CAIRO (AP) ? Mideast heavyweights had a first high-level meeting in Cairo on Monday as part of newly-formed quartet tasked to end Syria's civil war, cautioning that a solution would not come easy but that common ground exists between Damascus' staunchest regional ally and its opponents.
The gathering was the first time foreign ministers from the "Islamic Quartet" met for the dialogue as part of an initiative launched by Egypt's new Islamist president Mohammed Morsi.
"Nobody should expect from one meeting an immediate action plan which we agree upon and could be presented to others," said Turkish Foreign Minister Ahmet Davutoglu, adding that what counted was "regional ownership" of the crisis.
Davutoglu was speaking to reporters in a press conference alongside his Egyptian and Iranian counterparts after the meeting in Cairo's Foreign Ministry.
The four-nation group brings together three supporters of the Syrian rebellion ? Turkey, Saudi Arabia and Egypt ? with the Syrian regime's top regional ally, Iran.
The U.N.'s special envoy for Syria, Lakhdar Ibrahimi, and Arab League chief Nabil Elaraby had discussed Ibrahimi's three-day trip to Syria over the weekend, where he met Syrian President Bashar Assad, before meeting the ministers for dinner.
Egyptian Foreign Minister Mohamed Kamel Amr also acknowledged that a plan had not emerged from Monday night's meeting, "but there is discussion about this."
Speaking in Arabic, the Iranian foreign minister praised Egypt for its own successful uprising, which ousted the country's longtime authoritarian leader last year and helped spark Syria's own revolt.
"The common ground between us is more than our differences," Ali Akbar Salehi said. "Finding a peaceful solution is important."
While the Turkish foreign minister stressed that the ultimate goal should be "a strong Syria" based on the "legitimate rights and demands of the Syrian people," Salehi said "the solution in Syria should be a Syrian solution," not "imposed from the outside."
Asked whether the Shiite Muslim country had sent military forces to Lebanon and Syria, Salehi did not reply. Earlier in the week a top commander of Iran's powerful Revolutionary Guard said Tehran had sent advisers, the clearest indication to date of Iran's direct assistance to the Syrian regime.
Notably absent was Saudi Arabia's Foreign Minister Prince Saud al-Faisal, who earlier this month was recovering from abdominal surgery in the United States. Last week, Saudi Arabia said that the 72-year-old foreign minister would spend several weeks in Los Angeles to recover.
It was initially suggested that Saudi Arabia would send its deputy foreign minister to the meeting in Cairo, but the kingdom did not. No explanation was given. Saudi Arabia, though, did send the deputy to Cairo last week to attend a preparatory session for Monday's meeting, and the kingdom remains part of the talks.
Earlier in the day, the Turkish foreign minister met with Egypt's Morsi to discuss the Syrian crisis.
Morsi's Sunni Muslim Brotherhood backers, Egypt's most powerful political group since the revolt, are opposed to Shiite Iran's staunch backing of the Syrian regime and its lethal crackdown on largely Sunni protesters. Assad is a follower of the Alawite sect, an offshoot of Shiite Islam.
Turkey, which hosts some 80,000 Syrian refugees, has accused its southern neighbor Syria of "state terrorism" and allowed rebels to use its territory as a base. Saudi Arabia has taken a leading role in supporting the opposition seeking to topple the regime, while Egypt's president has urged Assad to take a lesson from the Arab Spring uprisings that deposed other leaders and step down.
Syria has responded by saying Morsi's comments were "blatant interference in Syrian internal affairs" and accused Turkey of "practicing terrorism against the Syrian people by harboring, supporting and training armed terrorist groups."
Cairo is trying to convince Iran to drop its unquestioned support of Assad in exchange for help in easing Tehran's regional isolation, officials close to the Egyptian presidency said last week.
Morsi was said to have offered a package of incentives for Tehran, including the restoration of full diplomatic ties and efforts toward reconciliation with wealthy Gulf nations ? a significant diplomatic prize for the Islamic Republic, especially as it comes under mounting pressure over its disputed nuclear program.
Meanwhile, the carnage shows no sign of abating. Syrian activists say nearly 5,000 people were killed in August, the highest monthly total since the crisis began in March 2011 ? bringing the overall death toll from the conflict to some 23,000.
