�Researchers at The Wistar Institute accept deciphered the structure of the dynamic region of telomerase, an enzyme that plays a major role in the development of nearly all human cancers. The landmark achievement opens the door to the creation of new, broadly speaking effective malignant neoplastic disease drugs, as well as anti-aging therapies.
Researchers have attempted for more than than a decade to find drugs that keep out down telomerase - widely considered the No. 1 target for the development of young cancer treatments - only have been hampered in large part by a lack of knowledge of the enzyme's structure.
The findings, published on-line August 31 in
Nature, should help researchers in their efforts to excogitation effective telomerase inhibitors, says Emmanuel Skordalakes, Ph.D., helper professor in Wistar's Gene Expression and Regulation Program, who light-emitting diode the study.
"Telomerase is an ideal mark for chemotherapy because it is participating in most all human tumors, simply inactive in most normal cells," Skordalakes says. "That means a drug that deactivates telomerase would likely work against all cancers, with few side effects."
The study elucidates the active region of telomerase and provides the first full-length view of the telomerase molecule's decisive protein constituent. It reveals surprising inside information, at the atomic grade, of the enzyme's configuration and how it works to reduplicate the ends of chromosomes - a process critical to both tumor development and the aging process.
Achieving immortality
In human race, telomerase adds multiple repeats of a short DNA sequence to the ends of chromosomes, known as telomeres, so preventing harm and the loss of genetic information during cubicle division.
When telomerase is torpid, telomeres contract each time a cubicle divides, leading eventually to genetic unstableness and cell death. By preserving chromosomes' integrity, telomerase allows cells to continue living and dividing. The enzyme is active in cells that multiply ofttimes, such as embryonic stem cells, but is switched off virtually entirely in normal adult cells to prevent the dangers of runaway cellular telephone proliferation.
Cancer cells, however, a great deal regain the ability to activate telomerase, which has been implicated in 90 percent of human tumors. The enzyme permits cells to replicate indefinitely and achieve the cellular "immortality" that is the trademark of cancer. Deactivating telomerase would stop tumor growth.
In addition to its role in cancer, telomerase holds significant implications for the development of therapies to combat ripening and other age-related diseases. Finding slipway to aerate telomerase under controlled conditions and admit some cells to commence dividing once again could final result in healthier, younger-looking tissue paper that lives longer.
An knotty enzyme
Telomerase is a composite structure made up of multiple protein domains and a debase of RNA, which contains the guide the enzyme uses to synthesize telomeres.
Last year, Skordalakes and his team solved the body structure of a key segment of the molecule - the alleged TRBD world, where RNA binding occurs. However, the complexity of telomerase has proved a roadblock to determining the enzyme's overall architecture - a destination pursued by researchers world for more than 15 years.
To do the necessary studies, scientists first must gather big quantities of the enzyme in a specific form. Because the complex structure of telomerase most likely allows it to change configuration, that process has been ambitious, Skordalakes says.
To find sufficient quantities of the enzyme for the study, Skordalakes and his team looked beyond commonly relied-on sources such as humans and yeast. By screening a wide variety of organisms, including phylum Protozoa and insects, they discovered that a gene from the red flour beetle could develop telomerase in copious amounts, and a stable form.
"That was very the breakthrough," Skordalakes says. "Once we found that the gene from this organism uttered the protein in the quantities we needed, we were able to proceed quickly."
The researchers used X-ray crystallography, a technique that analyzes the diffraction patterns of X-rays beamed at crystals of a mote, to determine the three-d structure of the enzyme's active region - the catalytic ingredient called telomerase reverse transcriptase protein, or TERT.
The study revealed surprising features, including the fact that the molecule's trey domains ar organized into a sinker shape, an unexpected constellation. Knowledge of the construction allowed the researchers to create a model of the enzyme's function.
"It's extremely exciting," Skordalakes says. "For the low time, we can see how telomerase assembles at the oddment of chromosomes to initiate telomere replication."
Looking ahead
Skordalakes plans to further study TERT and search for new telomerase inhibitors that could become cancer therapies. He also will look at modifying existing drugs. Previous attempts to target telomerase have fallen flat, just knowledge of the enzyme's structure will help researchers to settle the limitations of existing agents and make them more effective.
Skordalakes began his studies of telomerase when he joined The Wistar Institute in 2006 and established his first research laboratory. "I've constantly been interested in sympathy, on a molecular level, the function of protein nucleic acid assemblies and using that information in the handling of human disease," he says. "Telomerase, because of its important role in cancer and aging, was an obvious target for me."
He says though the process was frustrating at times, his team was determined to solve the structure. "It required a lot of perseverance and effort, just we genuinely wanted to do this," he says.
