NEW YORK (AP) ? New father Jack Osbourne is facing a diagnosis of multiple sclerosis.
The former reality star and son of Ozzy and Sharon Osbourne revealed his health crisis in an interview with People released Sunday. He told the magazine he was angry and frustrated when he found out, and he's concerned about his family.
Osbourne and his fianc?e Lisa Stelly had daughter Pearl in April.
Multiple sclerosis attacks the brain and spinal cord, and can cause somewhat mild problems or serious disability, such as paralysis.
Jack Osbourne gained fame as a teen when his heavy metal father and his mother allowed the family to be profiled in the MTV reality show "The Osbournes."
By Dan Levine and Sarah McBride SAN FRANCISCO (Reuters) - Facebook Inc has agreed to pay $10 million to charity to settle a lawsuit that accused the site of violating users' rights to control the use of their own names, photographs and likenesses, according to court documents made public over the weekend. The lawsuit, brought by five Facebook members, alleged the social networking site violated California law by publicizing users' "likes" of certain advertisers on its "Sponsored Stories" feature without paying them or giving them a way to opt out, the documents said. A "Sponsored Story" is an advertisement that appears on a member's Facebook page and generally consists of another friend's name, profile picture and an assertion that the person "likes" the advertiser. The settlement was reached last month but made public this weekend. Facebook declined to comment on Saturday. The proposed class-action lawsuit, filed in federal court in San Jose, California, could have included nearly one of every three Americans, with billions of dollars in damages, according to previous court documents. In the lawsuit, Facebook Chief Executive Mark Zuckerberg was quoted as saying that a trusted referral was the "Holy Grail" of advertising. In addition, the lawsuit cited comments from Facebook chief operating officer Sheryl Sandberg, saying that the value of a "Sponsored Story" advertisement was at least twice and up to three times the value of a standard Facebook.com ad without a friend endorsement. U.S. District Judge Lucy Koh said the plaintiffs had shown economic injury could occur through Facebook's use of their names, photographs and likenesses. "California has long recognized a right to protect one's name and likeness against appropriation by others for their advantage," Koh wrote. The settlement arrangement is known as a cy-pres settlement, meaning the settlement funds can go to charity. The case in U.S. District Court, Northern District of California is Angel Fraley et al., individually and on behalf of all others similarly situated vs. Facebook Inc., 11-cv-1726. Facebook shares closed at $30.01 on Friday, down 21 percent since the company's initial public offering last month. (Editing by Jackie Frank)
16 June 2012Last updated at 03:08 GMTBy Richard BlackEnvironment correspondent, BBC News, Rio de Janeiro
UN talks on sustainable development are encountering disputes, delays and diplomatic wrangling, days before world leaders arrive to sign a new agreement.
The talks, in Rio de Janeiro, are aimed at putting the world economy on a more sustainable path, helping people out of poverty while protecting nature.
Yet developing countries have walked out over money, and the presence of Palestinians has brought complications.
Campaigners say there is little hope of momentous changes being agreed here.
"That's not even a question anymore," said Lasse Gustavsson, executive director of conservation with WWF International.
"It's clear we will get something, but it's equally clear we will not get what the planet needs," he told BBC News.
Preparatory talks broke down on Thursday evening as the G77/China bloc of 131 developing countries walked out of a number of sessions.
They said they could not talk about issues such as the green economy - which some see as likely to put a brake on development - unless western nations were clear about the amount of financial aid they were prepared to pledge.
The draft agreement negotiators are working on contains paragraphs that would commit the developed world to providing either $30bn per year or $100bn per year - but western governments are not prepared to agree to either figure.
Long weekend
Discussion groups reconvened on Friday morning; and Nikhil Seth, head of the Rio+20 secretariat, told reporters there was a "sense of cautious optimism and constructive engagement".
Continue reading the main story
Access and Benefit Sharing (ABS)
Granting countries the right to gain financially from the exploitation of biological resources discovered on their territory. Aims to prevent biopiracy. Agreement made at the UN CBC meeting in Nagoya, Japan in 2010. Rio+20 will see further discussion particularly of resources from international waters.