President Barack Obama boards Air Force One, Monday, Sept. 17, 2012, at Andrews Air Force Base, Md., en route to Ohio. (AP Photo/Carolyn Kaster)
President Barack Obama boards Air Force One, Monday, Sept. 17, 2012, at Andrews Air Force Base, Md., en route to Ohio. (AP Photo/Carolyn Kaster)
President Barack Obama salutes as he boards Air Force One, Monday, Sept. 17, 2012, at Andrews Air Force Base, Md., en route to Ohio. At left is Col. Michael Minihan. (AP Photo/Carolyn Kaster)
Republican presidential candidate and former Massachusetts Gov. Mitt Romney boards his campaign charter plane in Kansas City, Mo., after a refueling as he travels to Los Angeles, Sunday, Sept. 16, 2012. (AP Photo/Charles Dharapak)
After a dead-heat race for months, President Barack Obama is narrowly leading Republican challenger Mitt Romney in major polls, both nationally and in key states.
Some of the edge could be a bounce from the Democratic convention, and such lifts are subject to fading. But both campaigns are paying close attention to any shift in the polls since there's been so little movement all summer, and they're adjusting their campaign strategies accordingly.
Romney, coming off two rough weeks, was addressing the U.S. Hispanic Chamber of Commerce in Los Angeles, a fast-growing crucial voting bloc that Obama won in 2008 and continues to favor him now.
At the same time, Romney's campaign was launching a new advertising offensive emphasizing the GOP nominee's plans to lift the economy rather than just focusing on slamming Obama.
"My plan is to help the middle class," Romney says, speaking directly to the camera. "Trade has to work for America. That means crack down on cheaters like China. That means open up new markets."
Romney has accused Obama of policies that resulted in U.S. jobs being shipped to China. The Obama campaign blames Romney's former equity firm for doing the same thing.
Almost if on cue, the Obama administration on Monday sought a World Trade Organization ruling telling China to stop subsidizing auto parts made for export. It argues the practice undercuts manufacturers in Ohio and elsewhere and encourages U.S. companies to outsource.
And, not coincidentally, Obama had campaign rallies Monday in Cincinnati and Columbus, Ohio
Ohio is a crucial swing state, as it has been for the last several elections, and no Republican has ever won the presidency without carrying it.
Seven weeks out, Obama leads Romney in Ohio, Florida and Virginia, according to NBC News/Wall Street Journal/Marist polls in those states.
___
Follow Tom Raum on Twitter: http://www.twitter.com/tomraum. For more AP political coverage, look for the 2012 Presidential Race in AP Mobile's Big Stories section. Also follow https://twitter.com/APcampaign and AP journalists covering the campaign: https://twitter.com/AP/ap-campaign-2012
Each week our friends at Inhabitat recap the week's most interesting green developments and clean tech news for us -- it's the Week in Green.
Apple dominated the news cycle this week with the debut of the iPhone 5, as the internet was buzzing with details about the lighter, thinner and faster new iPhone. But not everyone was thrilled with the news. A journalist in China spent 10 days undercover working at a Foxconn factory, detailing the grueling conditions workers undergo to produce the new gadget. Apple wasn't the only tech company in the news this week, though; Google got some time in the spotlight this week too, as the company's new augmented-reality glasses were trotted down the runway at New York Fashion Week. Continuing the trend of high-tech fashion, British designer Dominic Wilcox unveiled a GPS shoe that guides you home from anywhere in the world.
Chiropractic therapy is all about natural healing method, but that does not mean that advanced methods are not used as well. As long as a method is non-invasive and no medicine or medical methods such as surgery are involved, it can be used. One Dallas cold laser chiropractor has given many upper back patients effective and long term pain relief
Also known as low level laser therapy or LLLT, it involves the stimulation of body cells which has the effect of accelerating the healing process. This is done using coherent light of a specific wavelength and frequency. The light is generated from a machine that produces low watt therapeutic light.
The term cold laser makes reference to the use of light of a particular wavelength. The standard range is 630nm to 980nm and this measured on an electromagnetic spectrum. Within this range, the energy can be taken into surface tissue safely without the patient experiencing heat or burning sensations. The ability of light to heal can thus be used to achieve the healing of muscles and tissues that are weak or injured.
