Every Friday in May and June our?News10 Meteorologist broadcasted?the forecast LIVE from a community event in?the StreetCast segment during News10 at 5 p.m. and 6 p.m.
Voting began Monday morning and ended Thursday at 5 p.m.
This week?Monica Woods?announced on Thursday's?5 p.m. newscast where?she?would be LIVE?on Friday's 5 and 6pm newscasts, weather permitting.
We hope to host the Weather Streetcast poll again.? If you'd like us to, let us know by clicking on Post a Comment.
LONDON (AP) ? Sammy Lee remembers it vividly: food rationing, bombed-out buildings, rubble.
The year was 1948, and London was hosting the Olympics amid severe austerity in the aftermath of World War II. Lee, an American diver, and fellow amateur athletes slept on cots at local air bases and schools, brought their own towels and were ferried to events in old London buses.
"We didn't mind," said Lee, who won a gold and bronze medal in the Empire Pool. "It was the spirit of the Olympics. We were there to compete against the best."
Sixty-four years later, Lee will return as a spectator next month when London welcomes the world again.
Saying these 2012 Olympics will be much different is in itself a gold-medal understatement. This will be a $14.5 billion extravaganza featuring multimillionaire professionals and global stars like Usain Bolt and Michael Phelps, shiny new purpose-built venues and a revitalized east London.
Britain's biggest peacetime project also entails a massive security operation. To guard the games from terrorist attack, the country is deploying 35,000 safety, police and military personnel, surface-to-air missiles on rooftops, fighter jets, helicopters and two warships on the River Thames.
Yet, put aside worries about trouble and whether the city's stretched public transportation network can transport millions of extra riders, and this should be London's finest hour. A chance to throw a rousing five-ring celebration, a global bear hug that restores the festive atmosphere lacking at the past two Olympics, in Athens and Beijing.
"London this summer is going to be the place to have a party," Olympics Minister Hugh Robertson said.
The city will provide a stunning mix of old and new:
? Beach volleyball players diving across the sand in Horse Guards Parade, practically on the doorstep of the prime minister's 10 Downing Street residence.
? Marathon runners and road cyclists winding past Buckingham Palace.
? Tennis stars dueling on the Centre Court grass at Wimbledon.
? Archers firing their arrows at the hallowed Lord's cricket ground.
? Sprinters and swimmers competing in brand new arenas erected in a once-derelict area of east London brought back to life as the Olympic Park.
Headlining the show will be 10,000 athletes from more than 200 countries ? none bigger than ? who else? ? Bolt and Phelps. What can Bolt possibly do for an encore after his jaw-dropping three gold medals and three world records on the track in Beijing? Can 14-time gold medalist Phelps ? winner of a record eight golds in the pool in Beijing ? hold off American rival Ryan Lochte in what Phelps says will be his final Olympics?
Also at stake will be the top spot in the medals table between the world's two sporting superpowers: the United States and China. The U.S. won the most medals (110) in Beijing, but China took the most golds (51). Expect a tight race on both fronts this time.
Away from the playing fields, the city is dressing up, from the giant Olympic rings on Tower Bridge, to the party venues and giant screens in Hyde Park, to the landscaped gardens inside the 560-acre Olympic Park.
Four years ago, China used the Beijing Olympics as a coming-out spectacle to underscore its presence as a world power. It spent $40 billion on the games, erecting iconic venues like the Bird's Nest stadium and the Water Cube natatorium and staging a grandiose opening ceremony.
But London never tried to compete with the epic scale of Beijing, largely because of a global economic crisis that triggered bailouts, mounting debt and political turmoil across Europe.
Still, the Olympic budget of 9.3 billion pounds ($14.5 billion) is more than triple the estimated cost when London secured the games in 2005. The government says the games are expected to come in about 500 million pounds ($778 million) under budget. The local organizing committee's separate privately financed operating budget of 2 billion pounds ($3.1 billion) is on course to be met through sponsorships, TV rights, merchandising and ticket sales.
"This is the first time London got the games with no particular crisis around, but then they marched right into the worst financial crisis since before World War II," senior International Olympic Committee member Dick Pound of Canada said. "But they have succeeded remarkably well in spite of that."
London organizers look more closely to the 2000 Sydney Games as their model, hoping to channel the same vibrant energy, passionate crowds and Olympic buzz.
While Beijing suffered from empty seats at some venues and a disconnected public, London promises full arenas and knowledgeable spectators. The capital has residents of countless nationalities and cultures, providing a "home" crowd for teams from Namibia to Nepal. Live sites, music concerts and other attractions should keep visitors entertained day and night.
The tone will be set at the opening ceremony on July 27 at the 80,000-seat Olympic Stadium, a three-hour spectacle directed by Oscar-winning filmmaker Danny Boyle of "Slumdog Millionaire" fame. Inspired by William Shakespeare's "The Tempest," the ceremony will include a segment involving Daniel Craig's James Bond and a closing act by former Beatle Paul McCartney.
Boyle has revealed that the opening sequence will feature an idyllic British countryside setting complete with live farm animals ? 70 sheep, 12 horses, 10 chickens and nine geese to be precise. He's even promising a cloud that produces rain ? in case there isn't enough of the real stuff around.
The Economist magazine couldn't resist a little zinger: "Opening ceremonies are a country's opportunity to sell itself to the world. Britain appears to be selling irony."