But by Thursday evening, he said, only 28% of the negotiating text had been agreed - an increase of 8% in two days.
Responsibility for the talks passed to the Brazilian government on Friday evening.
Luiz Alberto Figueiredo, director of environment in Brazil's foreign ministry, said the pace would pick up in order to finish the talks by Tuesday, when heads of government arrive.
"Only essential issues will be discussed so we can reach a text as soon as possible," he said. "Now it's the final hour."
A further stumbling block concerns the participation of Palestinian delegates.
As a recently admitted member of Unesco, the Palestinian delegation believed it had a seat at the table here under what is known as the All States rule.
But as talks began, the US objected to this interpretation. So officially, the preparatory talks did not begin; as of Friday afternoon, the situation had not been clarified.
It is unclear whether or how the Palestinian presence will affect next week's three-day summit, at which their minister will be entitled to make a set-piece speech.
More than 26,000 delegates have now been registered for the summit, including politicians, government negotiators, journalists and business leaders.
But the biggest contingent comes from groups campaigning either for poverty alleviation or environmental protection; and they appear uniformly frustrated by how much time is being taken up on detailed haggling rather than on agreeing a visionary outcome.
"It is developing countries and the world's poorest people who have the most to lose from a weak outcome at Rio+20," said Stephen Hale of Oxfam.
"We urgently need Brazil to step forward and persuade other countries to make commitments that match the urgency of the challenge."
WWF suggested that European heads of government, who are in the main staying away, should re-assess their priorities.
The UK's David Cameron and Germany's Angela Merkel are among those who are scheduled to attend the G20 meeting in Mexico on Monday and Tuesday before flying back to handle any fallout from Sunday's general election in Greece, rather than making the comparatively short hop to Rio.
"We have most of the heads of government, even heads of state, coming in from emerging economies - their GDP is about 30% of the world total, Greece's is about 0.37%," said Mr Gustavsson.
"We may look back on this as a historic moment when Europe handed over the sustainable development baton to the emerging economies."
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RIYADH (Reuters) - To outsiders, the al-Saud ruling family's succession process often appears opaque. But behind the ornate doors of Riyadh's palaces, the senior princes in a family thousands strong have long planned the next step in a complex dance of power.
Saudi Arabia's Defence Minister Prince Salman bin Abdulaziz is widely seen as the next most senior prince in the world's top oil exporter after the death of Crown Prince Nayef, which was reported on Saturday, just eight months after he had become the heir himself.
Unlike in European monarchies, the line of royal succession in Saudi Arabia does not move directly from father to eldest son, but is passed down a line of brothers born to the kingdom's founder King Abdulaziz Ibn Saud, who died in 1953.
So far, five brothers have become kings and around 20 are still alive.
But only a few of those are thought to be realistic candidates to rule the country where Islam was born some 14 centuries ago. Some have already been passed over or renounced their claims to rule.
"The inner circle of the al-Saud (family) can and do exclude from succession those found lacking in lineage, leadership and personal character," said an American embassy assessment of the succession process as detailed in a 1995 diplomatic cable released by WikiLeaks.
Under rules drawn up soon after Abdullah, the current monarch, became king in 2005, succession decisions lie with an "allegiance council" of the ruling al-Saud family.
When a king dies, his crown prince accedes to power and nominates a new crown prince.
The allegiance council, which has 34 princely members who each represent the family of a son of Ibn Saud, votes to approve the king's choice and has the power to elect its own nominee.
The council swore allegiance to Nayef as crown prince after the death of his predecessor Prince Sultan last year, but it was unclear if it actually voted.
While the next stage of the power planning transfer process appears straightforward and uncontroversial, there will be keen interest in how the council handles more complex succession decisions in the future.
FRONTRUNNERS
To avert a repeat of the situation that unfolded after King Fahd fell ill, when Abdullah's leadership was undermined by his ambiguous position as de facto regent without the formal title, the council has the power to remove a king or crown prince who is too sick to rule.
Given that Abdullah is nearly 90, the clause might prove an important failsafe in a country where power emanates from the top.
