Molecular key to exhaustion following sleep deprivation

Mar. 7, 2013 ? It happens to everyone: You stay up late one night to finish an assignment, and the next day, you're exhausted. Humans aren't unique in that; all animals need sleep, and if they don't get it, they must make it up.

The biological term for that pay-the-piper behavior is "sleep homeostasis," and now, thanks to a research team at the Perelman School of Medicine, University of Pennsylvania, one of the molecular players in this process has been identified -- at least in nematode round worms.

David Raizen, MD, PhD, assistant professor of Neurology, and his colleagues report in Current Biology that even in Caenorhabditis elegans, a tiny nematode worm that feeds on bacteria, loss of sleep is "stressful."

The researchers forced the animals to stay awake during a developmental stage when they normally sleep, called "lethargus." These sleep-deprived worms, like college students after an all-nighter, exhibited signs of sleep homeostasis -- they were harder to wake up compared to control worms.

While nematode worms do not sleep as vertebrates do, lethargus is a sleep-like state, says Raizen, characterized by episodic reversible immobility, elevated arousal thresholds, and homeostasis.

On the molecular level, loss of sleep in the worm was associated with migration of the stress-related DNA-binding protein DAF-16, also called FOXO, from the cell cytoplasm into the nucleus. Here, the protein activates expression of stress-related genes. Knocking out that DAF-16 gene eliminated the animals' homeostatic response -- the equivalent of giving an up-all-night college student a free pass on sleep deprivation.

"You might think that is a good thing," Raizen says, "but a good percentage of DAF-16 mutants died" -- as many as half of the worms in some cases. That, Raizen says, suggests that the movement of DAF-16 into the nucleus is not merely a consequence of sleep deprivation, but rather a key to the homeostatic response.

"There's something important about being able to mount a homeostatic behavioral response," Raizen concludes. "We don't know what that is, but it's clearly important to the animal."

Sleep homeostasis is critical to human health. Sleep deprivation in humans has been linked to weight gain and insulin resistance, and in laboratory rats, has been linked to death, Raizen says.

Whether DAF-16/FOXO will play the same role in humans as in nematodes is an open question. But it turns out that C. elegans is actually a useful model organism for studying vertebrate neurobiology, Raizen says. Many key observations made in the invertebrate have carried over to vertebrate systems.

Interestingly, when the team asked which tissue requires DAF-16 activity in order to restore sleep homeostasis in mutant animals, they found to their surprise that it isn't neurons. But restoring DAF-16 activity in muscle tissue did restore homeostasis, suggesting an extra-neuronal component of sleep.

"The muscle must somehow communicate with the nervous system to coordinate this response," Raizen says.

Co-authors include Robert J. Driver and Annesia Lamb from the Department of Neurology, and Abraham Wyner, from the Wharton School.

The research was funded by the National Institutes of Health's National Institute of Neurological Disorders and Stroke (NS064030) and Office of Research Infrastructure (OD010440) and the Brain & Behavior Research Foundation.

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The above story is reprinted from materials provided by Perelman School of Medicine at the University of Pennsylvania, via Newswise.

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. Robert J. Driver, Annesia L. Lamb, Abraham J. Wyner, David M. Raizen. DAF-16/FOXO Regulates Homeostasis of Essential Sleep-like Behavior during Larval Transitions in C. elegans. Current Biology, March 2013 DOI: 10.1016/j.cub.2013.02.009

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/health_medicine/genes/~3/BQWa9xa_C8s/130307122917.htm

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Scientists focus on another Sandy loss _ lab mice

In this Jan. 18, 2013 photo provided by the NYU Langone Medical Center, a researcher holds a laboratory mouse in a research building at the hospital's complex in New York. During Superstorm Sandy on Oct. 29, 2012, a storm surge flooded the basement housing some 7,000 cages of mice used for studying cancer, diabetes, brain development and other health issues. Each cage held up to five of the little rodents, and even four months later, nobody knows exactly how many perished. (AP Photo/New York University)

In this Jan. 18, 2013 photo provided by the NYU Langone Medical Center, a researcher holds a laboratory mouse in a research building at the hospital's complex in New York. During Superstorm Sandy on Oct. 29, 2012, a storm surge flooded the basement housing some 7,000 cages of mice used for studying cancer, diabetes, brain development and other health issues. Each cage held up to five of the little rodents, and even four months later, nobody knows exactly how many perished. (AP Photo/New York University)