Queen Elizabeth II, fresh off a round of Jubilee celebrations marking her 60 years on the throne, will formally open the games. The big question: Who will light the cauldron that burns until the closing of the games on Aug. 12? Britain's five-time rowing gold medalist, Steve Redgrave, is the bookies' favorite, followed by soccer star David Beckham ? the global icon who was bypassed for Britain's Olympic soccer team despite playing a key role in bringing the games to his hometown.
Roger Bannister ? the first runner to break the 4-minute barrier for the mile in 1954 ? is another possibility for lighting the flame. But who's to say the honor won't go to an unknown? A young athlete from one of the poor boroughs surrounding the Olympic Park, a symbol of youth and the future generation that was the central theme of London's winning bid?
The queen won't be the only royal in the Olympic spotlight. Her 31-year-old granddaughter, Zara Phillips, will be competing for the British equestrian team. Prince William and wife Kate are sure to be spotted around town, providing a dash of stately glamour to the proceedings.
And there are plenty of bold-face names at the venues: Bolt running in the 100 and 200 meters and 4x100 relay, Phelps swimming in multiple events again and going head-to-head with Lochte, who beat him twice at last year's world championships.
The star-studded U.S. basketball team features new NBA champion LeBron James, Kobe Bryant and Kevin Durant. Just three weeks after chasing a Grand Slam title at Wimbledon, Novak Djokovic, Rafael Nadal, Roger Federer, Serena Williams and Maria Sharapova will be back at the All England Club vying for gold medals instead of trophies ? wearing colorful team outfits instead of the all-white dress code
Women boxers will be competing in the Olympics for the first time, and the IOC is negotiating with Saudi Arabia to send its first female athletes to the games.
Others to watch include South African double-amputee Oscar Pistorius, who failed to qualify for the 400 meters but could still become the first amputee runner to compete in the Olympics if he's picked for the 4x400 relay; China's Lin Dan, widely considered the greatest badminton player of all-time going for a second Olympic gold medal; Brazilian goal-scoring star Neymar in men's soccer; and Hiroshi Hoketsu, competing for Japan in equestrian at the age of 71.
The locals should have plenty to cheer about as Britain seeks to equal its surprising fourth-place medals table finish in Beijing. Among the contenders from Team GB are diver Tom Daley, heptathlete Jessica Ennis, swimmer Rebecca Adlington, three-time gold medalists Chris Hoy (track cycling) and Ben Ainslie (sailing), and a powerful team of rowers.
Despite 6.5 billion pounds ($10 billion) of improvements, serious concerns remain over whether the Underground system can cope with the millions of extra passenger journeys. Officials have warned of expected overcrowding and long delays at some key stations and urged Londoners to work from home or change their travel habits.
As for driving, the message has been: Don't even think about it. Many locals have complained that they are being inconvenienced while miles of dedicated Olympic roads and lanes are reserved for Olympic officials, athletes, media and VIPs.
The games will be protected by 12,000 police officers during peak times and 23,700 security staffers ? a number that includes 7,500 troops. A no-fly zone will be established over Olympic venues.
London knows the threats all too well. Homegrown suicide bombers attacked the city's public transport system, killing 56 people, on July 7, 2005, the day after London was awarded the games.
"The games present an attractive target for our enemies," said Jonathan Evans, head of Britain's domestic spy agency MI5. "But the games are not an easy target, and the fact that we have disrupted multiple terrorist plots here and abroad in recent years demonstrates that the U.K. as a whole is not an easy target for terrorism."
No one has more riding on these games than Sebastian Coe, the two-time Olympic gold medalist in the 1,500 meters who led London's winning bid and has spearheaded the seven years of preparations. This project, he said, tops anything he accomplished on the track.
"It doesn't get any bigger," Coe said. "I remember the feeling I had 40 minutes before setting out on the track in front of 100,000 people. Now I wonder how I will measure that against the 40 minutes before the opening ceremony."
___
Follow Stephen Wilson on Twitter at: http://twitter.com/stevewilsonap
BELMONT - Belmont United Baptist Church is celebrating a special milestone next week.
The church is honouring its 125th anniversary
with a special evening of music and a guest speaker on July 6 at 7 p.m. The guest speaker is Rev. Leslie Jobb and music will be provided by the combined choirs of Debert and Belmont United Baptist churches. Refreshments and fellowship will follow.
The festivities will continue on July 7 with a coffee house from 3 to 4 p.m. at Belmont United Church. A barbecue supper will be held between 4 and 5:30 p.m. and a coffee house bands session will take place from 5:30 to 7 p.m., followed by a 7 p.m. special service with special speaker Rev. Chuck Sawatsky. Coffee house bands as well as Debert and Belmont Baptist choirs will also participate.
On Sunday, Rev. Dennis Leamont will lead the 11 a.m. church service at Belmont United Church. Refreshments will be served after the service from noon to 2 p.m. and everyone is welcome to attend.
Mobile health and fitness apps are increasingly popular but they?re often predicated on the notion that you have to feed in a lot of data to make them useful. The problem is that information entry often appeals more to data junkies and really disciplined users. But for the masses, that can be a high bar to overcome, preventing many from getting the most of out of these apps.
That painful truth is one of the main drivers behind Noom, a maker of Android-based fitness and health apps, and one of the reasons it?s created a success with its flagship app Noom Weight Loss Coach. The New York City-based company, which received $2 million last year led by Kleiner Perkins, doesn?t require users to enter in every meal or track every physical activity. The app assumes casual, light usage and tries to still deliver timely coaching lessons and tips that can still motivate and educate users.
