Symptoms of Prader-Willi syndrome associated with interference in circadian, metabolic genes

June 25, 2013 ? Researchers with the UC Davis MIND Institute and Agilent Laboratories have found that Prader-Willi syndrome -- a genetic disorder best known for causing an insatiable appetite that can lead to morbid obesity -- is associated with the loss of non-coding RNAs, resulting in the dysregulation of circadian and metabolic genes, accelerated energy expenditure and metabolic differences during sleep.

The research was led by Janine LaSalle, a professor in the UC Davis Department of Medical Microbiology and Immunology who is affiliated with the MIND Institute. It is published online in Human Molecular Genetics.

"Prader-Willi syndrome children do not sleep as well at night and have daytime sleepiness," LaSalle said. "Parents have to lock up their pantries because the kids are rummaging for food in the middle of the night, even breaking into their neighbors' houses to eat."

The study found that these behaviors are rooted in the loss of a long non-coding RNA that functions to balance energy expenditure in the brain during sleep. The finding could have a profound effect on how clinicians treat children with Prader-Willi, as well as point the way to new, innovative therapies, LaSalle said.

The leading cause of morbid obesity among children in the United States, Prader-Willi involves a complex, and sometimes contradictory, array of symptoms. Shortly after birth children with Prader-Willi experience failure to thrive. Yet after they begin to feed themselves, they have difficulty sleeping and insatiable appetites that lead to obesity if their diets are not carefully monitored.

The current study was conducted in a mouse model of Prader-Willi syndrome. It found that mice engineered with the loss of a long non-coding RNA showed altered energy use and metabolic differences during sleep.

Prader-Willi has been traced to a specific region on chromosome 15 (SNORD116), which produces RNAs that regulate gene expression, rather than coding for proteins. When functioning normally, SNORD116 produces small nucleolar (sno) RNAs and a long non-coding RNA (116HG), as well as a third non-coding RNA implicated in a related disorder, Angelman syndrome. The 116HG long non-coding RNA forms a cloud inside neuronal nuclei that associates with proteins and genes regulating diurnal metabolism in the brain, LaSalle said.

"We thought the cloud would be activating transcription, but in fact it was doing the opposite," she said. "Most of the genes were dampened by the cloud. This long non-coding RNA was acting as a decoy, pulling the active transcription factors away from genes and keeping them from being expressed."

As a result, losing snoRNAs and 116HG causes a chain reaction, eliminating the RNA cloud and allowing circadian and metabolic genes to get turned on during sleep periods, when they should be dampened down. This underlies a complex cycle in which the RNA cloud grew during sleep periods (daytime for nocturnal mice), turning down genes associated with energy use, and receded during waking periods, allowing these genes to be expressed. Mice without the 116HG gene lacked the benefit of this neuronal cloud, causing greater energy expenditure during sleep.

The researchers said that the work provides a clearer picture of why children with Prader-Willi syndrome can't sleep or feel satiated and may change therapeutic approaches. For example, many such children have been treated with growth hormone because of short stature, but this actually may boost other aspects of the disease.

"People had thought the kids weren't sleeping at night because of the sleep apnea caused by obesity," said LaSalle. "What this study shows is that the diurnal metabolism is central to the disorder, and that the obesity may be as a result of that. If you can work with that, you could improve therapies, for example figuring out the best times to administer medications."

The study's other study authors include Weston T. Powell, Rochelle L. Coulson, Florence K. Crary, Spencer S. Wong, Robert A. Ach and Dag H. Yasui, all of UC Davis, and Peter Tsang and N. Alice Yamada of Agilent Laboratories.

The work was funded by National Institutes of Health grants F31NS073164 and 1R01NS076263 and the Prader-Willi Foundation.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/health_medicine/genes/~3/JgN0Vq4Ecko/130625141219.htm

bats

Will iRobot and Cisco's New Robot Take a Bite Out of Business ...