In this Jan. 18, 2013 photo provided by the NYU Langone Medical Center, a technician examines mice in order to determine their clinical health in a research building at the hospital's complex in New York. During Superstorm Sandy on Oct. 29, 2012, a storm surge flooded the basement housing some 7,000 cages of mice used for studying cancer, diabetes, brain development and other health issues. Each cage held up to five of the little rodents, and even four months later, nobody knows exactly how many perished. (AP Photo/New York University)

This Jan. 18, 2013 photo provided by the NYU Langone Medical Center shows genetically engineered mice used to model human diseases in a cage with nesting material in a research building at the hospital's complex in New York. During Superstorm Sandy on Oct. 29, 2012, a storm surge flooded the basement housing some 7,000 cages of mice used for studying cancer, diabetes, brain development and other health issues. Each cage held up to five of the little rodents, and even four months later, nobody knows exactly how many perished. (AP Photo/New York University)

NEW YORK (AP) ? It was one of the most dramatic stories from Superstorm Sandy: more than 300 patients including tiny babies safely removed from a flooded New York hospital that lost power. But in a research building at the complex, where thousands of lab mice were kept, the story had a sadder ending.

A storm surge into the basement swamped some 7,000 cages of mice used for studying cancer, diabetes, brain development and other health issues. Each cage held up to five of the little rodents, and even four months later, nobody knows exactly how many perished.

Now, about 50 scientists at the NYU Langone Medical Center are going through the slow process of replacing them. What they lost in a few minutes one terrible night in October will take more than a year to recover, at a cost of tens of millions of dollars.

That's because, for the most part, they can't simply buy the mice off the shelf. Most were tailor-made, engineered to carry specific genetic mutations to mimic human diseases and conditions like autism. Some breeds can be found only in a few labs worldwide. Others were too new to have been shared yet with researchers elsewhere and will take many months or even two years to recreate.

Besides the mice, researchers lost precious specimens and suffered damage to sensitive equipment from the blackouts and flooding from the nearby East River. The 700-bed hospital closed for almost two months; the emergency room is still shut down.

For researcher Sergei Koralov, the flooding meant the loss of about 600 mice. Gone, for example, were his animals that helped illuminate how genetic changes in white blood cells lead to lymphoma and those he used to study what triggers chronic lung inflammation in asthma. An experiment for improving lung function was also washed away.

"I was devastated," he recalls.

Koralov has contacted scientists in the U.S., Switzerland and Germany in an effort to rebuild his mouse colonies. Scientists often share mice with other labs, which comes in handy at a time like this.

But it's not as easy as just shipping mice to New York. The mice at NYU live in a super-clean environment, and those imported from other labs carry a risk of contamination. So scientists use them to create a new generation of animals that are quarantined and checked for germs before they enter their NYU home.

Not all the mice in the basement died in the flood; those in about 600 cages were rescued about a week afterward. Their handlers had put extra food in their cages just in case before the storm. But because of contamination, new generations have to be created from them, too, in sterile surroundings.

When no mice with the right genetic makeup are available, researchers have to start from scratch. Koralov works with mice that have many genetic modifications, perhaps as many as seven per mouse, and recreating such animals can require breeding over half a dozen generations.

In all, he figures it will take two years to recover the most complicated ones. But the storm has given him the chance to take a new look at his research.

"The silver lining of the whole storm, what little there is, is the fact it allows me to refocus myself," he said. Now he can "go after what is interesting to me now, not what was interesting to me two years ago."

Much of the effort to replace the mice is taking place elsewhere. The Jackson Laboratory in Bar Harbor, Maine, which distributes more than 6,000 kinds of modified mice to labs around the world, is working on at least 200 types for the New York researchers, said the lab's Stephen Linnell.

So what can be done to prepare for the next big storm?

At NYU Langone, officials will consider waterproofing strategies for one building that houses mice underground and they are working on "an aggressive evacuation plan," said Dafna Bar-Sagi, the center's vice dean for science.

A new science building is due to open in 2016, with one feature planned even before the storm: It will keep mice on the third floor.

___

Malcolm Ritter can be followed at http://www.twitter.com/malcolmritter

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/b2f0ca3a594644ee9e50a8ec4ce2d6de/Article_2013-03-06-US-SCI-Superstorm-Need-New-Mice/id-e80c3a43cd3e4226a25d74aa6bc02c11

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iOS gains on Android in January as Windows Phone remains stagnant

RIO DE JANEIRO, March 5 (Reuters) - Brazil coach Luiz Felipe Scolari stood up for specialist dribbler Neymar on Tuesday, saying the flamboyant forward's reputation for falling down easily was undeserved and exaggerated. "He gets fouled 10 times a match, and possibly one or two of those free kicks shouldn't be awarded, but then that is normal in football," Scolari told a news conference on Tuesday. "The coaches who criticise Neymar, who claim he falls over or simulates fouls, do that because it's an easy way out for them. ...

