 70, said the gunman rang the doorbell of his apartment building on the pretext of delivering a package, and when Hedegaard opened the front door, the man pulled out a gun and fired a shot that narrowly missed the writer's head.

"The bullet flew past my right ear, after which I attacked him and punched him in the face, which made him lose the gun," Hedegaard told AP. He said the gunman then fled.

Hedegaard heads the Free Press Society in Denmark and its international offshoot, the International Free Press Society. He is also among the publishers of a weekly anti-Islam newsletter.

In 2011, he was convicted of hate speech and fined 5,000 kroner ($1,000) for making a series of insulting and degrading statements about Muslims.

Denmark's Prime Minister Helle Thorning-Schmidt condemned what she called a "despicable" act.

"It is even worse if the attack is rooted in an attempt to prevent Lars Hedegaard to use his freedom of expression," she said.

Hedegaard has expressed support for a range of outspoken Islam critics in Europe, including Swedish artist Lars Vilks and Dutch lawmaker Geert Wilders.

"Failed attack on my friend and Islam critic Lars Hedegaard in Denmark this morning. My thoughts are with him. Terrible," Wilders tweeted.

The Free Press Society said it was "shaken and angry," but "relieved that the perpetrator did not succeed."

Several Scandinavian writers, artists and journalists have been exposed to threats and violence from extremists since the 2005 publication of Danish newspaper cartoons of the Prophet Muhammad triggered an uproar in Muslim countries.

Many Muslims believe the prophet should not be depicted at all ? even in a flattering way ? because it might encourage idolatry

In 2010, a Somali man living in Denmark used an ax to break into the home of one of the cartoonists, who escaped unharmed by locking himself into a panic room.

Last year, four Swedish residents were convicted of terrorism in Denmark for plotting a shooting spree at the newspaper that first published the Muhammad caricatures.

In Sweden, Vilks has lived under police protection after a drawing he made depicting Muhammad as a dog led to death threats from militant Islamists.

Source: http://news.yahoo.com/danish-critic-islam-says-gunman-shot-him-170835901.html

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France: 4 detained suspected of extremist links

PARIS (AP) ? France's interior minister says police have detained four people in a counterterrorist operation targeting those suspected of trying to join Islamist extremists abroad.

Manuel Valls said on France's BFM television Tuesday that an operation is under way in the Paris region, linked to the arrest of a French citizen in recent months on the Mali-Niger border. No details were immediately available.

Valls said French authorities are worried about French extremists joining rebels in Syria or the desert region around northern Mali, where Islamist radicals seized power last year and imposed harsh rule on local populations.

France, which fears northern Mali could become haven for international terrorists, launched a military intervention there last month after the extremists starting advancing toward the capital.

Source: http://news.yahoo.com/france-4-detained-suspected-extremist-links-085134756.html

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