If Cisco and iRobot have their way, robot CEOs may invade boardrooms from Tokyo to New York in 2014. The two companies?recently announced collaboration on the autonomous Ava 500 telepresence robot for business. The firms hope the Ava 500 will allow business people to attend daily meetings in person, across the planet?without ever changing a plane or time zone.

The navigation technology behind iRobot?s Roomba robot vacuum cleaner and the RP Vita medical telepresence robot will guide the five foot five inch, 100 pound Ava 500. Meanwhile, a Cisco TelePresence EX60 personal video endpoint will broadcast a worker?s face and voice from its?21.5? screen and send back sounds and images via an onboard camera and microphone.

Using a special app on a tablet, remote workers will wake the robot up and tell it where to go. The Ava 500 can map and autonomously navigate the halls of its home office, freeing the telecommuter to make small talk along the way (or leave the screen off until it reaches its destination). After a meeting, the unit dutifully returns to its charging station to catch a few winks and juice up for its next appointment.

iRobot CEO, Colin Angle, told the Boston Herald the Ava 500 gives folks the chance to be in the same room as the people they?re meeting, to see facial expressions, and to go in the hall after for a private chat. Angie Mistretta, director of telepresence solutions at Cisco, says, ?The real value of the robot is that spontaneity.?

The question is whether that spontaneity is worth the robot?s $70,000 price tag?(or?$2,000 ? $2,500 a month to rent). iRobot and Cisco are targeting executives, corporate trainers, site inspectors, and remote employees. Travel costs for these folks can stack up fast.?If Ava 500 saves even a few trips a month, the robot could pay its way.

But businesses are cost cutting machines. If telepresence robots are attractive at $70,000, then they?re even more appealing at $7,000, and exponentially sexier as the price tag approaches $0.?And already, firms can order a simpler telepresence robot from Double Robotics for $2,599. Businesses may be willing to sacrifice a little screen real estate and autonomous navigation for $67,000 in saved costs.

Double Robotics iPad telepresence robot.

And they may not need to make that sacrifice very long.?Advanced AI and robotics are entering the consumer market at drastically reduced prices.

We recently wrote about AI startup Anki. Anki?s robot cars drive themselves around a track at top speed, avoiding each other, the wall, making evasive maneuvers?all this runs on iOS with an expected cost of $200.?But Anki isn?t just about toy cars. It?s an iOS-powered consumer AI and robotics platform.

Such technology will just as easily guide an autonomous telepresence robot through the office. And soon. Offering enterprise solutions at enterprise prices in a world where AI and robotics are hitting consumer markets at consumer prices?how long will such products make sense?

Source: http://singularityhub.com/2013/06/21/will-irobot-and-ciscos-new-robot-take-a-bite-out-of-business-travel/

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Western and Arab allies try to coordinate rebel aid

By Lesley Wroughton and Amena Bakr

DOHA (Reuters) - Western and Arab opponents of Bashar al-Assad met in Qatar on Saturday to tighten coordination of their stepped up support for rebels battling to overthrow the Syrian president.

Ministers from 11 countries including the United States, European and regional Sunni Muslim powers, held talks that Washington said should commit participants to direct all aid through the Western-backed Supreme Military Council, which it hopes can offset the growing power of jihadist rebel forces.

After a series of military offensives by Assad's troops, including the recapture of a strategic border town two weeks ago, President Barack Obama said the United States would increase military support for the rebels.

Two Gulf sources told Reuters on Saturday that Saudi Arabia, which has taken a lead role among Arab opponents of Assad, had also accelerated delivery of advanced weapons to the rebels.

"In the past week there have been more arrivals of these advanced weapons. They are getting them more frequently," one source said, without giving details. Another Gulf source described them as "potentially balance-tipping" supplies.

Rebel fighters say they need anti-aircraft and anti-tank weapons to stem the fightback by Assad's forces in a civil war that has already killed 93,000 people and driven 1.6 million refugees into neighboring countries.