Source: http://news.yahoo.com/ios-gains-android-january-windows-phone-remains-stagnant-194134528.html

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'Es Chavista': The time Venezuelan fans booed Magglio Ordonez at the World Baseball Classic

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Grotesque Mummy Head Reveals Advanced Medieval Science

In the second century, an ethnically Greek Roman named Galen became doctor to the gladiators. His glimpses into the human body via these warriors' wounds, combined with much more systematic dissections of animals, became the basis of Islamic and European medicine for centuries.

Galen's texts wouldn't be challenged for anatomical supremacy until the Renaissance, when human dissections ? often in public ? surged in popularity. But doctors in medieval Europe weren't as idle as it may seem, as a new analysis of the oldest-known preserved human dissection in Europe reveals.

The gruesome specimen, now in a private collection, consists of a human head and shoulders with the top of the skull and brain removed. Rodent nibbles and insect larvae trails mar the face. The arteries are filled with a red "metal wax" compound that helped preserve the body. [Gallery: Historic Images of Human Anatomy]

The preparation of the specimen was surprisingly advanced. Radiocarbon dating puts the age of the body between A.D. 1200 and A.D.1280, an era once considered part of Europe's anti-scientific "Dark Ages." In fact, said study researcher Philippe Charlier, a physician and forensic scientist at University Hospital R. Poincare in France, the new specimen suggests surprising anatomical expertise during this time period.? ?

"It's state-of-the-art," Charlier told LiveScience. "I suppose that the preparator did not do this just one time, but several times, to be so good at this."

Myths of the middle ages

Historians in the 1800s referred to the Dark Ages as a time of illiteracy and barbarianism, generally pinpointing the time period as between the fall of the Roman Empire and somewhere in the Middle Ages. To some, the Dark Ages didn't end until the 1400s, at the advent of the Renaissance.

But modern historians see the Middle Ages quite differently. That's because continued scholarship has found that the medieval period wasn't so ignorant after all. [Busted! 10 Medieval Myths]

"There was considerable scientific progress in the later Middle Ages, in particular from the 13th century onward," said James Hannam, an historian and author of "The Genesis of Science: How the Christian Middle Ages Launched the Scientific Revolution" (Regnery Publishing, 2011).

For centuries, the advancements of the Middle Ages were forgotten, Hannam told LiveScience. In the 16th and 17th centuries, it became an "intellectual fad," he said, for thinkers to cite ancient Greek and Roman sources rather than scientists of the Middle Ages. In some cases, this involved straight-up fudging. Renaissance mathematician Copernicus, for example, took some of his thinking on the motion of the Earth from Jean Buridan, a French priest who lived between about 1300 and 1358, Hannam said. But Copernicus credited the ancient Roman poet Virgil as his inspiration.

Much of this selective memory stemmed from anti-Catholic feelings by Protestants, who split from the church in the 1500s.

As a result, "there was lots of propaganda about how the Catholic Church had been holding back human progress, and it was great that we were all Protestants now," Hannam said.?

Anatomical dark ages?

From this anti-Catholic sentiment arose a great many myths, such as the idea that everyone believed the world to be flat until Christopher Columbus sailed to the Americas. ("They thought nothing of the sort," Hannam said.)

Similarly, Renaissance propagandists spread the rumor that the Medieval Christian church banned autopsy and human dissection, holding back medical progress.

In fact, Hannam said, many societies have banned or limited the carving up of human corpses, from the ancient Greeks and Romans to early Europeans (that's why Galen was stuck dissecting animals and peering into gladiator wounds). But autopsies and dissection were not under a blanket church ban in the Middle Ages. In fact, the church sometimes ordered autopsies, often for the purpose of looking for signs of holiness in the body of a supposedly saintly person.

The first example of one of these "holy autopsies" came in 1308, when nuns conducted a dissection of the body of Chiara of Montefalco, an abbess who would be canonized as a saint in 1881. The nuns reported finding a tiny crucifix in the abbess' heart, as well as three gallstones in her gallbladder, which they saw as symbolic of the Holy Trinity.

Other autopsies were entirely secular. In 1286, an Italian physician conducted autopsies in order to pinpoint the origin of an epidemic, according to Charlier and his colleagues.