The next prince presumed to be in line for power is Prince Salman, who was made defence minister in November after Sultan's death, cementing his role near the top of the family hierarchy.
He served for five decades as governor of Riyadh province, a role that made him responsible for settling disputes between other members of the ruling family.
An owner of several major media outlets that have pushed a pro-government position and supported King Abdullah's cautious reforms, he said in 2007 that social change in the kingdom had to be slow and that the country was not ready for democracy, according to a U.S. embassy cable released by WikiLeaks.
Because Ibn Saud had so many sons born over a period of nearly five decades, various groups of princes have envisaged different paths for the kingdom's future.
The most powerful bloc within the variegated ranks of the al-Saud family is thought to comprise the sons born to Ibn Saud by his favorite wife Hassa bint Ahmed al-Sudairi: the so-called "Sudairi Seven".
They included the late King Fahd, Prince Sultan, Prince Nayef and Prince Salman. Three other brothers include a former defence minister, a former deputy defence minister and a deputy interior minister.
GRANDSONS
To many analysts, the key question is what will happen when the succession moves beyond the sons of Ibn Saud to one of his grandsons.
That decision might not be made for some years, but outside observers already see the emergence of a handful of contenders who appear better qualified to rule than their cousins.
There are no formal rules to dictate how the generational transition will be made other than through Abdullah's allegiance council. But any candidate would need broad support among the family as well as a strong record of political experience.
That might point to one of the Sudairis, such as Fahd's son Mohammed, who is governor of the Eastern Province, Sultan's son Khaled, who is deputy defence minister, or Nayef's son Mohammed, who as deputy interior minister was partly responsible for the successful suppression of an al Qaeda uprising six years ago.
Salman's son Sultan is the tourism minister and was the first Arab astronaut.
Another potential candidate among the third generation is Prince Khaled al-Faisal, son of the former King Faisal and the well regarded governor of Mecca Province, one of the most prestigious jobs in the country.
Prince Miteb bin Abdullah, the son of the present king, has inherited his father's position as head of the Saudi Arabian National Guard, a military unit that is separate from the ordinary armed forces whose role is to protect the kingdom from coups d'etats.
Having grooved to DocFest?s unique vibe when we experienced it for the first time last year, the Wandercats were just scratching to get back to Sheffield to enjoy the magic all over again. It has only been on for a day, but already DocFest 2012 ? tagline ?The Truth is ? In Here? ? seems set to be every bit as exciting, innovative and downright cool as its predecessor.
There were docs from the early morning, but we have never been morning cats, and so preferred to wait for the two big events of the day. The first, From the Sea to the Land Beyond, was something of a pre-official opening treat, and served to highlight the sort of media cross-pollination which DocFest seeks to foster. The film, directed by Penny Woolcock, brings together archive footage of the British coastline from the past 100 years, accompanied by a soundtrack from the group British Sea Power. The band was on hand to provide a live accompaniment for this special session, which took place in Sheffield Crucible theatre and was live-streamed. The project involved the cooperation of The Space, ?a new way to access and experience all of the arts ? for free?, the BFI, the BBC and the DocFest team themselves (festival director Heather Croall was co-producer). It was remarkable to see the last 100 years of British history play out in such a fashion ? the images were often startlingly beautiful, sometimes haunting, other times hilarious ? I can?t imagine that Blackpool council will be too happy with the way their town is portrayed in the more recent footage! The music was similarly captivating. We had only heard one song by British Sea Power (their single ?It Ended on an Oily Stage? was featured on The Bands 05 II compilation) but their anthemic, touching score for this film showed that they have some serious talent.