The increasingly sectarian dynamic of the war pits mainly Sunni Muslims against forces loyal to Assad, from the Alawite minority which is an offshoot of Shi'ite Islam, and has split the Middle East along Sunni-Shi'ite lines.

Qatar's Prime Minister Sheikh Hamad bin Jassim al-Thani, whose country has been one of the most open backers of the anti-Assad rebels, said that supplying them with weapons was the only way to resolve the conflict.

"Force is necessary to achieve justice. And the provision of weapons is the only way to achieve peace in Syria's case," Sheikh Hamad told ministers at the start of the talks.

"We cannot wait due to disagreement among Security Council members over finding a solution to the problem," he said. He also called on Lebanon's government to halt intervention by Lebanese factions in the neighboring conflict.

Lebanese Hezbollah guerrillas led the assault by Assad's forces to recapture the town of Qusair earlier this month.

Speaking before Secretary of State John Kerry arrived in Doha, a U.S. official said the United States wanted to ensure that "every kind of assistance" offered by the 11 countries attending the meeting go through the Supreme Military Council, led by General Salim Idriss, a former commander in Assad's army.

A diplomat who had seen the draft communiqu? of the meeting said it also spoke of putting pressure on Assad to allow greater access for humanitarian aid after the United Nations launched a $5 billion appeal earlier this month - its biggest ever.

But he said there was no mention of establishing a no-fly zone - a move which diplomats have said the United States was studying but which the White House has played down - or specific mention of weapons supplies to the rebels.

COUNTERING JIHADI REBELS

The meeting in Qatar brings together ministers of countries that support the anti-Assad rebels - France, Germany, Egypt, Italy, Jordan, Qatar, Saudi Arabia, Turkey, United Arab Emirates, Britain and the United States.

Western countries hope by channeling assistance through Idriss they can reduce the influence in the opposition ranks of radical Islamist groups such as the al Qaeda-linked Nusra Front.

British Foreign Secretary William Hague reiterated that London had yet to take a formal decision on arming the rebels, but said that only by strengthening the opposition could the West hope to bring about talks for a political settlement.

"We won't get a political solution if Assad and his regime think they can eliminate all legitimate opposition by force, and so we do have to give assistance to that opposition," he told reporters before the start of Saturday's talks.

The United States and Russia, which back opposing sides in the conflict, hope to bring them together for negotiations in Geneva originally scheduled for this month. Hague said there was little prospect of that happening "in the next few weeks".

"This crisis is on a worse trajectory, it is set to get worse ... I don't want to underestimate the severity and the bleakness of it," Hague said.

Moscow, which says it will not break off military supply contracts with Damascus, opposes arming rebel forces that it says include terrorist groups, and has warned that a swift exit by Assad would risk a dangerous power vacuum.

In northern Syria, rebels announced an offensive that they said aimed to capture the western districts of the city of Aleppo from government forces.

Assad's troops are have been fighting rebels in rural areas around Syria's biggest city and are believed to be reinforcing in the region, ahead of their own expected assault on rebel-held parts of the contested northern hub.

In Damascus, the army sustained its bombardment of the eastern rebel-held district of Qaboun and soldiers clashed rebels in the Barzeh district, the Britain-based Syrian Observatory for Human Rights said.

Before his departure from Washington, Kerry spent Thursday briefing Congress on the administration's Syria plans, with some lawmakers pressing for the United States to do more and others decrying any deeper involvement in the civil war.

Having withdrawn U.S. troops from Iraq and working to wind down American forces in Afghanistan, some lawmakers are wary of getting involved in another costly conflict. Some worry that the weapons could end up in the hands of radical Islamist groups who could one day use them against Western interests.

Until now the United States has been providing non-lethal aid - food and medicine - to the rebels.

(Additional reporting by Yara Bayoumy; Writing by Dominic Evans; Editing by Alison Williams)

Source: http://news.yahoo.com/putin-warns-arming-syrian-rebels-conflict-widens-083445291.html

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