Some of the belief that the church frowned on autopsies may have come from a misinterpretation of a papal edict from 1299, in which the Pope forbade the boiling of the bones of dead Crusaders. That practice ensured Crusaders' bones could be shipped back home for burial, but the Pope declared the soldiers should be buried where they fell.

"That was interpreted in the 19th century as actually being a stricture against human dissection, which would have surprised the Pope," Hannam said.

Well-studied head

While more investigation of the body was going on in the Middle Ages than previously realized, the 1200s remain the "dark ages" in the sense that little is known about human anatomical dissections during this time period, Charlier said. When he and his colleagues began examining the head-and-shoulders specimen, they suspected it would be from the 1400s or 1500s.

"We did not think it was so antique," Charlier said.

But radiocarbon dating put the specimen firmly in the 1200s, making it the oldest European anatomical preparation known. Most surprisingly, Charlier said, the veins and arteries are filled with a mixture of beeswax, lime and cinnabar mercury. This would have helped preserve the body as well as give the circulatory system some color, as cinnabar mercury has a red tint. ?

Thus, the man's body was not simply dissected and tossed away; it was preserved, possibly for continued medical education, Charlier said. The man's identity, however, is forever lost. He could have been a prisoner, an institutionalized person, or perhaps a pauper whose body was never claimed, the researchers write this month in the journal Archives of Medical Science.

The specimen, which is in private hands, is set to go on display at the Parisian Museum of the History of Medicine, Charlier said.??

"This is really interesting from a historical and archaeological point of view," Charlier said, adding, "We really have a lack of skeletons and anthropological pieces."

Email Stephanie Pappas?or follow her @sipappas. Follow LiveScience on Twitter @livescience, on?Facebook?or?Google+. Original article on LiveScience.com.

Copyright 2013 LiveScience, a TechMediaNetwork company. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

Source: http://news.yahoo.com/grotesque-mummy-head-reveals-advanced-medieval-science-152557854.html

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Second sinkhole appears in Tampa area

SEFFNER, Florida (Reuters) - A second sinkhole appeared in the Tampa area on Monday, just miles from one that opened beneath a home last week and swallowed a man from his bed, though the latest one appeared not to pose immediate danger, police said.

The latest sinkhole opened between two homes and was about 12-feet round, 3 feet deep around the edge and about 5 feet deep in the center, said Hillsborough County spokesman Willie Puz.

He said the latest sinkhole appears to be unrelated to the one that opened last Thursday under the home of 37-year-old Jeff Bush.

"It is not geologically connected," Puz said.

Bush disappeared into the hole that opened up under his bedroom on Thursday night. The other occupants of the house, which is owned by the family of Jeremy Bush's fiancee, had been preparing for bed when they heard a loud crash and Jeff Bush screaming.

The hole was about 30 feet wide and 60 feet deep and filled with clay and debris. It is unlikely that Bush's body will ever be retrieved, officials said.

On Monday, demolition crews returned to Bush's home to demolish the rest of the house before efforts will begin to stabilize the sinkhole.

Two nearby houses have been evacuated because the sinkhole has weakened the ground underneath them, and their residents probably will never be allowed inside again, said Jessica Damico of Hillsborough County Fire Rescue.

Bush, a landscaper who mowed highway medians for a living, had moved into the four-bedroom home only two months ago which he shared with his brother, Jeremy Bush, 36, and four others.

Workers recovered a family Bible, flag, military medals, a purse, teddy bears and generations of photos. On Monday they recovered two antique rifles that were family heirlooms.

With the sinkhole expanding, engineers placed listening devices, microphones, ground-penetrating radar and other equipment testing the soil on the site to seek a safety zone to work and any sign of life below. They detected no such sign.

Jeremy Bush said the family was discussing plans for a memorial service and a possible marker at the site.

"I'm the only one who tried to get him out," he said, while begging county authorities to do more to find his brother's body when the lot is cleared.

Sinkholes in Florida are caused by the state's porous geological bedrock, according to the Florida Department of Environmental Protection.

As acidic rainwater filters into the ground, it dissolves the rock, causing erosion that can lead to underground caverns, which cause sinkholes when they collapse.

The latest sinkhole did not cause any injuries or structural damage to the homes around it.

(Editing by David Adams, Edith Honan, David Gregorio, Gary Hill)

Source: http://news.yahoo.com/demolition-continues-scene-missing-florida-sinkhole-victim-002318453.html

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