Keeping on a musical theme, the proper official opening night film was Searching for Sugar Man. Before the film we had opening night speeches from festival chair, Alex Graham, and Heather Croall. The latter was thrilled to have Sugar Man as the opening film, and after seeing it we could understand why. Incredible in the truest sense of the word, the film tells the story of some South African journalists who decided to try and find out about one of their favourite singers, Rodriguez, who made two albums and then disappeared, apparently burning himself to death on stage after a failed concert. Or else shooting himself in the head. Or perhaps taking a drug overdose? Basically there were more rumours of his death than there are for Kel Mitchell from Kenan & Kel! Nowadays,?with Wikipedia available to answer our every question, it is hard to imagine a time when musicians could be genuinely mythical beings, but Rodriguez (spoiler alert ? he?s still alive!) has managed to maintain an air of mystery simply by retaining his normality. For years unaware that he had such popularity on the other side of the world ? one of the Afrikaners describes him as ?much bigger than the Rolling Stones? and it is noted that ?Bob Dylan was mild compared to this guy?, but his records bombed in the States and he was dropped from his label ? he remains seemingly unchanged by fame.
Rodriguez himself was present, along with the director Malik Bendjelloul, and thrilled the audience with his self-effacing manner and heartfelt appreciation for applause he received. The screening was followed by a party at which he sang a few songs and chatted to the slightly awestruck delegates. We predict that a lot of people will be doing a lot of music shopping in the coming weeks ? us included! In the Q&A after the film, Bendjelloul was described as the luckiest documentary director in the world - tonight he must feel pretty close to it. All in all this was a pretty marvellous start to what looks set to be another rollicking celebration of all that it brilliant about documentary. Be sure to tune in tomorrow for more of our adventures!
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The founder and leader of a Georgia megachurch--who was arrested last week on charges of choking his teenage daughter, slamming her into the ground and hitting her with a shoe--told churchgoers on Sunday that he did not beat her. "The truth is, she was not choked, she was not punched," Creflo Dollar, the pastor, said [??
Nowadays, with the evolvement of internet marketing, websites are growing rapidly because it provides great benefit as well as affordability to customers. Most of the trusted online retailers and ecommerce shopping cart application solution stores would not have significantly knowledge about product sales taxation and they believe there is absolutely no sales tax about on the internet selling online. Nevertheless the reality is totally different. On the web sales are usually dealt with same as your bricks-and-mortar sales (buy from local merchants) and the sales are usually taxable. If trusted online stores don?t collect sales tax coming from customers, company is to blame for remitting the Use levy on online buying directly to their state.
Sales tax service Automobile on the internet seller offers bodily presence in the usa say for example a store, stockroom, business offices, or even sales rep soliciting revenue, owner must collect Make use of tax from their customers on these online net sales.But each condition has legal guidelines determining the ?engagement of economic inside state? to determine whether or not a business has nexus. These kind of laws alter among states, and many on-line online business merchants find themselves liable to pay out overdue sales tax with huge fines in a few states. Sales tax talking to The aim of imposing revenue and employ taxes is always to develop a level stage both for in-state and out-of-state stores. Sales & use taxes are intake taxes and gathered through consumers. Sales impose is collected following your retail sale made regarding tangible personalized property or particular solutions at the point of sale by way of a store store. Employ tax is due upon the storage, take advantage of or consumption of obvious personal property and even of certain companies when sales tax has not been paid. Use taxes is a complementary tax about purchases made out of out-of-state retailers without getting the particular sales tax. Currently, you have to be able to know how sophisticated the rules and also restrictions of sales & employ taxes are usually. Unlike income tax where firms pay tax inside net income, there is no tax liability if an corporation does not make a net gain. Sales tax is due for the selling price even if a company sells the merchandise confused. The sale tax costs range from 6% to 15.5% depending on the state the spot that the shipment of the rucksacks are delivered. The net income for that business is eroded through such relevant duty rate.
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If men and women have recently thrown out their backs and want to know how to relieve back pain, they may need to take their time in finding a workable solution. While some doctors may recommend complicated daily regimens that will loosen the muscles and gradually bring the area into tiptop shape, there are a number of treatments that are simpler in scope. Simply resting the back for a few days will allow it to regain some of its flexibility. In fact, experts often suggest that sleeping on a hard board instead of a soft mattress for a few nights can facilitate progress.