For those suffering with pain in the upper back, LLLT has successfully been used to manage and reduce severe or chronic pain resulting from an injury or the back muscles and spine being strained with heavy physical activity. Ruptured or herniated spinal discs can also be healed with this form of therapy.
Patients get pain relief right from the initial therapy and they regain unlimited and painless motion with every session. The light is beamed directly over the back which hastens the time it takes for the problem to be resolved. It cuts recovery time by as much as half. Exposing the cells to the light invigorates the function of the cells directly and also strengthens the immune system. It also encourages tissue regeneration and collagen synthesis.
The Dallas cold laser chiropractor has been an answered prayer for upper back pain sufferers. Not only have they found lasting relief for the problem, but the problem has also been resolved faster. They have thus been able to get on with their lives that much sooner with no pain and with no limitation of motion.
Chiropractic care alleviates elbow, neck and upper back pain safely. You can get more information about an experienced Dallas cold laser chiropractor at http://www.coldlaser.com now.
After some worrisome moments for Randy Jackson ? to?paraphrase the song, ?Is he is, or is he ain?t?? ? the four judges for this season of American Idol are: Mariah Carey, Randy Jackson, Nicki Minaj and Keith Urban.
The official press release follows the jump.
?AMERICAN IDOL? JUDGES ANNOUNCED
GLOBAL ICON MARIAH CAREY AND
MUSIC INDUSTRY VETERAN RANDY JACKSON WELCOME
RENOWNED RAPPER, SINGER AND SONGWRITER NICKI MINAJ AND
COUNTRY MUSIC SUPERSTAR KEITH URBAN TO JUDGES? TABLE
When AMERICAN IDOL?s 12th season debuts in January 2013, superstar judge Mariah Carey ? the best-selling female recording artist of all time ? and returning judge Randy Jackson, a Grammy Award-winning producer whose expertise and beloved persona have been instrumental in discovering IDOL talent from the beginning, will be joined by two new judges: quadruple-platinum singer, songwriter, rapper and fashion icon Nicki Minaj; and Keith Urban, a four-time Grammy Award winner who has sold more than 15 million albums.
Hopefuls will meet host Ryan Seacrest and the new four-person panel of Carey, Jackson, Minaj and Urban today, when the auditions begin in New York City. Other audition cities include Los Angeles, Chicago, Charlotte, San Antonio, Baton Rouge and Oklahoma City.
Carey is a multiple Grammy Award-winning global superstar with more than 200 million records sold worldwide and more No. 1 songs than any solo artist in history, whose 18 Billboard No. 1 singles (17 of which Carey wrote) rival all but The Beatles. Jackson is a Grammy Award-winning producer who has worked on more than 1,000 gold and multi-platinum albums, which have sold more than 200 million albums worldwide. His amazing talent, vast studio knowledge, performing, touring and record company experience have made him one of today?s most coveted music industry experts. Known for her unique performance style and iconic fashion, Minaj became the first female solo artist to have seven singles simultaneously on the Billboard Hot 100 chart. Urban, one of country music?s biggest stars of the decade, has four Grammy Awards and 14 No. 1 hits, and was named Male Vocal Artist of the Year three times, as well as Entertainer of the Year, by the Country Music Association.
?I am thrilled about this year?s judges? panel! We?ve got global icon Mariah Carey and IDOL?s heart and soul Randy Jackson, who will be joined by Nicki Minaj and Keith Urban. Nicki?s an unbelievably captivating international phenomenon who has made an indelible mark on rap and pop. And Keith is another great addition to IDOL ? he?s one of the biggest stars in country music and I know that our fans and contestants will fall in love with him,? said Mike Darnell, President of Alternative Entertainment, Fox Broadcasting Company. ?With an unparalleled star like Mariah, fan-favorite Randy, chart-toppers like Nicki and Keith and our incomparable host Ryan, we?ve put together one of the most exciting judging panels around.?
?We?re ecstatic to welcome Nicki Minaj and Keith Urban to the AMERICAN IDOL family, joining Mariah and Randy at the judges? table,? said Cecile Frot-Coutaz, CEO, FremantleMedia. ?Nicki is someone who represents a different side of the music industry, who has now crossed into mainstream culture with her unique artistry, style and flair. Keith is one of country music?s true stars who brings with him charm, wit and knowledge about the industry.?