?Other apps are focused on data input but the process of analyzing the data is not addressed,? said co-founder and CTO Artem Petakov, a former Googler. ?We?re trying to keep you on the bandwagon. It?s not about day 1, it?s about day 3, day 10.?
A look at version 3.0 of Noom Weight Loss Coach
Weight Loss Coach lets people set their weight goals and allows people to log in their food intake and activity in a simple manner. But it can dispense advice, tasks and tips based on a few entries. Each day it gives people reminders to exercise and log meals and then throws in extra optional challenges, quizzes, suggestions and stories, based on how they?re doing. If, for example, you?re eating too much junk food, Weight Loss Coach can give you a quiz on fast food. If you tell Weight Loss Coach when you plan on going shopping, it will challenge you to take the stairs or ask you afterwards?how many bags you carried.
A $10 a month premium version provides a more intense level of coaching as well as the ability to customize your coach to different styles and goals. As it learns about users and notices their progress, Weight Loss Coach tailors its tasks and suggestions to keep people moving toward their weight goals. And it can even remind people to follow through on previously scheduled activities.?The app also includes a workout mode that captures activity using an accelerometer and GPS so users can log in their activity as well.
To date, Noom has had 13 million downloads of its apps, mostly split between Noom Weight Loss Coach and Cardio Trainer, a Runkeeper competitor. ?Version 3.0 of Weight Loss Coach, which Noom is starting to preview, will feature a more integrated list-based dashboard that combines the app?s different features into one view and will offer better on-boarding features for new users. An iPhone app is planned though there is no set date as most of the company?s resources are still focused on its Android apps.
Saeju Jeong, Noom?s CEO and co-founder, said the key is ensuring that people don?t get bored and find reasons to drop the service. He said the goal is to go after the 85 percent of people who don?t regularly exercise and keep them engaged over long periods of time. He said 70 percent of Weight Loss Coach?s users are women.
Noom co-founders Saeju Jeong and Artem Petakov
The story of how Jeong and Petakov got together is interesting in itself. Petakov, who founded the user-created Maps project for Google Maps, met Jeong at a dinner party at Princeton in 2005. Jeong was in New York, working as a producer for the international production of Bye Bye Birdie. He had previously tried running his own online shopping site in his native South Korea. The two got to talking about building a health startup and eventually they founded WorkSmart Labs, which changed its name to Noom in December. The company was initially focused on bringing innovation to the gym business but they found that dealing with hardware manufacturers was slow going. Smartphones, however, provided the perfect blend of mobile sensors and computing, Jeong said.
?We realized the smartphone has all the features you need ? why buy something different?? he said.
Noom is part of a new generation of mobile health products that are designed for more casual use. Massive Health has helped to improve people?s diets with its Eatery app, which lets people take pictures of their meals and get ratings on healthiness of their diet from other users. Striiv, a smart pedometer, is going after the Zynga audience with its gamified device, which includes a Farmville like mini-game. What?s cool to see is that these products don?t simply revel in data or demand a lot of input. They work to find creative and fun ways to push people to get healthy. That?s more inviting for casual users, who want some feedback and motivation but can?t always be counted on to record a lot of information. And it?s potentially more effective over the long run, said Petakov.
?Wellness is long-term activity, so cracking the code involves long-term stuff,? he said.
Related research and analysis from GigaOM Pro: Subscriber content. Sign up for a free trial.
BRUSSELS -- Leaders of the deeply divided European Union met into the early hours of Friday in search of a common response to the continent's growing economic crisis but were unable to bridge their differences.
Even a modest package intended to boost growth and employment was approved only in principle after Spain and Italy objected that the EU had not agreed to provide emergency relief for their troubled economies.
Markets in Europe and the United States fell Thursday amid low expectations that the leaders of Spain and Italy could convince German Chancellor Angela Merkel of the need for special measures to help stem the rapidly rising interest rates that have made it increasingly difficult for the two countries to borrow money to pay for the operation of their governments.
The discussion of steps to assist the two major European countries didn't even begin until late Thursday, the European Council president, Herman van Rompuy of Belgium, told reporters. This was because the discussion of a $150 billion jobs and growth package, which four of the biggest European powers had agreed to in advance, ran hours longer than planned when Spain and Italy refused to give their final approval.
The meeting was cast in dire terms, with some commentators saying the future of the euro, used by 17 European countries, was at stake. If the leaders needed reminding of where previous European crises had led, Martin Schulz, the German president of the European Parliament, used the fact that Thursday was the 98th anniversary of the start of World War I to recall the "decades of hatred, war, genocide and the displacement of peoples" that followed.
People throughout Europe "are casting worried eyes towards Brussels, towards this summit meeting, because they fear that our European project is one step away from disaster."
Calling for "quick and decisive action," he also chided European leaders in circumventing the European Parliament, the sole representative of the citizens of Europe, as they planned reforms and changes.
Rompuy issued a report that proposed a banking union, introducing European-wide regulation of the continent's troubled banks, a deposit insurance plan to head off runs on banks, as well as a fiscal union, which would introduce supervision at an all-European level of the budgets of governments that have use the euro as their currency.
The report also laid out a strategy for "mutualizing" individual nations' debt, a step that Spain and Italy have urged the EU to undertake in some form to prevent their countries from heading into a Greek-style default.
But Merkel has made clear that Germany would never agree to such an idea "as long as I am alive."