Icepacks are important in the first few hours after any kind of muscle injury. In some rarer cases, heat pads can be applied, but ice is the more acceptable medium. If individuals have been in a car accident and have suffered some degree of whiplash, they may have to treat the neck and back at the same time. Ice will keep the swelling to a minimum, which will ultimately help with the pain in the days ahead. Pharmacies usually sell icepacks that are protected with an outer covering, which will prevent the skin itself from growing too cold.
Sufferers might also try seeing a chiropractor. These professionals usually have a knack for increasing flexibility and healing sprains and strains. In fact, men and women with spinal misalignments often go to chiropractors to have work performed on the vertebrae. Patients should schedule their appointments ahead of time. If the pain is quite severe, then they may need to visit the office several times before they find a permanent solution to the problem. Chiropractors might also be able to recommend certain physical exercises that can be done to make the back stronger. While crunches and sit-ups are widely popular, there are other activities that are better at working more localized muscle groups.
In learning how to relieve back pain, men and women might also turn to strength training to tone their muscles and make them stronger. Many fitness centers and gyms have various machines for just this kind of training. The best fitness centers will even have some tutorials on how to work specific muscles groups while using a certain machine. Rowing devices are particularly good for the back area. As long as people try to make their muscles more flexible in the long run, they should end up with less of a chance of getting injured. Even if they are currently suffering from back pain, they can still use weight machines in a controlled and effective manner.
The information contained in this article is provided for informational purposes only and is not, nor is it ever intended to be, a substitute for professional medical advice or professional recommendations, diagnosis, or treatment. Always seek the advice of your physician(s) or other qualified healthcare provider(s).
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JOHANNESBURG, June 7 (Reuters) - The seeds of prosperity for some rural Africans may lie in a crop that has sustained them with calories for centuries but has generated virtually no wealth for their poor countries. ...
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This week, Teen Mom star Amber Portwood was sentenced to five years in prison, after refusing to complete a court-ordered drug rehabilitation program. There was some speculation about whether she knew that "opting out" of rehab would mean jail time; even the prosecuting attorney said he didn't think Portwood realized what she was doing. But in a new interview with ABC News, the 22-year-old mother of Leah Shirley explained her rationale for choosing prison over rehab.
A 17-year-long study upends the most common evolutionary explanation of female infidelity
By Sarah Fecht
?|
June 6, 2012?|
Image: Flickr/grandslam05
Why do testicles hang the way they do? Is there an adaptive function to the female orgasm? What does it feel like to want to kill yourself? Does ?free will?...
Read More??
Infidelity is easy to explain in males. By sleeping around, a guy can potentially impregnate more females and sire more offspring than if he just had one mate. But females cheat, too, even though a woman will only be able to have roughly one baby per year no matter how many male sex partners she has had.
One leading evolutionary hypothesis suggests that a female who mates with multiple males ensures the genetic diversity and quality of her offspring; having higher-quality offspring could theoretically give her more grandchildren later. A 17-year study, published in the June issue of The American Naturalist, challenges this hypothesis.
"This is one of the most careful and most robust studies to explore whether polyandry is adaptive in females," says Tommaso Pizzari, a University of Oxford biologist who was not involved in the research. "The answer is: not really."
Previous studies tested the "quality" hypothesis indirectly. In socially monogamous species, researchers would compare the legitimate and illegitimate offspring of cheating females by asking: Which offspring were larger? Which lived longer? But a better way to understand why female promiscuity evolved, says Jane Reid, a biologist at the University of Aberdeen in Scotland and author on the new study, is to determine whether those illegitimate offspring actually have more babies.
Reid and her team studied the isolated population of wild song sparrows on Mandarte Island in Canada. Like their mainland counterparts, these birds are socially monogamous. Males and females pair up for an entire breeding season or for several breeding seasons, and work together to feed the hatchlings and defend the nest. But they're not always faithful; blood tests showed that in this particular population, 28 percent of hatchlings were fathered by other males.
The researchers studied three generations of song sparrows (including more than 2,300 hatchlings) to see whether the cheating females' illegitimate sons and daughters would have higher reproductive success. It turned out that the bastard hatchlings actually fared worse than their legitimate siblings, producing about half as many offspring, on average. "It's not what people expected," Reid says.