Executive producer Simon Fuller noted, ?With the exciting addition of Mariah Carey, Keith Urban and Nicki Minaj, alongside Randy Jackson, AMERICAN IDOL?s star power has never been so great. For this we have to thank the ongoing commitment and belief of FOX and the dedication and focus of the IDOL production team. We have all been together since the very beginning and we are focused on making IDOL Season 12 the best ever.?
?IDOL has truly never looked better,? said Marc Graboff, President of CORE Media Group (owner, 19 Entertainment). ?We couldn?t be more pleased about this new team of judges, and, along with our partners at FOX and Fremantle, look forward to a terrific Season 12.?
About Mariah Carey:
With a distinct five-octave vocal range, prolific songwriting and producing talent, Carey has defined the modern pop performance. As a singer/songwriter/producer, she has been recognized with multiple Grammy Awards, nine American Music Awards, Billboard?s Artist of the Decade Award, the World Music Award for World?s Best Selling Female Artist of the Millennium and BMI?s Icon Award, to name a few. She has two consecutive and unparalleled Billboard Song of the Decade titles: One Sweet Day (with Boyz II Men); and We Belong Together, further marking her massive presence on the charts since her 1990 song debut Vision of Love. Mariah became the second artist in history and the first female performer to have a song debut at No. 1 with Fantasy (1995), the groundbreaking collaboration with O.D.B. of the innovative rap group Wu-Tang Clan. Carey?s original holiday classic, All I Want For Christmas Is You, redefined its place in pop culture as one of the greatest holiday hits of all time when it reached No. 1 on the Billboard charts in 2011, 17 years after its debut. Carey?s influential and stellar contribution to the music industry spans multiple genres and is showcased through a multifaceted hit catalog as well as a long list of diverse collaborations.
Carey?s ongoing impact transcends the music industry and has left an indelible imprint upon the world at large. She recently made a substantial mark in film with her critically acclaimed role as a social worker in Precious, the 2009 film based on the novel Push,by Sapphire. A Congressional Award recipient, Carey has generously donated her time and energy to a range of domestic and international philanthropic causes near to her heart, including The Fresh Air Fund/Camp Mariah (a retreat where inner-city children explore career development), Save the Music Foundation and Make-a-Wish Foundation, among several others.
Carey is currently in the studio, writing, recording and executive-producing her next album for Island Def Jam Music Group, with the lead single Triumphant.
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About Randy Jackson:
A music industry veteran of more than 20 years and a Grammy Award-winning producer, Randy Jackson began playing bass guitar at age 13 and got his big break when he joined the band Journey. A prolific producer, Jackson spent eight years as Vice President of A&R at Columbia Records, followed by four years as Senior Vice President of A&R at MCA Records. However, it was AMERICAN IDOL that propelled Jackson into the mainstream.
Jackson has since expanded into television production, setting up his Dream Merchant 21 Entertainment banner at Warner Horizon Television and launching the hit reality-competition series Randy Jackson Presents: America?s Best Dance Crew.
While working on more than 1,000 gold and multi-platinum albums, which have sold more than 200 million albums worldwide, Jackson?s amazing talent, vast studio knowledge, performing, touring and record company acumen have made him one of today?s most coveted music industry experts.
?
In 2006, Jackson executive-produced and performed on the legendary Sam Moore?s Grammy-nominated album ?Overnight Sensational.? Jackson also teamed with country music superstar Travis Tritt, and most recently, he brought together an eclectic mix of artists on Randy Jackson?s Music Club, Vol. 1, the first release from his Dream Merchant 21 record label.
Also a published author, Jackson has penned two books: What?s Up, Dawg? How to Become a Superstar In The Music Business and Body With Soul: Steady Your Sugar, Cut Your Cholesterol and Get a Jump on Your Best Health.