On the eve of the summit, she reinforced the message.
"I emphatically reject that perspective contained in the report that puts priority on the mutualization (of debt)," she told the German Parliament. "Besides the fact that instruments such as euro bonds, euro bills, debt retirement funds and much more would not be constitutionally permissible in Germany, I also view them as economically wrong and counterproductive," she said. She called instead for an emphasis on austerity and discipline rather than common liability.
Italian Prime Minister Mario Monti, a widely respected economist who this week won Italian parliamentary approval for a major labor reform package, has warned of the risks if the EU didn't come to the rescue of countries that had pursued austerity and reforms as Germany had demanded, but whose economies are in the doldrums. Spanish Prime Minister Mariano Rajoy warned that Spain "cannot long finance itself" if it had to continue paying up to 7 percent interest to sell government bonds.
The significance of May's election in France, which saw the ascent of Socialist Francois Hollande to the presidency, was also clear. Hollande, who replaced Merkel ally Nicolas Sarkozy, endorsed the Rompuy proposal.
The split between France and Germany, the two engines behind the European Union, is the most ominous development in the current crisis. The Frankfurter Allgemeine Zeitung, a conservative German paper, said in an editorial Thursday that an accord between the two countries was the "sine qua non" - the indispensable item - for resolving the current problems.
The newspaper also noted that money devoted to the growth and employment initiative was too small to spur growth in Europe, and in any case was just a reallocation of funds that had been earmarked for other purposes.
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Contact: Kristin Kessler krk@stowers.org 816-926-4139 Stowers Institute for Medical Research
'Paper of the week' shows that a master regulator protein brings plethora of coactivators to gene expression sites
KANSAS CITY, MOMolecular geneticists call big boss proteins that switch on broad developmental or metabolic programs "master regulators," as in master regulators of muscle development or fat metabolism. One such factor, the Activating Transcription Factor 6? (ATF6?) protein, takes charge following a cellular crisis known as endoplasmic reticulum (ER) stress, which is triggered by the accumulation of misfolded and aggregated proteins.
Molecularly, the ER stress pathway is always poised for action. Inactive ATF6? is normally embedded in cellular membranes, but at the first hint of protein overload, its working end springs superman-like into the nucleus, binds DNA and kicks on a host of target genes whose job is to clear a protein logjam.
Now, in a study published in the June 29 issue of The Journal of Biological Chemistry, and selected as "Paper of the Week" by the journal's editors, a team led by Stowers investigators Ron and Joan Conaway reveal that unlike the real superman ATF6? does not work solo. Using the ATF6? target gene HSPA5 as a probe, they apply mass spectrometry analysis to show that ATF6? recruits a fleet of coactivators to assist in target activation.
"We knew that as a master regulator, ATF6? was needed to turn on downstream genes in the ER stress response," says Ron Conaway, Ph.D., who with Joan Conaway, Ph.D., is co-corresponding author of the study. "Our goal was to determine what ATF6? was bringing with it to these genes' control elements."
"By devising a clever mix of state-of-the-art mass spectrometry and good old-fashioned biochemistry, this study has revealed that ATF6? is a virtual magnet for a wide range of 'A-list' co-regulators," said Michael K. Reddy, Ph.D., who oversees transcription mechanism grants at the National Institutes of Health's National Institute of General Medical Sciences, which partly supported the work. "These co-regulators offer a large array of proteins to target in efforts to control the ER stress response and to treat diseases that result from misfolded proteins."
That task of identifying co-regulators was challenging: labor-intensive molecular techniques the group applied to identify candidate interactors early on were not sensitive enough. At that point, the Conaways turned to their frequent collaborators Proteomics' Center director, Michael Washburn, Ph.D., and Laurence Florens, Ph.D., who heads the Stowers proteomics cores. Both had helped develop a sensitive mass spectrometry approach that can detect protein-protein interactions in highly complex mixtures, a technology known as MudPIT.
The group then set up a test-tube comparison. They genetically engineered a strand of DNA flanking the HSPA5 target gene, the so-called "enhancer" region recognized by ATF6?. They then dipped two identical DNA test strips into respective pots of cellular extractsone containing ATF6? and one notreasoning that factors in the ATF6? entourage would be recruited to the first but not the second. They then applied a single run of MudPIT to identify each ATF6?-specific partner.
In short, they found that it takes not a village but a metropolis to activate an ATF6? target. Many proteins bound the enhancer in both samples, meaning either that they're just background, or else that they must bind DNA even when the gene is inactive. But more than 40 were present in about 5-fold excess only in ATF6??spiked samples, suggesting they are tethered to the enhancer by ATF6?.
Among the latter were components of a multi-subunit behemoth protein known as Mediator, which bridges specific genetic switches (like ATF6?) and the catalytic machinery that copies a gene. Other proteins recruited by ATF6? through overlapping but not identical domains belonged to other large complexes known as SAGA and ATAC, which enzymatically relax chromosome structure to allow gene expression.
Researchers know that all DNA-binding factors partner with other proteins to switch genes on or off. What is remarkable here is their sheer number. "It would be very interesting to find out whether this is the norm," says Ron Conaway. "This work raises a ton of little questions about mechanism."
Among them is how do ATF6?-interacting factors arrange themselves on the test strip, and does a single ATF6? bind to all of them at once? "There are three separate ATF6? binding sites on the HSPA5 enhancer and ATF6? itself forms a dimer," explains Dotan Sela, Ph.D., a Conaway lab postdoc and the study's first author, "So potentially within this region there could be as many six activation domains," he explains.