David Westneat, a behavioral ecologist at the University of Kentucky, agrees. "It's essentially saying that there's no evidence for a hypothesis that's been very popular." But the theory is not dead yet, because the results need to be confirmed in other populations and other species. Westneat and Pizzari also expressed some concern over the fact that the study took place on an island?these small and isolated populations have a tendency to evolve in weird ways.
Nevertheless, the scientists agree that female promiscuity does not appear to have reproductive advantages for most of the female song sparrows on Mandarte Island. So what's the point of cheating, if it doesn?t help them to have greater evolutionary success?
Some theories blame it on the boys: Female promiscuity may be an ecological by-product of male promiscuity. If males are under strong selection to mate with multiple females, then in a closed environment females might be forced to mate with multiple males.
Reid is also investigating whether female promiscuity is a genetic by-product of the male version. If there are genes that encourage a male to be promiscuous, he might pass those genes on to his daughters, even though they may not benefit from the behavior. A recent study in zebra finches found support for this hypothesis. If it turns out that genetics have a heavy influence on feminine infidelity, Reid's team would like to try to pin down which genes are contributing to promiscuous behaviors.
If you want to make your home yard beautiful then hire a reliable landscape Naperville company offering comprehensive services for its clients. The company you hire should have horticultural professionals as well as brick paving experts that will help you to design and maintain your residential landscapes. The company that you go for should be able to understand the requirements of the clients accordingly provide aesthetic services within your budget.
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Your investment should be important to the company you choose. They should be able to understand both function and aesthetic aspect that will help you to get a perfect design for your home lawn. The landscapers should provide constant attention so that your landscape can have a stellar profile. The company should be able to provide you with lawn maintenance tips that will help ensure that your lawn is green and gorgeous.
You want results that would show and your landscape Naperville Company should be able to give you that. Reliability and professionalism should be the watchwords of the company you hire. Trees and bushes are an integral part of any housing project. Choose a company that will make your home yard or lawn an attractive addition of your home environment. Your friends and family members will definitely be jealous once they check out the lawn or yard at your home.
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Find out a reliable and experienced landscape Naperville company which will assist you in renovating your home lawn or yard. If you want to get detailed information naperville landscapers then check out www.kdlandscapeinc.com
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Douglas Barrios was a fourth-year student of economics at Metropolitan University at the time. He was 20 years old, so, like most of his classmates, he was part of the first generation of young Venezuelans to come of age under Chavez. Barrios was in sixth grade when Chavez was first elected, so he didn?t really remember what it was like to have anyone other than Hugo Chavez as president. But he does remember sitting at home on the night of May 27, 2007. In the months leading up to that day, Barrios and many of his friends in school had watched in disbelief as no one came forward to organize opposition to the president?s decree. ?When I try to explain it to people, I say it?s like they shut down NBC, ABC, and CBS at the same time,? says Barrios. And that night, precisely at midnight, RCTV went dark. The final image people saw was of the station?s journalists, news anchors, actors, and employees singing the national anthem, many of them crying, as they waved goodbye. ?You were sitting in front of your TV, probably the lights were off, and you saw this TV station go to static,? recalls Barrios. ?It just represented how choice can go away, how your options can go away, how something that?s very very established can just go to static.?
As for Sally and Glen?s trip to the Museum of Natural History, I loved their awkward rapport and the speed with which their banter about the exhibits soured. Glen?s confession that he?d bragged about Sally as a conquest prompts her to say, defensively, ?I?m not sure that?s the way I like you,? which prompts him to feign relief, saying she?s like a kid sister, ?but smart.? It?s not where either of them wants that conversation to go, I suspect?short-circuiting the possibility of a romance?but it goes there anyway. And then right on time, Sally gets her period and is inducted into the misery of grown-up life, with its responsibilities and hardships. (When Betty told Sally about the special obligations of womanhood, I couldn?t help but think of Megan, who takes on Sally-care responsibilities all weekend as Don works.)