About Nicki Minaj:
Nicki Minaj is a Trinidadian-born American rapper, singer, songwriter and voice actress. Known for her underground mix-tape presence, Minaj garnered the attention of Lil Wayne, who signed her to his record label, Cash Money. She immediately rose to prominence when she released her debut album Pink Friday, in November 2010. It quickly became a commercial success, peaking at No. 1 on the U.S. Billboard 200 and was certified platinum by the Recording Industry Association of America (RIAA) a month after its release. She simultaneously became the featured It girl on a string of high-profile singles from artists such as Madonna, Mariah Carey, Jay-Z, Kanye West, Eminem, Rihanna, Lil Wayne, Drake, Britney Spears, Christina Aguilera, Usher, Ludacris, Justin Bieber, Trey Songz and Alicia Keys. Minaj also has become the first female solo artist to have seven singles on the Billboard Hot 100 at the same time. Her seventh single Super Bass, has since been certified quadruple-platinum by the RIAA and has sold more than four million copies, becoming one of the best-selling singles in the United States.
Minaj released her second studio album Pink Friday: Roman Reloaded, in April 2012, which topped charts internationally, and spawned the Top 10 single Starships and Pound the Alarm. Since then, the album has sold one million copies worldwide, and has become one of the best-selling albums of 2012, according to Nielsen SoundScan. At the 2012 MTV Video Music Awards, she won Best Female Video for Starships. At the 2011 MTV Video Music Awards, she won Best Hip-Hop Video for ?Super Bass.?
Nominated for a 2012 Grammy Award in the category of Best New Artist, Minaj?s rapping technique has been hailed by critics for its use of alter-egos, accents (notably, British) and rapid-fire pace. Equally well-known for her unique sense of style, her use of colorful wigs and outlandish costumes ranks her as one of the world?s leading fashion icons. Minaj is in the midst of her Pink Friday: RELOADED Tour.
About Keith Urban:
In 2001, the Country Music Association honored Keith Urban with its Horizon Award, designating him a talented artist with a bright future. He is the first Horizon Award winner in history to go on to win the CMA?s Male Vocalist of the Year, a title he?s captured three times, and the coveted Entertainer of the Year. More than 15 million albums later, Urban is a four-time Grammy Award winner, who has also won a People?s Choice and American Music Award. He?s won five Academy of Country Music Awards and had 14 No. 1 songs, including 28 Top 5 hits. In 2012, he became a member of the Grand Ole Opry. His latest CD, ?Get Closer,?comes on the heels of his fifth consecutive platinum or multi-platinum release. It has produced three consecutive No. 1 singles: You Gonna Fly, Long Hot Summer and Without You.
In 2009, Urban was named radio?s most-played country artist, thanks to No. 1 hits such as Sweet Thing, You?ll Think Of Me, Only You Can Love Me This Way, Better Life and Days Go By. In addition, his 2002 smash, Somebody Like You, was named the No. 1 Country Song of the Decade by Nielsen BDS (based on radio airplay and audience impressions).
But Urban?s reputation as an elite songwriter, musician, vocalist and virtuoso guitarist is no more evident than when he is onstage. His electrifying concerts have played to sold-out venues in Australia, Germany, England, Canada and the United States, all while receiving high praise from critics. In fact, 2009?s Escape Together World Tour, as well as 2007?s Love, Pain & The Whole Crazy World Tour, were both, according to Pollstar, one of the top-grossing tours for their respective years. Last year, his Get Closer 2011 World Tour solidified Urban as one of the music industry?s best live performers.
AMERICAN IDOL has been the No. 1 entertainment program among Total Viewers for the past nine consecutive seasons. To date, IDOL alums have produced 356 No. 1 Billboard hits and garnered nearly 250 million iTunes downloads. Season 11 winner Phillip Phillips? first single, Home, which was released May 23, has been certified platinum. Last year, Season 10 winner Scotty McCreery released his debut album Clear As Day, which dominated the Billboard Country Albums chart and has gone platinum, selling more than one million copies. McCreery is the youngest male artist to ever enter the U.S. albums charts at the No. 1 spot.
AMERICAN IDOL is produced by 19 Entertainment, a division of Core Media Group and FremantleMedia North America, Inc.
Visit www.americanidol.com for exclusive videos, interviews and photos, as well as special behind-the-scenes information and all of your AMERICAN IDOL news. ?Like? AMERICAN IDOL on Facebook at www.facebook.com/AmericanIdol. Follow the series on Twitter @AmericanIdol and join the discussion at #idol. Follow host Ryan Seacrest at @RyanSeacrest, and follow the judges: @MariahCarey; @yo_randyjackson; @nickiminaj; and @keithurban.