Solving these puzzles could reveal molecular targets for seemingly unrelated diseases. While a little ATF6? signaling is absolutely essential for cellular housekeeping, unrelieved ER stress is a hallmark of neurodegenerative conditions like Alzheimer's and Huntington's Diseases and is correlated with insulin insensitivity and type II diabetes.
A direct role for ATF6? in what some now call "misfolded protein diseases" is unclear. Nonetheless, the study suggests ways to dampen ER stress signaling molecularly. "We show that the Mediator is relevant to HSPA5 expression," says Sela. "So one way to keep ATF6? from turning on a gene might be to devise ways to block binding of the Mediator to ATF6?."
Joan Conaway also points out that MudPIT data analysis does not require previous identification of a "suspect." "Our approach complements methods that test candidate interactors one by one," says Joan Conaway. "Because the analysis is unbiased, it could reveal novel proteins interacting with a particular enhancer, which then could be confirmed using other methods."
The Conaways began their pioneering studies of mammalian gene expression over three decades ago, when only laborious biochemical techniques were available. As a result, both deeply appreciate what a technological leap the current work represents. "This study provides proof of principle for the utility of mass spectrometry in defining novel transcriptional activators," says Ron Conaway. "We want to compare this data with that from other activatorsit's what we will be working on in the future."
###
In addition to Washburn and Florens, Lu Chen of the Conaway lab and Skylar Martin-Brown of the Washburn lab also contributed to the work.
Funding for the study came from the Stowers Institute for Medical Research, the National Institute of General Medical Science (GM041628) and the Helen Nelson Medical Research Fund at the Greater Kansas City Community Foundation.
About the Stowers Institute for Medical Research
The Stowers Institute for Medical Research is a non-profit, basic biomedical research organization dedicated to improving human health by studying the fundamental processes of life. Jim Stowers, founder of American Century Investments, and his wife, Virginia, opened the Institute in 2000. Since then, the Institute has spent over 900 million dollars in pursuit of its mission.
Currently, the Institute is home to nearly 550 researchers and support personnel; over 20 independent research programs; and more than a dozen technology-development and core facilities.
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Contact: Kristin Kessler krk@stowers.org 816-926-4139 Stowers Institute for Medical Research
'Paper of the week' shows that a master regulator protein brings plethora of coactivators to gene expression sites
KANSAS CITY, MOMolecular geneticists call big boss proteins that switch on broad developmental or metabolic programs "master regulators," as in master regulators of muscle development or fat metabolism. One such factor, the Activating Transcription Factor 6? (ATF6?) protein, takes charge following a cellular crisis known as endoplasmic reticulum (ER) stress, which is triggered by the accumulation of misfolded and aggregated proteins.
Molecularly, the ER stress pathway is always poised for action. Inactive ATF6? is normally embedded in cellular membranes, but at the first hint of protein overload, its working end springs superman-like into the nucleus, binds DNA and kicks on a host of target genes whose job is to clear a protein logjam.
Now, in a study published in the June 29 issue of The Journal of Biological Chemistry, and selected as "Paper of the Week" by the journal's editors, a team led by Stowers investigators Ron and Joan Conaway reveal that unlike the real superman ATF6? does not work solo. Using the ATF6? target gene HSPA5 as a probe, they apply mass spectrometry analysis to show that ATF6? recruits a fleet of coactivators to assist in target activation.
"We knew that as a master regulator, ATF6? was needed to turn on downstream genes in the ER stress response," says Ron Conaway, Ph.D., who with Joan Conaway, Ph.D., is co-corresponding author of the study. "Our goal was to determine what ATF6? was bringing with it to these genes' control elements."
"By devising a clever mix of state-of-the-art mass spectrometry and good old-fashioned biochemistry, this study has revealed that ATF6? is a virtual magnet for a wide range of 'A-list' co-regulators," said Michael K. Reddy, Ph.D., who oversees transcription mechanism grants at the National Institutes of Health's National Institute of General Medical Sciences, which partly supported the work. "These co-regulators offer a large array of proteins to target in efforts to control the ER stress response and to treat diseases that result from misfolded proteins."
That task of identifying co-regulators was challenging: labor-intensive molecular techniques the group applied to identify candidate interactors early on were not sensitive enough. At that point, the Conaways turned to their frequent collaborators Proteomics' Center director, Michael Washburn, Ph.D., and Laurence Florens, Ph.D., who heads the Stowers proteomics cores. Both had helped develop a sensitive mass spectrometry approach that can detect protein-protein interactions in highly complex mixtures, a technology known as MudPIT.
The group then set up a test-tube comparison. They genetically engineered a strand of DNA flanking the HSPA5 target gene, the so-called "enhancer" region recognized by ATF6?. They then dipped two identical DNA test strips into respective pots of cellular extractsone containing ATF6? and one notreasoning that factors in the ATF6? entourage would be recruited to the first but not the second. They then applied a single run of MudPIT to identify each ATF6?-specific partner.
In short, they found that it takes not a village but a metropolis to activate an ATF6? target. Many proteins bound the enhancer in both samples, meaning either that they're just background, or else that they must bind DNA even when the gene is inactive. But more than 40 were present in about 5-fold excess only in ATF6??spiked samples, suggesting they are tethered to the enhancer by ATF6?.