??Novak Djokovic saved four match points and came back to beat Jo-Wilfried Tsonga 6-1, 5-7, 5-7, 7-6 (6), 6-1 in the French Open quarterfinals Tuesday, moving closer to a fourth consecutive Grand Slam title.
UT Southwestern investigators provide first atomic-level images of the CLOCK complexPublic release date: 4-Jun-2012 [ | E-mail | Share ]
Contact: Deborah Wormser deborah.wormser@utsouthwestern.edu 214-648-3404 UT Southwestern Medical Center
Drives circadian rhythm in mammals' cells
DALLAS June 4, 2012 UT Southwestern Medical Center researchers have taken a major step toward understanding the cellular clock, mapping for the first time the atomic-level architecture of a key component of the timekeeper that governs the body's daily rhythms.
The daily, or circadian, cycles guided by the body's clocks affect our ability to get a good night's sleep, how fast we recover from jet lag, and even the best time to give cancer treatments, said Dr. Joseph Takahashi, senior author of the Science study published online and a pioneer in the study of circadian rhythms.
Understanding the structure of the cellular clock could lead to better treatments for insomnia, diabetes, and even cancer.
"The clock is found in virtually every cell of the body, and is important for controlling many different metabolic functions," said Dr. Takahashi, chairman of neuroscience and a Howard Hughes Medical Institute (HHMI) investigator at UT Southwestern.
Mapping the 3-D structure of the key component in the cellular clock called the CLOCK:BMAL1 transcriptional activator complex will have a great impact on the study of circadian rhythms and in other areas like toxicology and the growth of nerve cells, in which proteins in the same family play central roles, he said.
"Ultimately, we have to go to the atomic level to really understand how these proteins work" Dr. Takahashi said.
The Takahashi laboratory has spent years determining the 3-D structure of the CLOCK:BMAL1 complex using X-ray crystallography. The breakthrough came in the spring of 2011 when Yogarany Chelliah, an HHMI research specialist at UT Southwestern, was able to crystallize the proteins. The structure was determined in collaboration with Dr. Hong Zhang, associate professor of biochemistry.
The researchers found that the CLOCK protein is tightly wrapped around the BMAL1 protein in an unusually asymmetrical fashion. They identified three distinct areas for interactions between CLOCK and BMAL1 as well as regions for interactions with other molecules that might affect the cellular clock by changing the sleep-wake cycle or other body processes that depend on circadian rhythm, he said.
Dr. Takahashi's research on the subject goes back almost 20 years. That's when he began a behavioral study of mice looking for those animals in which their biological clocks seemed out of sync. After screening hundreds of mice, his laboratory in 1994 identified one mutant mouse whose daily cycle was four hours longer than normal. He named that mouse the Clock mutant.
Dr. Takahashi then used that mouse to identify the world's first circadian rhythm gene in a mammal. Researchers in his laboratory cloned the Clock gene in 1997. In 1998, they discovered that the CLOCK protein worked in concert with the BMAL1 protein in a study done in collaboration with Dr. Charles Weitz at Harvard Medical School.
Two years ago, Dr. Takahashi's team in collaboration with Dr. Joseph T. Bass at Northwestern University Feinberg School of Medicine in Chicago reported in Nature that disruptions in the Clock and Bmal1 genes in mice can alter the release of insulin by the pancreas, which results in diabetes.
"We started on this path a long time ago, and it actually began with a mouse, which then allowed us to find the Clock gene, and then from this gene we now see the proteins from their crystal structure," Dr. Takahashi said. "For that to all happen after such a long quest is particularly satisfying."
###
Other UT Southwestern researchers involved in the study include Nian Huang, postdoctoral researcher in biochemistry; Dr. Yongli Shan, postdoctoral researcher in neuroscience; Clinton A. Taylor, student research assistant; Dr. Seung-Hee Yoo, instructor of neuroscience; and Dr. Carla Green, professor of neuroscience. Dr. Carrie Partch a former postdoctoral researcher in biochemistry, neuroscience, and the HHMI is now an assistant professor of chemistry and biochemistry at UC Santa Cruz.