Tags: American Idol, Fox Television, Keith Urban, Marian Carey, Nicki Minaj, Randy Jackson, Television
Contact: Mika Ono mikaono@scripps.edu 858-784-2052 Scripps Research Institute
Ads in Craigslist lead to potential medical advance
LA JOLLA, CA -- Scientists from The Scripps Research Institute and Sea Lane Biotechnologies have solved the co-crystal structure of a human antibody that can neutralize influenza viruses in a unique way. The antibody recognizes the crucial structure that flu viruses use to attach to host cells, even though previously this structure had been thought too small for an antibody to grab effectively. The immune protein manages to hit this precise spot by using just a small part of its target-grabbing apparatus. In so doing, it can neutralize a broad range of dangerous flu viruses.
"This highly focused binding to the receptor binding site using only a single loop on the antibody has never been seen before, and it's really fascinating; it gives us some good ideas about designs for vaccines and therapies," said Ian A. Wilson, the Hansen Professor of Structural Biology at Scripps Research. Wilson was senior investigator of the study along with Ramesh R. Bhatt of Sea Lane Biotechnologies. The report appears online ahead of print on September 16, 2012, in the journal Nature.
The Power of Large Numbers
Sea Lane Biotechnologies, advised by Richard Lerner, the Lita Annenberg Hazen Professor of Immunochemistry at Scripps Research, began by collecting bone marrow from patients who had been exposed to certain key strains of flu. Because the bone marrow is a "fossil record" of all the antibodies a person has ever made, those at Sea Lane felt confident that the antibodies they were looking for would be there. Sea Lane's efforts even went as far as to include advertised appeals on Craigslist for individuals who had certain strains of the flu. Using the internationally and locally collected bone marrow, Sea Lane generated a "comprehensive flu library" of billions of antibodies.
Sea Lane Biotechnologies scientists, led by Bhatt, isolated the unusual new antibody, which they dubbed C05, by screening this enormous library for antibodies that could bind to proteins from a variety of influenza A virusesthe most dangerous family of flu viruses.
C05 also protected cells in the lab dish from infection by these viruses. In mice, relatively low doses of C05 prevented infections despite influenza A exposures that would have been lethal. The antibody worked as a therapy, too, rescuing 100 percent of mice when administered up to three days after a flu infection had begun.
An Unusual Grip for a Tricky Target
Further tests revealed a curious property of C05. Almost uniquely among broadly neutralizing antibodies against influenza A, it specifically recognizes and blocks the part of the flu virus that mediates viral attachment to host cells. Known as the "receptor binding site" (RBS), this viral site is located on the heads of viral hemagglutinins, spiky structures of sugar and protein that coat the viral envelope.
The RBS is a key functional site on flu viruses and is relatively exposed to the immune system compared to other viral regions. It would be an ideal target for antibodies, except that it is quite small compared to an antibody's usual grip area.
An antibody binds targets using two arm-like structures, each of which has six protein fingers or loops. To get a good grip on the flu RBS with some or all these loops, a typical antibody has to grab not only the RBS, but also some of the surrounding structures in the head, which vary from one flu strain to another. Thus, an antibody that does get a firm grip on this region for one flu strain generally will lose that grip once the strain mutates. "This is why universal flu vaccine strategies in recent years have been focused more on the hemagglutinin stem than on the head," noted Damian C. Ekiert, formerly of Wilson's laboratory at Scripps Research and now of University of California, San Francisco. Ekiert was first author of the paper with Arun K. Kashyap of Sea Lane Biotechnologies.
Wilson's laboratory specializes in the use of X-ray crystallography and other techniques to determine precisely where and how such antibodies bind to their viral targets. Using these methods, his team found that C05 effectively avoids grabbing the hypervariable regions around the flu RBS. Instead it uses a single elongated protein loop to reach in and make a "one-handed"or "one-fingered"grab of the RBS itself. The antibody apparently works best when two of these active loops, one on each arm, grab two viral RBSs on separate hemagglutinins. "It looks like these antibodies need to cross-link two hemagglutinins to have maximum effect," said Wilson.