Among the latter were components of a multi-subunit behemoth protein known as Mediator, which bridges specific genetic switches (like ATF6?) and the catalytic machinery that copies a gene. Other proteins recruited by ATF6? through overlapping but not identical domains belonged to other large complexes known as SAGA and ATAC, which enzymatically relax chromosome structure to allow gene expression.
Researchers know that all DNA-binding factors partner with other proteins to switch genes on or off. What is remarkable here is their sheer number. "It would be very interesting to find out whether this is the norm," says Ron Conaway. "This work raises a ton of little questions about mechanism."
Among them is how do ATF6?-interacting factors arrange themselves on the test strip, and does a single ATF6? bind to all of them at once? "There are three separate ATF6? binding sites on the HSPA5 enhancer and ATF6? itself forms a dimer," explains Dotan Sela, Ph.D., a Conaway lab postdoc and the study's first author, "So potentially within this region there could be as many six activation domains," he explains.
Solving these puzzles could reveal molecular targets for seemingly unrelated diseases. While a little ATF6? signaling is absolutely essential for cellular housekeeping, unrelieved ER stress is a hallmark of neurodegenerative conditions like Alzheimer's and Huntington's Diseases and is correlated with insulin insensitivity and type II diabetes.
A direct role for ATF6? in what some now call "misfolded protein diseases" is unclear. Nonetheless, the study suggests ways to dampen ER stress signaling molecularly. "We show that the Mediator is relevant to HSPA5 expression," says Sela. "So one way to keep ATF6? from turning on a gene might be to devise ways to block binding of the Mediator to ATF6?."
Joan Conaway also points out that MudPIT data analysis does not require previous identification of a "suspect." "Our approach complements methods that test candidate interactors one by one," says Joan Conaway. "Because the analysis is unbiased, it could reveal novel proteins interacting with a particular enhancer, which then could be confirmed using other methods."
The Conaways began their pioneering studies of mammalian gene expression over three decades ago, when only laborious biochemical techniques were available. As a result, both deeply appreciate what a technological leap the current work represents. "This study provides proof of principle for the utility of mass spectrometry in defining novel transcriptional activators," says Ron Conaway. "We want to compare this data with that from other activatorsit's what we will be working on in the future."
###
In addition to Washburn and Florens, Lu Chen of the Conaway lab and Skylar Martin-Brown of the Washburn lab also contributed to the work.
Funding for the study came from the Stowers Institute for Medical Research, the National Institute of General Medical Science (GM041628) and the Helen Nelson Medical Research Fund at the Greater Kansas City Community Foundation.
About the Stowers Institute for Medical Research
The Stowers Institute for Medical Research is a non-profit, basic biomedical research organization dedicated to improving human health by studying the fundamental processes of life. Jim Stowers, founder of American Century Investments, and his wife, Virginia, opened the Institute in 2000. Since then, the Institute has spent over 900 million dollars in pursuit of its mission.
Currently, the Institute is home to nearly 550 researchers and support personnel; over 20 independent research programs; and more than a dozen technology-development and core facilities.
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Ann Curry is out as co-host of The Today Show, Savannah Guthrie is in and Matt Laurer's marriage is safe.
Wait... what?!?
The National Enquirer claims Lauer's wife, Annette Roque, was very concerned that her husband was pushing for long-time correspondent Natalie Morales to take over the seat next to him every morning, a situation that allegedly would have led to Roque filing for divorce.
Why? Well, take a look at Morales...
"When she heard about Ann getting the boot, the first thing she told Matt was she didn't want him cozying up any closer to Natalie," a tabloid source said of Lauer and Roque.
"In fact, Annette drew a line in the sand and said if he pushed show bosses to make Natalie his new co-host, she'd divorce him."
This isn't the first time that split rumors have sprung up between this couple.
In May 2010, insiders also told the Enquirer that Lauer was having an affair. Nothing came of the story, the marriage remained intact and now, thanks to the hiring of Guthrie, it appears as if the same applies here.
(CNN) ? Dr. Stuart Fischbein chuckled when he read the title of the press release: ?Women with a fear of childbirth endure a longer labor.?
The release was promoting a study published this week in BJOG: An International Journal of Obstetrics and Gynecology. Researchers at Akershus University Hospital in Norway found women who feared giving birth were in labor for 1 hour and 32 minutes longer, on average, than those who had no fear.
?I?m glad there?s now evidence to say that,? Fischbein said, ?but it?s obvious.?
For those of us who aren?t OB/GYNs, it may seem more like a cruel joke. Women who are afraid of the pain and the possible medical complications associated with giving birth have to suffer through it longer?
Study author Dr. Samantha Salvesen Adams initially thought her team would find the prolonged labor could be explained by other factors ? women who feared birth the most were first time mothers, who are known to have longer labors anyway, or obstetric interventions like epidurals. But when those factors were taken into consideration, the difference in time between the fearless and the fearful was still 47 minutes.
?Mental stress is associated with physiological arousal and release of stress hormones,? Adams wrote in an e-mail. ?During labour, high levels of stress hormones may weaken uterine [contractions].?
In other words, the adrenaline released when a body is stressed stops the oxytocin hormone production that makes a woman?s uterus contract, slowing labor. It?s a natural, biological response to fear, Fischbein said.
Fischbein, who?s also a co-author of ?Fearless Pregnancy,? said women today are afraid of giving birth because they?re surrounded by horror stories.