Wistar's Andrew J. Gillis and Anthony P. Schuller aided with the study.
The research was supported in part by the Commonwealth Universal Research Enhancement Program of the Pennsylvania Department of Health and the Ellison Medical Foundation.
The Wistar Institute is an international leader in biomedical research with special expertness in genus Cancer research and vaccine development. Founded in 1892 as the number one independent nonprofit biomedical research institute in the area, Wistar has long held the honored Cancer Center designation from the National Cancer Institute. The Institute works actively to guarantee that inquiry advances impress from the laboratory to the clinic as promptly as possible. The Wistar Institute: Today's Discoveries -Tomorrow's Cures. On the Web at The Wistar Institute.
Source: Abbey J. Porter
The Wistar Institute
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Tuesday 2 September 2008
Sunday 24 August 2008
Download Hearse mp3
 Artist: Hearse: mp3 download Genre(s): Rock Metal: Death,Black Discography:  In These Veins Year: 2007 Tracks: 9  Armageddon, Mon Amour Year: 2004 Tracks: 11  Dominion Reptilian Year: 2003 Tracks: 11 Hearse ar a Swedish death metallic element banding mark together by vocalist/bassist Johan Liiva following his dismissal from Arch Enemy. Together with guitarist Mattias Ljung and drummer Max Thornell, Liiva has since unbroken extremely fussy recording several albums (2003's Rule Reptilian, 2004's Armageddon, Mon Amour, 2005's The Last Ordeal, and 2006's In These Veins) and EPs (2002's Torch and 2005's Cambodia), but their classical student stab at Swedish destruction metal spiked with a small tonic pattern and Entombed-style "rott & hum" has yet to forget a significant print on the metal community of interests. |
Thursday 14 August 2008
Britney Spears Praises Leona Lewis, Madonna, Rihanna And Duffy
Britney Spears has paid tribute to a host of her female contemporaries, including British singers Duffy and Leona Lewis.
In her first interview for 2 years, Spears said that she �really liked Rihanna�, thinks Duffy is �amazing� and revealed that she was a big fan of the new Madonna album.
As previously reported on Gigwise, Spears has also claimed that songs she has been writing for her next studio album are amongst some of her �best work ever�.
"I'm writing every day, right here at the piano in this living room. This is my charles Herbert Best work ever,� she told OK Magazine.
Spears is expected to release her followup to 2007's 'Blackout' early in 2009.
Spears is currently in negotiation to perform at next months MTV Video Music Awards in Los Angeles.
The singer is already appearing in adverts for the awards ceremonial alongside host Russell Brand.
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Wednesday 6 August 2008
The Velvet Underground and Nico
Artist: The Velvet Underground and Nico
Genre(s):
Rock
Discography:
Andy Warhol
Year: 1967
Tracks: 11
Friday 27 June 2008
Terra Ambient
Artist: Terra Ambient
Genre(s):
Ambient
Discography:
The Gate
Year: 2004
Tracks: 7
The Darker Space
Year: 2002
Tracks: 7
Thursday 19 June 2008
Velvet Revolver's Singer Search: Could An Unknown Be Chosen As The New Frontman?
Since it was revealed two months ago that singer Scott Weiland had been excised from Velvet Revolver, the rest of the guys have been searching for his replacement. They hosted auditions and even rejected an offer from reality-TV producer Mark Burnett, who wanted to make VR the subject of his next "Rock Star" series.
Not long after Weiland's departure, guitarist Slash stated that VR would be using the Internet to audition potential frontmen, adding that the band was even toying with the idea of launching a Web site, where audition videos could be posted for public review. That site never took off, unfortunately, but there are still hundreds of aspiring singers out there who are all at the band's beck and call, should the Revolver need them.
While the names of several established musicians (including Linkin Park's Chester Bennington) have been kicked around as rumored replacements, it hasn't deterred these unknown rockers, who claim they're ready to step into Weiland's imposing shoes at the drop of a hat. Some of them have taken their cases to YouTube and other video sites, where, with a little shameless self-promotion, they've manufactured their own hype, generating a groundswell of support from VR fans. Some are even claiming they're front-runners in the race to return the band to the stage, but none explicitly claim they've been contacted by VR.
Dale Toth, who sings in a band called Rogosonic and sounds frighteningly like Axl Rose, had an interesting take with his audition tape. The video, which features an original song from his band, shows nothing but images of Toth trying to look tough. He chose not to cover a VR track, because he figured "it's going to be new material they're more focused on right now, so maybe this is a better idea of what I can offer," he wrote in a post alongside the video. "If it goes further (crossing fingers), I'd be glad to do some vocal tracks to the other VR tunes so they know what I can do on that stuff."