Potentially Useful
The RBS has such an important function that it does not change much from strain to strainand thus C05 can neutralize a broad range of dangerous influenza A viruses, including H1, H2, H3, and H9 subtypes.
The fact that C05 can make such a precision grab suggests that it and perhaps even more potent antibodies could contribute to antibody-based therapies for severe influenza infections. A universal flu vaccine also might be significantly more effective if it could be designed to elicit such antibodies in people.
"If we can figure out how to induce this sort of antibody in a vaccine, we would have something that's very useful," said Lawrence Horowitz, CEO of Sea Lane Biotechnologies.
###
In addition to Wilson, Bhatt, Ekiert, Kashyap, and Horowitz, authors of the paper, "Neutralization of Influenza A viruses by insertion of a single antibody loop into the receptor binding site," included Michael A. Dillon, Ryann E. O'Neil, Aleksandr M. Faynboym, and Michael Horowitz of Sea Lane; John Steele and Peter Palese of the Mount Sinai School of Medicine; Adam Rubrum and Richard Webby of St. Jude Children's Research Hospital of Memphis, Tennessee; and Gira Bhabha, Reza Khayat, Jeong Hyun Lee, and Andrew B. Ward of Scripps Research.
The study was funded in part by grants from the National Institutes of Health (P01 AI058113 and GM080209) and the Skaggs Institute for Chemical Biology at Scripps Research.
About The Scripps Research Institute
The Scripps Research Institute is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. Over the past decades, Scripps Research has developed a lengthy track record of major contributions to science and health, including laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. The institute employs about 3,000 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientistsincluding three Nobel laureateswork toward their next discoveries. The institute's graduate program, which awards Ph.D. degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.
About Sea Lane Biotechnologies, LLC
Sea Lane Biotechnologies, LLC is focused on innovating biotherapeutic discovery with transformative technologies and platforms that are necessary to meet contemporary pharmaceutical biologic portfolio requirements. Founded in 2005 in the Silicon Valley, the company is dedicated to the discovery and development of biotherapeutic drugs based upon a novel class of proteins called Surrobodies and world-class antibodies for the treatment of serious human diseases, such as cancer and viral infection. Sea Lane currently has several proprietary product candidates in pre-clinical testing.
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Contact: Mika Ono mikaono@scripps.edu 858-784-2052 Scripps Research Institute
Ads in Craigslist lead to potential medical advance
LA JOLLA, CA -- Scientists from The Scripps Research Institute and Sea Lane Biotechnologies have solved the co-crystal structure of a human antibody that can neutralize influenza viruses in a unique way. The antibody recognizes the crucial structure that flu viruses use to attach to host cells, even though previously this structure had been thought too small for an antibody to grab effectively. The immune protein manages to hit this precise spot by using just a small part of its target-grabbing apparatus. In so doing, it can neutralize a broad range of dangerous flu viruses.
"This highly focused binding to the receptor binding site using only a single loop on the antibody has never been seen before, and it's really fascinating; it gives us some good ideas about designs for vaccines and therapies," said Ian A. Wilson, the Hansen Professor of Structural Biology at Scripps Research. Wilson was senior investigator of the study along with Ramesh R. Bhatt of Sea Lane Biotechnologies. The report appears online ahead of print on September 16, 2012, in the journal Nature.
The Power of Large Numbers
Sea Lane Biotechnologies, advised by Richard Lerner, the Lita Annenberg Hazen Professor of Immunochemistry at Scripps Research, began by collecting bone marrow from patients who had been exposed to certain key strains of flu. Because the bone marrow is a "fossil record" of all the antibodies a person has ever made, those at Sea Lane felt confident that the antibodies they were looking for would be there. Sea Lane's efforts even went as far as to include advertised appeals on Craigslist for individuals who had certain strains of the flu. Using the internationally and locally collected bone marrow, Sea Lane generated a "comprehensive flu library" of billions of antibodies.
Sea Lane Biotechnologies scientists, led by Bhatt, isolated the unusual new antibody, which they dubbed C05, by screening this enormous library for antibodies that could bind to proteins from a variety of influenza A virusesthe most dangerous family of flu viruses.