?We have a society where sensationalism sells. They?re pounded with information [about] things that can go wrong with childbirth. Of course you develop fears.?
To understand Fischbein?s lack of surprise at the study results, you have to take a look at the way other mammals give birth. For example, when cats, dogs or horses are in labor, they find dark places to have their offspring in peace. They eat when they?re hungry, pace if they?re in pain and run if something comes near them.
Compare that to a hospital setting, where a woman is given ice chips, strapped to machines while laying in bed and surrounded by people who are constantly interrupting. Though the machines and medical personnel are sometimes necessary, Fischbein says the stress comes from being in an unfamiliar environment.
He recommends women find a doctor or midwife who will take the time to talk through their fears and dispense honest advice about the birthing process.
Nowadays, it cannot be denied that many people are still trapped in the cycle of debt. A single loan is easy to manage but it you have to deal with a couple of payment notices and bills week after week, it is really difficult. Getting the services of a professional debt management consultant becomes a necessity if you want to be freed from the troubles of managing several loans all at once.
Debt management consultants are expert in waiving late payments, negotiating lower interest rates, consolidating several smaller loans to a single larger one and producing a payment schedule that is favorable for both creditor and the borrower
If you having a hard time dealing with several loans, debt consolidation can be of great help in overcoming your present financial situation. You just need to talk to the right people, ome to the right place and converse to a reliable debt management consultant who would help you instead of taking advantage of your present financial instability.
Consumers should choose a debt management consultant who is capable of providing effective and sound advice. Whether you are choosing for permanent or freelance consultant, be sure to select a professional and licensed one.
You should search for the consultant?s accreditation and license to ensure that the best financial advice will be provided. Check their licenses and accreditations with the online services of the Better Business Bureau. You can also check them out with the Attorney General?s Office and Consumer Protection Agency.
A professional and reliable debt management consultant can offer you with great relief in fixing your financial problem easily. Choose the one who has acquired extensive knowledge in resolving debt repayment concerns easily in a legal way.
When choosing for a debt management consultant, make sure that he is capable of pulling you out of your present financial instability. He must be able to produce an effective game plan that would eliminate your debt within just a short period of time.
You should stay from consultants who would recommend the application of new Employer Identification Number or EIN to get rid of your present debt record. This process is known as file segregation and it is considered as a federal crime.
You should always be cautious about con artists who will always take advantage of you present financial instability. After promising great results, they will ask for huge upfront fees and never show up again.
It is normal to be charged with $50-$100 as upfront fees but beyond that, better think twice. Whatever you pay, better put it in writing to protect your interest. Never be tricked by companies who require application fees, enrollment fees, consultation fees and even maintenance fees. When choosing for a debt management consultant, choose the one who charges a nominal monthly fee that range from $2-$5 per creditor.
Choose a debt management consultant who is known for his ability to disburse payments to creditors on time. Many companies are notorious for their unhealthy practice of sending late payments to creditors which causes trouble between borrowers and creditors.
The experts at Abbot and Edwards are waiting to help you sort out your financial difficulties. Why not follow the link to get free advice about debt management now, you?ll feel better for taking that first step.
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New mechanism of bacterial pathogenesis discoveredPublic release date: 27-Jun-2012 [ | E-mail | Share ]
Contact: Arto Pulliainen, Ph.D. arto.pulliainen@utu.fi 358-233-37238 Academy of Finland
Scientists have identified a new mechanism of bacterial pathogenesis. The results of the research project, partly funded by the Academy of Finland, have been published in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).
Bacteria that cause chronic infections have an amazing but yet poorly known ability to subvert immune response, live and produce offspring, enter and wake up from a dormant phase to cause, in some instances, deadly complications.
Bartonella bacteria cause chronic infections in mammals (incl. humans), and are typically transmitted to new hosts mainly by arthropod vectors such as fleas, lice and ticks, but also via direct tissue trauma (e.g. cat scratches).
One very notable feature of these bacteria is their ability to cause vasoproliferative tumours that resemble Kaposi's sarcoma in patients suffering from immunodeficiency (e.g. AIDS, aggressive cancer treatments, organ transplantation). If left untreated, these foci of inflammation maintain a chronic infection and contribute to transmitting bacteria to new hosts.
In his research, biologist Arto Pulliainen (University of Turku) has demonstrated that Bartonella henselae injects a protein called BepA into vascular endothelial cells and that this protein manipulates cAMP-mediated cell signalling using a previously unknown mechanism.
BepA directly binds the host cell adenylyl cyclase, which is an enzyme responsible for the production of cAMP. However, the binding of BepA to the adenylyl cyclase does not activate cAMP production per se, but the adenylyl cyclase rather becomes more sensitive to its natural activator, stimulatory G-protein (G?s). The cellular concentration of cAMP increases and prevents the death of the host cell. BepA significantly prolongs the lifespan of the host cell and partly contributes to the formation of vasoproliferative tumours.
Several bacterial species are known to manipulate host cell functions via cAMP-mediated cell signalling. The symptoms are typically very strong and may even be deadly. The best-known example is Vibrio cholerae and its cholera toxin, which modifies G?s into a permanently adenylyl cyclase-stimulating form. BepA, in turn, manipulates host cell signalling in a subtle sophisticated manner, which is ideal for chronic persistence of Bartonella henselae in the infected vascular endothelium.
The research has been carried out at the Universities of Basel and Turku.