"The vocals are amazing," complimented one fan. "Here's to blowing away the competition."
But Toth admitted on his YouTube page that the band "may have someone already, but I have to contact the VR camp again next week. Hearin' a lot of rumors of people they may already have in mind. Guess we just have to wait for [the] official release."
Another hopeful is Weiland sound-alike Sam Serinsky, who sings for a rock band called Lasting Factor. For his grainy, low-budget audition tape, Serinsky sang one of his own band's originals, and the video has been well-received — with some fans saying it would be a crime if he weren't asked to join the band.
"Damn, you are the real deal," wrote one user, pointing out that Serinsky can also play guitar, which Weiland didn't. "You would be a perfect fit for VR and then some."
"I think it would be good to get someone that is not already 'known' because it would give the band a new, fresh and unbiased sound," wrote another supporter. "I wouldn't be surprised if this kid got a call from Slash and offered the gig."
But perhaps the most-produced (and longest) audition tape belongs to Brian Phyll Miller, a man who desperately wants the gig. In his video (which features some classy footage of a dog licking itself), Miller — wearing a "Brutal Rockers" T-shirt — belts out a cover of AC/DC's "Whole Lotta Rosie," and follows it up with VR's "Slither" and "Fall to Pieces." In the video, Miller talks of his love for "vodka, cigarettes and Jack [Daniels]," discusses some of his influences ("Anybody that's cool"), and talks about the vocal and breathing exercises he does before a performance. He also confesses that, since the age of 14, he's wanted to be in a band.
Google Miller's name, and you'll find he has a lot of online support, whether self-manufactured or not.
On the Rolling Stone site, an already-deleted comment on a Flobots piece read, "Flobots? Hmmm I don't think so ... Velvet Revolver is talking with a guy to be the new singer of their band. He is good, he has some epic vocal cords. Judge for yourself. Go to YouTube and search for Brian Phyll Miller. Make it happen, spread the word on this guy and give him support. He is already talking with the band, but it would be nice to have all the fans' support behind him."
On Monday, several comments popped up on our Newsroom blog, following a post on the VR singer search, mostly praising Miller's abilities.
"A lot of talk about who will be the next Velvet Revolver frontman. ... There is a new guy in town that would be very worthy of filling those shoes," one commenter said. "Brian Phyll Miller is getting a lot of comments on his YouTube and MySpace site. A lot of people are saying he should be the next Velvet Revolver lead singer. I would have to agree. This guy is awesome, great range with his vocals, something I think Slash and the guys should take a serious look at."
"Just watched his YouTube video — he's amazing," another commenter wrote.
On Miller's YouTube page, where he admits he hasn't been contacted or spoken with anyone representing VR, the remarks (the origin and authenticity of which we can't verify) are more of the same: He rules and is the best replacement for Weiland.
"How come this guy isn't signed with some band and changing the world with his epic vocal cords?" wrote one fan, adding that his voice is "much better than Scott Weiland's."
But will these guys ever get their shot at a proper audition? It's doubtful that a band as established as VR, with its members' vaunted history, would opt to add a complete unknown to its ranks over someone who's road-tested, studio-savvy and has a recognizable name. But then again, stranger things have happened.
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Wednesday 11 June 2008
Mendes drops drama for laughs
Oscar winning director Sam Mendes is set to helm a new comedy, currently titled 'This Must Be the Place'.
The film will follow a young couple as they travel across the US in search of the perfect place to raise their baby.
The 'American Beauty' director is currently finishing 'Revolutionary Road' for DreamWorks, starring his wife Kate Winslet and Leonardo DiCaprio. The drama is due for release at the end of this year.
Originally it was thought that his next project would be his first UK film, 'Middlemarch'. The drama is a rendering of George Eliot's 19th century classic novel, which is being adapted for the big screen by Andrew Davies.
However, according to Variety magazine, after working on so much heavy-duty drama, Mendes decided instead that it was time to flex his comedic muscles.
No cast has been confirmed yet for the new 'This Must Be the Place' and principal photography will begin in March.
The film will follow a young couple as they travel across the US in search of the perfect place to raise their baby.
The 'American Beauty' director is currently finishing 'Revolutionary Road' for DreamWorks, starring his wife Kate Winslet and Leonardo DiCaprio. The drama is due for release at the end of this year.
Originally it was thought that his next project would be his first UK film, 'Middlemarch'. The drama is a rendering of George Eliot's 19th century classic novel, which is being adapted for the big screen by Andrew Davies.
However, according to Variety magazine, after working on so much heavy-duty drama, Mendes decided instead that it was time to flex his comedic muscles.
No cast has been confirmed yet for the new 'This Must Be the Place' and principal photography will begin in March.
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