C05 also protected cells in the lab dish from infection by these viruses. In mice, relatively low doses of C05 prevented infections despite influenza A exposures that would have been lethal. The antibody worked as a therapy, too, rescuing 100 percent of mice when administered up to three days after a flu infection had begun.
An Unusual Grip for a Tricky Target
Further tests revealed a curious property of C05. Almost uniquely among broadly neutralizing antibodies against influenza A, it specifically recognizes and blocks the part of the flu virus that mediates viral attachment to host cells. Known as the "receptor binding site" (RBS), this viral site is located on the heads of viral hemagglutinins, spiky structures of sugar and protein that coat the viral envelope.
The RBS is a key functional site on flu viruses and is relatively exposed to the immune system compared to other viral regions. It would be an ideal target for antibodies, except that it is quite small compared to an antibody's usual grip area.
An antibody binds targets using two arm-like structures, each of which has six protein fingers or loops. To get a good grip on the flu RBS with some or all these loops, a typical antibody has to grab not only the RBS, but also some of the surrounding structures in the head, which vary from one flu strain to another. Thus, an antibody that does get a firm grip on this region for one flu strain generally will lose that grip once the strain mutates. "This is why universal flu vaccine strategies in recent years have been focused more on the hemagglutinin stem than on the head," noted Damian C. Ekiert, formerly of Wilson's laboratory at Scripps Research and now of University of California, San Francisco. Ekiert was first author of the paper with Arun K. Kashyap of Sea Lane Biotechnologies.
Wilson's laboratory specializes in the use of X-ray crystallography and other techniques to determine precisely where and how such antibodies bind to their viral targets. Using these methods, his team found that C05 effectively avoids grabbing the hypervariable regions around the flu RBS. Instead it uses a single elongated protein loop to reach in and make a "one-handed"or "one-fingered"grab of the RBS itself. The antibody apparently works best when two of these active loops, one on each arm, grab two viral RBSs on separate hemagglutinins. "It looks like these antibodies need to cross-link two hemagglutinins to have maximum effect," said Wilson.
Potentially Useful
The RBS has such an important function that it does not change much from strain to strainand thus C05 can neutralize a broad range of dangerous influenza A viruses, including H1, H2, H3, and H9 subtypes.
The fact that C05 can make such a precision grab suggests that it and perhaps even more potent antibodies could contribute to antibody-based therapies for severe influenza infections. A universal flu vaccine also might be significantly more effective if it could be designed to elicit such antibodies in people.
"If we can figure out how to induce this sort of antibody in a vaccine, we would have something that's very useful," said Lawrence Horowitz, CEO of Sea Lane Biotechnologies.
###
In addition to Wilson, Bhatt, Ekiert, Kashyap, and Horowitz, authors of the paper, "Neutralization of Influenza A viruses by insertion of a single antibody loop into the receptor binding site," included Michael A. Dillon, Ryann E. O'Neil, Aleksandr M. Faynboym, and Michael Horowitz of Sea Lane; John Steele and Peter Palese of the Mount Sinai School of Medicine; Adam Rubrum and Richard Webby of St. Jude Children's Research Hospital of Memphis, Tennessee; and Gira Bhabha, Reza Khayat, Jeong Hyun Lee, and Andrew B. Ward of Scripps Research.
The study was funded in part by grants from the National Institutes of Health (P01 AI058113 and GM080209) and the Skaggs Institute for Chemical Biology at Scripps Research.
About The Scripps Research Institute
The Scripps Research Institute is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. Over the past decades, Scripps Research has developed a lengthy track record of major contributions to science and health, including laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. The institute employs about 3,000 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientistsincluding three Nobel laureateswork toward their next discoveries. The institute's graduate program, which awards Ph.D. degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.
About Sea Lane Biotechnologies, LLC
Sea Lane Biotechnologies, LLC is focused on innovating biotherapeutic discovery with transformative technologies and platforms that are necessary to meet contemporary pharmaceutical biologic portfolio requirements. Founded in 2005 in the Silicon Valley, the company is dedicated to the discovery and development of biotherapeutic drugs based upon a novel class of proteins called Surrobodies and world-class antibodies for the treatment of serious human diseases, such as cancer and viral infection. Sea Lane currently has several proprietary product candidates in pre-clinical testing.
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Public release date: 16-Sep-2012
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