###
More information:
Arto Pulliainen, PhD
Institute of Biomedicine
University of Turku
Kiinamyllynkatu 10
FI-20520 TURKU
tel. +358 2 333 7238
arto.pulliainen@utu.fi
Article: Pulliainen, A.T., Pieles, K., Brand, C.S., Hauert, B., Bhm, A., Quebatte, M., Webf, A., Gstaiger, M., Aebersold, R., Dessauer, C.W. and Dehio, C. (2012). "Bacterial effector binds host cell adenylyl cyclase to potentiate G?s-dependent cAMP production". PNAS 109:9581-9586.
Academy of Finland Communications
Juho Karjalainen
tel. +358 40 670 7755
firstname.lastname(at)aka.fi
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
New mechanism of bacterial pathogenesis discoveredPublic release date: 27-Jun-2012 [ | E-mail | Share ]
Contact: Arto Pulliainen, Ph.D. arto.pulliainen@utu.fi 358-233-37238 Academy of Finland
Scientists have identified a new mechanism of bacterial pathogenesis. The results of the research project, partly funded by the Academy of Finland, have been published in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).
Bacteria that cause chronic infections have an amazing but yet poorly known ability to subvert immune response, live and produce offspring, enter and wake up from a dormant phase to cause, in some instances, deadly complications.
Bartonella bacteria cause chronic infections in mammals (incl. humans), and are typically transmitted to new hosts mainly by arthropod vectors such as fleas, lice and ticks, but also via direct tissue trauma (e.g. cat scratches).
One very notable feature of these bacteria is their ability to cause vasoproliferative tumours that resemble Kaposi's sarcoma in patients suffering from immunodeficiency (e.g. AIDS, aggressive cancer treatments, organ transplantation). If left untreated, these foci of inflammation maintain a chronic infection and contribute to transmitting bacteria to new hosts.
In his research, biologist Arto Pulliainen (University of Turku) has demonstrated that Bartonella henselae injects a protein called BepA into vascular endothelial cells and that this protein manipulates cAMP-mediated cell signalling using a previously unknown mechanism.
BepA directly binds the host cell adenylyl cyclase, which is an enzyme responsible for the production of cAMP. However, the binding of BepA to the adenylyl cyclase does not activate cAMP production per se, but the adenylyl cyclase rather becomes more sensitive to its natural activator, stimulatory G-protein (G?s). The cellular concentration of cAMP increases and prevents the death of the host cell. BepA significantly prolongs the lifespan of the host cell and partly contributes to the formation of vasoproliferative tumours.
Several bacterial species are known to manipulate host cell functions via cAMP-mediated cell signalling. The symptoms are typically very strong and may even be deadly. The best-known example is Vibrio cholerae and its cholera toxin, which modifies G?s into a permanently adenylyl cyclase-stimulating form. BepA, in turn, manipulates host cell signalling in a subtle sophisticated manner, which is ideal for chronic persistence of Bartonella henselae in the infected vascular endothelium.
The research has been carried out at the Universities of Basel and Turku.
###
More information:
Arto Pulliainen, PhD
Institute of Biomedicine
University of Turku
Kiinamyllynkatu 10
FI-20520 TURKU
tel. +358 2 333 7238
arto.pulliainen@utu.fi
Article: Pulliainen, A.T., Pieles, K., Brand, C.S., Hauert, B., Bhm, A., Quebatte, M., Webf, A., Gstaiger, M., Aebersold, R., Dessauer, C.W. and Dehio, C. (2012). "Bacterial effector binds host cell adenylyl cyclase to potentiate G?s-dependent cAMP production". PNAS 109:9581-9586.
Academy of Finland Communications
Juho Karjalainen
tel. +358 40 670 7755
firstname.lastname(at)aka.fi
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
4 beds, 2 full, 1 part baths Home size: 3,614 sq ft Lot Size: 22,215 sq ft Property Type: DETACHD MLS Number: 12121165
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Imagine a world where pokemon were people. This world would probably look something like Renovia. Once a peaceful land now thrown into chaos by the evil Darkrai.
Owner:
Game Masters:
This topic is an Out Of Character part of the roleplay, ?Pokepeople?. Anything posted here will also show up there.
Topic Tags:
Forum for completely Out of Character (OOC) discussion, based around whatever is happening In Character (IC). Discuss plans, storylines, and events; Recruit for your roleplaying game, or find a GM for your playergroup. This is the auto-generated OOC topic for the roleplay "Pokepeople"
You may edit this first post as you see fit.
Billard
Member for 0 years
I was wondering if I could reserve the spot for a female skitty. I will have the profile up soon.
~Living-Dead Doll~
Member for 2 years
Yeah absolutely! I'm glad someone wants to join. This is the first roleplay I've made so fingers crossed it goes well :) If you have any suggestions for the story just PM me :D
Billard
Member for 0 years
Post a reply
RolePlayGateway is a site built by a couple roleplayers who wanted to give a little something back to the roleplay community. The site has no intention of earning any profit, and is paid for out of their own pockets.
If you appreciate what they do, feel free to donate your spare change to help feed them on the weekends. After selecting the amount you want to donate from the menu, you can continue by clicking on PayPal logo.
Mobile health and fitness apps are increasingly popular but they?re often predicated on the notion that you have to feed in a lot of data to make them useful. The problem is that information entry often appeals more to data junkies and really disciplined users. But for the masses, that can be a high bar to overcome, preventing many from getting the most of out of these apps.
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Public release date: 28-Jun-2012
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