This work was supported by the HHMI, the American Heart Association, and the National Institutes of Health.
This news release is available on our World Wide Web home page at
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UT Southwestern investigators provide first atomic-level images of the CLOCK complexPublic release date: 4-Jun-2012 [ | E-mail | Share ]
Contact: Deborah Wormser deborah.wormser@utsouthwestern.edu 214-648-3404 UT Southwestern Medical Center
Drives circadian rhythm in mammals' cells
DALLAS June 4, 2012 UT Southwestern Medical Center researchers have taken a major step toward understanding the cellular clock, mapping for the first time the atomic-level architecture of a key component of the timekeeper that governs the body's daily rhythms.
The daily, or circadian, cycles guided by the body's clocks affect our ability to get a good night's sleep, how fast we recover from jet lag, and even the best time to give cancer treatments, said Dr. Joseph Takahashi, senior author of the Science study published online and a pioneer in the study of circadian rhythms.
Understanding the structure of the cellular clock could lead to better treatments for insomnia, diabetes, and even cancer.
"The clock is found in virtually every cell of the body, and is important for controlling many different metabolic functions," said Dr. Takahashi, chairman of neuroscience and a Howard Hughes Medical Institute (HHMI) investigator at UT Southwestern.
Mapping the 3-D structure of the key component in the cellular clock called the CLOCK:BMAL1 transcriptional activator complex will have a great impact on the study of circadian rhythms and in other areas like toxicology and the growth of nerve cells, in which proteins in the same family play central roles, he said.
"Ultimately, we have to go to the atomic level to really understand how these proteins work" Dr. Takahashi said.
The Takahashi laboratory has spent years determining the 3-D structure of the CLOCK:BMAL1 complex using X-ray crystallography. The breakthrough came in the spring of 2011 when Yogarany Chelliah, an HHMI research specialist at UT Southwestern, was able to crystallize the proteins. The structure was determined in collaboration with Dr. Hong Zhang, associate professor of biochemistry.
The researchers found that the CLOCK protein is tightly wrapped around the BMAL1 protein in an unusually asymmetrical fashion. They identified three distinct areas for interactions between CLOCK and BMAL1 as well as regions for interactions with other molecules that might affect the cellular clock by changing the sleep-wake cycle or other body processes that depend on circadian rhythm, he said.
Dr. Takahashi's research on the subject goes back almost 20 years. That's when he began a behavioral study of mice looking for those animals in which their biological clocks seemed out of sync. After screening hundreds of mice, his laboratory in 1994 identified one mutant mouse whose daily cycle was four hours longer than normal. He named that mouse the Clock mutant.
Dr. Takahashi then used that mouse to identify the world's first circadian rhythm gene in a mammal. Researchers in his laboratory cloned the Clock gene in 1997. In 1998, they discovered that the CLOCK protein worked in concert with the BMAL1 protein in a study done in collaboration with Dr. Charles Weitz at Harvard Medical School.
Two years ago, Dr. Takahashi's team in collaboration with Dr. Joseph T. Bass at Northwestern University Feinberg School of Medicine in Chicago reported in Nature that disruptions in the Clock and Bmal1 genes in mice can alter the release of insulin by the pancreas, which results in diabetes.
"We started on this path a long time ago, and it actually began with a mouse, which then allowed us to find the Clock gene, and then from this gene we now see the proteins from their crystal structure," Dr. Takahashi said. "For that to all happen after such a long quest is particularly satisfying."
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Other UT Southwestern researchers involved in the study include Nian Huang, postdoctoral researcher in biochemistry; Dr. Yongli Shan, postdoctoral researcher in neuroscience; Clinton A. Taylor, student research assistant; Dr. Seung-Hee Yoo, instructor of neuroscience; and Dr. Carla Green, professor of neuroscience. Dr. Carrie Partch a former postdoctoral researcher in biochemistry, neuroscience, and the HHMI is now an assistant professor of chemistry and biochemistry at UC Santa Cruz.
This work was supported by the HHMI, the American Heart Association, and the National Institutes of Health.
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Public release date: 4-Jun-2012
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